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Surgery_Schwartz_9502 | Surgery_Schwartz | secretion. Gastrin and acetylcholine, both stimulants of gastric acid secretion, are also weak stimulants of pancreatic bicarbonate secretion.4 Truncal vagotomy produces a myriad of complex effects on the downstream digestive tract, but the sum effect on the exocrine pancreas is a reduction in bicarbonate and fluid secretion.5 The endocrine pancreas also influences the adjacent exocrine pan-creatic secretions. Somatostatin, pancreatic polypeptide (PP), and glucagon are all thought to inhibit exocrine secretion.The acinar cells release pancreatic enzymes from their zymogen granules into the lumen of the acinus, and these pro-teins combine with the water and bicarbonate secretions of the centroacinar cells. The pancreatic juice then travels into small intercalated ducts. Several small intercalated ducts join to form an interlobular duct. Cells in the interlobular ducts contribute fluid and electrolytes to adjust the final concentrations of the pancreatic fluid. Interlobular ducts then | Surgery_Schwartz. secretion. Gastrin and acetylcholine, both stimulants of gastric acid secretion, are also weak stimulants of pancreatic bicarbonate secretion.4 Truncal vagotomy produces a myriad of complex effects on the downstream digestive tract, but the sum effect on the exocrine pancreas is a reduction in bicarbonate and fluid secretion.5 The endocrine pancreas also influences the adjacent exocrine pan-creatic secretions. Somatostatin, pancreatic polypeptide (PP), and glucagon are all thought to inhibit exocrine secretion.The acinar cells release pancreatic enzymes from their zymogen granules into the lumen of the acinus, and these pro-teins combine with the water and bicarbonate secretions of the centroacinar cells. The pancreatic juice then travels into small intercalated ducts. Several small intercalated ducts join to form an interlobular duct. Cells in the interlobular ducts contribute fluid and electrolytes to adjust the final concentrations of the pancreatic fluid. Interlobular ducts then |
Surgery_Schwartz_9503 | Surgery_Schwartz | ducts join to form an interlobular duct. Cells in the interlobular ducts contribute fluid and electrolytes to adjust the final concentrations of the pancreatic fluid. Interlobular ducts then join to form about 20 secondary ducts that empty into the main pancreatic duct. Brunicardi_Ch33_p1429-p1516.indd 143601/03/19 6:44 PM 1437PANCREASCHAPTER 33Table 33-1Pancreatic enzymesENZYMESUBSTRATEPRODUCTCarbohydrate Amylase (active)Starch, glycogenGlucose, maltose, maltotriose, dextrinsProtein Endopeptidases Trypsinogen (inactive) Enterokinase Trypsin (active) Chymotrypsinogen (inactive) EnterokinaseTrypsin Chymotrypsin (active) Proelastase (inactive) EnterokinaseTrypsin Elastase (active) Exopeptidases Procarboxy peptidase A&B (inactive) Enterokinase Carboxypeptidase A&B (active)Cleave bonds between amino acidsCleave amino acids from end of peptide chainsAmino acids, dipeptides—Fat Pancreatic lipase (active) Phospholipase A2 (inactive) Trypsin Phospholipase A2 (active) Cholesterol | Surgery_Schwartz. ducts join to form an interlobular duct. Cells in the interlobular ducts contribute fluid and electrolytes to adjust the final concentrations of the pancreatic fluid. Interlobular ducts then join to form about 20 secondary ducts that empty into the main pancreatic duct. Brunicardi_Ch33_p1429-p1516.indd 143601/03/19 6:44 PM 1437PANCREASCHAPTER 33Table 33-1Pancreatic enzymesENZYMESUBSTRATEPRODUCTCarbohydrate Amylase (active)Starch, glycogenGlucose, maltose, maltotriose, dextrinsProtein Endopeptidases Trypsinogen (inactive) Enterokinase Trypsin (active) Chymotrypsinogen (inactive) EnterokinaseTrypsin Chymotrypsin (active) Proelastase (inactive) EnterokinaseTrypsin Elastase (active) Exopeptidases Procarboxy peptidase A&B (inactive) Enterokinase Carboxypeptidase A&B (active)Cleave bonds between amino acidsCleave amino acids from end of peptide chainsAmino acids, dipeptides—Fat Pancreatic lipase (active) Phospholipase A2 (inactive) Trypsin Phospholipase A2 (active) Cholesterol |
Surgery_Schwartz_9504 | Surgery_Schwartz | bonds between amino acidsCleave amino acids from end of peptide chainsAmino acids, dipeptides—Fat Pancreatic lipase (active) Phospholipase A2 (inactive) Trypsin Phospholipase A2 (active) Cholesterol esteraseTriglyceridesPhospholipaseNeutral lipids2-Monoglycerides, fatty acids——Concentration (mEq/L)18016014012010080604020 000.40.81.21.6Secretory rate (mL/min)Pancreatic juice180160140120100806040200PlasmaNaHCO3ClKNa=151.5HCO3=26.0Cl=110.0K=5.38Figure 33-9. Composition of pancreatic exocrine secretions. Greater concentrations of bicarbonate are secreted at higher secretory rates, and chloride secretion varies inversely with bicarbonate secretion. In contrast, sodium and potassium concentrations are independent of the secretory rate. (Reproduced with permission from Bro-Rasmussen F, Killmann SA, Thaysen JH: The composition of pancreatic juice as compared to sweat, parotid saliva and tears, Acta Physiol Scand. 1956 Sep 26;37(2-3):97-113.)Table 33-2Pancreatic Islet Peptide | Surgery_Schwartz. bonds between amino acidsCleave amino acids from end of peptide chainsAmino acids, dipeptides—Fat Pancreatic lipase (active) Phospholipase A2 (inactive) Trypsin Phospholipase A2 (active) Cholesterol esteraseTriglyceridesPhospholipaseNeutral lipids2-Monoglycerides, fatty acids——Concentration (mEq/L)18016014012010080604020 000.40.81.21.6Secretory rate (mL/min)Pancreatic juice180160140120100806040200PlasmaNaHCO3ClKNa=151.5HCO3=26.0Cl=110.0K=5.38Figure 33-9. Composition of pancreatic exocrine secretions. Greater concentrations of bicarbonate are secreted at higher secretory rates, and chloride secretion varies inversely with bicarbonate secretion. In contrast, sodium and potassium concentrations are independent of the secretory rate. (Reproduced with permission from Bro-Rasmussen F, Killmann SA, Thaysen JH: The composition of pancreatic juice as compared to sweat, parotid saliva and tears, Acta Physiol Scand. 1956 Sep 26;37(2-3):97-113.)Table 33-2Pancreatic Islet Peptide |
Surgery_Schwartz_9505 | Surgery_Schwartz | F, Killmann SA, Thaysen JH: The composition of pancreatic juice as compared to sweat, parotid saliva and tears, Acta Physiol Scand. 1956 Sep 26;37(2-3):97-113.)Table 33-2Pancreatic Islet Peptide ProductsHORMONESISLET CELLFUNCTIONSInsulinBetaDecreases gluconeogenesis, glycogenolysis, fatty acid breakdown, and ketogenesisIncreased glycogenesis, protein synthesis and glucose uptakeGlucagonAlphaOpposite effects of insulin; increases hepatic glycogenolysis and gluconeogenesisSomatostatinDeltaInhibits secretion and action of all pancreatic and gut peptides, inhibits cell growthPancreatic PolypeptidePP or FInhibits pancreatic exocrine secretion and facilitates hepatic action of insulinAmylin (IAPP)BetaCounter-regulates insulin secretion and functionPancreastatinBetaDecreases insulin and somatostatin secretion, increases glucagon secretion, decreases exocrine secretionGhrelinEpsilonDecreases insulin secretion and actionPeptide YY (PYY)not knownIncreases insulin secretion and beta cell | Surgery_Schwartz. F, Killmann SA, Thaysen JH: The composition of pancreatic juice as compared to sweat, parotid saliva and tears, Acta Physiol Scand. 1956 Sep 26;37(2-3):97-113.)Table 33-2Pancreatic Islet Peptide ProductsHORMONESISLET CELLFUNCTIONSInsulinBetaDecreases gluconeogenesis, glycogenolysis, fatty acid breakdown, and ketogenesisIncreased glycogenesis, protein synthesis and glucose uptakeGlucagonAlphaOpposite effects of insulin; increases hepatic glycogenolysis and gluconeogenesisSomatostatinDeltaInhibits secretion and action of all pancreatic and gut peptides, inhibits cell growthPancreatic PolypeptidePP or FInhibits pancreatic exocrine secretion and facilitates hepatic action of insulinAmylin (IAPP)BetaCounter-regulates insulin secretion and functionPancreastatinBetaDecreases insulin and somatostatin secretion, increases glucagon secretion, decreases exocrine secretionGhrelinEpsilonDecreases insulin secretion and actionPeptide YY (PYY)not knownIncreases insulin secretion and beta cell |
Surgery_Schwartz_9506 | Surgery_Schwartz | secretion, increases glucagon secretion, decreases exocrine secretionGhrelinEpsilonDecreases insulin secretion and actionPeptide YY (PYY)not knownIncreases insulin secretion and beta cell growthDestruction of the branching ductal tree from recurrent inflam-mation, scarring, and deposition of stones in chronic pancreatitis eventually contributes to destruction of the exocrine pancreas and exocrine pancreatic insufficiency.Endocrine PancreasThere are nearly 1 million islets of Langerhans in the normal adult pancreas. They vary greatly in size from 40 to 900 μm. Larger islets are located closer to the major arterioles and smaller islets are embedded more deeply in the parenchyma of the pancreas. Most islets contain 3000 to 4000 cells of five major types: alpha cells that secrete glucagon, beta-cells that secrete insulin, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin, and PP cells that secrete PP (Table 33-2).Insulin is the best-studied pancreatic hormone. The | Surgery_Schwartz. secretion, increases glucagon secretion, decreases exocrine secretionGhrelinEpsilonDecreases insulin secretion and actionPeptide YY (PYY)not knownIncreases insulin secretion and beta cell growthDestruction of the branching ductal tree from recurrent inflam-mation, scarring, and deposition of stones in chronic pancreatitis eventually contributes to destruction of the exocrine pancreas and exocrine pancreatic insufficiency.Endocrine PancreasThere are nearly 1 million islets of Langerhans in the normal adult pancreas. They vary greatly in size from 40 to 900 μm. Larger islets are located closer to the major arterioles and smaller islets are embedded more deeply in the parenchyma of the pancreas. Most islets contain 3000 to 4000 cells of five major types: alpha cells that secrete glucagon, beta-cells that secrete insulin, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin, and PP cells that secrete PP (Table 33-2).Insulin is the best-studied pancreatic hormone. The |
Surgery_Schwartz_9507 | Surgery_Schwartz | that secrete insulin, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin, and PP cells that secrete PP (Table 33-2).Insulin is the best-studied pancreatic hormone. The discovery of insulin in 1920 by Frederick Banting, an orthopedic Brunicardi_Ch33_p1429-p1516.indd 143701/03/19 6:44 PM 1438SPECIFIC CONSIDERATIONSPART IIsurgeon, and Charles Best, a medical student, was recognized with the awarding of the Nobel Prize in Physiology or Medicine. They produced diabetes in dogs by performing total pancreatectomy and then treated them with crude pancreatic extracts from dog and calf pancreata using techniques to prevent the breakdown of insulin by the proteolytic enzymes of the exocrine pancreas. Insulin was subsequently purified and found to be a 56-amino acid peptide with two chains, an alpha and a beta chain, joined by two disulfide bridges and a connecting peptide, or C-peptide. Proinsulin is made in the endoplasmic reticulum and then is transported to the | Surgery_Schwartz. that secrete insulin, delta cells that secrete somatostatin, epsilon cells that secrete ghrelin, and PP cells that secrete PP (Table 33-2).Insulin is the best-studied pancreatic hormone. The discovery of insulin in 1920 by Frederick Banting, an orthopedic Brunicardi_Ch33_p1429-p1516.indd 143701/03/19 6:44 PM 1438SPECIFIC CONSIDERATIONSPART IIsurgeon, and Charles Best, a medical student, was recognized with the awarding of the Nobel Prize in Physiology or Medicine. They produced diabetes in dogs by performing total pancreatectomy and then treated them with crude pancreatic extracts from dog and calf pancreata using techniques to prevent the breakdown of insulin by the proteolytic enzymes of the exocrine pancreas. Insulin was subsequently purified and found to be a 56-amino acid peptide with two chains, an alpha and a beta chain, joined by two disulfide bridges and a connecting peptide, or C-peptide. Proinsulin is made in the endoplasmic reticulum and then is transported to the |
Surgery_Schwartz_9508 | Surgery_Schwartz | with two chains, an alpha and a beta chain, joined by two disulfide bridges and a connecting peptide, or C-peptide. Proinsulin is made in the endoplasmic reticulum and then is transported to the Golgi complex, where it is packaged into granules and the C-peptide is cleaved off. There are two phases of insulin secretion. In the first phase, stored insulin is released. This phase lasts about 5 minutes after a glucose challenge. The second phase of insulin secretion is a longer, sustained release due to ongoing production of new insulin. beta-cell synthesis of insulin is regulated by plasma glucose levels, neural signals, and the paracrine influence of other islet cells. The diagnosis of diabetes is made by using oral and intravenous (IV) glucose tolerance tests. Oral glucose not only enters the bloodstream but also stimulates the release of enteric hormones such as gastric inhibitory peptide (also known as glucose-dependent insulinotropic polypeptide or GIP), glucagon-like peptide-1 | Surgery_Schwartz. with two chains, an alpha and a beta chain, joined by two disulfide bridges and a connecting peptide, or C-peptide. Proinsulin is made in the endoplasmic reticulum and then is transported to the Golgi complex, where it is packaged into granules and the C-peptide is cleaved off. There are two phases of insulin secretion. In the first phase, stored insulin is released. This phase lasts about 5 minutes after a glucose challenge. The second phase of insulin secretion is a longer, sustained release due to ongoing production of new insulin. beta-cell synthesis of insulin is regulated by plasma glucose levels, neural signals, and the paracrine influence of other islet cells. The diagnosis of diabetes is made by using oral and intravenous (IV) glucose tolerance tests. Oral glucose not only enters the bloodstream but also stimulates the release of enteric hormones such as gastric inhibitory peptide (also known as glucose-dependent insulinotropic polypeptide or GIP), glucagon-like peptide-1 |
Surgery_Schwartz_9509 | Surgery_Schwartz | the bloodstream but also stimulates the release of enteric hormones such as gastric inhibitory peptide (also known as glucose-dependent insulinotropic polypeptide or GIP), glucagon-like peptide-1 (GLP-1), and CCK that augment the secretion of insulin and are therefore referred to as incretins. As a result, oral glucose is a more vigorous stimulus to insulin secretion than IV glucose. In the oral glucose tolerance test (OGTT), the patient is fasted overnight, and a basal glucose value is determined. Forty g/m2 or 75 g of glucose is given orally over 10 minutes. Blood samples are taken every 30 minutes for 2 hours. Normal values and criteria for diabetes vary by age, but essentially all values should be <200 mg/dL, and the 120-minute value should be <140 mg/dL.Insulin secretion by the beta-cell is also influenced by plasma levels of amino acids such as arginine, lysine, leucine, and free fatty acids. Glucagon, GIP, GLP-1, and CCK stimulate insulin release, while somatostatin, amylin, | Surgery_Schwartz. the bloodstream but also stimulates the release of enteric hormones such as gastric inhibitory peptide (also known as glucose-dependent insulinotropic polypeptide or GIP), glucagon-like peptide-1 (GLP-1), and CCK that augment the secretion of insulin and are therefore referred to as incretins. As a result, oral glucose is a more vigorous stimulus to insulin secretion than IV glucose. In the oral glucose tolerance test (OGTT), the patient is fasted overnight, and a basal glucose value is determined. Forty g/m2 or 75 g of glucose is given orally over 10 minutes. Blood samples are taken every 30 minutes for 2 hours. Normal values and criteria for diabetes vary by age, but essentially all values should be <200 mg/dL, and the 120-minute value should be <140 mg/dL.Insulin secretion by the beta-cell is also influenced by plasma levels of amino acids such as arginine, lysine, leucine, and free fatty acids. Glucagon, GIP, GLP-1, and CCK stimulate insulin release, while somatostatin, amylin, |
Surgery_Schwartz_9510 | Surgery_Schwartz | is also influenced by plasma levels of amino acids such as arginine, lysine, leucine, and free fatty acids. Glucagon, GIP, GLP-1, and CCK stimulate insulin release, while somatostatin, amylin, and pancreastatin inhibit insulin release.6 Cholinergic fibers and alpha-sympa-thetic fibers stimulate insulin release, while beta-sympathetic fibers inhibit insulin secretion.Insulin’s glucoregulatory function is to inhibit endogenous (hepatic) glucose production and to facilitate glucose transport into cells, thus lowering plasma glucose levels. Insulin also inhibits glycogenolysis, fatty acid breakdown, and ketone formation, and stimulates protein synthesis. There is a considerable amount of functional reserve in insulin secretory capacity. If the remaining portion of the pancreas is healthy, about 80% of the pancreas can be resected without the patient becoming diabetic.7 In patients with chronic pancreatitis, or other conditions in which much of the gland is diseased, resection of a smaller | Surgery_Schwartz. is also influenced by plasma levels of amino acids such as arginine, lysine, leucine, and free fatty acids. Glucagon, GIP, GLP-1, and CCK stimulate insulin release, while somatostatin, amylin, and pancreastatin inhibit insulin release.6 Cholinergic fibers and alpha-sympa-thetic fibers stimulate insulin release, while beta-sympathetic fibers inhibit insulin secretion.Insulin’s glucoregulatory function is to inhibit endogenous (hepatic) glucose production and to facilitate glucose transport into cells, thus lowering plasma glucose levels. Insulin also inhibits glycogenolysis, fatty acid breakdown, and ketone formation, and stimulates protein synthesis. There is a considerable amount of functional reserve in insulin secretory capacity. If the remaining portion of the pancreas is healthy, about 80% of the pancreas can be resected without the patient becoming diabetic.7 In patients with chronic pancreatitis, or other conditions in which much of the gland is diseased, resection of a smaller |
Surgery_Schwartz_9511 | Surgery_Schwartz | 80% of the pancreas can be resected without the patient becoming diabetic.7 In patients with chronic pancreatitis, or other conditions in which much of the gland is diseased, resection of a smaller fraction of the pancreas can result in pancreatogenic, or type 3c diabetes (Table 33-3).Insulin receptors are dimeric, tyrosine kinase–containing transmembrane proteins that are located on all cells. Insulin defi-ciency (seen in type 1 and type 3c diabetes) results in an overex-pression or upregulation of insulin receptors, which causes an enhanced sensitivity to insulin in muscle and adipocytes (and therefore increases the risk of insulin-induced hypoglycemia). Type 2 diabetes is associated with a downregulation of insulin receptors and relative hyperinsulinemia, with resulting insulin resistance. Some forms of diabetes are associated with selected impairments of hepatic or peripheral insulin receptors, such as pancreatogenic or type 3c diabetes (T3cDM) or maturity-onset diabetes of the | Surgery_Schwartz. 80% of the pancreas can be resected without the patient becoming diabetic.7 In patients with chronic pancreatitis, or other conditions in which much of the gland is diseased, resection of a smaller fraction of the pancreas can result in pancreatogenic, or type 3c diabetes (Table 33-3).Insulin receptors are dimeric, tyrosine kinase–containing transmembrane proteins that are located on all cells. Insulin defi-ciency (seen in type 1 and type 3c diabetes) results in an overex-pression or upregulation of insulin receptors, which causes an enhanced sensitivity to insulin in muscle and adipocytes (and therefore increases the risk of insulin-induced hypoglycemia). Type 2 diabetes is associated with a downregulation of insulin receptors and relative hyperinsulinemia, with resulting insulin resistance. Some forms of diabetes are associated with selected impairments of hepatic or peripheral insulin receptors, such as pancreatogenic or type 3c diabetes (T3cDM) or maturity-onset diabetes of the |
Surgery_Schwartz_9512 | Surgery_Schwartz | Some forms of diabetes are associated with selected impairments of hepatic or peripheral insulin receptors, such as pancreatogenic or type 3c diabetes (T3cDM) or maturity-onset diabetes of the young (MODY).Glucagon is a 29-amino-acid, single-chain peptide that promotes hepatic glycogenolysis and gluconeogenesis and counteracts the effects of insulin through its hyperglycemic action. Glucose is the primary regulator of glucagon secretion, as it is with insulin, but it has an inhibitory rather than stimulatory effect. Glucagon release is stimulated by hypoglycemia and by the amino acids arginine and alanine. GLP-1 inhibits glucagon secretion in vivo, and insulin and somatostatin inhibit glucagon Table 33-3Clinical and laboratory findings in types of diabetes mellitusPARAMETERTYPE 1TYPE 2TYPE 3C IDDMNIDDMPancreatogenicKetoacidosisCommonRareRareHyperglycemiaSevereUsually mildMildHypoglycemiaCommonRareCommonPeripheral insulin sensitivityNormal or increasedDecreasedIncreasedHepatic insulin | Surgery_Schwartz. Some forms of diabetes are associated with selected impairments of hepatic or peripheral insulin receptors, such as pancreatogenic or type 3c diabetes (T3cDM) or maturity-onset diabetes of the young (MODY).Glucagon is a 29-amino-acid, single-chain peptide that promotes hepatic glycogenolysis and gluconeogenesis and counteracts the effects of insulin through its hyperglycemic action. Glucose is the primary regulator of glucagon secretion, as it is with insulin, but it has an inhibitory rather than stimulatory effect. Glucagon release is stimulated by hypoglycemia and by the amino acids arginine and alanine. GLP-1 inhibits glucagon secretion in vivo, and insulin and somatostatin inhibit glucagon Table 33-3Clinical and laboratory findings in types of diabetes mellitusPARAMETERTYPE 1TYPE 2TYPE 3C IDDMNIDDMPancreatogenicKetoacidosisCommonRareRareHyperglycemiaSevereUsually mildMildHypoglycemiaCommonRareCommonPeripheral insulin sensitivityNormal or increasedDecreasedIncreasedHepatic insulin |
Surgery_Schwartz_9513 | Surgery_Schwartz | 3C IDDMNIDDMPancreatogenicKetoacidosisCommonRareRareHyperglycemiaSevereUsually mildMildHypoglycemiaCommonRareCommonPeripheral insulin sensitivityNormal or increasedDecreasedIncreasedHepatic insulin sensitivityNormalNormal or decreasedDecreasedInsulin levelsLowHighLowGlucagon levelsNormal or highNormal or highLowPP levelsNormal or low (late)HighLowGIP levelsNormal or lowNormal or highLowGLP-1 levelsNormalNormal or highNormal or highTypical age of onsetChildhood or adolescenceAdulthoodAnyAbbreviations: IDDM = insulin dependent diabetes mellitus; NIDDM = non–insulin-dependent diabetes mellitus; PP = pancreatic polypeptide; GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide 1.Reproduced with permission from Slezak LA, Andersen DK: Pancreatic resection: effects on glucose metabolism, World J Surg. 2001 Apr;25(4):452-460.Brunicardi_Ch33_p1429-p1516.indd 143801/03/19 6:44 PM 1439PANCREASCHAPTER 33secretion in a paracrine fashion within the islet. The same | Surgery_Schwartz. 3C IDDMNIDDMPancreatogenicKetoacidosisCommonRareRareHyperglycemiaSevereUsually mildMildHypoglycemiaCommonRareCommonPeripheral insulin sensitivityNormal or increasedDecreasedIncreasedHepatic insulin sensitivityNormalNormal or decreasedDecreasedInsulin levelsLowHighLowGlucagon levelsNormal or highNormal or highLowPP levelsNormal or low (late)HighLowGIP levelsNormal or lowNormal or highLowGLP-1 levelsNormalNormal or highNormal or highTypical age of onsetChildhood or adolescenceAdulthoodAnyAbbreviations: IDDM = insulin dependent diabetes mellitus; NIDDM = non–insulin-dependent diabetes mellitus; PP = pancreatic polypeptide; GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide 1.Reproduced with permission from Slezak LA, Andersen DK: Pancreatic resection: effects on glucose metabolism, World J Surg. 2001 Apr;25(4):452-460.Brunicardi_Ch33_p1429-p1516.indd 143801/03/19 6:44 PM 1439PANCREASCHAPTER 33secretion in a paracrine fashion within the islet. The same |
Surgery_Schwartz_9514 | Surgery_Schwartz | on glucose metabolism, World J Surg. 2001 Apr;25(4):452-460.Brunicardi_Ch33_p1429-p1516.indd 143801/03/19 6:44 PM 1439PANCREASCHAPTER 33secretion in a paracrine fashion within the islet. The same neural impulses that regulate insulin secretion also regulate glucagon secretion, so that the two hormones work together in a balance of actions to maintain glucose levels. Cholinergic and alpha-sympathetic fibers stimulate glucagon release, while beta-sympathetic fibers inhibit glucagon release.8 In pancreatogenic or type 3c diabetes, glucagon responsiveness to a fall in blood glucose is lost, thereby increasing the risk for hypoglycemia.Although originally isolated from the hypothalamus, somatostatin is a peptide that is now known to have a wide ana-tomic distribution, not only in neurons but also in the pancreas, gut, and other tissues. It is a highly conserved peptide hormone, as it is found in lower vertebrates, and is now realized to be of fundamental importance in regulatory | Surgery_Schwartz. on glucose metabolism, World J Surg. 2001 Apr;25(4):452-460.Brunicardi_Ch33_p1429-p1516.indd 143801/03/19 6:44 PM 1439PANCREASCHAPTER 33secretion in a paracrine fashion within the islet. The same neural impulses that regulate insulin secretion also regulate glucagon secretion, so that the two hormones work together in a balance of actions to maintain glucose levels. Cholinergic and alpha-sympathetic fibers stimulate glucagon release, while beta-sympathetic fibers inhibit glucagon release.8 In pancreatogenic or type 3c diabetes, glucagon responsiveness to a fall in blood glucose is lost, thereby increasing the risk for hypoglycemia.Although originally isolated from the hypothalamus, somatostatin is a peptide that is now known to have a wide ana-tomic distribution, not only in neurons but also in the pancreas, gut, and other tissues. It is a highly conserved peptide hormone, as it is found in lower vertebrates, and is now realized to be of fundamental importance in regulatory |
Surgery_Schwartz_9515 | Surgery_Schwartz | but also in the pancreas, gut, and other tissues. It is a highly conserved peptide hormone, as it is found in lower vertebrates, and is now realized to be of fundamental importance in regulatory processes throughout the body. One gene encodes for a common precursor that is dif-ferentially processed to generate tissue-specific amounts of two bioactive products, somatostatin-14, and somatostatin-28. These peptides inhibit endocrine and exocrine secretion and affect neurotransmission, GI and biliary motility, intestinal absorption, vascular tone, and cell proliferation.Five different somatostatin receptors (SSTRs) have been cloned and the biologic properties of each are different.9 The hexapeptide and octapeptide analogues such as octreotide bind only to SSTR2, SSTR3, and SSTR5. These analogues have a longer serum half-life, and their potent inhibitory effect has been used clinically to treat both endocrine and exocrine disor-ders. For example, octreotide has been shown to decrease | Surgery_Schwartz. but also in the pancreas, gut, and other tissues. It is a highly conserved peptide hormone, as it is found in lower vertebrates, and is now realized to be of fundamental importance in regulatory processes throughout the body. One gene encodes for a common precursor that is dif-ferentially processed to generate tissue-specific amounts of two bioactive products, somatostatin-14, and somatostatin-28. These peptides inhibit endocrine and exocrine secretion and affect neurotransmission, GI and biliary motility, intestinal absorption, vascular tone, and cell proliferation.Five different somatostatin receptors (SSTRs) have been cloned and the biologic properties of each are different.9 The hexapeptide and octapeptide analogues such as octreotide bind only to SSTR2, SSTR3, and SSTR5. These analogues have a longer serum half-life, and their potent inhibitory effect has been used clinically to treat both endocrine and exocrine disor-ders. For example, octreotide has been shown to decrease |
Surgery_Schwartz_9516 | Surgery_Schwartz | have a longer serum half-life, and their potent inhibitory effect has been used clinically to treat both endocrine and exocrine disor-ders. For example, octreotide has been shown to decrease fistula output and speed the time it takes for enteric and pancreatic fistulas to close.10Endocrine release of somatostatin occurs during a meal. The major stimulant is probably intraluminal fat. Acidification of the gastric and duodenal mucosa also releases somatostatin in isolated perfused organ preparations. Acetylcholine from the cholinergic neurons inhibits somatostatin release.Pancreatic polypeptide (PP) is a 36-amino-acid, straight-chain peptide discovered by Kimmel in 1968 during the process of insulin purification. Protein is the most potent enteral stimu-lator of PP release, closely followed by fat, whereas glucose has a weaker effect.11 Hypoglycemia, whether or not it is insulin induced, strongly stimulates PP secretion through cholinergic stimulation.12 Phenylalanine, tryptophan, and | Surgery_Schwartz. have a longer serum half-life, and their potent inhibitory effect has been used clinically to treat both endocrine and exocrine disor-ders. For example, octreotide has been shown to decrease fistula output and speed the time it takes for enteric and pancreatic fistulas to close.10Endocrine release of somatostatin occurs during a meal. The major stimulant is probably intraluminal fat. Acidification of the gastric and duodenal mucosa also releases somatostatin in isolated perfused organ preparations. Acetylcholine from the cholinergic neurons inhibits somatostatin release.Pancreatic polypeptide (PP) is a 36-amino-acid, straight-chain peptide discovered by Kimmel in 1968 during the process of insulin purification. Protein is the most potent enteral stimu-lator of PP release, closely followed by fat, whereas glucose has a weaker effect.11 Hypoglycemia, whether or not it is insulin induced, strongly stimulates PP secretion through cholinergic stimulation.12 Phenylalanine, tryptophan, and |
Surgery_Schwartz_9517 | Surgery_Schwartz | by fat, whereas glucose has a weaker effect.11 Hypoglycemia, whether or not it is insulin induced, strongly stimulates PP secretion through cholinergic stimulation.12 Phenylalanine, tryptophan, and fatty acids in the duodenum stimulate PP release, probably by inducing CCK, GIP, and secretin release. Vagal stimulation of the pancreas is the most important regulator of PP secretion. In fact, vagotomy eliminates the rise in PP levels usually seen after a meal. This can be used as a test for the completeness of a surgical vagot-omy or for the presence of diabetic autonomic neuropathy.PP has been shown to inhibit choleresis (bile secretion), gallbladder contraction, and secretion by the exocrine pan-creas. However, PP’s most important role is in glucose regu-lation through its regulation of hepatic insulin receptor gene expression. A deficiency in PP secretion due to proximal pan-createctomy, severe chronic pancreatitis, or cystic fibrosis, is associated with diminished hepatic insulin | Surgery_Schwartz. by fat, whereas glucose has a weaker effect.11 Hypoglycemia, whether or not it is insulin induced, strongly stimulates PP secretion through cholinergic stimulation.12 Phenylalanine, tryptophan, and fatty acids in the duodenum stimulate PP release, probably by inducing CCK, GIP, and secretin release. Vagal stimulation of the pancreas is the most important regulator of PP secretion. In fact, vagotomy eliminates the rise in PP levels usually seen after a meal. This can be used as a test for the completeness of a surgical vagot-omy or for the presence of diabetic autonomic neuropathy.PP has been shown to inhibit choleresis (bile secretion), gallbladder contraction, and secretion by the exocrine pan-creas. However, PP’s most important role is in glucose regu-lation through its regulation of hepatic insulin receptor gene expression. A deficiency in PP secretion due to proximal pan-createctomy, severe chronic pancreatitis, or cystic fibrosis, is associated with diminished hepatic insulin |
Surgery_Schwartz_9518 | Surgery_Schwartz | hepatic insulin receptor gene expression. A deficiency in PP secretion due to proximal pan-createctomy, severe chronic pancreatitis, or cystic fibrosis, is associated with diminished hepatic insulin sensitivity due to reduced hepatic insulin receptor availability.13 This effect is reversed by PP administration.14Recent studies have shown that a fifth islet peptide, ghre-lin, is secreted from a distinct population of islet cells, called epsilon cells.15,16 Ghrelin also is present in the gastric fundus in large amounts and stimulates growth hormone secretion via growth hormone releasing hormone release from the pituitary. It is an orexigenic, or appetite-stimulating, peptide the plasma levels of which are increased in obesity. Ghrelin has also been shown to block insulin effects on the liver, and inhibits the beta-cell response to incretin hormones and glucose.17 Therefore, ghrelin secretion from and within the islet may modulate the responses of other islet cells to nutrient and | Surgery_Schwartz. hepatic insulin receptor gene expression. A deficiency in PP secretion due to proximal pan-createctomy, severe chronic pancreatitis, or cystic fibrosis, is associated with diminished hepatic insulin sensitivity due to reduced hepatic insulin receptor availability.13 This effect is reversed by PP administration.14Recent studies have shown that a fifth islet peptide, ghre-lin, is secreted from a distinct population of islet cells, called epsilon cells.15,16 Ghrelin also is present in the gastric fundus in large amounts and stimulates growth hormone secretion via growth hormone releasing hormone release from the pituitary. It is an orexigenic, or appetite-stimulating, peptide the plasma levels of which are increased in obesity. Ghrelin has also been shown to block insulin effects on the liver, and inhibits the beta-cell response to incretin hormones and glucose.17 Therefore, ghrelin secretion from and within the islet may modulate the responses of other islet cells to nutrient and |
Surgery_Schwartz_9519 | Surgery_Schwartz | liver, and inhibits the beta-cell response to incretin hormones and glucose.17 Therefore, ghrelin secretion from and within the islet may modulate the responses of other islet cells to nutrient and hormonal stimuli.In addition to the five main peptides secreted by the pan-creas, there are a number of other peptide products of the islet cells, including amylin, peptide YY (PYY), and pancreastatin, as well as neuropeptides such as VIP, galanin, and serotonin. Amylin or islet amyloid polypeptide (IAPP) is a 37-amino-acid polypeptide that is predominantly expressed by the pancreatic beta-cells, where it is stored along with insulin in secretory granules.18 The function of IAPP seems to be the modulation or counterregulation of insulin secretion and function. Pancre-astatin is a recently discovered pancreatic islet peptide prod-uct that inhibits insulin, and possibly somatostatin release, and augments glucagon release.19,20 In addition to this effect on the endocrine pancreas, | Surgery_Schwartz. liver, and inhibits the beta-cell response to incretin hormones and glucose.17 Therefore, ghrelin secretion from and within the islet may modulate the responses of other islet cells to nutrient and hormonal stimuli.In addition to the five main peptides secreted by the pan-creas, there are a number of other peptide products of the islet cells, including amylin, peptide YY (PYY), and pancreastatin, as well as neuropeptides such as VIP, galanin, and serotonin. Amylin or islet amyloid polypeptide (IAPP) is a 37-amino-acid polypeptide that is predominantly expressed by the pancreatic beta-cells, where it is stored along with insulin in secretory granules.18 The function of IAPP seems to be the modulation or counterregulation of insulin secretion and function. Pancre-astatin is a recently discovered pancreatic islet peptide prod-uct that inhibits insulin, and possibly somatostatin release, and augments glucagon release.19,20 In addition to this effect on the endocrine pancreas, |
Surgery_Schwartz_9520 | Surgery_Schwartz | discovered pancreatic islet peptide prod-uct that inhibits insulin, and possibly somatostatin release, and augments glucagon release.19,20 In addition to this effect on the endocrine pancreas, pancreastatin inhibits pancreatic exocrine secretion.21 PYY is structurally related to PP and was initially found in hormone-secreting “L” cells of the small intestine, where it colocalizes with GLP-1. Recently, PYY has been local-ized to the islets22 where it appears to regulate insulin secretion through an autocrine mechanism.Islet DistributionThe beta-cells are generally located in the central portion of each islet and make up about 70% of the total islet cell mass. The other cell types are located predominantly in the periphery. The delta cells are least plentiful, making up only 5%; the 〈-cells make up 10%, and the PP cells make up 15%.23 In contrast to the acinar cells that secrete the full gamut of exocrine enzymes, the islet cells seem to specialize in the secretion of predominantly one | Surgery_Schwartz. discovered pancreatic islet peptide prod-uct that inhibits insulin, and possibly somatostatin release, and augments glucagon release.19,20 In addition to this effect on the endocrine pancreas, pancreastatin inhibits pancreatic exocrine secretion.21 PYY is structurally related to PP and was initially found in hormone-secreting “L” cells of the small intestine, where it colocalizes with GLP-1. Recently, PYY has been local-ized to the islets22 where it appears to regulate insulin secretion through an autocrine mechanism.Islet DistributionThe beta-cells are generally located in the central portion of each islet and make up about 70% of the total islet cell mass. The other cell types are located predominantly in the periphery. The delta cells are least plentiful, making up only 5%; the 〈-cells make up 10%, and the PP cells make up 15%.23 In contrast to the acinar cells that secrete the full gamut of exocrine enzymes, the islet cells seem to specialize in the secretion of predominantly one |
Surgery_Schwartz_9521 | Surgery_Schwartz | make up 10%, and the PP cells make up 15%.23 In contrast to the acinar cells that secrete the full gamut of exocrine enzymes, the islet cells seem to specialize in the secretion of predominantly one hormone. However, individual islet cells can secrete mul-tiple hormones. For example, the beta-cells secrete both insulin and amylin, which counter regulates the actions of insulin. In reality, more than 20 different hormones are secreted by the islets, and the exact functions of this milieu are very complex. There is diversity among the islets depending on their location within the pancreas. The beta and delta cells are evenly distrib-uted throughout the pancreas, but islets in the head and uncinate process (ventral anlage) have a higher percentage of PP cells and fewer alpha cells, whereas islets in the body and tail (dorsal anlage) contain the majority of alpha cells and few PP cells. This is clinically significant because pancreatoduodenectomy removes 95% of the PP cells in the | Surgery_Schwartz. make up 10%, and the PP cells make up 15%.23 In contrast to the acinar cells that secrete the full gamut of exocrine enzymes, the islet cells seem to specialize in the secretion of predominantly one hormone. However, individual islet cells can secrete mul-tiple hormones. For example, the beta-cells secrete both insulin and amylin, which counter regulates the actions of insulin. In reality, more than 20 different hormones are secreted by the islets, and the exact functions of this milieu are very complex. There is diversity among the islets depending on their location within the pancreas. The beta and delta cells are evenly distrib-uted throughout the pancreas, but islets in the head and uncinate process (ventral anlage) have a higher percentage of PP cells and fewer alpha cells, whereas islets in the body and tail (dorsal anlage) contain the majority of alpha cells and few PP cells. This is clinically significant because pancreatoduodenectomy removes 95% of the PP cells in the |
Surgery_Schwartz_9522 | Surgery_Schwartz | islets in the body and tail (dorsal anlage) contain the majority of alpha cells and few PP cells. This is clinically significant because pancreatoduodenectomy removes 95% of the PP cells in the pancreas. This may partially explain the higher incidence of glucose intolerance after the Whipple procedure compared to a distal pancreatectomy with an equivalent amount of tissue resected. In addition, chronic pan-creatitis, which disproportionately affects the pancreatic head, is associated with PP deficiency and pancreatogenic diabetes.24 The relative preponderance of alpha cells in the body and tail of the pancreas explains the typical location of glucagonomas.ACUTE PANCREATITISDefinition, Incidence, and EpidemiologyAcute pancreatitis is an inflammatory disorder of the pancreas that is characterized by edema and, when severe, necrosis. It is a common and challenging disease that can develop local and systemic complications. As such, it ranges from a mild, self-limiting inflammation of the | Surgery_Schwartz. islets in the body and tail (dorsal anlage) contain the majority of alpha cells and few PP cells. This is clinically significant because pancreatoduodenectomy removes 95% of the PP cells in the pancreas. This may partially explain the higher incidence of glucose intolerance after the Whipple procedure compared to a distal pancreatectomy with an equivalent amount of tissue resected. In addition, chronic pan-creatitis, which disproportionately affects the pancreatic head, is associated with PP deficiency and pancreatogenic diabetes.24 The relative preponderance of alpha cells in the body and tail of the pancreas explains the typical location of glucagonomas.ACUTE PANCREATITISDefinition, Incidence, and EpidemiologyAcute pancreatitis is an inflammatory disorder of the pancreas that is characterized by edema and, when severe, necrosis. It is a common and challenging disease that can develop local and systemic complications. As such, it ranges from a mild, self-limiting inflammation of the |
Surgery_Schwartz_9523 | Surgery_Schwartz | by edema and, when severe, necrosis. It is a common and challenging disease that can develop local and systemic complications. As such, it ranges from a mild, self-limiting inflammation of the pancreas to severe and critical disease characterized by infected pancreatic necrosis, multiple Brunicardi_Ch33_p1429-p1516.indd 143901/03/19 6:44 PM 1440SPECIFIC CONSIDERATIONSPART IITable 33-4Etiologies of acute pancreatitisAlcoholBiliary tract diseaseHyperlipidemiaHereditaryHypercalcemiaTrauma External Surgical Endoscopic retrograde cholangiopancreatographyIschemia Hypoperfusion Atheroembolic VasculitisPancreatic duct obstruction Neoplasms Pancreas divisum Ampullary and duodenal lesionsInfectionsVenomDrugsIdiopathicReproduced with permission from Townsend CM, Sabiston DC: Sabiston’s Textbook of Surgery: the biological basis of modern surgical practice, 16th ed. Philadelphia, PA: Saunders/Elsevier; 2000.organ failure, and a high mortality.25 The traditional view is that acute pancreatitis | Surgery_Schwartz. by edema and, when severe, necrosis. It is a common and challenging disease that can develop local and systemic complications. As such, it ranges from a mild, self-limiting inflammation of the pancreas to severe and critical disease characterized by infected pancreatic necrosis, multiple Brunicardi_Ch33_p1429-p1516.indd 143901/03/19 6:44 PM 1440SPECIFIC CONSIDERATIONSPART IITable 33-4Etiologies of acute pancreatitisAlcoholBiliary tract diseaseHyperlipidemiaHereditaryHypercalcemiaTrauma External Surgical Endoscopic retrograde cholangiopancreatographyIschemia Hypoperfusion Atheroembolic VasculitisPancreatic duct obstruction Neoplasms Pancreas divisum Ampullary and duodenal lesionsInfectionsVenomDrugsIdiopathicReproduced with permission from Townsend CM, Sabiston DC: Sabiston’s Textbook of Surgery: the biological basis of modern surgical practice, 16th ed. Philadelphia, PA: Saunders/Elsevier; 2000.organ failure, and a high mortality.25 The traditional view is that acute pancreatitis |
Surgery_Schwartz_9524 | Surgery_Schwartz | of Surgery: the biological basis of modern surgical practice, 16th ed. Philadelphia, PA: Saunders/Elsevier; 2000.organ failure, and a high mortality.25 The traditional view is that acute pancreatitis completely resolves with no morphological, functional, or symptomatic sequelae. But necrotizing pancreati-tis can leave significant scarring, strictures, and impairment of exocrine and endocrine pancreatic function. The overall clinical outcome has improved over recent decades, even in the absence of specific treatments that target outcome-determining patho-physiology, probably because of a more standardized approach to diagnosis, monitoring, and management.Acute pancreatitis is the most common inpatient princi-pal gastrointestinal discharge diagnosis in the United States (274,119 in 2009), with an increasing incidence (30% since 2000) and is associated with the highest aggregate inpatient costs at 2.6 billion dollars per year.26 The crude mortality rate of 1 per 100,000 population ranks | Surgery_Schwartz. of Surgery: the biological basis of modern surgical practice, 16th ed. Philadelphia, PA: Saunders/Elsevier; 2000.organ failure, and a high mortality.25 The traditional view is that acute pancreatitis completely resolves with no morphological, functional, or symptomatic sequelae. But necrotizing pancreati-tis can leave significant scarring, strictures, and impairment of exocrine and endocrine pancreatic function. The overall clinical outcome has improved over recent decades, even in the absence of specific treatments that target outcome-determining patho-physiology, probably because of a more standardized approach to diagnosis, monitoring, and management.Acute pancreatitis is the most common inpatient princi-pal gastrointestinal discharge diagnosis in the United States (274,119 in 2009), with an increasing incidence (30% since 2000) and is associated with the highest aggregate inpatient costs at 2.6 billion dollars per year.26 The crude mortality rate of 1 per 100,000 population ranks |
Surgery_Schwartz_9525 | Surgery_Schwartz | an increasing incidence (30% since 2000) and is associated with the highest aggregate inpatient costs at 2.6 billion dollars per year.26 The crude mortality rate of 1 per 100,000 population ranks it as the 14th most common overall and the 9th most common noncancer cause of gastrointestinal deaths. Worldwide, the incidence of acute pancreatitis ranges from 5 to 80 per 100,000 population, with the highest incidence recorded in Finland and the United States.27 The incidence of acute pancreatitis also shows significant variation related to the prevalence of etiological factors and ethnicity. The annual inci-dence of acute pancreatitis in Native Americans is 4 per 100,000 population; in whites, it is 5.7; and in blacks it is 20.7.28 Smok-ing is an independent risk factor for acute pancreatitis.29EtiologyMany factors are causally related to the onset of acute pan-creatitis, but the mechanism is often poorly understood. The most common causes are gallstones and alcohol (Table 33-4), | Surgery_Schwartz. an increasing incidence (30% since 2000) and is associated with the highest aggregate inpatient costs at 2.6 billion dollars per year.26 The crude mortality rate of 1 per 100,000 population ranks it as the 14th most common overall and the 9th most common noncancer cause of gastrointestinal deaths. Worldwide, the incidence of acute pancreatitis ranges from 5 to 80 per 100,000 population, with the highest incidence recorded in Finland and the United States.27 The incidence of acute pancreatitis also shows significant variation related to the prevalence of etiological factors and ethnicity. The annual inci-dence of acute pancreatitis in Native Americans is 4 per 100,000 population; in whites, it is 5.7; and in blacks it is 20.7.28 Smok-ing is an independent risk factor for acute pancreatitis.29EtiologyMany factors are causally related to the onset of acute pan-creatitis, but the mechanism is often poorly understood. The most common causes are gallstones and alcohol (Table 33-4), |
Surgery_Schwartz_9526 | Surgery_Schwartz | factors are causally related to the onset of acute pan-creatitis, but the mechanism is often poorly understood. The most common causes are gallstones and alcohol (Table 33-4), accounting for up to 80% of cases, but it is not uncommon to diagnose acute pancreatitis in the absence of these etiological factors (“idiopathic acute pancreatitis”), and it is important that a systematic approach is taken to the identification of other, less common and potentially modifiable factors. The median age at index presentation of acute pancreatitis varies with etiology: with alcoholand drug-induced pancreatitis presenting in the third or fourth decade compared with gallstone and trauma in the sixth decade. The gender difference is probably more related to etiology: in males alcohol is more often the cause while in females it is gallstones.GallstonesEvidence that passage of a gallstone is related to the onset of acute pancreatitis comes from the characteristic transient derangement of liver function | Surgery_Schwartz. factors are causally related to the onset of acute pan-creatitis, but the mechanism is often poorly understood. The most common causes are gallstones and alcohol (Table 33-4), accounting for up to 80% of cases, but it is not uncommon to diagnose acute pancreatitis in the absence of these etiological factors (“idiopathic acute pancreatitis”), and it is important that a systematic approach is taken to the identification of other, less common and potentially modifiable factors. The median age at index presentation of acute pancreatitis varies with etiology: with alcoholand drug-induced pancreatitis presenting in the third or fourth decade compared with gallstone and trauma in the sixth decade. The gender difference is probably more related to etiology: in males alcohol is more often the cause while in females it is gallstones.GallstonesEvidence that passage of a gallstone is related to the onset of acute pancreatitis comes from the characteristic transient derangement of liver function |
Surgery_Schwartz_9527 | Surgery_Schwartz | while in females it is gallstones.GallstonesEvidence that passage of a gallstone is related to the onset of acute pancreatitis comes from the characteristic transient derangement of liver function tests and the high retrieval rate of gallstones from feces within 10 days of an attack of acute pancreatitis compared with those without acute pancreatitis (88% vs. 11%).30 The mechanism by which small gallstones cause acute pancreatitis in migrating through to the duodenum is not clear. Opie made the seminal observation of a gallstone impacted in the sphincter of Oddi in two fatal cases of acute pancreatitis, which lead to the “common channel” hypothesis. It was proposed that this allowed bile to reflux into the pancre-atic duct, but this cannot be reliably reproduced in experimen-tal models. Another proposal was that transient incompetence caused by the passage of a stone through the sphincter might allow duodenal fluid and bile to reflux into the pancreatic duct, but this is not supported | Surgery_Schwartz. while in females it is gallstones.GallstonesEvidence that passage of a gallstone is related to the onset of acute pancreatitis comes from the characteristic transient derangement of liver function tests and the high retrieval rate of gallstones from feces within 10 days of an attack of acute pancreatitis compared with those without acute pancreatitis (88% vs. 11%).30 The mechanism by which small gallstones cause acute pancreatitis in migrating through to the duodenum is not clear. Opie made the seminal observation of a gallstone impacted in the sphincter of Oddi in two fatal cases of acute pancreatitis, which lead to the “common channel” hypothesis. It was proposed that this allowed bile to reflux into the pancre-atic duct, but this cannot be reliably reproduced in experimen-tal models. Another proposal was that transient incompetence caused by the passage of a stone through the sphincter might allow duodenal fluid and bile to reflux into the pancreatic duct, but this is not supported |
Surgery_Schwartz_9528 | Surgery_Schwartz | proposal was that transient incompetence caused by the passage of a stone through the sphincter might allow duodenal fluid and bile to reflux into the pancreatic duct, but this is not supported by the failure of this to commonly occur after endoscopic sphincterotomy. A third possibility is that acute pancreatitis is due to the gallstone obstructing the pancreatic duct and leading to ductal hypertension. It has been postulated that this backpressure might lead to minor ductal dis-ruption, extravasation of pancreatic juice into the less alkaline interstitium of the pancreas, and promotion of enzyme activa-tion. When gallstones and other etiological factors cannot be identified, there is still the possibility of finding microlithiasis, seen as birefringent crystals, on bile microscopy.31 This occult microlithiasis is probably responsible for up to half of those with idiopathic acute pancreatitis.AlcoholAlcohol ingestion is associated with acute pancreatitis, and sus-tained alcohol | Surgery_Schwartz. proposal was that transient incompetence caused by the passage of a stone through the sphincter might allow duodenal fluid and bile to reflux into the pancreatic duct, but this is not supported by the failure of this to commonly occur after endoscopic sphincterotomy. A third possibility is that acute pancreatitis is due to the gallstone obstructing the pancreatic duct and leading to ductal hypertension. It has been postulated that this backpressure might lead to minor ductal dis-ruption, extravasation of pancreatic juice into the less alkaline interstitium of the pancreas, and promotion of enzyme activa-tion. When gallstones and other etiological factors cannot be identified, there is still the possibility of finding microlithiasis, seen as birefringent crystals, on bile microscopy.31 This occult microlithiasis is probably responsible for up to half of those with idiopathic acute pancreatitis.AlcoholAlcohol ingestion is associated with acute pancreatitis, and sus-tained alcohol |
Surgery_Schwartz_9529 | Surgery_Schwartz | This occult microlithiasis is probably responsible for up to half of those with idiopathic acute pancreatitis.AlcoholAlcohol ingestion is associated with acute pancreatitis, and sus-tained alcohol ingestion is associated with recurrent acute pan-creatitis and development of chronic pancreatitis in susceptible individuals who have been drinking for more than a decade. The type of alcohol consumed is less important than the amount consumed (typically 100–150 grams per day) and the pattern of drinking. It is common for patients with alcohol-associated acute pancreatitis to have a history of excess alcohol consumption prior to the first attack. There are several mechanisms by which ethanol causes acute pancreatitis by acting on the acinar and stellate cells.32 The acinar cell metabolizes ethanol by oxidative and nonoxidative pathways, and exhibits changes that predis-pose the cell to autodigestive injury, necroinflammation, and cell death. The stellate cells are activated on exposure to | Surgery_Schwartz. This occult microlithiasis is probably responsible for up to half of those with idiopathic acute pancreatitis.AlcoholAlcohol ingestion is associated with acute pancreatitis, and sus-tained alcohol ingestion is associated with recurrent acute pan-creatitis and development of chronic pancreatitis in susceptible individuals who have been drinking for more than a decade. The type of alcohol consumed is less important than the amount consumed (typically 100–150 grams per day) and the pattern of drinking. It is common for patients with alcohol-associated acute pancreatitis to have a history of excess alcohol consumption prior to the first attack. There are several mechanisms by which ethanol causes acute pancreatitis by acting on the acinar and stellate cells.32 The acinar cell metabolizes ethanol by oxidative and nonoxidative pathways, and exhibits changes that predis-pose the cell to autodigestive injury, necroinflammation, and cell death. The stellate cells are activated on exposure to |
Surgery_Schwartz_9530 | Surgery_Schwartz | by oxidative and nonoxidative pathways, and exhibits changes that predis-pose the cell to autodigestive injury, necroinflammation, and cell death. The stellate cells are activated on exposure to ethanol to a myofibroblast phenotype, stimulating synthesis of proinflam-matory mediators and cytokines. Ethanol causes a brief secretory increase followed by inhibition. The secretory burst coupled with ethanol induced spasm of the sphincter of Oddi probably incites acute pancreatitis. Ethanol also induces ductal permeability, which allows prematurely activated enzymes to cause damage to the pancreatic parenchyma. Ethanol also increases the protein content of pancreatic juice and decreases bicarbonate levels and trypsin inhibitor concentration. The formation of protein plugs may also contribute by causing an obstructive element to pancre-atic outflow, more often seen in chronic pancreatitis.Brunicardi_Ch33_p1429-p1516.indd 144001/03/19 6:44 PM 1441PANCREASCHAPTER 33Figure 33-10. Schema of | Surgery_Schwartz. by oxidative and nonoxidative pathways, and exhibits changes that predis-pose the cell to autodigestive injury, necroinflammation, and cell death. The stellate cells are activated on exposure to ethanol to a myofibroblast phenotype, stimulating synthesis of proinflam-matory mediators and cytokines. Ethanol causes a brief secretory increase followed by inhibition. The secretory burst coupled with ethanol induced spasm of the sphincter of Oddi probably incites acute pancreatitis. Ethanol also induces ductal permeability, which allows prematurely activated enzymes to cause damage to the pancreatic parenchyma. Ethanol also increases the protein content of pancreatic juice and decreases bicarbonate levels and trypsin inhibitor concentration. The formation of protein plugs may also contribute by causing an obstructive element to pancre-atic outflow, more often seen in chronic pancreatitis.Brunicardi_Ch33_p1429-p1516.indd 144001/03/19 6:44 PM 1441PANCREASCHAPTER 33Figure 33-10. Schema of |
Surgery_Schwartz_9531 | Surgery_Schwartz | causing an obstructive element to pancre-atic outflow, more often seen in chronic pancreatitis.Brunicardi_Ch33_p1429-p1516.indd 144001/03/19 6:44 PM 1441PANCREASCHAPTER 33Figure 33-10. Schema of key loco-regional pathophysiological events in the pancreas and intestine and how they interact to drive the severity and outcome of acute pancreatitis. (Adapted with permission from Flint RS, Windsor JA: The role of the intestine in the pathophysiology and management of severe acute pancreatitis, HPB (Oxford). 2003;5(2):69-85.)IatrogenicAcute pancreatitis can occur due to trauma to the ducts or parenchyma after surgical procedures, including biopsy, bile duct exploration, distal gastrectomy, and splenectomy. As the pancreas is susceptible to ischemia, it can also occur second-ary to splanchnic hypoperfusion with cardiopulmonary bypass, cardiac transplant, hemorrhagic shock, and major trauma. The most common iatrogenic cause is ERCP in which acute pancre-atitis occurs after about 5% to 10% | Surgery_Schwartz. causing an obstructive element to pancre-atic outflow, more often seen in chronic pancreatitis.Brunicardi_Ch33_p1429-p1516.indd 144001/03/19 6:44 PM 1441PANCREASCHAPTER 33Figure 33-10. Schema of key loco-regional pathophysiological events in the pancreas and intestine and how they interact to drive the severity and outcome of acute pancreatitis. (Adapted with permission from Flint RS, Windsor JA: The role of the intestine in the pathophysiology and management of severe acute pancreatitis, HPB (Oxford). 2003;5(2):69-85.)IatrogenicAcute pancreatitis can occur due to trauma to the ducts or parenchyma after surgical procedures, including biopsy, bile duct exploration, distal gastrectomy, and splenectomy. As the pancreas is susceptible to ischemia, it can also occur second-ary to splanchnic hypoperfusion with cardiopulmonary bypass, cardiac transplant, hemorrhagic shock, and major trauma. The most common iatrogenic cause is ERCP in which acute pancre-atitis occurs after about 5% to 10% |
Surgery_Schwartz_9532 | Surgery_Schwartz | hypoperfusion with cardiopulmonary bypass, cardiac transplant, hemorrhagic shock, and major trauma. The most common iatrogenic cause is ERCP in which acute pancre-atitis occurs after about 5% to 10% of procedures, and in many series, it is the third most common identified etiological fac-tor. The risk of post-ERCP acute pancreatitis is increased if the contrast agent is infused repeatedly under high pressure by the endoscopist and in patients with sphincter of Oddi dysfunction. Recent evidence demonstrates that the risk can be decreased with prophylactic rectal nonsteroidal drugs,33 and this may be a better strategy than prophylactic pancreatic duct stenting.34Hereditary PancreatitisHereditary pancreatitis is an autosomal dominant disorder usually related to mutations of the cationic trypsinogen gene (PRSS1). Mutations in this gene cause premature activation of trypsinogen to trypsin and causes abnormalities of ductal secre-tion, both of which promote acute pancreatitis. Mutations in | Surgery_Schwartz. hypoperfusion with cardiopulmonary bypass, cardiac transplant, hemorrhagic shock, and major trauma. The most common iatrogenic cause is ERCP in which acute pancre-atitis occurs after about 5% to 10% of procedures, and in many series, it is the third most common identified etiological fac-tor. The risk of post-ERCP acute pancreatitis is increased if the contrast agent is infused repeatedly under high pressure by the endoscopist and in patients with sphincter of Oddi dysfunction. Recent evidence demonstrates that the risk can be decreased with prophylactic rectal nonsteroidal drugs,33 and this may be a better strategy than prophylactic pancreatic duct stenting.34Hereditary PancreatitisHereditary pancreatitis is an autosomal dominant disorder usually related to mutations of the cationic trypsinogen gene (PRSS1). Mutations in this gene cause premature activation of trypsinogen to trypsin and causes abnormalities of ductal secre-tion, both of which promote acute pancreatitis. Mutations in |
Surgery_Schwartz_9533 | Surgery_Schwartz | gene (PRSS1). Mutations in this gene cause premature activation of trypsinogen to trypsin and causes abnormalities of ductal secre-tion, both of which promote acute pancreatitis. Mutations in the SPINK1 protein, which blocks the active binding site of trypsin, is likely to also have a role in predisposing to acute pancreatitis. Variations in penetration and phenotype are common, and there are many other mutations that have become implicated. Mutant enzymes activated within acinar cells can overwhelm the first line of defense (pancreatic secretory trypsin inhibitor) and resist backup defenses (e.g., proteolytic degradation, enzyme Y, and trypsin itself) allowing activated mutant cationic trypsin to trig-ger the entire zymogen activation cascade.35TumorsA pancreatic or periampullary tumor should be considered in patients with idiopathic acute pancreatitis, especially in those over 50 years old. Approximately 1% to 2% of patients with acute pancreatitis have a pancreatic tumor, and an | Surgery_Schwartz. gene (PRSS1). Mutations in this gene cause premature activation of trypsinogen to trypsin and causes abnormalities of ductal secre-tion, both of which promote acute pancreatitis. Mutations in the SPINK1 protein, which blocks the active binding site of trypsin, is likely to also have a role in predisposing to acute pancreatitis. Variations in penetration and phenotype are common, and there are many other mutations that have become implicated. Mutant enzymes activated within acinar cells can overwhelm the first line of defense (pancreatic secretory trypsin inhibitor) and resist backup defenses (e.g., proteolytic degradation, enzyme Y, and trypsin itself) allowing activated mutant cationic trypsin to trig-ger the entire zymogen activation cascade.35TumorsA pancreatic or periampullary tumor should be considered in patients with idiopathic acute pancreatitis, especially in those over 50 years old. Approximately 1% to 2% of patients with acute pancreatitis have a pancreatic tumor, and an |
Surgery_Schwartz_9534 | Surgery_Schwartz | should be considered in patients with idiopathic acute pancreatitis, especially in those over 50 years old. Approximately 1% to 2% of patients with acute pancreatitis have a pancreatic tumor, and an episode of acute pancreatitis can be the first clinical indicator. Cross-sectional imaging after the resolution of the acute pancreatitis is required.HyperlipidemiaPatients with types I and V hyperlipoproteinemia can experience episodes of abdominal pain, and these often occur in association with marked hypertriglyceridaemia. Lipase is thought to liberate toxic fatty acids into the pancreatic microcirculation, leading to microcirculatory impairment and ischemia. Dietary modifica-tions and drug treatment are used to lower triglycerides.DrugsIsolated cases of acute pancreatitis have been associated with exposure to certain drugs, such as thiazide diuretics, furosemide, estrogen replacement therapy, and steroid therapy in children. In addition, certain chemotherapy agents and anti-immune | Surgery_Schwartz. should be considered in patients with idiopathic acute pancreatitis, especially in those over 50 years old. Approximately 1% to 2% of patients with acute pancreatitis have a pancreatic tumor, and an episode of acute pancreatitis can be the first clinical indicator. Cross-sectional imaging after the resolution of the acute pancreatitis is required.HyperlipidemiaPatients with types I and V hyperlipoproteinemia can experience episodes of abdominal pain, and these often occur in association with marked hypertriglyceridaemia. Lipase is thought to liberate toxic fatty acids into the pancreatic microcirculation, leading to microcirculatory impairment and ischemia. Dietary modifica-tions and drug treatment are used to lower triglycerides.DrugsIsolated cases of acute pancreatitis have been associated with exposure to certain drugs, such as thiazide diuretics, furosemide, estrogen replacement therapy, and steroid therapy in children. In addition, certain chemotherapy agents and anti-immune |
Surgery_Schwartz_9535 | Surgery_Schwartz | with exposure to certain drugs, such as thiazide diuretics, furosemide, estrogen replacement therapy, and steroid therapy in children. In addition, certain chemotherapy agents and anti-immune drugs have been associated with acute pancreatitis, and lipid-based drugs or solutions, such as propofol, have been shown to cause acute pancreatitis.PathophysiologyAcute pancreatitis occurs in various degrees of severity, the determinants of which are multifactorial. The generally prevalent belief today is that pancreatitis begins with the activation of diges-tive zymogens inside acinar cells, which cause acinar cell injury. Studies suggest that the ultimate severity of the resulting pancre-atitis may be determined by the events that occur subsequent to acinar cell injury.36 These include inflammatory cell recruitment and activation, as well as generation and release of cytokines and other chemical mediators that cause systemic inflammation and multiple organ dysfunction/failure (Figure | Surgery_Schwartz. with exposure to certain drugs, such as thiazide diuretics, furosemide, estrogen replacement therapy, and steroid therapy in children. In addition, certain chemotherapy agents and anti-immune drugs have been associated with acute pancreatitis, and lipid-based drugs or solutions, such as propofol, have been shown to cause acute pancreatitis.PathophysiologyAcute pancreatitis occurs in various degrees of severity, the determinants of which are multifactorial. The generally prevalent belief today is that pancreatitis begins with the activation of diges-tive zymogens inside acinar cells, which cause acinar cell injury. Studies suggest that the ultimate severity of the resulting pancre-atitis may be determined by the events that occur subsequent to acinar cell injury.36 These include inflammatory cell recruitment and activation, as well as generation and release of cytokines and other chemical mediators that cause systemic inflammation and multiple organ dysfunction/failure (Figure |
Surgery_Schwartz_9536 | Surgery_Schwartz | cell recruitment and activation, as well as generation and release of cytokines and other chemical mediators that cause systemic inflammation and multiple organ dysfunction/failure (Figure 33-10).Precipitating EventsIn 1896, Chiari proposed that pancreatitis was due to the premature, intrapancreatic activation of digestive enzymes, resulting in “auto-digestion” of the organ. Since then the Brunicardi_Ch33_p1429-p1516.indd 144101/03/19 6:44 PM 1442SPECIFIC CONSIDERATIONSPART IIFigure 33-11. Schematic representation of the acinar cell events in acute pancreatitis. When acinar cells are pathologically stimulated, their lysosomal (L) and zymogen (Z) contents colocalize, and consequently trypsinogen is activated to trypsin by cathepsin B. Increased cytosolic calcium is required for colocalization. Once trypsin has permeabilized the contents of the cytosol, cathepsin B and other contents of these colocalized organelles are released. Once in the cytosol, cathepsin B activates apoptosis | Surgery_Schwartz. cell recruitment and activation, as well as generation and release of cytokines and other chemical mediators that cause systemic inflammation and multiple organ dysfunction/failure (Figure 33-10).Precipitating EventsIn 1896, Chiari proposed that pancreatitis was due to the premature, intrapancreatic activation of digestive enzymes, resulting in “auto-digestion” of the organ. Since then the Brunicardi_Ch33_p1429-p1516.indd 144101/03/19 6:44 PM 1442SPECIFIC CONSIDERATIONSPART IIFigure 33-11. Schematic representation of the acinar cell events in acute pancreatitis. When acinar cells are pathologically stimulated, their lysosomal (L) and zymogen (Z) contents colocalize, and consequently trypsinogen is activated to trypsin by cathepsin B. Increased cytosolic calcium is required for colocalization. Once trypsin has permeabilized the contents of the cytosol, cathepsin B and other contents of these colocalized organelles are released. Once in the cytosol, cathepsin B activates apoptosis |
Surgery_Schwartz_9537 | Surgery_Schwartz | Once trypsin has permeabilized the contents of the cytosol, cathepsin B and other contents of these colocalized organelles are released. Once in the cytosol, cathepsin B activates apoptosis by causing cytochrome c to be released from the mitochondria. Activation of PKC results in a sudden activation of nuclear factor kappa beta (NFκβ), which in turn triggers the release of cytokines that attract inflammatory response cells that mediate local and systemic inflammation cascades.intra-acinar activation of zymogens has been demonstrated consistently in multiple animal models of acute pancreatitis and is considered a key precipitating event.37,38 The key role of trypsin activation in acute pancreatitis has gained additional support from recent studies showing that mice lacking trypsinogen-7 (the isoform of trypsinogen that is activated during acute pancreatitis in mice) have significantly less pancreatic injury during acute pancreatitis39 and that intra-acinar expression of active trypsin | Surgery_Schwartz. Once trypsin has permeabilized the contents of the cytosol, cathepsin B and other contents of these colocalized organelles are released. Once in the cytosol, cathepsin B activates apoptosis by causing cytochrome c to be released from the mitochondria. Activation of PKC results in a sudden activation of nuclear factor kappa beta (NFκβ), which in turn triggers the release of cytokines that attract inflammatory response cells that mediate local and systemic inflammation cascades.intra-acinar activation of zymogens has been demonstrated consistently in multiple animal models of acute pancreatitis and is considered a key precipitating event.37,38 The key role of trypsin activation in acute pancreatitis has gained additional support from recent studies showing that mice lacking trypsinogen-7 (the isoform of trypsinogen that is activated during acute pancreatitis in mice) have significantly less pancreatic injury during acute pancreatitis39 and that intra-acinar expression of active trypsin |
Surgery_Schwartz_9538 | Surgery_Schwartz | isoform of trypsinogen that is activated during acute pancreatitis in mice) have significantly less pancreatic injury during acute pancreatitis39 and that intra-acinar expression of active trypsin causes pancreatitis in mice.40 The role of trypsin activation in the pathophysiology of acute pancreatitis has also been suggested by clinical studies. Hereditary pancreatitis is associated with mutations that lead to elevated intracellular trypsin activation,41 and activation of trypsinogen causes clinical pancreatitis.42Significant progress has been made in understanding the mechanisms by which injurious stimuli lead to intra-acinar activation of trypsinogen and autodigestion of the gland (Figure 33-11). Under physiologic conditions, several protective mechanisms have evolved to prevent autodigestion of the pancreas by these enzymes. This includes synthesis of enzymes as inactive precursors, separation of the site of production, and activation of the enzymes and presence of trypsin | Surgery_Schwartz. isoform of trypsinogen that is activated during acute pancreatitis in mice) have significantly less pancreatic injury during acute pancreatitis39 and that intra-acinar expression of active trypsin causes pancreatitis in mice.40 The role of trypsin activation in the pathophysiology of acute pancreatitis has also been suggested by clinical studies. Hereditary pancreatitis is associated with mutations that lead to elevated intracellular trypsin activation,41 and activation of trypsinogen causes clinical pancreatitis.42Significant progress has been made in understanding the mechanisms by which injurious stimuli lead to intra-acinar activation of trypsinogen and autodigestion of the gland (Figure 33-11). Under physiologic conditions, several protective mechanisms have evolved to prevent autodigestion of the pancreas by these enzymes. This includes synthesis of enzymes as inactive precursors, separation of the site of production, and activation of the enzymes and presence of trypsin |
Surgery_Schwartz_9539 | Surgery_Schwartz | autodigestion of the pancreas by these enzymes. This includes synthesis of enzymes as inactive precursors, separation of the site of production, and activation of the enzymes and presence of trypsin inhibitors in the pancreas. It is thought that acute pancreatitis occurs when these protective mechanisms are overwhelmed with erroneously activated enzymes, causing injury. It has been shown that intra-acinar activation of trypsinogen goes hand-in-hand with inhibition of acinar secretion.43,44 Furthermore, with injurious stimuli the zymogens responsible for initiating the disease are not secreted outside, but colocalize with cytoplasmic vacuoles that contain lysosomal enzymes such as cathepsin B45 that activate trypsinogen. Thus, inhibition of cathepsin B by pharmacological inhibitors46 or by genetic deletion of cathepsin B eliminates trypsin activation and decreases the severity of pancreatitis in animal models.47 What leads to the colocalization of zymogens and lysosomal hydrolases is | Surgery_Schwartz. autodigestion of the pancreas by these enzymes. This includes synthesis of enzymes as inactive precursors, separation of the site of production, and activation of the enzymes and presence of trypsin inhibitors in the pancreas. It is thought that acute pancreatitis occurs when these protective mechanisms are overwhelmed with erroneously activated enzymes, causing injury. It has been shown that intra-acinar activation of trypsinogen goes hand-in-hand with inhibition of acinar secretion.43,44 Furthermore, with injurious stimuli the zymogens responsible for initiating the disease are not secreted outside, but colocalize with cytoplasmic vacuoles that contain lysosomal enzymes such as cathepsin B45 that activate trypsinogen. Thus, inhibition of cathepsin B by pharmacological inhibitors46 or by genetic deletion of cathepsin B eliminates trypsin activation and decreases the severity of pancreatitis in animal models.47 What leads to the colocalization of zymogens and lysosomal hydrolases is |
Surgery_Schwartz_9540 | Surgery_Schwartz | genetic deletion of cathepsin B eliminates trypsin activation and decreases the severity of pancreatitis in animal models.47 What leads to the colocalization of zymogens and lysosomal hydrolases is unclear, but injurious stimuli leading to sustained cytosolic calcium increase have been indicted. Blocking this calcium increase prevents colocalization and activation of trypsin, and it decreases injury due to pancreatitis.48 Based on these data, pre-ERCP supplementation of magnesium, a natural antagonist of calcium, is currently being evaluated as a strategy to decrease post-ERCP pancreatitis.49 Recent work has led to the novel hypothesis that the lysosomal hydrolase cathepsin B activates trypsinogen to trypsin within the colocalization vacuoles. Trypsin then permeabilizes these colocalization vacuoles causing the release of cathepsin B into the cytosol. Once in the cytosol, cathepsin B initiates apoptotic cell death by permeabilizing mitochondrial membranes, which allows cytochrome C to | Surgery_Schwartz. genetic deletion of cathepsin B eliminates trypsin activation and decreases the severity of pancreatitis in animal models.47 What leads to the colocalization of zymogens and lysosomal hydrolases is unclear, but injurious stimuli leading to sustained cytosolic calcium increase have been indicted. Blocking this calcium increase prevents colocalization and activation of trypsin, and it decreases injury due to pancreatitis.48 Based on these data, pre-ERCP supplementation of magnesium, a natural antagonist of calcium, is currently being evaluated as a strategy to decrease post-ERCP pancreatitis.49 Recent work has led to the novel hypothesis that the lysosomal hydrolase cathepsin B activates trypsinogen to trypsin within the colocalization vacuoles. Trypsin then permeabilizes these colocalization vacuoles causing the release of cathepsin B into the cytosol. Once in the cytosol, cathepsin B initiates apoptotic cell death by permeabilizing mitochondrial membranes, which allows cytochrome C to |
Surgery_Schwartz_9541 | Surgery_Schwartz | vacuoles causing the release of cathepsin B into the cytosol. Once in the cytosol, cathepsin B initiates apoptotic cell death by permeabilizing mitochondrial membranes, which allows cytochrome C to be released into the cytosol. This initiates the apoptotic cascade and results in the apoptotic death of the acinar cells50 (see Figure 33-11).Intrapancreatic EventsAlthough intra-acinar events initiate acute pancreatitis, events occurring subsequent to acinar cell injury determine the severity of pancreatitis. Activated neutrophils are attracted and activated in the pancreas releasing superoxide (the respiratory burst) and proteolytic enzymes (cathepsins, elastase, and collagenase) that cause further pancreatic injury. In addition, macrophages release cytokines (including tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1, IL-2, IL-6, and IL-8) that mediate local and systemic inflammation.38These inflammatory mediators cause an increased pancre-atic vascular permeability, leading | Surgery_Schwartz. vacuoles causing the release of cathepsin B into the cytosol. Once in the cytosol, cathepsin B initiates apoptotic cell death by permeabilizing mitochondrial membranes, which allows cytochrome C to be released into the cytosol. This initiates the apoptotic cascade and results in the apoptotic death of the acinar cells50 (see Figure 33-11).Intrapancreatic EventsAlthough intra-acinar events initiate acute pancreatitis, events occurring subsequent to acinar cell injury determine the severity of pancreatitis. Activated neutrophils are attracted and activated in the pancreas releasing superoxide (the respiratory burst) and proteolytic enzymes (cathepsins, elastase, and collagenase) that cause further pancreatic injury. In addition, macrophages release cytokines (including tumor necrosis factor-alpha (TNF-α) and interleukins (IL-1, IL-2, IL-6, and IL-8) that mediate local and systemic inflammation.38These inflammatory mediators cause an increased pancre-atic vascular permeability, leading |
Surgery_Schwartz_9542 | Surgery_Schwartz | (TNF-α) and interleukins (IL-1, IL-2, IL-6, and IL-8) that mediate local and systemic inflammation.38These inflammatory mediators cause an increased pancre-atic vascular permeability, leading to hemorrhage, edema, and Acinar cell deathTo pancreatic ductTrypsinogenCathepsin BActive trypsinEarly stagesLeaky colocalizedorganellesColocalizationSustainedRise in Ca2+PKC activationInsultSystemic in‘ammationRelease of cytokinesand chemokinesRecruitment ofin‘ammatory cellsLater stagesNF–KBactivationLocal injury: PancreatitisZLBrunicardi_Ch33_p1429-p1516.indd 144201/03/19 6:44 PM 1443PANCREASCHAPTER 33Figure 33-12. Computed tomography scan showing well perfused interstitial edematous acute pancreatitis of the neck and tail of the pancreas with a confluent area of necrosis of the pancreatic body. The pancreas is surrounded by fluid, inflammation, and possible peripancreatic fat necrosis.Table 33-5Local complications of acute pancreatitisCONTENT ACUTE (<4 WEEKS, NO DEFINED WALL)CHRONIC (>4 | Surgery_Schwartz. (TNF-α) and interleukins (IL-1, IL-2, IL-6, and IL-8) that mediate local and systemic inflammation.38These inflammatory mediators cause an increased pancre-atic vascular permeability, leading to hemorrhage, edema, and Acinar cell deathTo pancreatic ductTrypsinogenCathepsin BActive trypsinEarly stagesLeaky colocalizedorganellesColocalizationSustainedRise in Ca2+PKC activationInsultSystemic in‘ammationRelease of cytokinesand chemokinesRecruitment ofin‘ammatory cellsLater stagesNF–KBactivationLocal injury: PancreatitisZLBrunicardi_Ch33_p1429-p1516.indd 144201/03/19 6:44 PM 1443PANCREASCHAPTER 33Figure 33-12. Computed tomography scan showing well perfused interstitial edematous acute pancreatitis of the neck and tail of the pancreas with a confluent area of necrosis of the pancreatic body. The pancreas is surrounded by fluid, inflammation, and possible peripancreatic fat necrosis.Table 33-5Local complications of acute pancreatitisCONTENT ACUTE (<4 WEEKS, NO DEFINED WALL)CHRONIC (>4 |
Surgery_Schwartz_9543 | Surgery_Schwartz | The pancreas is surrounded by fluid, inflammation, and possible peripancreatic fat necrosis.Table 33-5Local complications of acute pancreatitisCONTENT ACUTE (<4 WEEKS, NO DEFINED WALL)CHRONIC (>4 WEEKS, DEFINED WALL)NO INFECTIONINFECTIONNO INFECTIONINFECTIONFluidAcute pancreatic fluid collection (APFC)Infected APFCPseudocystInfected pseudocystSolid ± fluidAcute necrotic collection (ANC)Infected ANCWalled off necrosis (WON)Infected WONReproduced with permission from Windsor JA, Petrov MS: Acute pancreatitis reclassified, Gut. 2013 Jan;62(1):4-5.microthrombi. Fluid may collect in and around the pancreas. The failure of the pancreatic microcirculation, a feature of more severe acute pancreatitis, results in pancreatic hypoperfusion and necrosis. Acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but with no recognizable necrosis, is termed interstitial edematous pancreatitis.25 When necrosis is present, as evidenced by pancreatic hypoperfusion with contrast CT, | Surgery_Schwartz. The pancreas is surrounded by fluid, inflammation, and possible peripancreatic fat necrosis.Table 33-5Local complications of acute pancreatitisCONTENT ACUTE (<4 WEEKS, NO DEFINED WALL)CHRONIC (>4 WEEKS, DEFINED WALL)NO INFECTIONINFECTIONNO INFECTIONINFECTIONFluidAcute pancreatic fluid collection (APFC)Infected APFCPseudocystInfected pseudocystSolid ± fluidAcute necrotic collection (ANC)Infected ANCWalled off necrosis (WON)Infected WONReproduced with permission from Windsor JA, Petrov MS: Acute pancreatitis reclassified, Gut. 2013 Jan;62(1):4-5.microthrombi. Fluid may collect in and around the pancreas. The failure of the pancreatic microcirculation, a feature of more severe acute pancreatitis, results in pancreatic hypoperfusion and necrosis. Acute inflammation of the pancreatic parenchyma and peripancreatic tissues, but with no recognizable necrosis, is termed interstitial edematous pancreatitis.25 When necrosis is present, as evidenced by pancreatic hypoperfusion with contrast CT, |
Surgery_Schwartz_9544 | Surgery_Schwartz | and peripancreatic tissues, but with no recognizable necrosis, is termed interstitial edematous pancreatitis.25 When necrosis is present, as evidenced by pancreatic hypoperfusion with contrast CT, it is termed necrotizing pancreatitis (Figure 33-12). The updated morphological definitions and the contrast enhanced CT criteria for the diagnosis of the local complications of acute pancreatitis are in the revised Atlanta statement51 and summa-rized in Table 33-5.52Systemic EventsAn important aspect of the pathophysiology of acute pancre-atitis is the mechanism by which events occurring in the pan-creas induce systemic inflammation and multiorgan failure. The NFκB-dependent inflammatory pathway is an important mechanism (see Figure 33-11). Activation of NFκB parallels trypsin activation in acute pancreatitis but appears to be inde-pendent of it, as it occurs in trypsin knockout mice.39 Sustained calcium increase, which leads to trypsinogen activation, is criti-cal for NFκB activation since | Surgery_Schwartz. and peripancreatic tissues, but with no recognizable necrosis, is termed interstitial edematous pancreatitis.25 When necrosis is present, as evidenced by pancreatic hypoperfusion with contrast CT, it is termed necrotizing pancreatitis (Figure 33-12). The updated morphological definitions and the contrast enhanced CT criteria for the diagnosis of the local complications of acute pancreatitis are in the revised Atlanta statement51 and summa-rized in Table 33-5.52Systemic EventsAn important aspect of the pathophysiology of acute pancre-atitis is the mechanism by which events occurring in the pan-creas induce systemic inflammation and multiorgan failure. The NFκB-dependent inflammatory pathway is an important mechanism (see Figure 33-11). Activation of NFκB parallels trypsin activation in acute pancreatitis but appears to be inde-pendent of it, as it occurs in trypsin knockout mice.39 Sustained calcium increase, which leads to trypsinogen activation, is criti-cal for NFκB activation since |
Surgery_Schwartz_9545 | Surgery_Schwartz | pancreatitis but appears to be inde-pendent of it, as it occurs in trypsin knockout mice.39 Sustained calcium increase, which leads to trypsinogen activation, is criti-cal for NFκB activation since attenuation of cytosolic calcium abrogates NFκB activation.53 Once activated, NFκB regulates synthesis of multiple cytokines and chemokines, leading to recruitment of various inflammatory cells that then magnify and propagate systemic inflammation.54 The infiltrating neutrophils can also further augment the pancreatic injury.55,56 Inhibition of many of these cytokines have led to reduced local and systemic injury in animal models of acute pancreatitis. But these results did not translate to clinical improvement.57 New strategies are required to reduce the systemic inflammatory response.58-60Organ failure can develop at any stage of acute pancreati-tis, associated with an overwhelming proinflammatory response early, or later secondary to the development of infected local complications. The | Surgery_Schwartz. pancreatitis but appears to be inde-pendent of it, as it occurs in trypsin knockout mice.39 Sustained calcium increase, which leads to trypsinogen activation, is criti-cal for NFκB activation since attenuation of cytosolic calcium abrogates NFκB activation.53 Once activated, NFκB regulates synthesis of multiple cytokines and chemokines, leading to recruitment of various inflammatory cells that then magnify and propagate systemic inflammation.54 The infiltrating neutrophils can also further augment the pancreatic injury.55,56 Inhibition of many of these cytokines have led to reduced local and systemic injury in animal models of acute pancreatitis. But these results did not translate to clinical improvement.57 New strategies are required to reduce the systemic inflammatory response.58-60Organ failure can develop at any stage of acute pancreati-tis, associated with an overwhelming proinflammatory response early, or later secondary to the development of infected local complications. The |
Surgery_Schwartz_9546 | Surgery_Schwartz | failure can develop at any stage of acute pancreati-tis, associated with an overwhelming proinflammatory response early, or later secondary to the development of infected local complications. The drivers of the systemic response are poorly understood, although factors include the elaboration of proin-flammatory cytokines, and it appears that mesenteric lymph, bypassing the liver and containing these constituents, may con-tribute to the development of organ failure61 (see Figure 33-10). The development of pancreatic necrosis, the breakdown of the intestinal barrier, and the suppression of the immune response through the compensatory inflammatory response contribute to the development of infected pancreatic necrosis, the incidence of which peaks in the third to fourth week. This is usually asso-ciated with deterioration in the patient’s condition and may be associated with the late development of the systemic inflam-matory response syndrome (SIRS) and multiorgan dysfunction | Surgery_Schwartz. failure can develop at any stage of acute pancreati-tis, associated with an overwhelming proinflammatory response early, or later secondary to the development of infected local complications. The drivers of the systemic response are poorly understood, although factors include the elaboration of proin-flammatory cytokines, and it appears that mesenteric lymph, bypassing the liver and containing these constituents, may con-tribute to the development of organ failure61 (see Figure 33-10). The development of pancreatic necrosis, the breakdown of the intestinal barrier, and the suppression of the immune response through the compensatory inflammatory response contribute to the development of infected pancreatic necrosis, the incidence of which peaks in the third to fourth week. This is usually asso-ciated with deterioration in the patient’s condition and may be associated with the late development of the systemic inflam-matory response syndrome (SIRS) and multiorgan dysfunction |
Surgery_Schwartz_9547 | Surgery_Schwartz | is usually asso-ciated with deterioration in the patient’s condition and may be associated with the late development of the systemic inflam-matory response syndrome (SIRS) and multiorgan dysfunction syndrome/failure (MODS/F).Organ failure is scored using the Marshall or Sequential Organ Failure Assessment (SOFA) systems (Table 33-6). The three organ systems most frequently involved are cardiovas-cular, respiratory, and renal. Multiple organ failure is defined as two or more organs registering two or more points on these scoring systems.51 Monitoring organ failure over time and in response to treatment is important in the care and timing of intervention in these patients.Management of Acute PancreatitisGeneral Considerations. The management of acute pancre-atitis covers a wide spectrum of severity. All patients with sus-pected acute pancreatitis should be admitted to hospital. Those with mild acute pancreatitis usually remain in hospital for less than a week, while those with severe | Surgery_Schwartz. is usually asso-ciated with deterioration in the patient’s condition and may be associated with the late development of the systemic inflam-matory response syndrome (SIRS) and multiorgan dysfunction syndrome/failure (MODS/F).Organ failure is scored using the Marshall or Sequential Organ Failure Assessment (SOFA) systems (Table 33-6). The three organ systems most frequently involved are cardiovas-cular, respiratory, and renal. Multiple organ failure is defined as two or more organs registering two or more points on these scoring systems.51 Monitoring organ failure over time and in response to treatment is important in the care and timing of intervention in these patients.Management of Acute PancreatitisGeneral Considerations. The management of acute pancre-atitis covers a wide spectrum of severity. All patients with sus-pected acute pancreatitis should be admitted to hospital. Those with mild acute pancreatitis usually remain in hospital for less than a week, while those with severe |
Surgery_Schwartz_9548 | Surgery_Schwartz | severity. All patients with sus-pected acute pancreatitis should be admitted to hospital. Those with mild acute pancreatitis usually remain in hospital for less than a week, while those with severe and critical acute pan-creatitis may require many weeks or months of intensive treat-ment. The risk of mortality reflects this spectrum of severity. The risk is less than 1% for those with mild disease, increasing to around 10% for those with moderate disease, but for severe (20–40%) and critical (>50%) disease the mortality risk is much higher. The earlier identification of these high-risk categories and their transfer to specialized centers is an important priority of management.62The management of acute pancreatitis is multidisciplinary, and it is important that this is coordinated care plan is carefully supervised.63 The essential requirements for the management Brunicardi_Ch33_p1429-p1516.indd 144301/03/19 6:44 PM 1444SPECIFIC CONSIDERATIONSPART IITable 33-6Sequential organ failure | Surgery_Schwartz. severity. All patients with sus-pected acute pancreatitis should be admitted to hospital. Those with mild acute pancreatitis usually remain in hospital for less than a week, while those with severe and critical acute pan-creatitis may require many weeks or months of intensive treat-ment. The risk of mortality reflects this spectrum of severity. The risk is less than 1% for those with mild disease, increasing to around 10% for those with moderate disease, but for severe (20–40%) and critical (>50%) disease the mortality risk is much higher. The earlier identification of these high-risk categories and their transfer to specialized centers is an important priority of management.62The management of acute pancreatitis is multidisciplinary, and it is important that this is coordinated care plan is carefully supervised.63 The essential requirements for the management Brunicardi_Ch33_p1429-p1516.indd 144301/03/19 6:44 PM 1444SPECIFIC CONSIDERATIONSPART IITable 33-6Sequential organ failure |
Surgery_Schwartz_9549 | Surgery_Schwartz | is carefully supervised.63 The essential requirements for the management Brunicardi_Ch33_p1429-p1516.indd 144301/03/19 6:44 PM 1444SPECIFIC CONSIDERATIONSPART IITable 33-6Sequential organ failure assessment (SOFA) score in acute pancreatitis 01234Respiration (PaO2FIO2) (mmHg)>400≤400≤300≤200 with respiratory support≤100 with respiratory supportCoagulation Platelets (xl01 per μL)>150≤150≤100≤50≤20Liver Bilirubin (μmol/L)<2020–3233–101102–204>204Cardiovascular HypotensionNo hypotensionMAP <70 mmHgDopamine ≤5 or dobutamine (any dose)aDopamine >5 or epi ≤0.1a or norepi ≤0.1aDopamine >15 or epi >0.1a or norepi >0.1aCentral nervous system Glasgow coma score1513–1410–126–9<6Kidney Creatinine (μmol/L) or urine output<110110–170171–299300–440 or <500 mL/day>440 or <200 mL/dayaAdrenergic agents administered for at least 1 h (doses given in μg/kg per min). A score of 2 or more in any two systems indicates the presence of multiple organ failure.Abbreviations: MAP = | Surgery_Schwartz. is carefully supervised.63 The essential requirements for the management Brunicardi_Ch33_p1429-p1516.indd 144301/03/19 6:44 PM 1444SPECIFIC CONSIDERATIONSPART IITable 33-6Sequential organ failure assessment (SOFA) score in acute pancreatitis 01234Respiration (PaO2FIO2) (mmHg)>400≤400≤300≤200 with respiratory support≤100 with respiratory supportCoagulation Platelets (xl01 per μL)>150≤150≤100≤50≤20Liver Bilirubin (μmol/L)<2020–3233–101102–204>204Cardiovascular HypotensionNo hypotensionMAP <70 mmHgDopamine ≤5 or dobutamine (any dose)aDopamine >5 or epi ≤0.1a or norepi ≤0.1aDopamine >15 or epi >0.1a or norepi >0.1aCentral nervous system Glasgow coma score1513–1410–126–9<6Kidney Creatinine (μmol/L) or urine output<110110–170171–299300–440 or <500 mL/day>440 or <200 mL/dayaAdrenergic agents administered for at least 1 h (doses given in μg/kg per min). A score of 2 or more in any two systems indicates the presence of multiple organ failure.Abbreviations: MAP = |
Surgery_Schwartz_9550 | Surgery_Schwartz | mL/dayaAdrenergic agents administered for at least 1 h (doses given in μg/kg per min). A score of 2 or more in any two systems indicates the presence of multiple organ failure.Abbreviations: MAP = mean arterial pressure; Epi = epineptvine; Norepi = norepinephrine.of acute pancreatitis are accurate diagnosis, appropriate triage, high-quality supportive care, and monitoring for and treatment of complications.64DiagnosisThe diagnosis of acute pancreatitis requires the patient to pres-ent with abdominal pain consistent with acute pancreatitis (acute onset of a severe constant epigastric pain that often radiates through to the mid back) and the elevation of serum amylase or lipase (>3 times upper limit of normal). Imaging (usually by contrast-enhanced CT scanning) is only required for the diagnosis of acute pancreatitis when these diagnostic criteria are not met.51 Because of the many causes of hyperamylasemia, it is important to use either the pancreatic isoenzyme of amylase or | Surgery_Schwartz. mL/dayaAdrenergic agents administered for at least 1 h (doses given in μg/kg per min). A score of 2 or more in any two systems indicates the presence of multiple organ failure.Abbreviations: MAP = mean arterial pressure; Epi = epineptvine; Norepi = norepinephrine.of acute pancreatitis are accurate diagnosis, appropriate triage, high-quality supportive care, and monitoring for and treatment of complications.64DiagnosisThe diagnosis of acute pancreatitis requires the patient to pres-ent with abdominal pain consistent with acute pancreatitis (acute onset of a severe constant epigastric pain that often radiates through to the mid back) and the elevation of serum amylase or lipase (>3 times upper limit of normal). Imaging (usually by contrast-enhanced CT scanning) is only required for the diagnosis of acute pancreatitis when these diagnostic criteria are not met.51 Because of the many causes of hyperamylasemia, it is important to use either the pancreatic isoenzyme of amylase or |
Surgery_Schwartz_9551 | Surgery_Schwartz | the diagnosis of acute pancreatitis when these diagnostic criteria are not met.51 Because of the many causes of hyperamylasemia, it is important to use either the pancreatic isoenzyme of amylase or lipase.63The serum amylase concentration increases almost imme-diately with the onset of disease and peaks within several hours and remains elevated for 3 to 5 days.64 There is no correlation between the extent of serum amylase elevation and severity of pancreatitis; in fact, a milder form of acute pancreatitis is often associated with higher levels of serum amylase compared with that in a more severe form of the disease. It is important to note that hyperamylasemia can also occur in association with other diseases. For example, it can occur in a patient with small bowel obstruction, perforated duodenal ulcer, or other intra-abdominal inflammatory conditions. In contrast, a patient with acute pancreatitis can have a normal serum amylase level, for several different reasons. In patients with | Surgery_Schwartz. the diagnosis of acute pancreatitis when these diagnostic criteria are not met.51 Because of the many causes of hyperamylasemia, it is important to use either the pancreatic isoenzyme of amylase or lipase.63The serum amylase concentration increases almost imme-diately with the onset of disease and peaks within several hours and remains elevated for 3 to 5 days.64 There is no correlation between the extent of serum amylase elevation and severity of pancreatitis; in fact, a milder form of acute pancreatitis is often associated with higher levels of serum amylase compared with that in a more severe form of the disease. It is important to note that hyperamylasemia can also occur in association with other diseases. For example, it can occur in a patient with small bowel obstruction, perforated duodenal ulcer, or other intra-abdominal inflammatory conditions. In contrast, a patient with acute pancreatitis can have a normal serum amylase level, for several different reasons. In patients with |
Surgery_Schwartz_9552 | Surgery_Schwartz | duodenal ulcer, or other intra-abdominal inflammatory conditions. In contrast, a patient with acute pancreatitis can have a normal serum amylase level, for several different reasons. In patients with hyperlipidemia, values might appear to be normal because of interference with chemical determination of serum amylase by lipids. In some cases, urinary clearance of pancreatic enzymes from the circu-lation increases during pancreatitis, meaning that urinary levels may be more sensitive than serum levels. For these reasons, it is recommended that amylase concentrations also be measured in the urine. Urinary amylase levels usually remain elevated for several days after serum levels have returned to normal. In patients with severe pancreatitis associated with significant necrosis, the pancreas may not have the capacity to release large amounts of enzymes into the circulation. With more severe dis-ease, there is also hemoconcentration from third space fluid loss, and this can affect the serum | Surgery_Schwartz. duodenal ulcer, or other intra-abdominal inflammatory conditions. In contrast, a patient with acute pancreatitis can have a normal serum amylase level, for several different reasons. In patients with hyperlipidemia, values might appear to be normal because of interference with chemical determination of serum amylase by lipids. In some cases, urinary clearance of pancreatic enzymes from the circu-lation increases during pancreatitis, meaning that urinary levels may be more sensitive than serum levels. For these reasons, it is recommended that amylase concentrations also be measured in the urine. Urinary amylase levels usually remain elevated for several days after serum levels have returned to normal. In patients with severe pancreatitis associated with significant necrosis, the pancreas may not have the capacity to release large amounts of enzymes into the circulation. With more severe dis-ease, there is also hemoconcentration from third space fluid loss, and this can affect the serum |
Surgery_Schwartz_9553 | Surgery_Schwartz | not have the capacity to release large amounts of enzymes into the circulation. With more severe dis-ease, there is also hemoconcentration from third space fluid loss, and this can affect the serum concentration of amylase.The clinical signs of acute pancreatitis include abdominal tenderness, often with signs of peritonitis in the upper abdomen. Rarely, pancreatic fluid and bleeding from the pancreas into the retroperitoneum may result in a bruise-like discoloration around the umbilicus (Cullen’s sign) or in the flanks (Grey Turner’s sign). Another rare sign is tetany as a result of hypocalcaemia. In addition to hemoconcentration, patients with acute pancreati-tis often have azotemia with elevated blood urea nitrogen and creatinine levels, hyperglycemia, and hypoalbuminemia.Pain ManagementPain is the cardinal symptom of acute pancreatitis, and its relief is a clinical priority. There is a lack of high-quality evidence to guide the choice of analgesic. Because of unpredictable | Surgery_Schwartz. not have the capacity to release large amounts of enzymes into the circulation. With more severe dis-ease, there is also hemoconcentration from third space fluid loss, and this can affect the serum concentration of amylase.The clinical signs of acute pancreatitis include abdominal tenderness, often with signs of peritonitis in the upper abdomen. Rarely, pancreatic fluid and bleeding from the pancreas into the retroperitoneum may result in a bruise-like discoloration around the umbilicus (Cullen’s sign) or in the flanks (Grey Turner’s sign). Another rare sign is tetany as a result of hypocalcaemia. In addition to hemoconcentration, patients with acute pancreati-tis often have azotemia with elevated blood urea nitrogen and creatinine levels, hyperglycemia, and hypoalbuminemia.Pain ManagementPain is the cardinal symptom of acute pancreatitis, and its relief is a clinical priority. There is a lack of high-quality evidence to guide the choice of analgesic. Because of unpredictable |
Surgery_Schwartz_9554 | Surgery_Schwartz | is the cardinal symptom of acute pancreatitis, and its relief is a clinical priority. There is a lack of high-quality evidence to guide the choice of analgesic. Because of unpredictable absorption, analgesia should be administered intravenously, at least at the outset and before oral intake has been established. Those with mild pain can usually be managed with a nonsteroidal anti-inflammatory drugs (e.g., metamizole 2 g/8 h IV), while those with more severe pain are best managed with opioid analgesia (e.g., buprenorphine 0.3 mg/4 h IV). Administration of buprenorphine, pentazocine, procaine hydrochloride, and meperidine are all of value in controlling abdominal pain. Morphine is to be avoided because of its potential to cause sphincter of Oddi spasm.Predicting SeverityWhereas classification relates to the present or past severity of acute pancreatitis, prediction is about the future and ultimate severity and outcome of the patient. Accurately predicting acute | Surgery_Schwartz. is the cardinal symptom of acute pancreatitis, and its relief is a clinical priority. There is a lack of high-quality evidence to guide the choice of analgesic. Because of unpredictable absorption, analgesia should be administered intravenously, at least at the outset and before oral intake has been established. Those with mild pain can usually be managed with a nonsteroidal anti-inflammatory drugs (e.g., metamizole 2 g/8 h IV), while those with more severe pain are best managed with opioid analgesia (e.g., buprenorphine 0.3 mg/4 h IV). Administration of buprenorphine, pentazocine, procaine hydrochloride, and meperidine are all of value in controlling abdominal pain. Morphine is to be avoided because of its potential to cause sphincter of Oddi spasm.Predicting SeverityWhereas classification relates to the present or past severity of acute pancreatitis, prediction is about the future and ultimate severity and outcome of the patient. Accurately predicting acute |
Surgery_Schwartz_9555 | Surgery_Schwartz | classification relates to the present or past severity of acute pancreatitis, prediction is about the future and ultimate severity and outcome of the patient. Accurately predicting acute Brunicardi_Ch33_p1429-p1516.indd 144401/03/19 6:44 PM 1445PANCREASCHAPTER 33Table 33-7Ranson’s prognostic signs of pancreatitisCriteria for acute pancreatitis not due to gallstonesAt admissionDuring the initial 48 h Age >55 y Hematocrit fall >10 points WBC >16,000/mm3 BUN elevation >5 mg/dL Blood glucose >200 mg/dL Serum calcium <8 mg/dL Serum LDH >350 IU/L Arterial PO2 <60 mmHg Serum AST >250 U/dL Base deficit >4 mEq/L Estimated fluid sequestration >6 LCriteria for acute gallstone pancreatitisAt admissionDuring the initial 48 h Age >70 y Hematocrit fall >10 points WBC >18,000/mm3 BUN elevation >2 mg/dL Blood glucose >220 mg/dL Serum calcium <8 mg/dL Serum LDH >400 IU/L Base deficit >5 mEq/L Serum AST >250 U/dL Estimated fluid sequestration >4 LNote: Fewer than three positive criteria predict | Surgery_Schwartz. classification relates to the present or past severity of acute pancreatitis, prediction is about the future and ultimate severity and outcome of the patient. Accurately predicting acute Brunicardi_Ch33_p1429-p1516.indd 144401/03/19 6:44 PM 1445PANCREASCHAPTER 33Table 33-7Ranson’s prognostic signs of pancreatitisCriteria for acute pancreatitis not due to gallstonesAt admissionDuring the initial 48 h Age >55 y Hematocrit fall >10 points WBC >16,000/mm3 BUN elevation >5 mg/dL Blood glucose >200 mg/dL Serum calcium <8 mg/dL Serum LDH >350 IU/L Arterial PO2 <60 mmHg Serum AST >250 U/dL Base deficit >4 mEq/L Estimated fluid sequestration >6 LCriteria for acute gallstone pancreatitisAt admissionDuring the initial 48 h Age >70 y Hematocrit fall >10 points WBC >18,000/mm3 BUN elevation >2 mg/dL Blood glucose >220 mg/dL Serum calcium <8 mg/dL Serum LDH >400 IU/L Base deficit >5 mEq/L Serum AST >250 U/dL Estimated fluid sequestration >4 LNote: Fewer than three positive criteria predict |
Surgery_Schwartz_9556 | Surgery_Schwartz | mg/dL Blood glucose >220 mg/dL Serum calcium <8 mg/dL Serum LDH >400 IU/L Base deficit >5 mEq/L Serum AST >250 U/dL Estimated fluid sequestration >4 LNote: Fewer than three positive criteria predict mild, uncomplicated disease, whereas more than six positive criteria predict severe disease with a mortality risk of 50%.Abbreviations: AST = aspartate transaminase; BUN = blood urea nitrogen; LDH = lactate dehydrogenase; PO2 = partial pressure of oxygen; WBC = white blood cell count.Data from Ranson JHC. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol. 1982;77:633 and from Ranson JH, Rifkind KM, Roses DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139:69.pancreatitis severity is important in making triage decisions about whether a patient should be transferred to a tertiary hospital or an intensive care unit and in making decisions about fluid therapy and whether an ERCP is | Surgery_Schwartz. mg/dL Blood glucose >220 mg/dL Serum calcium <8 mg/dL Serum LDH >400 IU/L Base deficit >5 mEq/L Serum AST >250 U/dL Estimated fluid sequestration >4 LNote: Fewer than three positive criteria predict mild, uncomplicated disease, whereas more than six positive criteria predict severe disease with a mortality risk of 50%.Abbreviations: AST = aspartate transaminase; BUN = blood urea nitrogen; LDH = lactate dehydrogenase; PO2 = partial pressure of oxygen; WBC = white blood cell count.Data from Ranson JHC. Etiological and prognostic factors in human acute pancreatitis: a review. Am J Gastroenterol. 1982;77:633 and from Ranson JH, Rifkind KM, Roses DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet. 1974;139:69.pancreatitis severity is important in making triage decisions about whether a patient should be transferred to a tertiary hospital or an intensive care unit and in making decisions about fluid therapy and whether an ERCP is |
Surgery_Schwartz_9557 | Surgery_Schwartz | important in making triage decisions about whether a patient should be transferred to a tertiary hospital or an intensive care unit and in making decisions about fluid therapy and whether an ERCP is indicated, as well as other issues.65 There is a very long history of attempts to find prognostic or predictive markers that accurately stratify the risk, with the most widely used being the Ranson’s criteria (Table 33-7) or modified Glasgow criteria. Both use clinical and biochemical parameters scored over the first 48 hours of admission. When there are three or more positive criteria, the disease is considered “predicted severe.” There are many other approaches to predicting severity. At 24 hours after admission an APACHE II score of 8 or more or a serum C-reactive protein level of >150 mg/dL has a similar accuracy in predicting severity as Ranson’s criteria.66 The more recently proposed Bedside Index for Severity of Acute Pancreatitis (BISAP) is calculated from blood urea nitrogen (> 25 | Surgery_Schwartz. important in making triage decisions about whether a patient should be transferred to a tertiary hospital or an intensive care unit and in making decisions about fluid therapy and whether an ERCP is indicated, as well as other issues.65 There is a very long history of attempts to find prognostic or predictive markers that accurately stratify the risk, with the most widely used being the Ranson’s criteria (Table 33-7) or modified Glasgow criteria. Both use clinical and biochemical parameters scored over the first 48 hours of admission. When there are three or more positive criteria, the disease is considered “predicted severe.” There are many other approaches to predicting severity. At 24 hours after admission an APACHE II score of 8 or more or a serum C-reactive protein level of >150 mg/dL has a similar accuracy in predicting severity as Ranson’s criteria.66 The more recently proposed Bedside Index for Severity of Acute Pancreatitis (BISAP) is calculated from blood urea nitrogen (> 25 |
Surgery_Schwartz_9558 | Surgery_Schwartz | has a similar accuracy in predicting severity as Ranson’s criteria.66 The more recently proposed Bedside Index for Severity of Acute Pancreatitis (BISAP) is calculated from blood urea nitrogen (> 25 mg/dL), impaired mental status (GCS <15), presence of systemic inflammatory response syndrome, age >60 years, and pleural effusion. Although it has the advantage of simplicity and can be performed within the first 24 hours of admission, it performed no better than other predictors.67 The presence of SIRS also has prognostic significance.68 There remains some controversy as to how important obesity is as a risk factor for severe and critical acute pancreatitis.69 Another approach has been taken in seeking to predict those with the “harmless acute pancreatitis score”70 using three factors that can be determined on admission: absence of rebound tenderness or guarding, normal hematocrit, and normal serum creatinine. The accuracy of this approach appears to be over 90% and triages most patients | Surgery_Schwartz. has a similar accuracy in predicting severity as Ranson’s criteria.66 The more recently proposed Bedside Index for Severity of Acute Pancreatitis (BISAP) is calculated from blood urea nitrogen (> 25 mg/dL), impaired mental status (GCS <15), presence of systemic inflammatory response syndrome, age >60 years, and pleural effusion. Although it has the advantage of simplicity and can be performed within the first 24 hours of admission, it performed no better than other predictors.67 The presence of SIRS also has prognostic significance.68 There remains some controversy as to how important obesity is as a risk factor for severe and critical acute pancreatitis.69 Another approach has been taken in seeking to predict those with the “harmless acute pancreatitis score”70 using three factors that can be determined on admission: absence of rebound tenderness or guarding, normal hematocrit, and normal serum creatinine. The accuracy of this approach appears to be over 90% and triages most patients |
Surgery_Schwartz_9559 | Surgery_Schwartz | be determined on admission: absence of rebound tenderness or guarding, normal hematocrit, and normal serum creatinine. The accuracy of this approach appears to be over 90% and triages most patients away from intensive care.Unfortunately, these and many other single and combined predictors of severity have an accuracy of around 70%66. This means that there is misclassification error of 30% that limits the value in predicting the severity of acute pancreatitis in indi-vidual patients. In the absence of any new biomarkers of pancre-atitis severity, making better use of existing predictors through sequencing tests, combining tests, or using artificial neural network methodologies has shown some promise.71 Scoring systems should augment clinical judgment, but not replace it.64 Over the first 2 to 3 days the clinician must be alert to patients with an elevated BUN or creatinine and/or persistent SIRS after adequate fluid resuscitation because these patients are at risk of developing severe | Surgery_Schwartz. be determined on admission: absence of rebound tenderness or guarding, normal hematocrit, and normal serum creatinine. The accuracy of this approach appears to be over 90% and triages most patients away from intensive care.Unfortunately, these and many other single and combined predictors of severity have an accuracy of around 70%66. This means that there is misclassification error of 30% that limits the value in predicting the severity of acute pancreatitis in indi-vidual patients. In the absence of any new biomarkers of pancre-atitis severity, making better use of existing predictors through sequencing tests, combining tests, or using artificial neural network methodologies has shown some promise.71 Scoring systems should augment clinical judgment, but not replace it.64 Over the first 2 to 3 days the clinician must be alert to patients with an elevated BUN or creatinine and/or persistent SIRS after adequate fluid resuscitation because these patients are at risk of developing severe |
Surgery_Schwartz_9560 | Surgery_Schwartz | to 3 days the clinician must be alert to patients with an elevated BUN or creatinine and/or persistent SIRS after adequate fluid resuscitation because these patients are at risk of developing severe acute pancreatitis.64Classification of SeverityAccurately classifying or staging acute pancreatitis severity is important for clinical decision-making, communication, and enrolment into trials. The wide spectrum of pancreatitis severity was not captured in the previous binary classifica-tions (mild or severe). The key determinants of severity are local complications (absent, sterile, or infected) and systemic complications (absent, transient organ failure, persistent organ failure).25,72 Two classification systems have recently been proposed: the three grades (mild, moderately severe, and severe) of the Revised Atlanta Criteria (RAC)51 and the four categories (mild, moderate, severe, critical) of the Determi-nants Based Classification (DBC)73 (Table 33-8). The DBC Table 33-8Definitions for | Surgery_Schwartz. to 3 days the clinician must be alert to patients with an elevated BUN or creatinine and/or persistent SIRS after adequate fluid resuscitation because these patients are at risk of developing severe acute pancreatitis.64Classification of SeverityAccurately classifying or staging acute pancreatitis severity is important for clinical decision-making, communication, and enrolment into trials. The wide spectrum of pancreatitis severity was not captured in the previous binary classifica-tions (mild or severe). The key determinants of severity are local complications (absent, sterile, or infected) and systemic complications (absent, transient organ failure, persistent organ failure).25,72 Two classification systems have recently been proposed: the three grades (mild, moderately severe, and severe) of the Revised Atlanta Criteria (RAC)51 and the four categories (mild, moderate, severe, critical) of the Determi-nants Based Classification (DBC)73 (Table 33-8). The DBC Table 33-8Definitions for |
Surgery_Schwartz_9561 | Surgery_Schwartz | of the Revised Atlanta Criteria (RAC)51 and the four categories (mild, moderate, severe, critical) of the Determi-nants Based Classification (DBC)73 (Table 33-8). The DBC Table 33-8Definitions for the classification of acute pancreatitis severity according to Revised Atlanta Classification11 and the Determinants Based Classification14. (Transient organ failure has a duration of <48 hours, persistent organ failure has duration of >48 hours.)Determinant Based Classification (2012)Revised Atlanta Classification (2013)MildNo local complicationNo systemic complicationNo local complicationNo systemic complicationModerateSterile local complication and/orTransient organ failureLocal or systemic complications without persistent organ failureorexacerbation of preexisting comorbiditySevereinfected local complicationorPersistent organ failurePersistent organ failure (single or multiple)CriticalInfected local complication and Persistent organ failure-Brunicardi_Ch33_p1429-p1516.indd | Surgery_Schwartz. of the Revised Atlanta Criteria (RAC)51 and the four categories (mild, moderate, severe, critical) of the Determi-nants Based Classification (DBC)73 (Table 33-8). The DBC Table 33-8Definitions for the classification of acute pancreatitis severity according to Revised Atlanta Classification11 and the Determinants Based Classification14. (Transient organ failure has a duration of <48 hours, persistent organ failure has duration of >48 hours.)Determinant Based Classification (2012)Revised Atlanta Classification (2013)MildNo local complicationNo systemic complicationNo local complicationNo systemic complicationModerateSterile local complication and/orTransient organ failureLocal or systemic complications without persistent organ failureorexacerbation of preexisting comorbiditySevereinfected local complicationorPersistent organ failurePersistent organ failure (single or multiple)CriticalInfected local complication and Persistent organ failure-Brunicardi_Ch33_p1429-p1516.indd |
Surgery_Schwartz_9562 | Surgery_Schwartz | local complicationorPersistent organ failurePersistent organ failure (single or multiple)CriticalInfected local complication and Persistent organ failure-Brunicardi_Ch33_p1429-p1516.indd 144501/03/19 6:44 PM 1446SPECIFIC CONSIDERATIONSPART IITable 33-9The Modified Determinant Based Classification (MDBC) (Acevedo) of acute pancreatitis severity compared with the Revised Atlanta Classification (RAC) and Determinants Based Classification (DBC). Note that the DBC has a narrower definition for local complications than RAC, leading to a slightly broader range of mild acute pancreatitis in this table.RACMild(No OF, No LC)Moderately severe(TOF and/or LC)Severe(POF)DBCMild(No OF, No LC)Moderate(TOF and/or SN)Severe(POF or IN)Critical(POF and IN)MDBC ExcludedGroup 1(TOF and/or SN)Group 2(IN without POF)Group 3(POF without IN)Group 4(POF and IN)Abbreviations: OF = organ failure; LC = local complication; TOF = transient organ failure; POF = persistent organ failure; SN = sterile necrosis; IN | Surgery_Schwartz. local complicationorPersistent organ failurePersistent organ failure (single or multiple)CriticalInfected local complication and Persistent organ failure-Brunicardi_Ch33_p1429-p1516.indd 144501/03/19 6:44 PM 1446SPECIFIC CONSIDERATIONSPART IITable 33-9The Modified Determinant Based Classification (MDBC) (Acevedo) of acute pancreatitis severity compared with the Revised Atlanta Classification (RAC) and Determinants Based Classification (DBC). Note that the DBC has a narrower definition for local complications than RAC, leading to a slightly broader range of mild acute pancreatitis in this table.RACMild(No OF, No LC)Moderately severe(TOF and/or LC)Severe(POF)DBCMild(No OF, No LC)Moderate(TOF and/or SN)Severe(POF or IN)Critical(POF and IN)MDBC ExcludedGroup 1(TOF and/or SN)Group 2(IN without POF)Group 3(POF without IN)Group 4(POF and IN)Abbreviations: OF = organ failure; LC = local complication; TOF = transient organ failure; POF = persistent organ failure; SN = sterile necrosis; IN |
Surgery_Schwartz_9563 | Surgery_Schwartz | POF)Group 3(POF without IN)Group 4(POF and IN)Abbreviations: OF = organ failure; LC = local complication; TOF = transient organ failure; POF = persistent organ failure; SN = sterile necrosis; IN = infected necrosis.was developed on the principle of casual inference, derived by meta-analysis, and refined by an international multidis-ciplinary process,73 and both classifications have been inde-pendently validated, which suggests that they are broadly equivalent. More recently a prospective multicenter study has modified the DBC to address the ongoing issue that patients considered to have severe acute pancreatitis represent several subgroups with different morbidity, mortality, and interven-tion profiles74 (Table 33-9).The classification of patient severity is helpful in tracking the clinical trajectory of a patient, and it can be applied on a daily or more frequent basis. It can also be used in retrospect for audit purposes.Determining EtiologyThe history of alcohol ingestion must be | Surgery_Schwartz. POF)Group 3(POF without IN)Group 4(POF and IN)Abbreviations: OF = organ failure; LC = local complication; TOF = transient organ failure; POF = persistent organ failure; SN = sterile necrosis; IN = infected necrosis.was developed on the principle of casual inference, derived by meta-analysis, and refined by an international multidis-ciplinary process,73 and both classifications have been inde-pendently validated, which suggests that they are broadly equivalent. More recently a prospective multicenter study has modified the DBC to address the ongoing issue that patients considered to have severe acute pancreatitis represent several subgroups with different morbidity, mortality, and interven-tion profiles74 (Table 33-9).The classification of patient severity is helpful in tracking the clinical trajectory of a patient, and it can be applied on a daily or more frequent basis. It can also be used in retrospect for audit purposes.Determining EtiologyThe history of alcohol ingestion must be |
Surgery_Schwartz_9564 | Surgery_Schwartz | trajectory of a patient, and it can be applied on a daily or more frequent basis. It can also be used in retrospect for audit purposes.Determining EtiologyThe history of alcohol ingestion must be ascertained and preferably confirmed with blood ethanol levels. Gallstones should be investigated by ultrasonography. A gallstone etiology is more likely in females over the age of 50 with an elevation of alkaline phosphatase (>300 iu/L), alanine transferase (>100 iu/L), and amylase (>4000 iu/L). In the absence of gallstones and alcohol, a systematic approach to the identification of another factor will include taking a history of drugs, trauma, ERCP, infection, and measuring serum triglycerides, calcium, and others (see Table 33-4).Fluid ResuscitationFluid therapy to restore and maintain circulating blood volume is the most important intervention in the early management of acute pancreatitis75. However, a recent systematic review has shown that the evidence base for fluid therapy is | Surgery_Schwartz. trajectory of a patient, and it can be applied on a daily or more frequent basis. It can also be used in retrospect for audit purposes.Determining EtiologyThe history of alcohol ingestion must be ascertained and preferably confirmed with blood ethanol levels. Gallstones should be investigated by ultrasonography. A gallstone etiology is more likely in females over the age of 50 with an elevation of alkaline phosphatase (>300 iu/L), alanine transferase (>100 iu/L), and amylase (>4000 iu/L). In the absence of gallstones and alcohol, a systematic approach to the identification of another factor will include taking a history of drugs, trauma, ERCP, infection, and measuring serum triglycerides, calcium, and others (see Table 33-4).Fluid ResuscitationFluid therapy to restore and maintain circulating blood volume is the most important intervention in the early management of acute pancreatitis75. However, a recent systematic review has shown that the evidence base for fluid therapy is |
Surgery_Schwartz_9565 | Surgery_Schwartz | circulating blood volume is the most important intervention in the early management of acute pancreatitis75. However, a recent systematic review has shown that the evidence base for fluid therapy is scant,76 and most recommendations are based on expert opinion.64 It is not known which fluid to give, how aggressively to adminis-ter it, or what goal to use to guide and monitor the response to it. While there are proponents for vigorous fluid therapy (5–10 mL per kilogram per hour), especially in the first 24 hours, and for specific resuscitation goals,77 it is prob-ably best to resuscitate with a balanced crystalloid and aim to restore normal blood volume, blood pressure, and urine output. In one study, lactated Ringer’s solution was supe-rior to normal saline in reducing the systemic inflammatory response.78 Caution needs to be exercised in those with car-diac and renal disease and in the elderly, where the risks of over-resuscitation are greater.Nutritional SupportIn contrast to | Surgery_Schwartz. circulating blood volume is the most important intervention in the early management of acute pancreatitis75. However, a recent systematic review has shown that the evidence base for fluid therapy is scant,76 and most recommendations are based on expert opinion.64 It is not known which fluid to give, how aggressively to adminis-ter it, or what goal to use to guide and monitor the response to it. While there are proponents for vigorous fluid therapy (5–10 mL per kilogram per hour), especially in the first 24 hours, and for specific resuscitation goals,77 it is prob-ably best to resuscitate with a balanced crystalloid and aim to restore normal blood volume, blood pressure, and urine output. In one study, lactated Ringer’s solution was supe-rior to normal saline in reducing the systemic inflammatory response.78 Caution needs to be exercised in those with car-diac and renal disease and in the elderly, where the risks of over-resuscitation are greater.Nutritional SupportIn contrast to |
Surgery_Schwartz_9566 | Surgery_Schwartz | inflammatory response.78 Caution needs to be exercised in those with car-diac and renal disease and in the elderly, where the risks of over-resuscitation are greater.Nutritional SupportIn contrast to analgesia and fluid therapy, there is a sound evidence base for nutritional support in acute pancreatitis. It is no longer acceptable to “rest the pancreas” by avoiding enteral nutrition, now the mainstay of nutritional support.79 Parenteral nutrition is now known to be more expensive, riskier, and not more effective than enteral nutrition and should only be offered if the patient’s calculated nutritional requirements cannot be achieved by the enteral route. Early initiation of enteral nutrition (within the first 24 hours of admission) is not superior to delaying an oral diet until 72 hours.80 If this is not tolerated over 48 to 72 hours, then nasogastric tube feedings can be started and increased in step-wise fashion over 2 to 3 days.81 The tube can be advanced to the jejunum, by | Surgery_Schwartz. inflammatory response.78 Caution needs to be exercised in those with car-diac and renal disease and in the elderly, where the risks of over-resuscitation are greater.Nutritional SupportIn contrast to analgesia and fluid therapy, there is a sound evidence base for nutritional support in acute pancreatitis. It is no longer acceptable to “rest the pancreas” by avoiding enteral nutrition, now the mainstay of nutritional support.79 Parenteral nutrition is now known to be more expensive, riskier, and not more effective than enteral nutrition and should only be offered if the patient’s calculated nutritional requirements cannot be achieved by the enteral route. Early initiation of enteral nutrition (within the first 24 hours of admission) is not superior to delaying an oral diet until 72 hours.80 If this is not tolerated over 48 to 72 hours, then nasogastric tube feedings can be started and increased in step-wise fashion over 2 to 3 days.81 The tube can be advanced to the jejunum, by |
Surgery_Schwartz_9567 | Surgery_Schwartz | hours.80 If this is not tolerated over 48 to 72 hours, then nasogastric tube feedings can be started and increased in step-wise fashion over 2 to 3 days.81 The tube can be advanced to the jejunum, by endoscopy or fluoroscopy, if there is evidence of feeding intolerance. A delay in commencing enteral nutrition may contribute to the development of intestinal ileus and feeding intolerance, but aggressive early enteral feeding, particularly before adequate resuscitation, may put the patient at risk of nonocclusive mesenteric ischemia. There is no evidence to support the use of elemental or immune-enhancing formulas over standard polymeric formulas.82 In predicted mild acute pancreatitis the recommencement of oral fluids and then food was delayed until resolution of abdominal pain and normalization of serum levels of amylase, but it appears safe to allow patients to resume intake ad libitum (i.e., patient-controlled nutrition). If after 3 to 5 days there is evidence of feeding | Surgery_Schwartz. hours.80 If this is not tolerated over 48 to 72 hours, then nasogastric tube feedings can be started and increased in step-wise fashion over 2 to 3 days.81 The tube can be advanced to the jejunum, by endoscopy or fluoroscopy, if there is evidence of feeding intolerance. A delay in commencing enteral nutrition may contribute to the development of intestinal ileus and feeding intolerance, but aggressive early enteral feeding, particularly before adequate resuscitation, may put the patient at risk of nonocclusive mesenteric ischemia. There is no evidence to support the use of elemental or immune-enhancing formulas over standard polymeric formulas.82 In predicted mild acute pancreatitis the recommencement of oral fluids and then food was delayed until resolution of abdominal pain and normalization of serum levels of amylase, but it appears safe to allow patients to resume intake ad libitum (i.e., patient-controlled nutrition). If after 3 to 5 days there is evidence of feeding |
Surgery_Schwartz_9568 | Surgery_Schwartz | and normalization of serum levels of amylase, but it appears safe to allow patients to resume intake ad libitum (i.e., patient-controlled nutrition). If after 3 to 5 days there is evidence of feeding intolerance, tube feeding should be commenced.Cross-Sectional ImagingIt may be necessary to perform a CT scan to diagnose acute pancreatitis in patients who are severely ill or in those presenting with undifferentiated abdominal pain. But there is no advantage in using CT scanning to predict the severity of acute pancreatitis.51,63 The primary purpose of cross-sectional imaging is the diagnosis of local complications; in particular, the development and extent of pancreatic necrosis and the different collections (see Table 33-5). CT scanning is also important to guide the insertion of percutaneous drains, now assuming a greater role in the management of the local complications (discussed later). Magnetic resonance imaging (MRI) is superior to CT scanning in detecting any solid content | Surgery_Schwartz. and normalization of serum levels of amylase, but it appears safe to allow patients to resume intake ad libitum (i.e., patient-controlled nutrition). If after 3 to 5 days there is evidence of feeding intolerance, tube feeding should be commenced.Cross-Sectional ImagingIt may be necessary to perform a CT scan to diagnose acute pancreatitis in patients who are severely ill or in those presenting with undifferentiated abdominal pain. But there is no advantage in using CT scanning to predict the severity of acute pancreatitis.51,63 The primary purpose of cross-sectional imaging is the diagnosis of local complications; in particular, the development and extent of pancreatic necrosis and the different collections (see Table 33-5). CT scanning is also important to guide the insertion of percutaneous drains, now assuming a greater role in the management of the local complications (discussed later). Magnetic resonance imaging (MRI) is superior to CT scanning in detecting any solid content |
Surgery_Schwartz_9569 | Surgery_Schwartz | drains, now assuming a greater role in the management of the local complications (discussed later). Magnetic resonance imaging (MRI) is superior to CT scanning in detecting any solid content within collections (Figure 33-13). And when a bleed is suspected, in association with a local complication, an arterial phase CT scan (CTa) is useful in detecting a pseudoaneurysm, active bleeding, and/or hematoma.3Brunicardi_Ch33_p1429-p1516.indd 144601/03/19 6:44 PM 1447PANCREASCHAPTER 33ABFigure 33-13. Corresponding computed tomography (CT) (A) and MR (B) images of a patient with a symptomatic pseudocyst. CT image reveals a well circumscribed homogenous collection (arrows) exerting mass effect on antrum of stomach. The T2-weighted MR image clearly distinguishes necrotic pancreas (black arrows) from fluid (white arrows). (Reproduced with permission from Bollen TL: Imaging of acute pancreatitis: update of the revised Atlanta classification, Radiol Clin North Am. 2012 | Surgery_Schwartz. drains, now assuming a greater role in the management of the local complications (discussed later). Magnetic resonance imaging (MRI) is superior to CT scanning in detecting any solid content within collections (Figure 33-13). And when a bleed is suspected, in association with a local complication, an arterial phase CT scan (CTa) is useful in detecting a pseudoaneurysm, active bleeding, and/or hematoma.3Brunicardi_Ch33_p1429-p1516.indd 144601/03/19 6:44 PM 1447PANCREASCHAPTER 33ABFigure 33-13. Corresponding computed tomography (CT) (A) and MR (B) images of a patient with a symptomatic pseudocyst. CT image reveals a well circumscribed homogenous collection (arrows) exerting mass effect on antrum of stomach. The T2-weighted MR image clearly distinguishes necrotic pancreas (black arrows) from fluid (white arrows). (Reproduced with permission from Bollen TL: Imaging of acute pancreatitis: update of the revised Atlanta classification, Radiol Clin North Am. 2012 |
Surgery_Schwartz_9570 | Surgery_Schwartz | pancreas (black arrows) from fluid (white arrows). (Reproduced with permission from Bollen TL: Imaging of acute pancreatitis: update of the revised Atlanta classification, Radiol Clin North Am. 2012 May;50(3):429-445.)Therapeutic Endoscopic Retrograde CholangiopancreatographyRandomized trials have demonstrated that early ERCP (within 24 or 48 hours of admission) reduce complications, but not mortality, in patients with predicted severe gallstone associated acute pancreatitis. While the benefits of this inva-sive modality are clear (e.g., treatment of cholangitis and release of impacted stone), this can be offset by the risks of increasing the severity of pancreatitis, bleeding, cholan-gitis, and perforation. More recent evidence has suggested that early ERCP confers no benefit in the absence of con-comitant cholangitis,83 as the offending common duct stone usually passes before ERCP can be performed. This may be evidenced by improvement in the liver function tests over the first 2 to | Surgery_Schwartz. pancreas (black arrows) from fluid (white arrows). (Reproduced with permission from Bollen TL: Imaging of acute pancreatitis: update of the revised Atlanta classification, Radiol Clin North Am. 2012 May;50(3):429-445.)Therapeutic Endoscopic Retrograde CholangiopancreatographyRandomized trials have demonstrated that early ERCP (within 24 or 48 hours of admission) reduce complications, but not mortality, in patients with predicted severe gallstone associated acute pancreatitis. While the benefits of this inva-sive modality are clear (e.g., treatment of cholangitis and release of impacted stone), this can be offset by the risks of increasing the severity of pancreatitis, bleeding, cholan-gitis, and perforation. More recent evidence has suggested that early ERCP confers no benefit in the absence of con-comitant cholangitis,83 as the offending common duct stone usually passes before ERCP can be performed. This may be evidenced by improvement in the liver function tests over the first 2 to |
Surgery_Schwartz_9571 | Surgery_Schwartz | of con-comitant cholangitis,83 as the offending common duct stone usually passes before ERCP can be performed. This may be evidenced by improvement in the liver function tests over the first 2 to 3 days. If there is persistent cholestasis, an MRCP can be used to detect a common duct stone and can be used as a prerequisite for attempting an ERCP.84 Persistent cholesta-sis without cholangitis may require an ERCP but not usually in the acute setting.AntibioticsAlthough the use of broad-spectrum antibiotics to treat estab-lished infection in acute pancreatitis is a well-established prac-tice, there has been considerable controversy surrounding the use of prophylactic antibiotics.63 The overuse of antibiotics has been associated with a documented rise in fungal infec-tions and resistant organisms. Overall, it appears that the most recent and generally better designed studies do not support the use of prophylactic antibiotics to reduce the frequency of pancreatic infectious complications, | Surgery_Schwartz. of con-comitant cholangitis,83 as the offending common duct stone usually passes before ERCP can be performed. This may be evidenced by improvement in the liver function tests over the first 2 to 3 days. If there is persistent cholestasis, an MRCP can be used to detect a common duct stone and can be used as a prerequisite for attempting an ERCP.84 Persistent cholesta-sis without cholangitis may require an ERCP but not usually in the acute setting.AntibioticsAlthough the use of broad-spectrum antibiotics to treat estab-lished infection in acute pancreatitis is a well-established prac-tice, there has been considerable controversy surrounding the use of prophylactic antibiotics.63 The overuse of antibiotics has been associated with a documented rise in fungal infec-tions and resistant organisms. Overall, it appears that the most recent and generally better designed studies do not support the use of prophylactic antibiotics to reduce the frequency of pancreatic infectious complications, |
Surgery_Schwartz_9572 | Surgery_Schwartz | Overall, it appears that the most recent and generally better designed studies do not support the use of prophylactic antibiotics to reduce the frequency of pancreatic infectious complications, surgical intervention, and death.85Managing Local ComplicationsVigilance is required for the timely and accurate diagnosis of local complications. The decisions regarding how and when to intervene are often difficult. While guided by the information gained by cross-sectional imaging, the decision to intervene is based on the clinical status and trajectory of the patient and the poor response to maximal intensive care support. This means close monitoring of the patient by serial examination, supplemented by regular measurement of inflammatory markers (e.g., C-reactive protein) and a pancreatic protocol CT scan if a local complication is suspected and intervention considered warranted. In practice, intervention is delayed in order to allow demarcation and to reduce the risk of bleeding, | Surgery_Schwartz. Overall, it appears that the most recent and generally better designed studies do not support the use of prophylactic antibiotics to reduce the frequency of pancreatic infectious complications, surgical intervention, and death.85Managing Local ComplicationsVigilance is required for the timely and accurate diagnosis of local complications. The decisions regarding how and when to intervene are often difficult. While guided by the information gained by cross-sectional imaging, the decision to intervene is based on the clinical status and trajectory of the patient and the poor response to maximal intensive care support. This means close monitoring of the patient by serial examination, supplemented by regular measurement of inflammatory markers (e.g., C-reactive protein) and a pancreatic protocol CT scan if a local complication is suspected and intervention considered warranted. In practice, intervention is delayed in order to allow demarcation and to reduce the risk of bleeding, |
Surgery_Schwartz_9573 | Surgery_Schwartz | protocol CT scan if a local complication is suspected and intervention considered warranted. In practice, intervention is delayed in order to allow demarcation and to reduce the risk of bleeding, disseminated infection, and collateral damage to adjacent organs by an intervention (Figure 33-14). Appreciation of this has resulted in a notable trend toward delayed Figure 33-14. Operative view of infected acute pancreatitis. Peripancreatic infection, characterized by mucopurulent exu-date, extends far beyond the boundaries of the pancreas in the retroperitoneum.Brunicardi_Ch33_p1429-p1516.indd 144701/03/19 6:44 PM 1448SPECIFIC CONSIDERATIONSPART IIStomachPeritoneal spacePeripancreaticfluid collectionwith necrotic tissueEndoscope(with balloon dilatation)PancreasRPOSTERIORLATERAL VIEWNecrotic tissuein snareLStomachSpleenPeripancreaticfluid collectionwith necrotic tissueAccess toretroperitonealspaceCostal marginPancreasPancreasLiverNecrotictissueLong | Surgery_Schwartz. protocol CT scan if a local complication is suspected and intervention considered warranted. In practice, intervention is delayed in order to allow demarcation and to reduce the risk of bleeding, disseminated infection, and collateral damage to adjacent organs by an intervention (Figure 33-14). Appreciation of this has resulted in a notable trend toward delayed Figure 33-14. Operative view of infected acute pancreatitis. Peripancreatic infection, characterized by mucopurulent exu-date, extends far beyond the boundaries of the pancreas in the retroperitoneum.Brunicardi_Ch33_p1429-p1516.indd 144701/03/19 6:44 PM 1448SPECIFIC CONSIDERATIONSPART IIStomachPeritoneal spacePeripancreaticfluid collectionwith necrotic tissueEndoscope(with balloon dilatation)PancreasRPOSTERIORLATERAL VIEWNecrotic tissuein snareLStomachSpleenPeripancreaticfluid collectionwith necrotic tissueAccess toretroperitonealspaceCostal marginPancreasPancreasLiverNecrotictissueLong |
Surgery_Schwartz_9574 | Surgery_Schwartz | VIEWNecrotic tissuein snareLStomachSpleenPeripancreaticfluid collectionwith necrotic tissueAccess toretroperitonealspaceCostal marginPancreasPancreasLiverNecrotictissueLong graspingforcepsLaparoscopeStomachSpleenPeripancreaticfluid collectionwith necrotic tissueEndoscopeStomach wallFluid collectionAortaPOSTERIORFigure 33-15. Two minimally invasive interventions for local complications of acute pancreatitis: A. video-assisted retroperitoneal debridement and B. endoscopic transgastric necrosectomy. (Reproduced with permission from Bakker OJ, van Santvoort HC, van Brunschot S, et al: Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial, JAMA. 2012 Mar 14; 307(10):1053-1061.)intervention, now uncommon before 3 to 4 weeks from the onset of symptoms. An important emerging approach is the increasing use of percutaneous catheter drainage in patients with suspected infected collections.86 Fine-needle aspiration is now rarely used to confirm | Surgery_Schwartz. VIEWNecrotic tissuein snareLStomachSpleenPeripancreaticfluid collectionwith necrotic tissueAccess toretroperitonealspaceCostal marginPancreasPancreasLiverNecrotictissueLong graspingforcepsLaparoscopeStomachSpleenPeripancreaticfluid collectionwith necrotic tissueEndoscopeStomach wallFluid collectionAortaPOSTERIORFigure 33-15. Two minimally invasive interventions for local complications of acute pancreatitis: A. video-assisted retroperitoneal debridement and B. endoscopic transgastric necrosectomy. (Reproduced with permission from Bakker OJ, van Santvoort HC, van Brunschot S, et al: Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial, JAMA. 2012 Mar 14; 307(10):1053-1061.)intervention, now uncommon before 3 to 4 weeks from the onset of symptoms. An important emerging approach is the increasing use of percutaneous catheter drainage in patients with suspected infected collections.86 Fine-needle aspiration is now rarely used to confirm |
Surgery_Schwartz_9575 | Surgery_Schwartz | An important emerging approach is the increasing use of percutaneous catheter drainage in patients with suspected infected collections.86 Fine-needle aspiration is now rarely used to confirm infection because the insertion of a needle at the time of planned drainage allows confirmation of the suspected infection. Preemptive drainage with one or more catheters often produces improvement or stabilization of the patient’s overall clinical status.87 In this way, drainage “buys time” and allows the lesion to become more walled off and safer to treat. Recent data suggests that primary percutaneous catheter drainage may be the only intervention required in a third to a half of patients and that this proportion might increase further if there were a policy of regular catheter exchange, upsizing, and irrigation.87 A proportion of patients do, however, require further treatment when they fail to respond and there is a wide array of minimally invasive options to choose from88 (Figure 33-15). | Surgery_Schwartz. An important emerging approach is the increasing use of percutaneous catheter drainage in patients with suspected infected collections.86 Fine-needle aspiration is now rarely used to confirm infection because the insertion of a needle at the time of planned drainage allows confirmation of the suspected infection. Preemptive drainage with one or more catheters often produces improvement or stabilization of the patient’s overall clinical status.87 In this way, drainage “buys time” and allows the lesion to become more walled off and safer to treat. Recent data suggests that primary percutaneous catheter drainage may be the only intervention required in a third to a half of patients and that this proportion might increase further if there were a policy of regular catheter exchange, upsizing, and irrigation.87 A proportion of patients do, however, require further treatment when they fail to respond and there is a wide array of minimally invasive options to choose from88 (Figure 33-15). |
Surgery_Schwartz_9576 | Surgery_Schwartz | and irrigation.87 A proportion of patients do, however, require further treatment when they fail to respond and there is a wide array of minimally invasive options to choose from88 (Figure 33-15). These interventions can be classified on the basis of the method of visualization, route taken to the lesion, and the purpose of the intervention.89 In practice, the approach taken will depend on local expertise and equipment as well as the location and type of the specific local complication. A large Dutch randomized trial has shown that open surgical techniques should only be considered in those who fail to respond to the step-up approach, that is, prior percutaneous drainage and minimally invasive intervention.90 The exception is to be found in the rare situation where an abdominal compartment syndrome requires open decompression, but this is usually earlier than the optimal time to intervene for local complications. A recent landmark randomized trial has compared two minimally invasive | Surgery_Schwartz. and irrigation.87 A proportion of patients do, however, require further treatment when they fail to respond and there is a wide array of minimally invasive options to choose from88 (Figure 33-15). These interventions can be classified on the basis of the method of visualization, route taken to the lesion, and the purpose of the intervention.89 In practice, the approach taken will depend on local expertise and equipment as well as the location and type of the specific local complication. A large Dutch randomized trial has shown that open surgical techniques should only be considered in those who fail to respond to the step-up approach, that is, prior percutaneous drainage and minimally invasive intervention.90 The exception is to be found in the rare situation where an abdominal compartment syndrome requires open decompression, but this is usually earlier than the optimal time to intervene for local complications. A recent landmark randomized trial has compared two minimally invasive |
Surgery_Schwartz_9577 | Surgery_Schwartz | syndrome requires open decompression, but this is usually earlier than the optimal time to intervene for local complications. A recent landmark randomized trial has compared two minimally invasive techniques, endoscopic transgastric drainage, and the videoscope-assisted retroperitoneal debridement through a flank incision (see Figure 33-15). The data shows that the former approach is superior, although the latter has a role when the walled-off necrosis is remote from the stomach or duodenum, as in the left flank.91The management of an acute noninfected pseudocyst is usually conservative, as about half of these will resolve sponta-neously. When symptoms of pain or the inability to eat persist or infection occurs, intervention is required. The indications for intervention are therefore no longer based on size and duration alone. Pseudocysts persist because of communication with the main pancreatic duct and/or distal ductal stenosis. Percutaneous drainage should be avoided in this | Surgery_Schwartz. syndrome requires open decompression, but this is usually earlier than the optimal time to intervene for local complications. A recent landmark randomized trial has compared two minimally invasive techniques, endoscopic transgastric drainage, and the videoscope-assisted retroperitoneal debridement through a flank incision (see Figure 33-15). The data shows that the former approach is superior, although the latter has a role when the walled-off necrosis is remote from the stomach or duodenum, as in the left flank.91The management of an acute noninfected pseudocyst is usually conservative, as about half of these will resolve sponta-neously. When symptoms of pain or the inability to eat persist or infection occurs, intervention is required. The indications for intervention are therefore no longer based on size and duration alone. Pseudocysts persist because of communication with the main pancreatic duct and/or distal ductal stenosis. Percutaneous drainage should be avoided in this |
Surgery_Schwartz_9578 | Surgery_Schwartz | no longer based on size and duration alone. Pseudocysts persist because of communication with the main pancreatic duct and/or distal ductal stenosis. Percutaneous drainage should be avoided in this situation because of the risk of external pancreatic fistula.92 EUS-guided internal drainage into stomach or duodenum or transpapillary stenting is the pre-ferred approach.Managing Organ FailureThe specific management of multiple organ failure is beyond the scope of this chapter. The early identification of organ dysfunc-tion and failure is important because it is a key determinant of severity and outcome and to facilitate the timely transfer of the patient to an intensive care unit to optimize management, pro-vide organ support and allow more intensive monitoring. The severity of organ failure can be scored (see Table 33-6). The responsiveness of organ failure to resuscitation over the first 48 hours is an important prognostic clue; those that respond have transient organ failure and have | Surgery_Schwartz. no longer based on size and duration alone. Pseudocysts persist because of communication with the main pancreatic duct and/or distal ductal stenosis. Percutaneous drainage should be avoided in this situation because of the risk of external pancreatic fistula.92 EUS-guided internal drainage into stomach or duodenum or transpapillary stenting is the pre-ferred approach.Managing Organ FailureThe specific management of multiple organ failure is beyond the scope of this chapter. The early identification of organ dysfunc-tion and failure is important because it is a key determinant of severity and outcome and to facilitate the timely transfer of the patient to an intensive care unit to optimize management, pro-vide organ support and allow more intensive monitoring. The severity of organ failure can be scored (see Table 33-6). The responsiveness of organ failure to resuscitation over the first 48 hours is an important prognostic clue; those that respond have transient organ failure and have |
Surgery_Schwartz_9579 | Surgery_Schwartz | can be scored (see Table 33-6). The responsiveness of organ failure to resuscitation over the first 48 hours is an important prognostic clue; those that respond have transient organ failure and have a better outlook than those who do not respond and have persistent organ failure.93 Organ failure that develops later in the disease course is usually Brunicardi_Ch33_p1429-p1516.indd 144801/03/19 6:44 PM 1449PANCREASCHAPTER 33Table 33-10Algorithm for the evaluation and management of acute pancreatitis 1. Diagnosis • History of abdominal pain consistent with acute pancreatitis • >3x elevation of pancreatic enzymes • CT scan if required to confirm diagnosis 2. Initial assessment/management (first 4 hrs) • Analgesia • Fluid resuscitation • Predict severity of pancreatitis • Ranson’s criteria • HAPS score • Assess systemic response • SIRS score • SOFA (organ failure) 3. Reassessment/management (4 to 6 hrs) • Assess response to fluid resuscitation • mean arterial pressure • heart | Surgery_Schwartz. can be scored (see Table 33-6). The responsiveness of organ failure to resuscitation over the first 48 hours is an important prognostic clue; those that respond have transient organ failure and have a better outlook than those who do not respond and have persistent organ failure.93 Organ failure that develops later in the disease course is usually Brunicardi_Ch33_p1429-p1516.indd 144801/03/19 6:44 PM 1449PANCREASCHAPTER 33Table 33-10Algorithm for the evaluation and management of acute pancreatitis 1. Diagnosis • History of abdominal pain consistent with acute pancreatitis • >3x elevation of pancreatic enzymes • CT scan if required to confirm diagnosis 2. Initial assessment/management (first 4 hrs) • Analgesia • Fluid resuscitation • Predict severity of pancreatitis • Ranson’s criteria • HAPS score • Assess systemic response • SIRS score • SOFA (organ failure) 3. Reassessment/management (4 to 6 hrs) • Assess response to fluid resuscitation • mean arterial pressure • heart |
Surgery_Schwartz_9580 | Surgery_Schwartz | criteria • HAPS score • Assess systemic response • SIRS score • SOFA (organ failure) 3. Reassessment/management (4 to 6 hrs) • Assess response to fluid resuscitation • mean arterial pressure • heart rate • urine output • hematocrit • Determine etiology • Ultrasound for gallstones/sludge • History of alcohol consumption • Laboratory evaluation of other causes • MRCP and/or Urgent ERCP if concomitant cholangitis is present • not for cholestasis or predicted severe disease per se • Transfer to ICU or specialist center as needed • Deterioration or failure to respond to initial management • Intensive support for persistent organ failure • Commence enteral nutrition • Once normovolemia restored (usually after 6 hours) • Commence via NG tube if no gastric stasis • No prophylactic antibiotics or probiotics 4. Conservative management and monitoring (at least daily) • Clinical evaluation • Assess cardiovascular, respiratory, and renal function • Detect peritonitis and abdominal compartment | Surgery_Schwartz. criteria • HAPS score • Assess systemic response • SIRS score • SOFA (organ failure) 3. Reassessment/management (4 to 6 hrs) • Assess response to fluid resuscitation • mean arterial pressure • heart rate • urine output • hematocrit • Determine etiology • Ultrasound for gallstones/sludge • History of alcohol consumption • Laboratory evaluation of other causes • MRCP and/or Urgent ERCP if concomitant cholangitis is present • not for cholestasis or predicted severe disease per se • Transfer to ICU or specialist center as needed • Deterioration or failure to respond to initial management • Intensive support for persistent organ failure • Commence enteral nutrition • Once normovolemia restored (usually after 6 hours) • Commence via NG tube if no gastric stasis • No prophylactic antibiotics or probiotics 4. Conservative management and monitoring (at least daily) • Clinical evaluation • Assess cardiovascular, respiratory, and renal function • Detect peritonitis and abdominal compartment |
Surgery_Schwartz_9581 | Surgery_Schwartz | or probiotics 4. Conservative management and monitoring (at least daily) • Clinical evaluation • Assess cardiovascular, respiratory, and renal function • Detect peritonitis and abdominal compartment syndrome • Daily C-reactive protein • Classify severity (mild, moderate, severe, critical) • Detect intolerance of NG EN • Advance tube for NJ feeding if needed • Consider supplemental parenteral nutrition by day 4 5. Indications for “pancreatic protocol CT scan” (rarely in first week) • For significant clinical deterioration and elevated CRP • For suspicion of local pancreatic complications • For suspected bowel ischemia • For acute bleeding (CTa) (if stable enough and consider embolization) • For abdominal compartment syndrome 6. Invasive intervention • For deteriorating patient with suspected infected local complication • “Step up approach” with initial drain guided by current CT scan (percutaneous or endoscopic drainage) • Delay for 3 to 4 weeks with intensive care support, if | Surgery_Schwartz. or probiotics 4. Conservative management and monitoring (at least daily) • Clinical evaluation • Assess cardiovascular, respiratory, and renal function • Detect peritonitis and abdominal compartment syndrome • Daily C-reactive protein • Classify severity (mild, moderate, severe, critical) • Detect intolerance of NG EN • Advance tube for NJ feeding if needed • Consider supplemental parenteral nutrition by day 4 5. Indications for “pancreatic protocol CT scan” (rarely in first week) • For significant clinical deterioration and elevated CRP • For suspicion of local pancreatic complications • For suspected bowel ischemia • For acute bleeding (CTa) (if stable enough and consider embolization) • For abdominal compartment syndrome 6. Invasive intervention • For deteriorating patient with suspected infected local complication • “Step up approach” with initial drain guided by current CT scan (percutaneous or endoscopic drainage) • Delay for 3 to 4 weeks with intensive care support, if |
Surgery_Schwartz_9582 | Surgery_Schwartz | suspected infected local complication • “Step up approach” with initial drain guided by current CT scan (percutaneous or endoscopic drainage) • Delay for 3 to 4 weeks with intensive care support, if possible • If failure to respond or secondary deterioration, repeat CT scan, and select appropriate minimally invasive technique based on available expertise and equipment • Video-assisted retroperitoneal debridement or percutaneous nephroscopic debridement • Endoscopic transluminal debridement • Ongoing large bore drainage and irrigation 7. Indication for laparotomy • Failed “step-up approach” for further debridement/drainage • Acute abdomen (perforation or ischemia) • Severe abdominal compartment syndrome (rarely)secondary to infection of a local complication and should be managed accordingly (see Figure 33-9).CholecystectomyWhile it is widely accepted that cholecystectomy is essential to prevent recurrent gallstone associated pancreatitis, the ques-tion relates to the timing of it. | Surgery_Schwartz. suspected infected local complication • “Step up approach” with initial drain guided by current CT scan (percutaneous or endoscopic drainage) • Delay for 3 to 4 weeks with intensive care support, if possible • If failure to respond or secondary deterioration, repeat CT scan, and select appropriate minimally invasive technique based on available expertise and equipment • Video-assisted retroperitoneal debridement or percutaneous nephroscopic debridement • Endoscopic transluminal debridement • Ongoing large bore drainage and irrigation 7. Indication for laparotomy • Failed “step-up approach” for further debridement/drainage • Acute abdomen (perforation or ischemia) • Severe abdominal compartment syndrome (rarely)secondary to infection of a local complication and should be managed accordingly (see Figure 33-9).CholecystectomyWhile it is widely accepted that cholecystectomy is essential to prevent recurrent gallstone associated pancreatitis, the ques-tion relates to the timing of it. |
Surgery_Schwartz_9583 | Surgery_Schwartz | (see Figure 33-9).CholecystectomyWhile it is widely accepted that cholecystectomy is essential to prevent recurrent gallstone associated pancreatitis, the ques-tion relates to the timing of it. Index cholecystectomy, done in the same admission and prior to discharge, appears safe and can almost always be accomplished laparoscopically.94 But index cholecystectomy is not suitable for all patients, particu-larly some who have had local pancreatic complications, which includes a large inflammatory mass that extends into the porta hepatis. These patients may require an interval cholecystec-tomy after resolution of the inflammatory process. If surgery is required for the management of local complications, then a cholecystectomy is often performed at that time.DiabetesRecent evidence indicates that prediabetes and diabetes are com-mon after acute pancreatitis and occur in nearly 40% of patients after hospital discharge.95 The prevalence of newly diagnosed diabetes is much higher after acute | Surgery_Schwartz. (see Figure 33-9).CholecystectomyWhile it is widely accepted that cholecystectomy is essential to prevent recurrent gallstone associated pancreatitis, the ques-tion relates to the timing of it. Index cholecystectomy, done in the same admission and prior to discharge, appears safe and can almost always be accomplished laparoscopically.94 But index cholecystectomy is not suitable for all patients, particu-larly some who have had local pancreatic complications, which includes a large inflammatory mass that extends into the porta hepatis. These patients may require an interval cholecystec-tomy after resolution of the inflammatory process. If surgery is required for the management of local complications, then a cholecystectomy is often performed at that time.DiabetesRecent evidence indicates that prediabetes and diabetes are com-mon after acute pancreatitis and occur in nearly 40% of patients after hospital discharge.95 The prevalence of newly diagnosed diabetes is much higher after acute |
Surgery_Schwartz_9584 | Surgery_Schwartz | prediabetes and diabetes are com-mon after acute pancreatitis and occur in nearly 40% of patients after hospital discharge.95 The prevalence of newly diagnosed diabetes is much higher after acute pancreatitis (23%) than the prevalence of diabetes in the general population (4–9%). The risk of diabetes increases by at least twofold after 5 years as compared with 12 months. Interestingly, the severity of acute pancreatitis appears to have minimal effect on risk of diabetes.95 The implica-tion is that patients recovered from an attack of acute pancreatitis may need follow-up and screening for glucose intolerance.The management of acute pancreatitis remains a formidable challenge (Table 33-10) due to the variety and severity of the many associated complications (Table 33-11), and continues to evolve. Although specific treatments for acute pancreatitis remain elusive, progress has been made in the management of pain, fluid resuscitation, antibiotic prophylaxis, enteral nutrition, | Surgery_Schwartz. prediabetes and diabetes are com-mon after acute pancreatitis and occur in nearly 40% of patients after hospital discharge.95 The prevalence of newly diagnosed diabetes is much higher after acute pancreatitis (23%) than the prevalence of diabetes in the general population (4–9%). The risk of diabetes increases by at least twofold after 5 years as compared with 12 months. Interestingly, the severity of acute pancreatitis appears to have minimal effect on risk of diabetes.95 The implica-tion is that patients recovered from an attack of acute pancreatitis may need follow-up and screening for glucose intolerance.The management of acute pancreatitis remains a formidable challenge (Table 33-10) due to the variety and severity of the many associated complications (Table 33-11), and continues to evolve. Although specific treatments for acute pancreatitis remain elusive, progress has been made in the management of pain, fluid resuscitation, antibiotic prophylaxis, enteral nutrition, |
Surgery_Schwartz_9585 | Surgery_Schwartz | to evolve. Although specific treatments for acute pancreatitis remain elusive, progress has been made in the management of pain, fluid resuscitation, antibiotic prophylaxis, enteral nutrition, therapeutic ERCP, and cholecystectomy. Progress has also been made in the intensive care management of systemic complications and in the development of less invasive interventions for the treatment of local complications, particularly infected pancreatic necrosis.4Brunicardi_Ch33_p1429-p1516.indd 144901/03/19 6:44 PM 1450SPECIFIC CONSIDERATIONSPART IITable 33-11Complications of acute pancreatitis I. Local A. Pancreatic phlegmon B. Pancreatic abscess C. Pancreatic pseudocyst D. Pancreatic ascites E. Involvement of adjacent organs, with hemorrhage, thrombosis, bowel infarction, obstructive jaundice, fistula formation, or mechanical obstruction II. Systemic A. Pulmonary 1. Pneumonia, atelectasis 2. Acute respiratory distress syndrome 3. Pleural | Surgery_Schwartz. to evolve. Although specific treatments for acute pancreatitis remain elusive, progress has been made in the management of pain, fluid resuscitation, antibiotic prophylaxis, enteral nutrition, therapeutic ERCP, and cholecystectomy. Progress has also been made in the intensive care management of systemic complications and in the development of less invasive interventions for the treatment of local complications, particularly infected pancreatic necrosis.4Brunicardi_Ch33_p1429-p1516.indd 144901/03/19 6:44 PM 1450SPECIFIC CONSIDERATIONSPART IITable 33-11Complications of acute pancreatitis I. Local A. Pancreatic phlegmon B. Pancreatic abscess C. Pancreatic pseudocyst D. Pancreatic ascites E. Involvement of adjacent organs, with hemorrhage, thrombosis, bowel infarction, obstructive jaundice, fistula formation, or mechanical obstruction II. Systemic A. Pulmonary 1. Pneumonia, atelectasis 2. Acute respiratory distress syndrome 3. Pleural |
Surgery_Schwartz_9586 | Surgery_Schwartz | thrombosis, bowel infarction, obstructive jaundice, fistula formation, or mechanical obstruction II. Systemic A. Pulmonary 1. Pneumonia, atelectasis 2. Acute respiratory distress syndrome 3. Pleural effusion B. Cardiovascular 1. Hypotension 2. Hypovolemia 3. Sudden death 4. Nonspecific ST-T wave changes 5. Pericardial effusion C. Hematologic 1. Hemoconcentration 2. Disseminated intravascular coagulopathy D. GI hemorrhage 1. Peptic ulcer 2. Erosive gastritis 3. Portal vein or splenic vein thrombosis with varices E. Renal 1. Oliguria 2. Azotemia 3. Renal artery/vein thrombosis F. Metabolic 1. Hyperglycemia 2. Hypocalcemia 3. Hypertriglyceridemia 4. Encephalopathy 5. Sudden blindness (Purtscher’s retinopathy) G. Central nervous system 1. Psychosis 2. Fat emboli 3. Alcohol withdrawal syndrome H. Fat necrosis 1. Intra-abdominal saponification 2. Subcutaneous tissue necrosisReproduced with permission from Isselbacher KJ: Harrison’s Principles of Internal Medicine, 13th ed. New York, NY: | Surgery_Schwartz. thrombosis, bowel infarction, obstructive jaundice, fistula formation, or mechanical obstruction II. Systemic A. Pulmonary 1. Pneumonia, atelectasis 2. Acute respiratory distress syndrome 3. Pleural effusion B. Cardiovascular 1. Hypotension 2. Hypovolemia 3. Sudden death 4. Nonspecific ST-T wave changes 5. Pericardial effusion C. Hematologic 1. Hemoconcentration 2. Disseminated intravascular coagulopathy D. GI hemorrhage 1. Peptic ulcer 2. Erosive gastritis 3. Portal vein or splenic vein thrombosis with varices E. Renal 1. Oliguria 2. Azotemia 3. Renal artery/vein thrombosis F. Metabolic 1. Hyperglycemia 2. Hypocalcemia 3. Hypertriglyceridemia 4. Encephalopathy 5. Sudden blindness (Purtscher’s retinopathy) G. Central nervous system 1. Psychosis 2. Fat emboli 3. Alcohol withdrawal syndrome H. Fat necrosis 1. Intra-abdominal saponification 2. Subcutaneous tissue necrosisReproduced with permission from Isselbacher KJ: Harrison’s Principles of Internal Medicine, 13th ed. New York, NY: |
Surgery_Schwartz_9587 | Surgery_Schwartz | necrosis 1. Intra-abdominal saponification 2. Subcutaneous tissue necrosisReproduced with permission from Isselbacher KJ: Harrison’s Principles of Internal Medicine, 13th ed. New York, NY: McGraw-Hill Education; 1994.CHRONIC PANCREATITISDefinition, Incidence, and PrevalenceChronic pancreatitis is an incurable, chronic inflammatory con-dition that is multifactorial in its etiology, highly variable in its presentation, and a challenge to treat successfully. Autopsy studies indicate that evidence of chronic inflammation, such as fibrosis, duct ectasia, and acinar atrophy is seen in up to 5% of the population,96 although these data are difficult to interpret because many of these changes are also present in asymptomatic elderly patients.97 Population studies suggest a prevalence that ranges from 5 to 40 persons per 100,000 population, with con-siderable geographic variation.98 Differences in diagnostic crite-ria, regional nutrition, alcohol consumption, and medical access account for | Surgery_Schwartz. necrosis 1. Intra-abdominal saponification 2. Subcutaneous tissue necrosisReproduced with permission from Isselbacher KJ: Harrison’s Principles of Internal Medicine, 13th ed. New York, NY: McGraw-Hill Education; 1994.CHRONIC PANCREATITISDefinition, Incidence, and PrevalenceChronic pancreatitis is an incurable, chronic inflammatory con-dition that is multifactorial in its etiology, highly variable in its presentation, and a challenge to treat successfully. Autopsy studies indicate that evidence of chronic inflammation, such as fibrosis, duct ectasia, and acinar atrophy is seen in up to 5% of the population,96 although these data are difficult to interpret because many of these changes are also present in asymptomatic elderly patients.97 Population studies suggest a prevalence that ranges from 5 to 40 persons per 100,000 population, with con-siderable geographic variation.98 Differences in diagnostic crite-ria, regional nutrition, alcohol consumption, and medical access account for |
Surgery_Schwartz_9588 | Surgery_Schwartz | from 5 to 40 persons per 100,000 population, with con-siderable geographic variation.98 Differences in diagnostic crite-ria, regional nutrition, alcohol consumption, and medical access account for variations in the frequency of the diagnosis, but the overall incidence of the disease has risen progressively over the past 50 years.EtiologyThere are multiple etiologies of chronic pancreatitis, includ-ing genetic mutations, alcohol exposure, duct obstruction due to trauma, gallstones, and tumors, metabolic diseases such as hyperlipidemia and hyperparathyroidism, and auto-immune dis-ease. In addition, nutritional causes include so-called tropical pancreatitis, which has been thought to result from ingestion of certain starches. A significant number of patients have no discernible cause of the disease despite extensive testing, and are said to have “idiopathic” chronic pancreatitis.Genetic CausesIn 1952, Comfort and Steinberg reported a kindred of “heredi-tary chronic relapsing | Surgery_Schwartz. from 5 to 40 persons per 100,000 population, with con-siderable geographic variation.98 Differences in diagnostic crite-ria, regional nutrition, alcohol consumption, and medical access account for variations in the frequency of the diagnosis, but the overall incidence of the disease has risen progressively over the past 50 years.EtiologyThere are multiple etiologies of chronic pancreatitis, includ-ing genetic mutations, alcohol exposure, duct obstruction due to trauma, gallstones, and tumors, metabolic diseases such as hyperlipidemia and hyperparathyroidism, and auto-immune dis-ease. In addition, nutritional causes include so-called tropical pancreatitis, which has been thought to result from ingestion of certain starches. A significant number of patients have no discernible cause of the disease despite extensive testing, and are said to have “idiopathic” chronic pancreatitis.Genetic CausesIn 1952, Comfort and Steinberg reported a kindred of “heredi-tary chronic relapsing |
Surgery_Schwartz_9589 | Surgery_Schwartz | of the disease despite extensive testing, and are said to have “idiopathic” chronic pancreatitis.Genetic CausesIn 1952, Comfort and Steinberg reported a kindred of “heredi-tary chronic relapsing pancreatitis” after treating the proband, a 24-year-old woman, at the Mayo Clinic.99 Subsequently, familial patterns of chronic, nonalcoholic pancreatitis have been described worldwide, and a familiar pattern has emerged. Typically, patients first present in childhood or adolescence with abdominal pain and are found to have chronic calcific pan-creatitis on imaging studies. Progressive pancreatic dysfunction is common, and many patients present with symptoms due to pancreatic duct obstruction. The risk of subsequent carcinoma formation is increased, reaching a prevalence, in some series, of 40%, but the age of onset for carcinoma is typically >50 years old.100 The disorder is characterized by an autosomal dominant pattern of inheritance, with 80% penetrance and variable expres-sion. The | Surgery_Schwartz. of the disease despite extensive testing, and are said to have “idiopathic” chronic pancreatitis.Genetic CausesIn 1952, Comfort and Steinberg reported a kindred of “heredi-tary chronic relapsing pancreatitis” after treating the proband, a 24-year-old woman, at the Mayo Clinic.99 Subsequently, familial patterns of chronic, nonalcoholic pancreatitis have been described worldwide, and a familiar pattern has emerged. Typically, patients first present in childhood or adolescence with abdominal pain and are found to have chronic calcific pan-creatitis on imaging studies. Progressive pancreatic dysfunction is common, and many patients present with symptoms due to pancreatic duct obstruction. The risk of subsequent carcinoma formation is increased, reaching a prevalence, in some series, of 40%, but the age of onset for carcinoma is typically >50 years old.100 The disorder is characterized by an autosomal dominant pattern of inheritance, with 80% penetrance and variable expres-sion. The |
Surgery_Schwartz_9590 | Surgery_Schwartz | 40%, but the age of onset for carcinoma is typically >50 years old.100 The disorder is characterized by an autosomal dominant pattern of inheritance, with 80% penetrance and variable expres-sion. The incidence is equal in both sexes.Whitcomb and colleagues,101 and separately LeBodic and associates,102 performed gene-linkage analysis and identified a linkage for hereditary pancreatitis to chromosome 7q35. Subse-quently, the region was sequenced and revealed eight trypsino-gen genes. Mutational analysis revealed a missense mutation resulting in an Arg-to-His substitution at position 117 of the cat-ionic trypsinogen gene, or PRSS1, one of the primary sites for proteolysis of trypsin. This gain-of-function mutation results in an excess production of trypsinogen, which results in persistent and uncontrolled proteolytic activity and autodestruction within the pancreas.103 The position 117 mutation of PRSS1 and an addi-tional mutation, now known collectively as the R122H and N291 mutations | Surgery_Schwartz. 40%, but the age of onset for carcinoma is typically >50 years old.100 The disorder is characterized by an autosomal dominant pattern of inheritance, with 80% penetrance and variable expres-sion. The incidence is equal in both sexes.Whitcomb and colleagues,101 and separately LeBodic and associates,102 performed gene-linkage analysis and identified a linkage for hereditary pancreatitis to chromosome 7q35. Subse-quently, the region was sequenced and revealed eight trypsino-gen genes. Mutational analysis revealed a missense mutation resulting in an Arg-to-His substitution at position 117 of the cat-ionic trypsinogen gene, or PRSS1, one of the primary sites for proteolysis of trypsin. This gain-of-function mutation results in an excess production of trypsinogen, which results in persistent and uncontrolled proteolytic activity and autodestruction within the pancreas.103 The position 117 mutation of PRSS1 and an addi-tional mutation, now known collectively as the R122H and N291 mutations |
Surgery_Schwartz_9591 | Surgery_Schwartz | uncontrolled proteolytic activity and autodestruction within the pancreas.103 The position 117 mutation of PRSS1 and an addi-tional mutation, now known collectively as the R122H and N291 mutations of PRSS1, account for about two-thirds of cases of hereditary pancreatitis. Masson and associates described a gain-of-function mutation in the anionic trypsinogen gene, PRSS2, that is also present in some cases.104Similarly, SPINK1, an inflammation-induced trypsin inhibitor secreted in acinar cells, has been found to have a role in hereditary pancreatitis. SPINK1 specifically inhibits trypsin action by competitively blocking the active site of the enzyme. Witt and colleagues investigated96 unrelated children with chronic pancreatitis in Germany and found a variety of SPINK1 mutations in 23% of the patients.105 Several studies have now confirmed an association of loss-of-function SPINK1 mutations with familial and idiopathic forms of chronic pancreatitis, as well as so-called tropical | Surgery_Schwartz. uncontrolled proteolytic activity and autodestruction within the pancreas.103 The position 117 mutation of PRSS1 and an addi-tional mutation, now known collectively as the R122H and N291 mutations of PRSS1, account for about two-thirds of cases of hereditary pancreatitis. Masson and associates described a gain-of-function mutation in the anionic trypsinogen gene, PRSS2, that is also present in some cases.104Similarly, SPINK1, an inflammation-induced trypsin inhibitor secreted in acinar cells, has been found to have a role in hereditary pancreatitis. SPINK1 specifically inhibits trypsin action by competitively blocking the active site of the enzyme. Witt and colleagues investigated96 unrelated children with chronic pancreatitis in Germany and found a variety of SPINK1 mutations in 23% of the patients.105 Several studies have now confirmed an association of loss-of-function SPINK1 mutations with familial and idiopathic forms of chronic pancreatitis, as well as so-called tropical |
Surgery_Schwartz_9592 | Surgery_Schwartz | of the patients.105 Several studies have now confirmed an association of loss-of-function SPINK1 mutations with familial and idiopathic forms of chronic pancreatitis, as well as so-called tropical pancreatitis.106,107 SPINK1 mutations Brunicardi_Ch33_p1429-p1516.indd 145001/03/19 6:44 PM 1451PANCREASCHAPTER 33BasolateralmembraneAcinar callKeyZymogensClaudin-2CFTRCalcium regulationCAZymogens: Including;trypsinogens (PRSS1, PRSS2)chymotrypsin C (CTRC)(SPINK1 in“ammation-induced trypsin inhibitor)Calcium sensing receptor (CASR)CFTRDuodenumZymogensecretionAbnormalclaudin-2localizationDuct cellBicarbonateSodiumWaterTrypsinogenZymogensEKTrypsinActive digestiveenzymesCASRFigure 33-16. Schematic model of genetic causes of chronic pan-creatitis. A pancreatic acinus is portrayed showing the pathway for digestive enzymes (zymogens) to be secreted by the acinar cell into the ductal system where water, sodium, and bicarbonate are secreted by the duct and centroacinar (CA) cells. Mutations in | Surgery_Schwartz. of the patients.105 Several studies have now confirmed an association of loss-of-function SPINK1 mutations with familial and idiopathic forms of chronic pancreatitis, as well as so-called tropical pancreatitis.106,107 SPINK1 mutations Brunicardi_Ch33_p1429-p1516.indd 145001/03/19 6:44 PM 1451PANCREASCHAPTER 33BasolateralmembraneAcinar callKeyZymogensClaudin-2CFTRCalcium regulationCAZymogens: Including;trypsinogens (PRSS1, PRSS2)chymotrypsin C (CTRC)(SPINK1 in“ammation-induced trypsin inhibitor)Calcium sensing receptor (CASR)CFTRDuodenumZymogensecretionAbnormalclaudin-2localizationDuct cellBicarbonateSodiumWaterTrypsinogenZymogensEKTrypsinActive digestiveenzymesCASRFigure 33-16. Schematic model of genetic causes of chronic pan-creatitis. A pancreatic acinus is portrayed showing the pathway for digestive enzymes (zymogens) to be secreted by the acinar cell into the ductal system where water, sodium, and bicarbonate are secreted by the duct and centroacinar (CA) cells. Mutations in |
Surgery_Schwartz_9593 | Surgery_Schwartz | for digestive enzymes (zymogens) to be secreted by the acinar cell into the ductal system where water, sodium, and bicarbonate are secreted by the duct and centroacinar (CA) cells. Mutations in at least five genes have been identified as risk factors for chronic pancreatitis: gain-of function mutations in the cationic trypsinogen genes (PRSS1, PRSS2) cause hereditary pancreatitis. Cationic and anionic trypsinogen are normally active in the duodenum by entero-kinase (EK). Premature activation of the trypsin in the acinar cell leads to zymogen activation, local cellular injury, and inflamma-tion. Mutations of the trypsin inhibitors SPINK1 or chymotrypsin C (CTRC), or of the calcium sensing receptor CASR, result in pre-mature activation of trypsinogen. Mutations in the cystic fibrosis transmembrane receptor CFTR results in trypsinogen stasis within the ducts due to insufficient secretion by duct cells. A mutation in claudin-2 (CLDN2) results in abnormal expression in acinar cells, | Surgery_Schwartz. for digestive enzymes (zymogens) to be secreted by the acinar cell into the ductal system where water, sodium, and bicarbonate are secreted by the duct and centroacinar (CA) cells. Mutations in at least five genes have been identified as risk factors for chronic pancreatitis: gain-of function mutations in the cationic trypsinogen genes (PRSS1, PRSS2) cause hereditary pancreatitis. Cationic and anionic trypsinogen are normally active in the duodenum by entero-kinase (EK). Premature activation of the trypsin in the acinar cell leads to zymogen activation, local cellular injury, and inflamma-tion. Mutations of the trypsin inhibitors SPINK1 or chymotrypsin C (CTRC), or of the calcium sensing receptor CASR, result in pre-mature activation of trypsinogen. Mutations in the cystic fibrosis transmembrane receptor CFTR results in trypsinogen stasis within the ducts due to insufficient secretion by duct cells. A mutation in claudin-2 (CLDN2) results in abnormal expression in acinar cells, |
Surgery_Schwartz_9594 | Surgery_Schwartz | transmembrane receptor CFTR results in trypsinogen stasis within the ducts due to insufficient secretion by duct cells. A mutation in claudin-2 (CLDN2) results in abnormal expression in acinar cells, instead of its normal location between duct cells, and is associated with the accelerated development of chronic pancreatitis in alcohol abusers. (Modified with permission from Solomon S, Whitcomb DC: Genetics of pancreatitis: an update for clinicians and genetic coun-selors, Curr Gastroenterol Rep. 2012 Apr;14(2):112-711.)are common in the general population as well, and the frequency of these mutations varies in different cohorts of idiopathic chronic pancreatitis, from 6.4% in France108 to 25.8% in the United States.109 Thus, hereditary pancreatitis results from one or more mutational defects that incapacitate an auto-protective process that normally prevents proteolysis within the pancreas.Cystic fibrosis, originally termed cystic fibrosis of the pancreas, results from a variety of | Surgery_Schwartz. transmembrane receptor CFTR results in trypsinogen stasis within the ducts due to insufficient secretion by duct cells. A mutation in claudin-2 (CLDN2) results in abnormal expression in acinar cells, instead of its normal location between duct cells, and is associated with the accelerated development of chronic pancreatitis in alcohol abusers. (Modified with permission from Solomon S, Whitcomb DC: Genetics of pancreatitis: an update for clinicians and genetic coun-selors, Curr Gastroenterol Rep. 2012 Apr;14(2):112-711.)are common in the general population as well, and the frequency of these mutations varies in different cohorts of idiopathic chronic pancreatitis, from 6.4% in France108 to 25.8% in the United States.109 Thus, hereditary pancreatitis results from one or more mutational defects that incapacitate an auto-protective process that normally prevents proteolysis within the pancreas.Cystic fibrosis, originally termed cystic fibrosis of the pancreas, results from a variety of |
Surgery_Schwartz_9595 | Surgery_Schwartz | that incapacitate an auto-protective process that normally prevents proteolysis within the pancreas.Cystic fibrosis, originally termed cystic fibrosis of the pancreas, results from a variety of mutations of the cystic fibro-sis transmembrane receptor (CFTR). The CFTR is present in pancreatic duct cells and controls the amount of chloride and bicarbonate secreted into the normally alkaline pancreatic juice. The CFTR gene contains over 4300 nucleotides, divided into 24 exons, which encode a 1480-amino acid protein. Over 1000 polymorphisms have been reported, and many are common. The CFTR mutation associated with the classic pulmonary dis-ease, F508, is rarely observed in chronic pancreatitis. But other CFTR mutations have been noted to be associated with chronic idiopathic pancreatitis, auto-immune pancreatitis, and pancreas divisum, in which the pulmonary, intestinal, and cutaneous manifestations of the disease are silent.110Many studies have been undertaken to determine whether | Surgery_Schwartz. that incapacitate an auto-protective process that normally prevents proteolysis within the pancreas.Cystic fibrosis, originally termed cystic fibrosis of the pancreas, results from a variety of mutations of the cystic fibro-sis transmembrane receptor (CFTR). The CFTR is present in pancreatic duct cells and controls the amount of chloride and bicarbonate secreted into the normally alkaline pancreatic juice. The CFTR gene contains over 4300 nucleotides, divided into 24 exons, which encode a 1480-amino acid protein. Over 1000 polymorphisms have been reported, and many are common. The CFTR mutation associated with the classic pulmonary dis-ease, F508, is rarely observed in chronic pancreatitis. But other CFTR mutations have been noted to be associated with chronic idiopathic pancreatitis, auto-immune pancreatitis, and pancreas divisum, in which the pulmonary, intestinal, and cutaneous manifestations of the disease are silent.110Many studies have been undertaken to determine whether |
Surgery_Schwartz_9596 | Surgery_Schwartz | auto-immune pancreatitis, and pancreas divisum, in which the pulmonary, intestinal, and cutaneous manifestations of the disease are silent.110Many studies have been undertaken to determine whether specific genetic abnormalities are associated with alcoholic chronic pancreatitis and which might confer susceptibility to the disease.105 In 2012, a landmark study by Whitcomb and associates demonstrated a likely genetic cause of the predisposition to alcohol-induced chronic pancreatitis in men.111 In a genome-wide association study of more than 2000 patients, these researchers discovered that a common DNA variant on the X chromosome is present in 26% of men without pancreatitis, but jumps to nearly 50% of men diagnosed with alcoholic pancreatitis. The variant involves the claudin 2 (CLDN2) gene, which encodes a tight junction protein normally present in ductal cells. In cases of chronic pancreatitis, the CLDN2 protein is abnormally expressed in acinar cells and may alter the secretory | Surgery_Schwartz. auto-immune pancreatitis, and pancreas divisum, in which the pulmonary, intestinal, and cutaneous manifestations of the disease are silent.110Many studies have been undertaken to determine whether specific genetic abnormalities are associated with alcoholic chronic pancreatitis and which might confer susceptibility to the disease.105 In 2012, a landmark study by Whitcomb and associates demonstrated a likely genetic cause of the predisposition to alcohol-induced chronic pancreatitis in men.111 In a genome-wide association study of more than 2000 patients, these researchers discovered that a common DNA variant on the X chromosome is present in 26% of men without pancreatitis, but jumps to nearly 50% of men diagnosed with alcoholic pancreatitis. The variant involves the claudin 2 (CLDN2) gene, which encodes a tight junction protein normally present in ductal cells. In cases of chronic pancreatitis, the CLDN2 protein is abnormally expressed in acinar cells and may alter the secretory |
Surgery_Schwartz_9597 | Surgery_Schwartz | gene, which encodes a tight junction protein normally present in ductal cells. In cases of chronic pancreatitis, the CLDN2 protein is abnormally expressed in acinar cells and may alter the secretory dynamics of enzyme release. The abnormality does not appear to cause pancreatitis, but if pancreatitis occurs for any reason in a person with the CLDN2 variant, it is more likely that the person will develop chronic pancreatitis; the risk is increased even further among alcohol users. Only 10% of women have the X chromosome–linked variant on both X chromosomes, and most women with the CLDN2 variant on one X chromosome appear to be protected from alcoholic chronic pancreatitis by the other X chromosome, if it is normal. Men, with only one X chromosome, have no protection if they inherit a CLDN2 mutation. This helps to explain the high prevalence of alcoholic chronic pancreatitis among men, although the mechanism remains unclear. This study does not demonstrate a genetic cause for all cases | Surgery_Schwartz. gene, which encodes a tight junction protein normally present in ductal cells. In cases of chronic pancreatitis, the CLDN2 protein is abnormally expressed in acinar cells and may alter the secretory dynamics of enzyme release. The abnormality does not appear to cause pancreatitis, but if pancreatitis occurs for any reason in a person with the CLDN2 variant, it is more likely that the person will develop chronic pancreatitis; the risk is increased even further among alcohol users. Only 10% of women have the X chromosome–linked variant on both X chromosomes, and most women with the CLDN2 variant on one X chromosome appear to be protected from alcoholic chronic pancreatitis by the other X chromosome, if it is normal. Men, with only one X chromosome, have no protection if they inherit a CLDN2 mutation. This helps to explain the high prevalence of alcoholic chronic pancreatitis among men, although the mechanism remains unclear. This study does not demonstrate a genetic cause for all cases |
Surgery_Schwartz_9598 | Surgery_Schwartz | mutation. This helps to explain the high prevalence of alcoholic chronic pancreatitis among men, although the mechanism remains unclear. This study does not demonstrate a genetic cause for all cases of alcohol-related chronic pancreatitis, but it shows that a genetic element contributes to many patients with the disease (Fig. 33-16).AlcoholIn 1878, Friedreich proposed that “a general chronic interstitial pancreatitis may result from excessive alcoholism (drunkard’s pancreas).”112 Since that observation, numerous studies have shown that a causal relationship exists between alcohol and chronic pancreatitis, but the prevalence of alcohol as the etiol-ogy of the disease in Western countries ranges widely, from 38% to 94%113 (Fig. 33-17).There is a linear relationship between exposure to alcohol and the development of chronic pancreatitis.114 The risk of dis-ease is present in patients with even a low or occasional expo-sure to alcohol (1 to 20 g/d), perhaps due to the CLDN2 gene mutation | Surgery_Schwartz. mutation. This helps to explain the high prevalence of alcoholic chronic pancreatitis among men, although the mechanism remains unclear. This study does not demonstrate a genetic cause for all cases of alcohol-related chronic pancreatitis, but it shows that a genetic element contributes to many patients with the disease (Fig. 33-16).AlcoholIn 1878, Friedreich proposed that “a general chronic interstitial pancreatitis may result from excessive alcoholism (drunkard’s pancreas).”112 Since that observation, numerous studies have shown that a causal relationship exists between alcohol and chronic pancreatitis, but the prevalence of alcohol as the etiol-ogy of the disease in Western countries ranges widely, from 38% to 94%113 (Fig. 33-17).There is a linear relationship between exposure to alcohol and the development of chronic pancreatitis.114 The risk of dis-ease is present in patients with even a low or occasional expo-sure to alcohol (1 to 20 g/d), perhaps due to the CLDN2 gene mutation |
Surgery_Schwartz_9599 | Surgery_Schwartz | and the development of chronic pancreatitis.114 The risk of dis-ease is present in patients with even a low or occasional expo-sure to alcohol (1 to 20 g/d), perhaps due to the CLDN2 gene mutation described previously, so there is no threshold level of alcohol exposure below which there is no risk of develop-ing chronic pancreatitis. Furthermore, although the risk of dis-ease is dose related and highest in heavy (>150 g/d, or about 11 1 oz shots, or 12 beers per day) drinkers, the prevalence of chronic pancreatitis among confirmed alcohol abusers is only 5% to 15%.115 However, the duration of alcohol consumption is definitely associated with the development of pancreatic dis-ease. The onset of disease typically occurs between ages 35 to 40 years, after 16 to 20 years of heavy alcohol consumption. Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years.116In their 1946 classic study, Comfort, Gambrill, and Baggenstoss proposed that chronic | Surgery_Schwartz. and the development of chronic pancreatitis.114 The risk of dis-ease is present in patients with even a low or occasional expo-sure to alcohol (1 to 20 g/d), perhaps due to the CLDN2 gene mutation described previously, so there is no threshold level of alcohol exposure below which there is no risk of develop-ing chronic pancreatitis. Furthermore, although the risk of dis-ease is dose related and highest in heavy (>150 g/d, or about 11 1 oz shots, or 12 beers per day) drinkers, the prevalence of chronic pancreatitis among confirmed alcohol abusers is only 5% to 15%.115 However, the duration of alcohol consumption is definitely associated with the development of pancreatic dis-ease. The onset of disease typically occurs between ages 35 to 40 years, after 16 to 20 years of heavy alcohol consumption. Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years.116In their 1946 classic study, Comfort, Gambrill, and Baggenstoss proposed that chronic |
Surgery_Schwartz_9600 | Surgery_Schwartz | Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years.116In their 1946 classic study, Comfort, Gambrill, and Baggenstoss proposed that chronic pancreatitis was the result of multiple episodes of acute inflammation, with residual and Brunicardi_Ch33_p1429-p1516.indd 145101/03/19 6:44 PM 1452SPECIFIC CONSIDERATIONSPART IITimeDegree of pancreatic damage= Episode of acute pancreatitisNecrosis-fibrosis sequenceFigure 33-18. “Multiple hit” theory of the etiology of chronic pancreatitis. Multiple episodes of acute pancreatitis cause progres-sively more organized inflammatory changes that ultimately result in chronic inflammation and scarring. (Reproduced with permission from Apte MV, Wilson JS: Alcohol-induced pancreatic injury, Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):593-612.)Very heavy drinking (15%)Alcohol + genetic (3%)Idiopathic(42%)Genetic(24%)CFTR(14%)CFTR +SPINK1(3%)SPINK1(4%)PRSS1(3%)Hyperlipidemia,Autoimmune,Other | Surgery_Schwartz. Recurrent episodes of acute pancreatitis are typically followed by chronic symptoms after 4 or 5 years.116In their 1946 classic study, Comfort, Gambrill, and Baggenstoss proposed that chronic pancreatitis was the result of multiple episodes of acute inflammation, with residual and Brunicardi_Ch33_p1429-p1516.indd 145101/03/19 6:44 PM 1452SPECIFIC CONSIDERATIONSPART IITimeDegree of pancreatic damage= Episode of acute pancreatitisNecrosis-fibrosis sequenceFigure 33-18. “Multiple hit” theory of the etiology of chronic pancreatitis. Multiple episodes of acute pancreatitis cause progres-sively more organized inflammatory changes that ultimately result in chronic inflammation and scarring. (Reproduced with permission from Apte MV, Wilson JS: Alcohol-induced pancreatic injury, Best Pract Res Clin Gastroenterol. 2003 Aug;17(4):593-612.)Very heavy drinking (15%)Alcohol + genetic (3%)Idiopathic(42%)Genetic(24%)CFTR(14%)CFTR +SPINK1(3%)SPINK1(4%)PRSS1(3%)Hyperlipidemia,Autoimmune,Other |
Surgery_Schwartz_9601 | Surgery_Schwartz | Res Clin Gastroenterol. 2003 Aug;17(4):593-612.)Very heavy drinking (15%)Alcohol + genetic (3%)Idiopathic(42%)Genetic(24%)CFTR(14%)CFTR +SPINK1(3%)SPINK1(4%)PRSS1(3%)Hyperlipidemia,Autoimmune,Other (4%)Obstructive(9%)Gallstone /severe AP(3%)Figure 33-17. Etiologies of chronic pancreatitis. (Reproduced with permission from Whitcomb DC: Going MAD: development of a “matrix academic division” to facilitate translating research to personalized medicine, Acad Med. 2011 Nov;86(11):1353-1359.)progressively increasing chronic inflammation.117 Subsequently, Kondo and associates showed that other, additional factors were necessary for repeated exposure to alcohol to cause chronic pancreatitis.118 Regardless of the requirement for other predisposing or facilitative factors, the concept that multiple episodes (or a prolonged course) of pancreatic injury ultimately leads to chronic disease is widely accepted as the pathophysiologic sequence119 (Fig. 33-18).Although direct alcohol exposure to the | Surgery_Schwartz. Res Clin Gastroenterol. 2003 Aug;17(4):593-612.)Very heavy drinking (15%)Alcohol + genetic (3%)Idiopathic(42%)Genetic(24%)CFTR(14%)CFTR +SPINK1(3%)SPINK1(4%)PRSS1(3%)Hyperlipidemia,Autoimmune,Other (4%)Obstructive(9%)Gallstone /severe AP(3%)Figure 33-17. Etiologies of chronic pancreatitis. (Reproduced with permission from Whitcomb DC: Going MAD: development of a “matrix academic division” to facilitate translating research to personalized medicine, Acad Med. 2011 Nov;86(11):1353-1359.)progressively increasing chronic inflammation.117 Subsequently, Kondo and associates showed that other, additional factors were necessary for repeated exposure to alcohol to cause chronic pancreatitis.118 Regardless of the requirement for other predisposing or facilitative factors, the concept that multiple episodes (or a prolonged course) of pancreatic injury ultimately leads to chronic disease is widely accepted as the pathophysiologic sequence119 (Fig. 33-18).Although direct alcohol exposure to the |
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