Long-term follow-up of a randomized controlled trial of observation versus surgery for acute cholecystitis: non-operative management is an option in some patients.

BACKGROUND: Cholecystectomy is routinely recommended to prevent recurrent disease after an initial episode of acute cholecystitis. Therefore, randomized controlled trials have mainly focused on the timing of surgery, but many patients scheduled for cholecystectomy have deferred surgery with long periods of symptom-free intervals. Our present aim is to examine the long-term feasibility and safety of observation compared with surgery. METHODS: Trial of 64 patients with acute cholecystitis previously randomized to observation or cholecystectomy, which examined outcome in terms of completed randomized treatment and appearance of further symptoms and the need for surgical treatment. Thirty-three patients were randomized to observation and 31 patients to cholecystectomy. Median follow-up was 14 years. RESULTS: Of the 33 patients randomized to observation, 11 (33%) experienced a new event of gallstone-related disease (eight (24.2%) had acute cholecystitis) and 11 (33%) were operated. No significant difference (p = 0.565) was found between the two randomized groups with regard to recurrent disease or complications. Virtually no surgery took place after 5 years of follow-up. The difference in completed randomized treatment between the groups was not significant (p = 0.077). Long-term mortality was equal in those operated and in those observed. CONCLUSIONS: Twenty-four percent of the patients experienced recurrent cholecystitis, but escalation of disease severity or increased mortality was not observed. Long-term observation after acute cholecystitis was feasible in two-thirds of the patients as the risk for recurrent disease was negligible after 5 years.

A randomized controlled study of uncomplicated gallstone disease with a 14-year follow-up showed that operation was the preferred treatment.

BACKGROUND/AIMS: Cholecystectomy is considered the treatment of choice for symptomatic gallstone disease. Some patients abstain from surgery and provide the opportunity to study the natural history of cholelithiasis. The aim of the present study was to examine the feasibility and safety of observation after extended long-term follow-up in a randomized controlled trial. METHODS: A total of 137 patients (40.5% of those assessed) were randomized to observation or cholecystectomy and followed up for 14 years. The prevalence of symptomatic events or major complications after treatment was the primary end point. A secondary end point was completion of randomized treatment. RESULTS: There were no differences in outcome between the observation group and the surgical group (p = 0.298). Virtually no cholecystectomy was performed after 5 years of follow-up, and no clear escalation in the severity of the disease was observed. A total of 50.7% of patients from the observation group and 88.2% from the surgical group underwent surgery. The group randomized to surgery completed their designated treatment significantly more often (p < 0.001), especially among patients younger than 70 years of age (p = 0.005). CONCLUSION: Cholecystectomy was the preferred treatment after extended long-term follow-up, but conservative management for symptomatic gallstone disease is an alternative to surgery in the elderly.

Association between gallstone-evoked pain, inflammation and proliferation of nerves in the gallbladder: a possible explanation for clinical differences.

OBJECTIVE: To investigate whether enhanced neuroproliferation could be involved in the pathogenesis of gallstone pain. MATERIAL AND METHODS: Gallbladders from 117 patients with gallstones and 43 controls were examined. The gallbladder samples were immunostained against the pan-neuronal marker PGP 9.5 and the number of nerves and nerve area per tissue area estimated. RESULTS: More nerves and an increased nerve area per tissue area were found in uncomplicated symptomatic gallstone disease. In comparison, acute cholecystitis displayed a significantly (p=0.01) decreased number of nerves and nerve area per tissue area. In both categories, the gallbladder neck contained more nerves (p=0.06 and 0.04, respectively) and an increased nerve area per tissue area (p=0.034 and 0.008, respectively) than the body. CONCLUSIONS: Uncomplicated disease showed enhanced neuroproliferation, significantly more in the gallbladder neck, whereas significantly fewer nerves were observed in acute cholecystitis. Nerve growth alteration may play a role in uncomplicated gallstone pain but the pathology may be different in inflammation.

Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study.

OBJECTIVE: The cardinal indication for surgical treatment of gallstones is pain attacks. However, following cholecystectomy, 20% of patients remain symptomatic. It is unclear to what extent post-cholecystectomy symptoms can be ascribed to persistence of preoperative symptoms or to new pathology. The pain and digestive pattern in gallstone patients has not been defined in a recent setting with ultrasonography as the diagnostic method. The aim of this study was to characterize a pain pattern that is typical for gallstone disease and to describe the extent of associated dyspepsia. MATERIAL AND METHODS: A total of 220 patients with symptomatic gallstone disease including complicated disease (acute cholecystitis and common bile duct stones) were interviewed using detailed questionnaires to disclose pain patterns and symptoms of indigestion. RESULTS: All patients had pain in the right upper quadrant (RUQ) including the upper midline epigastrium. The pain was localized to the right subcostal area in 20% and to the upper epigastrium in 14%, and in the rest (66%) it was more evenly distributed. An area of maximal pain could be defined in 90%. Maximal pain was located under the costal arch in 51% of patients and in the epigastrium in 41%, but in 3% behind the sternum and in 5% in the back. The pain was referred to the back in 63% of the patients. The mean visual analogue scale (VAS) score was very high: 90 mm on a 0-100 scale. A pattern of incipient or low-grade warning pain with a subsequent relatively steady state until subsiding in the same fashion was present in 90% of the patients. An urge to walk around was experienced by 71%. Pain attacks usually occurred in the late evening or at night (77%), with 85% of the attacks lasting for more than one hour and almost never less than half an hour. Sixty-six percent of the patients were intolerant to at least one kind of food, but only 48% to fatty foods. Symptoms of functional indigestion (gastroesophageal reflux, dyspepsia or irritable bowel symptoms) were seen in the vast majority in association with attacks. CONCLUSIONS: Gallstone-associated pain follows a certain pattern in the majority of patients. The pain is located in a defined area with a point of maximum intensity, is usually referred, and occurs mainly at night with duration of more than one hour. The majority of patients experience functional indigestion, mainly of the reflux type or dyspepsia.

Pain persists in many patients five years after removal of the gallbladder: observations from two randomized controlled trials of symptomatic, noncomplicated gallstone disease and acute cholecystitis.

After removal of the gallbladder, pain may persist in some patients. To study this condition, 124 patients from two randomized trials, including those with symptomatic noncomplicated gallbladder stones (n = 90) and acute cholecystitis (n = 34), were interviewed, while 139 patients (90%) excluded from both trials responded to a questionnaire 5 years after the operation. Thirty-four patients (27%) of those randomized had pain; 23 (18%) had diffuse, steady pain; and 11 (9%) had pain attacks resembling their preoperative symptoms. A significant dominance of diffuse pain occurred in women (P = 0.024), especially those younger than 60 years (P = 0.004). A tendency for the diffuse type to be dominant was also present in the group of female patients with symptomatic noncomplicated gallbladder stones (P = 0.052). Of the excluded patients, 18% (25/139) had pain, but 88% of them (96% of the men and 87% of the women) were satisfied with the result of the operation. The overall number of patients with postoperative pain was 22% (59/263). We conclude that persisting abdominal pain 5 years after the operation was mainly of a nonspecific type, found mostly in younger women who had had noncomplicated gallstone disease. Eighty-eight percent of the excluded patients declared themselves satisfied with the result of cholecystectomy.