Risk of pancreatitis with mutation of the cystic fibrosis gene.

BACKGROUND: Between 5% and 15% of patients with recurrent pancreatitis have no identified etiology after routine investigation and advanced endoscopic evaluation. OBJECTIVE: To determine whether mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene is a risk factor for idiopathic pancreatitis. METHODS: We compared the frequency of CFTR mutations as measured by DNA probe analysis in a case group of persons with idiopathic pancreatitis and a control group without pancreatitis, all of whom underwent endoscopic retrograde cholangiopancreatography. A separate analysis compared the prevalence of CFTR mutations between the case group and controls with pancreatitis of known etiology. A subgroup comparison was made between cases of pancreas divisum with pancreatitis and controls with pancreas divisum and no pancreatitis. RESULTS: CFTR mutations were present in 19 (19%) of 96 cases and 7 (3.5%) of 198 controls without pancreatitis (odds ratio, OR = 6.7; 95% CI, 2.8-16.3; p < 0.00001). Compared to the controls with a known cause of pancreatitis (N = 78), cases had a higher prevalence of CFTR mutations (19% vs 2.6%, OR = 9.4; CI, 2.1-41.7; p= 0.0005). Among subjects with pancreas divisum, CFTR mutations were present in 8 (22%) of 37 cases compared to 0 (0%) of 20 controls (OR = 11.8; CI, 8.9-14.7; p= 0.02). CONCLUSION: The risk of idiopathic pancreatitis is greater among persons with CFTR mutations as compared to persons without CFTR mutations. Among persons with pancreas divisum, CFTR mutations appear to increase the risk for pancreatitis.

Success of ERCP at a referral center after a previously unsuccessful attempt.

BACKGROUND: The diagnostic and therapeutic success of endoscopic retrograde cholangiopancreatography (ERCP) depends on a number of factors. When an attempt at ERCP fails, the physician must decide whether to repeat the procedure, rely on another imaging procedure (noninvasive or invasive), or refer to another endoscopist/center. Our aim in this prospective study was to determine the role of a second attempt at ERCP at a referral ERCP center. METHODS: Five hundred sixty-two patients were referred for ERCP after having undergone a previous unsuccessful attempt to visualize the clinically relevant duct(s). RESULTS: The overall success in visualizing the desired duct was 96.4% (542 of 562). Advanced techniques for cannulation were used in 41% (229 of 562). Anatomic abnormalities possibly contributing to the previous lack of success were present in 27% of cases. ERCP with or without manometry identified a cause or potential cause for the signs and symptoms in 86% of patients. Sixty complications occurred in 57 patients (10.1%). ERCP was unsuccessful in 20 patients (3.6%). CONCLUSIONS: The cannulation success rate and diagnostic yield of further ERCP with an acceptable complication rate warrant consideration of referral to centers with available resources and expertise.

Pancreatitis and cystic fibrosis gene mutations.

Cystic fibrosis (CF) is a genetic disease with multisystem involvement in which defective chloride transport across membranes causes dehydrated secretions. The protein encoded by the CF gene--the cystic fibrosis transmembrane conductance regulator (CFTR)--functions as a cyclic adenosine monophosphate-regulated chloride channel. The ability to detect CFTR mutations has led to the recognition of its association with a variety of conditions, including chronic bronchitis, sinusitis with nasal polyps, pancreatitis, and, in men, infertility. This article reviews the impact of CF on the pancreas, the role of the CFTR protein in pancreatic secretion, and some of the exciting research identifying mutations in the CFTR gene as a risk factor for idiopathic acute and chronic pancreatitis.

Therapeutic biliary endoscopy.

Therapeutic biliary endoscopy continues to evolve; some small but important developments were seen during the last year. Competing technologies are continuing to develop.

Management of acute gastrointestinal hemorrhage in anticoagulated patients.

Bleeding is the major risk associated with anticoagulation therapy. The gastrointestinal tract is the most common site of bleeding. Anticoagulated patients who present with acute gastrointestinal hemorrhage pose great therapeutic challenges. In patients who experience a life-threatening hemorrhage, difficult decisions must be made regarding reversal of anticoagulation, timing of endoscopy and endoscopic therapy, and when to reinstitute anticoagulation. The current literature on the approach to patients who present with major gastrointestinal bleeding while on anticoagulant therapy is reviewed.

Reduced long-term survival following major peptic ulcer haemorrhage.

BACKGROUND: The late outcome of patients who present with major peptic ulcer haemorrhage is unclear. An examination was made of the hypothesis that prognosis may be poor because many such patients have severe co-morbid diseases. METHODS: Some 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median of 36 (range 30-76) months and outcome was compared with that of age- and sex-matched controls. RESULTS: Thirty patients (25 per cent) died during the follow-up period and Kaplan-Meier plots showed reduced survival in patients with ulcers (P < 0.01). Death was restricted largely to patients who had co-morbid diseases. Eight of the remaining 91 patients had further peptic ulcer bleeding; two of these were taking maintenance acid-reducing therapy and only one had significant dyspepsia before rebleeding. Eighty-three per cent of surviving patients had little or no dyspepsia. CONCLUSIONS: The late prognosis of patients who present with major ulcer haemorrhage is poor, but most deaths are a consequence of co-morbid disease and not recurrent ulcer bleeding. Most patients have little dyspepsia and those who rebleed are largely free from dyspepsia.

The outcome of urgent surgery for major peptic ulcer haemorrhage following failed endoscopic therapy.

OBJECTIVE: To review the outcome of patients who underwent emergency surgery for major peptic ulcer haemorrhage after failed endoscopic therapy. To address whether 'conservative' or 'aggressive' surgery is best. DESIGN: A retrospective analysis of emergency surgery for ulcer bleeding which could not be controlled by endoscopic therapy. SETTING: The four admitting units in the Lothian region of Scotland. PARTICIPANTS: Sixty-seven patients who failed endoscopic therapy for bleeding peptic ulcer and underwent emergency surgery between December 1990 and December 1995. Simple underrunning or excision of ulcer alone was done in 31 patients whilst 36 had more radical surgery. MAIN OUTCOME MEASURES: Rebleeding and 30-day mortality rates. RESULTS: Rebleeding was significantly higher in patients treated by underrunning (7 versus 1, P < 0.013). There were fewer deaths in the radically treated group (5 versus 7, not significant). CONCLUSION: Patients undergoing surgical operation for severe peptic ulcer haemorrhage after failed endoscopic therapy may be best served by a relatively aggressive approach.

Peptic ulcer bleeding: perspectives on some common dilemmas.

Not all patients who present with peptic ulcer bleeding need endoscopic therapy, intensive care, or even hospital admission; clinical signs and endoscopic findings determine the need for various levels of care.

Age-related mortality in patients treated endoscopically for bleeding peptic ulcer.

Before the widespread use of endoscopic therapy, mortality from peptic ulcer hemorrhage was highest in elderly patients, and many deaths in this group were a consequence of postoperative complications. Endoscopic intervention greatly reduces the need for an emergency surgical operation, and consequently increasing age may no longer be a risk factor for death from bleeding ulcer. To examine this hypothesis, the outcome of 326 patients undergoing endoscopic therapy for bleeding peptic ulcer was related to age. One hundred two patients were less than 60 years of age (group I), 116 were 61 to 74 years of age (group II), and 108 were older than 75 years (group III). More group III patients were women (p < .0001) and were receiving nonsteroidal anti-inflammatory drugs (p < .0001). Associated concomitant diseases were significantly more common in group II and group III patients (p < .001). Forty-nine (45%) group III patients bled from gastric ulcers. More of group II patients were receiving anticoagulant drugs (p < .005). A previous history of peptic ulcer was most common in group I (p < .005), and duodenal ulcer was usually the cause of bleeding in this group. The three groups were well matched in terms of endoscopic stigmata (active bleeding and nonbleeding vessel), admission hemoglobin concentration, the presence of shock, and total transfusion requirements. Endoscopic therapy (injection or heater probe) was possible in 95% of all patients. The need for surgical intervention tended to be lowest in group I (11%, 19%, and 18%), whereas hospital mortality (3%, 6%, and 5%) was very similar. In this large group of unselected patients with major peptic ulcer bleeding, age did not significantly influence response to endoscopic therapy or hospital mortality.

Distal biliary stricture as a complication of sclerosant injection for bleeding duodenal ulcer.

A patient undergoing repeated endoscopic injection therapy for important bleeding from a duodenal ulcer developed intestinal perforation followed by extrahepatic obstructive jaundice resulting from benign biliary stricture. It is proposed that these complications were a consequence of the use of ethanolamine oleate as part of the injection regimen and caution against the use of this material is needed, particularly as current clinical trials suggest that sclerosants offer no advantage over injection therapy with dilute adrenaline alone.

Failures of endoscopic therapy for bleeding peptic ulcer: an analysis of risk factors.

OBJECTIVES: The role of therapeutic endoscopy in bleeding peptic ulcer is well documented. Nevertheless, failures of endoscopic therapy occur, and such patients could be put at an increased risk of death by delays in definitive surgery. The aim of this study was to define factors associated with failed endoscopic therapy. METHODS: Endoscopic intervention was attempted in 326 consecutive patients presenting with bleeding peptic ulcer using injection or heater probe therapy. RESULTS: Endoscopic therapy was possible in 308 (94%) patients, and permanent hemostasis was achieved in 269 (82.5%) of these. Fifty-seven (17.5%) patients continued to bleed or rebled in hospital. Patients who presented with active hemorrhage, shock on admission, and the lowest hemoglobin concentration did less well than those without these risk factors (p < 0.001). A history of nonsteroidal anti-inflammatory drugs or aspirin usage, coagulopathy, previous peptic ulceration, and concomitant cardiorespiratory disease did not predict outcome of endoscopic therapy. Age of the patient was not an independent risk factor for outcome of therapy. The position of a gastric ulcer did not affect outcome, but a posterior duodenal ulcer was significantly more often associated with failed endoscopic therapy than was the case with an anterior ulcer (p = 0.02). CONCLUSION: Endoscopic interventional treatment should be offered to all high-risk bleeding ulcer patients; no subgroup of patients unlikely to benefit from therapy could be identified.

The outcome of peptic ulcer haemorrhage in relation to consumption of nonsteroidal anti-inflammatory drugs or aspirin.

AIM: To compare the outcome of 76 patients who presented with severe peptic ulcer haemorrhage whilst taking nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin with that of 112 patients who were not taking these drugs and who developed peptic ulcer haemorrhage over the same time period. METHODS: The two groups of patients were managed identically and endoscopic therapy was attempted in all cases. RESULTS: The group taking NSAIDs or aspirin tended to be older and had a higher prevalence of cardio-respiratory disease. The severity of bleeding (as assessed by the presence of shock, anaemia and endoscopic stigmata) was similar in the two groups. Outcome in terms of uncontrolled haemorrhage, rebleeding and blood transfusion requirements did not differ significantly in the two groups. The NSAID group had a significantly longer duration of admission, almost certainly attributable to a higher prevalence of co-morbid diseases. CONCLUSIONS: Despite the deleterious effects of NSAIDs and aspirin upon renal and platelet function, the prognosis of peptic ulcer bleeding is not adversely affected by NSAID or aspirin therapy.

Endoscopic injection therapy for bleeding peptic ulcer; a comparison of adrenaline alone with adrenaline plus ethanolamine oleate.

One hundred and seven consecutive patients presenting with significant peptic ulcer haemorrhage were randomised to endoscopic injection with 3-10 ml of 1:100,000 adrenaline (55 patients, group 1) or to a combination of adrenaline and 5% ethanolamine (52 patients, group 2). All had major stigmata of haemorrhage and endoscopic injection was undertaken by a single endoscopist. The groups were well matched with regard to risk factors. Rebleeding occurred in eight of the group 1 patients and seven in the group 2 patients; surgical operation rates, median blood transfusion requirements, and hospital stay were similar in both groups. The efficacy of either form of injection was similar whether patients presented with active bleeding or a non-bleeding visible vessel. No complications occurred. In patients presenting with significant peptic ulcer bleeding, the addition of a sclerosant confers no advantage over injection with adrenaline alone.

Acute gastrointestinal haemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment.

The underlying diagnosis and clinical course of 52 patients who presented with severe acute gastrointestinal haemorrhage while taking the anticoagulant warfarin is reviewed. A bleeding site was identified in 83% of cases, only slightly fewer than the 92% found in a control of group of 710 patients not taking warfarin who presented in the same four year period. The degree or duration of anticoagulation was unrelated to the frequency of establishing a diagnosis. The commonest diagnosis was peptic ulcer (25 cases) and endoscopic treatment by injection or heater probe was attempted in 23 of these. The outcome in this subgroup was compared with that in 50 closely matched control subjects who had similar risk factors for rebleeding from peptic ulcer. Permanent haemostasis was achieved in (91%) of the anticoagulated and in 92% of the control patients. There were no complications related to endoscopy. Patients who present with acute gastrointestinal haemorrhage while taking warfarin usually bleed from mucosal disease. They should be endoscoped after resuscitation and those with major bleeding from a peptic ulcer should be offered endoscopic treatment.