Chapter 30 Pancreas
Principles of Surgery Companion Handbook
|Cysts and Pseudocysts|
|Carcinoma of the Pancreas and Periampullary Carcinoma|
|Islet Cell Tumors|
The pancreas lies behind the stomach in a lesser sac. It is composed of the head (over L2), the body, and the tail. The uncinate process curls behind the head. The superior mesenteric vein and artery lie behind the neck of the pancreas. The duct of Wirsung is major duct, 34 mm diameter, that joins the common bile duct at the papilla of Vater. The minor duct is the duct of Santorini, which joins the main duct in the neck and drains via the minor papilla into the duodenum. In 510 percent of persons, major drainage of the pancreas is via the duct of Santorini, with a vestigial Wirsung duct; this is pancreas divisum, which can cause pancreatitis. Arterial supply to the head is via anterosuperior and posterosuperior pancreaticoduodenal arcades from the gastroduodenal artery, which anastomose with anteroinferior and posteroinferior pancreaticoduodenal arteries from the superior mesenteric artery. The splenic and transverse pancreatic arteries supply the body. Venous drainage closely parallels arterial supply. In up to 25 percent of persons, the right hepatic artery arises from the superior mesenteric artery and courses behind the pancreas and bile duct. Lymphatic drainage is diffuse. Innervation is sympathetic via splanchnic nerves and parasympathetic via the celiac branch of the posterior (right) vagus.
Anatomic Variants Annular pancreas is rare. The duodenum is encircled by the head of the pancreas. Symptoms are from duodenal obstruction. Cure is duodenojejunostomy. Ectopic pancreas most common in the stomach (antrum, greater curvature) or Meckel's diverticulum.
Fluid and electrolyte secretion is 10002000 mL/day (pH 8.08.3), and secretion is isosmotic, from centroacinar cells. The Na+/K+ content is similar to plasma. The principal anions are and Cl, with increased Cl (110 mmol/L) and decreased (50 mmol/L) at low secretory rates and decreased Cl (20 mmol/L) and increased (140 mmol/L) at high secretory rates. Alkaline secretions neutralize gastric acid. The major stimulus is secretion released from duodenal mucosa in response to acid.
Enzymes are released by cholecystokinin (CCK) and vagal cholinergics. CCK is released from the proximal small bowel by fatty acids and oligopeptides. Proteases are trypsin, chymotrypsin, elastase, ribonuclease, and carboxypeptidase. Lipases are lipase, colipase, phospholipase A2. Amylase digests starches. Lipase and amylase are secreted in active forms; the others are secreted as zymogens, which are activated by trypsin. Trypsinogen is activated by enterokinase. Lysosomal enzymes and zymogens are segregated intracellularly.
Enzyme secretion is 90 percent in excess of enzymes needed for digestion. Malabsorption occurs only when secretion falls to about 10 percent of normal. This may be from ductal blockage (cancer), destruction (chronic pancreatitis), or surgical procedures. Insufficiency results mainly in fat malabsorption and steatorrhea. Fat-soluble vitamins, however, are not affected. Therapy is oral lipase, a low-fat diet, and histamine H2 blockers.
The islets of Langerhans constitute 12 percent of the pancreatic mass, 6080 percent beta (insulin), 1520 percent alpha (glucagon), 510 percent delta (somatostatin), and 1520 percent pancreatic polypeptide (PP). PP cells are located mainly in head, and alpha cells are seen mostly in body and tail.
Insulin comes from beta cells as proinsulin. It decreases the blood glucose level, increases cellular glucose uptake, increases glycogenesis, decreases gluconeogenesis, increases lipogenesis, decreases lipolysis, increases protein synthesis, and increases amylase synthesis. Its release is stimulated by hyperglycemia, arginine, and free fatty acids.
Glucagon comes from alpha cells. It increases the blood glucose level, increases glycogenolysis, increases gluconeogenesis, and relaxes gastrointestinal smooth muscle. Its release is stimulated by hypoglycemia, stress, CCK, and sympathetics. Insulin and hyperglycemia suppress glucagon release.
Somatostatin comes from delta cells. It inhibits insulin release and most gastrointestinal hormones. It is an important pancreatic regulator.
Pancreatic polypeptide comes from PP cells. Its release is stimulated by proteins, vagal cholinergic stimulation, and hypoglycemia. It decreases pancreatic exocrine secretion.
Definition Nonbacterial inflammation of pancreas caused by pancreatic enzymes.
Etiology About 40 percent is caused by gallstones, but the mechanism is unclear. Bile reflux (common channel theory) may have a role, from transient obstruction of the ampulla by a stone. However, sterile bile in the pancreatic duct that is not under pressure does not cause pancreatitis. Deconjugated bile salts and lysolecithin are toxic to the pancreas. Another 40 percent results from alcoholism, probably due to increased pancreatic ductal pressure with hypersecretion, protein precipitation, spasm of the sphincter of Oddi, calcium precipitation, and increased ductal permeability. Dietary-induced hypertriglyceridemia may play a role in alcoholics. Postoperative pancreatitis, which may occur after biliary, gastric, cardiac, or splenic procedures, has a high mortality. Metabolic factors have been associated, such as hyperparathyroidism, aminoaciduria, hypertriglyceridemia (Type IV), and possibly hemochromatosis. Other factors include vascular stasis, drugs and toxins (e.g., methyl alcohol, chlorothiazide), and viral illnesses (e.g., mumps, Coxsackie viruses), pancreas divisum, and idiopathic (1520 percent).
Clinical Manifestations Severe midepigastric pain is seen that radiates through to the back; it is relieved by sitting and frequently is accompanied by severe retching. Upper abdominal tenderness and guarding are present. About 90 percent of patients have fever, leukocytosis, and tachycardia. Ileus is common. Shock from fluid sequestration and myocardial depression may be present. Jaundice is seen in 2030 percent. Occasionally, there is carpopedal spasm from hypocalcemia. About 1 percent of patients have retroperitoneal blood around the umbilicus (Cullen's sign) or in the flanks (Grey-Turner's sign).
Laboratory Studies Patients may show hyperamylasemia, which can be very nonspecific. Cholecystitis, cholangitis, perforated peptic ulcer, strangulated small bowel obstruction, salpingitis, renal failure, macroamylasemia, and mumps are among many disorders that may cause an elevated amylase level. A serum lipase determination might be more specific. A urine amylase clearance determination can be useful. The calcium level may fall; a value of less than 7.5 mg/dL indicates a poor prognosis. Radiographs may show a sentinel loop of bowel air. A computed tomographic (CT) scan can be very useful in predicting the severity of disease and in the diagnosis of complications.
Treatment Critical to care are replacement of fluid and electrolyte losses, monitoring of vascular volume (e.g., by Foley catheter, central line), repeated assessments of hematocrit and electrolytes (including calcium), and bowel rest. Nasogastric suction is of no proven benefit in uncomplicated pancreatitis without uncontrolled vomiting. Likewise, drugs such as glucagon, Trasylol, and atropine show no benefit. The routine use of antibiotics is not proven in uncomplicated pancreatitis. Cholycystectomy is indicated in biliary pancreatitis, but surgery is generally contraindicated in uncomplicated pancreatitis. Peritoneal lavage can decrease cardiopulmonary complications but does not decrease mortality. Surgery may be needed for impacted stones, debridement of necrosis, and abscess drainage.
Complications, Morbidity, and Mortality Overall mortality can be predicted via Ranson's criteria (Table 30-1). Across the board, mortality is 10 percent. Pseudocyst is the most common complication, usually occurring after 2 3 weeks. Pseudocyst may resolve, but persistence or symptoms require surgical drainage. Infected pseudocysts are generally drained externally. Abscess is uncommon but has high mortality and demands effective drainage, without which mortality is 100 percent. Most common organisms are coliforms, Streptococcus faecalis, and clostridia. Pancreatic necrosis is diagnosed by contrast-enhanced CT scan. Infected pancreatic necrosis requires operative debridement and placement of drainage catheters. Multiple operations are frequently employed. Likewise, necrosis may lead to biliary or enteric perforation. Systemic complications include adult respiratory distress syndrome (ARDS), renal failure, and myocardial depression. Biliary obstruction may occur, more often in chronic disease. Hemorrhage may occur from the splenic artery or erosion of the mesenteric or portal vessels.
TABLE 30-1 Ranson's Prognostic Criteria for Acute Pancreatitis Morbidity and Mortality Rates Correlate with the Number of Criteria Present: 02 = 2% Mortality; 34 = 15% Mortality; 56 = 40% Mortality; 78 = 100% Mortality
The definition is vague but generally includes changes that result after repeated episodes of acute pancreatitis. Pancreas becomes small, indurated, and nodular with acini and islets surrounded by fibrous tissue. There is ductal stricture and dilatation; calcification is common.
Clinical Manifestations Symptoms include continuous or intermittent epigastric/back pain, anorexia, and weight loss. Vomiting occurs with acute attacks. Steatorrhea and diabetes may be present. Pseudocysts are common. Personality deficits are also common. This picture almost never occurs with repeated episodes of biliary pancreatitis, compared with alcoholism.
Diagnosis Diagnosis is difficult at best. There are few physical findings. Endoscopic retrograde choleangiopancreatography (ERCP) and CT scan are useful and may show ductal dilatation, calculi, and strictures. Amylase and lipase levels are of little use. Calcification is pathognomonic.
Treatment Recurrent biliary pancreatitis is best avoided by performing cholecystectomy and possible bile duct exploration at the index attack; this is of little use in alcoholics. With chronic alcoholic pancreatitis, chronic pain, and alternating ductal dilatation and strictures (chain of lakes), longitudinal pancreaticojejunostomy (Peustow procedure) is appropriate. When chronic pancreatitis is associated with a stricture of the pancreatic duct in the head of the pancreas, pancreaticoduodenectomy is effective. With a small duct, a 95 percent pancreatectomy may be of some benefit, but morbidity is high. Abstinence is critical. Chronic pain is difficult to manage (Fig. 30-1).
FIGURE 30-1 Algorithm for the surgical management of patients with chronic pancreatitis.
Mechanisms of Injury Penetrating trauma accounts for 7080 percent of pancreatic injuries. Adjacent organs are also injured in 7090 percent. Blunt trauma may contuse or fracture the pancreas. Disruption usually occurs at the neck, and associated injuries are less frequent. The consequences of injury usually are the result of parenchymal and ductal disruption, leading to fistula, pseudocyst, or abscess.
Clinical Manifestations Blunt injuries may result in delayed presentation. Abdominal findings may be minimal in the absence of hemorrhage or other injuries. CT scans may be helpful. Clinical suspicion and mechanism of injury are important. Negative paracentesis does not exclude injury. Hyperamylasemia is very nonspecific in the multiple-trauma patient.
Treatment Careful and total inspection via lesser space exploration and the Kocher maneuver is paramount. Hematomas may indicate deeper injury. Damaged tissue should be gently debrided. Without ductal injury or with minor ductal injury, drainage alone usually suffices. Major distal injuries are best treated by resection, generally as a distal pancreatectomy with splenectomy. Major injury to the head can be treated with debridement and drainage with or without Roux-en-Y reconstruction or pyloric exclusion. Pancreaticoduodenectomy is indicated when severe injuries involve two of the three structures near or within the head of the pancreas: the bile duct, pancreatic duct, and duodenum. Occasionally, major hemorrhage within or behind the head requires pancreaticoduodenectomy. Definition of ductal injury is critical.
Morbidity and Mortality Complications include fistulas, pseudocysts, infection, and delayed hemorrhage and usually occur in around 30 percent of patients. Complications are more common after blunt injury. Mortality averages 20 percent.
CYSTS AND PSEUDOCYSTS
True cysts are fluid-filled, with an epithelial lining. They may be congenital, parasitic, retention, or neoplastic. Most are rare. Cystadenoma and cystadenocarcinoma are relatively uncommon.
Pseudocysts are so called because there is no epithelial lining. They consist of fibrous wall surrounding pancreatic juice. Most are seen in the lesser sac. Etiology is usually ductal disruption from pancreatitis (75 percent, alcoholism, biliary) or trauma (25 percent).
Clinical Manifestations Symptoms include persistent pain, fever, and ileus, usually 23 weeks after acute pancreatitis or trauma. Pain is usually epigastric or back pain. There may be a palpable mass (75 percent), nausea, vomiting, and jaundice from duodenal and bile duct compression. The serum amylase level usually remains moderately elevated.
Diagnosis Diagnosis is most readily made with CT scan or ultrasound. ERCP is usually unnecessary.
Morbidity Associates morbidity includes secondary infection (14 percent), gastric outlet obstruction (3 percent), erosion into adjacent organs, rupture (7 percent), hemorrhage into the cyst (6 percent), and bile duct obstruction (6 percent).
Treatment Enlarging pseudocysts or those present for more than 6 weeks should be treated. The cysts should be allowed to mature prior to intervention; usually this takes 6 weeks. Most efficacious is internal drainage, usually via cystogastrostomy, but cystojejunostomy, cystoduodenostomy, and distal pancreatectomy are options. External drainage is indicated only for thin, flimsy cysts or true abscesses. Infected mature cysts may be drained internally via cystogastrostomy. Percutaneous CT-guided drainage is being used more frequently and is successful in a significant portion of patients but is best reserved for infected pseudocysts. Ruptured cysts and pancreatic ascites are treated by internal drainage. Mature, asymptomatic pseudocysts of more than 5 cm may be observed. The possibility of a cystic pancreatic neoplasm must be ruled out by biopsy.
Pancreatic Ascites This is seen following pancreatic ductal disruption or a leaking pseudocyst. Initial therapy is with total parenteral nutrition and somatostatin. Persistent disease is diagnosed with ERCP, and then appropriate surgical drainage, resection, or enteric anastomosis can be done.
Carcinoma of the Pancreas and Periampullary Carcinoma
Incidence Pancreatic carcinoma is the most common periampullary tumor; manifestations are similar for all. It is the fourth leading cause of cancer death in the United States. Average age at onset is 60 years; males are affected more than females. Etiologies are unclear; links with smoking and coffee consumption are unproved. Twenty-eight thousand deaths per year are seen in the United States. Fewer than 20 percent of carcinomas are resectable at diagnosis, and median survival, even after resection, is 20 months.
Pathology Adenocarcinoma arises from the ducts in 90 percent and acini in 10 percent. Often a major portion of the tumor is fibrous stroma with a zone of pancreatitis. About 75 percent arise from the head of the pancreas, causing biliary obstruction that may lead to an earlier diagnosis. The tumor may invade the portal vein or adjacent organs or metastasize to the liver or peritoneum. The lymph nodes are positive in 90 percent of patients. Ampullary and duodenal carcinomas may be diagnosed as pancreatic, cause jaundice early, and thus may be small at presentation. Cystadenoma and cystadenocarcinoma are slow growing, have a better prognosis, and should be treated aggressively.
Clinical Manifestations Painless jaundice alone is seen in 13 percent. About 75 percent of patients with carcinoma of the head of the pancreas present with obstructive jaundice, weight loss, and pain. Pain is dull, aching, midepigastric, and often radiates to the back. Back pain suggests retroperitoneal invasion. Cystadenocarcinoma may be asymptomatic. Anorexia, fatigue, and pruritus are common. Cholangitis is uncommon. Examination shows jaundice, palpable liver (5070 percent), and palpable gallbladder (30 percent, if nontender and jaundiced, diagnostic for pancreatic cancer; Courvoisier's sign). Recent onset diabetes is seen in 20 percent. With ampullary carcinoma, pain is less frequent, often colicky, and jaundice is intermittent. Body and tail tumors produce symptoms late and therefore are more advanced at diagnosis. Left supraclavicular node (Virchow's node), umbilical (Sister Mary Joseph's node), and pelvic floor (Blumer's shelf) metastases indicate incurable disease on examination.
Laboratory and Diagnostic Studies A laboratory test may reveal an elevated bilirubin level (which tends to be higher than with benign causes), an increased alkaline phosphatase level, and only mild transaminase elevation (contrast with hepatitis). Amylase elevations are uncommon. Screening tests would be useful, but none are available. CA 19-9 is a serum tumor marker that is 80 percent sensitive and 90 percent specific and sometimes useful. Many patients are evaluated with abdominal ultrasound first, but a spiral CT scan is most accurate overall. ERCP may be useful, particularly when no mass is found on CT scan. Fine-needle aspiration is indicated primarily when there is CT evidence of unresectability so that a tissue diagnosis can be confirmed without operation. (Negative aspiration does not rule out disease.) Percutaneous transhepatic cholangiography and stenting are an alternative to ERCP. Angiography may be indicated if CT has not adequately evaluated vascular anatomy. Magnetic resonance imaging (MRI) does not appear to be superior to CT. On occasion, MR cholangiography and MR angiography may be informative. Endoscopic ultrasound is highly sensitive in the detection of small masses in the pancreas and assessing tumor invasion of the mesenteric blood vessels. It is highly user dependent. Fine-needle aspiration is justified when the result will change the patient's treatment. It is not required when the patient's tumor is deemed resectable by appropriate radiographic evaluation. Laparoscopy can be used to stage for unresectability in a high-risk patient and obtain tissue for diagnosis when fine-needle aspiration is unsuccessful. It is not necessary routinely. Spiral CT provides the best overall initial assessment and may be the only test required. Chronic pancreatitis or focal acute pancreatitis occasionally present clinically as a possible pancreatic carcinoma. History, particularly with regard to risk factors for pancreatitis or prior episodes, is often telling. On occasion, an interval CT scan may demonstrate resolution of the apparent mass. It may be impossible to distinguish between chronic pancreatitis and cancer even at operation.
Treatment and Prognosis Rapidly correct nutrition, anemia, and volume status and assess renal function. Transhepatic biliary drainage usually is unwarranted. Pancreaticoduodenectomy is the only hope for cure of tumors in the head of the pancreas and is most useful in localized ampullary, duodenal, or distal bile duct carcinoma. It may be helpful in small, confined pancreatic head adenocarcinomas. Overall, only 20 percent of patients with pancreatic carcinoma are potentially resectable for cure. The rate is even lower with distal pancreatic lesions because of their late presentation.
Unresectable patients may benefit from palliative cholecystoor choledochoduodenostomy and gastrojejunostomy (duodenal obstruction in 30 percent). Intraoperative celiac plexus injection may alleviate pain. Patients with widely metastatic disease or poor-risk patients with locally unresectable disease are unlikely to benefit from surgery unless duodenal obstruction requires bypass. ERCP or transhepatic drainage may benefit the poor-risk patient. Combined radiation therapy and 5-fluorouracil (5-FU) may be of some value as an adjuvant and as palliation (Table 30-2).
TABLE 30-2 PROGNOSIS OF PERIAMPULLARY TUMORS
Pancreaticoduodenal Resection Classically, this included resection of the antrum of the stomach with the duodenum, distal bile duct, and head of the pancreas to the neck, just at the level of the mesenteric vessels. Currently, a pylorus-preserving resection is performed most often. Reconstruction is via choledocho-, pancreatico-, and gastrojejunostomy (or duodenojejunostomy if the pylorus was preserved), with the gastric anastomosis below the others to prevent marginal ulceration. Vagotomy is not necessary. Most patients lose weight, with some malabsorption postoperatively. Exocrine supplements may be necessary. Total pancreatectomy is of questionable, if any, advantage, has severe morbidity, and shows no documented increased survival.
These are of duct cell origin. Serous (microcystic) neoplasms are benign, whereas mucinous cystadenoma is premalignant and may evolve into cystadenocarcinoma. They often present with vague discomfort; jaundice is seen in less than 10 percent, along with anorexia and weight loss. Surgery is indicated for symptoms and any question of malignancy. All macrocystic lesions should be excised. It may be possible to distinguish mucinous from serous tumors by needle aspiration with cytology, mucin stains, and carcinoembryonic antigen (CEA) and CA 19-9 levels.
Islet Cell Tumors
The most common islet cell neoplasm, the insulinoma, is from the beta cell. Hyperinsulinemia causes severe hypoglycemia and leads to convulsions, depression, and coma. Glucose promptly reverses symptoms. The classic diagnostic criteria, Whipple's triad, include fasting hypoglycemia (< 50 mg/dL) during attacks, central nervous system changes and hypoglycemic symptoms brought on by fasting, and reversal of changes with glucose. Measurement will show insulin inappropriately high for ambient glycemia. About 80 percent are benign adenomas, and 15 percent are malignant. Moreover, 15 percent are multiple. Most are 13 cm in size. They may be seen in multiple endocrine neoplasia, Type I (MEN-I) syndrome (5 percent). Preoperative localization is difficult and may be aided by angiography, selective venous sampling, CT scan, or octreotide scintigraphy.
Treatment is surgical, except in advanced metastatic disease, where streptozotocin is helpful (destroys islets). Intraoperative management includes meticulous inspection of the entire gland with enucleation of the adenoma. Intraoperative ultrasound can be useful. Resection is performed for malignancy. Distal pancreatectomy may be of benefit when no lesion is located. In children, nesidioblastosis is diffuse islet hyperplasia, usually controlled with adrenocorticotropic hormone (ACTH), cortisone, and diet. If necessary, the surgical approach is a distal subtotal pancreatectomy.
Clinical Manifestations Original Zollinger-Ellison triad: fulminant, atypically located peptic ulcers; extreme gastric hypersecretion; and non-beta pancreatic islet cell tumor. Gastrinoma may start as a simple disease and end up with severe complications (e.g., perforation, obstruction, hemorrhage, intractability). It is unresponsive to standard medical and surgical therapy. Patients may have high-output diarrhea and steatorrhea.
Diagnosis High basal secretory rates are seen and a BAO/MAO ratio of more than 0.6, hypertrophic gastric folds, a fasting hypergastrinemia (> 200 pg/mL) or paradoxical rise in gastrin after secretin infusion, and a pancreatic mass on CT scan.
Pathology and Pathophysiology These are 2-mm to 10-cm non-beta pancreatic islet cell neoplasms. There are various reports of malignant potential, although it may be more than 90 percent. There may be a lesion in the duodenal wall. Lesions are slow growing and metastasize late; death is often the result of ulcer disease. Gastrinomas are seen in MEA-I syndrome (Wermer's: pituitary, parathyroid, pancreas), where lesions are multiple and benign.
Treatment Originally, patients with gastrinoma were treated with total gastrectomy; however, the use of histamine H2 antagonists and omeprazole with or without parietal cell vagotomy may control patients with unresectable disease. Efforts should be to completely excise lesions in patients without metastatic disease because of the high malignant potential. Lesions are often found in the gastrinoma triangle: (1) junction of the cystic and common ducts, (2) junction of the second and third parts of the duodenum, and (3) junction of the neck and body of the pancreas.
OTHER ISLET CELL TUMORS
VIPomas may produce diarrhea, pancreatic cholera, the WDHA syndrome (watery diarrhea, hypokalemia, and gastric achlorhydria). About 50 percent are malignant. Glucagonomas show cutaneous lesions (migratory necrolytic erythema), diabetes, glossitis, anemia, weight loss, depression, and venous thrombosis. About 75 percent are malignant. They are best treated by resection. Somatostatinomas manifest diabetes, diarrhea, steatorrhea, achlorhydria, gallstones, malabsorption, and abdominal pain. Symptoms are all attributable to somatostatin excess. They are most often treated with streptozocin, dacarbazine, and doxorubicin.
For a more detailed discussion, see Reber HA: Pancreas, chap. 30 in Principles of Surgery, 7th ed.
Copyright © 1998 McGraw-Hill
Seymour I. Schwartz
Principles of Surgery Companion Handbook