Gregory B. Haber

The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.

Endoscopic biliary prostheses as treatment for benign postoperative bile duct strictures

We evaluated the efficacy of endoscopically placed biliary stents as treatment for 32 benign postoperative biliary strictures in 29 patients. Five patients also had bile fistulas. Stents were inserted for a mean of 162 days and then removed. ERCPs were obtained before stent insertion and again after removal. Responses were followed and categorized as excellent, good, or poor. Stent insertion was successful in 25 patients (86%), 23 of which have a mean follow-up of 19 months (range, 2 to 42 months) after stent removal. Seventy-four percent had an excellent (48%) or good (26%) response. Early postoperative strictures and fistulas responded favorably. We conclude that benign postoperative biliary strictures can be treated successfully by endoscopic prostheses.

Ampullary adenoma: clinical manifestations, diagnosis, and treatment

Ampullary adenomas occur sporadically and in the setting of familial polyposis syndromes. In either case, and whether symptomatic at presentation or found asymptomatically in the setting of endoscopic screening programs, they are premalignant lesions with risk for malignant degeneration to carcinoma following the adenoma-to-carcinoma sequence that is well recognized in colonic adenocarcinoma. Accordingly, many experts advocate excision, although others cite the low rate of histologic progression suggested by some recent studies as justification for close endoscopic surveillance rather than excision before demonstration of dysplastic change. This recommendation, however, is complicated by considerable data underscoring the limited accuracy of endoscopic forceps biopsy in detecting occult foci of carcinoma within ampullary adenoma. Thus, the optimal management of these lesions continues to generate considerable controversy. Indications for excision of an ampullary adenoma include treatment of immediate symptoms as well as prevention of malignant degeneration. Although pancreaticoduodenectomy has long been considered the standard procedure for ampullary carcinoma, much controversy exists regarding the procedure of choice for ampullary adenoma. Radical surgery (pancreaticoduodenectomy) possesses the advantage of low recurrence rate but at the expense of higher morbidity (25%-65%) and mortality (0%-10%). Local surgical excision (surgical ampullectomy) possesses the advantages of lower morbidity (0%-25%), essentially nil mortality, and possibly decreased length of hospital stay, but decidedly higher recurrence rates (generally 5%-30%) and the need for postoperative endoscopic surveillance. Snare ampullectomy is a newer endoscopic excisional technique for which limited data are available; advantages compared with radical surgery mirror those of local surgical excision, with apparent lower mortality (0%-1%) and lower morbidity (12%). Presumed advantages compared with local surgical excision include lack of necessity for general anesthesia and laparotomy with comparable morbidity. Disadvantages seem to include limited availability of experienced operators, procedural complexity sometimes requiring adjunctive modalities such as fulguration, the need for multiple procedures (mean, 2.0 procedures) to effect complete excision, and recurrence rates approaching 30%, with a requirement for continued endoscopic surveillance. Ultimately, choice is driven by availability of local expertise, patient tolerance of or expected compliance with long-term endoscopic surveillance programs, presence or absence of coexisting familial polyposis syndromes, medical comorbidities, and overall life expectancy.

Management of advanced duodenal polyposis in familial adenomatous polyposis

Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of periampullary cancer. The aim of this study was to evaluate the roles of endoscopic and surgical therapy in the management of advanced duodenal polyposis in FAP. From 1990 to 1995, seventy-four FAP patients were enrolled in a prospective endoscopic surveillance protocol. Among these, 11 (14.8%) developed advanced duodenal polyposis and one had duodenal adenocarcinoma. Six patients underwent endoscopic resection of duodenal (n=5) or ampullary adenomas (n=1). The following operations were performed in the remaining six patients: ampullectomy in four, open polypectomy in one, and a Whipple procedure in one. There was one patient who died of acute pancreatitis following endoscopic ampullectomy. The patient with invasive duodenal cancer died of local recurrence. Small polyps were observed at the site of previous resection in all (9 of 9) patients undergoing repeat endoscopy during a mean follow-up of 18 months (range 4 to 34 months). An endoscopic and local surgical resectional approach to advanced duodenal polyposis in FAP is fraught with high recurrence rates, although recurrent polyps are small and may be amenable to retreatment in the future. Long-term follow-up is necessary to prove that deaths from duodenal or ampullary cancer are prevented with this strategy.

Endoscopic sphincterotomy in outpatients.

We retrospectively reviewed 137 cases of outpatient endoscopic sphincterotomy (ES) performed over a 4-year period in a single center and compared them with an equal number of inpatient ES. The indications for ES in outpatients as compared with inpatients were, respectively: choledocholithiasis, 60% and 70%; papillary stenosis, 35% and 15% (p less than 0.001); stent insertion, 3.6% and 14% (p less than 0.01); and ampullary tumor, 1.4% and 0.7%. Complications were noted within 2 to 4 hours of ES in 6.6% of outpatients, a rate similar to that of inpatients--7.3%. Outpatients with complications were immediately admitted and stayed in the hospital for a mean of 5 days. No delayed complications were noted and no deaths occurred. Thus, a policy whereby selected individuals undergo ES as outpatients, with hospitalization reserved only for those in whom a complication develops, is reasonable and safe.

Small colonic adenomas with adenocarcinoma

The purpose of this study is to alert colonoscopists to a relatively high incidence of small colonic adenomas with invasive adenocarcinoma among a group of colonic adenomas with invasive adenocarcinoma removed colonoscopically. Retrospective analysis (1973 to 1983) documented nine such lesions that were 1 cm or smaller, representing 15 percent of all colonic adenomas with invasive adenocarcinoma removed during that period. These lesions had no distinctive gross features and could be easily confused with hyperplastic polyps. It is recommended that all colonic polyps be removed at colonoscopy regardless of their size, because even lesions 1 cm and smaller, with “benign” gross appearance, may harbor invasive adenocarcinoma.

Role of endoscopy in inflammatory bowel disease.

Over the past two decades, endoscopy has emerged as the single most important tool in the initial diagnosis and subsequent follow-up of inflammatory bowel disease. This article is an overview of the applicability of the various endoscopic procedures in the management of inflammatory bowel disease and its complications.Over the past two decades, endoscopy has emerged as the single most important tool in the initial diagnosis and subsequent follow-up of inflammatory bowel disease. This article is an overview of the applicability of the various endoscopic procedures in the management of inflammatory bowel disease and its complications.

Percutaneous deflation of a gastric balloon: Technical note

Gastric balloons have been used extensively as an adjunct to diet and behavioral modification in the treatment of exogenous obesity. Small bowel obstruction occurred in a 42-year-old female after her balloon migrated through the pyloric channel. The authors describe a simple method for percutaneous deflation which permitted the balloon to pass through the gastrointestinal tract thus relieving the obstruction.

Management of nonvariceal, nonangiodysplastic gastrointestinal lesions with argon plasma coagulation, band ligation, and endoscopic clips/loops

The management of nonvariceal, nonangiodysplastic gastrointestinal lesions continues to evolve. In this article, argon plasma coagulation, endoscopic band ligation, and endoscopic clips/loops are discussed, with particular focus on new applications to treat bleeding lesions of the upper gastrointestinal tract.

4670 Endoscopic therapy in 207 bile leaks: validation of a treatment strategy.

Background: Bile leak is the most common post-cholecystectomy complication with a variety of highly successful endoscopic therapies. In 1994, one author (MB) proposed a grading system to distinguish the severity of leak into low-grade (LG, leak identified only after intra-hepatic filling of contrast) or high-grade (HG, leak seen prior to intrahepatic filling). Subsequent therapy was based on this classification with sphincterotomy (BS) alone in LG and a stent (St) to bridge the leak in HG. Results: During a 10 yr period, 207 pts (mean age 54 yrs, 127 F) with bile leaks were referred to our unit for endoscopic management. Of these, 134 underwent laparoscopic cholecystectomy, 72 open cholecystectomy and 1 had spontaneous rupture of the bile duct. Pts presented 11.8 d (mean, range 1-50 d) after surgery. Modes of presentation were leakage of bile (drains 37%, T tube 11%, incisions 12%), pain (56%), jaundice (16%), fever (11%) and abdominal distension (7%). ERCP identified the site of leak in 204 pts: cystic duct stump in 159 (78%), duct of Luschka in 26 (13%) and other in 19 (9%). A review of the initial 85 pts classified leaks into LG and HG (see above). BS alone for LG leaks and St for HG leaks proved effective in 82/85 pts (96%). This strategy was then prospectively validated in the subsequent 122 pts. Results of the combined group (104 LG, 100 HG) are presented here. In the LG group, 75/104 pts had BS alone with improvement in 68 pts (91%). Further treatment was required in 7 pts (6 had St, 1 underwent surgery). St was the initial treatment in the remaining 29/104 pts. The reasons for this were: CBD stricture (11/29), coagulopathy preventing BS (8/29), severe sepsis (3/29), prior BS with inadequate drainage (2/29) and unclear indications (5/29). In the HG group, 97/100 pts had St. Persistent leakage necessitated re-stenting in 4/97 pts. Healing of the leak was documented on follow-up ERCP in all 97 pts. Three pts were not amenable to endoscopic therapy (2 with clips across CBD and 1 with incomplete cholecystectomy) and were referred for surgery. CBD stones were identified in 41 pts (28/104 LG, 13/100 HG) and extracted in all. The distribution of stone cases indicates no impact on severity of leak. Only 3 complications occured: 2 pts developed post-ERCP pancreatitis and 1 had duodenal perforation. There was no mortality. Conclusion: The use of this simple grading system for bile leaks and the relevent therapy has proven to be a useful tool for choice of endotherapy. The role of a stent without sphincterotomy or naso-biliary tube alone has not been evaluated in this series.