33: Pancreas Flashcards

Question

Non-functional pancreatic endocrine neoplasms most commonly metastasize to where?

Answer 1

1. Gallstones (obstructs ampulla of vater causing impaired extrusion of zymogen granules and activation of degradation enzymes) 2. ETOH (Causes auto-activation of enzymes while still in pancreas) [Other etiologies: ERCP, trauma, hyperlipidemia, hypercalcemia, viral infection, medications] [UpToDate: Gallstones (including microlithiasis) are the most common cause of acute pancreatitis in most areas of the world accounting for 35% to 40% of cases. However, only 3% to 7% of patients with gallstones develop pancreatitis Alcohol is responsible for approximately 30% of cases of acute pancreatitis in the United States. Approximately 10% of chronic alcoholics develop attacks of clinically acute pancreatitis that are indistinguishable from other forms of acute pancreatitis. Alcohol may act by increasing the synthesis of enzymes by pancreatic acinar cells to synthesize the digestive and lysosomal enzymes that are thought to be responsible for acute pancreatitis or over-sensitization of acini to cholecystokinin. However, the exact mechanism of pancreatic injury, the genetic and environmental factors that influence the development of pancreatitis in alcoholics, and the reason why only a small proportion of alcoholics develop pancreatitis, are unclear.]

Answer 2

1. Hct drop more than 10% from admission 2. BUN increase more than 5 mg/dL from admission 3. Ca less than 8 mg/dL within 48 hours 4. PaO2 less than 60 mmHg within 48 hours 5. Base deficit (24 - HCO3) more than 4 mg/dL within 48 hours 6. Fluid needs more than 6L within 48 hours [UpToDate: A score based upon Ranson's criteria is one of the earliest scoring systems for severity in AP. Ranson's criteria consist of 11 parameters. Five of the factors are assessed at admission and six are assessed during the next 48 hours. A later modification for biliary pancreatitis included only 10 points. Mortality increases with an increasing score. Using the 11 component score, mortality was 0% to 3% when the score was \<3, 11% to 15% when the score was ≥3, and 40% when the score was ≥6. Although the system continues to be used, a meta-analysis of 110 studies found the Ranson score to be a poor predictor of severity.]

Answer 3

Resection with primary closure (Be sure to check pancreas for primary tumor) [May need a whipple if extensive] [UpToDate: Patients with a sporadic gastrinoma who do not have evidence of metastatic spread of disease should be offered exploratory laparotomy and resection with curative intent, even in the event of negative imaging studies in approximately 17% of patients. This recommendation is derived from the observation that in addition to eliminating or at least decreasing the need for antisecretory medical therapy, successful resection of sporadic gastrinomas protects against the possibility of eventual morbidity and death from metastatic spread of the tumor. In the hands of an experienced surgeon, up to 50% of these patients will be cured. Lymphadenectomy exceeding more than 10 lymph nodes at the time of surgery has been shown to achieve a higher biochemical cure as compared with selective or no lymphadenectomy. The likelihood for surgical cure is especially high for extrapancreatic gastrinomas (eg, those in the duodenum or peripancreatic lymph nodes). In contrast, laparotomy is not routinely recommended for patients with Zollinger-Ellison syndrome (ZES) as part of MEN 1 since the multifocal nature of the tumors in this disorder almost uniformly precludes cure of gastrin hypersecretion. However, because a minority of MEN-1 tumors can have aggressive growth patterns, some recommend imaging techniques or even surgical exploration to identify those exceeding 2 cm with the intent of resecting them. 80% of curable gastrinomas lie within the gastrinoma triangle comprised of the head of the pancreas and the duodenal sweep. The combination of preoperative localization techniques makes it possible for the experienced surgeon to identify over 90% of sporadic gastrinomas. Intraoperative transduodenal illumination and duodenotomy are of particular value in detecting very small gastrinomas arising in the wall of the duodenum. In the unlikely event that a sporadic gastrinoma cannot be identified at surgery, we suggest deferring a Whipple's procedure in favor of closure, with the intent of serial imaging every 6 months to try to localize the neoplasm. Gastric secretion may not return to the normal range following gastrinoma resection because of a residual excess of gastric parietal cells, a consequence of the trophic effect of chronically elevated gastrin levels. Up to 40% of patients will require prolonged antisecretory therapy to control hyperacidity following curative resection, and such patients need continued monitoring for acid hypersecretion. Of 50 patients who underwent curative resection for ZES, gastric hypersecretion was observed for a mean of 8 years in 62% of patients and was judged to be extreme in 28% despite normal blood gastrin levels. A parietal cell (proximal gastric) vagotomy performed at the time of tumor resection has been advocated to reduce (and in some cases obviate) the need for postoperative medical therapy, particularly when complete resection of the gastrinoma tissue cannot be accomplished. However, it is currently uncommonly performed because of the efficacy of proton pump inhibitors. Furthermore, relatively few surgeons currently perform this procedure. The reduction in mortality associated with surgical therapy for patients without metastatic disease was illustrated in a prospective study of 124 patients with gastrinoma presumed to be free of metastasis by imaging studies. Only 3% of the 98 patients who underwent resection developed liver metastases during a mean follow-up period of 6.3 years. By contrast, 23% of 26 patients treated medically developed metastatic disease over a slightly longer follow-up period (8.7 years). Two deaths due to metastatic gastrinoma occurred in the medically treated group compared with no disease-specific deaths in the operative group.]

Answer 4

Parenchymal fibrosis [UpToDate: Morphologically, chronic pancreatitis is a patchy focal disease characterized by a mononuclear infiltrate and fibrosis. In contrast, acute pancreatitis diffusely involves a large portion of the entire pancreas with a predominantly neutrophilic inflammatory response.]

Answer 5

1. Glucagon 2. Insulin 3. Somatostatin 4. Pancreatic polypeptide 5. Vasoactive intestinal peptide (VIP) 6. Serotonin

Answer 6

Ultrasound [Positive common bile stones and no mass = ERCP, No common bile stones and no mass = MRCP, Positive for mass = MRCP] [UpToDate: The diagnostic approach to the jaundiced patient begins with a careful history, physical examination, and initial laboratory studies. A differential diagnosis is formulated based on those results and additional testing is performed to narrow the diagnostic possibilities. If there is evidence of biliary obstruction or intrahepatic cholestasis (eg, elevated conjugated bilirubin and alkaline phosphatase), the first step in the evaluation is hepatic imaging (eg, ultrasound, magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP]) to look for evidence of intra- or extrahepatic bile duct dilation. If imaging is negative, the evaluation typically will also include obtaining an antimitochondrial antibody to evaluate for primary biliary cholangitis.]

Answer 7

1. Watery diarrhea 2. Hypokalemia (from diarrhea) 3. Achlorhydria [UpToDate: The majority of patients with VIPoma have VIPoma syndrome, which is also called the pancreatic cholera syndrome, Verner-Morrison syndrome, and the watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria (WDHA) syndrome. VIPoma syndrome is characterized by watery diarrhea that persists with fasting. Stools are tea-colored and odorless with stool volumes exceeding 700 mL/day. In 70% of patients, stool volume can exceed 3000 mL/day. Abdominal pain is mild or absent. Associated symptoms include flushing episodes in 20% of patients and symptoms related to hypokalemia and dehydration, such as lethargy, nausea, vomiting, muscle weakness, and muscle cramps.]

Answer 8

Octreotide scan [UpToDate: After the diagnosis of Zollinger-Ellison syndrome (ZES) is made, the gastrinoma must be located and staged. Tumor localization begins with an upper endoscopy if not already performed, cross-sectional imaging with helical, contrast-enhanced, triple-phase computed tomography (CT) or magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS)/Gallium-68-DOTA-D-Phe1-Tyr3-Octreotate (Gallium Ga-68 DOTATATE PET/CT). Because of its greater sensitivity, 68-Ga DOTATATE PET/CT is preferred over conventional SRS with 111-In pentetreotide. If CT/MRI and SRS/68-Ga DOTATATE PET/CT are negative, and surgery is being considered, an endoscopic ultrasound (EUS) should be performed because of its greater sensitivity in detecting small tumors. EUS also permits fine-needle aspiration for histological identification.]

Answer 9

Duct of Santorini

Answer 10

6th and 7th decade of life [UpToDate: In the United States, approximately 53,070 patients are diagnosed with cancer of the exocrine pancreas annually, and almost all are expected to die from the disease. Pancreatic cancer is the fourth leading cause of cancer-related death in the United States among both men and women. The majority of these tumors (85%) are adenocarcinomas arising from the ductal epithelium. Worldwide, pancreatic cancer is the eighth leading cause of cancer deaths in men (138,100 deaths annually) and the ninth in women (127,900 deaths annually). In general, pancreatic cancer affects more individuals inhabiting the Western/industrialized parts of the world; the highest incidence is reported among Maoris in New Zealand, native Hawaiians, and Black American populations, while people living in India and Nigeria have the lowest reported incidence. The disease is rare before the age of 45, but the incidence rises sharply thereafter. Incidence and death rates vary by sex and race. The incidence is greater in males than females (male-to-female ratio 1.3:1) and in blacks than in whites (14.8 per 100,000 in black males compared with 8.8 per 100,000 in the general population). However, more recent data suggest that these racial differences may be diminishing.]

Answer 11

Morphine (it can contract the spincter of Oddi and worsen attack)

Answer 12

Increases pancreatic enzymes

Answer 13

1. Pain that interferes with quality of life 2. Nutrition abnormalities 3. Addiction to narcotics 4. Failure to rule out cancer 5. Biliary obstruction

Answer 14

Gemcitabine [Gemcitabine monotherapy represents a standard approach. FOLFIRINOX (leucovorin, 5-FU, Irinotecan, Oxaliplatin) is an option for patients with good ECOG status. Gemcitabine plus Paclitaxel or Capecitabine represent acceptable and potentially less toxic alternatives to FOLFIRINOX. For patients with ECOG status of 0-1 Gemcitabine alone is recommended. Radiotherapy as a single modality may be considered in the setting of palliation of pain for a nonresectable patient.] [UpToDate: In general, multiagent regimens are associated with higher response rates than single-agent gemcitabine, and at least two combinations, leucovorin plus short-term infusional fluorouracil (FU) plus oxaliplatin and irinotecan (FOLFIRINOX) and gemcitabine plus nanoparticle albumin-bound paclitaxel (nabpaclitaxel), have been associated with significantly prolonged survival as compared with gemcitabine alone. However, combination therapy is also associated with more adverse effects, which can have a negative impact on quality of life (QOL). As a result, single-agent therapy, typically with gemcitabine alone, remains a reasonable first-line therapy option.]

Answer 15

1. Abdominal pain radiating to back 2. Nausea 3. Vomiting 4. Anorexia [Can also get jaundice, left pleural effusion, ascites, or sentinel loop (dilated small bowel near the pancreas as a result of the inflammation)]

Answer 16

Patients with gallstone pancreatitis should undergo cholecystectomy when recovered from pancreatitis (same hospital admission)

Answer 17

Release of proteases

Answer 18

2/3 [UpToDate: One-third to one-half of PNETs have no defined clinical syndrome and no elevated hormone levels. As such, the presentation of nonfunctional PNETs is often delayed. Patients often present late in their course with symptoms of mass effect or with symptoms related to metastases including abdominal pain, weight loss, and jaundice. But patients with nonfunctional tumors can also present with an incidental finding on cross-sectional imaging performed for an unrelated reason. Patients with functional (ie, hormone-secreting) tumors present clinically with syndromes of excess gastrointestinal hormone production (insulin, serotonin, gastrin, VIP (vasoactive intestinal peptide), glucagon, or somatostatin). In general, the aggressiveness of PNETs (grade based on histologic features) does not correlate with presence or type of hormone production. Once a diagnosis of a functional tumor has been made biochemically, it is generally unnecessary to repeat any studies.]

Answer 19

Digestive enzymes [The pancreatic acinar cell is the functional unit of the exocrine pancreas. It synthesizes, stores, and secretes digestive enzymes. Under normal physiological conditions, digestive enzymes are activated only once they have reached the duodenum.]

Answer 20

Pancreatic tissue outside boundaries of pancreas without anatomic or vascular connections to pancreas

Answer 21

MRCP [Signs of cancer on MRCP include: duct with irregular narrowing, displacement, destruction; MRCP can also detect vessel involvement] [UpToDate: An alternative to diagnostic ERCP is MRCP. MRCP uses magnetic resonance technology to create a three-dimensional image of the pancreaticobiliary tree, liver parenchyma, and vascular structures. MRCP is better than CT for defining the anatomy of the biliary tree and pancreatic duct, has the capability to evaluate the bile ducts both above and below a stricture, and can also identify intrahepatic mass lesions. It is at least as sensitive as ERCP in detecting pancreatic cancers, and unlike conventional ERCP, it does not require contrast material to be administered into the ductal system. Thus, the morbidity associated with endoscopic procedures and contrast administration is avoided.]

Answer 22

Failure of the pancreatic ducts to fuse [Can result in pancreatitis from duct of Santorini stenosis]

Answer 23

HCO3 solution (have carbonic anhydrase)

Answer 24

Stones, severe pancreatitis, failure to improve, or suspected infection [UpToDate: Up to 20% of patients with acute pancreatitis develop an extrapancreatic infection (eg, bloodstream infections, pneumonia, and urinary tract infections). Extrapancreatic infections are associated with an increase in mortality. When an infection is suspected, antibiotics should be started while the source of the infection is being determined. However, if cultures are negative and no source of infection is identified, antibiotics should be discontinued. Prophylactic antibiotics are not recommended in patients with acute pancreatitis, regardless of the type (interstitial or necrotizing) or disease severity (mild, moderately severe, or severe).]

Answer 25

Infection [Usually gram negative rods] [UpToDate: The occurrence of pancreatic infection is a leading cause of morbidity and mortality in acute necrotizing pancreatitis. Approximately 1/3 of patients with pancreatic necrosis develop infected necrosis. There is no correlation between the extent of necrosis and the risk of infection. Although infection can occur early in the course of necrotizing pancreatitis, it is more often seen late in the clinical course (after 10 days). The majority of infections (approximately 75%) are monomicrobial with gut-derived organisms (eg, Escherichia coli, Pseudomonas, Klebsiella, and Enterococcus).]

Answer 26

Fasting glucagon level [UpToDate: The diagnosis of a glucagonoma requires the demonstration of increased plasma glucagon levels (\>500 pg/mL). Plasma glucagon levels are usually elevated 10- to 20-fold in patients with glucagonoma (normal \<50 pg/mL). Concentrations above 1000 pg/mL are virtually diagnostic of glucagonoma. However, up to 70% of the immunoreactive glucagon may be biologically inactive. Conditions other than glucagonoma that can induce moderate elevations in the serum glucagon concentration (\<500 pg/mL) include hypoglycemia, fasting, trauma, sepsis, acute pancreatitis, abdominal surgery, Cushing's syndrome, and renal and hepatic failure. Idiopathic hyperglucagonemia syndrome, either familial or sporadic, is associated with a large molecular weight form of the peptide. In addition, other neuroendocrine tumors, such as carcinoid tumors, insulinomas, and gastrinomas, can secrete glucagon, although rarely in high enough levels to cause the classic clinical syndrome. However, some glucagonomas are associated with serum levels of the peptide in the "physiologically elevated" range, even in the presence of necrolytic migratory erythema. Thus, in patients with the classic syndrome, a serum glucagon concentration below 500 pg/mL does not exclude a glucagonoma.]

Answer 27

* Nomal patients respond with a reduction in gastrin levels * Gastrinoma patients respond with increased gastrin levels [UpToDate: The secretin stimulation test is used to differentiate patients with gastrinomas from other causes of hypergastrinemia. Secretin stimulates the release of gastrin by gastrinoma cells, and patients with ZES tumors have a dramatic rise in serum gastrin. In contrast, normal gastric G cells are inhibited by secretin. False-negative response can occur in 6% to 20% of patients. False-positive results occurred in 15% to 39% of patients with achlorhydria induced by PPIs or due to chronic atrophic gastritis. However, if PPIs are discontinued abruptly, patients with ZES are at high risk to develop complications (such as acute bleeding and perforation) during the interim week. One week prior to the secretin study we substitute PPIs with high-dose H2 receptor antagonists (eg, ranitidine 450 to 750 mg every 6 hours until 24 hours prior to the test). Oral antacids are then taken as needed until midnight prior to the study. Patients should be advised to seek immediate medical attention for nasogastric aspiration if they develop significant exacerbation of ZES symptoms (eg, vomiting, pain, diarrhea) during the taper period. The secretin stimulation test is performed by administering 2 units/kg by rapid infusion intravenously over one minute; a baseline serum gastrin is measured twice before the secretin is administered and 2, 5, 10, 15, and 20 minutes later. Several criteria have been proposed to define a positive test; an increase in gastrin levels of greater than 120 pg/mL over basal fasting levels has a sensitivity and a specificity of 94% and 100%, respectively. Serum gastrin levels usually peak by 10 minutes. The secretin stimulation test should not be performed in patients with severe manifestations of ZES. This includes patients with severe abdominal pain, vomiting and diarrhea to the point of dehydration, or endoscopic findings of thickened gastric folds or multiple ulcers, as they are at particular risk for life-threatening consequences of discontinuing acid suppression. In such patients, tumor localization studies should be performed.]

Answer 28

Nodal invasion and ability to get a clear margin [UpToDate: Even in the setting of completely resected, node-negative pancreatic cancer, the majority of patients die of their disease. The most important prognostic factor for completely resected patients is nodal status. 5-year survival after pancreaticoduodenectomy is only about 10% for node-positive disease (even if only one node is positive), while it is 25% to 30% for node-negative disease.]

Answer 29

Close spontaneously [Especially if low output less than 200 cc/day] [UpToDate: With supportive care, case series have reported fistula closure in approximately 80% of external and 50% to 65% of internal fistulas over 4 to 6 weeks. We obtain follow-up abdominal imaging with an abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) in 6 to 8 weeks to evaluate the size of peripancreatic fluid collections. Imaging should be repeated sooner if the patient develops abdominal pain, fever, chills, jaundice, or early satiety. In patients with clinical symptoms, sepsis physiology, or increasing white blood cell count, pancreatic fluid should be sent for Gram stain and culture to rule out an infection. Systemic antibiotics should be administered in patients with evidence of infected pancreatic fluid collections.]

Answer 30

Head of pancreas [UpToDate: Somatostatinomas are rare neuroendocrine tumors with an annual incidence of 1 in 40 million. The mean age at diagnosis of somatostatinomas is 50 to 55 years (range 26 to 84), with a roughly equal gender distribution. Approximately 55% of somatostatinomas are in the pancreas, and, of these, two-thirds arise within the head of the pancreas. The remainder arises in the ampulla and periampullary region of the duodenum or rarely in the jejunum. Other rare primary sites include the liver, colon, and rectum. Approximately 75% of somatostatinomas are malignant, and 70% to 92% present with metastatic disease. Although 45% of somatostatinomas occur in association with multiple endocrine neoplasia (MEN)-1 syndrome, somatostatinomas are among the least common functioning pancreatic neuroendocrine tumors in patients with MEN-1 syndrome, occurring in less than 1% of patients. Up to 10% of patients with neurofibromatosis I (NF-1; von Recklinghausen disease) develop somatostatinomas. NF-1-associated somatostatinomas are characteristically duodenal, are rarely associated with somatostatinoma syndrome, and are less likely to metastasize as compared with sporadic somatostatinomas.]

Answer 31

* Anterior to aorta * Posterior to superior mesenteric vein

Answer 32

* Alpha cells: Glucagon * Beta cells: Insulin * Delta cells: Somatostatin * PP or F cells: Pancreatic polypeptide [Vasoactive intestinal peptide (VIP) and serotonin are also secreted by pancreatic islet cells.]

Answer 33

Surgical debridement (gas is indication for open debridement) [CT-guided drainage of pancreatic abscess is generally not effective]

Answer 34

1. Distal pancreatic resection (Only distal portion of the gland affected) 2. Whipple (Isolated pancreatic head disease) 3. Beger-Frey procedures (Isolated pancreatic head enlargement)

Answer 35

1. Common bile duct 2. Neck of the pancreas 3. Third portion of the duodenum [90% of gastrinomas occur in this region] [Radiopaedia.org: The triangle is formed by joining the following three points: * superiorly: confluence of the cystic and common bile ducts * inferiorly: junction of the second and third portions of the duodenum * medially: junction of the neck and body of the pancreas] [UpToDate: 80% of curable gastrinomas lie within the gastrinoma triangle comprised of the head of the pancreas and the duodenal sweep. The combination of preoperative localization techniques makes it possible for the experienced surgeon to identify over 90% of sporadic gastrinomas. Intraoperative transduodenal illumination and duodenotomy are of particular value in detecting very small gastrinomas arising in the wall of the duodenum. In the unlikely event that a sporadic gastrinoma cannot be identified at surgery, we suggest deferring a Whipple's procedure in favor of closure, with the intent of serial imaging every 6 months to try to localize the neoplasm.]

Answer 36

Fat-soluble vitamins (malabsorption) [Treatment is pancrelipase]

Answer 37

Distal pancreas [10% extrapancreatic (retroperitoneal, thorax)] [UpToDate: VIPomas are detected in 1 in 10 million people per year. The majority of VIPomas arise within the pancreas, and are classified as functioning pancreatic neuroendocrine (islet cell) tumors. In adults, VIPomas are intrapancreatic in over 95% of cases. However, other VIP-secreting tumors have been reported, including lung cancer, colorectal cancer, ganglioneuroblastoma, pheochromocytoma, hepatoma, and adrenal tumors. In children, VIPomas can occur in sympathetic ganglia and the adrenal glands. VIPomas are usually diagnosed between 30 and 50 years of age in adults and between two and four years of age in children. Symptomatic pancreatic VIPomas are usually solitary, more than 3 cm in diameter, and occur in the tail of the pancreas in 75% of patients. Approximately 60% to 80% of VIPomas have metastasized by the time of diagnosis. VIPomas usually occur as isolated tumors, but in 5% of patients they are part of the multiple endocrine neoplasia syndrome type 1 (MEN1) and occur in association with parathyroid and pituitary tumors, gastrinoma, and other tumors.]

Answer 38

Perform duodenostomy and look inside the duodenum for the tumor [15% of microgastrinomas are there] [UpToDate: Patients with a sporadic gastrinoma who do not have evidence of metastatic spread of disease should be offered exploratory laparotomy and resection with curative intent, even in the event of negative imaging studies in approximately 17% of patients. This recommendation is derived from the observation that in addition to eliminating or at least decreasing the need for antisecretory medical therapy, successful resection of sporadic gastrinomas protects against the possibility of eventual morbidity and death from metastatic spread of the tumor. In the hands of an experienced surgeon, up to 50% of these patients will be cured. Lymphadenectomy exceeding more than 10 lymph nodes at the time of surgery has been shown to achieve a higher biochemical cure as compared with selective or no lymphadenectomy. The likelihood for surgical cure is especially high for extrapancreatic gastrinomas (eg, those in the duodenum or peripancreatic lymph nodes). In contrast, laparotomy is not routinely recommended for patients with Zollinger-Ellison syndrome (ZES) as part of MEN 1 since the multifocal nature of the tumors in this disorder almost uniformly precludes cure of gastrin hypersecretion. However, because a minority of MEN-1 tumors can have aggressive growth patterns, some recommend imaging techniques or even surgical exploration to identify those exceeding 2 cm with the intent of resecting them. 80% of curable gastrinomas lie within the gastrinoma triangle comprised of the head of the pancreas and the duodenal sweep. The combination of preoperative localization techniques makes it possible for the experienced surgeon to identify over 90% of sporadic gastrinomas. Intraoperative transduodenal illumination and duodenotomy are of particular value in detecting very small gastrinomas arising in the wall of the duodenum. In the unlikely event that a sporadic gastrinoma cannot be identified at surgery, we suggest deferring a Whipple's procedure in favor of closure, with the intent of serial imaging every 6 months to try to localize the neoplasm. The reduction in mortality associated with surgical therapy for patients without metastatic disease was illustrated in a prospective study of 124 patients with gastrinoma presumed to be free of metastasis by imaging studies. Only 3% of the 98 patients who underwent resection developed liver metastases during a mean follow-up period of 6.3 years. By contrast, 23% of 26 patients treated medically developed metastatic disease over a slightly longer follow-up period (8.7 years). Two deaths due to metastatic gastrinoma occurred in the medically treated group compared with no disease-specific deaths in the operative group.]

Answer 39

90% [Resect these lesions] [UpToDate: Surgery is the only known cure for sporadic PNETs, whether functional or nonfunctional. Surgery is indicated in patients with PNETs to alleviate systemic symptoms due to hormone overproduction, compressive symptoms due to local mass effect, and to prevent malignant transformation or dissemination. Tumor functionality, grade, and stage are important factors in choosing patients for surgical treatment and determining the operative approach. As an example, for patients with a clinical syndrome consistent with insulinoma (most of which are benign), who appear to have an isolated pancreatic lesion, surgical resection is the treatment of choice. Patients with metastatic disease may be considered for debulking surgery if symptoms from excess insulin are refractory to medical treatment. By contrast, the majority of glucagonomas, VIPomas, somatostatinomas, and gastrinomas are malignant. Most nonfunctional, well-differentiated PNETs are also malignant. With malignant tumors, the primary consideration in determining surgical treatment is whether or not the patient has distant metastatic disease, whether or not the extrapancreatic disease is potentially resectable, and whether it is high-volume or low-volume. Aggressive resection of PNETs has acceptable morbidity and mortality with studies demonstrating improved survival across all stages of disease, supporting resection for patients with localized, locoregional, and even metastatic disease, as long as the metastatic sites can be completely resected. In a review of surgical resection for 125 nonfunctional and functional tumors, the most favorable outcomes were in patients with benign, functional tumors and completely resected, malignant tumors.]

Answer 40

Increases HCO3 and enzymes

Answer 41

p16 mutation [Tumor suppressor, binds cyclin complexes] [UpToDate: As a general rule, multiple combinations of genetic mutations are commonly found in pancreatic adenocarcinomas. These can be divided into three broad categories: 1. Mutational activation of oncogenes such as KRAS 2. Inactivation of tumor suppressor genes such as TP53, **p16**/CDKN2A, and SMAD4 3. Inactivation of genome maintenance genes, such as hMLH1 and MSH2, which control the repair of DNA damage The p16/CDKN2A gene on chromosome 9p is somatically inactivated in almost all pancreatic cancers (approximately 95%). Most of these inactivating mutations lead to loss of function of p16, the protein product of the CDKN2A gene. In 40% of the cancers, the gene is inactivated by homozygous deletion; in 40%, there is an intragenic mutation coupled with deletion of the second allele; and in 15%, gene inactivation is through hypermethylation of the p16/CDKN2A gene promoter. Inactivation of the p16/CDKN2A gene in pancreatic cancer is important for several reasons: * Loss of gene function abrogates an important control of the cell cycle in these tumors. * Inherited mutations in the p16/CDKN2A gene are one of the causes of the Familial Atypical Multiple Mole Melanoma (FAMMM) syndrome. Patients with the FAMMM syndrome have an increased risk of developing melanoma and a 20- to 34-fold increased risk of developing pancreatic cancer. Screening for pancreatic cancer in these kindreds is discussed in detail elsewhere. * The homozygous deletions that inactivate the p16/CDKN2A gene frequently also inactivate an adjacent gene, the methylthioadenosine phosphorylase (MTAP) gene. Data from cell lines suggest that inactivation of the MTAP gene in some pancreatic cancers could theoretically be exploited therapeutically.]

Answer 42

Inguinal ecchymosis in a pancreatitis patient that indicates bleeding

Answer 43

Into the portal system

Answer 44

90% [UpToDate: The commonly used term "pancreatic cancer" usually refers to a ductal adenocarcinoma of the pancreas (including its subtypes), which represents about 85% of all pancreatic neoplasms. Of the several subtypes of ductal adenocarcinoma, most share a similar poor long-term prognosis, with the exception of colloid carcinomas, which have a better prognosis. The more inclusive term "exocrine pancreatic neoplasms" includes all tumors that are related to the pancreatic ductal and acinar cells and their stem cells (including pancreatoblastoma), and is preferred.]

Answer 45

Tobacco [UpToDate: Cigarette smoking increases the risk for pancreatic cancer, and it alone accounts for approximately 25% of all cases. In multiple cohort and case-control studies, the relative risk for developing pancreatic cancer among smokers was at least 1.5. The risk increases with the amount of cigarettes consumed and may be particularly high in heavy smokers who also have homozygous deletions of the gene for the carcinogen metabolizing enzyme glutathione S-transferase T1 (GSTT1). Excess risk decreases with smoking cessation. In a large prospective study, the relative risk of pancreatic cancer among current smokers was 2.5. The risk fell by 48% by two years after discontinuing smoking and leveled off 10 to 15 years after stopping, eventually falling to the level of nonsmokers. It has been estimated that cessation of smoking could eliminate approximately 25% of pancreatic cancer deaths in the United States.]

Answer 46

Delayed gastric emptying [Other complications include: Fistula, leak, marginal ulceration] [UpToDate: Vomiting after oral intake is resumed can be a manifestation of delayed gastric emptying. The mean incidence of delayed gastric emptying is 17%, although the range varies widely among trials. The incidence of delayed gastric emptying following conventional and pylorus-preserving pancreaticoduodenectomy appear to be similar. Possible risk factors for delayed gastric emptying include prior abdominal surgery, history of cholangitis, and diabetes mellitus. It is important to not overlook the possibility of pancreatic fistula with an intra-abdominal fluid collection as a cause of delayed gastric emptying. Thus, an abdominal CT scan should be done if vomiting occurs.]

Answer 47

1. Ultrasound (needed to check for gallstones and possible CBD dilatation) 2. Abdominal CT (to check for complications such as necrotic pancreas (will not uptake contrast))

Answer 48

Cystograstrostomy (open or percutaneous) [Cysts that are growing must be resected to rule out cancer] [UpToDate: Surgical management can be performed with an open surgical procedure or with a laparoscopic approach. Most of the surgical literature is based on open surgical drainage procedures. Open surgical drainage can be accomplished via cystgastrostomy, cystenterostomy (direct drainage or via a Roux limb), or resection. However, these approaches are associated with substantial morbidity and mortality (25% and 5%, respectively). Drainage can also be accomplished laparoscopically. Laparoscopic cystgastrostomy can be performed via an anterior transgastric approach, which requires an anterior gastrotomy for access and cystgastrostomy creation through the posterior gastric wall, or a posterior approach through the lesser sac (requiring only a single gastrotomy in continuity with the walled-off pancreatic fluid collection). It can also be performed through a lesser sac approach, which is considered technically easier and is associated with less intraoperative bleeding. Walled-off pancreatic fluid collections that are not in close proximity to the stomach require creation of a cystojejunostomy. The cystojejunostomy is sometimes created via a Roux limb of jejunum. Left-sided pancreatectomy, either open or laparoscopic, may be preferred in the setting of a communicating walled-off pancreatic fluid collection in the tail, particularly in the setting of chronic pancreatitis or disconnected pancreatic tail syndrome.]

Answer 49

10% [UpToDate: Advances in diagnostic and therapeutic interventions have led to a decrease in mortality from acute pancreatitis, especially in those with severe, often necrotizing pancreatitis. Mortality in acute pancreatitis is usually due to systemic inflammatory response syndrome and organ failure in the first two-week period, while after two weeks it is usually due to sepsis and its complications. A multicenter prospective study of 1005 patients with acute pancreatitis reported overall mortality of 5% (1.5% in mild acute pancreatitis and 17% in severe pancreatitis). While the overall mortality in all hospitalized patients with acute pancreatitis is approximately 10% (range 2% to 22%), the mortality in the subset with severe acute pancreatitis may be as high as 30%.]

Answer 50

Gastrinoma (Zollinger-Ellison syndrome)

Answer 51

* Octreotide * Allow drainage * NPO * TPN [If failure to resolve with medical management, can try ERCP, sphincterotomy, and pancreatic stent placement (fistula will usually close, then remove stent)] [UpToDate: With supportive care, case series have reported fistula closure in approximately 80% of external and 50% to 65% of internal fistulas over 4 to 6 weeks. We obtain follow-up abdominal imaging with an abdominal computed tomography (CT) scan or magnetic resonance imaging (MRI) in 6 to 8 weeks to evaluate the size of peripancreatic fluid collections. Imaging should be repeated sooner if the patient develops abdominal pain, fever, chills, jaundice, or early satiety. In patients with clinical symptoms, sepsis physiology, or increasing white blood cell count, pancreatic fluid should be sent for Gram stain and culture to rule out an infection. Systemic antibiotics should be administered in patients with evidence of infected pancreatic fluid collections.]

Answer 52

Resolve spontaneously [Especially if under 5cm] [UpToDate: Watchful waiting is an appropriate option in patients with walled-off pancreatic fluid collections with minimal or no symptoms and no evidence of a pseudoaneurysm: A retrospective review of 68 patients with a walled-off pancreatic fluid collection followed conservatively showed a 9% incidence of serious complications, with the majority occurring in the first eight weeks after diagnosis. Complications included pseudoaneurysm formation in three patients, free perforation in two, and spontaneous abscess formation in one. An additional third of the patients underwent elective surgery, generally for fluid collection enlargement associated with pain. However, 43 patients (63%) either had spontaneous fluid collection resolution or remained well without symptoms or complications at a mean follow-up of 51 months.]

Answer 53

Yes [Gemcitabine monotherapy represents a standard approach. FOLFIRINOX (leucovorin, 5-FU, Irinotecan, Oxaliplatin) is an option for patients with good ECOG status. Gemcitabine plus Paclitaxel or Capecitabine represent acceptable and potentially less toxic alternatives to FOLFIRINOX. For patients with ECOG status of 0-1 Gemcitabine alone is recommended. Radiotherapy as a single modality may be considered in the setting of palliation of pain for a nonresectable patient.] [UpToDate: We recommend adjuvant chemotherapy for all patients with resected pancreatic cancer, including those with resected T1N0 disease. This recommendation is consistent with guidelines from ASCO, the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO). All patients should be offered information about clinical trials. Enrollment in available clinical trials is preferred, if available. One such ongoing study, RTOG 0848, is attempting to assess the independent contributions of chemotherapy and chemoradiotherapy in patients with resected tumors of the head of the pancreas. If protocol therapy is not available or declined, we suggest six months of combination chemotherapy with gemcitabine plus capecitabine rather than gemcitabine monotherapy for most patients. However, therapy with gemcitabine alone or, where available, S-1 alone is a reasonable option, particularly for patients with a borderline performance status or a comorbidity profile that precludes intensive therapy. For most patients, we suggest the addition of concurrent chemoradiotherapy to adjuvant chemotherapy. However, others disagree, arguing that a survival benefit from chemoradiotherapy has not been conclusively shown, particularly in patients receiving adjuvant chemotherapy. Ideally, patients should be encouraged to enroll in clinical trials testing the benefit of chemoradiotherapy when given in conjunction with systemic chemotherapy. In the United States, such a trial, RTOG 0848, is open for enrollment.]

Answer 54

Resection unless the cyst is purely serous and non-complex (purely serous and non-complex cysts have an extremely low malignancy risk and can be followed) [Worry about papillary-mucinous neoplasms or mucinous cystadenocarcinoma]

Answer 55

Octreotide [Octreotide is a long acting somatostatin analogue.]

Answer 56

Decrease exocrine function

Answer 57

Metoclopramide [UpToDate: The only two prokinetic agents that are commercially available in the US are metoclopramide and erythromycin; neither agent is ideal. In countries in which it remains available, we suggest cisapride rather than metoclopramide or erythromycin for subacute or chronic delayed gastric emptying (Grade 2B). Several precautions must be taken (avoidance of concurrent drugs that are inhibitors of CYP3A4,) and the maximum dose should be kept below 1 mg/kg or 60 mg per day in adults. In settings where cisapride is not available, we suggest domperidone (40 to 80 mg orally per day in four divided doses) in countries where it is approved, or metoclopramide (either subcutaneous or orally, 5 to 10 mg three to four times daily), or erythromycin (125 to 250 mg orally three times daily) (Grade 2B). Potential side effects of erythromycin remain a concern, especially the risk of sudden death due to long QT syndrome when used in patients taking medications that inhibit CYP3A4. The risk of adverse effects from metoclopramide can be reduced if the dose is kept at or below 40 mg per day but the risk of potentially permanent extrapyramidal side effects with long-term use beyond three months must be discussed with patients. All these prokinetics should be administered 10 to 15 minutes before meals; an additional dose before bedtime might be useful.]

Answer 58

Malignant [UpToDate: Somatostatinomas are rare neuroendocrine tumors with an annual incidence of 1 in 40 million. The mean age at diagnosis of somatostatinomas is 50 to 55 years (range 26 to 84), with a roughly equal gender distribution. Approximately 55% of somatostatinomas are in the pancreas, and, of these, two-thirds arise within the head of the pancreas. The remainder arises in the ampulla and periampullary region of the duodenum or rarely in the jejunum. Other rare primary sites include the liver, colon, and rectum. Approximately 75% of somatostatinomas are malignant, and 70% to 92% present with metastatic disease. Although 45% of somatostatinomas occur in association with multiple endocrine neoplasia (MEN)-1 syndrome, somatostatinomas are among the least common functioning pancreatic neuroendocrine tumors in patients with MEN-1 syndrome, occurring in less than 1% of patients. Up to 10% of patients with neurofibromatosis I (NF-1; von Recklinghausen disease) develop somatostatinomas. NF-1-associated somatostatinomas are characteristically duodenal, are rarely associated with somatostatinoma syndrome, and are less likely to metastasize as compared with sporadic somatostatinomas.]

Answer 59

Supportive (pain control and nutritional support with pancrelipase) [Surgery if indicated] [UpToDate: Chronic pancreatitis typically presents as chronic unrelenting pain with episodic flares. Although it is sometimes stated that chronic pancreatitis "burns out" over time, the duration of time over which this may occur is highly variable, if it occurs at all. In addition, pancreatic endocrine and exocrine dysfunction may develop as the disease progresses, and a variety of complications can occur, including pseudocysts, bile duct or duodenal obstruction, pancreatic ascites, splenic vein thrombosis, and pseudoaneurysms. Thus, the natural history of chronic pancreatitis is relatively bleak. Most therapies are aimed at "resting" the pancreas by minimizing exocrine pancreatic secretion; unfortunately, this is relatively ineffective. The goals of treatment include pain management, correction of pancreatic insufficiency, and management of complications. Therapy is similar in patients with acquired and hereditary pancreatitis.]

Answer 60

90% [They are usually evenly distributed throughout the pancreas]

Answer 61

* Sterile necrosis should be left alone * Infected necrosis (fever, sepsis, positive blood cx) requires surgical debridement * Gas in infected necrosis requires open surgical debridement [CT-guided drainage of infected pancreatic necrosis is generally not effective] [UpToDate: Pancreatic necrosis can lead to secondary infection or symptomatic sterile necrosis, which is characterized by chronic low grade fever, nausea, lethargy, and inability to eat. Both infected pancreatic necrosis and symptomatic sterile necrosis are accepted indications for debridement. The goal of pancreatic debridement is to excise all dead and devitalized pancreatic and peripancreatic tissue while preserving viable functioning pancreas, controlling resultant pancreatic fistulas, and limiting extraneous organ damage. For patients with biliary pancreatitis, cholecystectomy with intraoperative cholangiography is an important secondary objective of the surgery because it will prevent recurrent disease. Secondary infection of the necrotic pancreatic or peripancreatic tissue with either bacteria or fungus occurs soon after the initial inflammatory reaction subsides and is heralded by tachycardia, hypotension, fevers, and/or deteriorating organ function. Bacterial or fungal infections occur either by bacterial translocation from the gastrointestinal tract or via seeding through transient bacteremia that can occur in the setting of invasive intravenous lines, endotracheal intubation, or prolonged bladder catheterization. The risk of secondary bacterial infections can be minimized with early enteral feeding, central line catheter maintenance programs, ventilator protocols, and early urinary catheter removal. There is no benefit from probiotics, protease inhibitors, or early surgical debridement for the prevention of infected pancreatic necrosis. The use of prophylactic systemic antibiotics in acute pancreatitis is controversial.]

Answer 62

Pancreaticoduodenal arteries off of the gastroduodenal artery

Answer 63

20% [UpToDate: Even in the setting of completely resected, node-negative pancreatic cancer, the majority of patients die of their disease. The most important prognostic factor for completely resected patients is nodal status. 5-year survival after pancreaticoduodenectomy is only about 10% for node-positive disease (even if only one node is positive), while it is 25% to 30% for node-negative disease. Tumor stage is the most important prognostic factor. The influence of tumor stage on survival can be illustrated by a series of 21,512 patients undergoing pancreatectomy for pancreatic adenocarcinoma and reported to the National Cancer Database between 1992 and 1998 (at a time when adjuvant therapy was not typically administered); outcomes stratified according to stage at diagnosis are illustrated in the table. Although 5-year overall survival rates remain poor overall, survival estimates for individual patients are dynamic, and they may change over time, based upon the time already survived (a concept referred to as “conditional survival”). This was illustrated in a retrospective analysis of 1822 patients undergoing curative-intent surgery for pancreatic cancer at Johns Hopkins between 1970 and 2008. The two-year conditional survival at three years (ie, the probability of surviving to postoperative year 5 given that the patient had already survived three years) was 66%, versus a 5-year actuarial survival calculated from the time of surgery of 18%. Patients with high lymph node ratios (the number of metastatic divided by the total number of resected nodes) or positive margins saw the greatest increases in two-year conditional survival as more time elapsed since treatment.]

Answer 64

1/3 [Resect these lesions as 90% are malignant] [UpToDate: One-third to one-half of PNETs have no defined clinical syndrome and no elevated hormone levels. As such, the presentation of nonfunctional PNETs is often delayed. Patients often present late in their course with symptoms of mass effect or with symptoms related to metastases including abdominal pain, weight loss, and jaundice. But patients with nonfunctional tumors can also present with an incidental finding on cross-sectional imaging performed for an unrelated reason. Patients with functional (ie, hormone-secreting) tumors present clinically with syndromes of excess gastrointestinal hormone production (insulin, serotonin, gastrin, VIP (vasoactive intestinal peptide), glucagon, or somatostatin). In general, the aggressiveness of PNETs (grade based on histologic features) does not correlate with presence or type of hormone production. Once a diagnosis of a functional tumor has been made biochemically, it is generally unnecessary to repeat any studies.]

Answer 65

* Enucleate if less than 2 cm * Formal resection if greater than 2 cm [5-FU, streptozocin, and octreotide for metastatic disease] [UpToDate: Surgical removal of the insulinoma is the treatment of choice. Experience with systemic chemotherapy is limited. The traditional regimen of choice has been streptozocin and doxorubicin. Although objective response rates as high as 69% were initially reported for metastatic islet cell tumors, the true radiologic response rate is probably lower, between 10% and 40%. Uncertainty as to efficacy, as well as the toxicity of this regimen (nausea, prolonged myelosuppression, renal failure), has prevented its widespread acceptance as a standard first-line therapy. Antitumor activity has also been shown for regimens containing the orally active alkylating agent temozolomide. In the absence of comparative trials, the choice of first-line streptozocin/doxorubicin or a temozolomide-based regimen must be individualized, taking into account the convenience of oral rather than intravenous treatment, performance status, and the anticipated side effect profile of both combinations.]

Answer 66

Pancreaticoduodenal arteries off of the superior mesenteric artery

Answer 67

Fasting somatostatin level [UpToDate: Somatostatinoma syndrome should be suspected in patients with the classical triad of diabetes/glucose intolerance, cholelithiasis, and diarrhea/steatorrhea. In patients with somatostatinoma syndrome, the diagnosis is established by the presence of a fasting plasma somatostatin level exceeding 30 pg/mL. However, somatostatinoma syndrome is rare, and most somatostatinomas are detected as pancreatic or duodenal masses during the course of evaluation of abdominal pain, jaundice, or weight loss. In such patients, the diagnosis is often established by histopathology of the surgical specimen that demonstrates well-differentiated islet cells that stain positive for somatostatin on immunohistochemistry.]

Answer 68

50% [UpToDate: Although gastrinomas are one of the most common functional pancreatic neuroendocrine tumors, only 25% of gastrinomas arise in the pancreas. Approximately 50% to 88% of patients with sporadic ZES, and 70% to 100% of patients with ZES associated with MEN1, have duodenal gastrinomas. Duodenal gastrinomas are predominantly found in the first part of the duodenum. As compared with pancreatic gastrinomas, duodenal gastrinomas are usually small (\<1 cm), are often multiple, and are less likely to have metastasized to the liver at diagnosis (0% to 10% vs 22% to 35%). In 5% to 15% of patients, gastrinomas arise in non-pancreatic, non-duodenal abdominal (stomach, peripancreatic lymph nodes, liver, bile duct, ovary), and extra-abdominal (heart, small cell lung cancer) locations.]

Answer 69

Surgical resection [UpToDate: A pancreatic rest (also known as ectopic pancreas, aberrant pancreas, and heterotopic pancreas) refers to ectopic pancreatic tissue. These rare submucosal tumors most commonly consist of cystically dilated exocrine cells. Endocrine pancreatic tissue or a combination of exocrine and endocrine cell types may also be seen. Pancreatic rests are most frequently found in the distal stomach, duodenum, or proximal jejunum, but have also been reported within a Meckel's diverticulum, the gallbladder, bile ducts, and the minor and major papillae. They are typically discovered incidentally during endoscopy, surgery, or autopsy. They are also occasionally found on computed tomography (CT) scan. The diagnosis can be made histologically from tissue obtained by biopsy forceps or snare excision, although techniques to obtain deeper biopsies (using jumbo biopsy forceps, tunnel biopsy, unroofing, or endoscopic ultrasound-guided fine-needle aspiration) may be required. The management strategy should be guided by symptoms and suspicion for malignancy. Asymptomatic lesions can be followed expectantly. Endoscopic resection can be performed by standard snare, band ligation-assisted, or cap-assisted polypectomy technique. Ligation-induced ischemia using a 20-mm loop deployed through an 18-mm cap attachment was reported as an alternative approach to treat three patients with symptomatic pancreatic rests. Surgical resection is preferred to endoscopic resection when the muscularis propria is involved.]

Answer 70

Duct of Wirsung

Answer 71

Release of phospholipases

Answer 72

Long-standing pancreatitis or total pancreatectomy [Over 90% of function must be lost- Generally refers to exocrine function] [UpToDate: Chronic pancreatitis is the most common cause of exocrine pancreatic insufficiency in adults. Progressive inflammatory changes in the pancreas in chronic pancreatitis results in permanent structural damage, which can lead to impairment in exocrine function of pancreatic duct and acinar cells. Cystic fibrosis is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator protein. This protein regulates the transport of chloride and sodium across endothelial cell membranes in the lungs and exocrine glands. Approximately 80% of patients with cystic fibrosis also develop progressive pancreatic damage due to the blockage of ductules resulting from inspissated pancreatic secretion. Gastric resection and extensive small bowel resection may lead to secondary exocrine pancreatic insufficiency due to loss of sites of secretin and cholecystokinin-pancreozymin synthesis and inadequate mixing of chyme with pancreatic enzymes due to rapid gastric emptying. Total or a partial resection of the pancreas may result in varying degrees of exocrine pancreatic insufficiency due to reduction of glandular tissue or postoperative pancreatic duct occlusion. Extensive denervation following lymph node dissection can result in postcibal asynchrony and decreased pancreatic stimulation. Atrophy of the pancreas secondary to pancreatic/ampullary tumor-induced pancreatic duct obstruction and fibrosis can lead to exocrine pancreatic insufficiency. Shwachman-Diamond syndrome is an autosomal recessive syndrome that generally presents in infancy with bone marrow failure, particularly neutropenia, and exocrine pancreatic dysfunction. Other rare causes of exocrine pancreatic insufficiency include hereditary hemochromatosis, which results in progressive iron deposition in the pancreas. Patients with gastrinoma (Zollinger-Ellison syndrome) may develop exocrine pancreatic insufficiency due to inactivation of pancreatic enzymes by gastric acid. Small bowel mucosal disease (eg, celiac disease) can result in decreased cholecystokinin release, which in turn can result in reduced pancreatic secretion.]

Answer 73

* High-carbohydrate, high-protein, low-fat diet * Pancreatic enzymes (pancrease)

Answer 74

* Insulin to glucose ratio greater than 0.4 after fasting * Increased C peptide and proinsulin (if not elevated, suspect Munchaussen's syndrome) [UpToDate: Fasting for a maximum of 72 hours has been the standard test for the diagnosis of insulinoma. A 48-hour maximum has been proposed as a simpler alternative based upon a report of 127 patients with insulinoma in which adequate information was obtained for diagnosis in all patients. The fast was terminated because of hypoglycemia (plasma glucose ≤45 mg/dL [2.5 mmol/L]) in 43% by 12 hours, 67% by 24 hours, and 95% by 48 hours. However, in our series of 205 patients with insulinoma, 14% did not develop Whipple's triad until after 48 hours of fasting. Thus, to avoid misdiagnosis, we recommend the standard 72-hour fast. The decision to end the fast may not be easy. Some patients have slightly low plasma glucose values, but no symptoms or signs of hypoglycemia, while others have the same symptoms during fasting that they have in ordinary life at a time when plasma glucose values are normal. In the latter patients, the symptoms cannot be attributed to hypoglycemia. To complicate matters further, young, lean, healthy women may have plasma glucose concentrations in the range of 40 mg/dL (2.2 mmol/L) or even lower after prolonged periods of fasting. Careful questioning and testing for subtle symptoms or signs of hypoglycemia should be conducted repeatedly when the patient's plasma glucose is near or in the hypoglycemic range. To end the fast solely on the basis of a low plasma glucose value (except in those patients who have had Whipple's triad documented previously), in the absence of symptoms or signs of hypoglycemia, jeopardizes the possibility of discriminating between normal persons and those with hypoglycemia not mediated by insulin. A low plasma glucose value is a necessary but not sufficient finding for the diagnosis of hypoglycemia. The absence of symptoms or signs of hypoglycemia and lack of a low plasma glucose concentration during a 72-hour fast indicates a normal 72-hour fast, but does not preclude the existence of a hypoglycemic disorder that causes only postprandial symptoms. Interpretation of the data obtained at the end of the 72-hour fast is the same as that performed during the occurrence of a spontaneous hypoglycemic episode or during a postprandial evaluation (mixed meal test). These data will help distinguish hyperinsulinemia (endogenous or exogenous) from other causes of hypoglycemia. Ratios of insulin-to-glucose or of glucose-to-insulin are not helpful in the establishment of hyperinsulinemia; absolute values for insulin are preferable.]

Answer 75

Enterokinase (Released by the duodenum) [Trypsin activates other pancreatic enzymes including trypsinogen]

Answer 76

1. Fasting hypoglycemia (less than 50) 2. Symptoms of hypoglycemia (palpitations, Tachycardia, diaphoresis) 3. Relief with glucose [Indicative of insulinoma] [UpToDate: The presence of a hypoglycemic disorder in a person without diabetes should not be suspected solely on the basis of a low plasma glucose concentration, as this observation is necessary but insufficient for a diagnosis and in some cases may be misleading. Only those patients in whom Whipple's triad is documented require evaluation and management of hypoglycemia. In the patient without diabetes, the definition of hypoglycemia is based upon the presence of Whipple's triad: symptoms, signs, or both consistent with hypoglycemia, a low plasma glucose concentration at the time of symptoms, and resolution of those signs and symptoms after raising the plasma glucose concentration.]

Answer 77

If patient appears to have metastatic disease, a biopsy is indicated to direct therapy [Patients with resectable mass (no signs of metastasis) do not need a biopsy because the mass needs to be resected anyway]

Answer 78

ETOH [Second most common is idiopathic]

Answer 79

Pain [Other symptoms include anorexia, weight loss, malabsorption, steatorrhea, recurrent acute pancreatitis]

Answer 80

NPO and aggressive fluid resuscitation [ERCP is needed in patients with gallstone pancreatitis and retained CBD stones. Should perform sphincterotomy and stone extraction]

Answer 81

Islet cells [After islets, blood goes to acinar cells]

Answer 82

1. Diabetes 2. Gallstones 3. Steatorrhea 4. Hypochlorhydria [UpToDate: The most common symptoms in patients with somatostatinomas, regardless of their location, are abdominal pain and weight loss. Less often, patients present with somatostatinoma syndrome, characterized by diabetes mellitus or glucose intolerance, cholelithiasis, and diarrhea/steatorrhea. Somatostatinoma syndrome is more common in patients with pancreatic somatostatinomas as compared with duodenal somatostatinomas (19% vs 2%), due to differences in their secretion of somatostatin. Duodenal somatostatinomas usually present with symptoms caused by local complications. These symptoms include abdominal pain, obstructive jaundice, and gastrointestinal bleeding.]

Answer 83

Amylase [Hydrolyzes alpha 1-4 linkages of glucose chains]

Answer 84

Increases HCO3 excretion

Answer 85

Fecal fat testing [Pancreatic insufficiency causes malabsorption and steatorrhea] [UpToDate: The diagnosis of exocrine pancreatic insufficiency should be suspected in patients with chronic diarrhea/steatorrhea and chronic abdominal pain. Exocrine pancreatic insufficiency should also be suspected in patients with milder symptoms of bloating with overt morphological abnormalities on pancreatic imaging that are suggestive of chronic pancreatitis (eg, calcifications and/or main pancreatic duct dilation). We begin with an indirect test of pancreas function (fecal elastase-1) to establish the diagnosis of exocrine pancreatic insufficiency. In patients in whom indirect tests are inconclusive, but the clinical suspicion of exocrine pancreatic insufficiency remains high, we perform direct pancreas function testing with an endoscopic secretin test. Indirect tests measure the consequence of exocrine insufficiency (maldigestion). Indirect tests are simpler, easier to perform, and less expensive as compared with direct pancreas function tests. Their main role is in diagnosis of advanced exocrine pancreatic insufficiency. They are much less sensitive as compared with direct tests for diagnosis of earlier stages of exocrine pancreatic insufficiency. Other disadvantages include false positive results with non-pancreatic gastrointestinal diseases and the need for stool collection. Fecal elastase in the most sensitive and specific indirect test of pancreatic function. Fecal elastase-1 is an enzymatic product of pancreatic secretion that remains relatively stable during transport through the gastrointestinal tract. There is a direct correlation in pancreatic elastase-1 concentrations in pancreatic fluid and stool. Fecal elastase-1 \<200 mcg/g is considered abnormal. Fecal elastase-1 between 200 mcg/g and 250 mcg/g may be considered borderline and retesting should be considered. The sensitivity of fecal elastase-1 for mild, moderate, and severe exocrine pancreatic insufficiency in patients with chronic pancreatitis are 63%, 100%, and 100%, respectively. Fecal elastase has a specificity of 93% in patients with exocrine pancreatic insufficiency. Watery diarrhea from nonpancreatic diseases or medications may dilute the fecal specimen and produce false positive results owing to dilution, resulting in artificially low levels of the enzyme. This limitation can be ameliorated by lyophilizing (concentrating) the stool sample.]

Answer 86

1. Zinc 2. Amino acids 3. Fatty acids

Answer 87

They lay posterior to the neck of the pancreas

Answer 88

ERCP [Minor papilla will show long and large duct of Santorini, major papilla will show short duct of Wirsung]

Answer 89

It forms from the ventral pancreatic bud failing to rotate clockwise [Double bubble sign on abdominal xray] [UpToDate: In symptomatic neonates, a plain abdominal radiograph will show the classic "double bubble" sign with air in the stomach and duodenum. However, the double bubble sign is not specific for annular pancreas since it can also be seen in other conditions including duodenal atresia and intestinal malrotation.]

Answer 90

Ventral pancreatic bud

Answer 91

Bleeding from isolated gastric varices that form as collaterals [Treatment is splenectomy]

Answer 92

70% [UpToDate: The commonly used term "pancreatic cancer" usually refers to a ductal adenocarcinoma of the pancreas (including its subtypes), which represents about 85% of all pancreatic neoplasms. Of the several subtypes of ductal adenocarcinoma, most share a similar poor long-term prognosis, with the exception of colloid carcinomas, which have a better prognosis. The more inclusive term "exocrine pancreatic neoplasms" includes all tumors that are related to the pancreatic ductal and acinar cells and their stem cells (including pancreatoblastoma), and is preferred. The initial presentation of pancreatic cancer varies according to tumor location. Approximately 60% to 70% of exocrine pancreatic cancers are localized to the head of the pancreas, while 20% to 25% are in the body/tail and the remainder involve the whole organ. Compared with tumors in the body and tail of the gland, pancreatic head tumors more often present with jaundice, steatorrhea, and weight loss. As an example, in the above noted series, jaundice was present in 73% of the 114 patients with a tumor located in the head of the pancreas, compared with 11% of 19 body lesions, and none of the 11 tail lesions. Steatorrhea was present in 28% of the patients with pancreatic head lesions versus 11% of those with body, and none of those with tail lesions. Steatorrhea is attributable to loss of the pancreas’s ability to secrete fat-digesting enzymes or to blockage of the main pancreatic duct.]

Answer 93

Dilation of both the pancreatic duct and the common bile duct dues to pancreatic head tumor

Answer 94

1. 5FU 2. Streptozocin [Streptozocin-based combination therapy has been an historical treatment standard for patients with advanced pancreatic NET.] [UpToDate: Streptozocin-based combination therapy has been an historical treatment standard for patients with advanced pancreatic NET. Antitumor efficacy can be illustrated by the following data: In an early randomized trial, streptozocin plus doxorubicin had a combined biochemical and radiologic response rate of 69% and a median survival of 2.2 years. A retrospective analysis of 84 patients with either locally advanced or metastatic pancreatic NET treated with streptozocin, FU, and doxorubicin and using current standard response criteria reported a 39% objective radiographic response rate and a median survival duration of 37 months. Another retrospective analysis of 96 patients with pancreatic NET treated with streptozocin plus FU reported an objective response rate of 43%, and an additional 41% had stable disease as the best response. While streptozocin-based regimens are clearly active in patients with advanced pancreatic NET, widespread use has been limited by a relatively cumbersome administration schedule and by concerns about toxicity, which can include myelosuppression, nausea, hair loss, and renal dysfunction.]

Answer 95

Malignant [UpToDate: VIPomas are detected in 1 in 10 million people per year. The majority of VIPomas arise within the pancreas, and are classified as functioning pancreatic neuroendocrine (islet cell) tumors. In adults, VIPomas are intrapancreatic in over 95% of cases. However, other VIP-secreting tumors have been reported, including lung cancer, colorectal cancer, ganglioneuroblastoma, pheochromocytoma, hepatoma, and adrenal tumors. In children, VIPomas can occur in sympathetic ganglia and the adrenal glands. VIPomas are usually diagnosed between 30 and 50 years of age in adults and between two and four years of age in children. Symptomatic pancreatic VIPomas are usually solitary, more than 3 cm in diameter, and occur in the tail of the pancreas in 75% of patients. Approximately 60% to 80% of VIPomas have metastasized by the time of diagnosis. VIPomas usually occur as isolated tumors, but in 5% of patients they are part of the multiple endocrine neoplasia syndrome type 1 (MEN1) and occur in association with parathyroid and pituitary tumors, gastrinoma, and other tumors.]

Answer 96

1. Great pancreatic artery 2. Inferior pancreatic artery (Also known as transverse pancreatic artery) 3. caudal pancreatic artery [These are branches off of the splenic artery]

Answer 97

* Abdominal CT (Pancreas will be shrunken with calcifications) * Ultrasound (Pancreatic ducts greater than 4mm, cysts, atrophy) * ERCP (very sensitive for chronic pancreatitis) [UpToDate: The diagnosis of chronic pancreatitis can be challenging since laboratory studies and imaging procedures may be normal. In addition, patients may have symptoms suggestive of chronic pancreatitis but in fact have pancreatic carcinoma. On the other hand, the classic triad of pancreatic calcifications, steatorrhea, and diabetes mellitus strongly suggests the diagnosis, but are usually seen together only in late, very advanced disease. The diagnosis is confirmed if there are calcifications within the pancreas on abdominal plain films or computed tomography (CT) scan, an abnormal pancreatogram revealing beading of the main pancreatic duct or ectatic side branches, or an abnormal secretin pancreatic function test.]

Answer 98

Dorsal pancreatic bud

Answer 99

1. Splenic artery 2. Gastroepiploic artery 3. Dorsal pancreatic artery [UpToDate: The arterial supply to the duodenum and pancreas is derived from the celiac artery, providing the superior pancreaticoduodenal arteries (anterior and posterior branches), and the superior mesenteric artery, providing the inferior pancreaticoduodenal arteries (anterior and posterior branches). The splenic artery supplies primarily the body and tail of the pancreas. The venous drainage follows the arteries to provide tributaries to the splenic vein and superior mesenteric vein which drain into the portal vein.]

Answer 100

Somatostatin

Answer 101

Gram negative rods

Answer 102

1. Diabetes 2. Stomatitis 3. Dermatitis (Rash - Necrolytic migratory erythema) 4. Weight loss [UpToDate: As the clinical features of glucagonoma syndrome are non-specific, the majority of patients are diagnosed late when the disease has metastasized. Weight loss, often significant, is the most common presenting feature, occurring in 80% of patients with glucagonoma syndrome. Necrolytic migratory erythema (NME) is the presenting feature of glucagonoma syndrome in approximately 70% of patients. Although the rash can occasionally be the only symptom, in most cases patients have associated systemic symptoms. NME characteristically begins as erythematous papules or plaques involving the face, perineum, and extremities. Over the ensuing 7 to 14 days, the lesions enlarge and coalesce. Central clearing then occurs, leaving bronze-colored, indurated areas centrally, with blistering, crusting, and scaling at the borders. The affected areas are often pruritic and painful. The same process often affects the mucous membranes, resulting in glossitis, angular cheilitis, stomatitis, and blepharitis. Patients with NME often have associated hair loss and nail dystrophy. Glucose intolerance occurs in 75% to 95% of patients with glucagonoma. However, clinically significant hyperglycemia with diabetes mellitus is present at diagnosis in approximately 40% of patients. Hyperglycemia due to glucagonoma syndrome does not usually result in diabetic ketoacidosis, since beta cell function is preserved and insulin secretion is normal.]

Answer 103

Dorsal pancreatic bud [The ventral bud has the duct of Wirsung.]

Answer 104

Puestow procedure: Pancreaticojejunostomy (Open along main pancreatic duct and drain into jejunum) [Most patients improve] [UpToDate: Decompression procedures have generally been recommended for patients with refractory pain who have a dilated main pancreatic duct. The normal pancreatic duct ranges from 2 to 4 mm in diameter (most narrow in the tail, enlarging as it passes toward the ampulla). A dilated duct (from a surgical standpoint) is one that would permit anastomosis to a loop of jejunum. Consensus has not been achieved at the threshold at which this can be achieved; some surgeons will perform such a procedure in those with ducts that are only 5 to 6 mm in diameter, while others require dilation to around 10 mm. Multiple series have described the outcome of this procedure and its variants. A review of these data in a consensus statement from the American Gastroenterological Association (AGA) focused on five reports that were selected because of their relatively large numbers of patients, longer follow-up, and methodologic quality. The data suggest that short-term pain relief is achieved in approximately 80% of patients. Morbidity and mortality related to the operation are generally low when the procedure has been performed by experienced surgeons (0% to 5%). However, pain relief persists for more than two years in only about 60% of patients. Patients with recurrent pain may require additional surgery. The cause of pain recurrence is unclear. It may be related to progressive pancreatic injury or inadequate drainage of secondary ducts. How these outcomes compare with resection procedures has not been extensively studied in randomized studies, but tend to favor drainage approaches.]

Answer 105

Angioembolization [The tissue planes are very friable early after surgery, and bleeding is hard to control operatively]

Answer 106

Retroperitoneal leakage of pancreatic fluid from the pancreatic duct or pseudocyst (not from a pancreatic-pleural fistula) [Majority close on their own]

Answer 107

Non-functional pancreatic endocrine neoplasms

Answer 108

Predicting the severity of acute pancreatitis [Nearly 100% mortality if 8 Ranson's criteria met]

Answer 109

* Enucleate if less than 2 cm * Formal resection if greater than 2 cm * Debulking can improve symptoms [Excise the suspicious nodes in metastatic disease] [UpToDate: The type and extent of resection depends on the location of the gastrinoma. Ideally, all gastrinoma tissue is resected. Regional lymphadenectomy should also be performed as required. Small gastrinomas (\<2 cm) in the head of the pancreas can be enucleated as these are likely to be benign, though larger tumors may require pancreaticoduodenectomy. Enucleation may be attempted for small pancreatic gastrinomas that are not abutting the pancreatic duct. Small tumors in the duodenal wall may be amenable to full-thickness excision and primary closure. With gastrinoma \>2 cm, there is a higher risk of malignancy and potential for nodal disease, and these should be removed via a traditional resection. Gastrinomas in the body or tail of the pancreas are best managed with a distal pancreatectomy. Although enucleation has been described for pancreatic tail lesions, traditional resection is preferred because of the more aggressive nature of gastrinoma to the left of the superior mesenteric vein. The role of laparoscopy in the surgical management of gastrinomas is controversial. Open operations are still more commonly performed for gastrinoma because they usually are not localized preoperatively, are often located in the duodenum, and are commonly associated with lymph node metastases. Indeed, accessing the “gastrinoma triangle” where most gastrinomas are located can be difficult laparoscopically. In the past, if the tumor was not able to be localized, a parietal cell vagotomy or total gastrectomy was performed. With the advent of proton-pump inhibitors, these procedures are no longer advocated. In general, the cure rate for sporadic, nonmetastatic gastrinoma is 60 percent and 30% to 40% respectively at 1 and 5 years.]

Answer 110

Cholecystectomy [UpToDate: In patients with somatostatinomas, cholelithiasis may result from inhibition of cholecystokinin release, which reduces gallbladder contractility. Diminished insulin secretion leads to glucose intolerance/diabetes. Inhibition of pancreatic enzyme and bicarbonate secretion and intestinal absorption of lipids causes diarrhea and steatorrhea.]

Answer 111

Duodenojejunostomy or duodenoduodenostomy (Possible sphincteroplasty) [Pancreas is not resected] [UpToDate: Most patients with annular pancreas are asymptomatic, and thus the presence of annular pancreas does not necessarily indicate that symptoms can be attributed to it. Surgery remains the procedure of choice in patients in whom symptoms can be attributed to annular pancreas. The goal of surgery is to relieve duodenal or gastric outlet obstruction by bypassing the annulus. Resection of the annulus should be avoided since it is associated with pancreatitis, pancreatic fistula formation, and incomplete relief of obstruction. In neonates, relief of obstruction is accomplished with a duodenoduodenostomy. In adults, a duodenojejunostomy or gastrojejunostomy is recommended as the duodenum is less mobile. In patients with annular pancreas associated with obstructive jaundice, biliary bypass with choledochoenterostomy or placement of a biliary stent may be necessary to relieve the obstruction. Pancreaticoduodenectomy has been recommended when annular pancreas is associated with obstructive pancreatic duct stones in the setting of chronic pancreatitis or a periampullary lesion that is suspicious for a malignancy.]

Answer 112

1. Amylase 2. Lipase 3. Trypsinogen 4. Chymotrypsinogen 5. Carboxypeptidase 6. HCO3

Answer 113

* 75% are spontaneous * 25% are MEN-1 related

Answer 114

1. Age over 55 2. WBC over 16 3. Glucose over 200 4. AST over 250 5. LDH over 350 [UpToDate: A score based upon Ranson's criteria is one of the earliest scoring systems for severity in AP. Ranson's criteria consist of 11 parameters. Five of the factors are assessed at admission and six are assessed during the next 48 hours. A later modification for biliary pancreatitis included only 10 points. Mortality increases with an increasing score. Using the 11 component score, mortality was 0% to 3% when the score was \<3, 11% to 15% when the score was ≥3, and 40% when the score was ≥6. Although the system continues to be used, a meta-analysis of 110 studies found the Ranson score to be a poor predictor of severity.]

Answer 115

Malignant [UpToDate: Glucagonomas are rare, with an annual incidence of 0.01 to 0.1 new cases per 100,000. Glucagonomas are usually solitary, and the majority are located in the distal pancreas. Patients typically present in their fifth decade. While most glucagonomas are sporadic, up to 20% may be associated with the multiple endocrine neoplasia syndrome type 1 (MEN1). However, glucagonomas occur in only 3% of MEN1 patients. Glucagonomas are usually large (\>3 cm), and approximately 50% to 80% are metastatic at diagnosis. Unlike carcinoid tumors, however, liver metastases are not a prerequisite for the clinical syndrome.]

Answer 116

Distal pancreas [UpToDate: Glucagonomas are rare, with an annual incidence of 0.01 to 0.1 new cases per 100,000. Glucagonomas are usually solitary, and the majority are located in the distal pancreas. Patients typically present in their fifth decade. While most glucagonomas are sporadic, up to 20% may be associated with the multiple endocrine neoplasia syndrome type 1 (MEN1). However, glucagonomas occur in only 3% of MEN1 patients. Glucagonomas are usually large (\>3 cm), and approximately 50% to 80% are metastatic at diagnosis. Unlike carcinoid tumors, however, liver metastases are not a prerequisite for the clinical syndrome.]