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patient_info_and_summary

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Name stringlengths 8 21	Age int64 18 45	Date_of_Birth stringlengths 8 10	Phone_Number stringlengths 4 22	Email stringlengths 16 30	Address stringlengths 13 36	Patient Progress Summary stringlengths 311 19.4k
Elina Rosario	34	1993/3/2	788-385-3010	[email protected]	144 Sherry Terrace	A 28-year old man presented with a three month history of an asymptomatic scrotal swelling. He had previously undergone orchidopexy in childhood for a mal-descended right testis. There is otherwise no other significant medical or family history. The mid-scrotally located mass measured 4 ? 7 cm and was nodular, hard and clinically separate from the testes. It was not attached to the scrotal skin or other underlying structures. Lymphadenopathy was not detected. Initial ultrasonography (Fig ) showed a large extra-testicular and multinodular mass in the midline of the scrotum. The largest nodule, located behind the right testis was cystic. Both testes appeared normal. Subsequent staging Computer Tomography (CT) of the scrotum, abdomen and chest was performed, which identified a similarly localised heterogeneous mass of 6.9 ? 3.7 cm, separate from the testes (Fig ) and did not extend into the tunica vaginalis. There was no evidence of distant or nodal metastases. An initial diagnostic wedge biopsy indicated the lesion could be an ancient schwannoma. Curative surgical excision with partial scrotectomy was undertaken for removal of the mass and for definitive diagnosis. At resection, the tumour appeared to be superficial to the tunica vaginalis, testes and corpus spongiosum. Inferiorly, the tumour was attached to the bulbospongiosus requiring partial resection of the superficial muscle fibres. The resected specimen (Fig ) was white and multinodular, with areas of cystic change and haemorrhage. Microscopically (Fig ), proliferation of spindled shaped cells with fibrillary cytoplasm was seen, with dense fibrous bands arranging the cells into nodules. In some cells, marked nuclear hyperchromaticism and atypia were seen. Mitoses were not present. Within the lesion, cellular areas were interspersed with looser myxoid and cystic areas. Blood vessels with thickened hyalinised walls were noted. Staining for S100 protein was positive in the tumour cells. The histological features are that of an ancient schwannoma. The margins of this specimen were ragged and the completeness of excision was difficult to assess.
Jedidiah Anthony	39	1993/6/18	638.454.8448	[email protected]	5953 Max Burg Apt. 352	A 53-year old woman was admitted to emergency room with one week history of purpuric lesions limited to both legs, accompanied by paresthesias, very painful arthralgias which confined her to wheel chair and distal edema in both lower extremities. She had a previous history of modified mastectomy with axillary lymphadenectomy for a retroareolar, canalicular breast carcinoma 6 months before, whose histological diagnosis was a ductal carcinoma measuring 4.5 cm of diameter, estrogen and progesterone receptor-positive and HER2 negative. She received adjuvant radiation and started tamoxifen 20 mg daily four months before admission. At the clinical examination, she had several purpuric papular lesions in both distal extremities, some were confluent, within a 1 cm diameter on the left external heel. Arthritis was also present in both ankles and knees. Liver function tests demonstrated a cholestatic damage, with increase of alkaline phosphatase (196; normal: 40??50 U/L), GGT (213; normal> 12??3), SGPT (249; normal 5??6 U/L), SGOT (110; normal 9??5 U/L); other liver tests, and the rest of laboratory, including SMA-18, blood cytology, coagulation studies, viral hepatitis infection markers, antinuclear antibodies, coagulation tests and crioaglutinines were normal. Tumor markers, including CA15-3 were negative or normal. Liver ultrasound showed none focal lesions and was considered normal. Histopathology analysis of skin biopsies showed deposits of fibrinoid material in the walls and infiltration by lymphocytes and neutrophils in dermis vessels, which was diagnosed as vasculitis. Tamoxifen was withdrawn and methylprednisolone at 1 g daily was administered during 3 days. Thereafter, 0.5 mg/kg prednisone was indicated during 7 days and subsequently decreased. Lesions disappeared after one week. Currently she is alive and well receiving anastrazole.
Macy Meadows	27	2003/9/15	826.717.2181x6818	[email protected]	296 Victor Knolls	The second girl (10 years old) complained about back pain after she had fallen from her bike. She had grown normal along the 50th height percentile. X rays of her spine revealed oedematous changes of 3 and compressions of 2 thoracic vertebrae (# 9, 11). At first these were considered trauma related, however, especially posterior oedematous changes of the 8th vertebra were considered not to be typical sequels of a trauma (figure figure ). In addition, a technetium bone scan did show an additional lesion in the right 4th rib (figure ). The rib lesion was also analysed by MRI of the thorax. It did show a strong T2/TIRM/STIR signal. Thus Langerhans' cell histiocytosis was suspected at that time. A biopsy of this rib, however, revealed a sterile lympho- plasmocytoid osteomyelitis suggesting multifocal CNO. There were no elevated inflammatory parameters (ESR, CRP, leukocytes). A differential blood count did not show signs of malignancy. Further workup revealed normal serum levels of beta-HCG (human choriogonadotropin), neuron specific enolase, cortisol and angiotensin converting enzyme. HLA B 27 was present. Total alkaline phosphatase levels (401, 426, 316, 378, 185, 189 U/l) measured over time were in the normal range. Compared to a cohort of genetically diagnosed childhood hypophosphatasia patients [,] these levels were considered unremarkable. However, a nephelometric measurement of the bone alkaline phosphatase revealed a reduced level (8.9 microg/l; normal 36??0 microg/l). Therefore, a more reliable and specific measurement of the tissue non-specific alkaline phosphatase in leukocytes was done. The result was below normal (1.8 nmol/min/mg Protein; normal: 2 ??18) []. In addition, pyridoxal phosphate in the plasma was slightly elevated (31 ng/ml; normal: 5 ??30 ng/ml), phosphoethanolamine excretion in the urine was normal. We suggested that a partial defect in the TNSALP gene was present. She may be a carrier of one severely mutated allele of alkaline phosphatase, because slight elevation of plasma pyridoxal levels has been demonstrated in obligatory heterozygotes (parents of index patients) with severe alleles []. Thus, the patient might be a carrier for the hypophosphatasia trait. The family refused a diagnostic genetic workup. Based on our experience in treating hypophosphatasia patients with non-steroidal anti-inflammatory agents [,], in addition to the anti-inflammatory treatment of chronic non-bacterial osteomyelitis patients [] we started a therapy using naproxen at a dose of 15 mg/kg/d in both patients. This therapeutic protocol was approved by the ethics committee of the University of Wuerzburg. The treatment rapidly reduced clinical symptoms including pain and soft tissue swelling (figure ). Parallel to this clinical improvement subsequent MRI analysis after 3, 6 and 12 months revealed subsequent reduction of bone marrow oedema and local gadolinium enhancement. 12 months later MRI showed almost unremarkable lesions (figure ). Mild hyperostosis of the os zygomaticum was still present after 12 months at treatment cessation. 24 months later the patient was still in remission. The medication did abrogate pain completely after the first 3 months of treatment. Parallel to this clinical improvement subsequent MRI analysis (figure ) after 3, 6 and 12 (figure ) months revealed subsequent reduction of bone marrow oedema and local gadolinium enhancement. 12 months later MRI showed an unremarkable 8th thoracic vertebra, whereas the 9th and 11th still showed compression without sign of acute inflammation (figure ). The rib lesion was unremarkable after 6 months of treatment. No further structural improvement was noted after 24 months. Thus, treatment was terminated.
Wayne Dougherty	39	1997/1/17	772-295-3519	[email protected]	367 Brandi Garden Suite 299	A 78-year-old woman presented with a 6-month history of dyspeptic symptoms, epigastric pain and weight loss. Gastroscopy showed mucosal nodularity and ulceration at the proximal gastric body with an "hour glass" deformity, an appearance suggestive of malignancy. Multiple mucosal biopsies were obtained and histopathology revealed a poorly differentiated adenocarcinoma and chronic gastritis. Computed tomography of the abdomen showed diffuse thickening of the gastric wall and a few enlarged lymph nodes in the lesser sac. The patient underwent an elective D2 total gastrectomy with splenectomy as the bulky gastric tumour was extending into the splenic hilus and a Roux-en-Y reconstruction was performed. The histopathological examination of the specimen macroscopically showed firm texture of the proximal stomach and vague nodular appearance of the mucosa over a 100 by 80 mm area. Microscopically the proximal stomach showed transmural infiltration by poorly differentiated diffuse adenocarcinoma, which had reached the serosal surface. There was vascular invasion, infiltration of 10 out of 34 nodes and numerous extranodal tumour deposits. A nodule of firm white tissue, 9mm diameter, was present on the external surface of the gastric antrum. Histological examination revealed this nodule to be a benign gastrointestinal stromal tumour (GIST), which had arisen from the muscularis propria. It was composed of interwoven cytologically bland spindle shaped cells that were demonstrated by immunohistochemistry to be uniformly positive for CD117. Scattered spindle cells of the GIST also expressed smooth muscle actin, desmin and S-100 (Fig. , , ). Cytoceratin immunohistochemistry was negative. An additional finding was the presence within the GIST of numerous cytokeratin positive polygonal-shaped gastric carcinoma cells (Fig. ). These cells were cytologically similar to those of the main gastric tumour. They were seen mainly around the peripheral parts of the GIST but were also present within its centre.
Alisson Roberson	32	1979/10/1	001-387-623-0689x0533	[email protected]	07322 Kayla Rue Suite 414	B.S. a 4-year-old male child was admitted to the pediatric surgical ward at Jordan University Hospital because of two days history of swelling, redness and pain of his scrotum (Fig. ). There was no history of trauma. The pain was moderate, not characteristic of torsion, and not the chief complaint. Oral temperature was 37.8簞C and pulse 94/min. Physical examination revealed bilateral red swollen scrotum, moderately hot and tender allowing examination of the testes, which were in normal position and of equal size and not tender. There was a small amount of fluid bilaterally detected on transillumination. The rest of the physical examination was unremarkable. Laboratory work up showed Hb. 10.5 gm/dl, Hct. 32%, WBC 12.7 ? 103/mm3 and normal serum amylase. Ultrasound examination confirmed the equal sized testes, with normal echogenicity, the presence of small amount of fluid in the scrotum, and the edematous scrotum. On further examination of the scrotum, a streak of redness extended along the midline raphe to the perineum, where a visible wire through an eroded perianal skin was seen (Fig ). The patient underwent a Thiersch wire insertion for a rectal prolapse one year before. The patient was started on broad-spectrum antibiotics (Ampicillin, Gentamycin and Metronidazol). It was decided that the Thiersch wire has to be removed in theatre under general anesthesia. While examination under anesthesia the perineum appeared healthy, without signs of inflammation, or suppuration but moderate amount of induration. Rectal exam was normal; there was moderate narrowing and fibrosis at the anal verge. After removal of the wire the tract was intact with minimal discharge, which cleared in few days following wire removal. The sinus tract was very short lived and closed without any problems thereafter. Culture taken from the site of the wound grew streptococcus fecalis sensitive to the administered antibiotics. The scrotal swelling and redness subsided gradually. The child was discharged without any complications. Follow up was uneventful for both the scrotal redness and swelling as well as the rectal prolapse.
Shepherd O’Connell	21	1989/5/11	+1-837-474-7430x3408	[email protected]	477 Ashlee Parks	A 3-year-old boy presented with a large bosselated swelling over the cheek extending to the submandibular, submental, postauricular region and which was still further increasing in size (Figure ). A trucut簧 biopsy was suggestive of fibromatosis. Computerized tomogram (CT) scan revealed a large soft tissue mass infiltrating the massetter, parotid gland, floor mouth, submandibular gland, the lateral oro-nasopharyngeal wall and the pterygoid muscle. The horizontal ramus of mandible was eroded and the mass extended across the midline. Excision of the mass with segmental mandibulectomy was performed. Reconstruction with a free fibula was deferred for a later stage in view of the young age, large mass and concern of recurrent disease. Since the mucosal defect following excision was not large enough primary closure was performed. Histopathology confirmed juvenile fibromatosis and all cut margins of resection were free of tumour. The patient presented after 13 months with recurrent swelling over the cheek with significant difficulty in swallowing and constant dribbling of saliva due to inadequate mouth closure (Figure ). A CT scan revealed presence of a large recurrent mass in the floor of mouth, infiltrating the infratemporal fossa (ITF) and reaching up to the base of skull (Figure ). In view of the extensive recurrence low dose chemotherapy (weekly vinblastine, methotrexate and tamoxifen) was started. After completion of 12 weeks of chemotherapy, a partial response was achieved. Excision of the mass with ITF clearance was performed subsequently. A portion of tongue and its base along with the lateral oropharyngeal and the soft palate was also excised (Figure. ) The defect following resection was large and a free flap was not feasible as the external carotid artery was ligated at previous surgery. Reconstruction with a PMMC flap for providing mucosal cover and soft tissue bulk for defect was considered. In view of the large mucosal defect a large skin paddle was taken incorporating the nipple-areola complex. The technique for harvesting the PMMC has been described previously [] (Figure ). The edges of the flap were sutured circumferentially to the mucosa of the oral cavity except superiorly where the mucosa was deficient; the flap was anchored to the hard palate with non-absorbable sutures. Patient had an uneventful recovery and was discharged after ten days. The flap was well taken without any necrosis or other complication. Guide bite prosthesis was used after a week of surgery to prevent malocclusion. Histopathological examination revealed all cut margins to be free of tumour. Patient further received 12 weeks of low dose chemotherapy. At one year follow-up the patient is having normal speech and swallowing and is free from recurrent disease.
Jillian Sawyer	38	1990/3/6	576-638-0049	[email protected]	766 Pearson Cove Apt. 895	Patient 1 is a 29-year-old Iranian-Jewish woman diagnosed at age 24 years. She presented at age 17 with inability to abduct her legs against any resistance on an exercise machine; other muscle groups were strong. Following her first pregnancy at age 20, she noticed weakness, difficulty climbing stairs, and tripping and falling that progressed in frequency over the next 3 years from once a month to once a week. A muscle biopsy and genetic testing confirmed the diagnosis of HIBM with homozygous M712T mutations in GNE. At age 25, she noted difficulty fastening snaps and could not raise her arms to pull back her hair. Progression was gradual, with more significant decline following illnesses. Treatments included solumederol, 1 g intravenously for 3 days, which resulted in improved strength but was followed by relapse. On one occasion, IVIG (dose unknown) was given over 3 days, providing no improvement but complicated by aseptic meningitis requiring hospitalization. For the 6 months prior to admission, the patient used a wheelchair and required assistance walking and with transfers. Medications included sertraline for depression and anxiety, and vitamins. At the NIH Clinical Center, the patient was wheelchair dependent, but could go from sit to stand and ambulate a few feet with support. She had bilateral foot drop and significant weakness of upper and lower extremities, with some sparing of the quadriceps. Muscle atrophy was universally apparent. Cranial nerves and sensation were intact. MRI of the calf showed pronounced fatty involution of the musculature bilaterally, worse proximally. The lateral soleus and posterior tibial muscles were somewhat spared distally. A quadriceps muscle biopsy revealed moderate type II fiber predominance. The muscles were atrophic (type II worse than type I) and demonstrated necrosis, active degeneration, and red rimmed vacuoles, consistent with severe chronic myopathy without inflammation. Imunohistochemical staining for NCAM, a surface glycoprotein reflecting muscle regeneration [,], showed a significant number of positive fibers.
Jefferson Li	27	1990/7/26	001-972-852-5865x8866	[email protected]	80606 English Knoll Suite 830	Patient 2 is the 42-year-old brother of patient 1. He was diagnosed with HIBM at 37 years of age, following the diagnosis of his sister. Weakness upon raising his arms overhead first appeared at age 27. At 34, he began tripping and, in the subsequent year, had difficulty climbing stairs and lifting his son. The upper extremities were most affected, but leg weakness was evident by decreased endurance, speed of walking, and getting in and out of a car. He occasionally used his hands to lift his legs. Symptoms were largely stable, but exacerbated by emotional events. He did not receive any treatment for his myopathy, and medications included only multivitamins. At the NIH Clinical Center, there was wasting of the triceps and the interosseus and thenar muscles of the hand. Contractures of approximately 5??0 degrees were present in the elbows, with decreased range of motion upon supination of the forearm. The patient had no foot drop. Muscles of the shoulder girdle, pinch, grip, and proximal lower extremities exhibited weakness. The gait was normal, and cranial nerves and sensation were intact. MRI of the thigh revealed advanced atrophy with fatty involution in the proximal posterior compartment and adductor magnus muscles bilaterally. The sartorius and rectus femoris muscles were also involved. There was relative sparing of the quadriceps with the exception of the rectus femoris muscles. On biopsy, the quadriceps muscle showed several small vacuolated fibers with a few degenerating fibers, but no inflammation. Immunohistochemical staining was negative for NCAM, indicating negligible damage to individual muscle fibers.
Paige Silva	42	1992/4/23	001-507-861-3303x376	[email protected]	471 Rodriguez Estate	Patient 3 is a 39-year-old woman of Bohemian/Czech/French Canadian ancestry diagnosed with HIBM at the age of 31 years. Following a year of progressive tripping and falling, she awoke one day with numbness from the waist down that spread to her entire body. She was diagnosed with mild multiple sclerosis, based on the presence of oligoclonal bands in her cerebrospinal fluid and a brain MRI showing a possible "spot." Muscle biopsy also provided evidence of inclusion body myopathy. Currently, she has difficulty arising from a supine position due to weak abdominal muscles, weakness in her hands, arms, and shoulders, and inability to climb stairs. She wears ankle braces to walk. She uses bronchodilators for asthma and sertraline for depression. Confirmatory mutational analysis demonstrated compound heterozygous GNE mutations, i.e., R246Q and A631V, affecting the epimerase and kinase domains, respectively. At the NIH Clinical Center, the patient had bilateral foot drop with a compensated gait. She was able to transfer independently from sit to stand and from stand to sit. There was proximal muscle and neck weakness and limited endurance. Cranial nerves and sensation were intact. MRI of the calf showed end-stage myopathy with advanced fatty involution, but with preservation of muscle volume. Signal alteration was present in areas of non-atrophic muscle. The popliteal muscles in the upper calves and the distal posterior tibial muscles were relatively spared. On biopsy, the quadriceps muscle showed significant necrosis with replacement of muscle by fat and connective tissue, but without inflammation. NCAM staining was minimal.
Luka Weaver	33	1992/7/22	564.387.7960x9366	[email protected]	3711 Renee Station Suite 391	Patient 4 is the 46-year-old brother of patient 3. He was diagnosed with HIBM at the age of 33 years following a one-year history of progressive tripping and falling, decreased muscle strength and inability to lift his foot. As a cabinetmaker, he relied on this action to support the cabinets as he made them. A muscle biopsy was initially read as consistent with either polymyositis or inclusion body myopathy, but intravenous steroids provided no relief, and HIBM was diagnosed. Plateaus were interspersed with declines, which occurred with lack of exercise but not with illnesses. The lower extremity weakness extended throughout the body. The patient currently wears ankle braces to walk, uses an electric wheelchair for distances, and has assistive devices to drive. He has difficulty holding a pen. Medications include acyclovir, Metamucil, multivitamins, tramadol and diazepam. At the NIH Clinical Center, there was muscle wasting of the triceps and the interosseus muscles of the hands, along with tightness of the heel cords, hips, and hamstrings. The patient was partially independent when going from sit to stand, and when executing transfers to and from his wheelchair. He could ambulate a few steps using ankle-foot orthotics and support from the wall. He had significant weakness in the proximal upper extremities, triceps, wrist and hand, and decreased strength on hip flexion, hip extension, ankle dorsiflexion, and plantar flexion. Deep tendon reflexes could not be elicited in the upper or lower extremities. Sensation and cranial nerve functions were intact. MRI of the calf showed end-stage myopathy with advanced fatty involution but preservation of muscle contours. Signal alteration occurred in areas of the remaining muscle. There was relative sparing of the popliteus, the tibialis posterior, and the flexor digitorum longus muscles. Quadriceps muscle histology revealed vacuolated and moth-eaten muscle fibers, with degeneration and regeneration. Connective tissue was slightly increased with no signs of inflammation. Immunohistochemical staining with NCAM was negative.
Teagan English	45	2003/2/5	001-382-405-1083x1594	[email protected]	85362 Jillian Extensions	A 22-year-old female with two prior full-term deliveries underwent an elective abortion at 15 weeks gestation at a clinic, 8 weeks prior to admission at our medical center. The procedure was uncomplicated; the patient does not remember receiving antibiotics or being tested for GBS. Her past medical history was noncontributory although she reports a negative HIV test one month prior to admission. She denies using illicit drugs, any injection therapy, or any recent tattoos. One week after the abortion, she developed low-grade fever and malaise and returned for a repeat cervical dilation and uterine evacuation. Genital cultures grew GBS, Candida albicans, and oxacillin-sensitive Staphylococcus aureus. She was discharged with 7 days of amoxicillin. Two weeks later, she presented to another hospital complaining of fever, chills, productive cough, dyspnea, and diffuse chest pain of 5 days duration. She was febrile with enlarged tonsils, no evidence of cardiac abnormalities, rales in bilateral lung bases, and a benign abdomen. A sterile speculum exam revealed yellow-green discharge from the cervix; cultures were sent. She was admitted and treated with ceftriaxone, azithromycin, and metronidazole. CT showed diffuse, patchy infiltrates in the lower lobes with cavitations and no evidence of a pulmonary embolism. Blood cultures grew gram-positive cocci in chains presumed to be S pneumonia and nafcillin was added. She left against medical advice and two weeks later presented to our Emergency Department (ED) with worsening fevers, chills, SOB, productive cough, and pleuritic chest pain. In the ED, she was again treated with cefotaxime and azithromycin for presumed community acquired pneumonia and intravenous heparin for possible PE. On exam she was febrile, hypotensive, tachycardic, and tachypneic. Oxygen saturation was 87% on room air. She had pale conjunctivae and dry mucous membranes. Lung exam revealed diffuse rhonchi and decreased breath sounds on the right. On cardiovascular exam, her neck showed cannon v waves along with a 3/6 holosystolic murmur best heard at the lower left sternal border. Abdominal and extremity exams were benign. There were no signs of Osler's nodes or Janeway lesions. Her CBC revealed a WBC of 19.3, hemoglobin of 9.6, and platelets of 81 000. D-dimer was 4540 ng/mL; beta hCG was negative. Chest radiograph showed bilateral, fluffy, lower lobe infiltrates with peripheral cavitations. Ultrasound of the lower extremities for deep vein thromboses was negative. EKG revealed sinus tachycardia and right ventricular conduction delay (RSR'). CT of the chest, abdomen, and pelvis revealed large, bilateral, peripheral lower lobe cavitary lesions. She was admitted to the ICU and treated with penicillin G, gentamicin, and clindamycin. Transthoracic echocardiogram showed estimated pulmonary artery systolic pressures of 55 mmHg, right atrial and right ventricular dilation, and large tricuspid valve vegetation with severe tricuspid regurgitation (). Left ventricular ejection fraction was 56%. Blood cultures were reported positive in 12 hours with GBS, sensitive to penicillin (MIC 0.12) and cefotaxime (MIC 0.12). Clindamycin was stopped. Throughout her stay, the patient was persistently febrile. Repeat CT of the chest, 2 weeks after admission, showed improving pulmonary infiltrates; multiple, bilateral cavitary lesions increased in size; cardiomegaly with a very large right atrium and suprahepatic inferior vena cava, along with a severely enlarged liver suggesting right heart failure. She was treated with 3 weeks of gentamicin and discharged on continued intravenous penicillin G for a total of 6 weeks of therapy. Although her echocardiograms and CT scans showed evidence of right heart failure, she had no clinical evidence of this; it was decided to monitor the patient closely and forgo surgery. The patient missed two followup appointments after her discharge. She appeared in the ED a few months later complaining of chest pain and dyspnea on exertion. CT scan of chest showed left descending pulmonary artery aneurysm without clot or dissection but clear evidence of pulmonary hypertension. Echocardiogram in the ED revealed normal LV motion and ejection fraction, complete resolution of the vegetation, pulmonary artery peak systolic pressure of 41 mmHg, a thickened tricuspid valve with severe regurgitation, and septal flattening consistent with right ventricular volume overload. The cardiologist evaluated the patient and recommended her to followup for a possible tricuspid valve replacement. However, the patient was again lost to followup.
Junior Howell	33	1998/10/18	(623)921-4669x204	[email protected]	4791 Rogers Squares	A diabetic 55 year old woman was admitted to Zonguldak Karaelmas University emergency clinic with a complain of an insidious onset of swelling in the left part of vulva, a pain radiating to the left inguinal region, chills and high fever over a week. She has had hypertension and type II diabetes mellitus and has used oral anti-diabetic and anti-hypertension drugs for 8 years. She had no history of previous trauma, operation, underlying skin lesion, use of foreign body or human bite on her vulvar region. Two days after onset, her left part of the vulva became swelling and the lesions color turned to red. Even though she had used amoxicilline-clavulanic acid and ornidasole for three days, the lesion on the vulva and pain worsened. In clinical examination her fever 38簞C, pulse 96/dk, blood pressure 160/80 mmHg, in the left part of the vulva there was an erode lesion in the certain part of the inflammatory halo. The lesion was 5 ? 4 cm in size, red, hot, swollen, and painful and fluctuant. Local tenderness and edema were also marked (). The borders of the lesion was not elevated and sharply demarcated. Laboratory values were as follows: WBC count, 18200/ mm3 (82% neutrophils, 8% lymphocyte, 8% monocytes) [4000??0000/mm3]; erythrocyte sedimentation rate (ESR), 122 mm/hour [0??0 mm/hour]; C-reactive protein, (++++)[negatif]; and blood glucose, 235 mg/dL [70??10 mg/dL]. Vulvar abscess was diagnosed and it was drained. In Gram stain of the pus, granulocytes (80% neutrophil), Gram-negative rods and Gram-positive cocci were detected. Ampicilline-sulbactam 4 ? 1 gr IV/day, ciprofloxacin 2 ? 400 mg IV/day and local care with 2% eau borique fluid were started empirically. Her oral anti-diabetic drugs stopped and IV insulin treatment started. The blood glucose was in regular limits after IV insulin treatment began. Following drainage, her fever, leucocyt count became normal and, edema, pain and erythema of the lesion subsided. Eikenella corrodens and metisilline sensitive Staphylococcus epidermidis (MSSE) were isolated from culture of the pus. After 3 days of the treatment her fever, white blood cell count was normal, ESR was 100 mm/hour. The patient completed 14 days of treatment with resolution of signs and symptoms. The ESR was 72 mm/hour in the first week of the treatment, 30 mm/hour at the end of the treatment. An informed consent was obtained from the patient to use of her photographs.
Mckenna O’Connell	27	1981/2/15	361.730.9322x94926	[email protected]	13778 Davis Vista Suite 973	A 7-month-old female infant from a Sudanese western tribe was referred as a case of malnutrition. At presentation, the patient had confluent eyebrows that appeared arched and well-defined, long curly eyelashes, low front and back hairlines, turned-up nose, down-turned angles of the mouth and thin lips, long philtrum, small lower jaw and protruding upper jaw, microcephaly, excessive body hair, short neck, and small broad hands with simian crease and proximal insertion of the thumb, and clinodactyly of the fifth finger. X-ray showed delayed bone development. She had low-pitched cry, short neck with limited movement, stiff muscle tone (unable to sit, she was still fisting), fixed flexion of both elbows, and she did not show any sign of speaking or babble (Fig. and ). Moreover she had tied tongue and thin skin. Her brain stem evoked potential test showed conductive hearing loss. She was about 27 inches in length, her weight was 3 kilograms and there were no records about her birth weight. Her skull circumference was 35 cm. Finally, she showed a number of features not typical of BDLS, including crowded ribs by chest by X-ray (distance between each rib is short). Hepatomegally was shown by ultrasonography. Peripheral blood from the patient was subjected to short-term culture in RPMI 1640 medium for 72 hours. After metaphase arrest through exposure to Colcemide, cells were harvested, treated with hypotonic solution, and then fixed with methanol and acetic acid according to standard procedures. The harvested cells were dropped on clean slides and stained with Wright's stain, for chromosome banding []. The clonality criteria and the karyotypic descriptions were according to the ISCN recommendations []. Analysis of 11 metaphase cells showed 46, XX in all cells.
Jovanni Velazquez	30	1978/6/5	+1-756-532-9066x147	[email protected]	91981 Johnson Underpass	In August 2003, a 20-year-old 16-week pregnant mother of one, presented to the orthopaedic outpatient clinic with a 2-month history of a slowly growing painless mass located in the right hypothenar eminence. She was right-hand dominant and a housewife. There was no history of trauma, insect bites or drainage from the area. There was no significant past medical or surgical history. She was not on any prescribed medication. There was no family history of tumours. She denied smoking, alcohol and drug abuse. On examination, a non-tender, firm to palpation, well-demarcated and tethered to the subcutaneous tissues mass, surrounded by mild erythema, and measuring approximately 2.5 cm ? 3.0 cm was revealed, in the absence of palpable lymph nodes at the ipsilateral elbow or axilla. There were no other abnormal signs. Haematological and biochemical investigations were within the normal range. A plain X-ray of the right hand and forearm was unremarkable. Magnetic resonance imaging showed the mass to have infiltrated all skin layers and to have encircled the ulnar artery without involvement of the underlying bones (Figure ). The absence of a signal void from within the mass excluded a diagnosis of haemangioma. Ultrasound-guided needle biopsy showed lesional areas consistent with collagenous fibrous tissue of varying cellularity, with little evidence of mitotic activity. Immunohistochemistry showed focal positivity for smooth muscle actin (SMA), suggesting myofibroblastic differentiation. Histological appearances were in keeping with fibromatosis. Three weeks after initial presentation, the lesion was excised preserving the ulnar nerve and artery. Histology showed a multi-nodular, well-circumscribed uniform spindle cell lesion with varying cellularity and fibrosis. In one section, central cyst formation was observed. Occasional mitoses of normal morphology were seen. Necrosis was not a feature. In several areas, the lesion appeared to be intravascular, the vessel was lined by an apparent endothelium (Figure ). Scattered osteoclast-like multi-nucleate giant cells were also observed. Immunohistochemistry replicated diffuse positivity for SMA, but not for desmin, CD34 or S100 protein. Appearances were consistent with a myofibroblastic proliferation, confirming a diagnosis of intravascular fasciitis (IVF). The patient had an uneventful recovery and required no further therapy. She continues to be evaluated for local recurrence every 6 months, with no sign of recurrence at the 2-year follow-up.
Jaliyah Zuniga	34	1996/5/22	4033126299	[email protected]	9409 Walker Port	A 29 year old man, was referred complaining of mild exertional dyspnea, dizziness and chest pain during the last 3 years. These symptoms remained stable during this time. When he was 15 years old, he had meningitis complicated by a cerebral abscess; at that time, in another institution, a harsh cardiac murmur was heard at the left external border and an echocardiographic examination have shown a four millimeter VSD, right ventricular hypertrophy and increased pulmonary flow. The cerebral abscess was surgically drained and the patient, after recovery, remained asymptomatic for the following 11 y. In the current clinical evaluation, physical examination revealed no cyanosis, heart rate of 80 bpm, arterial blood pressure of 110 ? 70 mmHg; apical impulse was normopositioned at the 50 intercostal space. Cardiac rhythm was regular and there was a harsh intense ejection murmur in the low external border. The ECG showed: sinus rhythm, right axis deviation, right ventricular overload and a minor degree of right bundle branch block. Transthoracic echocardiography (Figure and Figure ) showed: a 17 mm perimembranous VSD associated to a slow velocity flow from left to right ventricle; aortic root was slightly deviated to the right. In addition, there was RV hypertrophy and a muscular septation inside this cavity causing obstruction with a peak gradient of 80 mmHg. There was no obstruction to flow in the right outflow tract and the site of the right obstruction was displaced proximally preserving the right ventricular infundibulum. The pulmonary valve was completely normal. Based solely on the echocardiographic findings, the patient was referred to surgery which confirmed anatomical and functional abnormalities. VSD was closed and the right anomalous muscle band (Figure ) was successfully removed. After the procedure, patient remains free of symptoms and medications.
Sincere Mitchell	24	1992/3/4	+1-475-969-8387x02103	[email protected]	723 Morrow Spur Suite 050	A 46-year-old male with chronic lymphocytic leukemia underwent allogenic non-myeloablative stem cell transplantation (HSCT). The post-transplant course was complicated by severe graft-versus-host disease (GvHD) of the skin, thrombocytopenia, and systemic cytomegalovirus (CMV) infection, causing treatment-induced renal failure that necessitated hemodialysis (Table ). Nine months after HSCT, he was admitted to the intensive care unit (ICU) with septic shock, which was treated with empiric antibiotics, vasoactive medication, and mechanical ventilation. Seven days after ICU admission, the FiO2 requirement suddenly increased to 1.0 and fresh blood was coming from the endotracheal tube. The platelet count was 10 ? 109 per liter and the activated partial thromboplastin time (APTT) was 40 seconds. Despite platelet transfusion to a platelet count of more than 100 ? 109 per liter and FFP administration to an APTT of less than 35 seconds (in addition to the standard treatment as described in Materials and methods), the bleeding increased in severity. rFVIIa was administered intravenously in doses of up to 120 弮g/kg without hemostatic effect. Bronchoscopy revealed fresh bleeding from both lungs. rFVIIa (50 弮g/kg) dissolved in saline was administered by BAL into the left and right main bronchi simultaneously with the systemic i.v. administration of 50 弮g/kg rFVIIa. This resulted in an immediate cessation of the bleeding from the endotracheal tube. The arterial oxygen pressure (PaO2)/FiO2 ratio increased the subsequent day. The hemostatic effect lasted for approximately 36 hours, after which bleeding recurred. The treatment was repeated twice also, and bleeding ceased for more than 24 hours. Hereafter, the patient received rFVIIa (50 弮g/kg) by BAL alone twice, and bleeding ceased for 24 to 36 hours after each administration. Complete hemostasis was obtained after the third BAL administration of rFVIIa and lasted for three months (Table ). The patient died three months after the first rFVIIa treatment, due to respiratory and circulatory failure secondary to septic shock without evidence of active pulmonary bleeding. Postmortem examination revealed no signs of acute respiratory distress syndrome (ARDS) in the alveoli or thromboembolic complications.
Willow Warner	27	1980/11/4	2326031278	[email protected]	113 Morris Parkway	A 63-year-old male with progressive neurosarcoidosis was treated with infusion of methotrexate. After the second treatment, he developed pancytopenia and septic shock and was transferred to the ICU, where he was intubated and mechanically ventilated. Fresh blood was observed from the tracheal tube, and chest x-ray showed interstitial diffuse alveolar infiltrates indicating pulmonary bleeding. Standard treatment was instituted, resulting in an increase in platelet count from 18 ? 109 per liter to 88 ? 109 per liter with a reduction in APTT from 45 to 36 seconds (Table ). Multiple organ failure developed and increasing amounts of fresh blood were observed from the tube while the FiO2 requirement increased from 0.7 to 1.0. A single dose (20 弮g) of i.v. desmopressin did not improve hemostasis. Bronchoscopy revealed ongoing bleeding from the distal bronchial tree bilaterally. A 50 弮g/kg dose of rFVIIa was administered via BAL, resulting in immediate cessation of the pulmonary bleeding. Four hours after rFVIIa administration, FiO2 could be reduced to 0.8 and was further reduced to 0.6 the following morning (Table ). Despite continued improvement in pulmonary function, increasing circulatory instability secondary to septic shock became evident and the patient died four days after rFVIIa treatment. No pulmonary bleeding or thromboembolic complications were found after the intrapulmonary administration of rFVIIa.
Jaxton Valencia	30	1980/2/28	+1-855-917-5394x51652	[email protected]	3004 Johnson Falls	A 44-year-old male with acute myeloid leukemia (AML) developed high fever and hemoptysis 14 days after induction of a combination of chemotherapy comprising cytarabine, amsacrine, and etoposide. Chest x-ray showed bilateral infiltrations, and BAL revealed Stenotrophomonas maltophilia. The patient was admitted to the ICU, where mechanical ventilation was instituted with an FiO2 of 1.0, and was started with inotropic support and antimicrobial therapy (i.v. ceftazidime and inhalation of colistin). Pulmonary bleeding increased despite standard treatment (Table ). Bronchoscopy revealed ongoing bleeding from the distal bronchial tree bilaterally, and rFVIIa (50 弮g/kg) was administered by BAL. The bleeding ceased and the FiO2 was decreased to 0.45 over the next 24 hours. Over the next 12 days, the situation stabilized and improvement of the pulmonary and the circulatory functions was observed and the patient could be weaned off of the ventilator and discharged from the ICU. No pulmonary bleeding or thromboembolic complications were observed after the intrapulmonary administration of rFVIIa.
Maddison Buck	33	1987/11/22	001-456-624-3258x714	[email protected]	371 Burke Point Apt. 102	A 34-year-old woman was suspected of having Wegener's granulomatosis on the basis of eosinophilia, positive anti-neutrophil cytoplasmatic antibodies, hematuria, and proteinuria. Treatment with systemic corticosteroids was instituted, but due to respiratory distress and the presence of hemoptysis, the patient was admitted to the ICU. Chest x-ray showed interstitial subtle bilateral alveolar infiltrates indicating pulmonary bleeding. The patient was intubated and mechanically ventilated with an FiO2 of 1.0, and systemic antibiotic treatment was initiated in conjunction with pulse treatment with methylprednisone (1,000 mg intravenously every day for three days and then 40 mg every day). Treatment including continuous aprotinin infusion was instituted. The pulmonary bleeding ceased, FiO2 demand was reduced to 0.35, and antifibrinolytic treatment was discontinued. Twelve hours after discontinuation of aprotinin, fresh pulmonary bleeding again became apparent, together with an increase in FiO2 requirements to 1.0. The bleeding was refractory to standard treatment, including aprotinin. Bronchoscopy revealed ongoing bleeding at the segmental level, and rFVIIa (50 弮g/kg) was administered by BAL, leading to immediate cessation of the bleeding; FiO2 was reduced to 0.3 at six hours after rFVIIa treatment, and the patient was extubated the following morning. A biopsy from the skin showed perivascular eosinophilic infiltration indicating Churg-Strauss vasculitis, and the patient responded to the corticosteroid therapy treatment with regression of paresis and normalization of urine tests. Three days after extubation, bleeding from the lungs reoccurred together with an increase in O2 demand. To avoid re-intubation, rFVIIa was administered through a jet nebulizer with a prompt hemostatic effect. The aerosolized rFVIIa was repeated twice over the following 12 hours. A sustained hemostasis and a decrease in O2 requirements from 15 to 4 liters/minute were obtained. The further clinical course was uneventful, and the patient was discharged from the ICU three days later.
Jon Swanson	23	1980/2/24	994.468.8533	[email protected]	24480 Wilson Spring Suite 860	A 44-year-old HIV-positive female with chronic hemodialysis requirement, severe critical illness polyneuropathy, and enterocolitis due to Clostridium difficile infection, for which she received i.v. vancomycin, underwent surgery due to gastrointestinal bleeding. Postoperatively, she was transferred to the ICU, receiving mechanical ventilator support, and developed ventilator-associated pneumonia due to Pseudomonas aeruginosa, which was treated successfully with broad-spectrum antibiotics. In addition, a systemic CMV infection developed for which she was treated with Foscarnet, leading to stabilization over the following weeks. At 51 days after ICU admission, however, fresh bleeding occurred from the tracheotomy but did not respond to standard treatment as described previously. BAL revealed localized bleeding at the segmental level bilaterally, and rFVIIa (50 弮g/kg) dissolved in 50 ml of sodium chloride was administered with 25 ml in each main bronchus. The pulmonary bleeding ceased but reappeared within 24 hours after the treatment, and rFVIIa administration by BAL was repeated. Hereafter, the bleeding ceased to occur. The patient expired due to infection and respiratory insufficiency 115 days after rFVIIa treatment, without any signs of thromboembolic complications.
Helen Vaughn	43	1996/8/21	001-343-830-1883x2415	[email protected]	80435 Amy Hills Suite 300	A 63-year-old male with AML underwent non-myeloablative stem cell transplantation. The post-transplant course was complicated by GvHD of the skin and temporary poor graft function with pancytopenia. Six months post-transplant, the patient was transferred to the ICU due to respiratory insufficiency secondary to pulmonary infection. The patient was intubated and mechanically ventilated with an FiO2 of 0.45. Diagnostic BAL showed fresh blood at segmental levels bilaterally, but the focus of bleeding could not be identified. The platelet count was 35 ? 109 per liter and APTT was 40 seconds, for which the patient received FFP to achieve an APTT of less than 30 seconds and PCs to achieve a platelet count of more than 80 ? 109 per liter but without significant effect on the bleeding. The patient received empirical broad-spectrum antibiotics and antimycotics, resulting in a decrease of the C-reactive protein over the next five days. Twelve days after ICU admission, the pulmonary bleeding increased and the FiO2 demand was increased to 0.6. The patient had a normal TEG (thrombelastografic in vitro coagulation) profile, a platelet count of 80 ? 109 per liter, and an APTT of 27 seconds, indicating a localized coagulopathy. Due to further increase in bleeding and FiO2 demand, a diagnostic BAL was performed, showing fresh bleeding bilaterally at segmental levels; rFVIIa at a dose of 50 弮g/kg dissolved in 50 ml of saline was administered, resulting in immediate cessation of the pulmonary bleeding. The FiO2 was reduced to 0.35 within the next eight hours, and the patient was extubated the following morning. Three days after treatment with local pulmonary rFVIIa, the patient was discharged from the ICU without further bleeding episodes.
Remy Dean	37	1992/2/2	981-819-9631	[email protected]	9395 Hensley Cliffs Suite 547	A 70-year old woman attended mammography screening. The mammograms revealed en equivocal lesion. Ultrasonography identified a 14 mm tumor that was suspicious for malignancy. A FNAC was done under ultrasound guidance. The smears were stained with Diff-Quick簧 (Dade AG, D羹dingen, Germany). The aspirates were cellular and consisted mainly of single spindle or polymorphic, polygonal cells with a few admixed groups of benign ductal epithelial cells (Figure ) and lymphocytes. The nuclei were generally large, ranging from 2 - > 5 ? RBC. Most nuclei had a distinct medium-sized nucleolus. The nuclear outlines were irregular with buds and folds. The chromatin was granular. A few cells showing intranuclear cytoplasmic vacuoles were found (Figure ). The cytoplasm was bluish, variable in amount and often dense (Figure ). In the background there was abundant granular metachromatic ground substance and some metachromatic stromal fragments (Figures , and ). A few mitotic figures were found (Figure ). There was no necrotic debris. The cytologic diagnosis was suspicious for malignancy and a metaplastic carcinoma where only the non-epithelial component had been aspirated, or a non-epithelial lesion, was suggested. No smears were available for immunocytochemistry. The histopathological characteristics are shown in Figures , , , , , , , , , , , . Macroscopically the tumor was round, seemingly well circumscribed, firm and with a white cut surface. The diameter was 14 mm. On microscopy, the lesion was cellular (Figures and ), consisting of spindled and polygonal cells with distinct pleomorphism (Figures , , ). There were variable amounts of eosinophilic ground substance (Figures , and ) and a focal admixture of lymphocytes (Figures and ). There were 6?? mitoses per high power field (HPF) (Figure ) The tumor infiltrated in the surrounding fatty tissue (Figures , , ). On immunohistochemistry, the tumor cells were positive for smooth muscle actin (DAKO, Glostrup, Denmark) (Figure ), keratin MNF 116 (a pan-keratin with both high- and low molecular weight keratins from DAKO, Glostrup, Denmark) (Figure ) and vimentin (DAKO, Glostrup, Denmark)(Figure ). About 30 % of the tumor cell nuclei were positive for Ki-67 (DAKO, Glostrup, Denmark) (Figure ). Desmin (DAKO, Glostrup, Denmark) and S-100 (DAKO, Glostrup, Denmark) were negative. Estrogen- and progesterone receptors (DAKO, Glostrup, Denmark) as well as HER-2 (Novocastra, Newcastle upon Tyne, UK) were all negative. Ultrastructurally, there were abundant tonofilaments (Figure ), including globular filamentous bodies and granulated endocytoplasmic reticulum with many dilated cisterna. Desmosomes were not identified, but the tissue was poorly preserved. A few lysosomes were seen. The histologic diagnosis was malignant myoepithelioma. The sentinel axillary lymph node was examined and was negative.
Julianna Pope	25	1978/7/30	+1-853-274-0592x849	[email protected]	6364 Grant Glen Suite 190	A 33-yr-old woman was admitted to Department of Hepatobiliary Surgery at Cancer Hospital of Tianjin Medical University, China, with the diagnosis of hepatic hamartoma. Eight years previously, she was diagnosed with hepatic hamartoma by fine needle biopsy. She did not accept effective treatment, and subsequently presented with epigastric distention. A history of hepatitis (HBV, HCV) and hepatic cirrhosis were excluded with appropriate tests. Physical examination revealed slight paleness of the skin and mucosa and no jaundice. Abdominal palpation demonstrated the presence of shifting dullness and hepatomegaly without obvious tenderness. No other abnormal signs were found. The patients' blood results were as follows: Hematology; RBC: 3.64 ? 1012/L, Hb: 61 g/L, WBC: 4.40 ? 109/L and PLT: 126 ? 109/L. Biochemistry; showed: ALT 23 U/L, AST 35 U/L, ALP 386 U/L, ALB 28.0 g/L, TP 50.4 g/L, GLB 22.4 g/L and GGT 254 U/L. Serum markers for HBV and HCV were negative. AFP, CA125, CA199 and CEA were normal. Both ultrasonography and spiral computerized tomography (CT) revealed an enlarged liver with rugositied surface. Multinodular focuses involved the whole liver accompanied with calcified plaques, cholecystolithiasis, multiple tiny nodules under the peritoneum and ascites (figure ). After a multidisciplinary consensus, the patient underwent surgery including omentectomy and excisional biopsy of liver tumors. In the operation, asymmetrical nodules were noticed on the whole liver and beneath the peritoneum. One was located at colic omentum with 1.5 cm diameter. Frozen section biopsy revealed angiosarcoma. Therefore, only colic omentum resection and hepatic multi-point biopsy were performed. Postoperative pathology revealed angiosarcoma (figure ) arising from hepatic hamartoma (figure ) accompaniedwith coelio-implantation metastasis. Subsequent immunohistochemistry revealed the lesions were CD34(+) (figure ), Vimentin(+) (figure ), S-100(-), CEA(-) and CK(-) (Zymed). The patient survived 4 months after surgery, and died from liver failure.
Gunnar Patel	38	1977/9/22	001-221-651-5894	[email protected]	621 Moran Lights	A 16-year-old boy presented with a history of headache of 8 months duration, progressively decreasing vision for 3 months and more recently had an episode of generalized seizure 1 month back. Neurological examination did not reveal any focal neurological deficit except bilateral papilledema on fundus examination. MRI scan revealed a large 10 ? 8 cm extra-axial hyperintense contrast enhancing mass lesion on the T1-weighted image, occupying the anterior cranial compartment [Fig ]. The tumor was compressing the frontal horns of lateral ventricles along with anterior part of corpus callosum. It was also seen encroaching upon the superior saggital sinus. A bifrontal free bone craniotomy was performed and total excision of the tumor was achieved. Intraoperatively, the tumor was seen adhering to the frontal bone, a part of which was excised with the tumor. Gross examination of the resected tumor showed a 10 ? 8 ? 2 cm soft tissue with its cut-section showing grayish-white, irregular surface with focal necrosis [Fig ]. Histopathological examination revealed a tumor tissue composed of sheets of cells arranged in perivascular pseudopapillary pattern [Fig ] along with few well formed papillae with central fibrovascular core [Fig , inset]. These papillary structures in some places were mixed with meningothelial sheets and whorls. The tumor cells in the papillary area displayed abundant eosinophilic cytoplasm, vesicular nuclei but frequent mitoses and foci of necrosis. MIB-1 labeling index was high with mean LI of 12% [Fig ]. Immunohistochemical positivity to epithelial membrane antigen (EMA) [Fig ] and vimentin was seen while Cytokeratin (CK), GFAP and S100 were non-reactive. A pathological diagnosis of Papillary meningioma, WHO grade 3 was given.
Madeline Cain	37	1987/12/30	313.931.4919x8598	[email protected]	1603 Clark Locks	A 64-year-old man was diagnosed 6 years earlier with cirrhosis secondary to chronic hepatitis B. He was noted to have splenomegaly in a routine follow up. Laboratory data were as follows: aspartate aminotransferase, 126 U/litre (normal, < 40); alanine aminotransferase, 66 U/litre (normal, < 36); alkaline phosphatase, 123 U/litre (normal, < 96); and 帠-glutamyltransferase, 178 IU/litre (normal, < 96). Serum fetoprotein was 256 弮g/litre (normal, < 20). Serum hepatitis B virus surface antigen was positive and antihepatitis C virus antibody was negative. Magnetic resonance imaging of the abdomen showed an approximately 3.5 cm in diameter with a heterogeneous, hypervascular enhancing mass in the left lateral segment of the liver. A multiple, small-to-moderate nodules composed of a low-density area throughout the parenchyma was present in the enlarged spleen. There were no tumor thrombi within the portal veins and lymphadenopathy (Figure ). Positron emission tomography findings revealed the ringed dense uptake of 18F-fluorodeoxyglucose in the spleen. It was not absorbed in the lymph nodes of the splenic hilus and behind the pancreatic head; there were no abnormal hot areas in the liver. After the liver tumor and spleen were resected, the serum fetoprotein concentrations returned to within the normal range. However, the patient who was treated symptomatically and not treated with chemotherapy due to poor general condition died 6 months after surgical resection. Grossly, the resected liver tissue measured 10 ? 7 ? 5 cm. There was a well circumscribed tumor measuring 4 ? 3 ? 3 cm. The mass was grey and soft with a small area of bleeding, necrosis and intact capsule. The non-tumorous portion showed obvious cirrhotic nodularity. The resected spleen measured 25 ? 17 ? 7.5 cm and weighed 1750 g. The outer capsule was smooth, glistening, and intact. Cut surface of the spleen was red-purple and had a diffuse reticulonodular appearance indicative of prominent white pulp. Splenic hilar and mesenteric lymph nodes were not enlarged obviously. On histologic sections, the tumor cells were growing in cords of variable thickness, which were separated by sinusoid-like blood spaces in the liver mass. Diffuse fatty change of tumor cells was found in small area (Figure ). The non-tumour part showed cirrhotic change. The tumor in the spleen was characterised by a micronodular lymphoid infiltrate located in white pulp, with variable red pulp infiltration, marginal zone differentiation and follicular replacement by neoplastic cells (Figure ). The white pulp tumoral nodules were composed of an inner central zone of small lymphocytes, located in the mantle zone and replacing the germinal center, and a peripheral zone of medium-sized cells with clear cytoplasm and scattered blasts (Figure ), the marginal zone component. Splenic hilar and mesenteric lymph nodes were not effaced with intact capsules, sinuses, and germinal centers. Immunohistochemical staining of the neoplastic cells showed positivity for CD20, CD79帢 (Figure ), Pax-5, bcl-2 and lacked co-expression of cyclin D, CD30, CD3, CD5, bcl-6, bcl-10, CD68, and cytokeratin, indicating that the tumor was B-cell lymphoma. The proliferative index is low, and Ki67 staining showed a distinctive annular pattern, outlining the presence of an increased growth fraction in the germinal center and marginal zone. Amplification of Immunoglobulin heavy chain genes was performed by semi-nested PCR, using primers directed to the framework 2 (FR-2) region and to the joining region (JH) as described previously [,] Gene rearrangement studies also supported a clonal B-cell process with heavy chain rearrangement (Figure ). Therefore, the liver mass was well and moderately differentiated HCC, the diagnosis of SMZL was made from the splenic specimen. The final pathological diagnosis was coexistent SMZL with HCC in the course of chronic HBV infection.
Benson Leon	29	2005/2/10	+1-459-939-6263x8641	[email protected]	71660 Kelsey Street	In August 2000, a 37 year old Native-American male received a cadaveric liver transplant after approximately 20 years of chronic HCV infection, genotype 1a. He was a former intravenous drug user (IVDU) and had been enrolled in a MMT program since 1990, taking between 80 and 100 mg methadone daily. He also had a history of anxiety and mood disorders, and had been taking clonazepam, 1 mg 4 times daily since 1999. At transplant evaluation, the patient had solid psychosocial support (family and counseling) and had a consistent ten year adherence to his MMT, including negative toxicological screens. The UCDMC transplant team determined that it would be in the patient's best interest to continue his MMT pre and post transplant. The patient had a MELD score of 15 at the time of transplant. He tolerated the operation well with no major complications during surgery, although he did require more intraoperative anesthesia than the average non-MMT patient. Post-operative pain management during hospitalization required consultation with pain specialists and the doses of hydromorphone and morphine were higher than the average non -MMT transplant patients. On post-operative day six, the patient resumed a normal diet; his pain was managed with oral narcotic analgesics; he was fully ambulatory and was discharged from the hospital. Immediately post-transplant, the patient's methadone was 100 mg daily. In June 2001, the patient showed biopsy proven recurrent HCV in the transplanted liver. There were no signs of rejection. The patient was continuing MMT ~80 mg daily and was compliant with his immunosuppressive therapy and transplant follow up care. In January 2002, the patient began HCV treatment using an escalating regimen of INF combined with RBV. He reached full dose INF (3 MIU three times per week) and RBV (1200 mg daily) at approximately 10 weeks of treatment. The intention was to treat for 48 weeks on combination therapy. The patient started treatment with a low viral load (410,760 IU/mL). At approximately six months of therapy, he was HCV-RNA quantitatively virus negative. Overall, the patient had common side effects to the combination therapy. His physical symptoms included fatigue, nausea, headaches, and flu-like symptoms. These side effects were treated symptomatically and either resolved or were well-tolerated. Although the patient was taking immunosuppressive drugs throughout his HCV therapy, his white blood cell and absolute neutrophil counts remained stable. By treatment week 12, he did experience significant hemolytic anemia (Hgb 10.7 g/dL) and was started on 40,000 units per week of erythropoietin. The patient's RBV was reduced to 800 mg daily for two weeks and then was increased to 1000 mg daily for the remainder of treatment. Due to a history of anxiety and mood disorders, the patient was started on low dose antidepressants, citalopram 10 mg daily, three months prior to starting treatment. Additionally, the patient experienced psychiatric side effects to IFN/RBV including mood swings, angry outbursts, insomnia, and forgetfulness. His citalopram, 10 mg daily, was increased twice (20 mg daily at week 12 and 40 mg daily at week 40). Quetiapine, 25 mg 1?? tabs daily, and bupropion, 150 mg twice daily, were also added halfway through treatment to further control these psychiatric side effects. These additional psychotropic medications were managed in conjunction with the patient's methadone clinic; during treatment the patient's methadone was gradually increased from 84 mg daily to a maximum of 110 mg daily. Twenty-four weeks after treatment, the patient's methadone was reduced to 80 mg daily and has incrementally decreased to his current dose of 4 mg daily in 2006. The patient has continued to take clonazepam, 1 mg 3 times daily, and quetiapine, 50 mg daily, post treatment. In 2004, he was able to find a job after many years of unemployment. In 2006, four years after treatment, he continues to be: (a) HCV free with annual liver biopsies showing no signs of disease or fibrosis, (b) stable on immunosuppression, (c) on minimal doses of methadone (15 mg/d), and (d) compliant with medical advice and medications.
Amora Lucas	40	1989/4/24	(858)568-3709x65505	[email protected]	1623 Williams Courts Apt. 845	A 54-year-old man was admitted for ascites and acute renal failure revealing Child-Pugh stage C13 alcoholic cirrhosis. A liver biopsy showed severe acute alcoholic hepatitis and treatment with prednisolone 1 mg/kg a day was started. Human immunodeficiency virus (HIV) serology was negative, as were viral hepatitis B (HBV) and viral hepatitis C (HCV) tests. Over the following 21 days, four episodes of hemorrhagic shock from grade II esophageal varices occurred. A transjugular intrahepatic portosystemic shunt was placed on day 21. On day 22, severe sepsis developed with middle lobe alveolar consolidation on the chest x-ray. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) was performed before initiating empirical antibiotic therapy with piperacillin-tazobactam and ofloxacin. Microbiological examination of the BAL fluid evidenced the presence of mycelia, hence the addition of fluconazole to the treatment. On day 23, the patient deteriorated and was admitted to the ICU (Simplified Acute Physiology Score II -SAPS2-61, Organ dysfunction and/or Infection -ODIN 4/7). The chest x-ray radiograph showed bilateral diffuse alveolar opacities. The patient was mechanically ventilated (PaO2/FiO2158 mmHg). The total neutrophil count was 21,000/mm3 (lymphocytes 219/mm3). Blood and urine samples, pleural and peritoneal fluids, and all catheters yielded negative cultures. Microbiological examination of repeated BAL fluid (performed on day 24) was negative, but the aspergillosis latex antigen agglutination test was positive at 1/256 (Platelia Aspergillus EIA for immunoenzymatic detection of galactomannan antigen of Aspergillus in serum; Bio-Rad, Marnes la Coquette, France). Aspergillus serology was negative (Protide Immunoelectrophoresis Aspergillus FSK1-MICROGEN, Beckman-Coulter, Fullerton, USA). Blood aspergillosis antigen tests (Platelia Aspergillus EIA for immunoenzymatic detection of galactomannan antigen of Aspergillus in serum; Bio-Rad, Marnes la Coquette, France) were positive on two occasions (possible false positive in the first instance because of the administration of piperacillin-tazobactam [,]). Fluconazole was switched to intravenous voriconazole (loading dose 400 mg two times on day 1, maintenance dose 200 mg twice daily) on day 27. The patient died on day 29. The family refused necropsy.
Chance Knox	43	1989/10/24	764-470-8031x687	[email protected]	68935 Reese Brooks	A 55-year-old man was first admitted for severe pneumonia with rhabdomyolysis, acute renal failure and encephalopathy, revealing Child-Pugh stage C12 alcoholic cirrhosis. Empirical antibiotic therapy with piperacillin-tazobactam and ofloxacin was started. The serology tests for HIV, HBV and HCV were negative. On day 2, septic shock developed and the patient was transferred to the ICU (SAPS2 92; ODIN 5/7). He was mechanically ventilated (PaO2/FiO2 104 mmHg), placed under continuous hemodiafiltration, and received hemodynamic support plus intravenous hydrocortisone hemisuccinate (50 mg every 6 hours, 6 days). Upon the results of initial blood cultures idenfying Streptococcus pneumoniae as the likely cause of the pneumonia, antibiotic therapy was switched to high dose amoxycillin (6 g daily). The patient improved. He could be weaned from mechanical ventilation after two weeks, and from continuous hemodiafiltration after three weeks. Mechanical ventilation was resumed two weeks later because of a catheter-related Staphylococcus infection causing septic shock. After one additional week, new bilateral pulmonary infiltrates appeared. Microbiological examination of BAL fluid was negative for bacteria, while the histopathological examination yielded signs of alveolar damage with alveolar hemosiderosis (Golde score 38). At this time, the total leucocyte count was 8,600/mm3 (258 lymphocytes). BAL fluid and plugged telescopic catheter specimen grew Aspergillus fumigatus (five colonies). Two serum aspergillosis antigen tests were positive at a four days interval, both at 6.3 ng/ml (Platelia Aspergillus EIA for immunoenzymatic detection of galactomannan antigen of Aspergillus in serum; Bio-Rad, Marnes la Coquette, France). Aspergillus serology was negative (Protide Immunoelectrophoresis Aspergillus FSK1-MICROGEN, Beckman-Coulter, Fullerton, USA). Intravenous voriconazole was prescribed (loading dose 400 mg two times on day 1, maintenance dose 200 mg twice daily) but the patient developed multiple organ failure and died on the second day of this treatment. The family refused necropsy.
Kallie Gallagher	40	1998/4/21	(282)541-2747x782	[email protected]	7493 Mason Canyon Suite 093	A 64-year-old woman with a C14 alcoholic cirrhosis (Child Pugh score) and a histologically proven alcoholic hepatitis was admitted after one month of oral corticosteroid therapy, with a diagnosis of hepatic encephalopathy, in the context of a Klebsiella urinary tract infection. Amoxicillin/clavulanic acid was prescribed. The serology tests for HIV, HBV and HCV were negative. Over the week following admission, the patient developed acute respiratory failure, with bilateral pulmonary infiltrates and severe hypoxemia (PaO2 57 mmHg with oxygen 10 L/min). There was fever (38.5簞C) and a total leucocyte count of 10,100/mm3 (300 lymphocytes). The patient was transferred to the ICU (SAPS2 39, ODIN 3/7) and fiberoptic bronchoscopy was performed. Microbiological examination of BAL fluid and bronchial aspiration showed hyphae, and both types of sample grew Aspergillus fumigatus. No other infectious agents were identified. Aspergillosis antigen tests were negative (Platelia Aspergillus EIA for immunoenzymatic detection of galactomannan antigen of Aspergillus in serum; Bio-Rad, Marnes la Coquette, France). The Aspergillus agglutination test was positive with one arch and a titer of 1/320 (Protide Immunoelectrophoresis Aspergillus FSK1-MICROGEN, Beckman-Coulter, Fullerton, USA). Intravenous voriconazole was prescribed (loading dose 400 mg two times on day 1, maintenance dose 200 mg twice daily). The patient developed multiple organ failure with severe hepatic dysfunction and died 2 weeks after admission (third day of voriconazole treatment). The family refused necropsy.
Marcos Norman	42	1977/12/8	001-423-262-7231x554	[email protected]	9531 Miller Ridge Apt. 385	A 23-year old male patient who had severe mandibular hypoplasia referred to the Department of Oral and Maxillofacial Surgery for treatment. His main complaints were unaesthetic appearance, snoring, wheezing, and difficulties during respiration, speech, and chewing. In the extraoral examination, severely convex profile with a receding chin and a prominent nose was observed. Intraoral examination revealed a Class II Division I malocclusion with an excessive overjet. Maxillary arch had a triangular form. Right lateral incisor was missing, mild rotation of the left central incisor, palatoversion of the left lateral incisor and buccoversion of the left canine were observed due to arch length deficiency. Lower second premolars, first and second molars were missing at both sides and first premolar was also absent at left side. Mesial tipping of right and left third molars was observed due to missing of the adjacent teeth (Figure , , and ). To determine the skeletal deformity, cephalometric analysis and measurements on stereolithographic three dimensional skull prototype model obtained through three dimensional computerized tomographic images of the patient were used. The stereolithographic model was built by Spectrum Z510 Color 3D Printers (Z Corporation-Burlington, USA). Cephalometric analysis indicated severe skeletal Class II discrepancy confirmed by an ANB of 13簞. Point A and point B were 6 mm and 42 mm behind the nasion vertical (NV), respectively. These norms supported each other and revealed that the patient had a severely retruded mandible. Ramus length (Ar-Go) was 41 mm and corpus length (Go-Gn) was 49 mm revealing deficiency of both ramus and corpus. Increases in the mandibular plane, gonial angle and Y-axis emphasized the posterior rotation of the mandible. The anterior facial height was 129 mm, posterior facial height was 64 mm and the ratio of these values was 49.61 % revealing that the patient had a long face. Overjet and overbite were measured as 15 mm and 4 mm, respectively. The cephalometric landmarks used in our report are demonstrated in Figures , and and the pre and post treatment measurements of the cephalograms are presented in Table . Ramus and corpus lengths were also measured on the stereolithographic models. The preoperative distance between condyle and gonion was 50 mm and the distance between gonion and menton was 69 mm for the right side. They were 44 mm and 68 mm, respectively for the left side. The patient had severe mandibular hypoplasia due to inadequate ramus and corpus length, therefore using an extraoral multiplanar distractor was inevitable. Tritrac簧 External Distractor (Ucmed Medical Ltd. Co.-Ankara, Turkey) was used for the treatment of the presented case. Preadjusted appliances (0.018 ? 0.022 inch) were placed in the maxillary and mandibular arch and open coil spring was used to open space for the left lateral incisor. Following the leveling phase, 0.016 ? 0.022 inch arch wires were placed on the upper and lower teeth. Because of the limitation of the mouth opening, nasotracheal intubation was performed with fiberoptic bronchoscope. Under general anaesthesia, after completing the intraoral incisions and exposing the cortex of mandibular corpus and ramus on both sides, the device was secured to the mandible via 6 percutaneous pins. This system had 3 pairs of pins to be secured; one pair to the ramus, the other to the angulus and the last one to the corpus region inferior to the mandibular canal. During this procedure extraoral incisions and trochar were used. The mandibular osteotomy was then performed with round and fissure burs and osteotomes. Two osteotomies on each ipsilateral side were planned. One of the osteotomies was on the ramus and the other one was anterior to the second molar. After the completion of the osteotomies, the distractors were tested and were placed paralell to each other. Then, the incisions were primarily closed. A 7 days of latency phase was waited for callus formation. Afterwards, distraction was performed at a rate of 0.5 mm, twice a day. Ramus was distracted for 7 days and corpus was distracted for 45 days. While the corpus was being distracted, the angles of distractors were reduced 5簞 on days 10, 20, 30, 40 so as to decrease the gonial angle. Paralellization of the distractors were protected during this procedure. Once the desired bone length had been acquired, 3 months of consolidation was allowed. Following the consolidation phase the distractor was removed under local anaesthesia and the extraoral wounds were debrided and primarily closed and left for recovery. The patient used class II intraoral elastics at night time in order to prevent relapse and elastic traction was completed after 3 months. The patient was followed-up for one more month in order to determine whether relapse would occur. Brackets were debonded 4 months after consolidation period. The total treatment time was 14 months. Finally the prosthetic rehabilitations of the missing teeth in the mandible were solved with stationary restorations.
Malani Swanson	43	1994/1/6	731-262-5390	[email protected]	92366 Jennifer Glens Suite 258	A 51-year-old female patient presented with a mass originating from the posterior wall of the right external auditory meatus. She had a history of progressive right sided hearing loss and recurrent external otitis over a period of 12 months. Physical examination revealed an ovoid mass covered with normal skin without any pigmentation or ulceration. The mass completely obliterated the lateral half of the right external auditory meatus hindering the visualization of underlying tympanic membrane. Pure tone audiometry revealed a mild conductive hearing loss on the lesion side. Computer tomography (CT) scan of the temporal bone demonstrated a well-circumscribed soft tissue mass, 16 ? 17 mm in size in the lateral part of the external auditory canal posterior wall (Fig. ). The mass showed patchy contrast enhancement with no invasion of middle ear or surrounding bone/cartilaginous structures. An excisional biopsy via transmeatal approach was performed under local anesthesia. The mass was totally removed while preserving the integrity of the overlying skin and the surrounding osteocartilaginous structures. At the end of the operation medial half of the canal wall and the tympanic membrane were seen to be intact and disease-free. Diagnosis was reported to be schwannoma by histopathologic examination (Fig. ). Schwann cells arranged in the 2 characteristic patterns referred to as Antoni A and B. Immunoperoxidase staining demonstrated a strong positivity to S-100 protein. There were no signs of local recurrence or narrowing of the external auditory canal during a 6 months of follow-up period.
Hugo Conrad	41	2001/8/18	+1-624-552-9849x9774	[email protected]	7050 Vasquez Corners Suite 785	Case 1, a 51-year-old male, had been employed in the plant since 1986 and moved to the unslaked lime process with two other co-workers in July 2000. In April 2001, he had a single episode of chest pain. In early May, while he was hospitalized for the operation of sudden onset retinal detachment, his liver function was abnormal [aspartate aminotransferase (AST), 317 IU/L; alanine aminotransferase (ALT), 156 IU/L; alkaline phosphatase (ALP), 225 IU/L; total bilirubin, 2.2 mg/dL]. Ten days later his liver function was improved. He returned to work in the separator process in September, and then moved to the dry evaporative incinerator in October. However, his liver function worsened in November and peaked in December (AST, 482 IU/L; ALT, 507 IU/L). After stopping work, his liver function normalized.
Bexley Rosas	35	1989/4/25	(786)568-0239x2997	[email protected]	101 Burke Views	Case 3, a 41-year-old female, had been a repair and maintenance worker since 1993. In early July 2001, she felt severe fatigue and took two packs of herbal medicine given to her by case 2. On 14 July, her liver function test was normal. However, 1 week later her urine darkened and jaundice developed in her eyes. She was admitted to the hospital on 30 July with markedly increased liver enzymes (AST, 1,670 IU/L; ALT, 1,223 IU/L; ALP, 495 IU/L). Her condition improved steadily, and she was discharged on 19 September 2001. After returning to her job for 3 days, she felt so fatigued that she did not return to the workplace afterward.
Remi Vega	21	1985/12/13	751-764-6504	[email protected]	6921 Davis Street Apt. 187	Case 5, a 26-year-old male, was employed in February 2001 and had been working in the dry evaporative incineration process. He was admitted to the hospital on 20 October 2001 due to jaundice and severely abnormal liver function results (AST, 1,336 IU/L; ALT, 1,368 IU/L; ALP, 198 IU/L). His condition improved, and he was discharged 8 November. summarizes the employment and exposure history and clinical characteristics of cases 1??. presents the clinical course of the cases as shown by AST concentration. Liver biopsy was performed on all but one case (case 2) in December 2001 (). The pathologic findings showed diffuse spotty hepatocytic necrosis. The portal tracts were slightly enlarged, and inflammatory infiltration was present in all cases. Clumped Kupffer cells containing periodic acid-Schiff (PAS)-positive material were abundant, especially around the terminal hepatic venule (). These findings were compatible with the remission stage of acute hepatitis and also with toxic hepatitis. Wide periportal necrosis was also identified in cases 1 and 4 (), and necrosis was found in the central-to-portal or portal-to-portal region, with bridging necrosis in all cases (). In case 4, regenerative nodules were present, suggesting the development of cirrhosis. Cholestasis and fatty changes were also evident in cases 4 and 3, respectively. Markers for hepatitis A (anti-HAV IgM) and B (HBsAg, HBeAg, anti-HBs, anti-HBc IgM) were negative in all cases. Anti-hepatitis C (anti-HCV) was positive in one case (case 1), but HCV was not detected on polymerase chain reaction (PCR). This study was approved by the institutional review board of Dongguk University, Gyeongju Hospital. Written informed consent was received from all of the cases.
Dakota Calderon	43	1995/6/16	750-360-0684	[email protected]	426 Cox Isle Apt. 583	In March 2002, a 27-year-old man presented with sudden loss of central vision in the right eye. Visual loss in the left eye followed within 18 days. At the time of onset, the patient was a very light occasional drinker and a moderate smoker (15 cigarettes/day for 5 years; unfortunately, cotinine and trans-3??hydroxycotinine were not measured to assess tobacco smoke exposure). He suffered from chronic headaches, which responded to common painkillers. The headaches had reportedly worsened when he started work in a glue factory in 1998 (he had previously been an electrician) and worsened remarkably when he was transferred to the glue preparation department, where he had worked for 6 months before the loss of vision. At fundus examination, both eyes showed micro-angiopathy and pseudoedema of the optic disc. A cycle of corticosteroids was ineffective at this time. One month later, visual acuity was 1/100 in the right eye and 7/10 in the left eye. We observed the patient in June 2002 and found a bilateral paleness of optic discs and the inability to count fingers with either eye; at that time, the patient complained of disturbing photopsias. A therapy with idebenone (270 mg/day) and brimonidine (2 drops, 3 times/day) was initiated (; ). Mitochondrial (mt) DNA testing on a blood sample was positive for homoplasmic 11778G ??A/ND4 mutation. Haplogroup definition showed that this patient? mtDNA belonged to haplogroup H (DdeI 10394-, AluI 7025-, MseI 14766-) (). These findings are consistent with a diagnosis of Leber hereditary optic neuropathy (LHON), a maternally inherited loss of central vision that preferentially affects young men (); three mtDNA point mutations (positions 11778G ??A/ND4, 3460G ??A/ND1, and 14484T ??C/ND6) are found in over 90% of patients worldwide. Until January 2003, visual function progressively deteriorated, reaching almost complete loss of vision (apart from hand motion) with rapid, involuntary eyeball oscillation (nystagmus). Progression of the fiber loss was documented by serial optical coherence tomography (). shows the retinal nerve fiber layer (RNFL) thickness in each quadrant, as measured by optical coherence tomography, for each of the patient? eyes after 9, 10, and 15 months, alongside values for historical groups of healthy subjects and of patients in an advanced stage of LHON (with atrophy of the optic nerve) (). Compared with the control group, both of the patient? eyes at 9, 10, and 15 months follow-up showed a progressively thinner RNFL in all quadrants. By January 2003 (10 month follow-up), the patient needed assistance to walk. After June 2003, he reported a slow but progressive improvement. A full clinical reevaluation was performed in September 2005; abnormal findings were limited to poor visual acuity, pale optic discs, and sluggish pupillary light reaction. On a standardized cycloergometer test (), serum lactic acid levels were almost normal (11.5, 11.9, 23.0, and 13.0 mg/dL; normal range, 5.8??2.0 mg/dL). Folate and vitamin B12 were normal, whereas creatine phosphokinase was high (289 U/L; normal value, < 170 U/L). Muscle biopsy showed nonspecific changes, with an observable parcellar subsarcolemmal increase of succinic dehydrogenase staining, indicating some mitochondrial proliferation. The patient is now able to count fingers and is without nystagmus (both eyes). He is able to walk without assistance and is continuing the same treatment. Because the mutations associated with LHON affect complex I subunits and, in most families, are homoplasmic (100% of mtDNA copies are mutant), we performed genealogical reconstruction for the maternal lineage of the patient? family. After obtaining informed consent, we collected blood from the patient? siblings and mother for mtDNA testing by restriction fragment length polymorphism analysis, as described by . These subjects were unaffected carriers of the homoplasmic 11778/ND4 LHON mutation. No history of occupational or environmental exposure to solvents (or other particular toxic substances) was reported for any of the family members tested (). These results are in accordance with the current concepts regarding LHON; the mtDNA mutation is a necessary but not sufficient condition for LHON, and only a minority of carriers develops optic neuropathy. Penetrance is incomplete (and lower in women), implying that additional mitochondrial/nuclear genetic factors and possibly also environmental factors contribute to phenotypic expression of LHON (); however, these triggering factors are poorly defined. Between 1998 and 2000 the patient had worked in the ?ot-melt??department, where he controlled hot layering of a synthetic adhesive containing styrene-isoprene copolymer, isopropilic alcohol, toluene, xylene, and octanes. An environmental exposure assessment requested by factory inspectors in 2003 indicated vapor levels of the individual solvents were 10??0% of American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit values (TLVs) (). During 1998??000, the patient recalled experiencing nausea, dizziness, asthenia, and paresthesia of the upper and lower limbs (in addition to chronic headaches) whenever he had to clean the machines? task he performed using a mixture of styrene, isopropilic alcohol, toluene, xylene, and octanes. In 2000??001 the patient worked in the rubber-mincing department, where he was indirectly exposed to n-hexane and toluene (no quantitative data are available). In the glues preparation department, where the patient worked from October 2001 to March 2002, exposure to n-hexane and toluene was presumably more direct because of the nature of his duties: He prepared coloring mixtures containing rubber, hydrocarbonic resin of toluene, and n-hexane in a closed production cycle, and he opened dissolver machines 5 times/day to determine if the tanks were empty. The only available environmental monitoring data for the department (again requested post hoc in 2003) report peak values of 10.7 mg/m3 for n-hexane (ACGIH TLV, 176 mg/m3) and 1.5 mg/m3 for toluene (ACGIH TLV, 188 mg/m3). In this department, the patient reported constantly feeling nauseous and dizzy. Also, during the 6-month period, four overflow accidents occurred, each reportedly followed by several hours of intensified dizziness and nausea, asthenia, tingling of the upper and lower limbs, and dysesthesia of the hands (the same set of symptoms the patient recalled experiencing after using solvents for cleaning tasks in the hot-melt department). Biological monitoring data routinely collected throughout the period of employment indicated that after the patient moved to the glue preparation department, he had a > 4-fold increase in urinary 2,5-hexandione (a neurotoxic metabolite of n-hexane) from 0.5??.9 to 4.1 mg/L, accompanied by a > 1.5-fold increase in urinary hippuric acid (a toluene metabolite) from 360??00 to 1,040 mg/L (roughly corresponding to an increase from 0.26??.5 to 0.74 g/g creatinine).
Oakley Moses	32	1998/8/31	+1-473-367-3011x781	[email protected]	271 Blair Mill Suite 100	A 22-year old woman was seen in the emergency department with acute onset of intractable nausea and vomiting. Nausea and vomiting were predominantly post-prandial and seemed to respond partially to metoclopramide. Over the next few weeks she also developed dysphagia, blurry vision, paresthesias involving her lower and upper extremities, and problems with balance. Physical exam was significant for nystagmus on lateral gaze, quadriparesis, absent deep tendon reflexes in all four extremities, a negative plantar reflex, and a positive finger-nose test. No history of vertigo was obtained, cranial nerves were intact, and fundoscopic examination was normal. Her hospital course was complicated by renal failure secondary to dehydration, which subsequently resolved. She had a jejunal feeding tube (J-tube) placed for nutritional support. Laboratory analysis was significant for elevated creatinine initially which later resolved. Cerebrospinal fluid (CSF) analysis was remarkable only for oligoclonal bands (OB's). Magnetic resonance imaging (MRI) of the head and the cervical spine revealed a focal area of demyelination near the cervico-medullary junction (Figure ). There was an interval increase in the size of this lesion over the next few weeks. A scintigraphic four-hour gastric emptying test (GET) was performed. The patient consumed a low fat (2%) Eggbeater meal (255 kcal) labeled with 1mCi99Tc sulfur colloid and 170 cc of water. 46% of the meal was retained at the end of 4 hours (Normal: < 10% retention at the end of 4 hours) Upper endoscopy (EGD) was negative for gastric outlet obstruction. As the patient's symptoms were worsening intravenous methylprednisolone at a dose of 1 gram daily for 2 weeks was instituted followed by a prednisone taper resulted in improvement in nausea, vomiting, and other neurological deficits. The total duration of corticosteroid use was for two months. A repeat MRI after treatment showed resolution of the lesion in the medulla (Figure ). A follow up GET was normal with 8 % retention of the radionuclide meal at the end of four hours. After the patient's oral intake improved and she could keep up with her nutritional requirements, the J-tube was discontinued after 6 months of initial presentation. At the 1-year follow up visit the patient had no neurological or gastrointestinal (GI) complaints, was off all medications, actively employed, and functioning with no complaints.
Karter Powers	19	2000/3/18	215.494.1733x03838	[email protected]	18998 Richardson Hollow	A 24 year old woman was referred to our hospital with symptoms of persistent post-prandial nausea, vomiting, new onset right sided weakness, and paresthesias. Symptoms started 2 weeks prior to presentation. Physical exam was positive for facial nerve palsy on the right side, reduced motor strength in the right upper and lower extremities, absent deep tendon reflexes on the right side, plantar- flexor response, abnormal finger-nose test, and a broad-based unsteady gait. Fundoscopic examination was normal. EGD was negative. GET performed by the previously described technique was conclusive for gastroparesis with 83% retention of food at the end of four hours. MRI revealed demylenating lesions in distal medulla, extending caudally through the cervico-medullary junction. The patient was started on 1 gram of methylprednisolone daily intravenously for 10 days, followed by a tapering dose of oral prednisone and this resulted in a gradual improvement of her nausea, vomiting, and neurological symptoms. GET repeated after 10 days showed remarkable improvement with only 13% retention of food at the end of 4 hours. Three months later, she developed additional neurological symptoms and was diagnosed with multiple sclerosis (MS). No recurrence of GI symptoms was reported.
Sean Kent	18	1997/1/30	413-960-2957	[email protected]	4296 Oconnell Way	A 67 year-old male with a past history of angina and arthritis presented with a one week history of melaena and lethargy. He was found to be anaemic (Hb 6.7 g/dl, MCV 92.2 fl). Endoscopy revealed moderate haemorrhagic gastritis and a Campylobacter-like organism (CLO) -positive duodenal ulcer, but no signs of recent bleeding. His non-steroidal anti-inflammatory medication was stopped and eradication therapy prescribed. He remained an in-patient for one week, during which time seven units of blood were transfused to correct his Hb to 11.6 g/dl. Six weeks later he presented with abdominal pain and further melaena requiring a 2-unit blood transfusion. Endoscopy revealed mild antral gastritis and a normal duodenum but no source of bleeding. Colonoscopy was normal. Two weeks later endoscopy was repeated which showed a small amount of fresh blood in the duodenal bulb, but no obvious lesion was seen to account for the bleeding. Three weeks later, he remained symptomatically anaemic, requiring further blood transfusion. Because of the history of melaena he underwent a fourth endoscopy which revealed a small, highly vascular polyp in the duodenum just beyond the angulus which bled easily on contact. Multiple biopsies were taken. The endoscopist was concerned about the possibility of a pancreatic neoplasm eroding into the duodenum and therefore an abdominal CT was arranged. Surprisingly, this demonstrated a large left renal mass with evidence of left adrenal and lung metastases, and a polypoidal mass in the medial wall of the second part of the duodenum arising from the pancreas (Figure ). Histology from the duodenal polyp showed small, vacuolated, clear cells highlighted by immunostaining with CAM 5.2 and showing strong reactivity with Vimentin. These findings confirmed the diagnosis of metastatic RCC. Over the three month period from initial presentation to diagnosis he required transfusion of a total of twenty units of blood for recurrent symptomatic anaemia. Given the history of recurrent melaena, coeliac angiography was undertaken with a view to trans-catheter embolisation. This was performed successfully via occlusion of the anterior and posterior pancreaticoduodenal vessels using coils (Figure and ). He subsequently underwent palliative left nephrectomy and histology from the resected specimen confirmed a grade 2 clear cell variant of RCC. He completed a course of interferon therapy and was able to lead a normal life for approximately 18 months, with no recurrence of anaemic symptoms or melaena. He subsequently developed painful maxillary metastases for which he received a course of radiotherapy, but died at home nearly two years after his initial presentation.
Jazmine Harding	35	1979/5/13	595.386.3694x194	[email protected]	12964 Miller Cliff	A 75 year old male with a past history of left nephrectomy 9 years previously for RCC was referred for out-patient investigation of iron-deficiency anaemia (Hb 10.3, MCV 78.9). Gastroscopy revealed a CLO-negative duodenal ulcer. Duodenal biopsies were within normal histological limits. Proton-pump inhibitor and iron therapy was prescribed and the patient was scheduled for review in the out-patient department. He remained anaemic three months later and repeat gastroscopy and a colonoscopy were arranged. Colonoscopy was normal, but gastroscopy revealed a fleshy vascular polyp in the duodenal bulb which was biopsied. A CT scan of the chest and abdomen, and a bone scan revealed a pancreatic mass invading the duodenum (Figure ) but no metastatic disease elsewhere. Histology from the polyp showed multiple large clear cells which stained positively for MNF116 and Vimentin, confirming the diagnosis of metastatic RCC. The patient was unable to tolerate interferon therapy. He became jaundiced due to tumour invasion of the distal common bile duct which was managed successfully by endoscopic biliary stenting. He received a total of 13-units of blood for symptomatic anaemia around the time metastatic disease was diagnosed, but since being commenced on a proton pump inhibitor his haemoglobin has remained stable.
Brodie Prince	20	2001/8/7	527.464.3208x1951	[email protected]	1356 Henderson Viaduct Apt. 853	A 78 year-old male presented to the emergency department with a ten day history of mild abdominal pain, nausea, and distention, worsening over the last day. He did not recall having a bowel movement for at least three days. His past medical history was significant for hypertension, gout, osteoarthritis, and an eighty-pack year smoking history. He had no prior surgeries and took only a blood pressure medication. He guarded during physical exam, and his abdomen was noted to be quiet, distended, and tender to palpation, but without rigidity or peritoneal signs. His laboratory evaluation was unremarkable. The emergency department obtained a CT scan of his abdomen and pelvis, which demonstrated a large amount of free air and fluid, and a mass could be visualized within the lumen of the cecum. A surgical consultation was emergently obtained (Figure ). After fluid resuscitation, he was brought to the operating room for exploration, where we encountered a minimal amount of fecal contamination and perforation of the cecum. A six centimeter non-obstructive mass and a hard mesenteric nodule were found in the cecum just distal to the site of perforation. The remainder of the colon was palpated and noted to be full of hard stool but otherwise without obvious abnormalities. We proceeded with copious irrigation of the peritoneal cavity and performed a right hemicolectomy with primary anastamosis without difficulty. Post-operatively, the patient was extubated but progressed slowly. Final radiologic interpretation of the CT obtained on arrival additionally noted a mass in the tail of the pancreas, a finding the surgical team did not detect on the CT prior to surgery or grossly at exploration. Pathologic evaluation found that the cecal mass contained only tubulovillous adenomatous components and the perforated area demonstrated localized mucosal ischemia but had relatively sharp margins. Well-differentiated metastatic adenocarcinoma was found within the mesenteric nodule, without lymphatic components (Figure ). The primary tumor responsible for this metastatic nodule was not contained within the surgical specimen. The patient had a slow return of bowel function consistent with ileus, but his abdominal distention increased dramatically overnight on post-operative day five. A repeat CT demonstrated colonic distention proximal to a now apparent mass at the splenic flexure, with distal colon decompression, concerning for a large bowel obstruction (Figure ). The patient returned to the operating room for reexploration and resection of the obstructive distal colon mass missed at initial operation. At the second exploration, the entire colon was mobilized, and this time, a mass could clearly be palpated at the splenic flexure of the colon. Continued mobilization revealed that this mass involved the splenic hilum and tail of the pancreas. An en bloc resection of the pancreatic tail, spleen, and left colon was completed without difficulty, and primary anastomosis was completed (Figure ). The patient was extubated postoperatively and progressed more quickly this time. Final pathologic evaluation of the second specimen was surprising, consistent with mucinous pancreatic adenocarcinoma, extending into the splenic flexure of the colon (T3, N0, M1). At three-month follow up, the patient is doing well living in an extended care facility.
Greta English	42	1984/4/3	+1-305-238-7823x96898	[email protected]	2807 Fletcher Lock	The patient was a 41-year-old male who presented with pain in the nape of the neck of one week duration in December 2005. Also there was a history of headache on and off for the past one year and vertigo for two and a half years. Magnetic resonance imaging showed a predominantly solid tumor with ill defined margins. The mass showed a heterogeneous hyper-intense signal on T2 weighted images with no obvious cystic degeneration. It was occupying the cerebral parenchyma of the left temporal and parieto-occipital regions. There was involvement of posterior part of body and splenium of the corpus callosum with extension of the lesion across midline to the right parietal region. The left side of midbrain, thalamus and basal ganglia appeared distorted along with tentorial herniation. The posterior part of the body of the left lateral ventricle was compressed and the third ventricle was displaced to the right side. The tumor was close to but did not reach the cortical surface. Calcification and perilesional edema were absent (Figure ). Craniotomy was done with near-total excision of the tumor. There were no post operative complications and the patient was discharged after a few days. No radiotherapy was offered to patient and there were no signs of recurrence till last follow up.
Junior Clayton	38	1984/8/12	594-953-2136x54698	[email protected]	033 Christopher Falls Apt. 666	A 60-year old male was admitted in the emergency ward with the history of massive hematemesis the previous night. Patient had difficulty in swallowing and retrosternal discomfort for the past 2 months for which he was being treated. Once in the hospital there was no fresh bout of hematemesis. On admission the patient's pulse rate was 124/minute and blood pressure was 100/70 mmHg. Hemoglobin level was 9.9 g/dl and the white blood cell count was 13,200/cmm. The chest X-ray showed bilateral emphysematous bullae. Upper GI endoscopy showed esophageal ulceration at 32 cm. Contrast enhanced chest CT images acquired at thoracic region showed a penetrating aortic ulcer into the thoracic esophagus and focal anterior aortic defect with pseudo aneurysm formation [Fig , , ]. There was no pleural effusion. A diagnosis of aortoesophageal fistula due to penetrating aortic ulcer was made and the patient taken up for an emergency surgery. He was intubated with double lumen endotracheal tube. Left radial and dorsalis pedis arteries were cannulated for the arterial pressures monitoring of upper and lower body respectively. A pulmonary artery catheter was introduced. An epidural catheter was placed to facilitate cold saline irrigation of the epidural space during aortic cross clamping. Injection Methylprednisolone 1 G was given intravenously for spinal cord protection. While securing of the femoral artery and vein in the left groin was being done, thoracotomy was performed through a posterolateral incision. There was no hematoma or effusion or pus in the pleural cavity. Descending thoracic aorta was enlarged but not to aneurismal proportions [Fig ], the medial portion of the lower lobe of the left lung was adherent to the esophagus in the region of the fistula. Aorta was mobilized from the left subclavian artery to the diaphragm except for the area with dense adhesions that contained the fistula. Heparin was given at 1 mg/Kg and after obtaining an ACT of > 400 seconds and aortic cannulation was done distal to the left subclavian artery and also the left femoral artery cannulated using appropriate arterial cannulae and were connected by an 1/4th inch polyvinyl chloride [PVC] tube establishing an aortofemoral shunt. The aorta was cross-clamped and the intercostals arteries were controlled with micro bulldog clamps. The distal aortic pressure maintained between 60 to 70 mmHg. Aorta was opened with a longitudinal incision and the aneurismal mouth was seen in the anteromedial aspect measuring 3 cm ? 2 cm in size and oval in shape [Fig ]. The base of the ulcer was filled with clots. Rest of the aorta appeared normal and edge of the defect appeared healthy. The defect was closed with a gelatin sealed Dacron vascular prosthesis [Vascutek Gelweave woven Dacron graft manufactured by Sulzer Vascutek USA, Inc., Austin, TX78752] cut into an oval shape measuring 3 cm ? 3 cm using 4/0 polypropylene continuous suture technique. The aortotomy was closed with 4/0 polypropylene sutures reinforced with Teflon felt on either side. Aortic cross-clamp was released and aortofemoral shunt clamped. The total cross-clamp time was 65 minutes. Heparin was reversed with protamine. Decannulation was performed and the femoral artery repaired with 6/0 polypropylene continuous sutures. Due to dense adhesions present between the pseudoaneurysm, the esophagus and the hilum of the left lung, further dissection of the esophagus was abandoned. A Ryle's tube was introduced and its' position in the distal esophagus confirmed by palpation. Chest and the mediastinum were copiously irrigated and drained with two 36 F chest tubes. Patient maintained stable haemodynamics with adequate urine output and was able to move both lower limbs. He was kept nil orally for the next 5 days with continuous Ryle's tube aspiration. Total parenteral nutrition was begun in the immediate postoperative period and he was maintained on peri-operative antibiotic coverage of Vancomycin, cefpirome, Metranidazole and Amikacin. The per-operative culture from the thoracic cavity revealed no growth of organisms 48 hours later. On the sixth postoperative day gastrograffin esophagography revealed no esophageal leak. A contrast enhanced CT scan of the chest revealed neither aortic nor esophageal leak [Fig. , ]. Patient was encouraged to take sips of sterile water. The patient was afebrile, tolerating soft diet and ambulatory on the ninth postoperative day when he was discharged from the hospital on an antihypertensive drug.
Saige Webster	22	1993/4/16	-6687	[email protected]	15409 Linda Cliffs	We present the case of a 65 year-old lady referred to us from a rural hospital where she was treated with thrombolytic therapy for a presumed acute anterior myocardial infarct. She had presented with central chest pain radiating down her left arm with ECG findings of 2 mm ST elevation in V2 and V3. There was no recent history of psychological stress although she had been on antidepressant drugs for two years. Four hours after thrombolysis she developed acute pulmonary oedema and a new systolic murmur. At this stage it was presumed she had acute mitral regurgitation secondary to a ruptured papillary muscle, ischaemic dysfunction or an acute ventricular septal defect. She was transferred on heparin and glyceryl trinitrate infusion, in acute pulmonary oedema (confirmed by chest X-ray), with a systolic blood pressure of 110 mmHg, and heart rate of 130/minute. Urgent echocardiogram showed severe mitral regurgitation (see Figure ). Her mitral valve annulus was slightly widened at 3.2 cm and subvalvular structures were intact. She also had left ventricular apical ballooning (LVAB) and systolic anterior motion (SAM) of the mitral valve leaflet with septal contact ??left ventricular outflow tract gradient (LVOT) 60??0 mmHg (see Figures and ). Coronary angiography fourteen hours after her presentation showed no obstructive coronary lesions. Ventriculogram revealed akinesis of the anterolateral wall and apex of her left ventricle, more extensive than any single coronary territory, and grade 4/4 mitral regurgitation (see Figures and ). She had an intra-aortic balloon pump (IABP) inserted and was transferred to theatre shortly thereafter. She was in cardiogenic shock, with severe MR and SAM still prominent, despite the IABP. We elected to replace her mitral valve, and at operation, the mitral valve was mildly myxomatous but there were no structural abnormalities, chordae and papillary muscles being intact. She had a mechanical mitral valve replacement (MVR) with a 29 mm St Jude valve. The anterior leaflet was excised and PTFE (gore-tex CV4) was used to reconstruct the subvalvular apparatus. The posterior leaflet was plicated to the annulus. Post-operatively there was no LV outflow obstruction and ventricular function improved to within normal limits by the 10th post-operative day. She recovered well.
Shawn Morgan	20	1987/9/29	2593700312	[email protected]	73048 Ballard Viaduct Apt. 897	A 62 year-old man with a history of hypertension, alcoholism, and mild renal insufficiency, presented to our hospital with a two-day history of fevers, lower back pain, and new onset of urinary retention. One week prior to admission, the patient had undergone diagnostic cardiac catheterization for new onset of atrial fibrillation and had been started on coumadin. Other medications prior to admission were digoxin, diltiazem, furosemide, lisinopril, metoprolol, omeprazole, simvastatin, coumadin. Vital signs on admission were: blood pressure 100/60, temperature 101.4簞F, heart rate 100, respiratory rate 20, He had an irregular heart rhythm without murmurs and mild right flank pain. There was a small non-tender and non-purulent ecchymotic area in the right groin at the site of previous catheterization. His neurologic exam was nonfocal except for new 4/5 bilateral lower extremity weakness. White blood cell count was 18.4 K/mm3, with 75% neutrophils and 12% bands. Hemoglobin and platelets were normal. Sodium 128 mmol/L, blood urea nitrogen 46 mmol/L, creatinine 1.7 mmol/L. INR was 11.21. Amylase and lipase were 557 and 325. A chest x-ray, and a computed tomography (CT) scan of the lumbar spine were unremarkable. A CT scan of the abdomen showed mild early pancreatitis without dilatation of the biliary tree. Blood and urine cultures were sent and the patient was diagnosed with mild pancreatitis and coagulopathy secondary to coumadin overdose. He was was started on intravenous levofloxacin 500 mg, with resolution of the fever by the next day. He received vitamin K and his coumadin was temporarily stopped.. Over the next days, his INR decreased to 1.3 and his abdominal pain and leukocytosis improved, but the back pain and urinary retention continued. By the sixth day of admission, he complained of stool incontinence. A magnetic resonance image (MRI) study of the lumbar spine showed inflammatory diskitis with fluid in the L5/S1 disc space, along with osteomyelitis and a posterior epidural abscess with moderate-to-severe vertebral canal stenosis. The Spine Surgery Service was consulted, but they felt that the neurological findings were not explained by the lesion seen on MRI and recommended non-operative management. Blood cultures from admission later grew Gram-positive bacilli, and repeat cultures confirmed Corynebacterium striatum bacteremia on the sixth day of admission. At this time, antibiotics were changed to vancomycin 1500 mg iv daily with subsequent improvement of the back pain, urinary retention and stool incontinence. Follow up blood cultures were negative. A transesophageal echocardiogram (TEE) revealed moderate aortic insufficiency and a 3?? mm vegetation on the non-coronary cusp of the aortic valve, with a perforation at the same site. Cardiovascular surgery recommended that a valve replacement be deferred pending initial antibiotic treatment. A follow-up MRI of the spine reported no significant change on the fluid collection. Surgery was offered, but the patient refused stating he felt decreased weakness and wanted to pursue a conservative management. Over the next days, the patient showed progressive improvement in his lower extremity strength and was able to ambulate with the help of a physical therapist. His urinary retention and bowel dysfunction improved as well. Three weeks later, the patient became febrile and acutely dyspneic. An emergent TEE showed an increase in the regurgitant jet through the aortic valve perforation. The patient underwent emergency coronary aortic bypass grafting and aortic valve replacement. Pathology of the aortic valve revealed a heavily calcified aortic valve, and the gram stain showed gram positive coccobacilli. Cultures of the valves were negative, however, the valve had been mistakenly placed on formalin prior to submission to the Microbiology Laboratory. The patient did well postoperatively and was discharged on intravenous vancomycin. At a two-month follow-up appointment the patient's back pain had resolved and an MRI showed resolution of the epidural abscess. Post treatment surveillance blood cultures were sterile after a total of 12 weeks of intravenous vancomycin after his discharge from the hospital. At follow up over two years later the patient remained infection free.
Delilah Andrade	23	1992/7/2	963-835-6538x3836	[email protected]	28272 Ruiz Mews	A 16-year old male, unrestrained passenger was a victim of high speed frontal collision of the car with an electricity pole, and 30 min thereafter was admitted to the emergency room (ER). On admission, he was complaining of thoracic and abdominal pain, and presented free airways, normal chest expansion, BP:70 ? 40 mmHg, HR: 120 bpm, RR: 18 epm, GCS: 15, RTS: 6.4, abdominal tenderness, and a closed right femur fracture. Plain X ray films suggested a widened mediastinum. After 3000 mL of warmed saline infusion, his BP was 60 ? 30 mmHg, and his HR was 120 bpm. A diagnostic peritoneal lavage was positive for blood. As ultrasonography was unavailable, a laparotomy was performed, with splenectomy and cauterization of a superficial liver injury. After infusion of 6000 more mL saline, 8 units PRBC, and 9 units fresh frozen plasma, the patient's conditions worsened, with muffled heart sounds, undetectable peripheral pulses, and CVP of 20 cmH20. Cardiac tamponade was suspected, and confirmed through a subxiphoid pericardial window. A thoracotomy was performed, with pericardiotomy and removal of blood clots from the pericardial cavity. A 0.5 cm bleeding tear in the apex of the RAA was found, and closed with sutures. The thoracotomy incision was closed. The patient was discharged from the hospital on the 20th postoperative day. His injury severity score (ISS) was 50, and his TRISSCAN was 0.31. The main data of this case are presented (see Table ) together with the main data of the 8 cases (cases 1 through 8) of isolated RAA rupture reported in the literature [,-]. Eleven other RAA cases mentioned in the literature without clear informative data are not included here [,]. The 9 cases (see Table) comprised 5 men and 4 women, aged 15 to 34 (mean: 28) years, all involved in high speed MVC (8 cars and 1 motorcycle). The victims were a motorcyclist (case 1), unrestrained car drivers (cases 2, 3, 4, 5, 8), or passengers (cases 7 and 9), or unspecified position (case 6). Overall, the main diagnostic findings in these 9 cases included hypotension or persistent unresponsive shock (cases 4, 5, 8, 9), muffled heart sounds (cases 1, 2, 3, 4, 9), high CVP values (cases 1, 3, 9), neck vein distension (cases 2, 5, 6), thoracic imaging alterations (cases 2, 4, 5, 6, 9), and traumatic ascitis (case 7). Cardiac tamponade was present in the 9 cases. All the patients underwent a thoracotomy allowing RAA injury identification and repair, and all patients survived. The length of hospital stay ranged from 8 to 20 days.
Abdiel Conley	42	1978/10/16	001-424-390-9288x3389	[email protected]	113 Lisa Forge Suite 093	A 6-day-old Pakistani boy was admitted to hospital in June 2005 for bleeding from the left nipple. His parents are first cousins. He has two siblings aged 8 and 6 years. There was no family history of bleeding diathesis. The mother had a normal pregnancy with full antenatal care. Mode of delivery at term was an elective Caesarean section due to previous Caesarean sections. His birth weight was 2.7 kg. 1 mg of Vitamin K was given intramuscularly at delivery. His first neonatal check was normal. He had a small amount of self-limiting bleeding from the umbilical cord on day 3 of life. He went home on day 4. On day 6 of life he had mild spontaneous left sided nipple bleeding, which presented as spots of blood stains on the left side of his baby dress. Over the next 7 days he had two further episodes of a similar nature. Baseline biochemistry and full blood count were normal but a coagulation screen showed a prolonged prothrombin time of 41 s (control 14 s), a prolonged partial thromboplastin time of 132 s (control 33 s) and normal thrombin time of 15 s (control 14 s). In view of the mild nature of bleeding, the child was only treated with 1 mg of i.v. vitamin K. Subsequent coagulation assays revealed a plasma factor V activity of less than 0.01 IU/ml (normal range 0.50??.50 IU/ml) determined by factor V clotting assay with all other coagulation factors in the normal range. Hence the diagnosis of congenital factor V deficiency was made. A cerebral ultrasound done at this stage was within normal limits. Oral transexamic acid at a dose of 15 mg/kg/dose 3 times daily was started. Mother was found to have a plasma factor V activity of 0.44 IU/ml (normal range 0.5??.50 IU/ml) and the father of 0.52 IU/ml by factor V clotting assay. Both levels are compatible with heterozygous factor V deficiency. The siblings had factor V activities of 0.61 and 1.1 IU/ml respectively. Genetic analysis at the St. Thomas Hospital hemophilia molecular genetics laboratory showed that the affected child is homozygous for a frame shift mutation resulting in a premature termination sequence at codon 2178 in exon 25 of the factor V gene and both parents are heterozygous for this mutation. The infant presented at day 15 of age with a further episode of bleeding from the umbilical stump. The bleeding stopped promptly following administration of 20 ml/kg of fresh frozen plasma (FFP, methyleneblue sterilized, single donor and US sourced). Small bruises were noted around the venepuncture sites from the previous admission. A hematoma measuring 2 cm in diameter was noted on the anterolateral aspect of the left thigh. It was attributed to the injection of vitamin K at birth. His head circumference was increasing within normal range and a repeat cerebral ultrasound was normal. The patient presented again at 5 weeks of age with pallor, irritability, lethargy and reduced feeding. His anterior fontanelle was bulging and tense. He was hemodynamically stable. His hemoglobin was 5.6 g/dl, which represented a significant drop from the previous estimation 3 weeks back. The cerebral ultrasound was repeated and showed a large intracerebral hemorrhage extending from the frontal lobe to the parieto-occipital region. There were a few cystic areas seen within this bleed, which suggested that the bleeding started at least a few weeks ago. The child was immediately transfused with 20 ml/kg of FFP and 15 ml/kg of packed red blood cells. He had a series of generalized fits within 5 hours of admission. The patient was transferred to the regional tertiary referral centre for specialised neurosurgical and haematological management. A cranial computed tomography (CT) scan showed a right, large, intracerebral bleed causing a shift of the midline to the left. The ventricles were not enlarged and the bleed did not extend into the ventricles (See Figure ). A Hickman line insertion was arranged to enable regular FFP infusions. Preoperatively he was transfused again with 20 ml/kg FFP and 10 ml/kg of platelet concentrate to achieve adequate hemostasis. Platelets are known to be a good source of factor V as it is stored in the platelet alpha granules. He was also given recombinant factor VIIa (Novoseven, NovoNordisk簧) as an empirical adjunctive agent in the peri-operative period in view of the fact that reliably hemostatic levels of factor V (0.25??.30 IU/ml) are difficult to achieve in this condition. Factor VIIa is unlikely to work in the absence of any factor V but can contribute to increased thrombin formation once factor V is present. Postoperatively a regime of FFP (15 ml/kg/dose) administration was set up: FFP twice a day for the first 10 days followed by once a day for the next 10 days. This was followed by at least alternate days (every 48 hours) of FFP at 20 ml/kg/day up to the present. Plasma factor V activity has been monitored: A maximum factor V level of 0.23 IU/ml was achieved within 20 minutes after transfusion. Trough levels were between <0.01 to 0.05 IU/ml. When undetectable factor V levels were noted inhibitor assays were performed. Inhibitors have not been detected so far. No further bleeding has been noted up to the present day. Immunisations including hepatitis B vaccination were given subcutaneously as is normal practice for children with severe bleeding disorders. Follow up until the present (21 months of age) revealed an appropriate increment in head circumference. Neurodevelopment has been within normal limits.
Salem Bradshaw	35	1992/4/8	373-601-7054x81823	[email protected]	4267 Benjamin Trace	The proband ??was a 19 year-old male, with no relevant personal or family history showing mild involuntary orofacial movements and chorea in all four limbs. Psychomotor assessment revealed no cognitive impairment. No psychiatric manifestations were evident and the Beck Depression Inventory Scale proved that there was no concomitant depression. EEG and brain MRI did not reveal any pathological findings. Normal EMG and NC activity was detected. Cardiomyopathy was excluded, fundoscopic examination showed no retinal degeneration, and the expression of the Kell blood group antigens was normal. Haematological parameters were within normal ranges, but a marked presence (95%) of abnormal shaped erythrocytes known as acanthocytes were identified on wet-film preparations. The patient's mother (age at examination: 37 years old) and sister did not show any neurological disorders, while a relevant presence of acanthocytic erythrocytes was observed in peripheral blood (35% and 39% respectively). A decreased content of 4.1R protein was evident in the patient, his mother, and his sister (Table ). A marked increase in spectrin dimers (35%, Reference Values < 15%) was apparent in the patient (Figure ). Self-association of spectrin dimers into tetramers is a critical interaction for membrane structure and function []. The percentage of spectrin dimers and tetramers in crude extract reflects their relative distribution in the red cell membrane in vivo. Increased percentage of spectrin dimers is indicative of membrane fragility. The presence of a 4.1 R protein defect seems to give rise to the cytoskeleton instability. The diagnosis of HD was excluded by DNA molecular testing and no disease mutations or single nucleotide polymorphisms (SNPs) were found in the ChAc gene.
Emory Curry	20	1993/4/20	001-428-601-8893x4759	[email protected]	9523 Melissa Rapid	The proband ??was a 72 year-old diabetic woman. She was hospitalized for two unexpected falls and the insidious onset of involuntary right arm movements. She developed a progression of continuous choreic-ballistic movements in all four limbs associated with impaired gait and orofaciolingual dyskinesias. Brain MRI scans showed bilateral putaminal T2 hyper intensities, however EEG did not reveal any pathological findings. The Beck Depression Inventory Scale showed a moderate depressive status. The EMG and NC results show axonal neuropathy. No cardiological anomalies were evident, retinal degeneration was absent, and the expression of the Kell blood group antigens was normal. Haematological parameters were within normal ranges, but numerous acanthocytes (77%) were observed on the peripheral blood film preparations. The patient's daughter showed no evidence of any neurodegenerative disorder, although acanthocytes were present in her blood (31%). Exclusion of Wilson's disease and non-Wilsonian hepatolenticular degeneration were presumed since hepatic copper content via liver biopsy was within the normal range and due to the absence of liver failure. Analysis of RBC membrane proteins (Fig. and Table ) showed a decreased content of 4.1R protein and protein band 3 (data not shown), while the spectrin dimers (Fig. ) were comparable to the control (11%, R.V. < 15%). Therefore the 4.1R defect might affect vertical interactions of skeletal attachment to membrane. Furthermore, the patient's daughter showed the erythrocyte 4.1R defect (Table ) in spite of the absence of neurological signs. The genetic analysis of the CAG distribution and adjacent polymorphic CCG repeats in the HD gene was normal and an absence of mutations in the ChAc gene was reported.
Alison Castro	22	1996/7/29	3065806211	[email protected]	50444 Jones Fall Suite 729	The proband ??was a 65 year-old man suffering from hypertension. He reported a five-year history of depression and orofaciolingual involuntary movements. The depression had been treated with tricyclic drugs and selective serotonine-uptake inhibitors. The neurological examination showed orofaciolingual diskinesias and right distal limb dystonia. The Beck Depression Inventory showed a moderate depressive status. EEG and brain MRI did not reveal any pathological findings. The EMG and NC recordings showed normal electrical activity. Cardiological assessment was normal, retinal degeneration was not present, and the expression of the Kell blood group antigens was normal. Haematological parameters were within normal ranges, although acanthocytes (32%) were observed on the peripheral blood film preparations. In this patient a decreased content of 4.1R protein was observed (Fig. and Table ) and an increased amount of spectrin dimers was measured (31%, R.V. < 15%) with an impairment of the dimer self-association into tetramers. A normal distribution of CAG and adjacent polymorphic CCG repeats in the HD gene was reported and a genetic search for ChAc gene mutations was negative.
Jasper Singh	42	1986/5/29	(720)285-3681x6698	[email protected]	82642 Frazier Causeway Apt. 638	The proband ??was a 38 year-old man who was admitted to hospital because of an isolated generalized tonic-clonic seizure. He reported a four-year history of abnormal involuntary upper limb movements of variable severity. In his case history an acute episode of aggressive behaviour associated with delirium of persecution was also reported. Neurological examination showed ballistic and choreic movements of the arms (left > right) associated with trunk dystonia and orofaciolingual diskinesias. Psychiatric evaluation revealed anxiety, paranoia, depression, obsessive behaviour, and marked emotional instability. EEG and brain MRI did not reveal any pathological findings. Axonal neuropathy was detected by EMG and NC recordings. Cardiomyopathy was not found, fundoscopic examination was normal, the same as the expression of the Kell blood group antigens. Haematological parameters were within normal ranges: however, acanthocytes (85%) were observed on the peripheral blood film preparations. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme activity in cells from cultured fibroblasts was normal, excluding adult onset Lesch-Nyhan syndrome. The diagnosis of Gilles de la Tourette syndrome was excluded by reason of onset after 18 years of age and because of the absence of both multiple motor and one or more vocal tics during the illness. In this patient a decreased content of 4.1R protein was observed (Fig. and Table ) and an increased amount of spectrin dimers was measured (25%, R.V. < 15%) with an impairment of the dimer self-association into tetramers. The CAG units and adjacent polymorphic CCG repeats in the HD gene were in the normal range and no disease-causing mutation was found in the ChAc gene.
Vivienne Barker	32	1985/6/26	+1-323-386-1739x6144	[email protected]	08781 Heidi Isle Apt. 105	A 69-year-old man was referred to us because of about 100 small submucosal rectal tumors detected at examination by his private physician. Multiple biopsies reported to be a tentative diagnosis of multiple carcinoid tumors. He had never been diagnosed as having multiple endocrine neoplasia (MEN) or other multiple tumor syndromes. His family history was not contributory. Physical examination revealed no abnormalities. Serum serotonin level was within normal range, 221 ng/ml. Tumor markers were within normal limits, CEA (carcinoembryonic antigen) 2.3 ng/ml, CA (carbohydrate antigen) 19-9 <2.0 U/ml. Computed tomographs of the brain, chest, abdomen and pelvis did not show any abnormality. He underwent abdominoperineal resection. Pathology revealed carcinoid tumors for about 30 submucosal nodules, which especially concentrated in the lower rectum (Figure , Figure ) and diffuse ganglioneuromotosis (Figure ). Both carcinoid tumors and ganglioneuroma located within the mucosal and submucosal layer. There was neither metastasis to the liver nor the lymph node. The patient had an uneventful recovery and is maintaining good health at 6 months after surgery at this writing.
Kade Weaver	20	1999/5/2	595.620.0148x530	[email protected]	46477 Cunningham Radial	A 15 year old girl with HIV since birth had to stop her antiretroviral treatment due to side effects. She started zidovudine monotherapy at the age of six, but continued to deteriorate clinically and immunologically during four years until she started HAART when it became available 1996. At the time she was hospitalized and severely ill with a Mycobacterium avium intracellulare sepsis. After treatment initiation with stavudine (30 mg QD), lamivudine (150 mg QD) and indinavir (600 mg TID) a remarkable recovery took place and her CD4-cell count increased from 10 to 410 in one year, and further to 920 ? 106/L during the following three years. However, the TID dosage of indinavir was inconvenient and to render BID dosing possible, a ritonavir boosted regimen with indinavir (800 mg BID) and ritonavir (100 mg BID) was started about 1.5 months before treatment cessation. It was not known at that time (2001) that such high indinavir dosage very often resulted in nephrotoxic side effects, and the serum creatinine concentration increased from 59 to 132 弮mol/L after the change. Consequently, her antiretroviral treatment was stopped and the creatinine concentration normalized again within two months. Twelve days after the treatment discontinuation she presented with fever (39??9.5簞C), lymphadenopathy, splenomegaly and abundant sweating during the nights. Her physical examination was normal and a chest radiography showed clear lung fields. Besides confirmed enlargement of the spleen, nothing abnormal was found with ultrasound or CT-scan of the abdomen. Blood cultures for bacteria, including mycobacteria, were negative. Serological testing for Epstein-Barr Virus (EBV), CMV and toxoplasmosis did not give any evidence of an ongoing infection. Routine laboratory showed discrete leucopenia and thrombocytopenia and slightly increased hepatic aminotransferase levels. Serum lactate and C-reactive protein were normal. Two weeks after treatment interruption the plasma HIV RNA level had increased from <50 copies/mL to >750000 copies/mL and the CD4 cell count decreased from 770 to 210 ? 106/L, figure . Treatment with stavudine (30 mg BID), lamivudine (150 mg BID) and efavirenz (600 mg QD) was re-started just over one months after cessation, resulting in decreased HIV RNA and increased CD4 cell count again. The fever disappeared a few days before treatment was re-initiated.
Teagan Atkinson	37	1984/2/10	(327)572-2032	[email protected]	39885 Boyle Cliff Suite 889	In October of 2006 a 41-year-old otherwise healthy man presented to the University of Maryland, Department of Oral and Maxillofacial Surgery for an evaluation of an expansile mass in the left zygomatic, preauricular region. Five months earlier the patient complained of headaches and increasing fatigue at the end of a normal work day. He then noticed increasing left jaw pain and trismus along with the headaches. He was seen and evaluated by his primary care physician. Initially he was treated for temporomandibular disorder. However, the patient's symptoms failed to subside and subsequently he was referred to an oral and maxillofacial surgeon. Computed tomography of his head and neck was obtained, revealing a destructive mass in the left condyle (Fig. ). He was subsequently referred to the University of Maryland Medical Center for definitive treatment. Examination of the patient revealed slight facial asymmetry with a nontender, slightly indurated mass in the left zygomatic, preauricular region. Further examination produced questionable paresthesia in the distribution of the maxillary division of the left trigeminal nerve. No facial nerve weakness was appreciated. Evaluation of the axial and coronal CTs revealed a 4.0 cm soft tissue mass involving the neck of the left condyle, infiltrating the masseter and pterygoid muscles. A whole body PET scan showed increased metabolic activity (SUV 9.2) in the left condyle. No other abnormal activity was seen in the neck, chest, abdomen or pelvis. Laboratory findings: WBC: 4.7 K/mcL, HGB: 13.9 g/dl, HCT: 41.0%, RBC: 4.77 M/mcL, Platelets: 308000 K/mcL. An open biopsy was performed in the operating room via a preauricular incision and a pathological diagnosis of malignant spindle cell tumor was made. In view of the diagnosis of sarcoma the patient subsequently underwent a vertical compartment resection with exposure via hemicoronal incision extending to a modified Blair incision. The specimen was removed en-bloc with a margin of normal tissue, preserving the facial nerve. The patient was primarily reconstructed with a microvascular free fibula flap from the contralateral leg. He was extubated on post-operative day one, and discharged from the intensive care unit on post-operative day three. The rest of his hospital course was uneventful and he was discharged on post-operative day seven. Following the final pathologic diagnosis he was discussed at the institutional tumor board and recommended for adjunctive radiotherapy.
Duke Blanchard	21	1985/10/5	881-561-0766	[email protected]	52470 Maynard Point	A 48 year-old man presented with gynaecomastia, having first noticed a swelling of the left breast twenty years previously. This had gradually increased in size. Following an episode of recent weight loss the swelling had become more prominent. On examination, he had a 4 ? 4 cm firm mass which appeared to be attached to the skin and was situated immediately below the left nipple. There was no fixation to the underlying muscle and no lymphadenopathy. In addition, there were no features of neurofibromatosis and in particular there were no caf矇 au lait spots. Mammograms showed a well-defined mass measuring 36 mm in its maximum diameter and immediately adjacent to the left nipple (Figure ). It was situated centrally within the breast tissue and immediately deep to the skin. The density of the mass was relatively low for its size. Fine needle aspiration cytology showed stromal fragments containing spindle cells suggesting a soft tissue lesion of neural origin. Core needle biopsy revealed a spindle cell infiltrate. The spindle cells had irregular nuclei, many expressing S-100 protein. No mitoses were seen. Although a neurofibroma was suspected, several atypical features were present, including hyperchromasia of some nuclei, increased cellularity and the presence of relatively broad and long fasicles. The tumour was excised under general anaesthetic with an ellipse of overlying skin but preserving the nipple areolar complex. The incision was an inferior periareolar incision to ensure optimum cosmesis. The overlying skin was taken because of the proximity of the tumour to the skin. Macroscopically the tumour measured 4 ? 3 ? 2.5 cm, was white and well circumscribed. Microscopically it was moderately cellular and it contained spindle cells with irregular and focally pleomorphic nuclei. No mitoses or necrosis were seen (Figure ). No Antoni A areas were present. A definitive histological diagnosis of a benign cellular neurofibroma was made. After 5-years no recurrence has been observed.
Layne Cantrell	24	1987/5/7	+1-908-517-3169x820	[email protected]	91933 Rebecca Heights Suite 376	A 77-year-old lady presented with the complaints of a left-sided breast lump of 1-month duration. She had been a heart patient and had been on treatment for the last 4 years. On clinical examination a 3 ? 2 cm firm, mobile, non-tender lump was identified in the outer quadrant of her left breast. The overlying skin of the breast along with nipple and areola were unremarkable. There was no significant axillary or cervical lymphadenopathy. The other breast was normal. She underwent a mammographic examination, followed by fine needle aspiration cytology (FNAC) that was essentially inconclusive. Subsequently, she underwent a frozen section for a primary diagnosis. On mammography, a 2 ? 2 cm ill-defined mass with irregular margins was identified in the left upper outer quadrant. No micro-calcifications were seen. The right-sided breast was normal. (Figure ). The lumpectomy specimen on cut surface revealed a firm, grey-white, fibrous, un-encapsulated nodular tumor measuring 2 ? 1.2 ? 0.8 cm with infiltrative borders. No area of calcification was identified. The closest margin was the base and was found to be 0.5 cm away from the tumor. Frozen sections revealed a tumor with predominant spindle cells showing mild atypia, amidst a sclerotic stroma and conspicuously infiltrated the adjacent fat. A diagnosis of a low-grade sarcoma was favored over a metaplastic carcinoma. Therefore, a sentinel lymph node biopsy and/or an axillary node dissection (ALND) were not conducted at the time of surgery. Histological sections revealed a spindle cell tumor showing an infiltrative growth pattern with prominent areas of sclerosis reminiscent of keloid formation. The cells were mainly arranged in fascicles and displayed tapering nuclei with mild anisonucleosis. Mitoses were inconspicuous. Occasionally, the cells were plump with epithelioid shapes and revealed mild atypia with an occasional small cluster formation. Interspersed were foci of benign ductal hyperplasia and papillary hyperplasia, including a micropapilloma along with focal aggregates of chronic inflammatory cells. The micropapilloma did not show any significant atypia. (Figure ). No discrete squamous differentiation was identified. No focus of Ductal-carcinoma-in-situ (DCIS) was seen in any of the sections. The two closest differential diagnoses considered were fibromatosis and a "fibromatosis like" metaplastic carcinoma. A wide panel of IHC antibody markers was performed (Table ). The tumor cells were simultaneously diffusely positive for epithelial markers i.e. the various cytokeratins CK, CK7, High molecular weight (HMWCK) and epithelial membrane antigen (EMA), along with a mesenchymal marker i.e. vimentin. (Figure and ). All the cytokeratins were positive in the interspersed benign ducts that acted as internal controls. The tumor cells were negative for Gross cystic disease fluid protein (GCDFP), estrogen (ER) and progesterone receptor (PR). The myoepithelial markers i.e. smooth muscle actin (SMA) and p63 showed focal, positive expression. (Figure ). S100 and Desmin were negative. Ki-67 (proliferation marker) showed focal positivity in less than 5% tumor cells (Figure ). The tumor cells were negative for CD34 and CerbB-2/HER-2/neu. (Figure ). A diagnosis of a low-grade "fibromatosis-like" metaplastic carcinoma, associated with a micropapilloma, was finally made. All the cut margins were free of tumor. A portion of fresh tumor tissue fixed in 3% glutaraldehyde was processed for electron microscopy. Ultra thin sections stained with uranyl acetate and lead citrate were observed under an electron microscope model: Zeiss 109, Germany. Ultrastructurally, the tumor cells embedded in a collagenous stroma showed fibroblastic and myoepithelial features along with presence of peripheral villous processes with a focal basal lamina and intercellular junctions (Figure ). After surgery, the patient completed adjuvant radiotherapy (RT). Thereafter, she has been on a regular 2 monthly follow-up; including her metastatic work-up with Positron emission tomography (PET-CT) of the body and bone scan. Due to a high cardiac risk, a second surgery for an ALND was not performed. Nevertheless, till 1 year and 4 months of her follow-up she has not been identified with any lymphadenopathy, recurrent lesion or metastatic lesions in her body.
Harris Shelton	37	1986/3/1	001-347-924-8199	[email protected]	9721 James Plaza	A 24 years old female with Thrombocytopenia absent radius syndrome (TAR) was admitted with fracture of pelvis in our department. Diagnosis of TAR syndrome had been made on the basis of radiographic findings of absent radii, radially deviated hands, presence of thumbs and a low platelet count. There was no family history of consanguinity or congenital malformations. USG was performed for recurrent urinary tract infections which revealed absent kidney on the right side. Further investigations including IVU, MRI scan and renal isotope scans revealed a crossed fused renal ectopia (fig , , ).
Makenzie Fitzgerald	23	1999/3/29	001-664-503-5799x399	[email protected]	11381 Richard Trafficway	A 52-year-old male with a history of hepatitis C, genotype 1b, was nearing completion of a one-year course of treatment with pegylated interferon 2a (180 ug subcutaneously each week) and ribavirin (1200 mg orally each day). His initial hepatitis C viral RNA had declined from 2.2 ? 106 IU/ml at onset of treatment, to <65 IU/ml by six months, and remained undetectable thereafter. Toward the end of his course of treatment, he developed fatigue, malaise, drenching night sweats, intermittent fever and chills. On the last visit for hepatitis C treatment, axillary and cervical lymphadenopathy was noticed. His symptoms were initially attributed to adverse effects of interferon 帢, prompting premature discontinuation of treatment after 10.5 months. One month after onset of symptoms, he presented to a nearby hospital for further workup. He was transferred to the Buffalo VA Western New York Healthcare System with complaints of malaise and left sided mid back pain. He had a documented weight loss of 40 lbs over the previous year. He appeared chronically ill and fatigued. He had a temperature of 101簞F and a heart rate of 105 beats per minute. Generalized lymphadenopathy was noted, including cervical, axillary, inguinal and right epitrochlear lymph nodes. The nodes were 1?? cm wide, firm, movable and nontender. He had left sided abdominal fullness and mild tenderness, but no guarding or rebound. The remainder of his examination was noncontributory. CBC revealed hemoglobin of 11.7 g/dl (13.5??7), white blood cell count of 7.6 K/cmm (4.4??0.7), platelet count of 511 K/cmm (140??75) and ESR of 80 mm/hr. Serum chemistries included a sodium of 130 mEq/L (135??45), creatinine of 0.9 mg/dl (0.7??.4). SGOT was 68 units/l (12??4), SGPT: 95 units/l (25??5). A serum ELISA for human immunodeficiency virus was negative. Rheumatoid and anti-nuclear antibody titers were also negative. Computerized tomography (CT) scan of chest and abdomen revealed mild lymphadenopathy and multiple contrast enhancing hypodense lesions in the spleen (Figure ). Initial clinical suspicion included lymphoma and he underwent a lymph node biopsy. Further history revealed exposure to numerous cats. He frequented a neighbor who had 6?? cats, including kittens, with which the patient had played, and from whom he received numerous scratches. Serologic studies were sent for antibodies to Bartonella, Chlamydia, Toxoplasma and Brucella. He was given ibuprofen for symptomatic relief. A biopsy of an epitrochlear lymph node displayed necrotizing granulomata with peripheral palisading epithelioid cells, with an admixture of plasma cells and lymphocytes. Areas of stellate necrosis with microabscesses were evident, consistent with cat scratch disease (Figure ). Stains for acid-fast bacilli and fungi showed no organisms. Lymph node biopsy material was cultured for routine pathogens, acid-fast bacilli and fungal organisms. Although the Gram stain displayed abundant white blood cells, all cultures were sterile. Over the next 3?? days, the patient defervesced and improved symptomatically on ibuprofen alone. By the eighth day, serum antibody titers (IgG and IgM) for Bartonella henselae were reported as >1:16,384. He continued to improve without further treatment. Six months later he was doing well and had regained 25 lbs of weight. An abdominal CT scan revealed complete resolution of splenic lesions.
Peyton Weeks	38	2003/9/16	+1-355-340-9347x516	[email protected]	6201 Smith Lock Suite 245	A 73 years old male patient was found to have calcified aortic stenosis after a syncopal episode. He had a history of hypertension and a previous diagnosis of obstructive chronic broncopneumopathy. He was 170 cm tall, his weight was 75 kilos and body surface area was 1.85 sqm. At preoperative investigations he was found to have a borderline dilated ascending aorta of about 45 mm (Figure ). At the time of aortic valve replacement a written informed consent was obtained even for treatment of the ascending aorta if needed but no specifications were made about the type of intervention. After median sternotomy, cannulations of distal ascending aorta, right atrio-caval, coronary sinus and left ventricle via right superior pulmonary vein were performed. For myocardial protection intermittent anterograde and retrograde warm blood cardioplegia was used. At inspection, the mid ascending aorta showed an external diameter of about 50 mm (Figure ). Aortic wrap was constructed before aortic cross-clamping: a vascular dacron prosthesis 12 ? 26 mm (Woven Dacron Gelweave, Vascutek Ltd, Inchinnan, Scotland, UK) was taken. The prosthesis was cut into two halves of 6 cm length (Figure ). Both halves were opened longitudinally by a curved cut. As a reference the black lines on the prostheses were used. The cuts were about 4 mm apart from the black line in the centre of the length of the prostheses, and 4 mm apart from the black line on the opposite sides at the extremities (Figure ). Thus two dacron sheets were obtained from the prostheses, each of them having one concave and one convex side. Finally the sheets were joined by suturing the two convex sides together and the two concave sides together too (Figure ). A curved dacron hose 5 cm in diameter was obtained for external wrapping of the ascending aorta (Figure ). The joining sutures of the two sheets were made of single separate stitches so that the extremities could be shortened if needed. After cross clamping, the aorta was cut transversally above the commissures at the sinotubular junction. Aortic valve replacement was then performed as usual. A 25-mm biological prosthetic aortic valve was inserted with 15 pledget-supported stitches. Then, before aortic closure, the posterior aspect of the ascending aorta was freed completely from the pericardial reflection up to the innominate artery. In this way the custom-built prosthesis was easily inserted, like a trouser leg, to wrap the ascending aorta. The aorta was closed by a continous running suture. The cross clamp was released after 64 min while extracorporeal circulation was arrested after 78 min without inotropes. Then, the prosthesis was pulled down to cover the suture line and fixed with few adventitial stitches. No solid transmural stitches were needed because the curved prosthesis fitted the curved ascending aorta best. Similarly, after decannulation, the prosthesis was pulled up to cover the cannulation site. Therefore the whole ascending aorta was covered by the prosthesis which appeared to fit perfectly without wrinkles or bends (Figure ).
Karen Barrett	41	1991/4/20	(296)236-7684	[email protected]	314 Arnold Row	An 81 years old lady had a right radical nephrectomy in 1999 for conventional renal cell cancer (RCC). She was discharged from the urology and oncology clinics in 2004 after 5 1/2 years follow-up with no signs of local or regional recurrence. In December 2004, she noticed a lump in the right breast after sustaining a fall. She was referred to the breast clinic in July 2005 for further assessment. Clinically, she had a mass in the upper outer quadrant of the right breast. The left breast was normal and there was no axillary lymphadenopathy. Abdominal examination was normal. Radiology confirmed a 17 ? 13 ? 9 mm well circumscribed hypoechoic mass in the right upper quadrant of the right breast (Figure ). The mass was core biopsied. The histopathological examination revealed tumour growth consistent with conventional renal cell carcinoma. Tumour cells strongly expressed vimentin. CT scan of the chest and abdomen showed a 12 mm mass in the right breast and a 2.7 cm metastatic deposit at the right renal bed (Figures and ). The lungs and the liver were normal. The lump was excised in October 2005. The gross examination of the specimen confirmed metastasis from a renal primary (Figure ). There was no evidence of in situ ductal or lobular disease. The patient was offered Interferon treatment, but she preferred to hold on therapy as an alternative. She is under regular follow-up in the oncology clinic.
Angelo Dunlap	41	1995/8/3	(683)538-0439	[email protected]	73284 Anita Plains	A 47-year-old male presented with a gradually increasing, painful soft tissue mass of 7?? months duration, measuring 4 ? 3 cm in the inner side of his right thigh. A computed tomogram (CT) scan revealed an abnormal enhancing lesion in the perianal region. All the visceral organs were found to be normal. No bowel wall thickening, free fluid or abdominal lymphadenopathies were noticed. Subsequently, he underwent a marginal excision for this mass, elsewhere. It was diagnosed as a poorly differentiated carcinoma on biopsy and referred to us in form of a single hematoxylin and eosin (H & E) stained micro section along with a paraffin block for review. At our Hospital, his tumor marker levels for carcino embryogenic antigen (CEA) were normal i.e. 1.8 ng/ml (normal range: 0.3??.7 ng/ml) On review histology, a diagnosis of a "proximal-type" epithelioid sarcoma was offered. The patient was recommended a wide excision post a magnetic resonance imaging (MRI) for fear of residual disease. However, he was lost to follow-up. Six moths later, he presented with an enlarging mass at the same location. During this time gap, he revealed a history of having undergone adjuvant chemotherapy (CT) and radiotherapy (RT) that were well tolerated. However, he developed difficulty in walking as a result of the persistent lesion. He underwent a chest X-ray along with CT scan and a real time B-mode high frequency ultrasonographic (USG) examination for the persistent mass that was re-excised and re-submitted to us for review. An oval, hypoechoic, solid lesion measuring 2.9 ? 2.2 ? 2.1 cms was seen in the deep subcutaneous region of the right, upper, inner thigh up to 5??0 mm superior and anterior to the scar of the earlier excision. Other, two, small oval hypoechoic solid lesions of sizes 10 and 8 mm were seen in the subcutaneous layer. The main lesion showed an ill-defined echogenic wall with peripheral echogenic linear echo entering the lesion, suggestive for a lymph node. Eccentric cortical parenchyma showed a distorted architecture. The overlying skin was normal with slightly prominent subcutaneous fat lobules. No significant flow lesion was seen in the color Doppler. Radiologically, the differential diagnoses included a tumor mass vs a lymph node mass. (Figure ). Grossly, the first excision specimen was in form of grey-white soft tissue bits aggregating to 3.5 ? 2 ? 2 cms. Details regarding the marginal status were unavailable. On histology, the tumor revealed a multi nodular pattern as a result of investing thin fibrous septa with cells predominantly arranged in a cohesive manner. At places cellular disintegration was observed in combination with hemorrhage resulting in a 'pseudoangiosarcomatous' pattern. The cells were oval to polygonal and exhibited moderate nuclear pleomorphism. Interspersed were larger cells with vesicular nuclei, prominent nucleoli and abundant cytoplasm, including intracytoplasmic inclusions reminiscent of a 'rhabdoid' morphology along with focal areas of tumoral necrosis. Mitoses were noted, however, not conspicuously. (Figure , and ). Special histochemical stains were carried out with a wide panel of IHC markers (Table ). The reticulin staining highlighted the nodular growth pattern of the tumor. (Figure ). IHC showed a diffuse strong positivity for CK and vimentin in the tumor cells. CK-7 and EMA were also strongly positive. (Figure and ). Desmin was focally positive (Figure ). In addition, CD34 was found to be strongly positive (Figure ). SMA, Myo-D1, CK-20, CEA, S-100, HMB-45, CD 31, C-kit and LCA were negative. A diagnosis of a proximal-type epithelioid sarcoma of was formed. The re-excision showed a similar histology. In addition, increased number of larger cells was noticed along with tumor giant cells and several mitoses.
Iliana Marin	19	1994/6/21	438-877-0498x59884	[email protected]	06795 Devin Estates Apt. 377	A 50-year-old woman had lacrimal mass presented with progressive exophthalmos and visual disturbance in the left eye in 2000. Orbital CT scan showed a well-circumscirbed mass at lateral aspect of the left orbit without bone involvement (Figure ). She underwent subtotal resection of a smooth, encapsulated, and multilobulated mass at the referring hospital. The histological diagnosis was pleomorphic adenoma of the lacrimal gland. The clinical course was uneventful until 4 years after the operation, when a local recurrence with protrusion of the left eye and swelling of the left temporal muscle area required subtotal resection at the Department of Ophthalmology, Yonsei University Hospital. The mass was extended to periorbital tissue, lateral orbital rim, and temporal muscle. The histological diagnosis was poorly differentiated adenocarcinoma, suggesting malignant carcinomatous changes in the recurrent pleomorphic adenoma (Figure ). MRI surveillance of the lesion was initiated. Six months after second surgery, MRI demonstrated increased extent of orbital mass, extending to the cavernous sinus. The patient underwent intensity-modulated radiation therapy (IMRT) with two different planning target volumes (PTVs): 1) 45 Gy to extracranial portion, 2) 30 Gy to intracranial portion. Six month later, the patient complained of the left eye pain and the left facial paresthesia. An ophthalmological examination revealed ptosis, exophthalmos, and ophthamoplegia of the left eye. Facial sensory change on the left whole trigeminal territories was noted. MRI revealed a well-circumscribed mass of the left cavernous sinus extending to the infratemporal fossa and clivus. The patient underwent Gamma Knife stereotactic radiosurgery with a marginal dose of 15 Gy and maximum dose of 30 Gy to 29.7 ml of tumor volume. Dose was adjusted to the right optic nerve and optic chiasm (8.4 Gy) and to the left optic nerve (15 Gy) (Figure ). Intentional high dose to the left optic nerve was planned due to useless vision caused by the left complete occulomtor nerve palsy. Six months later, follow-up MRI revealed a slightly decreased tumor size extending to orbital, cavernous sinus, infratemporal fossa, and clivus. However, small nodular enhancing lesion on the interhemispheric fissue and superior cerebellar peduncle, and leptomeningeal seeding was suspected (Figure ). Whole spinal MRI was indicated due to neck and back pain, and it revealed multiple nodular enhancing masses on the cervico-thoracic area (Figure ). Palliative radiotherapy for the intracranial and spinal metastases was planned, but the patient refused further active treatment. The patient was discharged and underwent hospice care. Five months later, the patient died due to pneumonia and sepsis related to terminal stage of metastatic cancer.
Aldo Butler	43	1984/9/28	319-222-2063	[email protected]	84369 Brown Village Suite 167	A 78-year-old man was referred to our Institution for the presence of an anal mass accidentally discovered during a routine physical exam. Past medical history was significant for cancer of the right lung, treated with right pneumonectomy 1 year before. Routine blood test were within normal limits as well as common neoplastic markers. The rectal exam showed a well defined mass on the left-anterior aspect of the anal canal, beginning at 1 cm from anal verge and extending cranially for about 4 cm. Endoanal ultrasonography confirmed the presence of a 4 ? 2 cm mass in the thickness of the sphincteric muscles (Fig and ). Total body CT scan confirmed the presence of the mass and did not show any lymph node enlargement in the proximity or distant metastases. The mass appeared circumscribed and not infiltrating the surrounding tissues (Fig. ). The patient was brought to the operating room, placed in jack-knife position, and a local excision was carried out, resecting just a small amount of fibers of the anal sphincter. This has been possible since the mass was well capsulated and not firmly adherent to the surrounding structures. Gross pathological examination showed a 3.5 ? 2 ? 1.2 cm fibrous-elastic mass. Histological examination showed a proliferation of densely packed spindle cells, with prominent nuclear palisading (Fig. ). Nuclear atypia was absent and mitotic count was of 4 mitosis/50HPF. Neoplastic cells showed diffuse and marked cytoplasmic positivity for KIT protein and CD34 in the majority of cells (Fig. ). Neoplastic cells were negative for desmin that stained residual smooth muscle fibers of bowel wall at the margins of the neoplasm. A diagnosis of GIST, with low risk aggressive behavior was made (Table )[], therefore no further treatment was necessary. Postoperative course was uneventful. No implications on anal continence were observed and the patient was discharged on postoperative day 3. The patient underwent follow up at 6 and at 12 months, and rectal ultrasonography as well as CT scan did not show local recurrence or distant spread.
Athena Sandoval	39	2000/4/9	(330)598-1711x50147	[email protected]	25400 Medina Landing Apt. 512	A 62 year-old man with a several month history of abdominal pain was referred to The Ohio State University Medical Center in June, 2006. His past medical history was significant for hypertension, arthritis and chronic back pain. On computed tomography scan he was found to have a heterogeneously enhancing solid mass at the junction of the head and body of the pancreas (Figure ). Based on initial imaging, the differential diagnosis included pancreatic ductal adenocarcinoma, pancreatic endocrine tumor, solid pseudopapillary tumor, and metastatic carcinoma. The patient was offered resection for diagnosis and definitive therapy. After undergoing diagnostic laparoscopy to rule out carcinomatosis in the peritoneal cavity, a distal pancreatectomy with splenectomy was completed. The patient tolerated the procedure well and was discharged after an uneventful hospital stay. Gross examination of the resected specimen demonstrated a 4.2 ? 2.5 ? 2.0 cm solid, well circumscribed, non-encapsulated mass adjacent to the pancreatic duct (Figure ). The cut surface of the tumor contained thick fibrous bands without hemorrhage or necrosis. The surrounding pancreatic parenchyma was noted to be grossly unremarkable, and surgical margins were negative. On hematoxylin and eosin stain, the architecture of the mass was solid with cells arranged in nests, acini and trabeculae, separated by thick, hypocellular fibrous bands (Figure ). Rare small cystic areas were seen microscopically (less than 1% of the tumor). The tumor was homogenous and consisted of polygonal cells with centrally placed small, round to ovoid nuclei (Figure ). No mitoses or cellular atypia were noted. The cells contained abundant clear cytoplasm which was PAS positive and diastase sensitive suggesting the presence of glycogen (Figure ). No vascular or perineural invasion was seen. Mucicarmine stain was negative. Immunohistochemistry showed positive staining for cytokeratin 7 (CK7), cytokeratin 19 (CK19), neuron-specific enolase (NSE), 帢-inhibin and calponin; and negative staining for vimentin, 帢1-antitrypsin (A1AT), synaptophysin, carcinoembryonic antigen (CEA), renal cell carcinoma stain (RCC), CD10, S-100 protein, and smooth muscle actin. These findings support the final diagnosis of solid microcystic adenoma.
Brantley Phan	42	1988/5/15	001-875-544-9316	[email protected]	8474 Caitlin Parkway Apt. 844	A 21-year-old gentleman initially was referred with weight loss, fevers and hepatosplenomegaly. He had previously been investigated for lymphadenopathy. A left inguinal lymph node excision 3 years earlier had shown "unusual histology, possibly reactive or due to a low-grade lymphoma" and a decision for close follow up was made. A second lymph node biopsy was performed 1 year later for persistent right cervical and right inguinal lymphadenopathy. Histology showed granulomatous lymphadenitis, again with unusual histology, reported as "possibly due to sarcoid or reactive secondary to infection". At this time he was also noted to have hepatosplenomegaly, abnormal liver function and pancytopenia. A liver biopsy was performed prior to referral showing abnormal architecture, lymphoid proliferation and multiple non-caseating epitheliod granulomas. On examination he was pale with low-grade pyrexia of 37.5簞C. Cardiovascular and respiratory examinations were normal, but he had cervical lymphadenopathy. Abdominal examination revealed massive hepatosplenomegaly without ascites. Computed Tomography of the chest and abdomen showed hepatosplenomegaly with mediastinal and para-aortic lymphadenopathy suspicious of lymphoma. Pulmonary function testing showed decrease in diffusion capacity. Liver function and full blood count were abnormal (Table ). Serum ACE (angiotensin converting enzyme) was raised at 80 U/L (normal range 8??2). Other bloods including liver screen, autoimmune screen and virology screen were all negative. A clinical diagnosis of sarcoidosis was made and he was commenced on steroid treatment with prednisolone 40 mg daily. Within two days his pyrexia settled, his liver function improved and his splenomegaly improved. He was discharged home on 20 mg prednisolone. Over the next twenty-four months, his liver function continued to improve and the patient remained clinically well. However, his pancytopenia worsened and a bone marrow biopsy revealed normal haematopoesis with a few non-caseating granulomas. The pancytopenia was felt to be due to hypersplenism and the decision was made for him to undergo splenectomy. During admission for splenectomy the patient complained of cough and was noted to be pyrexial and tachycardic. A chest radiograph revealed left basal consolidation with right basal changes. Despite a two-week course of moxifloxacin he remained symptomatic with cough, night sweats, fevers up to 40簞C and was noted to be hypoxic. Computed Tomography of the thorax showed mediastinal lymphadenopathy with extensive consolidation, and a lung biopsy showed non-specific inflammation. Microbiological culture of the biopsy specimen grew a bacteria belonging to the Burkholderia cepacia complex, Burkholderia multivorans which was subsequently confirmed on broncho-alveolar lavage. In light of the unusual organism, the histology was reviewed and the possibility of chronic granulomatous disease was raised. Neutrophil burst test (Figure ) showed impaired neutrophil oxidative burst consistent with CGD. Western blot showed decreased expression of the gp91phox protein consistent with X-linked CGD (Figure ). His mother and sister were also tested and found to be carriers as evidenced by dual population of normal and abnormal neutrophils (Figure ). Genetic analysis confirmed a mutation in exon 9 of the gp91phox gene. The patient was treated with cotrimoxazole and commenced on prophylactic itraconazole. He made a good clinical improvement and was discharged nine days later on prophylactic antibiotics and antifungals. The steroid dose was gradually tapered down. His splenomegaly has gradually improved with the spleen decreasing in size from 24 cm to 18 cm. The haemoglobin and platelet counts returned to normal. His lymphocytes remained low probably reflecting continued enlarged spleen. and after 18 months follow up remains well.
Elsa Meadows	23	2003/3/22	(204)237-3546x91865	[email protected]	405 Nathan Crescent Apt. 209	In April 2006, a 75-year old man who had been successfully treated for colon cancer 13 years ago, thyroid cancer 12 years ago, and was receiving endocrine therapy for prostate cancer from last year was transferred to our hospital for a fracture of his left proximal femur. The chest radiograph showed a solid mass in the hilum of left lung, and the thallium scintigram demonstrated abnormal uptake at the left proximal thigh and the hilum of left lung. In addition, the screening of tumor markers revealed extremely high level of CEA (1250 ng/ml), slightly high level of NSE (16.6 ng/ml) and SCC (2.2 ng/ml), and low level of thyroglobulin (0.3 ng/ml) and PSA (0.009 ng/ml). Thus the fracture was considered to be a bone metastasis from his fourth primary pulmonary cancer. Physical examination showed no hyperpigmentation of his all body surface. Laboratory investigation revealed serum sodium of 134 mmol/l, potassium 4.7 mmol/l, and plasma glucose 110 mg/dl, with normal renal and liver function. He uneventfully underwent local excision and proximal femur replacement with a mega-prosthesis under general anesthesia. The bone tumor was pathologically diagnosed to be moderately differentiated adenocarcinoma. Later, the immunohistochemical examination revealed that cytokeratin 7 (CK7) and thyroid transcription factor 1 (TTF-1) were distinctly detected but cytokeratin 20 (CK20) never expressed. Recently, Chhieng et al. described that an adenocarcinoma was likely a primary lung tumor when it was of the CK7 positive/CK20 negative and TTF-1 positive phenotype []. Thus, the bone tumor was finally diagnosed to be a metastatic lung cancer. The estimated intraoperative blood loss was 400 ml. The patient was extubated as usual, but the level of awakening was very poor. Postoperative laboratory examination demonstrated anemia and severe hyponatremia (126 mmol/l), but showed normokalemia (4.3 mmol/l) and normoglycemia (92 mg/dl). Despite the transfusion of blood and the administration of normal saline, the patient subsequently became hypotensive (SBP 60??0 mmHg), tachycardic, hypoxic, febrile (40.5簞C) and confused. Re-intubation was required for respiratory distress. A chest radiograph showed diffuse pulmonary edema. We initially suspected this condition of acute pulmonary emboli. Immediately, the patient underwent CT examination from head to abdomen. Enhanced chest CT revealed a left hilar mass suggesting a primary lung cancer but no pulmonary embolus. A ventilation/perfusion scan performed on the next day showed no perfusion defect and confirmed definitely no evidence of pulmonary embolism. Concomitant brain and abdominal CT scan also demonstrated a low density area in the parietal lobe of the left brain and massively enlarged bilateral adrenal glands consistent with metastases (Figure ). After the CT evaluation, we finally diagnosed adrenal crisis due to extensive destruction of adrenal tissue caused by metastases. Blood was drawn at 8:00 on the first postoperative day for serum cortisol levels that were found to be 2.0 弮g/dl on the third postoperative day. Betamethasone (2 mg) was given to the patient at first, and switched to hydrocortisone, 100 mg administered intravenously every 8 hours. Dramatic improvement occurred in the subsequent hours following administration of hydrocortisone. The fever and hypotension promptly subsided and hyponatremia instantly disappeared. The patient recovered his consciousness and could be successfully extubated. On postoperative day 3, he was started on early remobilization by physical therapy. On postoperative day 7, the patient could sit down on the edge of a bed without assistance, followed by transfer exercise to a wheelchair. Although he could not undergo a CT-guided biopsy of the adrenal gland due to the flat refusal of his family, the following CT examination on postoperative day 35 demonstrated that bilateral adrenal glands neither decreased in size nor showed atrophic change, suggesting that adrenal enlargement was mainly caused by metastasis rather than hemorrhagic complication. The patient was transferred to the related hospital for further rehabilitation on postoperative day 39.
Wayne Hendrix	40	1981/6/28	582-433-3264	[email protected]	2991 Valenzuela Rapid	A 50-year-old man presented to the emergency department after sustaining blunt trauma to the head secondary to a fall from a horse. The patient's forehead struck the ground with his neck extended. The patient complained of neck pain and left arm weakness and paresthesias, and denied loss of consciousness. The patient's past medical history was otherwise unremarkable, and did not include use of anticoagulants or anti-platelet agents. Laboratory studies, including coagulation profile and platelet count, were within normal limits both immediately after admission and on the following day. A rigid cervical collar was applied upon arrival to the emergency department. The patient's vital signs were stable and he was treated conservatively with intravenous maintenance fluid and opioid medication for pain control. The patient received no anticoagulation therapy (specifically no low molecular weight heparin), no platelet inhibitors or non-steroidal anti-inflammatory medications and no treatment modalities which could have potentially contributed to a coagulation disorder. Initial computed axial tomography (CT) of the cervical spine revealed bilateral fractures of the anterior arch of C1 and a fracture of the right C4 spinous process. Mild prominence of the prevertebral soft tissues was noted without significant encroachment on the pharynx (Figures , ). Approximately 20 hours after his initial presentation, the patient underwent magnetic resonance imaging (MRI) of the cervical spine to further evaluate his upper extremity neurologic deficits. While undergoing MRI, the patient developed sudden dyspnea and hoarseness. MRI demonstrated development of a marked increase in the prevertebral soft tissue prominence due to an enlarging retropharyngeal hematoma. Severe compromise of the oropharyngeal airway was evident (Fig. ). The patient was treated with oxygen at the MRI suite while members of both the surgery and anesthesiology department were contacted for emergent management. Upon their arrival, the patient had a blood pressure of 150/80 mmHg, pulse of 66 beats per minute, a 99% oxygen saturation level, respiratory rate of 24 breaths per minute, and appeared in mild distress. He was immediately transported to the intensive care unit by the physician team for definitive airway control. The patient was prepared for awake nasal fiberoptic intubation with intravenous glycopyrrolate and lidocaine spray topically to the nasopharynx. The bronchoscope was passed through the nasopharynx, vocal cords, and into the trachea. The pharynx and superior trachea were severely distorted and compressed. A 7.0 mm endotracheal tube was passed over the bronchoscope and positioned approximately 3 cm above the carina. The patient was comfortable and did not move during the procedure. Cervical spine immobilization was maintained throughout. Additionally, a surgeon and instruments were present throughout the procedure in anticipation of emergent tracheostomy if fiberoptic intubation were unsuccessful. After intubation, the patient was sedated and mechanically ventilated. The following day the patient underwent surgical decompression. A moderate sized hematoma at the level of C4 was evacuated and a drain was placed for further decompression. A follow-up MRI was performed which revealed a bi-lobed disc herniation (determined to be chronic in nature) with secondary spinal canal encroachment and mass effect on the cervical spinal cord (Figures , ). The retropharyngeal hematoma had resolved. The patient was successfully extubated with the use of a Cook exchange catheter on post-operative day one and discharged two days later.
Zhuri Pruitt	32	1978/6/10	712-679-5343x4339	[email protected]	900 Pennington Inlet	A 36 year old man sustained a degloving injury to his right, middle finger (which he caught in a machine, while at work) resulting in a large volar soft tissue defect extending from the tip of the distal phalanx to the mid portion of the middle phalanx. Bone and part of the profundus tendon was exposed (Fig. ). The tip of the distal phalanx was crushed, without any other bony injury. A primary debridment was done on the day of injury, because the wound was contaminated with grease and grit in the emergency operation theatre. The exposed tendon and bone was covered with a collagen dressing. When the wound was inspected on day 3, it was found to be healthy and a flap was planned to cover the exposed tissues. We have had a lot of experience with cross finger flaps and free flaps from the toe and foot. However, they have been associated with lack of patient compliance, morbidity to the donor areas and immobilization in the case of cross finger flaps. Therefore, we planned to do a free thenar flap, based on the superficial branch of the radial artery. We had carried out cadaver dissections and found the vascular supply consistently associated with this fasciocutaneous flap. This fasciocutaneous flap would have a texture similar to the pulp tissue. The other main advantage of the free thenar flap would be its sensory supply by either of the nerves (palmar cutaneous branch of median nerve, lateral antebrachial cutaneous nerve or branch of superficial radial nerve). On day 4, a free fasciocutaneous thenar flap was performed under regional block. A blue print of the flap is shown in the figure . No upper limb exsanguinations was done, which helped in identifying the thin vessels under the loupe. An upper limb tourniquet was used to minimize bleeding. A thenar flap measuring 4 ? 2.5 cms was dissected with the vascular and neural pedicle (a branch of the superficial radial nerve). The tourniquet was released intra-operatively after the neuro-vascular anastomosis was completed. Blood flow was adequate (figure ). The donor site over the palmar aspect was primarily sutured. The operation took approximately 6?? hrs. A rigid dressing was applied to reduce post operative edema. The middle finger along with the wrist was immobilized (4 days) to reduce postoperative pain and to help in initial wound healing. On day 9 (post-operative day 5), the digit was redressed. Both the donor and the recipient site were found healthy. Sutures were removed on day 15 (11 days after the operation). Physiotherapy was started for the middle finger and wrist, from the 4th post-operative day. 6 months after the injury, the patient is satisfied with the flap. He is happy about the texture of the flap which matched the other fingers (Figure and figure ). He has 90% deep touch sensations and approximately 50% soft touch sensations. The only uncomfortable sensation he has had was transient tightness over the palmar scar which had disappeared with time.
Gatlin Porter	21	2002/2/28	695-680-1062	[email protected]	614 Jones Club	A 25-year-old Caucasian female with skin type 2 (Fitzpatrick classification) presented because of a plum-sized pedunculated keloid on the upper part of her left helical rim. She reported that 10 years ago she had already experienced formation of a nodule in this area which became evident 6 months after an ear piercing. This keloid-like nodule was excised twice and injected with steroids. At the time of presentation the plum-sized keloid on her helical rim had been increasing in size and was accompanied by severe pruritus (Fig ). We introduced our patient to an audiology technician in order to design and build a specially silicon pressure splint for her left ear (Fig ). The keloid was then excised with cold steel. Immediately after the operation a combination of 0.5 ml triamcinolonacetonid and scandicain 2 % was intralesionally injected. The custom made silicon splint was applied directly after surgery and steroid injection (Fig ). The injections were repeated at intervals of 8 weeks for 12 months. The patient was instructed to wear the splint for 24 h a day, 7 days a week. A clinical check-up one year and 24 months after the last injection showed no tendency to relapse (Fig and Fig ).
Ryleigh Bernard	40	1993/9/28	(399)849-3843	[email protected]	943 Dawson Corners	A 14-year-old girl presented to the Emergency Room in December 1999 with her first episode of severe gross, painless hematuria. Past history was unremarkable. On examination she was pale, dehydrated and continually bleeding per urethram. Heart rate was 120/minute, blood pressure 90/55 mmHg and she was afebrile. Hemoglobin was 5.9 gm/dl, hematocrit 18 with coagulation profile and routine chemistry being normal. Urinalysis showed large amounts of RBC's and 08 WBC's/HPF. Urine culture and sensitivity was later negative for bacterial growth. At emergency cystoscopy following resuscitation, she was found to have an 8 ? 10 cm highly vascular, solid, infiltrative tumor occupying the right lateral wall and ipsilateral half of the trigone. The tumor involved the right ureteric orifice and extended to 1 cm short of the bladder neck. Preoperative intravenous pyelogram showed a non-excretory right kidney due to hydronephrosis with normal contralateral system. Transurethral resection of the tumor till bladder wall level was done. She needed 5 units of packed cells transfusion. Subsequently, right percutaneous nephrostomy was done, which was later internalized with a double J stent. Microscopic examination of the tissue revealed cohesive groups of cells arranged in lobules by dividing fibrous septae. There was no evidence of muscle invasion. The cells contained abundant granular eosinophilic cytoplasm with round monomorphic nuclei and showed focal positivity with PAS stain (Figure &). Immunohistochemical studies revealed diffuse positivity with S-100 protein, and negativity with Desmin and Vimentin, thus consistent with granular cell tumor instead of the suspected sarcoma. Positivity with neuron specific enolase, chromogranin and synaptophysin was not seen and S-100 staining was seen in tumor cells and not in sustentacular cells as noted in pheochromocytoma CT scan of the abdomen/pelvis and chest X-ray showed no metastases. There was localized thickening of the bladder wall with no extravesical extension. At repeat cystoscopy 2 weeks later, there was no obvious residual tumor and deep biopsies from previous resection site were clear. Hence, it was decided to treat the patient conservatively. Follow-up CT scan of the abdomen/pelvis 4 months later showed a normal-looking bladder (Figure ). Cystoscopy with multiple bladder biopsies was again negative for tumor recurrence and only showed acute on chronic inflammation. The double J stent was removed. Follow up IVP at 12 months was normal. She now remains free of disease at over 4 years since the operation.
Jair Miles	26	1996/7/13	478.771.3908	[email protected]	691 Koch Park	A 47-year-old lady, married with 6 children, diabetic and hypertensive, presented to the urology clinic in July 1995 with gross intermittent hematuria and dysuria for one year. She also complained of urgency and urge incontinence. About 25 years back, she had a laparotomy for intestinal obstruction secondary to tuberculosis and had received a one year course of antituberculous medical therapy. Physical examination was unremarkable except for some fullness in the left lower quadrant of abdomen. Hemoglobin was 8.5 gm/dl, hematocrit 26.2 (normal = 35.4 ??42.8%) with coagulation profile and routine chemistry being normal. Urinanalysis showed hematuria and pyuria while urine culture was negative for bacterial growth. Ultrasound revealed a 2.6 ? 1.8 cm polypoidal mass in the left posterior wall of urinary bladder with bladder wall irregularity. An IVP showed normal upper urinary tracts with a filling defect in the bladder. Cystoscopy revealed an approximately 4 ? 3 ? 3 cm solid tumor in the left postero-lateral wall, above the ureteric orifice. Multiple biopsies of the tumor from the base and edges, as well as random bladder biopsies, were obtained. The tumor was arranged in large clusters with diffuse sheets invading and insinuating in between the smooth muscle fibers. The tumor cells exhibited pleomorphism, nuclear hyperchromasia, with 2?? mitoses/10 HPF (Figure &). Random bladder biopsies were normal. Immunohistochemical studies showed the tumor cells to be S-100 positive and cytokeratin Cam 5.2, AE/A13 negative, illustrating a non-epithelial origin. The pathologic diagnosis of a muscle-invasive, malignant granular cell tumor of the urinary bladder was made. Neuroendocrine markers such as neuron specific enolase, chromogranin, synaptophysin were negative. A radionuclide bone scan was negative for metastasis. A CT scan of abdomen and pelvis showed no extravesical tumor extension or distant metastasis. A cystic left ovarian mass was recognized, which later turned out to be benign ovarian cyst with no malignancy. A planned radical cystectomy, bilateral salpingo-oophorectomy, hysterectomy, ileal conduit and pelvic lymph node clearance with resection of the anterior wall of the vagina was carried out in June 1995 realizing the malignant nature of the tumor. She made an uneventful recovery and histopathology confirmed a pT3N0M0 malignant granular cell tumor of the urinary bladder. She remains free of disease recurrence at 8 years since the operation.
Alessandra Pearson	44	2005/6/18	662-971-3103x6194	[email protected]	26149 Valdez Walk	A 19-year-old man with recently diagnosed HCM was referred for sudden death risk assessment. The patient had mild exertional dyspnea (New York Heart Association functional class II), but without syncope or chest pain. There was no family history of HCM or sudden death. The patient's blood pressure was 130/70 mmHg and a grade 3??/6 systolic ejection murmur was present at the apex. ECG showed a left ventricular (LV) hypertrophy with strain pattern. A two dimensional echocardiogram revealed an asymmetric type of LV hypertrophy; anterior ventricular septum = 49 mm; posterior ventricular septum = 20 mm; anterolateral free wall = 12 mm; and posterior free wall = 6 mm (Figure ). The patient had 2 types of obstruction; a LV outflow obstruction due to systolic anterior motion of both mitral leaflets (Doppler-estimated 38 mm Hg gradient at rest); and a midventricular obstruction (Doppler-estimated 43 mm Hg gradient), but without apical aneurysm or dyskinesia (Figure ) [see Additional file ]. The LV end diastolic diameter was 45 mm and the left atrium was 45 mm. The patient had a normal blood pressure response on exercise test and no episodes of non-sustained ventricular tachycardia in 24-h ECG recording. Cardiac MRI showed a gross late enhancement at the hypertrophied septum. Based on the extreme degree of LV hypertrophy and the myocardial hyperenhancement, an implantation of a cardioverter-defibrillator was recommended prophylactically for primary prevention of sudden death. Written consent was obtained from the patient for publication of study. This case is a rare example of a patient with subaortic and midventricular hypertrophic cardiomyopathy with extreme segmental hypertrophy exceeding the usual maximum wall thickness reported in the literature, although Maron et al have published a case of a patient with an even greater hypertrophy (60 mm) [].
Gunner Serrano	26	2004/6/30	(652)502-3375x719	[email protected]	990 William Ville Suite 833	A 57-year-old Caucasian male was first seen by a rheumatologist in 1998 for arthralgias and myalgias of his proximal upper extremities. His medical history included obesity and hypertension. There was no family history of rheumatologic disease. He worked as a glazier, and had no substance abuse history. Physical examination showed synovitis of his metacarpophalangeal joints and wrists. Erythrocyte sedimentation rate was >120 mm/hr, and rheumatoid factor was negative. He was diagnosed with seronegative rheumatoid arthritis, and prednisone was initiated at 10 mg daily in 1999. His arthralgias and myalgias responded clinically to the prednisone. In late 1999, because of new symptoms of fatigue, weight loss, and fevers, 10 mg of weekly methotrexate was added to his regimen. An infectious disease consultation was obtained to rule out infection as a cause of his symptoms, and an extensive workup was performed. A chest radiograph was normal, and computed tomography (CT) scans of the abdomen and pelvis were unremarkable. A bone marrow biopsy was normal and cultures for bacteria, mycobacteria, and fungi were negative. Multiple blood cultures for bacteria were negative. With the exception of a persistently elevated sedimentation rate of 133 mm/hr, laboratory results were normal, and no infectious etiology for his symptoms could be found. Because of a lack of response, his methotrexate was discontinued after 3 months of therapy. His weight loss and fevers stopped, and only his fatigue continued. In January 2002, still on oral prednisone, he was diagnosed with degenerative arthritis of both shoulders. His prednisone was increased to 15 mg daily, and azathioprine 100 mg daily was added. In April 2002, his left acromioclavicular joint was injected with a corticosteroid for symptomatic relief. In June 2002, both acromioclavicular joints were injected with corticosteroids. In December 2002, he first noted an erythematous, warm rash that began simultaneously on both shoulders at the sites of his shoulder injections. In April 2003, he transferred his rheumatological care to our institution. His immunosuppressant regimen consisted of prednisone 10 mg daily, azathioprine 100 mg daily, and hydroxychloroquine 200 mg twice daily. He complained of fevers, fatigue, worsening bilateral shoulder pain, and progressive bilateral shoulder rash. In addition, he noted new dyspnea without cough. His shoulder pain now prevented him from carrying objects and performing his job. His left shoulder rash, shown in Figure , was macular, warm, erythematous, non-tender, and blanched with pressure. At its center was a 5-centimeter crusted ulcer with modest serosanguinous drainage, overlying the acromioclavicular joint. The surrounding erythema had progressed to include his entire left breast to the level of the nipple. It extended slightly onto the left arm and upper back, and did not cross the midline. On the right shoulder, there was a 5-centimeter circular patch of mottled erythema and warmth without ulceration or drainage, overlying the right acromioclavicular joint and symmetric with the central focus of the left-sided rash. There was no appreciable lymphadenopathy. Physical examination of the shoulders was limited by pain with both active and passive range of motion in all directions. There was a palpable effusion of the left shoulder, but not the right. Physical examination of his fingers, wrists, elbows, knees, ankles, and feet was otherwise normal with no evidence of synovitis. The consulting rheumatologist concurred with the original diagnosis of seronegative rheumatoid arthritis. However, due to the presence of the unexplained rash, alternative and additional diagnoses were considered, including dermatomyositis, sarcoidosis, cutaneous leukemia or lymphoma, and infection. Erythrocyte sedimentation rate was >140 mm/hr, and C-reactive protein titer was 1:16. Anti-nuclear antibodies, uric acid, rheumatoid factor, C3, and C4 were normal. White blood cell count was 13,400 cells/mm3 with a neutrophilic predominance, hemoglobin was 10.6 g/dL and platelet count was 400,000 cells/mm3. Serum albumin was 2.8 gm/dL. Serum electrolytes, renal function, liver tests, and creatine kinase were normal. A serum electrophoresis showed polyclonal hypergammaglobulinemia, and ferritin was elevated at 356 ng/ml, suggesting chronic inflammation. A chest radiograph was normal. A skin biopsy of the left shoulder cellulitis in July 2003 revealed non-caseating granulomatous inflammation consistent with sarcoidosis. Stains for fungus and acid-fast bacilli (AFB) were negative, but cultures were not performed. He was diagnosed with cutaneous sarcoidosis and treated with azathioprine 100 mg daily, prednisone 40 mg daily, and rofecoxib 25 mg daily. Chest CT revealed subtle reticulonodular parenchymal changes with lower lung zone predominance. Though the CT findings were compatible with the diagnosis of sarcoidosis, the lower lobe involvement and absence of lymphadenopathy were atypical. Because the clinical syndrome was not entirely consistent with sarcoidosis, repeat skin biopsy was performed in September 2003, this time with fungal and AFB cultures in addition to the routine pathology stains. Once again, pathology revealed granulomatous inflammation consistent with sarcoidosis with negative fungal and AFB stains. However, AFB cultures grew mycobacteria after only eight days. The diagnosis of MAI was made by DNA probe, and confirmed by culture. Bacterial and fungal cultures were negative. Serology for HIV was negative. Antimicrobial therapy consisting of azithromycin, ciprofloxacin and ethambutol was initiated in December of 2003 by an infectious diseases consultant. Azathioprine was discontinued and corticosteroids were tapered to 7.5 mg po qd, which was the lowest tolerable dose for the patient because of a return of his myalgias and arthralgias. Shoulder plain films and magnetic resonance imaging (MRI) revealed large joint effusions and evidence for avascular necrosis, greater on the left side (Figure ). Joint aspiration of the left shoulder revealed MAI by culture, and surgical drainage and debridement was performed in January 2004. Intraoperative findings included multiple rice bodies within the joint and a large cloudy effusion. Post-operatively, he was prescribed intravenous amikacin, which was discontinued after 2 weeks due to the development of renal insufficiency. In March 2004, because the cutaneous lesions over his shoulders continued to progress despite initiation of antimicrobial therapy and decrease in immunosuppression, ciprofloxacin was changed to moxifloxacin, and rifabutin was added to his regimen. The patient completed 21 months of multi-drug therapy with relief but not complete resolution of his rash and shoulder pain. In September 2005, his azithromycin, moxifloxacin, ethambutol, and rifabutin were discontinued on a trial basis because of cumulative drug toxicities. Unfortunately, fevers returned and the rash over the left anterior shoulder worsened. A repeat aspiration of his left shoulder confirmed persistence of MAI septic arthritis with a sensitive isolate. A follow-up CT scan of the chest showed no progression of his previously seen nodules. Antimycobacterial therapy has been re-initiated, and he has undergone a second debridement of his left shoulder. He has since responded to continued antimicrobial therapy documented by a negative joint aspiration, although he continues to have severe arthritic pain from permanent joint damage. One of two possible mechanisms probably explains the occurrence of MAI in the skin and shoulder. The first possibility is that MAI was introduced directly into the tissue at the time of injection. MAI is ubiquitous in the environment, including water sources, and can contaminate injectable solutions []. Because MAI grows slowly, a six-month lag between injection and clinical presentation, as seen in our patient, is biologically plausible. Hoffman et al estimated that 40% of the 19 patients with septic arthritis due to atypical mycobacteria in his series had had previous joint injection; however, only 1 of the injected patients had MAI []. It is not reported whether any of the 7 MAI septic arthritis patients in Kozin et al had been previously injected or aspirated []. Czachor et al reported a kidney transplant patient who developed MAI septic arthritis months after a diagnostic arthrocentesis for the diagnosis of gout []. In our patient, the temporal relationship between the shoulder injections, the subsequent appearance of simultaneous bilateral MAI skin infections at the site of the injections, and the eventual occurrence of left shoulder MAI septic arthritis, provides strong circumstantial evidence for the causative role of joint injection in this patient. Cellulitis of the overlying skin has not been described in previous reports of MAI septic arthritis [-,]. The second possibility is that the patient had undiagnosed disseminated MAI at the time of joint injection, and the trauma of injection caused concentration of the organisms at the injection sites. There is some evidence that this phenomenon occurs in patients with disseminated MAC. Freed et al reported a case of MAI soft tissue infection documented post-mortem at an IV injection site in an HIV- and MAI-infected patient []. Meadows et al reported an abscess due to MAI at the site of an intramuscular injection in an HIV-infected patient []. Prior to intra-articular injection, our patient had been treated with corticosteroids for approximately 3 years as well as short-term methotrexate and azathioprine. While this degree of immunosuppression makes disseminated MAI possible, there is little evidence to support the theory of pre-existing undiagnosed disseminated MAI infection in our patient, though it remains a possibility. Another possibility may be increased susceptibility to mycobacterial disease due to an underlying genetic defect in the IFN-帠 response pathway [].
Allie Avila	26	1996/3/29	416-656-0788	[email protected]	7349 Pena Wall Apt. 370	We report on a 56 year old male patient diagnosed with an esophageal carcinoma located in the middle of the esophagus with a subtotal stenosis at 32 cm from the incisor teeth. Endosonography performed preoperatively revealed a locally advanced tumor (uT3, N+). Following the oncological recommendations the patient underwent neoadjuvant radiochemotherapy with a total of 50 Gy and a 5-fluorouracil (5-FU) based chemotherapy (5-FU 15 mg/kg body weight on days 1??, cisplatin 75 mg/qm on day 7, repeated in week five). Thereafter, a subtotal esophageal resection combined with mobilization of the stomach through midline laparatomy and of the esophagus through the fifth intercostal area was done. The esophagogastric anastomosis was performed with a 25 mm stapler. Histological evaluation of the resected specimen revealed complete response of the esophageal carcinoma to the neoadjuvant radiochemotherapy with no tumor tissue detectable (ypT0, ypN0, ypMx). Increasing concentrations of acute-phase reactants in line with a dramatically decreasing general condition of the patient indicated a leakage that was confirmed by a gastrografin swallow demonstrating a anastomotic leak with gastrografin effusion into the left mediastinum (Fig. ). After lavage of the mediastinum and abdomen both were drained by a chest tube. Additionally, total parenteral nutrition as well as broad spectrum antibiotics were given. However, this nonoperative management to close the leak was unsuccessful and endoscopic stent implantation was planned. The endoscopic examination showed a wide leak in the anastomosis located 25 cm from the incisor teeth (Fig. ). Because of the excellent prognosis of the patient, we initially used a Polyflex self-expanding covered plastic stent (Willy R羹sch GmbH, Kernen, Germany; stent dimensions: 25 mm flare with 21 mm body, length 120 mm) placed 2?? cm distal the upper esophageal entrance to close the leakage (three weeks after the esophageal resection). Clinical change for the worse was suspicious of stent migration, but the endoscopic examination revealed that the polyflex stent was placed correctly. However, the caliber of 21 mm was undersized to attach tightly to the mucosa of the esophageal wall enabling running of fluids through the anastomotic leak (Fig. ). Without a commercial available esophageal stent with a larger inner diameter on hand a resection of the esophageal remnant and a hand made cervical esophageal anastomosis was performed six weeks after the first operation. Unfortunately, a leak in the hand made anastomosis was detected again. To close the leak we decided to use for the first time a covered colorectal Hanarostent (MTW Endoskopie, Wesel, Germany) (stent dimensions: 30 mm body, length 60 mm) which was placed four weeks after the second operation. This stent is designed for colorectal applications. The unique structure of the membrane connects the several separated segments made of nitinol wire to increase the flexibility of the stent and to prevent migration and tumor growth. This stent was placed without complications. Control endoscopy demonstrated a close seat of the stent to the gastric tube with complete covering of the anastomotic leak (Fig. ). Thereafter, the general condition of the patient increased continuously in line with a decrease of the acute-phase reactants. One week after metal stent implantation, oral feeding was restarted and the patient could be discharged from the hospital after another three weeks. Sixteen weeks after the second stent implantation, the stent was extracted and follow up endoscopy and gastrografin swallow indicated complete mucosal healing of the esophageal leak (Fig. ).
Jaylen Wang	36	1996/3/4	411-999-3289x1488	[email protected]	53181 Lopez Gateway Suite 443	A 55 year old woman developed anorexia, vaginal bleeding, and a non-productive cough over one month. Her last menstrual period was 11 months earlier, and she had noted some vaginal spotting for 5 months. CT scans revealed a large uterine mass and multiple lung nodules. An endometrial curetting showed small fragments of tumor consisting of two components; aggregates of atypical plump mononuclear cells with hyperchromatic, pleomorphic nuclei were interspersed with numerous large multinucleated osteoclast-type giant cells, some of which had more than 30 benign-appearing nuclei (Figure , Top). Up to ten mitoses power high-power field were observed in the mononuclear cells. Immunoperoxidase stain for the histiocytic marker CD68 was positive in a subpopulation of mononuclear cells and in the osteoclast-type giant cells. These cells were negative for the epithelial marker cytokeratin (AE1/AE3) which highlighted scattered benign endometrial glands. A fine needle aspirate of the lung showed sheets of atypical mononuclear plump cells and numerous scattered benign-appearing osteoclast-type giant cells (Figure , Bottom). Some mononuclear cells were positive for the endometrial stromal marker CD10; all mononuclear and multinucleated cells were positive for the mesenchymal cell marker vimentin; CD117 (c-kit) was weakly positive in multinucleated cells. All cells were negative for estrogen receptors, cytokeratins (7, 20, AE1/AE3), muscle specific actin and mucin. On presenting to our clinic, her history was remarkable for anorexia, uterine bleeding, dyspnea on exertion, a non-productive cough, and a 10 pound weight loss during the previous month. Her past history was notable for treated hypertension and hypothyroidism, an episode of gout, and monoclonal gammopathy of undetermined significance. Her medications were lisinopril, L-thyroxine, and a multivitamin. Her physical examination was notable for scattered crackles and occasional wheezes, and mild lower abdominal tenderness and fullness. A repeat CT scan revealed prominent tumor progression during the preceeding month, with a 11.6 cm uterine mass and lung nodules, some >4 cm in diameter (Figure ). Hemoglobin was 8.5 g/dl, AST, alkaline phosphatase, bilirubin, creatinine, and electrolytes were normal. Treatment was begun with pegylated-liposomal doxorubicin (45 mg/m2, day 1), ifosfamide (9 g/m2 total dose given by continuous infusion over 6 days, days 1??) with mesna uroprotection [], and bevacizumab 5 mg/kg every 2 weeks, with pegfilgrastim 6 mg given subcutaneously on day 7, with cycles repeated every 28 days. After the first cycle of chemotherapy, repeat CT imaging revealed a tumor response in the lung nodules (Figure ), although her symptoms were unchanged. At the start of cycle 3 her cough, vaginal bleeding, and dyspnea on exertion had noticeably improved. The dose of pegylated-liposomal doxorubicin was decreased by 10% for the third and subsequent cycles due to mucositis and skin rash. A CT scan before cycle 4 showed continued tumor regression. Blood pressure remained controlled and no proteinuria was noted. After 7 cycles the tumor had stabilized by CT imaging (Figure ). The lung nodules had largely disappeared, but the uterine mass remained at about 8.5 cm. She was given cycle 8 without bevacizumab in anticipation of hysterectomy. Repeat CT imaging showed stable disease, and she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy 8 weeks after cycle 8. The uterus contained a poorly demarcated tumor that measured 4.8 ? 4.0 ? 3.5 cm arising in the left lateral wall (Figure , Top). Multiple leiomyomata ranging from 0.3 to 2.2 cm were also identified. Sections from the tumor (Figure , Bottom) showed atypical mononucleated plump to spindle shaped tumor cells diffusely infiltrating the myometrium and within dilated blood vessels. Tumor cells accounted for approximately 30 % of the cells. Vascular invasion was observed. Occasional multinucleated giant cells of osteoclastic-type were also recognized; however, these were rare and tended to form small aggregates. Extensive areas of necrosis showed dystrophic calcification. Large numbers of histiocytes with foamy cytoplasm and hemosiderin granules were observed throughout the tumor; these cells accounted for approximately 70% of the cellular population. A subpopulation of mononuclear cells was positive for CD10; osteoclastic cells were non-reactive. Some of the mononuclear plump and spindle cells were weakly positive for actin; they were negative for desmin and smooth muscle myosin. CD117 was weakly positive in the osteoclastic cells. The cell division marker Ki67 was positive in tumor cells and negative in histiocytes and osteoclasts; Stains for common leukocyte antigen (CD45) and for the histiocytic marker CD68 were positive in histiocytes and osteoclasts, but were negative in tumor cells. Stains for lysozyme were weakly positive in histiocytes and osteoclasts but were negative in tumor cells. Stains for cytokeratin (AE1/AE3), estrogen receptors, and progesterone receptors were negative. Pelvic washings were negative; the cervix, parametria, tubes, and ovaries were free of tumor. Two months after the hysterectomy, progression of the lung nodules was noted on CT imaging and therapy with pegylated-liposomal doxorubicin and bevacizumab was begun, but progression was noted after 2 months. Gemcitabine (675 mg/m2 intravenously over 90 min given days 1 and 14 with pegfilgrastim days 2 and 15 due to neutropenia on day 8 of the first cycle, with cycles repeated every 28 days) [,] with bevacizumab was begun, but progression was noted after two months. Therapy was then begun with ifosfamide and etoposide [] and bevacizumab, and a partial response was observed after two months, with stabilization at 4 months. The patient received a total of 6 cycles of ifosfamide, etoposide, bevacizumab, although bevacizumab was held on day 14 of cycle 6 due to proteinuria. Two months later significant progression was noted. She received 1 cycle of dacarbazine, mitomycin c, and cisplatinum, with a very good response, but prominent toxicity including myelosuppression and fatigue. Two months later tumor progression was noted.
Kailani Dodson	41	1991/9/19	(923)406-1091x695	[email protected]	561 Cruz Station	A 47 year old female who was otherwise healthy presented with a sudden onset vertical diplopia associated with right sided headache and right eye pain. On examination she had a right hypotropia measuring 20^ for distance. Eye movements were limited in dextroelevation with associated discomfort. Ocular motility testing with a Lees chart showed a restrictive profile (figure ). There was no proptosis, ptosis or lid retraction. Snellen visual acuities were 6/5 in each eye. Colour vision and visual fields were normal. Anterior segment and fundal examinations were unremarkable. Thyroid function tests and inflammatory markers were within normal limits (Free T4 14.2 pmol/L, Free T3 5.9 pmol/L, TSH 1.48 mu/L, C-Reactive Protein 13 mg/L). An initial diagnosis of orbital myositis was suspected due to the marked painful limitation in elevation of the right eye. MRI of the orbits revealed no muscle or tendon abnormality but an incidental pituitary lesion was identified. Further intracranial imaging with contrast delineated a cystic pituitary mass compressing the chiasm which showed ring enhancement of the tumour, measuring 1.72 cm ? 1.28 cm ? 1.29 cm (figures , ). There was no radiological evidence of any intracerebral aneurysm or of invasion into the cavernous sinus. Pituitary hormone levels and serum osmolality were within normal limits (Prolactin 446 miu/L, Testosterone 1.7 nmol/L, FSH 13.0 iu/L, LH 6.4 iu/L, Growth Hormone 1.19 miu/L, IGF 1 22 nmol/L, Serum Osmolality 297 mosm/kg). The following week the patient developed anisocoria, slight right sided ptosis and her visual acuities fell to 6/12 right eye and 6/9 in the left eye. Although initially a macroadenoma or craniopharyngioma was suspected, further histological analysis revealed a benign squamous epithelium lined lesion which was consistent with an epidermoid cyst, dermoid cyst or a teratoma. There were no signs of infarction or haemorrhage. The lesion was removed by transphenoidal resection, leading to a gradual resolution of symptoms. There have been reports of recurrent or intermittent third nerve palsy as well as ptosis as a presenting feature of pituitary tumours [-]. However, an acute presentation with pain on eye movements and a restricted ocular motility pattern has not been previously documented. A large pituitary mass may compress any of the cranial nerves within the lateral wall of the cavernous sinus however this tends to be late in the course of tumour growth []. The third and fourth cranial nerves are more susceptible as the abducent nerve affords some protection from the internal carotid artery. Direct invasion of the tumour through the sinus wall may also occur. Mechanical compression of the oculomotor nerve against the unyielding interclinoid ligament of the cavernous sinus wall tends to bring about a slow onset paralysis. Rapid onset of third nerve paralysis has been attributed to compromise of the vascular supply to the nerve [], due to compression of the vasa nervorum originating in the internal carotid artery []. Sudden symptoms have also been seen in pituitary apoplexy [], where immediate treatment with bromocriptine and steroids has been advocated, on the basis that most macroadenomas are prolactinomas []. Finally, the possibility of a coincidental pituitary tumour and a spontaneously recovering micro-infarctive third nerve palsy must also be considered.
Seven Torres	29	1986/3/21	476-287-0640	[email protected]	58145 Brian Villages Suite 482	A healthy 15-year-old girl was referred following a five day history of a unilateral red left eye. The eye was becoming progressively more inflammed, with epiphora, photophobia and blurred visual acuity. On examination, the visual acuity in the affected eye was 6/6 compared with 6/5 in the other eye. The conjunctiva was inflamed with a follicular reaction including the corneal margins superiorly. There were enlarged pre auricular nodes. A diagnosis of viral conjunctivitis was made and viral plus bacterial swabs were taken. The patient was commenced on fucithalmic to prevent secondary infection and told to re attend if she deteriorated. Five days later, she returned feeling that the eye had become more tender with increased swelling of the lids plus tenderness over the maxillary sinus. On examination, there was marked oedema of the upper and lower lids accompanied by erythema. The tarsal conjunctiva revealed follicles. Extra ocular movements were full but uncomfortable on elevation. Pupil, colour vision examination and direct visualisation revealed a healthy disc. She was apyrexial and systemically otherwise well. A secondary diagnosis of bacterial pre septal cellulitis was made and the treatment was changed to oral ciprofloxacin 750 mg twice daily for one week, plus two hourly topical exocin drops. Two days later the patient was reviewed. She now complained of a large amount of purulent discharge. The pre septal swelling was still marked and examination of the conjunctiva again revealed large numbers of follicles and large papillae. All bacteriology and viral swabs had been negative and the patient was re swabbed for chlamydia despite denying any genitourinary symptoms. Giemsa staining of conjunctival scrapings revealed cytoplasmic inclusion bodies and the patient received a one gram single dose of Azithromycin. She was asked to attend the local genitourinary clinic and to alert any current and previous sexual partners to their need to do likewise. Her symptoms completely resolved following administration of the Azithromycin and there were no further complications. Unfortunately, the patient declined to have photographs taken.
Violet Morris	29	2001/1/4	001-772-697-0498x8706	[email protected]	09332 Robert Cape	A 41-year-old man had tolerable pain in his shoulder, which developed gradually over a 10 years' period. The pain occurred with shoulder motion, particularly in relation to his golf swing, since he was aiming at a professional career as a golfer. On physical examination of the scapula, "clunking" was noted once from 90 degrees of abduction to 180 degrees. However, active range of motion (ROM) was normal. There was no winging of the scapula. The upper extremity and shoulder girdle muscle strength was normal. A trans-scapular roentgenogram showed a pedunculated type of a bony projection, which was continuous with the scapula (Figure ). Computed tomography (CT) images revealed a bone tumor on the anterior surface of the right scapula and inferior to the spine. The size of the tumor was 1.8 ? 1.5 ? 1.0 cm. The images demonstrated the continuity between the bone tumor and the scapula (Figure ). The lesion was diagnosed as an osteochondroma resulting in a snapping scapula syndrome. Removal of the tumor was performed to relieve pain with the "clunking" of the scapula. Under general anesthesia, the patient was placed in a prone position, with the right arm draped free to allow a full range of motion. The lesion was approached through a 2-cm incision along the lower lateral aspect of the scapula. The teres major muscle was dissected on the same line. Then scapula was elevated by a retractor and then the 2.7-mm-diameter, 30 degrees Hopkins telescope (Karl Storz, Tuttlingen, Germany) was introduced into this portal. Since the tumor was covered by the subscapularis muscle, a part of the muscle was removed to access the tumor by use of graspers. Consequently, the tumor was visualized and resected in a piece-by-piece manner by the use of graspers of different sizes (Figure ). Finally, a Black Max cutting burr (Anspach, Florida, USA) was applied to smooth the remnants of the tumor. Both the graspers and the burr were introduced through the same portal. The wound was closed over a suction drain, which was removed after 24 hours. The duration of surgery was 2 hour and a half. The patient did not need shoulder immobilization with sling. Immediately after the operation pain relief was obtained, and the "clunking" disappeared during full range of active shoulder motion. CT images showed complete tumor resection (Figure ). The patient could start playing golf one week after the surgery. Histology confirmed the clinical diagnosis of osteochondroma (Figure ). The scar was small to which the patient was satisfied (Figure ).
Christian Lugo	42	1985/12/28	(535)575-2303x655	[email protected]	52251 Nancy River	A 28-year-old woman presented to A&E with a short history of diarrhoea and vomiting associated with high fevers, sore throat and flushing of her skin. There had been no recent foreign travel, exposure to toxins or drugs, nor gynaecological symptoms. There had been no recent use of tampons. She had not been menstruating while using 3-monthly intramuscular injections of Depo-Provera, a long-acting progesterone, as contraception. Interestingly, 6 years earlier she had been admitted with a toxic shock-like syndrome to another hospital and required ITU care. At that time and without serological confirmation, it was presumed that a staphylococcal or possibly streptococcal infection had triggered her condition. On examination she looked unwell. She was distressed and flushed with widespread erythema of her skin. Her temperature was raised at 39.6簞C and pulse elevated at 120 beats per minute with regular rhythm. Her blood pressure was maintained at 110/70 mmHg. Cardiac auscultation was normal, as was the rest of the clinical examination. A subsequent pelvic examination was normal. Blood tests showed a white cell count of 9.4 ? 109/l with left shift of neutrophils. The CRP and ESR were raised at 250 ng/ml and 45 mm/hr respectively. Arterial blood gases demonstrated respiratory alkalosis with pH 7.57, pO2 13.8 kPa and pCO2 2.2 kPa. A chest radiograph was normal. She received aggressive intravenous fluid resuscitation. After blood was drawn for culture, intravenous cefuroxime and clarithromycin were empirically prescribed for a presumed bacterial septic illness. However the antibiotics failed to control either her pyrexia or her tachycardia. Her rash initially resembled severe sunburn but went on to exfoliate and then desquamate after two days. Dermatology opinion agreed that the skin condition was consistent with a diagnosis of TSS, and supportive treatment recommended. Her serum albumin dropped to 20 g/l during the first few days of her admission. Her temperature remained elevated at 38??9簞C. Repeated blood cultures were sterile while stool cultures were negative for bacterial pathogens. All throat, skin and high vaginal swabs yielded no growth. Paired acute and convalescent antistreptolysin 0 titres and antistaphylolysin 0 titres showed no rise. Rheumatoid factor, antinuclear and other autoantibodies were negative. C1 esterase inhibitor and complement levels were normal. Screens for viruses, toxic metals, cardiolipin antibody, urinary porphyrins and porphobilinogen were all negative. Five days after admission her fever rose to 40簞C and she became more unwell with delirium. Her pulse rose to140 beats per minute. An echocardiogram was normal. She was transferred to the ITU for further observation. Since no bacteria had been cultured after 5 days and since she had made no response to antibiotics and remained very unwell, a decision was made to empirically administer corticosteroids. This decision was based on anecdotal reports, and a retrospective analysis had suggested possible benefit from corticosteroid use []. She was given intravenous methylprednisolone 1 g daily for three days. Administration of this corticosteroid rapidly and dramatically improved her clinical condition with resolution of her temperature and tachycardia. She was converted to oral steroids and discharged home with prednisolone 30 mg daily. The dose was subsequently tapered over 6 weeks at outpatient follow up, and she remains well 2 years later.
Kaylie Bradford	40	1981/11/8	(403)552-7105x935	[email protected]	56611 Williams Rapid Apt. 711	A 38 year-old male ophthalmologist was seen at the Ophthalmic Accident and Emergency Department with a five-hour history of a right watery red eye. He had been exposed to several conjunctivitis patients during the preceding few days, whilst working at the same department. An initial diagnosis of probable viral conjunctivitis was made, and the patient was prescribed chloramphenicol eye drops. Conjunctival swabs were taken and sent to the microbiology laboratory for analysis. A day later the conjunctivitis had become bilateral and purulent. Several hours after the conjunctivitis became bilateral the patient also developed a sore throat. The previous swab cultures isolated Streptococcus pneumoniae as the infective pathogen. Three days later, the patient noticed tenderness and swelling of the proximal interphalangeal joint of the index finger in the left hand, which became progressively more swollen and tender over the next couple of days. The patient had become febrile; however, there were neither chills nor rigors. He was prescribed oral amoxicillin 500 mg TID and flucloxacillin 500 mg QID, in the belief this was septic arthritis. Two days after the swelling started he was seen by a rheumatologist, who made a diagnosis of reactive arthritis. The patient was fully investigated (see following text and Table ). Plain X-ray showed a little soft tissue swelling over the proximal interphalangeal joint of the left index finger. The patient was negative for antineutrophil cytoplasmic antibodies (ANCA), rheumatoid factor (RF), anti-DNA antibodies and antinuclear antibodies; complement factors C3 and C4 were within the reference range. No pathogen could be grown in blood culture and joint aspiration (performed by the rheumatologist) yielded no synovial fluid. The patient was HLA-B27 negative. A firm diagnosis of reactive arthritis as a sequel to pneumococcal conjunctivitis was made. Anti-inflammatory drugs resolved the swelling and pain within 48 hours. The conjunctivitis had already recovered though the antibiotics were continued until the course was completed.
Ander Leach	38	1984/6/30	(448)862-2465	[email protected]	71178 Ramsey Orchard	A 13-year old girl presented with a rapidly progressive paralysis and encephalopathy. She had a mild viral-like illness for the preceding week, with lethargy. Over the days preceding presentation she developed back pain and difficulty in walking. On the morning of admission, she developed a headache, vomiting, a fluctuating level of consciousness and became unable to move her limbs. Neurological examination showed an encephalopathic girl, with four limb paralysis, absent deep tendon and abdominal reflexes, and mild bilateral facial weakness. A high thoracic (C4) sensory level, severe urinary retention and stool incontinence was evident. Systemic examination did not reveal pyrexia, rash, lymphadenopathy, hepatosplenomegaly or sepsis. Her remote clinical history was notable: at age 2 years, she had developed acute lymphoblastic leukaemia (ALL), common B-cell variant. Six months after completing chemotherapy using the UKALLXI protocol, the girl re-presented with an encephalopathy due to a CNS and bone marrow relapse of the leukaemia. The girl received cranial irradiation and further chemotherapy on the MRC UKALL R2 relapse protocol which achieved a further remission. Because of the high risk of further relapses, she proceeded to have an bone marrow transplant (BMT) with a matched unrelated male donor. Total body irradiation was used in conditioning for the BMT. Following the BMT, the girl was in prolonged remission for the following 7 years with no overt CNS or systemic sequelae. Initial MR imaging showed diffuse involvement of the CNS (Figures and ). The spinal cord was diffusely swollen showing central cord T2 hyperintensity from C1 to the conus. There were multifocal grey and white matter lesions in the cerebral cortex, subcortical areas and cerebellum which showed diffuse gadolinium enhancement. The appearances were consistent with an infective or inflammatory encephalomyelitis, but the girl's remote history and presentation raised the concern of a recurrent CNS relapse of ALL. CSF examination revealed 125 white cells with a lymphoblastic appearance and 5 red cells. CSF protein (0.61 g/l) and CSF:blood lactate ratio (3.2:1.2 mmol/l) were raised with a low CSF: glucose ratio (4.3:8.9 mmol/l). CSF cytospin showed increased proportion of lymphocytes which further increased suspicion of ALL relapse (Figure ). Immunophenotyping of the CSF cells demonstrated the cells were CD10 negative, strongly CD2 and CD7 positive and terminal deoxynucleotidyl transferase (TdT) negative. These findings suggested that the cells were mature T-cells. Cytogenetic studies and FISH using centromeric X and Y-chromosome markers on the CSF lymphocytes confirmed that the overwhelming majority of cells were of male donor type (6??4% of cells were of host origin but not clonal). These CSF findings, along with a normal peripheral blood count and normal bone marrow biopsy confirmed that the girl's illness was not due relapse of her previous ALL. The girl was treated with intravenous high-dose methylprednisolone and aciclovir. Blood-brain barrier studies showed an abnormal CSF IgG index; oligoclonal bands were not detected. Further negative tests included: CSF culture; CSF PCR for HSV1 and 2, VZV, EBV, HHV6/7, adenovirus, echovirus, parechovirus, enterovirus and echovirus; serology for influenza, mycoplasma, Chlamydia, and toxoplasma; ASOT, ANA, ANCA, anticardiolipin antibodies, tissue autoantibodies. Immune function tests did not reveal an underlying inmmunosuppression. A presumptive diagnosis of ADEM with associated transverse myelitis was made. The girl's encephalopathy resolved over succeeding days without overt cerebral sequelae, but spinal recovery was much slower. A repeat MRI at 2 weeks after onset showed resolving brain and spinal lesions. Her disability slowly improved over several months: Barthel activities of daily living index was 15/100 at 3 weeks, 40/100 at 7 weeks, and 85/100 at discharge from hospital 3 months after onset. At last review, 10 months after onset, her Barthel index was 100/100. She was mobile on her feet without aids, and had just ceased intermittent catheterisation for urine voiding. She was unable to walk on her heels, and had lingering fatiguability.
Martha Roberts	44	1978/6/29	(542)385-2535	[email protected]	240 Emma Key Apt. 263	A 72-year old male was referred to the vascular outpatient clinic with an asymptomatic right carotid bruit, for work up before planned coronary artery bypass grafting. His duplex ultrasound showed a 70??0% stenosis of the right internal carotid artery. He was found also to have an incidental 5.6 cm infra-renal abdominal aortic aneurysm (AAA). He underwent multi-sequence MR imaging pre- and 36 hours post USPIO infusion. Multi spectral imaging was acquired at 1.5 Tesla using a whole body system (GE Medical Systems, Milwaukee) and a custom designed 4-channel phased array neck coil (Flick Engineering Solutions BV) along with a standard body coil to improve signal to noise ratio. The patient subsequently (24 hours) underwent a right carotid endarterectomy and was discharged home after an uncomplicated hospital stay of three days. The ex-vivo specimen was kept fresh and immersed in an MR inert fluid (Fomblin, Performance Fluids Ltd, UK) and imaged in a dedicated single channel micro-coil 4 hours after surgery. Following this, the specimen was washed, fixed in formalin and embedded in paraffin wax. The paraffin block was divided into 3 mm sections and thin sections were cut from each block. These sections were stained using various techniques including haematoxylin and eosin (H&E) and elastin Van Giesen (EVG). This histology was co-registered with the ex-vivo and in-vivo MR using the bifurcation as a point of reference. There were no problems with the co-registration of the in-vivo images with the ex-vivo images or the histology (see Figure ). An elective endovascular repair of his AAA has been scheduled.
Josiah Meyer	41	2004/4/11	910-476-0917x7472	[email protected]	2995 Henry Spurs	A 39-year-old woman had a left kidney tumor incidentally discovered during CT scan as part of a diagnostic workup for colonic diverticulosis. She had no personal or family history of TSC, lymphangioleiomyomatosis, renal cyst, renal malignancy, or estrogen hormonal therapy. The CT scan revealed a 2.5-cm complex cystic mass in the upper pole of the left kidney with a 1-cm enhancing nodule in its wall, radiologically worrisome for cystic renal cell carcinoma. In view of this concern of malignancy, the patient elected to undergo laparoscopic left partial nephrectomy for definitive surgical treatment. The entire tumor was surgically resected with an excellent margin of 5-mm of normal parenchyma surrounding the entire cyst wall, and the tumor was confined to the kidney. Grossly, the tumor was well demarcated and partially cystic, with the largest cyst measuring up to 1.1-cm. Sectioning of the tumor revealed part of the cyst wall contained a single 1-cm mural nodule with homogenous tan cut surface. The entire tumor was submitted for histological examination and revealed three components. The first component was cystic or multicystic spaces lined by epithelium, that ranged from flat to cuboidal to columnar. Whilst the cuboidal to columnar cells had unremarkable clear cytoplasm, the flat cells had abundant eosinophilic cytoplasm with nuclei that often protruded into the lumen, resulting in a hobnailed appearance (Figure ). The second component was a subepithelial "cambium-like" condensation of small stromal cells with indistinct cytoplasm immediately subjacent to the cyst epithelium. This subepithelial stroma showed prominent capillary vasculature (reminiscent of endometrial or mullerian-like stroma) and prominent lymphoplasmacytic infiltrate (Figure ). The third component was a thick exterior wall of plump smooth muscle cells with focally clear cytoplasm arranged in poorly formed fascicles, often appearing to emanate from irregular and tortuous blood vessels (Figure ). The third component was exterior to the subepithelial stroma and was typical of myomatous or muscle-predominant predominant AML. Additionally, non-cystic native renal tubules were observed entrapped within this exterior muscular wall (Figure ). Immunohistochemically, HMB45 (Figure ) and Melan-A labeling was patchy in the exterior muscle-predominant AML component, but were most intense and concentrated in the compact subepithelial cellular stroma. Conversely, smooth muscle actin (Figure ) and desmin labeling was most intense and concentrated in the exterior muscle-predominant AML component, but were patchy in the compact subepithelial cellular stroma. Similarly, the compact subepithelial cellular stroma showed strong and diffuse nuclear labeling for estrogen receptor (ER) (Figure ) and progesterone receptor (PR) (Figure ), along with strong and diffuse cytoplasmic labeling for CD10 (Figure ), but labeling for ER (Figure ), PR (Figure ), and CD10 (Figure ) were patchy in the exterior muscle-predominant AML component. However, vimentin (Figure ) showed strong and diffuse cytoplasmic labeling of all 3 components equally. The cyst lining was positive for epithelial markers (pancytokeratin [Figure ], AE1-AE3, and CK7), but negative for melanocytic (HMB-45 [Figure ] and Melan-A), muscular (smooth muscle actin [Figure ] and desmin), and hormonal (ER [Figure ] and PR [Figure ]) markers. The tumor showed low proliferative index with Ki67 labeling less than 1% of neoplastic cells (Figure ). Additionally, RCC marker antigen, inhibin, WT-1, c-kit (CD117), S-100 protein, and CK20 did not label any of the 3 components of the tumor (not shown). Except for patchy labeling of blood vessels, CD34 (endothelial markers) did not label any of the 3 components of the tumor (not shown). The patient herein presented is alive with no evidence of recurrence or metastatic disease, 12 months postoperatively, and follow-up with interval abdominal imaging studies is planned.
Sara Bridges	31	1977/10/6	(627)765-2649	[email protected]	5813 Brandon Curve	A 73 year old African American male with history of SCCA of the esophagus presented with mild dysphagia. Subsequent endoscopy (EGD) revealed recurrent SCCA of the esophagus. Seven years prior he was diagnosed with a T1-2, N1 SCCA of the left anterior tonsillar pillar and treated with radiation therapy (XRT) (6660 cyG to the primary tumor). Four years later he developed Stage III esophageal SCCA (T4, N0, M0), by chest CT, located at 33 cm from the incisors that was 3 cm in length. This lesion was treated with 5400 cGy XRT and chemotherapy with curative intent. On the third (current) presentation, a moderately differentiated, T2, by endoscopic ultrasound (EUS), SCCA lesion at 24 cm was discovered (Figure and ). This new lesion was above the prior field of XRT and proximal to the original stage III esophageal SCCA. The patient was evaluated by the institution's tumor board and deemed neither a surgical nor XRT candidate based on significant cardiac comorbidities and maximum dose XRT with his prior treatments. Palliative treatment options were explored. Based on the success with ablation of esophageal lesions as described above, palliation via CSA was pursued for this patient. At the time of this case, the device was under an investigational device exemption (IDE) issued by the FDA. Therefore, an FDA Humanitarian Use Device exemption was requested and granted for use of the CSA device. The patient signed a consent form approved by the authors IRB and the FDA. The patient's 2 cm long, hemi-circumferential SCCA was treated with two 30 second pulses of CSA under direct endoscopic visualization on an outpatient basis (Figure ). This particular dosimetry was chosen based on early clinical trials in Barrett's esophagus and swine data. The first CSA of Barrett's esophagus in clinical trials used a dose of 40 seconds (two 20 second applications separated by a 20??0 second thaw). Early animal studies at the author's institution (unpublished) have demonstrated that the depth of injury correlates with duration of freeze. High grade dysplasia has been effectively treated with CSA at 20 seconds times three cycles. Thus in hope of achieving greater depth of injury without excessive necrosis, two cycles of 30 seconds each were applied. CSA was applied in such a way that the entire tumor with margins of 1?? cm was frozen. This technique resulted in a near circumferential freeze of the esophagus but with a focus on the tumor which endoscopically appeared hemi-circumferential in distribution. Interestingly, freezing of the tumor under direct endoscopic visualization demonstrated that the tumor differentially retracted when frozen relative to the surrounding esophageal mucosa making the margins of the tumor more distinct. Prior to freezing, the margins of the tumor diffusely blended into the esophageal wall. This patient was treated with lansoprazole 30 mg BID throughout the CSA period. The patient experienced no initial complications. One month latter a follow-up EGD revealed endoscopic resolution of the tumor, but biopsies remained positive for moderately differentiated SCCA (Figure ). CSA of the area was repeated, treating 40% of the esophageal circumference 4 cm in length spanning the prior SCCA with three, 20 second pulses. This shorter pulsed duration of CSA was chosen because less depth of injury was desired based on the significant response with the initial treatment. Increased numbers of CSA cycles are associated with greater tissue injury. Therefore the intent was a more intense treatment but with less depth of injury. Twenty-four hours later, the patient experienced odynophagia requiring oral narcotics for 3 weeks followed by the development of a stricture at one month post-CSA. This was treated with Savary dilation but has subsequently become a persistent esophageal stricture at that the site. Biopsies at the cancer site 6 weeks after the second cryoablation and bimonthly in the subsequent 12 months of follow-up were completely negative for dysplasia or neoplasia. The persistent esophageal stricture (Figure ) has required multiple dilations with various types of dilators (with and without corticosteroid injections) and temporary (3 month) esophageal stent (Polyflex簧 by Wilson Cook) placement. The patient continues to work and remains cancer free 24 months post-treatment.
Mohammed Duarte	45	2000/3/9	+1-721-384-9987x4818	[email protected]	12121 Donald Loaf Suite 690	A 53-yr-old male with T3N2M1 non-small cell left upper lobe lung cancer with bilateral brain metastases diagnosed one-month prior was referred for management of dyspnea and hemoptysis. The patient had noted a dramatic increase in dyspnea over the prior 3 days. Past medical history was unremarkable and he had a negative smoking history. Physical exam revealed reduced breath sounds in the left lower zone. Chest x-ray demonstrated a left hilar mass with loss of volume and post obstructive pneumonia in the left lower lobe (Figure ). Axial Computed tomography (CT) angiogram of the chest also revealed multiple segmental and subsegmental pulmonary emboli and the patient was admitted for anticoagulation with low molecular weight heparin (enoxaparin). The CT study also confirmed total occlusion of the left mainstem bronchus by a tumor invading from the left hilum (Figure ). After two days of anticoagulation, rigid bronchoscopy was performed using an Efer-Dumon rigid bronchoscope. Normal vocal cords, trachea, carina and right bronchial tree were confirmed. A large endobronchial lesion with complete occlusion of the left mainstem bronchus was identified (Figure ). After an unsuccessful attempt to pass the lesion using a pediatric video bronchoscope, debulking was attempted using a combination of polypectomy snare and electrocautery. There was still 100% obstruction of the airway from the residual tumor and therefore the ERBE argon plasma electrocoagulator簧 (APC) was utilized to devitalize the tissue. The devitalized tissue was then debulked using the Straightshot簧 microdebrider with rotating tip (Figures , ) and the bevel of the rigid bronchoscope. The length of the microdebrider is 45 cm and outer diameter is 4 mm. The rotating tip is controlled by a fly-wheel on the hand-piece, which allows for better maneuverability and is angled at 12 degrees providing better visualization. The blade was serrated and an oscillator mode was used at 1000??200 RPMs. In this manner the left main stem was recanalized and the channel was opened into the left lower lobe bronchus. Hemostasis was achieved using a combination of suction and APC with less than 20cc blood loss. Visual examination revealed that there was some degree of extrinsic compression in the left lower lobe bronchus as well; however, the superior segment bronchus and the basal segmental bronchi were noted to be patent. Post procedure residual obstruction in the left main stem bronchus was estimated at less than 20%. Since the left upper lobe had been completely replaced by tumor, a guidewire was then placed into the left lower lobe bronchus and a 4 cm ? 14 mm covered nitinol self-expandable metal stent was placed over the guidewire under direct vision into the left lower lobe bronchus. The stent was deployed under direct vision and adjusted in terms of its position using rat-tooth forceps. At the end of optimal positioning, the distal aspect of the stent was noted to be just inside the left lower lobe basal segmental bronchus with the superior segment being ventilated through the uncovered portion of the stent. The proximal aspect of the stent was noted in the left main stem bronchus well above the proximal extent of the tumor (Figure ). Follow-up chest x-ray (Figure ) revealed aeration of the left lower lobe with resolution of dyspnea and hemoptysis.
Kynlee Walsh	42	1979/6/13	+1-410-498-7525x47860	[email protected]	076 Hughes Land	A 22-year-old lady was presented with an abdominal swelling?round a previous caesarian section scar?radually increasing in size for one year. In the last 2 days, it became tense, increased in size, and very painful. There was no vomiting or abdominal distention and she had normal bowl habits. She had mild fever but no otherwise significant symptoms. There was no past history of trauma or thorn prick injury to the site of the swelling and no other body swellings. She was not known diabetic or having any other chronic illness. On examination, she looked ill but not pale nor emaciated. Her pulse rate was 100 per minute, her temperature was 38簞C. Her abdomen was not distended; there was a subumblical midline scar. There was a swelling involving the umbilical region and encroaching the hypogastrium about 5 ? 8 cm, the swelling was tense, and did not increase in size with coughing, skin over it was normal. It was tense, tender, hot, firm in consistency, and nonreducible. There was no organomegaly and bowl sounds were heard normal. A provisional diagnosis of obstructed incisional hernia containing an omentocele was put and the patient was prepared for surgery. Her hemoglobin was 10.5 g/dl, her urine was clear, and her renal and liver function tests were within normal range. There was no peritoneal sac identified intraoperatively; instead a nodulated mass which involved the anterior and posterior walls of the rectus sheath together with the rectus abdominis muscle. The peritoneum was intact. On dissecting the mass, pus was found trickling from cavities containing black grains. The mass was excised with a margin of safety, the field was soaked with iodine tincture 2%, and the rent was closed. The patient was put on ketoconazole tablets 400 mg/d for 6 months to be followed in the referred clinic. Histopathological examination revealed macroscopically 4 masses of soft tissue measuring 1, 2, 4.5, and 4 cm. Microscopic sections showed grains of Madurella mycetomatis, surrounded by heavy neutrophilic inflammatory cells (type 1 reaction).
Bodhi Lang	39	1985/4/14	+1-609-631-0671x2517	[email protected]	098 Rodriguez Garden Apt. 919	A 50-year-old lady presented with a rapid increase in the size of a thyroid swelling of 20 years duration associated with pain, fever, dysphagia, hoarseness of voice and stridor. She was toxic, pale (Hb = 7 gm%) and tachypnoic with engorged neck veins. There was a 5 ? 3 cm ulcero-proliferative growth in the region of the thyroid(fig. ). Indirect laryngoscopy was suggestive of a paralyzed left cord and fine needle aspiration cytology (FNAC) revealed pus with necrotic debris consistent with diagnosis of thyroid abscess. Ultrasonography and CECT(contrast enhanced computed tomography) neck were however suspicious of thyroid malignancy with cystic degeneration and pressure effects on trachea (fig. ). Chest radiograph/ultrasound abdomen and thyroid function tests were normal. In view of the pressure symptoms and suspicion of malignancy, the patient underwent surgery in the form of left hemi-thyroidectomy with drainage of abscess and central neck dissection. Gross examination of the specimen revealed a weight of 35 grams with a nodule measuring 3 ? 3 ? 2 cm with a thin capsule. The cut surface was grey-white with focal areas of purulent material. On histopathological examination polygonal tumor cells were seen adjoining an area of lymphocytic thyroiditis and focal necrosis. Squamous differentiation of tumor cells was seen as cellular keratinization and keratin pearl formation. There was marked pleomorphism of nuclei and occasional abnormal mitosis and no evidence of associated follicular adenoma/carcinoma or papillary carcinoma. The level VI lymph nodes showed squamous cells with necrotic changes. Staining with mucicarmine and PAS (periodic shiff test) were negative. Immunohistochemistry showed pancytokeratin positivity while thyroglobulin and calcitonin were negative. Histopathological diagnosis was squamous cell carcinoma of thyroid with metastasis to pre and para tracheal lymph nodes (fig. ). The postoperative period was stormy but she eventually recovered and was discharged on the tenth day. She received adjuvant radiotherapy (50 Gy) but succumbed to her disease within 7 months of her surgery.
Amirah King	39	1991/1/28	001-488-209-6482x97962	[email protected]	548 Donald Place	A 60-year-old gentleman presented to the surgical emergency with difficulty in breathing, hoarseness of voice and stridor. He had undergone subtotal thyroidectomy for a non-toxic goitre 25 years previously at a remote district hospital. Emergency tracheostomy had to be done since he was in respiratory distress. There was a 5 ? 6 cm, hard, ulceroproliferative growth in the midline with hard, palpable lymph nodes in the pre and paratracheal region (fig. ). CECT head and neck revealed a thyroid growth infiltrating in to the larynx with metastatic (level-II, III, VI) cervical lymph nodes. No other site of malignancy could be detected inspite of an exhaustive battery of investigations including CECT (chest) and panendoscopy. Fine needle aspiration cytology from the swelling revealed a poorly differentiated squamous cell carcinoma of thyroid. Surgery in the form of wide local excision including the skin around the swelling and ulcer, total thyroidectomy with laryngectomy and resection of the anterior wall of pharynx was performed. Modified radical neck dissection (Type-I i.e. preserving internal jugular vein on left side) and radical neck dissection (on right side) along with central neck dissection were performed. In view of the skin and tissue loss the reconstruction was done using bilateral deltopectoral (DP) fasciocutaneous flaps. Histopathological examination of the specimen revealed squamous cell carcinoma of thyroid with anaplastic changes and clear margins. Postoperative period was stormy but the patient eventually recovered and received adjuvant radiotherapy (50 Gy) in fractionated doses. He however died of an acute attack of myocardial infarction nearly one year after his surgery.
Julian Burke	36	1985/4/3	764-902-1517	[email protected]	597 Claire Junctions Suite 207	A 58-year-old-male from an endemic zone of goiter (sub-Himalayan belt of north India) presented with a recurrent thyroid swelling which had been increasing in size rapidly for the past three months(fig. ). He had undergone subtotal thyroidectomy for goiter, 15 years back. He was in distress with engorged neck veins and stridor along with a midline 5 ? 5 cm ulcero-proliferative growth along and left cervical lymphadenopthy (levels-II, III, VI). The fine needle aspiration cytology of the swelling and the edge biopsy from the ulcer confirmed the diagnosis of squamous cell carcinoma of thyroid. No other site of the squamous cell carcinoma could be detected inspite of an exhaustive clinical and radiological/endoscopic evaluation. The patient was managed by curative wide local excision, including total thyroidectomy and left sided radical neck dissection. He received adjuvant radiotherapy (50 Gy in fractionated doses) and follow up of one year is satisfactory.
Vera Hardy	26	1994/6/18	001-981-319-7663x811	[email protected]	347 Shelby Plains	A 40-year-old para four obese Caucasian woman with two-year history of lower abdominal pain was referred from a peripheral hospital for the further management of bilateral adnexal masses. The computerised tomography (CT) scan of abdomen and pelvis revealed a complex cystic lesion of 7?? cm in the right adnexum and bilateral ureteric obstruction. All baseline blood tests including haematology and tumour markers (CA 125 -26 IU/ml) were normal. The serum tests showed normal liver function and moderately impaired renal function (creatinine 10??5, urea > 200). She had a complex medical history including obstructive sleep apnoea, asthma, glaucoma, hypothyroidism, hypertensive cardiomyopathy and bipolar disorder; registered disabled. She also had a copper intra uterine contraceptive device in situ for the past three years. Given her body habitus (BMI 42), abdominal and pelvic examination was difficult and non-specific. The only finding of relevance was bilateral adnexal fullness. She was managed within the gynaecological oncology multi disciplinary framework (MDT). On reviewing the CT films the features noted include bilateral basal pleural thickening, bilateral hydronephrosis, retroperitoneal lymphadenopathy associated with retroperitoneal fibrosis and bilateral adnexal cystic masses. There was a small volume of ascites. Magnetic resonance imaging (MRI) was performed for further characterisation of the adnexal masses. The right adnexal complex cystic lesion measured 8 ? 7 ? 7 cm in diameter and had a thick wall (up to 2 cm), which was irregular. There were several septations, some of which measured 3 ??4 mm. There were no enhancing papillary formations, although the wall and septa enhanced. The appearance suggested an ovarian lesion with possible involvement of the Fallopian tube. The left adnexal cyst measured 5 ? 6 ? 4 cm, had a smooth wall and contained a single thin septation, consistent with a benign ovarian cyst. Both cysts contained fluid, which was low on T1 and high on T2, with no evidence of fat or blood. Surrounding the cysts posteriorly, the fat was streaky in appearance and there was marked thickening of the adjacent fascial planes, with thickening of the mesorectal fascia up to 1 cm. The fascial thickening extended up the pre-sacral space and along the posterior aspect of the pelvic sidewalls, resulting in the obstruction of the ureters. Enlarged lymph nodes (up to 1.8 cm in short axis) were present along both pelvic sidewalls, which were striking due to the very high T2 signal intensity (Figure ). Nodes were also seen in the inguinal and para-aortic regions. Although the imaging appearances could not rule out an ovarian neoplasm, the features noted above were suggestive of an inflammatory process. In view of the woman's medical history and clinical status the MDT recommendation was clinical review and imaging guided biopsy of lymph nodes. The woman underwent CT guided right inter iliac node biopsy, following an unyielding biopsy of inguinal nodes. Histology revealed non-caseating granulomatous lymphadenitis with negative stains for acid-fast bacilli and fungi. There was no foreign body seen. Given the histological findings our attention was directed towards an inflammatory process. She was subsequently referred to respiratory physicians, with a working diagnosis of sarcoidosis. She was also referred to urologists for the management of retroperitoneal fibrosis and bilateral hydronephrosis. Abdominal pain prompted insertion of bilateral JJ ureteric stents. The physicians initiated a (step-down) course of prednisolone. Symptomatic improvement was observed but the renal function did not change. Repeat imaging demonstrated resolution of hydronephrosis. The woman was reviewed again clinically after the course of steroids. During this interval the physicians ordered an autoantibody screen as autoimmune disease can co-exist with sarcoidosis; the screen was negative (Rheumatoid factor, anti-DNA antibody and antinuclear antibody). On examination there was no evidence of any palpable lymphadenopathy. An ultra sonographic examination six months later demonstrated a bulky uterus and reduction in the size of the right adnexal cyst. Repeat imaging (MRI axial T2W image) a further two months later demonstrated resolution of the left adnexal cyst. There was a small residual cyst on the right and marked decrease in the thickening of the mesorectal fascia. The lymph nodes appeared normal (Fig ). The retroperitoneal fibrosis on imaging had resolved. Her CA125 remained normal. Currently the patient is under joint care between the respiratory and renal physicians with symptomatic improvement.
Jayceon Delgado	26	1991/10/22	001-985-359-7859	[email protected]	2062 Kevin Trafficway Suite 139	An eight year old Malay boy, with a history of Henoch-Schonlein Purpura and G-6-PD deficiency, presented with left hand swelling and punctate rashes on the dorsum of his left hand, four hours following his transfer out from intensive care unit (ICU). The history dated back to two weeks prior to admission when he noted rashes on the dorsum of his feet and had intermittent, diffuse abdominal pain. He then developed migratory pain in his ankle joints, knee, elbow and small finger joints in that order. He refused treatment. He had no drug allergies. Developmental milestones were normal and immunization was complete. A week later, he was admitted to the general pediatrics ward for intermittent vomiting, severe generalized abdominal pain and passing red-current stools. The pain was constant, unrelenting and aggravated by solid food intake despite intravenous omeprazole (16 mg bd), metoclopromide (3 mg tds) and tramadol (30 mg 4 hourly). Rashes now developed on his left flank, buttock and medial aspects of both feet. He was febrile and micturation was normal. His vital parameters were as follows: BP 127/96, PR 99/min, RR 24/min and SpO2 97% on room air. Clinical examination revealed non-blanching purpuric rashes on the dorsum of his feet, left flank and buttock [Fig. ]. There was also localized tenderness on deep palpation of his left iliac fossa. Hematological, coagulation and renal profiles were within normal limits. Urgent transabdominal ultrasound did not show any "pseudokidney" or "doughnut sign" to suggest intussusception." Peristalsis was normal. All intraabdominal organs were normal and there was no free fluid. There was, in the left iliac fossa, a bowel loop filled with echogenic material likely to be a stool." Thirty-six hours later, he was admitted to the pediatric ICU owing to poor intake, severe per rectal bleeding and deteriorating general conditions. Fluid challenge with 300 mls of Ringer's Lactate solution and 2 units of packed red cell transfusion were given. Intra-arterial cannulation of the left radial artery was performed for continuous blood-pressure monitoring. Intravenous fluids, methylprednisolone (16 mg od), PCA morphine (bolus 0.5 mg, lockout at 15 mg), intravenous ceftriaxone (800 mg od) and metronidazole (120 mg tds) were administered. Following two days of stabilization, he was transferred out from ICU after the removal of his arterial line and urine catheter. Clinical examination in the morning showed diffuse, oedematous swelling on the dorsum of the left hand and all fingers with non-blanching purpuric rash restricted to an area 4 cm in diameter. There were no signs of fluid extravasations, inflammation or infection at the site of cannulation. An urgent Doppler ultrasound of the left forearm was performed to exclude a thrombo-embolic event. Both radial and ulnar arteries and corresponding veins were patent. Normal Doppler flow pattern was obtained within these vessels up to the level of cubital fossa. In the late afternoon, the whole left hand was swollen intensely, with extension of the purpura from the hand, up the wrist into the forearm. The metacarpophalangeal joints of all the left fingers were extended with flexion of all the distal interphalangeal joints. Capillary refill was normal. Emergency fasciotomy decompression of the dorsal [Fig ], thenar and hypothenar compartments [Fig ] of the left hand were performed. Serous fluid accumulation was noted in all compartments with marked tissue oedema. Additional hematoma was noted in the hypothenar compartment. The rashes and swelling subsided quite quickly and he was discharged uneventfully on the fifth post-operative day.
Alani Chen	24	2003/5/31	+1-833-473-5585x50126	[email protected]	5430 Powers Hills Apt. 868	The patient was a 9 year old boy with Ewing Sarcoma initially diagnosed just before his 6th birthday. He underwent peripheral blood stem cell transplant. One year later he presented with recurrent disseminated disease and restarted chemotherapy and received radiation. He was also referred to the pediatric hospice program. His symptoms included lower extremity paralysis and significant weakness of the upper extremities. He developed a partial gastric outlet obstruction, which later resolved to the point that he was able to resume oral feeding, but had difficulty taking oral medications. At the time of treatment his weight was 23 kg. He had multiple pain complaints including headache, back pain and generalized arthralgia/myalgia. There was a particularly troubling bone pain involving his forearms, wrists and hands bilaterally. The arm pain was unpredictable, episodic and intense with aching and burning qualities. There were no shooting pains or electrical shock sensations, nor was there hyperalgesia or allodynia. Pain was assessed by verbal self-report as he did not want to use any of the standardized childhood pain scales, and by the nurse's assessment using the Canuck Place Comfort Assessment Tool. His pain was treated with continuous subcutaneous or transdermal fentanyl at 75 micrograms/hour. He had hydromorphone for breakthrough pain, 3 milligrams subcutaneously as needed every hour. Adjuvant analgesics included round-the-clock gabapentin and naproxen. He received lorazepam as needed and ondansetron and nabilone for nausea. PEG 3350 and docusate were used as laxatives. The above regimen achieved satisfactory analgesia for all his pains except for bone pain in the arms. The clinical team opted to try a bisphosphonate class drug for the bone pain. Selecting a medication route was a challenge; an indwelling vascular access device had been removed several weeks previously at the completion of chemotherapy. He refused to have a peripheral intravenous (IV) line placed because he found it uncomfortable and associated it with his previous unpleasant hospitalizations. Oral medications were considered, but with his recent history of gastric outlet obstruction, and his general reluctance (but not refusal) to take pills, this was not a reliable route. He refused rectal medications. We therefore opted for a subcutaneous route, which was acceptable to him. A dose of 300 milligram of clodronate (~15 mg/kg) was prepared in 40 ml of normal saline (7.5 mg/ml). It was infused subcutaneously over an 8 hour time period and vital signs were monitored. There were no side effects and the infusion did not cause localized pain. There was no subsequent bone pain exacerbation. Serum calcium levels 4 days post infusion were 2.3 mmol/L with an albumin level of 28 g/L. Four days after the infusion he reported the onset of relief of the bone pain in his arms. Functionally he was improved, for example being able to use a video game controller without pain and manipulate board game pieces. The Comfort Assessment Tool provided additional information that pain was improved. He required no increases in his other analgesics; because they were providing adequate relief for other pains he experienced we did not decrease them either. The analgesic effect lasted almost 4 1/2 weeks, when he again reported intense bone pain, and the 300 mg dose was repeated, with good results 4 days later. Thereafter he received regular infusions every 4 weeks, prior to the expected recurrence of pain. In order to minimize procedures in accordance with the emphasis on patient comfort, imaging studies were not obtained and laboratory studies were kept to a minimum. During this period he moved between home and hospice with readmissions for family care, respite and symptom management. He died peacefully at home 7 months after acceptance to the pediatric palliative program, and 19 days following his last clodronate infusion, When we decided to introduce a bisphosphonate because his extremity pain was not responsive to opiates or a series of adjuvant medications we were faced with the questions of which drug to use and by what route. Cancer-related bone pain is a particularly difficult symptom to treat. Bisphosphonates have gained acceptance as a standard approach to bone pain in adults. In the idealized scenario evidence exists to guide clinicians to the most effective drug with support for a dose and frequency. Similarly in the idealized scenario, the choice of medication route depends primarily on pharmacokinetic and pharmacy factors such as drug formulation. There is however a dearth of evidence regarding bisphosphonates in children, and controversy regarding dosing. The major effect of bisphosphonates is to decrease recruitment and function of osteoclasts and thereby reduce bone turnover. Bisphosphonates act via multiple mechanisms at the cellular and molecular level []. The initial widespread use of bisphosphonates was in Paget's disease in the late 1970's and early 1980's. Bisphosphonate therapy was extended to the treatment of a number of other adult conditions such as cancer associated with bone destruction and hypercalcemia. Noting the effectiveness in reducing bone turnover in a variety of adult conditions, bisphosphonates were then considered for use in children. Pamidronate is used routinely for children with Osteogenesis Imperfecta, given by IV. Since then bisphosphonate therapy has been trialed in a number of childhood diseases [,]. It should be noted, however, that none of the reports describe bisphosphonate use to treat malignancy-related pain in children. A recent publication describes treating two children with osteoporosis secondary to leukemia; however, there was no mention of pain []. Our patient expressed a strong preference not to have an IV. The oral route was not considered to be reliable. He expressed no objection to a subcutaneous line, having already experienced subcutaneous infusions for chemotherapy and analgesia. We therefore explored this route of administration for bisphosphonates. We reviewed the literature on bisphosphonates [Medline 1966??003] and engaged in email and telephone discussion with authors and expert clinicians in palliative medicine and pediatric endocrinology. []. The evidence was clear that pamidronate was safe and tolerable in children, but if given subcutaneously may have toxicities []. On the other hand, the best evidence for subcutaneous bisphosphonate infusions supported clodronate, but only for adults []. Zoledronic acid was also considered as it requires only a very brief IV infusion. There was no data, however, on its use in children; a subsequent report showed a high frequency of side effects in this population []. The only published report of clodronate use in children was by Zacharin and Cundy who gave it by IV infusion to a child with a genetic bone disease, osteoporosis pseudoglioma syndrome []. (An additional case report was published after we treated our patient []). The drug was well tolerated and helped to improve bone mineral density in their patient. These clinicians extrapolated from adult doses and used first 300 mg, then 600 mg, IV (10??0 mg/kg). [Personal communication. T. Cundy. Clodronate dosing [online]. Email to H. Siden () 19 Jan 2004]. Because there were no reports on using clodronate to treat malignancy-related bone pain in children, we developed the regimen empirically. We relied on the dose reported by Zacharin and Cundy; in order to reduce fluid in the subcutaneous infusion, the maximum concentration described for drug preparation was used. The 8 hour infusion was chosen to minimize localized swelling; a shorter time period may work as well. We closely monitored our patient following the first two infusions and determined that 300 mg repeated every 4 weeks appeared to prevent pain recurrence.
Emmanuel Sawyer	22	1988/12/24	460.498.7647x2746	[email protected]	1309 Debbie Glen	The proband was a 63 year-old, Caucasian male who presented to the NCI Clinical Genetics Branch in October 2004 for evaluation of familial testicular cancer. He developed a left testicular pure seminoma at age 28 (per medical records; no pathology was available for review); he underwent a left radical orchiectomy followed by adjuvant cobalt irradiation to the retroperitoneum, and has remained free of testicular cancer. At his initial NIH visit, the patient reported resection of multiple colonic polyps on successive colonoscopies, beginning in his early 50 s. Materials from several excised polyps were reviewed at the NIH Laboratory of Pathology, and revealed a mixed polyposis of 5 adenomatous polyps, 2 hamartomatous polyps (Figure ), and multiple hyperplastic polyps. Physical examination revealed a muscular, mesomorphic white male (he is an avid body-builder) with multiple subcutaneous lipomas in the extremities and trunk. He had multiple dark brown to black, irregularly-shaped pigmented macules on the chest, back, arms, and legs, which were clinically suggestive of dysplastic nevi. Biopsy of the clinically most atypical lesion showed a simple lentigo, without melanocytic atypia. Protocol-related blood work, including testosterone, estradiol, chemistry panel, prostate specific antigen, alpha-fetoprotein, follicle stimulating hormone, luteinizing hormone, and beta-HCG, were normal. Ultrasound of the right testis showed early microlithiasis. Computed tomography of the chest, abdomen, and pelvis revealed an unexpected left inferomedial renal mass (Figure ), which was confirmed by MRI. Further evaluation of the left kidney mass was recommended, but not pursued due to other medical issues. He returned for a scheduled clinic visit one year later and reported having an elevated growth hormone (GH) level detected during a complementary/alternative health evaluation. The patient also stated that his head and hands had been "getting bigger". He reported taking various dietary supplements, none of which was found to contain androgens upon review of their ingredients, as well as testosterone gel, which was started at the time of his complementary/alternative health evaluation due to a low serum testosterone level. On examination, he had an acromegalic appearance, including protruding supra-orbital ridges, a prognathic jaw, wide nose, and diffuse soft-tissue thickening of the hands, all of which were judged clinically to be more prominent when compared with the year before. Laboratory studies demonstrated a normal fasting glucose, elevated levels of insulin-like growth factor-I (IGF-I) [943 ng/ml; normal range 71??90 ng/ml] and IGF binding protein-3 [8.4 弮g/ml; normal range 3.2??.6 弮g/ml]. A pituitary MRI revealed a hypoenhancing, diffusely-enlarged pituitary measuring approximately 2 cm, consistent with an adenoma (Figure ). A follow-up renal CT showed the left inferomedial kidney mass had grown compared with the study performed one year earlier; the adrenal glands were normal. On January 23, 2006, the patient underwent trans-sphenoidal resection of the pituitary mass, yielding a GH-producing adenoma. On February 22, 2006, he underwent a left nephrectomy for a stage III, poorly-differentiated renal cell carcinoma, with sarcomatoid features (Figure ). By November 2006, his growth hormone levels had returned to normal, and he had no evidence of recurrent kidney cancer. Detailed family history review revealed a son with seminoma (confirmed by outside pathology report) at age 34 (cancer-free at age 36), and a sister who developed urinary bladder cancer (death certificate confirmation) at age 53. His son had no evidence of lipomatosis or multiple lentigines on examination at the time of study enrollment, and has had a negative screening colonoscopy. The proband's father was reported to have lipomatosis, but was deceased. There is no history of other benign or malignant neoplasms reported in the rest of the family. Based on his personal history of multiple cancers, a pituitary adenoma, multiple pigmented skin lesions, multiple lipomas, and multiple colon polyps with varying histology, the patient underwent genetic testing for Cowden syndrome (the PTEN gene), Carney complex (the PRKAR1A gene), and multiple endocrine neoplasia syndrome type 1 (the MEN1 or menin gene). No germline mutations were detected in any of these genes.
Marina Sosa	41	1981/9/10	(664)969-8004x528	[email protected]	16466 Ashley Drive	A 50-year-old female presented with complains of painless progressive swelling in right cheek region of two months duration. Examination revealed a 6 ? 4 cm bony hard swelling in right zygomatic region near and below lateral canthus of right eye (Figure ) Roentgenogram of the paranasal sinuses showed a lesion arising from right maxilla and right zygoma. Computerized tomographic (CT) scan revealed two separate masses one in right orbit and other infiltrating zygoma and maxilla (Figure ), radiographic picture was suggestive of osteogenic sarcoma or Ewing's sarcoma. A fine needle aspiration was carried out that showed typical polygonal and spindle cells with moderate amount of cytoplasm and vesicular nuclei with nucleoli, many with intracellular pigment; seen singly and clusters, the picture was suggestive of malignant melanoma (Figure ). The ophthalmologic consultation revealed that there was no useful vision in the right eye. A B-scan of the right eye showed an organized mass within the vitreous cavity indicating vitreous haemorrhage (figure ). A detailed clinical examination failed to show any other melanocytic lesion on skin and other mucus membranes. With a provisional diagnosis of melanoma of the maxilla and zygoma with vitreous haemorrhage and no useful vision in right eye a wide excision of the lesion including anterolateral maxillectomy, zygomectomy, and removal of superolateral wall and floor of orbit with en bloc exenteration of the right eyeball was carried out (Figure ). Histopathological examination of the resected eyeball specimen showed a neoplasm in choroid, filling posterior chamber with no extraoccular extensions, composed of sheets, nests and cords of polygonal cells and vesicular nuclei. Prominent nucleoli and eosinophilic cytoplasm containing abundant melanin pigment were noted (figure ). Similar tumours were seen in the extra ocular soft tissue and resected maxilla and zygomatic bones. A final diagnosis of choroidal melanoma metastasizing to maxillofacial bones was made. Differential diagnosis of primary bone melanoma with metastasis to choroids was kept. Surgical excision was followed by 40 Gy./15 fractions of radiotherapy to right face using lateral portal. Patient is on regular follow-up two years after surgery and is free of any local or systemic recurrences.
Emir Reyna	41	2004/4/11	986.583.6154	[email protected]	62657 Hannah Park	A 40-year-old woman with a diagnosis of bipolar illness presented in an acute manic state. Previous but not current medication included depot clopixol and lithium. There was recent usage of heroin and other illicit drugs. Current dosage of diazepam was 80 mg/day. After admission 2 doses of clopixol acuphase (75 and 100 mg respectively) given over 5 days had little effect other than some sedation. Immediately prior to being given IM olanzapine 10 mg her behaviour was loud, over familiar and intrusive. The patient requested an IM sedative and was not detained under the Mental Health Act (MHA). Neither concomitant benzodiazepines nor anticholinergics were given. PANSS-EC scores shown in table . The nursing staff reported the patient as being much "quieter" but not asleep after 60 minutes. Following a single dose of intramuscular olanzapine, depot clopixol was reinstated with valproate. No adverse events were reported.
Luella Velazquez	26	1993/12/18	6435863237	[email protected]	222 David Causeway	A 28-year-old woman with a diagnosis of schizophrenia presented in a psychotic and uncooperative state refusing medication. Medication prior to admission was 800 mg quetiapine and 1 mg lorazepam daily. Her behaviour became overtly aggressive including making a hole in the hospital bedroom wall and attempted assaults on staff. She was placed under the MHA and given IM olanzapine 10 mg. Neither concomitant benzodiazepines nor anticholinergics were given. PANSS-EC scores shown in table . Nursing observations showed that the patient was asleep after 120 minutes post-IM (01.00) and remained "quieter and more relaxed for the next 2 days". Patient feedback was that she felt calmer after IM olanzapine. No adverse events were reported by the patient or physician. Patient however continued to refuse oral medications and currently receives depot risperidone.
Drew Barnett	35	1980/3/5	477.928.7927x688	[email protected]	1795 Butler Radial Apt. 906	A 49-year-old woman with a long standing history of bipolar affective disorder presented in a mixed affective psychotic state having had no relapses for 2 years. Her previous medication regimens included citalopram, lithium, valproate and lamotrigine. At admission her medication was lamotrigine 100 mg. Her behaviour was reported as "aggressive, confrontational and entertaining beliefs suggestive of delusional jealousy and suspiciousness about family". Oral medication was refused and the patient was sectioned under the MHA. IM olanzapine 10 mg was given and no concomitant benzodiazepines or anticholinergics were administered. Nursing staff reported a moderate degree of tranquilisation (calm, relaxed and not sleeping) and that confrontation was avoided. Little effect upon delusional beliefs was noted. The patient began to engage with staff within 36 hours post IM olanzapine and at which stage oral olanzapine was accepted. No adverse events were reported.
Harlow Webb	44	2003/8/8	+1-979-658-7522x538	[email protected]	4624 Blevins Gardens Apt. 590	An 18-year old male with a diagnosis of schizophrenia was admitted in an acutely psychotic state under the MHA. He refused oral medication and presented in an extremely agitated state expressing paranoid delusions such as "people have put fish bones in my food". He was not currently on medication (although previously had received olanzapine 10 mg orally) and was known to have used illegal substances in the past. There was an additional forensic history. He was treated with 10 mg olanzapine IM and the nursing notes state, "he soon went to sleep". Around 12 hours later he became agitated again and barricaded himself in his room. He was given 10 mg olanzapine IM and 2 mg IM lorazepam. The nursing notes report that within 30 minutes he was "settled" and had "calmed down". Around 2 hours post-injection he was asleep. Subsequently he was transferred onto olanzapine 20 mg orally. No adverse events were reported.
Lorenzo Long	28	1984/7/3	(631)581-4627x666	[email protected]	9575 Robin Brooks	A 65-year old male with a diagnosis of schizoaffective disorder was admitted under the MHA in an extremely agitated state and expressing suicidal ideation. There was evidence of persecutory delusions. Around midnight he received 10 mg olanzapine IM. No benzodiazepines were administered. The nursing notes report that he "slept well" and "settled" soon after medication. No concomitant benzodiazepines were given. No adverse events were reported.
Jade Henry	22	1981/6/16	840.761.0354x50994	[email protected]	87006 Sean Squares	A 40-year old female with a diagnosis of bipolar disorder was admitted in an acutely manic state. Her normal medications included olanzapine 20 mg and sodium valproate. The nursing staff report that she was "restless, agitated, verbally aggressive and had evidence of an elevated mood". She was treated with 10 mg olanzapine IM. The notes report that she settled after medication and "slept undisturbed". No benzodiazepines were administered. Within the first 24 hours after IM olanzapine she was commenced on depot clopixol 200 mg/weekly. No adverse events were reported.
Carlos Parks	31	2002/9/12	(932)226-3559	[email protected]	8344 Jennifer Shoals	A 46-year old male with a 10-year history of schizophrenia was admitted in an acutely psychotic state. He had relapsed having been changed from IM depot haloperidol to risperidone LAIM. For the 2 weeks prior to admission he had received additional oral risperidone and sodium valproate He had showed features of paranoid and grandiose delusions together with elevated mood and had been asked to leave work, as "colleagues could not understand his talk". On admission, he was given a single injection of IM olanzapine 10 mg at around 18.00. No concomitant benzodiazepines were administered. The nursing reports state that "later that night he was no longer laughing without reason and was quiet. He slept well". The response was not maintained and he was reported as grossly psychotic again at midday the next day. No adverse events were reported.

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