James Toouli

The Efficacy of Endoscopic Sphincterotomy after Cholecystectomy in Patients with Sphincter-of-Oddi Dysfunction

Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction.

Guidelines for the management of acute pancreatitis

Level 1: Evidence obtained from systematic reviews of all relevant randomized controlled trials. Level 2: Evidence derived from at least one properly designed randomized controlled trial. Level 3: Evidence from a well-designed control trial without randomization; or from well-designed cohort or case–control analytical studies; preferably from more than one center or research group; or from multiple time series with or without intervention. Level 4: Opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees.This level signifies the need for further research. The final document was prepared and submitted to the Secretary General of OMGE for final scrutiny prior to publication for the World Congress of Gastroenterology. At the congress the recommendations were presented and questions and comments noted. These comments were incorporated into the final guidelines where appropriate.

Control of belching by the lower oesophageal sphincter.

The mechanism that controls venting of gas from the stomach into the oesophagus was studied manometrically in 14 healthy subjects. The stomach was distended abruptly with one litre of carbon dioxide. Gas reflux was characterised by an abrupt increase in basal oesophageal body pressure to intragastric pressure. Reflux of gas from the stomach into the oesophagus occurred during transient lower oesophageal sphincter relaxations that generally had a pattern distinctly different from swallow-induced lower oesophageal sphincter relaxation. Thus, at the onset of an episode of gas reflux lower oesophageal sphincter pressure had relaxed to 3 mmHg, or less, in 96% of instances. After gas loading of the stomach the prevalence of gas reflux was significantly less when the subjects were supine (1.2/10 min) than when they were sitting (6.8/10 min) (p less than 0.001). The lower oesophageal sphincter relaxations associated with most episodes of gas reflux had a distinctive pattern that resembled those of the lower oesophageal sphincter relaxations associated with acid gastro-oesophageal reflux.

Acalculous biliary pain: Cholecystectomy alleviates symptoms in patients with abnormal cholescintigraphy

A 45-minute infusion of an octapeptide of cholecystokinin (Kinevac; Squibb Diagnostics, New Brunswick, NJ) was used to measure the gallbladder ejection fraction during cholescintigraphy in 40 normal volunteers. Cholecystokinin cholescintigraphy was shown to be a reproducible test. The maximum mean gallbladder ejection fraction occurred 15 minutes after cholecystokinin infusion and was 74.5% +/- 1.9% (mean +/- SEM). A gallbladder ejection fraction greater than 40% (mean -3SD) was arbitrarily defined to be normal. The gallbladder ejection fraction test was then used to identify patients with acalculous biliary symptoms who may respond to cholecystectomy. A total of 103 patients was tested; 21 had abnormal gallbladder ejection fractions and were randomized into two groups, cholecystectomy or no operation. These patients were followed up symptomatically at 3-month intervals for 13-54 months (mean, 34 months). Of the 11 patients who underwent cholecystectomy, 10 (91%) lost their symptoms and 1 improved. Of the 10 patients in the group that did not undergo surgery, all continued to be symptomatic, 2 of whom requested cholecystectomy after 13 and 24 months, respectively. Of the 13 gallbladders obtained from surgery, 12 showed evidence of chronic cholecystitis, muscle hypertrophy, and/or narrowed cystic duct. A normal gallbladder ejection fraction was recorded in 82 patients, and further treatment was left to the discretion of their referring clinician. On follow-up, 50 patients were asymptomatic and 10 were symptomatic without specific treatment of the biliary tract; 14 underwent cholecystectomy, 8 of whom were asymptomatic. Pathological abnormalities were recorded in 6 of the removed gallbladders. It is concluded that the gallbladder ejection fraction obtained after a 45-minute infusion of cholecystokinin during cholescintigraphy is a reproducible measure of gallbladder emptying, and that cholecystectomy alleviates the biliary-type pain of patients with a reduced gallbladder ejection fraction.

Laparoscopic cholecystectomy for acute inflammation of the gallbladder.

OBJECTIVE The aim of this study was to prospectively assess the results of laparoscopic cholecystectomy in patients with acute inflammation of the gallbladder. SUMMARY BACKGROUND DATA Laparoscopic cholecystectomy has become the standard treatment for symptomatic gallbladder disease. Its role in the surgical treatment of acute cholecystitis has not been defined, although a number of recent reports suggest that there should be few contraindications to an initial laparoscopic approach. METHODS All patients presenting with symptomatic cholelithiasis from October 1990 until June 1992 were evaluated at laparoscopy with intention of proceeding to a laparoscopic cholecystectomy. The gross appearance of the gallbladder was categorized as acute inflammation, chronic inflammation, or no inflammation. Ninety-eight (23.4%) of 418 patients had acute inflammation of the gallbladder: 55 were edematous, 10 were gangrenous, 15 had a mucocele, and 18 had an empyema. RESULTS The authors assessed outcome in these patients. The frequency of conversion to an open operation was 33.7% for acute inflammation, 21.7% for chronic inflammation (p < 0.05), and 4% for no inflammation (p < 0.001). The conversion rate was highest for empyema (83.3%) and gangrenous cholecystitis (50%), while the conversion rate for edematous cholecystitis was 21.8% and for acute inflammation with a mucocele it was 7%. The median operation time for successful laparoscopic cholecystectomy for acute inflammation was 105 minutes, which was longer than that with no inflammation (90 minutes). However, the incidence of complications was not different from that for chronic or no inflammation. The median postoperative stay for patients with acute gallbladder inflammation was 2 days for successful laparoscopic cholecystectomy and 7 days for patients converted to an open operation. CONCLUSIONS Laparoscopic cholecystectomy for acute inflammation of the gallbladder is safe and is associated with a significantly shorter postoperative stay compared to open surgery. A greater number of patients required conversion to open operation compared to those with no obvious inflammation. Conversion to open operation was most frequent for empyema and gangrenous cholecystitis, suggesting that once this diagnosis is made, excessive time should not be spent in laparoscopic trial dissection before converting to an open operation.

The value of serum carcinoembryonic antigen in predicting recurrent disease following curative resection of colorectal cancer

Carcinoembryonic antigen (CEA) estimations are used to facilitate early diagnosis of recurrent disease after treatment for colorectal cancer. PURPOSE: This study was designed to determine the natural history of patients with normal and abnormal levels of CEA. METHODS: Patients undergoing potentially curative resection of colorectal tumors (Dukes Stage A-C) entered a prospective, randomized trial comparing two follow-up regimens (to be reported separately) had CEA levels measured every 3 months for two years; then every 6 months for the next three years. In the study protocol, a rise in CEA was not an indication for investigation to determine recurrence unless there was also other evidence of recurrent disease. RESULTS: Three hundred eleven patients were followed for a median of 4.5 (range, 2–5) years. Recurrent disease developed in 98 (32 percent) patients, 57 of whom had an elevated CEA (sensitivity 58 percent), with a median lead time of six (range, 1–30) months from first abnormal CEA to diagnosis of recurrent disease by other means. The specificity, positive predictive value, and negative predictive value of CEA as an indicator of subsequent recurrent disease was 93 percent, 79 percent, and 83 percent, respectively. The sensitivity of CEA for predicting hepatic metastases was 80 percent, with a median lead time of eight (range, 1–30) months, compared with only 46 percent for sites of recurrent disease other than the liver. CONCLUSIONS: CEA was the first indicator of recurrent disease in 58 percent of all patients and in 80 percent of patients with liver metastases. The diagnosis of recurrent disease may be made several months earlier by investigating the first abnormal CEA level, although any benefit in terms of survival remains to be proven.

Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction

BACKGROUND Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis). AIM To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry. METHODS Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months. RESULTS In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter. CONCLUSION In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.

Prospective randomized comparison of open versus laparoscopic appendectomy in men.

Abstract. A prospective, randomized trial was performed to compare open appendectomy with laparoscopic appendectomy in men with a clinical diagnosis of acute appendicitis. Sixty-four patients with a median age of 25 years (range 18–84 years) were randomized to open appendectomy (n = 31) or laparoscopic (n = 33) appendectomy. Of the 64 men, 56 (87.5%) had appendicitis (27 open, 29 laparoscopic procedures). The mean operating times were 50.6 ± 3.7 minutes (± SEM) for open and 58.9 ± 4.0 minutes for laparoscopic appendectomy (p = 0.13). Five (15%) patients randomized to laparoscopic appendectomy had an open operation. The mean postoperative hospital stay was significantly longer for open appendectomy (3.8 ± 0.4 days) than for laparoscopic appendectomy (2.9 ± 0.3 days) (t = 2.05,df = 62,p = 0.045). The complication rate after open appendectomy (25.8%) was not significantly different from that after laparoscopic appendectomy (12.1%). There was a single postoperative death due to a pulmonary embolus in the laparoscopic group and a single death due to cardiac and renal failure in the open group. The mean time to return to normal activities was significantly longer following open appendectomy (19.7 ± 2.4 days) than after laparoscopic appendectomy (10.4 ± 0.9 days), (t = 3.75,df = 49,p = 0.001). In conclusion, laparoscopic appendectomy in men has significant advantages in terms of a more rapid recovery compared to open appendectomy. There were no significant disadvantages to laparoscopic appendectomy compared to open appendectomy.

Factors that influence induction of gastroesophageal reflux in normal human subjects

Findings from recent studies indicate that transient relaxation of the lower esophageal sphincter (LES) is an important contributory mechanism to spontaneous episodes of gastroesophageal reflux (GER) in normal subjects as well as in patients with reflux esophagitis. Our study aim was to evaluate the interrelationship between reduction of LES pressure and elevation of intraabdominal pressure in the induction of GER in healthy subjects. Seven volunteers were studied supine after gastric loading with 0.1 N HCl. A pH probe recorded acid GER. Leg raising (LR) or abdominal compression (AC) were used as stress maneuvers to increase intraabdominal pressure, either alone or in combination with stimuli that concurrently lowered LES pressure, namely multiple rapid swallows (RS) or intraesophageal balloon distention (BD). Each individual stimulus and stimulus combination was tested three times, giving a total of 24 test maneuvers per subject. The test maneuvers elicited 2–12 GERs in each subject. The GER incidence for single maneuvers was: AC, 0%; LR, 0%; RS, 19%; and BD, 24%. LR in combination with RS or BD did not increase the incidence of GER above that induced by RS or BD alone. In contrast, AC concurrent with RS and BD increased the incidence of GER to 52% and 81%, respectively. For all test conditions, a prerequisite for the occurrence of GER was a fall in LES pressure to a minimal value of 3 mm Hg or less. GER never occurred when LES pressure was ≥4 mm Hg, even during intervals of increased intraabdominal pressure. We conclude that (1) virtually complete absence of LES pressure is an essential prerequisite for the induction of GER; (2) during intervals of negligible LES pressure, elevation of intraabdominal pressure increases the prevalence of GER;and (3) LR by normal subjects induces a substantial increase in the abdominal pressure but does not increase GER, probably due to a pinch-cock effect of the diaphragmatic hiatus on the intrahiatal esophageal segment.

Effect of Reversible Intermittent Intra-abdominal Vagal Nerve Blockade on Morbid Obesity The ReCharge Randomized Clinical Trial

IMPORTANCE Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. OBJECTIVE To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. INTERVENTIONS One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. MAIN OUTCOMES AND MEASURES The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. RESULTS In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target (P = .71), although weight loss was statistically greater in the vagal nerve block group (P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy-related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. CONCLUSION AND RELEVANCE Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01327976.