Recurrent Acute Pancreatitis: International State-of-the-Science Conference With Recommendations

Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research

Acute and chronic pancreatitis.

Acute pancreatitis has multiple causes, an unpredictable course, and myriad complications. The diagnosis relies on a combination of history, physical examination, serologic markers, and radiologic findings. The mainstay of therapy includes aggressive hydration, maintenance of NPO, and adequate analgesia with narcotics. Antibiotic and nutritional support with total parenteral nutrition should be used when appropriate.

Does mortality occur early or late in acute pancreatitis?

UNLABELLED: Several prior studies have suggested that 80% of deaths in acute pancreatitis occur late as a result of pan-creatic infection. Others have suggested that approx half of deaths occur early as a result of multisystem organ failure. The aim of the present study was to determine the timing of mortality of acute pancreatitis at a large tertiary-care hospital in the United States. METHODS: Patients with a diagnosis of acute pancreatitis (ICD-9 code 577.0) admitted to Brigham and Women's Hospital from October 1, 1982 to June 30, 1995 were retrospectively studied to determine total mortality, frequency of early vs late deaths, and clinical features of patients with early (< or = 14 d after admission) or late deaths (> 14 d after admission). RESULTS: The overall mortality of acute pancreatitis was 2.1% (17 deaths among 805 patients). Eight deaths (47%) occurred within the first 14 d of hospitalization (median d 8, range 1-11 d), whereas 9 occurred after 14 d (median d 56, range 19-81). Early deaths resulted primarily from organ failure. Late deaths occurred postoperatively in 8 patients with infected or sterile necrosis and 1 patient with infected necrosis treated medically. CONCLUSION: Approximately half of deaths in acute pancreatitis occur within the first 14 d owing to organ failure and the remainder of deaths occur later because of complications associated with necrotizing pancreatitis. Improvement in mortality in the future will require innovative approaches to counteract early organ failure and late complications of necrotizing pancreatitis.

Hemoconcentration as an early risk factor for necrotizing pancreatitis.

OBJECTIVE: The aim of our study was to determine whether measurement of serum hematocrit during the first 24 h helps in distinguishing necrotizing from mild pancreatitis. METHODS: From May 1992 to June 1996, a case-control study was performed with cases of patients with necrotizing pancreatitis. We selected as a control the next patient admitted with mild pancreatitis. RESULTS: There were 32 patients in each group. Logistic regression identified an admission hematocrit of > or = 47% and a failure of admission hematocrit to decrease at 24 h as the best binary risk factors for necrotizing pancreatitis. At admission, more patients with necrotizing pancreatitis than with mild pancreatitis had a hematocrit > or = 47% (11/32 vs 3/32; p = 0.03). At 24 h, 15 additional patients with necrotizing pancreatitis versus only one with mild pancreatitis showed no decrease in admission hematocrit (p < 0.01). Thus, by 24 h, 26 of 32 patients with necrotizing pancreatitis versus only four of 32 patients with mild pancreatitis met one or the other criterion (p < 0.01). The sensitivity and specificity at admission were 34% and 91%; at 24 h, 81% and 88%. CONCLUSIONS: Hemoconcentration with an admission hematocrit > or = 47% or failure of admission hematocrit to decrease at approximately 24 h were strong risk factors for the development of pancreatic necrosis.

Chronic ethanol administration selectively impairs endocytosis in the rat exocrine pancreas.

Release of GP2, a glycosyl phosphatidylinositol-linked protein on the apical plasma membrane of the pancreatic acinar cell, is associated with activation of endocytosis. Released GP2 is also an integral component of intraductal plugs in patients with alcohol-induced chronic pancreatitis. Our purpose was to determine the effect of ethanol on exocytosis and endocytosis and its association with release of membrane-bound GP2. Rats were fed Lieber-DeCarli diets with and without ethanol for 2 weeks. Endocytosis was then assessed in acini by measuring horseradish peroxidase (HRP) uptake, GP2 release by Western blotting, and exocytosis by measuring amylase release. In ethanol-fed rats, HRP uptake was inhibited by 90% compared to that in control rats. In contrast, no significant difference in cholecystokinin-stimulated amylase secretion was found. In vitro, ethanol inhibited HRP uptake in a dose-dependent manner, with 50% inhibition at 50 mM ethanol. Despite the inhibition of endocytosis, GP2 release increased linearly over 60 min and was significantly higher from acini incubated with ethanol compared to controls. These data indicate that ethanol selectively inhibits endocytosis in pancreatic acinar cells. The release of GP2 into the pancreatic duct was no longer coupled to endocytosis in animals fed ethanol.

Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis.

OBJECTIVE: Pancreatic enzyme therapy is widely used in the treatment of pain in chronic pancreatitis. The aim of our study was to perform a meta-analysis to determine whether pancreatic enzyme supplementation significantly decreases abdominal pain in patients with chronic pancreatitis. METHODS: From a MEDLINE search, we identified, evaluated, and subjected to a meta-analysis, six randomized, double-blind, placebo-controlled trials. Important features of data extraction included the method of subject inclusion, definition of disease, enzyme preparation, response to pancreatic enzyme therapy versus placebo, and modality for measuring response. RESULTS: In the meta-analysis, the pooled estimate of the percentage of patients per study who preferred enzymes relative to placebo was 52% (95% confidence interval, 45-60%). A test of homogeneity indicated that there was no statistically significant heterogeneity across studies in the percentage of patients preferring enzymes. CONCLUSION: Statistical analysis demonstrates no significant benefit of supplemental pancreatic enzyme therapy to relieve pain associated with chronic pancreatitis.

Pleural effusion as a predictor of severity in acute pancreatitis.

Our objective was to determine whether pleural effusion is a predictor of severity in acute pancreatitis and, if so, whether it is an independent predictor. One hundred ninety-six consecutive cases of acute pancreatitis from October 1, 1994, to September 30, 1995, were reviewed. Medical records were analyzed for evidence of pleural effusion by chest radiograph and severe acute pancreatitis by identification of pancreatic necrosis or organ system dysfunction. Data were analyzed to determine if identification of pleural effusion provided an early sign of severity. Among 135 patients who underwent chest radiography, pleural effusion was seen in 16 of 19 (84.2%) with severe pancreatitis and 10 of 116 (8.6%) of patients with mild pancreatitis (p < 0.001). Pleural effusion was noted in severe pancreatitis prior to clinical or computed tomography evidence of severity in only 20% of cases. Pleural effusion is strongly associated with severity in acute pancreatitis but provides independent information on severity in only a minority of cases.

Relationship of necrosis to organ failure in severe acute pancreatitis.

BACKGROUND & AIMS: Pancreatic necrosis and organ failure are principal determinants of severity in acute pancreatitis. The purpose of this study was to determine the relationship of necrosis to organ failure in severe acute pancreatitis. METHODS: Patients with necrotizing pancreatitis from May 1992 to January 1996 were retrospectively studied. Pancreatic necrosis was identified by characteristic findings on dynamic contrast-enhanced computerized tomography scan and infected necrosis by computerized tomography-guided percutaneous aspiration. Organ dysfunction was defined in accordance with the Atlanta symposium. RESULTS: Organ failure was present in only 26 of 51 patients (51%). There was no difference in the prevalence of organ failure in infected necrosis compared with sterile necrosis (approximately 50% in both groups). Patients with increased amounts of necrosis did not have an increased prevalence of organ failure or infected necrosis compared with those with lesser amounts of necrosis. Patients with organ failure had an increased morbidity and mortality compared with those without organ failure. CONCLUSIONS: Organ failure occurred in only one half of patients with necrotizing pancreatitis. Because organ failure increases the severity of illness, studies of patients with necrotizing pancreatitis must stratify for organ failure to facilitate interpretation of results.

Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis.

CONCLUSIONS: Urinary TAP obtained within the first 48 h of the onset of symptoms can distinguish patients with severe acute pancreatitis. BACKGROUND: Urinary trypsinogen activation peptide (TAP) has recently been described as an early marker of severity in acute pancreatitis. METHODS: In a multicenter study, urine samples were collected for TAP concentration at 6-12, 24, and 48 h after admission from 139 patients with acute pancreatitis (99 with mild disease, 40 with severe disease) and from 50 control patients. Severity of acute pancreatitis was defined by the presence of organ failure and/ or pancreatic necrosis on dynamic contrast-enhanced computed tomography. RESULTS: Median urinary TAP in the 139 patients with acute pancreatitis compared to the 50 control patients was significantly higher at admission, 4.6 vs 0.8 ng/mL (p < 0.001), and 6-12 h, 1.9 vs 0.55 ng/mL (p = 0.04). Among patients who presented within 48 h of the onset of symptoms, the median urinary TAP for severe pancreatitis (9 patients) compared to mild pancreatitis (40 patients) was significantly higher at admission, 29.6 vs. 3.6 ng/mL (p = 0.001). Also, when obtained within 48 h of the onset of symptoms, all patients with severe pancreatitis had an admission urinary TAP level > 10 ng/mL. The sensitivity and specificity of an admission urinary TAP > or = 10 for severe pancreatitis was 100 and 85%, respectively. Given a cutoff of 10 ng/mL for an admission urinary TAP obtained within 48 h of the onset of symptoms, the negative predictive value was 100% for mild pancreatitis.

Acute pancreatitis: nonsurgical management.

The care of patients with severe acute pancreatitis is complex. Although numerous medical therapies have been proposed, few interventions have been shown to be of benefit in patients with severe disease. This review summarizes the nonoperative management of patients with acute pancreatitis, including therapies shown to be of little value, the role of antibiotics in patients with acute pancreatitis, the importance of monitoring and supportive care, and the rationale of endoscopic and surgical intervention.

Intraductal mucin-hypersecreting neoplasm "mucinous ductal ectasia": endoscopic recognition and management.

OBJECTIVES: Intraductal mucin-hypersecreting neoplasm (IMHN), also termed mucinous ductal ectasia, is a rare disorder of the pancreas characterized by distension of the pancreatic duct with mucus. This study attempted to clarify the clinical, radiographic, histological, and treatment approaches to this entity. METHODS: The medical records, radiological imaging studies, and pathology specimens of eight patients with IMHN seen during a 3-yr period were reviewed. The diagnosis of IMHN was established by findings during ERCP, which included mucin plugging of the papilla, mucin extrusion from the papillary orifice after intraductal injection of contrast medium, mucinous filling defects in the main pancreatic duct, and dilated main and branch pancreatic ducts in the absence of obstructing ductal strictures. RESULTS: All patients presented with an initial clinical diagnosis of acute or chronic pancreatitis, suspected cystic neoplasm, or biliary obstruction. Noninvasive imaging studies such as transabdominal ultrasonography or CT and laboratory evaluation did not seem to help in defining the disease. Five patients underwent Whipple resection; pathology included papillary ductal hyperplasia in one, dysplastic mucinous epithelium in two, and mucinous cystadenocarcinoma in two. All five patients had associated histological evidence of chronic pancreatitis. All patients are alive and well after 21-53 months without evidence of residual disease. CONCLUSIONS: IMHN has a wide spectrum of clinical, radiological, and histological features. The indolent biologic behavior and favorable prognosis of IMHN suggest that it is one of the most curable forms of pancreatic malignancy.

Toothpick ingestion as a cause of acute and chronic duodenal inflammation.

Toothpicks are a common cause of foreign body ingestion. We present two patients with duodenal inflammation secondary to toothpick ingestion. In the first patient, there was acute onset of severe abdominal pain, with findings on computed tomography consistent with marked duodenal inflammation. Endoscopy revealed a toothpick embedded in the wall of the duodenum with associated ulceration. In the second patient, 4 months of chronic abdominal pain was evaluated by upper endoscopy which revealed a toothpick embedded in a 1-cm ulcer found in the third portion of the duodenum. Both patients denied memory of ingestion of the toothpicks. Endoscopic removal of the toothpicks resulted in rapid relief of symptoms.

Von Hippel-Lindau disease complicated by acute pancreatitis and Evan's syndrome.

Von Hippel-Lindau syndrome (VHL) is an autosomal dominant disorder characterized by renal cysts, retinal angiomas, central nervous system hemangioblastomas, and pancreatic cysts. Evan's syndrome is a hematologic disorder characterized by autoimmune thrombocytopenia and autoimmune hemolytic anemia. We present the first case of acute pancreatitis and Evan's syndrome that developed in a patient with von Hippel-Lindau syndrome.

Strangulation of the colon complicating acute pancreatitis.

We report a patient with alcohol-induced necrotizing pancreatitis who developed a severe ileus followed by incarceration of a portion of the transverse colon within a ventral hernia. Laparotomy 9 days after the onset of symptoms revealed infarction of the transverse colon and infection of the pancreas. This is the first report of a case of acute pancreatitis that led to a strangulated ventral hernia of the colon. We believe that the enteric organisms that infected the pancreas originated in the incarcerated transverse colon.