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Biliary stricture and duodenal obstruction have been increasingly recognized as complications of chronic pancreatitis. The anatomical relationship of the distal common bile duct and the duodenum with the head of the pancreas is the main factor for their involvement in chronic pancreatitis. In hospitalized patients with pancreatitis, the incidence of biliary stricture and duodenal obstruction is reported to be about 6% and 1.2%, respectively. For patients requiring an operation for chronic pancreatitis the incidence increases to 35% for biliary stricture and 12% for duodenal obstruction. Fibrosis around the distal common bile duct can cause stenosis with obstruction of bile flow. Clinically, the presentation of these patients ranges from being asymptomatic with elevated alkaline phosphatase or bilirubin, or both, to being septic with cholangitis. Jaundice, cholangitis, hyperbilirubinemia, and persistent elevation of serum alkaline phosphatase occur more frequently in patients with pancreatitis with a biliary stricture. A twofold elevation of alkaline phosphatase is a marker of possible common duct stenosis in patients with chronic pancreatitis. The incidence of both biliary cirrhosis and cholangitis in these patients is about 10%. ERCP reveals a characteristic long, smoothly tapered stricture of the intrapancreatic common bile duct. In duodenal obstruction, the factors that convert self-limiting edema to chronic fibrosis and stricture formation are unknown, but ischemia superimposed on inflammation may be the major cause. These patients present with a prolonged history of nausea and vomiting. Barium studies typically show a long constricting lesion of the duodenum, and endoscopy reveals reactive inflammatory changes in a narrowed duodenum. Operation is indicated in patients with common bile duct strictures secondary to chronic pancreatitis when there is evidence of cholangitis, biliary cirrhosis, common duct stones, progression of stricture, elevation of alkaline phophatase and/or bilirubin for over a month, and an inability to rule out cancer. The operation of choice is either choledochoduodenostomy or choledochojejunostomy. A cholecystoenterostomy is less favored because of its higher failure rate (23%). Endoscopic stenting plays a role in patients who are unfit for surgery, but it is not recommended as definitive therapy. For duodenal obstruction, failure to resolve the obstruction with 1-2 weeks of conservative therapy is an indication for bypass. The operation of choice is a gastrojejunostomy. Not uncommonly, combined obstruction of the pancreatic duct, common bile duct, and duodenum will develop. Combined drainage procedures or resection are used to manage these problems.

This study tests whether exposure to cigarette smoke alone or combined with cellophane wrapping of the pancreas increases the development of microscopic abnormalities in the pancreas of Syrian golden hamsters. Ninety hamsters were randomly divided into 4 groups. Thirty-five hamsters were exposed to 3 continuous hours of cigarette smoke daily for 3 months following celiotomy to cellophane wrap the gastric lobe of the pancreas (group 1). Thirty-two hamsters were not exposed to continuous cigarette smoke and had the wrap surgery alone (group 2). Twelve hamsters were exposed to cigarette smoke and had no surgery (group 3). Eleven hamsters had no exposure to cigarette smoke and no surgery (group 4). All of the hamsters were sacrificed after 3 months. The gastric (wrapped) and splenic (unwrapped) lobes of the pancreas were reviewed grossly and histologically. In all 4 groups, there were no gross abnormalities in either lobe of the pancreas. Histopathologic evaluation of the gastric lobes from group 1 showed that 13 of 35 lobes (37%) had pancreatitis (11 chronic, 1 acute, and 1 both). In group 2, 12 of 32 (38%) gastric lobes had pancreatitis (10 chronic, 2 acute). The incidence of pancreatitis in groups 1 and 2 was significantly higher than in groups 3 (0/12; p < 0.04) and 4 (0/11; p < 0.03), respectively. A significantly lower incidence of pancreatitis was found in the splenic lobes of all 4 groups when compared to gastric lobes in groups 1 and 2. Three of the 67 cellophane-wrapped glands had ductal hyperplasia. The effects of cellophane wrapping of the pancreas, both in the wrapped and unwrapped areas, induced changes of pancreatitis and hyperplasia that may be preneoplastic. Cigarette smoking, alone or combined with cellophane wrapping, did not cause these changes. Longer exposure to cigarette smoke may be needed to cause premalignant changes in the hamster pancreas., (Copyright 2002 S. Karger AG, Basel and IAP)

Background: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis., Methods: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained., Results: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV., Conclusions: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLN) and other extraintestinal organs is an important source of infection in acute pancreatitis (AP). Epidermal growth factor (EGF), a peptide hormone with trophic effects on gut mucosa, has decreased intestinal mucosal injury in septic rats and decreased burn-induced BT in mice. The purpose of this study is to examine whether EGF could affect BT in acute necrotizing pancreatitis. Forty-eight male Sprague-Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the biliopancreatic duct (1 ml/kg of body weight). Group III and Group IV underwent laparotomy without induction of acute pancreatitis. Group I rats received human recombinant EGF (100 micrograms/kg, subcutaneously twice daily) and Group II rats received a similar volume of 0.1% bovine serum albumin as a placebo postoperatively. Group III and Group IV received EGF and placebo, respectively. At 48 hr postoperatively, blood was drawn for culture and amylase determinations. Jejunum and ileum were obtained to measure mucosal protein content, mucosal thickness, villus height, and crypt depth. Specimens from MLN, spleen, liver, pancreas, and cecum were harvested for pathology and culture of gram positive (G+), gram negative (G-), and anaerobic bacteria. Ileal mucosal protein levels were increased significantly in Group I (1.96 +/- 0.14 mg/cm) compared to Group II (0.95 +/- 0.15 mg/cm intestinal segment) (P < 0.01). Jejunal and ileal mucosal thickness, villus height, and crypt depth in Group I were significantly increased when compared to Group II (P < 0.05). All 12 rats in Group II had BT to MLN compared to 58% (7 of 12 rats) in Group I (P < 0.05). Thirty-three percent (4 of 12 rats) had BT to distant sites such as pancreas, spleen, liver, and/or blood in Group I vs 83% (10 of 12 rats) in Group II (P < 0.05). EGF treatment minimizes intestinal damage, decreases BT to MLN and bacterial spread to distant sites, and may be beneficial in preventing septic complications in AP.

Background: The effect of granulocyte colony-stimulating factor (G-CSF) on the rate of secondary infections in acute pancreatitis was evaluated in a canine model. Infectious complications are the major determinant of morbidity and mortality in severe pancreatitis. Bacterial translocation has been shown to be a cause of these secondary infections. The relative immunosuppression found with pancreatitis may promote translocation and the spread of bacteria to the pancreas., Methods: Thirty-four mongrel dogs were studied. Pancreatitis was induced in 18 dogs; 9 were treated with 100 micrograms G-CSF/day and 9 were given only saline solution. Laparotomy alone was done in 16 dogs of which one half were given 100 micrograms G-CSF/day and one half were given saline solution. Daily blood counts and cultures were obtained. All dogs were killed on day 7, and the mesenteric lymph nodes, pancreas, liver, spleen, and peritoneal fluid were cultured and studied histologically., Results: G-CSF caused a significant and sustained increase in mature granulocytes in dogs given pancreatitis. No difference was found in the rate of translocation to mesenteric lymph nodes in dogs given G-CSF (n = 4) versus dogs given saline solution (n = 6). However, a significant decrease occurred in the spread of bacteria to distant sites in dogs given G-CSF (1 versus 15, p < 0.05)., Conclusions: Although G-CSF does not decrease the rate of translocation, it does decrease the rate of distant infection in severe acute pancreatitis.

Hyperparathyroidism is a rare cause of pancreatic inflammatory disease. Appropriate treatment of coexistent hyperparathyroidism and pancreatitis, especially when complicated by pseudocyst formation, is unsettled. We describe two patients with primary hyperparathyroidism who developed pancreatitis associated with multiple pseudocysts. The largest cyst in each patient was 9 and 5 cm, respectively. After correction of hyperparathyroidism and normalization of serum calcium levels by removal of a parathyroid adenoma, the pseudocysts resolved in both patients, as documented with computed tomography. We conclude that uncomplicated pancreatic pseudocysts in patients with primary hyperparathyroidism can be treated expectantly. Surgical correction of hyperparathyroidism and normalization of serum calcium levels should precede pancreatic intervention when possible, since pseudocyst resolution is likely and the risks of postoperative hypercalcemia are avoided.

To examine whether the gut is a source of infection in acute pancreatitis, bacterial translocation and alterations of intestinal microecology and morphology were studied in 16 dogs. Dogs were colonized with a strain of Escherichia coli (E. coli 6938K) bearing the plasmid pUC4K, which confers kanamycin resistance. In eight dogs (group I), pancreatitis was induced by sodium taurocholate/trypsin injection. Eight other dogs (group II) underwent laparotomy only. The pancreas, mesenteric lymph nodes, peritoneal fluid, liver, and spleen were harvested 7 days later for culturing and histologic analysis. Identification of E. coli 6938K was accomplished by plasmid DNA analysis. Group I dogs had severe pancreatitis and ischemic changes in small bowel mucosa. Group II dogs had no changes. Translocation to the pancreas occurred in five dogs and to mesenteric lymph nodes in six dogs with pancreatitis. No translocation occurred in group II dogs (p < 0.05). In addition to E. coli 6938K, other gram-negative kanamycin-resistant species were isolated, including E. coli (other than 6938K) and Enterobacter cloacae. Enteric origin of these strains was confirmed by antibiography and plasmid DNA analysis. No overgrowth of cecal gram-negative bacteria was found. This study suggests that the gut is a primary source of infection in pancreatitis and that ischemic damage of intestinal mucosa may promote bacterial translocation.

Chronic pancreatitis is primarily a medical disease but surgery is indicated to treat complications, rule out malignancy, and ameliorate intractable pain. The ideal operation for chronic pancreatitis would relieve this pain while preserving exocrine and endocrine function. No one procedure achieves these goals in all patients so surgeons must tailor their operations to individual patient needs. In patients with a dilated pancreatic duct, complete ductal decompression with a lateral pancreaticojejunostomy is usually indicated. Pancreatic resection is useful in patients with localized disease, nondialated ducts, or in whom cancer cannot be ruled out. More rigorous documentation of the type and outcome of therapeutic interventions for chronic pancreatitis and the patient populations to whom they are applied is needed. Subjective measurements must be replaced by objective findings so that the true benefits of these procedures can be better assessed and compared.

Chronic pancreatitis should be treated medically until a surgically correctable complication develops. Incapacitating abdominal pain refractory to medical therapy is the most common indication for operation. Preoperative evaluation of chronic pancreatitis should include a dynamic computed tomography scan to evaluate the pancreas and pancreatic duct. If the pancreatic duct is not seen or is not dilated on computed tomography, an endoscopic retrograde cholangiopancreatogram should be performed. If the pancreatic duct is dilated more than 5 mm, a side-to-side pancreaticojejunostomy should be performed in symptomatic patients. If the pancreatic duct is not dilated and all other causes of pain have been ruled out, a pylorus-preserving Whipple resection or duodenum-preserving pancreatic head resection should be performed. Distal pancreatectomy is reserved for disease isolated to the tail. Total pancreatectomy is used only as a salvage procedure and, whenever possible, should be accompanied by autotransplantation of the residual gland or islet cells.

Background: Infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have been proposed as distinct clinical entities in terms of treatment and outcome. To evaluate this classification, we reviewed the clinical course and bacteriologic findings of pancreatic infections., Methods: Of 1299 patients with pancreatitis or a related complication admitted over a 7-year period, 64 (4.9%) with culture-documented secondary pancreatic infections were reviewed with regard to cause, clinical course, bacteriologic findings, and outcomes., Results: Group I consisted of 23 patients with infected pseudocysts; group II, 20 patients with pancreatic abscesses; and group III, 21 patients with infected pancreatic necrosis. The causes were alcohol in 36%, biliary tract disease in 30%, and postoperative in 16%, with no significant difference between groups. Patients in group I had abdominal pain or a mass without accompanying signs of sepsis, whereas patients in groups II and III had sepsis. In group I, 15 patients were treated with internal drainage, four with percutaneous drainage, and four with external drainage. In group II, three had percutaneous drainage, 15 operative drainage, and two open packing. In group III, 19 patients had operative drainage and two had open packing. Morbidity occurred in 26% of patients in group I, 40% in group II, and 90% in group III (p less than 0.001). Mortality rates were 9% in group I, 25% in group II, and 48% in group III (p less than 0.01). Enteric organisms were present in 66% of isolates, with no difference between groups, suggesting a common mode of infection., Conclusions: Despite similar bacteriologic findings, infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have significantly different presentations, clinical courses, and outcomes, confirming that they are distinct entities. This distinction is important when therapeutic outcomes are compared.

To determine whether a synthetic somatostatin analogue, octreotide, and a cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes after the induction of pancreatitis, Group 1 received a subcutaneous injection of octreotide (200 micrograms/kg), Group 2 received an equal volume of the octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60 micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier. Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase were obtained before laparotomy, at bile injection, and at hourly intervals. The pancreas was removed after 8 hours for gross evaluation, measurement of water content, and histologic examination. A significant decrease in cardiac index and a significant increase in serum amylase and pancreatic edema occurred in all four groups 8 hours after the induction of pancreatitis (P less than 0.05), but there was no statistical difference between any group. Likewise, there was no difference in gross or histologic changes in the pancreas of any group. The somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L-364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in dogs.

The most severe form of acute pancreatitis is characterized by necrosis of the pancreatic parenchyma and/or peripancreatic tissue. Secondary infection of this necrotic tissue carries a high mortality because there is little limitation to the spread of this infection in the retroperitoneum. Improvements in the management of infected pancreatic necrosis have been achieved by techniques that allow complete removal of the infected debris. Problems still remain in identifying the extent of necrosis and removing all of it. Intraoperative endoscopy can be used to evaluate tracking of the infected process to other areas of the retroperitoneum. Direct visualization of the path that the necrotizing process has taken to areas of the retroperitoneum that are difficult to reach allows the dissection to be limited if there is no necrosis or expansion to remove all necrotic material completely. The endoscope can also be used to remove necrotic material either by irrigation or by direct debridement. The methodology of this technique is described.

Vascular mechanisms play an important but controversial role in the pathogenesis of acute pancreatitis. In experimental animals, injection of wax, powder, air, mercury, and microspheres into the pancreatic artery causes pancreatitis by end artery occlusion with resulting cellular infarction. Larger microspheres do not cause pancreatitis because collateral blood flow is preserved. Clinical evidence, such as microthrombi and atheromatous emboli in the pancreatic artery of patients with pancreatitis, supports pancreatic infarction as an etiologic agent. Experimental and clinical studies have suggested that pancreatic ischemia may also cause pancreatitis, but these studies have not been conclusive. We have compared five hours of total occlusion of the pancreaticoduodenal artery along with four hours of reperfusion to bile injection into the pancreatic duct as causes of pancreatitis. Bile injection caused a significant increase in serum amylase, activation of trypsin in pancreatic exudate, and histologic evidence of necrotizing pancreatitis. Pancreatic blood flow decreased as pancreatitis developed. Ischemia for five hours did not cause a significant increase in serum amylase or activation of trypsin in pancreatic exudate. Only edema was seen histologically, but there was no necrosis. Pancreatic blood flow increased with reperfusion. We believe ischemia aggravates, but does not initiate pancreatitis. Ischemia does not induce inflammation and necrosis in the pancreas, although infarction does.

Pancreatic duct drainage is an effective method of dealing with many of the surgical complications of chronic pancreatitis without sacrificing pancreatic endocrine or exocrine function. Between 65 and 90% of patients with intractable pain of chronic pancreatitis and a dilated pancreatic duct will have substantial pain relief with complete ductal drainage by a lateral pancreaticojejunostomy. The mortality of this procedure ranges from 0 to 5%. In spite of operation, late mortality of this disease remains high with 1/3 to 1/2 of patients dying within 10 years. Fixed biliary tract obstruction and upper gastrointestinal obstruction can also complicate chronic pancreatitis. We have combined drainage of the common bile duct and stomach with pancreaticojejunostomy to deal with these problems and have found no increase in morbidity or mortality. Pseudocysts occur more frequently in patients with chronic pancreatitis. We have also combined pseudocyst drainage with lateral pancreaticojejunostomy in 26 patients having both pseudocysts and chronic pancreatitis. These patients achieve the same degree of pain relief noted in patients undergoing lateral pancreaticojejunostomy alone without any increase in morbidity or mortality. Drainage procedures are safe and effective and are our preferred method of dealing with obstructive complications of chronic pancreatitis.

Chronic alcoholism is the etiologic factor initiating most instances of chronic pancreatitis and its complications in the United States of America. The goal of operative intervention is to relieve incapacitating abdominal and back pain, while preserving as much endocrine and exocrine function as possible. Ultrasound and computed tomography scans are helpful for the identification of gross anatomical changes in the pancreas, but endoscopic retrograde cholangiopancreatography is critical for the precise delineation of pancreatic ductal anatomy. In patients who exhibit dilation of the pancreatic duct secondary to single or multiple sites of obstruction, pancreatic ductal drainage will provide complete or significant relief of pain in greater than 80% of patients. Side-to-side pancreaticojejunostomy has evolved as the operation which permits the widest drainage of the entire pancreatic ductal system. Although, initially, it was hoped that pancreatic exocrine and endocrine function would improve or stabilize after pancreatic ductal drainage, follow-up studies show that the destructive process in the pancreatic islets and acinar cells initiated by chronic alcoholism continues during the years after operation with an increasing incidence of diabetes and steatorrhea. Late mortality is primarily related to continued alcoholism and death secondary to alcohol-(and-smoking-) associated diseases. Correction of coexistent complications secondary to chronic pancreatitis including pseudocyst and biliary and/or duodenal obstruction should be considered at the time of pancreatic ductal drainage.

In 55 patients undergoing pancreaticojejunostomy for intractable abdominal pain, common bile duct obstruction occurred in 29% (16/55) and duodenal obstruction occurred in 15% (8/55). Serum alkaline phosphatase and total and direct serum bilirubin levels were significantly higher in patients with intrapancreatic common bile duct stenosis. Transient upper gastrointestinal (UGI) tract obstruction was common with chronic pancreatitis; however, if symptoms persisted beyond 2 weeks, fixed duodenal obstruction was likely. Endoscopic retrograde cholangiopancreatography and UGI roentgenograms and endoscopy were useful in confirming mechanical obstruction to the biliary and UGI tracts, respectively. There was no difference in operative mortality and morbidity from combined drainage procedures compared with pancreaticojejunostomy alone. The biliary and UGI tracts should be investigated in symptomatic patients both before and after pancreaticojejunostomy. Combined drainage of the pancreatic duct and UGI and biliary tract is safe and effective treatment for obstructing complications of chronic pancreatitis.

Records from 87 consecutive patients undergoing lateral pancreaticojejunostomy (LPJ) for chronic pancreatitis were reviewed to determine the incidence of pseudocyst and the safety of combined pancreatic duct and pseudocyst drainage. Twelve patients had undergone previous pancreatic pseudocyst drainage; four of them also had pancreatic pseudocysts present at the time of LPJ. In addition, 22 patients had pseudocysts identified preoperatively and/or confirmed at operation. The overall incidence of pseudocyst was 39%. Twenty-six patients (group 1) underwent pancreaticojejunostomy combined with pseudocyst drainage. Sixty-one patients (group 2) underwent pancreaticojejunostomy only. Operative morbidity and mortality results (19% and 8%, respectively, in group 1; 18% and 2%, respectively, in group 2) were similar. Patient outcome was also similar in the two groups (81% and 84% of patients obtained pain relief in groups 1 and 2, respectively). There were no pseudocyst recurrences in either group. Thus, there is a high incidence (39%) of pancreatic pseudocyst in patients undergoing LPJ for chronic pancreatitis. Combined drainage of the pancreatic duct and pseudocyst is safe and effective.

During a ten-year period, 16 patients with gastric outlet and duodenal obstruction due to inflammatory pancreatic disease were seen. The cause of obstruction was chronic pancreatitis in ten patients, pseudocysts with associated pancreatitis in five patients, and pancreatic abscess in one patient. All patients had nausea and vomiting, 14 had abdominal pain, and five had weight loss greater than 4.5 kg. Diagnosis was made by plain abdominal film in one case, upper gastrointestinal tract roentgenographic series in 15 cases, and endoscopy in 11 cases. Mobilization of the duodenum relieved the obstruction in two patients. Fixed obstruction remained in 14 patients. This was relieved by gastrojejunostomy in 12 patients. Gastrojejunostomy was combined with drainage of a pseudocyst in three patients, a dilated pancreatic duct in three patients, and a dilated common bile duct in four patients. Obstruction was relieved by pseudocyst drainage in two patients. Associated common duct and pancreatic duct obstruction must be identified preoperatively.

Although the development of islet cell autotransplantation has focused attention on extended resections of the pancreas, drainage of a dilated pancreatic duct remains an effective means of relieving intractable pain of chronic pancreatitis. Between 1954 and 1980, 98 men and two women with chronic pancreatitis were treated for pain with ductal drainage. All patients had a history of chronic alcoholism. Pancreatic calculi were found in 68 patients. Operative procedures include: seven caudal pancreaticojejunostomies, 42 longitudinal pancreaticojejunostomies, and 54 side-to-side pancreaticojejunostomies. Two caudal pancreaticojejunostomies were converted to longitudinal pancreaticojejunostomies, and one longitudinal pancreaticojejunostomy required revision. The operative mortality rate was 4%. Follow-up studies, lasting up to 24 years, were conducted for all but seven patients. Eighty per cent of these patients have had substantial improvement or complete resolution of their pain. Diabetes, as evidence by an elevated fasting blood sugar level, was present prior to operation in 30% of the patients, and developed after operation in 14%. Only nine of 21 insulin-dependent diabetics in this series did not require insulin prior to pancreaticojejunostomy. Pancreatic enzyme replacement was needed for control of steatorrhea in 18 patients. Four patients with continued pain underwent total or near total pancreatectomies. Three of these patients died of uncontrolled diabetes. Only one patient with a drainage procedure alone has died of uncontrolled diabetes. In patients with dilated pancreatic ducts, pancreaticojejunostomy is a safe, reliable means of providing pain relief, with minimal loss of endocrine and exocrine function.

Between 1954 and 1975, 80 pancreaticojejunostomies were performed on 77 patients for intractable pain of chronic pancreatitis. All patients had a history of chronic alcoholism. Drainage operations done primarily for pseudocysts were excluded. Operative procedures included seven caudal pancreaticojejunostomies, 42 longitudinal pancreaticojejunostomies with splenectomy and implantation of the pancreas into the jejunum, and 31 side-to-side pancreaticojejunostomies. Eighty-one percent of the patients noted substantial improvement or complete resolution of their abdominal pain on follow-up that ranged up to 21 years. The operative mortality was 5%. Thirty-two patients died during the period of the follow-up. Continued alcohol abuse, carcinoma, and cardiovascular disease were the leading causes of mortality. Data from this review confirm the effectiveness of pancreaticojejunostomy in relieving the pain of chronic relapsing pancreatitis.

Fifty-one patients with chronic pancreatitis manifested distal common duct obstruction from fibrosis of pancreatitis. The cause of the pancreatitis was alcohol in most patients. An elevated serum alkaline phosphatase level was the most frequent abnormal laboratory finding. The serum bilirubin level elevation was never progressive; a rising and falling pattern was most often encountered. Percutaneous transhepatic cholangiography and endoscopic retrograde cholangiopancreatography are the most useful diagnostic tests. An operation was performed on 47 patients and included choledochoduodenostomy in 16 patients, choledochojejunostomy in 19 patients, cholecystenteric anastomosis in seven patients, common bile duct exploration with T-tube drainage in three patients, and sphincteroplasty in two patients. Abdominal pain was lessened after operation in 40 of 44 patients who survived surgery. Two patients with T-tube drainage and two with cholecystenteric anastomosis required conversion operations to choledochoduodenostomies. Identification of associated pancreatic duct obstruction and dilatation, pseudocysts, and duodenal obstruction is important.

Recurrent pain after a drainage procedure for chronic pancreatitis is considered an indication for pancreatectomy. To evaluate whether redrainage might be a better alternative, 14 patients who underwent redrainage after a failed pancreaticojejunostomy were reviewed. Patients with previous pseudocyst drainage were excluded. Initial operations included five caudal, three longitudinal, and six side-to-side pancreaticojejunostomies. Nine patients treated since 1974 had ERCP, which showed obstructed segments of pancreatic duct in the head of the gland. Two caudal pancreaticojejunostomies and one longitudinal pancreaticojejunostomy were revised to longitudinal pancreaticojejunostomies. The other 11 were revised to side-to-side pancreaticojejunostomies. Operative findings confirmed undrained segments of the pancreatic duct in the pancreatic head. Postoperatively, one patient died from hemorrhage and four patients had complications. At most recent follow-up from 6 months to 20 years postoperatively, three patients were pain free and six had substantial relief from pain (71 percent). Of eight patients who were not diabetic before redrainage, diabetes developed in only two. Only one of seven patients without pancreatic exocrine insufficiency required pancreatic enzymes after redrainage. Patients with recurrent pain after pancreaticojejunostomy should undergo ERCP. If segments of the pancreatic duct are obstructed, redrainage can provide satisfactory pain relief with a minimal loss of endocrine and exocrine function. This problem is best avoided by initial complete drainage of the major and minor pancreatic ducts.

The long-held tenet that a cause and effect relation exists between primary hyperparathyroidism and pancreatitis has recently been questioned. To clarify this association, records of 1475 patients seen with pancreatitis during a 10-year period were reviewed. Five patients (0.4%) were identified with primary hyperparathyroidism. The four men and one woman ranged in age from 31 to 57 years. Four had recurrent pancreatitis over a 2-10 yr period before hyperparathyroidism was diagnosed. One patient had hypercalcemia noted 1 year prior to developing pancreatitis. Four patients had associated potential causes of pancreatitis including alcohol abuse, gallstones, and hypotension. Pancreatitis was severe in each patient. Two patients had more than four admissions for acute pancreatitis, one patient underwent pseudocyst drainage and distal pancreatectomy for chronic pancreatitis, one patient underwent pancreaticojejunostomy for chronic pancreatitis, and one patient died from hemorrhagic pancreatitis. Four patients have undergone successful parathyroidectomy and have had no further attacks of pancreatitis on follow-up ranging from 1 to 4 years. Hyperparathyroidism is rarely associated with pancreatitis, but when this combination occurs, the pancreatitis is likely to be severe. Despite its rarity, a cause and effect relationship is still suggested by the fact that parathyroidectomy seems to prevent recurrence of pancreatitis.

Fibrosis of chronic pancreatitis can cause obstructive jaundice by compressing the intrapancreatic portion of the common bile duct. The frequency and clinical manifestations of common bile duct stricture from symptomatic chronic pancreatitis have been evaluated in 26 patients undergoing lateral pancreaticojejunostomy for intractable pain between 1974 and 1980. Four patients (15%) had a stricture with partial obstruction of the common duct in addition to pancreatic duct obstruction. Three of the four strictures were identified prior to operation by ERCP. The fourth developed biliary obstruction six months after pancreaticojejunostomy. Slight elevation of alkaline phosphatase was common and occurred in 12 of 22 patients with chronic pancreatitis without biliary obstruction. Alkaline phosphatase was elevated greater than four times normal in three of the four patients with a biliary stricture. Elevation of total and direct serum bilirubin occurred only in patients with stricture of the distal common duct. A waxing and waning picture of jaundice was seen in these four patients. When a fixed smooth stricture of the common duct is demonstrated in a patient with symptomatic chronic pancreatitis, drainage of the biliary tree should be combined with pancreatic duct drainage in order to prevent cholangitis, biliary cirrhosis, diagnostic confusion with pancreatic carcinoma, and persistence of pain.

Serum calcium changes in severe pancreatitis were studied in 23 dogs. Twelve dogs underwent duodenotomy and served as controls. Pancreatitis was induced in the other 11 by autologous bile injection (1 ml/kg) into the pancreatic duct. Serum amylase, total calcium, ionized calcium, albumin, magnesium, chloride, phosphorous, parathyroid hormone (PTH), and calcitonin were measured at 0, 1/2, 1, 3, 6, 24, 48, and 72 hours after duodenotomy or bile injection. Serum amylase levels became significantly elevated in all dogs with pancreatitis at 30 minutes (p less than 0.01) and remained so throughout the entire experiment. Total calcium levels dropped significantly 30 minutes after pancreatitis was induced from 10.0 +/- 0.3 mg/dl compared with 8.8 +/- 0.4 mg/dl in control dogs (p less than 0.05) and remained statistically lower for as long as 1 hour. Ionized calcium levels were significantly lower than were those of control dogs at 1/2, 1, 3, and 6 hours (p less than 0.05). Serum magnesium and chloride levels showed no significant changes between both groups. The only significant difference in phosphorus values was at 6 hours when they were higher in dogs with pancreatitis than in controls (6.2 +/- 0.3 mg/dl versus 4.8 +/- 0.4 mg/dl; p less than 0.05). Serum albumin levels remained unchanged throughout the study except for 48 hours when they were significantly lower in animals with pancreatitis (p less than 0.02). PTH levels were significantly greater in dogs with pancreatitis than in controls at 1, 3, 6, and 24 hours (p less than 0.05). There was no significant difference in calcitonin levels between both groups. Ionized calcium is a more reliable indicator of calcium fluxes in acute experimental pancreatitis since it remains depressed longer than total serum calcium. The time course of PTH elevation indicates a reaction to hypocalcemia, and failure of PTH secretion is not the cause of hypocalcemia in pancreatitis. This study does not support elevation of calcitonin as a cause of hypocalcemia in acute pancreatitis.

Coagulation abnormalities induced by pancreatitis were studied in 36 dogs. The 12 dogs in group I underwent a duodenotomy alone. The six dogs in groups II, III, IV, and V had pancreatitis induced by bile injection (1 cc/kg) into the pancreatic duct. Twenty minutes after bile-induced pancreatitis, group III was given 1.0 mg/kg aprotinin (trasylol), group IV was given 10 mg/kg S-2441, a new synthetic protease inhibitor, and group V was given 0.5 mg/kg alpha 2-antitrypsin by intravenous infusion over 10 min. Blood was drawn for amylase, protime (PT), partial thromboplastin time (PTT), fibrinogen, and platelets, in addition to markers of hypercoagulation, fibrinopeptide A, and antithrombin III, and markers of fibrinolysis, B beta 15-42 immunoreactive peptide (IP), and alpha 2-antiplasmin at baseline, 1/2, 1, 3, 6, 24, 48, and 72 hr after duodenotomy or bile injection. There was no significant difference in PT, platelets, antithrombin III, and fibrinopeptide A among the five groups. With the induction of pancreatitis (group II), serum amylase was significantly elevated but fibrinogen only became elevated at 24 hr and PTT at 48 hr. The increase in B beta 15-42 IP seen 30 min after induction of pancreatitis and the decrease in alpha 2-antiplasmin were blunted by aprotinin, alpha 1-antitrypsin, and S-2441, but inhibition of the rise in amylase and B beta 15-42 IP only reached significance with S-2441 (P less than 0.05). Pancreatitis-induced fibrinolysis was inhibited by S-2441 suggesting that synthetic protease inhibitors may play a therapeutic role in pancreatitis.

Clinical and experimental evidence suggests that myocardial depression occurs during severe pancreatitis, but this evidence is derived from techniques that are not optimal for assessing myocardial contractility (e.g., rate of rise in ventricular pressure [dP/dt]). The slope of the left ventricular (LV) and systolic pressure dimension relationship (Ees), a better indicator of myocardial function, has not been measured in pancreatitis. Ten mongrel dogs underwent surgical instrumentation to monitor systemic arterial and LV pressure, cardiac output, LV dP/dt, and anterior LV wall thickness. End of systole was defined by the peak negative dP/dt. The end-systolic points used to calculate Ees were obtained by aortic and vena caval occlusion. After surgical recovery, pancreatitis was induced via cannulation of the pancreatic duct and injection of autologous bile (1 ml/kg) at 200 mm Hg perfusion pressure. All measurements were taken during a control period and daily after pancreatitis was induced. Pancreatitis was confirmed by a significant increase in serum amylase throughout the study and by autopsy finding of hemorrhagic necrosis. Ees was increased throughout the experimental protocol (1 to 7 days) (p less than 0.05). Myocardial performance as assessed by Ees was significantly increased and myocardial depression did not occur in untreated, conscious dogs with severe pancreatitis. Peak positive LV dP/dt was a poor index of contractility during pancreatitis since it decreased while myocardial contractility was increased. Cardiac depression in pancreatitis noted in other reports was likely due to decreased preload and not to intrinsic cardiac dysfunction.