Giovanni Cucchiaro

Surgical treatment of 724 carcinomas of the gallbladder. Results of the French Surgical Association Survey.

ObjectiveThe objective of this study was to evaluate the benefit of an aggressive approach to gallbladder carcinoma on long-term survival. Summary Background DataRecent studies have shown that an aggressive surgical treatment of bile duct carcinoma can be associated with a surprising long-term survival. However, recent data on gallbladder carcinoma are not available. MethodsData were obtained from a questionnaire sent to 73 institutions in France, Europe, and overseas, and they were analyzed retrospectively. The review included an analysis of patient sex and age, associated hepatobiliary diseases, symptoms and signs, diagnostic tests, operative management, pathology reports, and survival.Results Seventy-eight per cent of the patients were woman, and 22% were men (p < 0.001). Gallstones were present in 86% of the cases. Four per cent of the patients had Tis stage lesions, 11 % had T1 to T2 stage lesions, and 85% had T3 to T4 stage lesions (p < 0.001). Pain was the most frequent symptom (77%). Twenty-three per cent of the patients underwent curative operations, and 77% had a palliative treatment (25% of the patients underwent exploratory laparotomy). Exploratory laparotomy was followed by the highest mortality rate (66%), and older patients (> 70 years) had a higher operative risk (p < 0.04). The overall median survival was 3 months, and long-term survival correlated with the cancer stage (Tis, > 60 months; T1 to T2, > 22 months, and T3 to T4, 2 to 8 months). No differences were observed among the different surgical procedures adopted. ConclusionsNo progress has been made in the last 10 years in the treatment of gallbladder malignancies.

Complications of Laparoscopic Cholecystectomy

Laparoscopic cholecystectomy is a safe and effective treatment of cholelithiasis in experienced hands. Mortality is rare. The Southern Surgeons Club data and several other recent large series indicate that major complications occur in less than 3% of patients. The most significant common complication is injury to the bile duct, for which the greatest risk factor is inexperience. Major biliary injury usually requires reoperations. Roux-en-Y hepaticojejunostomies, often multiple, are usually necessary for repair. The popularity of this technique continues, and further efforts should be focused on elimination of the learning curve for major biliary injury. If injuries do occur, they should be recognized early, and patients should be referred to centers experienced in their treatment.

Distal splenorenal shunt versus endoscopic sclerotherapy in the prevention of variceal rebleeding. First stage of a randomized, controlled trial.

In 1984 we started a prospective controlled trial comparing endoscopic sclerotherapy (ES) with the distal splenorenal shunt (DSRS) in the elective treatment of variceal hemorrhage in cirrhotic patients. The study population included 40 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1988. These patients were drawn from a pool of 173 patients who underwent either elective surgery or endoscopic sclerotherapy during this time. Patients were assigned to one of the two groups according to a random-number table: 20 to DSRS and 20 to ES. During the postoperative period, no DSRS patient died, while one ES patient died of uncontrolled hemorrhage. One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS. Four ES patients suffered at least one episode of gastrointestinal bleeding: two from varices and two from esophageal ulcerations. Five ES patients developed transitory dysphagia. Long-term follow-up was complete in all patients. Two-year survival rates for shunt (95%) and ES (90%) groups were similar. One DSRS patient rebled from duodenal ulcer, while three ES patients had recurrent bleeding from esophagogastric sources (two from varices and one from hypertensive gastropathy). One DSRS and two ES patients have evolved a mild chronic encephalopathy; four DSRS and two ES patients suffered at least one episode of acute encephalopathy. Two ES patients had esophageal stenoses, which were successfully dilated. Preliminary data from this trial seem to indicate that DSRS, in a subgroup of patients with good liver function and a correct portal-azygos disconnection, more effectively prevents variceal rebleeding than ES. However no significant difference in the survival of the two treatment groups was noted.

Selective distal splenorenal shunt versus side-to-side portacaval shunt. Clinical results of a prospective, controlled study.

A prospective, controlled study comparing the clinical results of the selective distal splenorenal shunt procedure and the side-to-side portacaval shunt procedure was undertaken in 1980. Ninety-three cirrhotic patients with previous episodes of bleeding from esophageal varices underwent a distal splenorenal shunt procedure (47 patients). The operative mortality rate was 2 percent in both groups. The intraoperative decrease of portal hypertension after the portacaval shunt procedure was higher than after the distal splenorenal shunt procedure (p less than 0.05), and in those with patent shunts, there was a 0 percent incidence of early variceal rebleeding after the portacaval shunt procedure compared with a 9 percent incidence after the distal splenorenal shunt procedure (p less than 0.05). Both shunts, however, had similarly satisfactory results in preventing long-term variceal rebleeding (portacaval shunt 2 percent and distal splenorenal shunt 0 percent). Postoperative ascites was more common after the distal splenorenal shunt procedure (58 percent versus 24 percent; p less than 0.01). Analysis of actuarial survival curves showed no difference between the two procedures. The incidences of long-term episodes of chronic encephalopathy were not statistically different after both procedures. The only three instances of severe encephalopathy occurred in patients with the portacaval shunt (p less than 0.05). The distal splenorenal shunt also seemed to have a less negative effect on postoperative liver function than the portacaval shunt. These data suggest that the selective shunt should be viewed as a first choice strategy in the treatment of portal hypertension.

Deaths from gallstones. Incidence and associated clinical factors.

The purpose of this study was to determine the incidence of death as the initial manifestation of cholelithiasis. Records of patients who died or underwent cholecystectomy for gallstone-related disease at Duke University Medical Center between 1976 and 1985 were reviewed. Thirty patients died, six of whom (20%) had previous episodes of biliary pain and stone documentation. Twenty-four (80%) were asymptomatic (three with previous incidental diagnosis of cholelithiasis). Reason for admission included acute cholecystitis (nine), pancreatitis (eight), biliary pain (six), cholangitis (four), jaundice (one), and endocarditis (one). Three patients died of gallstone complications without surgical intervention; one patient had renal failure and two had septicemia. Other causes of death were: sepsis (seven patients), cardiac failure (six), pulmonary complications (four), renal failure (three), cerebrovascular accident (three), liver failure (two), pancreatitis (one), and gastrointestinal bleeding (one). During this period, 1731 cholecystectomies were performed without mortality. In this group, the patients were younger (50 +/- 8 years vs. 64 +/- 13 years, p less than 0.001), and had a lower incidence of cirrhosis (p less than 0.001) and diabetes (p less than 0.002). The sex ratio was inverted (p less than 0.001). This study demonstrates that death from gallstones is uncommon (three cases per year), as is death from their initial clinical manifestation (1.2%). The risk of death is two- and ninefold higher in patients with acute cholecystitis or acute pancreatitis. Age, cirrhosis, and diabetes are important determinants of outcome.

Clinical significance of ultrasonographically detected coincidental gallstones

The clinical profiles of 139 patients with gallstones found coincidentally during ultrasonography were reviewed and the patients followed prospectively for five years. Indications for ultrasonography included follow-up of abdominal malignancy (33%), evaluation of abdominal aortic aneurysm or other arteriosclerotic vascular disease (22%), renal insufficiency (12%), and lower abdominal pain (7%). At the time of gallstone detection, 14 patients (10%) had symptoms attributable to cholelithiasis. Over the next five years, only 15 patients (11%) developed episodes resembling biliary pain. Nine patients underwent cholecystectomy during this period. Three of the cholecystectomies were incidental to other abdominal procedures. Two cholecystectomies were performed as emergencies for gallstone complications with no perioperative mortality. Interestingly, 54 patients (40%) with coincidental gallstones died during the follow-up period. All the deaths were unrelated to gallstones. These data indicate that Ultrasonographically detected coincidental gallstones rarely have clinical significance, lending strong support to the expectant management of most patients with purely coincidental gallstones.

The effects of liver denervation on the regulation of hepatic biliary secretion.

Effects of liver denervation on bile formation were studied in eight dogs prepared with chronic biliary fistulas. The animals were studied in the basal state, after feeding, and during infusion of glucagon 50 ng/kg/min, secretin 2 U/kg/hr, or somatostatin 200 ng/kg/min. After this first set of experiments the animals underwent a total hepatic denervation that consisted of section of the hepatic ligaments and a careful dissection of the portal vein, hepatic artery, and common duct with stripping of all the surrounding connective tissue and topical application of phenol. The above experiments were then repeated. Denervation did not modify bile flow, or bile salts, cholesterol, or phospholipid concentration or output. Biliary response to glucagon and secretin was similar before and after denervation. Somatostatin had an anticholerectic effect in both intact and denervated animals, but significantly reduced bile salt output only in the intact dogs. Feeding had a choleretic effect pre- and postdenervation, and the infusion of somatostatin following feeding decreased bile flow to the same degree before and after denervation. In the intact animals the output of all three biliary lipids was reduced by somatostatin after feeding but they were unaffected by somatostatin after denervation. Moreover, cholesterol and phospholipid outputs were stable after feeding in intact animals, but significantly decreased after denervation. 14C-erythritol clearance studies indicated no change in the canalicular component of bile flow with denervation, except again during somatostatin suppression of feeding. These data indicate that basal bile flow is normal after denervation but that innervation may play an important role in the modulation of responses to somatostatin and more complex stimuli such as feeding.

Biliary response to glucagon in humans.

Glucagon has been demonstrated to have profound effect on biliary secretion in several species. Glucagons biliary effects were studied in humans following biliary tract surgery. Nine patients underwent common bile duct exploration and insertion of a balloon-occludable t tube. An aliquot of the collected sample was kept and the enterohepatic circulation was maintained by reinfusion of the collected bile via the distal t-tube port. Glucagon increased bile flow and decreased cholesterol and phospholipid output during stable bile acid output. Furthermore high-performance liquid Chromatographie analysis of bile acid profiles revealed no significant changes in bile salt species or conjugation after glucagon infusion. Glucagon is probably important in the physiologic regulation of biliary secretion in humans.

Improved quality of life after distal splenorenal shunt. A prospective comparison with side-to-side portacaval shunt.

The distal splenorenal shunt (DSRS) was compared with the side-to-side portacaval shunt (PCS) in 93 prospectively matched patients with portal hypertension. After 38 months mean follow-up the two shunts had a different incidence of acute encephalopathy (22% in PCS group and 33% in DSRS group) and chronic encephalopathy (35% in PCS group and 17% in DSRS group), but the difference was not statistically significant. However, the only cases of severe and disabling chronic encephalopathy arose after PCS (p = 0.049). Actuarial curves of chronic encephalopathy showed that the maximum rate of encephalopathy (18%) in the DSRS group was reached 27 months after shunt surgery, whereas this value was reached and passed in PCS group only 4 months after shunt. Chronic encephalopathy occurred for a total duration of 20.1 months after PCS and only 11.1 months after DSRS (p = 0.003) and occupied 46.3% of the follow-up of PCS patients, as contrasted to 18.7% of the follow-up of DSRS patients (p = 0.0001). DSRS is associated with a lower global incidence of chronic HE without severe forms and provides a better quality of life than does a nonselective shunt.

A model for biliary and vascular access in the unanesthetized, unrestrained rat.

Conventional methods for vascular access and bile collection in the rat, such as the isolated perfused liver, study under anesthesia, and animal restraint, do not allow study of a physiologically intact rat. A simple technique for vascular access and monitoring of biliary secretions in the intact, unrestrained, unanesthetized rat for extended periods of time is described. Sample experiments demonstrated a 20% complication rate and an 85% 24-hour survival. This model may prove useful in studies requiring chronic vascular and visceral catheterization in the awake rat.