Obesity and surgical complications of pancreaticoduodenectomy: An observation study utilizing ACS NSQIP.

BACKGROUND: An estimated 38% of US adults are obese. Obesity is associated with socioeconomic disparities and increased rates of comorbidities, and is a known risk factor for development of pancreatic cancer. As a fourth leading cause of death in the United States, pancreatic cancer is commonly treated with a pancreatico-duodenectomy (PD), or Whipple procedure. Data regarding the effects of obesity on post-operative complication rate primarily comes from specialized centers, however the results are mixed. Our aim is to elucidate the effects that obesity has on outcomes after PD for pancreatic head cancer using a national prospectively maintained clinical database. METHOD: The 2010-2015 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) Participant Use Files (PUF) were used as the data source. We identified cases in which PD was performed (CPT code 48150) in the setting of a postoperative diagnosis of pancreatic cancer (ICD9 code 157.0). We excluded cases that had emergency admissions, BMI ≤18.5 kg/m2, intraoperative wound classification of III or IV, and disseminated cancer. Cases with missing BMI, preoperative albumin, operative time, LOS data were also excluded. Multiple imputation for missing sex, race, functional status, and ASA classification using chained equations was performed.16 Patients that had BMI ≥30 kg/m2 were considered obese, and patients with BMI <30 kg/m2 were used as control. RESULTS: 3484 patients underwent pancreaticoduodenectomy for pancreatic cancer. 860 patients were identified as obese. Propensity score analysis was performed matching age, sex, race, functional status, presence of dyspnea, diabetes, hypertension, acute renal failure, dialysis dependence, ascites, steroid use, bleeding disorders, history of chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), weight loss, American Society of Anesthesiologists (ASA) classification, and preoperative albumin levels. After matching, obese patients had higher risk of 30-day postoperative complications compared to control, including organ space wound infections (OR 1.38, 95% CI 1.07-1.79, p = 0.0128), returning to the operating room (OR 1.39, 95% CI 1.01-1.91, p = 0.0461), failure to extubate for greater than 48 h (OR 1.60, 95% CI 1.09-2.34, p = 0.0153), death (OR 1.68, 95% CI 1.01-2.78, p = 0.0453), septic shock (OR 2.22, 95% CI 1.46-3.38, p = 0.0002), pulmonary embolism (OR 2.42, 95% CI 1.07-5.45, p = 0.0332), renal insufficiency (OR 2.67, 95% CI 1.33-5.38, p = 0.0058). Sensitivity analysis yielded similar results with the exception of risk for return to the operating room, death, and pulmonary embolism, P > .05. CONCLUSION: In this large observational study using a national clinical database, obese patients undergoing PD for head of pancreas cancer had increased risk of postoperative complications and mortality in comparison to controls.

Analysis of surgical success in preventing recurrent acute exacerbations in chronic pancreatitis.

OBJECTIVE: To determine whether surgical intervention prevents recurrent acute exacerbations in chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: The primary goal of surgical intervention in the treatment of CP has been relief of chronic unrelenting abdominal pain. A subset of patients with CP have intermittent acute exacerbations, often with increasing frequency and often unrelated to ongoing ethanol abuse. Little data exist regarding the effectiveness of surgery to prevent acute attacks. METHODS: From 1985 to 1999, all patients identified with a diagnosis of CP were recruited to participate in an ongoing program of serial clinic visits and functional and clinical evaluations. Patients were offered surgery using standard criteria. Data were gathered regarding ethanol abuse, pain, narcotic use, and recurrent acute exacerbations requiring hospital admission before and after surgery. Patients were broadly categorized as having severe unrelenting pain alone (group 1), severe pain with intermittent acute exacerbations (group 2), and intermittent acute exacerbations only (group 3). RESULTS: Two hundred fifty-nine patients were recruited. One hundred eighty-five patients underwent 199 surgical procedures (124 modified Puestow procedure [LPJ], 29 distal pancreatectomies [DP], and 46 pancreatic head resections [PHR; 14 performed after failure of LPJ]). There were no deaths. The complication rate was 4% for LPJ, 15% for DP, and 27% for PHR. Ethanol abuse was causative in 238 patients (92%). Mean follow-up was 81 months. There were 104 patients in group 1 (86 who underwent surgery), 71 patients in group 2 (64 who underwent surgery), and 84 in group 3 (49 who underwent surgery). No patient without surgery had spontaneous resolution of symptoms. Postoperative pain relief (freedom from narcotic analgesics) was achieved in 153 of 185 patients (83%) overall: 106 of 124 (86%) for LPJ, 19 of 29 (67%) for DP, and 42 of 46 (91%) for PHR. The mean rate of acute exacerbations was 6.3 +/- 2.1 events per year before surgery in group 2 and 7.8 +/- 1.8 events per year in group 3. After surgery, no acute exacerbations occurred in 42 of 64 (66%) group 2 patients and in 40 of 49 (82%) group 3 patients. The mean number of episodes of acute exacerbation after surgery was 1.6 +/- 2.3 events in group 2 and 1.1 +/- 1.9 events in group 3. Only four patients in group 2 and one patient in group 3 had an equal or increased frequency of attacks after surgery. Preventing attacks was most effective with LPJ (58/64, 91%) and least effective for DP (6/18, 33%). CONCLUSIONS: Surgical intervention prevents recurrent acute exacerbations. The overall frequency of events was reduced in nearly all patients. Therefore, surgical intervention is indicated in patients with CP whose disease is characterized by recurrent acute exacerbations.

Percutaneous radiologic drainage of pancreatic abscesses.

OBJECTIVE: The purpose of our study was to review and report the patient selection, techniques, and results of percutaneous drainage of pancreatic abscesses by retrospective review. MATERIALS AND METHODS: Fifty-nine patients (46 men and 13 women) with a mean age of 44 years old had 80 pancreatic abscesses that were drained percutaneously under radiologic guidance (CT, n = 77; sonography, n = 2; and fluoroscopy, n = 1). Abscesses had a wide spectrum of causes, with alcoholic pancreatitis being most common, trauma second most common, and gallstones third. Ten patients had undergone surgery for pancreatic necrosis or abscess. Patients with pancreatic pseudocysts, necrosis, or acute fluid collections were excluded from this study. RESULTS: Of the 59 patients, 51 (86%) were cured with percutaneous drainage and antibiotic therapy. Of the patients who were not cured with percutaneous drainage, seven required surgery and one underwent repeat percutaneous drainage. In the 59 patients, complications included non-life-threatening bleeding in three patients. Ten of 59 patients (17%) had fistulas that spontaneously formed into the gastrointestinal tract. The duration of catheterization ranged from 4 to 119 days, with a mean duration of 33 days. The rate of mortality at 30 days after completion of percutaneous drainage was 8% (5 of 59). CONCLUSION: Percutaneous drainage was an effective therapy for this defined group of patients with pancreatic abscesses. Factors leading to the relatively high success rate described in this study likely included selection of patients; catheters of adequate size, number, and location; careful follow-up with appropriate catheter manipulations; and an integrated, cooperative approach whereby surgeons were willing to permit drainage to effect its benefits, rather than operating prematurely.

Long-term follow-up after bilioenteric anastomosis for benign bile duct stricture.

OBJECTIVE: The authors provide a prospective evaluation of long-term results after bilioenteric anastomoses for benign biliary stricture. SUMMARY BACKGROUND DATA: With the advent of laparoscopic techniques, the frequency of bile duct injury after operation has increased. Reports on the operative management of these injuries have not provided long-term follow-up. Over a similar period, reports of both endoscopic and invasive radiographic methods as primary treatment for bile duct stricture have compared success rates to antiquated surgical reports. METHODS: A protocol whereby preoperative radiographic (e.g., cholangiogram, computed tomographic scan, ultrasound), biochemical (e.g., alkaline phosphatase, and total bilirubin), and clinical evaluation was combined with ongoing postoperative evaluation and follow-up at approximately 6-month intervals. A total of 111 patients were evaluated from 1985 to 1995. Patients were categorized in three groups: 1) those with postoperative injuries during open and laparoscopic gallbladder surgery (31 patients), 2) those undergoing operation for pain associated with chronic pancreatitis who have distal common bile duct stenoses (64 patients), and 3) those with nonchronic pancreatitis-associated benign bile duct strictures (16 patients). RESULTS: Mean follow-up was 60 months. Overall preoperative alkaline phosphatase was 640 units/L with a range of 280 to 1860 units/L. All patients had abnormally elevated alkaline phosphatase. Only 3 of 111 patients have had mild persistent elevation after operation. Clinical jaundice, present in 49 of 111 patients, was resolved uniformly by operative decompression. Total bilirubin was elevated abnormally in 56 of 111 patients and also was uniformly corrected by operation. CONCLUSIONS: These data support the careful combined use of endoscopy, invasive radiology, and surgery in the management of benign strictures of the biliary tree. These data further suggest a success rate for surgical management that, over long-term follow-up, appears to exceed that found using alternative measures. Alternative methods should measure their success rates against success rates currently achieved by operative management.

Decreased plasma levels of cholecystokinin in healthy males after chronic ingestion of a heat-treated soya product.

Administration of raw soya containing a trypsin inhibitor stimulated excessive release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116, 1067). More postprandial CCK release in healthy humans was observed after ingestion of a single dose of raw soya than heat-treated soya (Calam et al. (1989) Br. J. Nutr., 58, 175). The effect of chronic ingestion of a heat-treated soya product on postprandial CCK release was investigated in six healthy adult males after ingestion of a 36-oz. portion of soymilk daily for 1 month and at 2-3 months after termination of soymilk ingestion. Subjects fasted for 15 h, ingested Lipomul (1.5 g/kg) and provided blood at timed intervals for CCK analysis. The results show that 1-month ingestion of soymilk decreased the magnitude of Lipomul-induced postprandial CCK release in plasma of all six subjects by 5-60% (P < 0.05) compared to those obtained at 2-3 months after the withdrawal from soymilk ingestion. Plasma pancreatic polypeptide (PP) levels were similarly decreased in five of the six subjects by 19-67% (P = 0.03) in line with the regulation of PP by CCK. Thus, prolonged exposure of humans to a heat-treated soya inhibited slightly meal-induced CCK release in contrast to that found in rats after raw soya diets.

Gastrinomas demonstrate amplification of the HER-2/neu proto-oncogene.

OBJECTIVE: This study determined whether genomic amplification of HER-2/neu or mutations of the p53 and ras genes were present in gastrinomas. SUMMARY BACKGROUND DATA: Amplification of HER-2/neu, a proto-oncogene related to the epidermal growth factor receptor, and mutation of the ras proto-oncogene and p53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers. Little is known about possible molecular alterations in gastrinomas, tumors that may be particularly virulent because of gastrin overproduction, resulting in the severe ulcer diathesis, the Zollinger-Ellison syndrome. METHODS: The differential polymerase chain reaction (PCR) procedure was used to detect amplification of the HER-2/neu gene in DNA samples from the novel human gastrinoma cell line (PT) and from paraffin-embedded samples of gastrinomas. Sequencing techniques were used to determine whether mutations of the p53 or ras (Ha-ras, N-ras, Ki-ras) genes were present. RESULTS: Amplification (> twofold) occurred in all gastrinoma tumor samples. Compared with normal pancreas or ileum, a 4- to 12-fold amplification of HER-2/neu was found in 3 gastrinomas, 3 to 3.3-fold in four samples and 2.1- to 2.4-fold in the remaining five tumors. A heterozygous point mutation in the p53 gene (codon 273) was found in a single sample; none of the gastrinomas contained a mutation of the ras genes. CONCLUSIONS: Amplification of the HER-2/neu gene, but not alterations of either p53 or ras, may be involved in the pathogenesis of gastrinomas. The unique PT cell line will be a useful model to further elucidate the molecular mechanisms that contribute to gastrinoma formation and growth.

Operative cholangiography performed during laparoscopic cholecystectomy.

Operative cholangiography is an important adjunct to laparoscopic cholecystectomy, a recently developed surgical procedure in which cholecystectomy is performed through four abdominal ports under sustained pneumoperitoneum and the direct vision of a video laparoscope. Operative cholangiogram can effectively identify incidental choledocholithiasis or anatomic variation in the biliary system that may significantly influence the surgical approach or postoperative management of the patient. Unique features portrayed on operative cholangiogram in patients undergoing laparoscopic cholecystectomy include unusual displays of pneumoperitoneum, subcutaneous emphysema, visualization of the unresected gallbladder, and overlying surgical hardware that must remain in the operating field during film exposure.

Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.

OBJECTIVE: This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). SUMMARY BACKGROUND DATA: The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. METHODS: Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. RESULTS: All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. CONCLUSIONS: These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.

Low-pressure balloon angioplasty of an occluded portacaval shunt.

Safe angioplasty of a portacaval shunt requires particular knowledge of the tissue characteristics of an anastomosis and the behavior of a balloon during inflation. The nature and true diameter of a portacaval shunt anastomosis are more difficult to evaluate than those of a peripheral arterial lesion, and complications are potentially more hazardous than those related to peripheral arterial angioplasty. We suggest that in some instances low pressure and incomplete balloon inflation are all that is necessary to yield safe and satisfactory results.

Roux-limb motility after total gastrectomy and Roux-en-Y anastomosis in patients with Zollinger-Ellison syndrome.

The Roux-en-Y syndrome was defined as chronic nausea, intermittent vomiting, and chronic abdominal pain worsened by eating in patients who have undergone a gastrojejunostomy Roux-en-Y reconstruction for peptic ulcer. When these patients fasted, the Roux limb showed striking abnormalities in motor function; when postprandial, they failed to convert to normal fed-state motor activity. In contrast, patients with Zollinger-Ellison syndrome do well after similar surgery; they can eat most foods and maintain their body weight. We studied the motility of the Roux limb and jejunum in six patients with Zollinger-Ellison after an esophagojejunostomy Roux-en-Y anastomosis. Roux-limb motor activity in these patients, as characterized by the migrating motor complex, was more frequent, well organized, and in synchrony with the remaining jejunum; most subjects also converted to the fed state after a liquid meal. We suggest that the enteric nervous system is intact and functions normally in patients who have had a Roux-en-Y reconstruction for ulcer disease secondary to Zollinger-Ellison, but not in patients with idiopathic peptic ulcer disease.

The role of endogenous prostaglandins in hormone-stimulated pancreatic exocrine secretion.

The authors have previously shown that neurotensin and secretin inhibit gastric acid secretion in the dog and that these actions are inhibited by the prostaglandin synthesis inhibitor indomethacin. Conversely, neurotensin and secretin share similar stimulatory effects on pancreatic exocrine secretion. In the present study, the effects of blockade of prostaglandin synthesis by indomethacin on neurotensin-, cholecystokinin-, and secretin-stimulated exocrine secretion are examined along with the effects of these same agents on the release of pancreatic polypeptide. The studies were performed on conscious dogs with chronic gastric and pancreatic cannulas. Dose-dependent increases in pancreatic exocrine secretion of water and bicarbonate were observed with IV infusion of neurotensin or secretin; however, inhibition of prostaglandin synthesis by indomethacin abolished this response. Protein secretion stimulated by either neurotensin or cholecystokinin was not affected by prostaglandin inhibition. Cholecystokinin and neurotensin infusion stimulated release of pancreatic polypeptide; only neurotensin-stimulated release of pancreatic polypeptide was inhibited by indomethacin treatment. It is concluded that intact prostaglandin synthesis is necessary for the actions of neurotensin and secretin (but not that of cholecystokinin) on pancreatic exocrine secretion of water and bicarbonate and for neurotensin- (but not cholecystokinin-) stimulated release of pancreatic polypeptide.

The economic burden of gallstone lithotripsy. Will cost determine its fate?

Gallstone lithotripsy (LITHO) was performed on 52 patients who underwent 107 procedures. Two hundred sixty-seven gallstone patients were screened and 215 (81%) were excluded. Excessive stone burden and nonvisualization by oral cholecystogram (OCG) were the most common reasons for exclusion. The hospital course of 100 excluded patients who later underwent elective cholecystectomy was evaluated for length of hospital stay (2.3 days) and total cost of treatment ($3685.00). Successful fragmentation to less than 5 mm was achieved in 43 LITHO patients (83%). Five LITHO patients (10%) required conversion to operative management. Complications of LITHO included acute cholecystitis (1 of 52 patients) and biliary colic (17 of 52 patients, or 33%). Multiple procedures in one patient were common. Costs for LITHO were calculated in two ways: first the individual cost for each of the 52 candidates; second the cost for successful LITHO was calculated by excluding five patients who required operation as well as five patients (10%) who are predicted failures of LITHO. Including the preoperative evaluation, treatment, recovery room, and follow-up, the individual LITHO cost for 52 patients was $8275.00. If the same total expenditure is calculated after excluding patients who required operation and those predicted to fail, the cost per 'successful' LITHO procedure was $10,245. The cost of 1 year of bile acid therapy is $1949.00 or $2413.00 per 'successful' procedure. Follow-up costs were $1232.00 per patient or $1525.00 per 'successful' procedure. The added LITHO cost incurred by screening eventual noncandidates was $904.00 per successful procedure. The sum of these individual costs was $15,087.00 per success, as compared to $3685.00 for cholecystectomy. No allowance was made for cost of stone recurrence. Lithotripsy costs appear to be sufficiently high to render the procedure unlikely to emerge as the treatment of choice.

Pancreas transplantation. A new program.

Sixteen pancreatico-duodenal transplants were performed on 15 insulin-dependent diabetics, aged 25-46, during a 20-month period beginning May 1, 1988. Fourteen patients received a combined cadaveric pancreas/renal transplant with bladder drainage. One patient received a second pancreas transplant 24 hours after the first pancreas graft failed due to portal vein thrombosis. One patient received a pancreas graft 3 years after kidney transplantation. Complications included five cases of hematuria, two bladder leaks, two wound infections, one cytomegalovirus pneumonia, three cases of graft pancreatitis, one pseudocyst, one urine reflux pancreatitis requiring conversion to pancreatico-enterostomy, and two late deaths. Average time to discharge was 17 days following transplant, with 2.9 re-hospitalizations per patient and an average of 38 in-hospital days during the first 6-12 months. Seventeen rejection episodes occurred in 12 patients, diagnosed by declining urine amylase and pH and/or finding of rejection on kidney biopsy. Patient and kidney graft survival is 87 per cent. Pancreas graft survival is 81 per cent (1-20 months follow-up). All patients are insulin-independent and normoglycemic. Mean glycosylated hemoglobin concentration is 4.0 +/- 0.9 post-transplant vs. 7.5 +/- 0.6 pretransplant. Mean serum creatinine is 1.4 +/- 0.7 mg/dl. A new program of pancreas transplantation can be successful in carefully selected diabetic patients, with special attention to avoidance of preservation injury to the pancreas during multiorgan donor procurement. Combined pancreatic/renal transplantation is believed to be the therapeutic treatment of choice in Type I diabetic patients who have impaired renal function and have no significant cardiovascular disease.

Proglumide inhibits cholecystokinin and meal-stimulated pancreatic secretion and release of pancreatic polypeptide.

Exogenously administered cholecystokinin is a potent stimulant of pancreatic exocrine secretion and pancreatic polypeptide release. Release of cholecystokinin by amino acids and fats is strongly correlated with both pancreatic exocrine secretion and pancreatic polypeptide release. Despite this correlation, direct evidence that cholecystokinin is a physiologic mediator of these actions is not available. We have studied this problem in fasted dogs with chronic pancreatic fistulas by means of a specific cholecystokinin antagonist, proglumide, to inhibit the effect of cholecystokinin. Secretion, neurotensin (with secretin stimulation infusion), or cholecystokinin-octapeptide was infused intravenously, either with saline solution or with proglumide (300 mg/kg/hr). For endogenous release of cholecystokinin, intraduodenal infusions of phenylalanine and tryptophan or of sodium oleate were given with either intravenous saline solution or intravenous proglumide. Pancreatic secretion and release of cholecystokinin and pancreatic polypeptide were measured in plasma. Cholecystokinin-octapeptide stimulated pancreatic secretion of water and protein; both of these were significantly inhibited by proglumide. Intraduodenal amino acids and sodium oleate both caused significant release of cholecystokinin, which was not altered by proglumide; however, proglumide inhibited pancreatic secretion stimulated by intraduodenal amino acids and sodium oleate. Release of pancreatic polypeptide stimulated by amino acid and sodium oleate was also significantly inhibited by proglumide. Since proglumide appears to block actions of cholecystokinin, our results show that cholecystokinin is physiologically important for pancreatic secretion and for release of pancreatic polypeptide.

Intravenous amino acids stimulate human gallbladder emptying and hormone release.

Gallbladder stasis during prolonged total parenteral nutrition (TPN) has been documented. We have examined the effect of intravenous amino acid infusion on human gallbladder contraction and release of cholecystokinin (CCK). Five healthy adult volunteers were given amino acid infusions at different rates (65, 125, 240, and 600 mg.kg-1.h-1). The volume of the gallbladder was calculated by means of ultrasonographic measurements. Plasma samples were analyzed for CCK immunoreactivity. Gallbladder and hormone responses after intravenous amino acids were compared with responses after a fat meal, after a protein meal, and after ingestion of an oral amino acid mixture. We found that intravenous amino acids stimulated human gallbladder contraction in a dose-related manner. The mechanism of stimulation may be through the release of CCK although significant correlation was not demonstrated. The magnitude of response is similar to that seen after meal stimulation. To compare the delivery of amino acids during a standard meal and during each dose of intravenous amino acids, peripheral plasma levels of dietary amino acids were measured after a standard commercially prepared enteral supplement meal and after each dose of intravenous amino acids. Our lower doses of amino acid infused resulted in levels of circulating amino acid comparable to those after a meal. The induction of gallbladder contraction and release of CCK in human recipients of parenteral nutrition may be of value in some circumstances.

Additive interactions of calcitonin gene-related peptide and calcitonin on pancreatic exocrine function in conscious dogs.

By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides.

Pancreatitis necessitating urinary undiversion in a bladder-drained pancreas transplant.

After successful combined pancreaticoduodeno-renal transplant in an insulin-dependent diabetic, recurrent episodes of transplant pancreatitis were treated with Foley catheter drainage. The apparent cause of pancreatitis was increased pressure on the pancreatic duct due to infrequent voiding and a large bladder. A frequent voiding program partially relieved the pancreatitis, but final resolution necessitated conversion of the pancreaticoduodeno-cystostomy to a Roux-en-Y duodenojejunostomy at 6 months posttransplant. Both renal and pancreatic function are stable after 1 year, with no recurrence of pancreatitis since urinary undiversion. We believe pressure pancreatitis or urine reflux pancreatitis to be an infrequently reported cause of graft dysfunction in bladder-drained pancreas transplant recipients.