John Baillie

American College of Gastroenterology guideline: management of acute pancreatitis.

This guideline presents recommendations for the management of patients with acute pancreatitis (AP). During the past decade, there have been new understandings and developments in the diagnosis, etiology, and early and late management of the disease. As the diagnosis of AP is most often established by clinical symptoms and laboratory testing, contrast-enhanced computed tomography (CECT) and/or magnetic resonance imaging (MRI) of the pancreas should be reserved for patients in whom the diagnosis is unclear or who fail to improve clinically. Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed. Patients with organ failure and/or the systemic inflammatory response syndrome (SIRS) should be admitted to an intensive care unit or intermediary care setting whenever possible. Aggressive hydration should be provided to all patients, unless cardiovascular and/or renal comorbidites preclude it. Early aggressive intravenous hydration is most beneficial within the first 12–24 h, and may have little benefit beyond. Patients with AP and concurrent acute cholangitis should undergo endoscopic retrograde cholangiopancreatography (ERCP) within 24 h of admission. Pancreatic duct stents and/or postprocedure rectal nonsteroidal anti-inflammatory drug (NSAID) suppositories should be utilized to lower the risk of severe post-ERCP pancreatitis in high-risk patients. Routine use of prophylactic antibiotics in patients with severe AP and/or sterile necrosis is not recommended. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis may be useful in delaying intervention, thus decreasing morbidity and mortality. In mild AP, oral feedings can be started immediately if there is no nausea and vomiting. In severe AP, enteral nutrition is recommended to prevent infectious complications, whereas parenteral nutrition should be avoided. Asymptomatic pancreatic and/or extrapancreatic necrosis and/or pseudocysts do not warrant intervention regardless of size, location, and/or extension. In stable patients with infected necrosis, surgical, radiologic, and/or endoscopic drainage should be delayed, preferably for 4 weeks, to allow the development of a wall around the necrosis.

ENDOSCOPIC SPHINCTEROTOMY IN 1000 CONSECUTIVE PATIENTS

Between 1983 and 1988, endoscopic sphincterotomy was attempted on 1000 consecutive patients with a clinical diagnosis of bileduct stones in a centre with a policy to establish immediate bileduct drainage for retained stones. Endoscopic cholangiography was successful in 985 patients, of whom 782 had visible stones and 203 had a dilated bileduct but no visible stones. Endoscopic sphincterotomy was successful in 975 of these patients, with eventual bileduct clearance in 674 of 772 patients (87.3%) with visible stones; immediate bileduct drainage was achieved in 160 of the 161 patients (99%) in whom bileduct clearance failed at the first attempt. Overall, 771 of 797 patients (96.7%) with visible bileduct stones had successful bileduct clearance or drainage. Complications occurred in 6.9%, with a 30-day mortality rate of 1.2%, but procedure-related mortality was only 0.6%.

Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas.

AbstractBackground: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer. Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT. Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months. Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.

Management of major biliary complications after laparoscopic cholecystectomy

OBJECTIVE A total of 50 major bile duct injuries after laparoscopic cholecystectomy were managed by the Duke University Hepatobiliary Service from 1990-1992. The management of these complex cases is reviewed. SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy is the preferred method for removing the gallbladder. Bile duct injury is the most feared complication of the new procedure. METHODS Review of videotapes, pathology, and management of the original operations were reviewed retrospectively, and the injuries categorized. Major biliary injury was defined as a recognized disruption of any part of the major extrahepatic biliary system. Biliary leakage was defined as a clinically significant biliary fistula in the absence of major biliary injury, i.e., with an intact extrahepatic biliary system. RESULTS Thirty-eight injuries were major biliary ductal injuries and 12 patients had simple biliary leakage. Twenty-four patients had the classic type injury or some variant of the classic injury. A standard treatment approach was developed which consisted of ERCP for diagnosis, preoperative PTC with the placement of stents, CT drainage immediately after the PTC for drainage of biliary ascites, and usually Roux-en-Y hepaticojejunostomy with placement of O-rings for future biliary access if necessary. Major ductal injuries were high in the biliary system involving multiple ducts in 31 of the 38 patients. Re-operation was required in 5 of the 38 patients with particularly complex problems. CONCLUSIONS Successful management of bile duct injury after laparoscopic cholecystectomy requires careful understanding of the mechanisms, considerable preoperative assessment by experts, and a multidisciplinary approach.

Alcohol and Smoking as Risk Factors in an Epidemiology Study of Patients With Chronic Pancreatitis

BACKGROUND & AIMS Alcohol has been implicated in the development of chronic pancreatitis (CP) in 60%-90% of patients, although percentages in the United States are unknown. We investigated the epidemiology of alcohol-related CP at tertiary US referral centers. METHODS We studied data from CP patients (n = 539) and controls (n = 695) enrolled in the North American Pancreatitis Study-2 from 2000 to 2006 at 20 US referral centers. CP was defined by definitive evidence from imaging or histologic analyses. Subjects and physicians each completed a study questionnaire. Using physician-assigned diagnoses, patients were assigned to an etiology group: alcohol (with/without other diagnoses), nonalcohol (any etiology of CP from other than alcohol), or idiopathic (no etiology identified). RESULTS The distribution of patients among etiology groups was: alcohol (44.5%), nonalcohol (26.9%), and idiopathic (28.6%). Physicians identified alcohol as the etiology more frequently in men (59.4% men vs 28.1% women), but nonalcohol (18% men vs 36.7% women) and idiopathic etiologies (22.6% men vs 35.2% women) more often in women (P < .01 for all comparisons). Nonalcohol etiologies were equally divided among obstructive, genetic, and other causes. Compared with controls, patients with idiopathic CP were more likely to have ever smoked (58.6% vs 49.7%, P < .05) or have a history of chronic renal disease or failure (5.2% vs 1.2%, P < .01). In multivariate analyses, smoking (ever, current, and amount) was independently associated with idiopathic CP. CONCLUSIONS The frequency of alcohol-related CP at tertiary US referral centers is lower than expected. Idiopathic CP and nonalcohol etiologies represent a large subgroup, particularly among women. Smoking is an independent risk factor for idiopathic CP.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study

Objective To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. Methods This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A–E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. Results Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. Conclusions This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.

Dieulafoy lesions: a review of 6 years of experience at a tertiary referral center

Dieulafoy lesions are uncommon sources of GI hemorrhage and predominantly occur in the proximal stomach. At one time a pathological diagnosis made postoperatively, Dieulafoy lesions are now routinely diagnosed and treated endoscopically. Their true incidence is unclear as quiescent Dieulafoy lesions are easily overlooked on endoscopy and bleeding lesions are occasionally misidentified. Over 6 yr (June 1993–November 1999), 40 Dieulafoy lesions were identified on upper endoscopy at our institution, of which seven were located in the duodenum and one in the right colon. Forty-seven percent of patients were hospitalized for other causes before onset of bleeding, and 17 of 40 were found to have other abnormal findings at endoscopy. In 90% of the cases, endoscopic treatment was successful. Seven patients died, but none as a result of hemorrhage. In 24 endoscopically-treated patients in whom follow-up data are available, Dieulafoy bleeding recurred in one patient. Dieulafoy lesions are rare and often difficult to diagnose, but must be considered in the evaluation of upper and lower GI tract hemorrhage, as they can usually be managed endoscopically.

Significance of Histological Response to Preoperative Chemoradiotherapy for Pancreatic Cancer

BackgroundNeoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. MethodsSince 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods.ResultsThe estimated overall survival (median ± SE) in the entire group of patients undergoing resection was 23 ± 4.2 months, with an estimated 3-year survival of 37% ± 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation.ConclusionsHistological response to neoadjuvant CRT—as measured by residual tumor load—may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Combined Bicarbonate Conductance-Impairing Variants in CFTR and SPINK1 Variants Are Associated With Chronic Pancreatitis in Patients Without Cystic Fibrosis

BACKGROUND & AIMS Idiopathic chronic pancreatitis (ICP) is a complex inflammatory disorder associated with multiple genetic and environmental factors. In individuals without cystic fibrosis (CF), variants of CFTR that inhibit bicarbonate conductance but maintain chloride conductance might selectively impair secretion of pancreatic juice, leading to trypsin activation and pancreatitis. We investigated whether sequence variants in the gene encoding the pancreatic secretory trypsin inhibitor SPINK1 further increase the risk of pancreatitis in these patients. METHODS We screened patients and controls for variants in SPINK1 associated with risk of chronic pancreatitis and in all 27 exons of CFTR. The final study group included 53 patients with sporadic ICP, 27 probands with familial ICP, 150 unrelated controls, 375 additional controls for limited genotyping. CFTR wild-type and p.R75Q were cloned and expressed in HEK293 cells, and relative conductances of HCO(3)(-) and Cl(-) were measured. RESULTS SPINK1 variants were identified in 36% of subjects and 3% of controls (odds ratio [OR], 18.1). One variant of CFTR not associated with CF, p.R75Q, was found in 16% of subjects and 5.3% of controls (OR, 3.4). Coinheritance of CFTR p.R75Q and SPINK1 variants occurred in 8.75% of patients and 0.38% of controls (OR, 25.1). Patch-clamp recordings of cells that expressed CFTR p.R75Q showed normal chloride currents but significantly reduced bicarbonate currents (P = .0001). CONCLUSIONS The CFTR variant p.R75Q causes a selective defect in bicarbonate conductance and increases risk of pancreatitis. Coinheritance of p.R75Q or CF causing CFTR variants with SPINK1 variants significantly increases the risk of ICP.

Safety and efficacy of India ink and indocyanine green as colonic tattooing agents

BACKGROUND Controversy exists concerning the safety and efficacy of colonic tattooing for the intraoperative identification of polypectomy sites. The purpose of this study was to determine (1) the concentrations of India ink and indocyanine green that resulted in high-visibility tattoos without significant tissue inflammation and (2) the India ink injection volume that produces best visibility at colonoscopy, laparoscopy, and laparotomy. METHODS Twenty-two New Zealand white rabbits (2 kg) were anesthetized and injected with India ink (undiluted 1:10, 1:50, 1:100, 1:1000, 1:10,000) and indocyanine green as an undiluted, concentrated formulation (25 mL/2 mL solvent) or in a diluted form (25 mg/5 mL solvent) at various concentrations (1:10, 1:50, 1:100). Tuberculin syringes were used to create a 0.1 mL serosal bleb at two injection sites 2 cm apart. Laparotomy was repeated at days 1, 3, and 7 after injection. Additionally, 16 rabbits were injected with India ink at laparotomy and re-explored at 1 and 5 months. Twelve mongrel dogs (20 kg) were injected with 1.0 mL volumes. Re-exploration by colonoscopy, laparoscopy, and laparotomy was done at 7 days and 1 month. Tattoo visibility at re-exploration in both animal models was graded on a scale (0 = agent not seen, 1 = seen with difficulty, 2 = easily seen). Histology in the rabbit was judged by degrees of inflammation (0 = no inflammation, 2 = mild inflammation, 4 = moderate inflammation, 6 = severe inflammation). RESULTS The concentrated indocyanine green solution was easily visible only on day 1 in the rabbit. Injections of both concentrated and diluted indocyanine green caused mucosal ulceration and moderate to severe inflammation. India ink studied at 7 days, 1 month, and 5 months after injection in the rabbit model was visible at all concentrations. The undiluted and 1:10 concentrations were easily seen and showed evidence of mucosal ulceration. Tattoos produced with all other India ink concentrations were visible without gross inflammation. India ink was also studied at 7 days and 1 month in dogs. The tattoo with the 1:100 concentration at 0.5 mL was seen consistently at colonoscopy, laparoscopy, and laparotomy with only a mild submucosal reaction at 7 days. The tattoos produced with the 1:100 and 1:1000 concentrations at 0.5 mL and 1.0 mL injection volumes were easily seen by all methods of intraabdominal visualization at 1 month with similar histology. CONCLUSION Indocyanine green was an ineffective colonic tattooing agent. India ink was an effective colonic tattooing agent. Dilute concentrations that caused little to no inflammation could be visualized at 7 days and 1 month in rabbits and dogs and at 5 months in rabbits. India ink, at appropriated concentrations, appears to be a safe short- and long-term colonic tattooing agent.