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Controlled clinical trial comparing early with interval cholecystectomy for acute cholecystitis.

The traditional management of acute cholecystitis is initial conservative treatment with antibiotics followed by elective cholecystectomy. Although early cholecystectomy has often been advocated, there has been only one randomized controlled clinical trial comparing the two methods of treatment. This paper reports the preliminary results of such a trial in which 32 patients have been studied so far. Of the 17 patients managed conservatively, there was a misdiagnosis in 2 (11-8 per cent). In the remaining 15 patients with acute cholecystitis 3 (20 per cent) required urgent operation because of failure of medical treatment. Elective cholecystectomy was not technically difficult. Of the 15 patients treated by early cholecystectomy, there was a misdiagnosis in 1 (6-8 per cent). Surgery was technically difficult in 2 patients but cholecystectomy was possible in all. The former 2 patients required blood transfusion, but in the remainder the estimated blood loss was only slightly more than in the elective group. There was no mortality in either group nor any complication directly attributable to the biliary surgery. The incidence of minor postoperative complications was only slightly greater in those treated by early operation. The length of postoperative stay was similar in both groups but those treated conservatively spent an average of 11 more days in hospital. The preliminary results indicate that those treated by early cholecystectomy spend less time in hospital and avoid the complications of failed conservative treatment without the added risk of increased postoperative mortality and major complications.

Acute Disease

Cholecystectomy and carcinoma of the colon. An experimental study.

The influence of cholecystectomy on the development of carcinoma of the colon is investigated. The experimental results show a significantly increased rate of carcinoma of the colon induced by subcutaneous injection of 1,2-Dimethylhydrazin (DMH) in the mouse after cholecystectomy. After 10 weekly injections of 15 mg/kg DMH, 70% of the animals with cholecystectomy developed carcinoma. Only 16% of the mice with similar treatment but without cholecystectomy had carcinoma. The cocarcinogenic effect of cholecystectomy is assumed to be due to the increased production of secondary bile salts by the colonic bacteria and the lacking of the resorptive function of the gallbladder for some carcinogenic substances passing through the liver. The background of this experimental studies are the clinical findings that 10% of patients with carcinoma of the large bowel had previous cholecystectomy.

Animals

[Cholecystectomy and experimental coloncarcinoma (author's transl)].

The influence of cholecystectomy on the development of carcinoma of the colon is investigated. The experimental results show a significant high rate of carcinoma of the colon induced by subcutaneous injection of 1,2-Dimethylhydrazin (DMH) in the mouse after cholecystectomy. After 10 weekly injections of 15 mg/kg DMH 70% of the animals with cholecystectomy developed carcinoma. Only 16% of the mice with similar treatment but without cholecystectomy had carcinoma. The cocarcinogenic effect of cholecystectomy is assumed to be due to the increased production of secondary bile salts by the colonic bacteria and the lacking of the resorptive function of the gall bladder for some carcinogenic substances passing through the liver. The background of this experimental studies is the clinical findings that 10% of patients with carcinoma of the large bowels had a cholecystectomy previously.

Adenocarcinoma

Incidental cholecystectomy during major abdominal surgery in the elderly.

Forty-four elderly patients with an average age of seventy-eight years were found to have cholelithiasis during unrelated major abdominal surgery. Thirty-nine of them underwent incidental cholecystectomy, one had cholecystostomy, and four had no surgical treatment of their gallbladder disease. Of the thirty-nine patients with an incidental cholecystectomy, none died and only sixteen had nonfatal complications. Of these complications, only one was clearly related to the cholecystectomy and resolved spontaneously. The results compare favorably with other reports of similar procedures in elderly patients. Incidental cholecystectomy does not seem to significantly alter the mortality and morbidity of elderly patients undergoing major abdominal surgery. We advocate incidental cholecystectomy for cholelithiasis in elderly patients as long as the gallbladder is easily accessible and the condition of the patient warrants the additional procedure.

Abdomen

Changes in hepatic bile secretion following cholecystectomy.

The volume and compositon of hepatic bile was studied in anesthetized dogs before and approximately 18 weeks after cholecystectomy. Dogs had common duct cannulation, cystic duct ligation, and temporary occlusion of the pylorus. An intravenous infusion of sodium taurocholate, 9 muEq per minute, was given throughout the experiment. Bile volume, electrolyte composition, bile salt output, and 14C-mannitol clearance were determined during infusion of sodium taurocholate alone and after addition of secretin, 4 U. per kilogram per hour, to the infusion. Cholecystectomy then was done and the same experiment was repeated 18 weeks later. Cholecystectomy significantly increased bile volume, sodium and chloride output, and 14C-mannitol clearance both in response to taurocholate alone and to taurocholate plus secretin. Bile salt output and bicarbonate output were unchanged. The study shows that cholecystectomy significantly alters the volume and composition of hepatic bile. The data indicate that cholecystectomy does not affect ductular function or hepatic secretion of bile salts but that canalicular function is altered significantly.

Animals

Wound sepsis after cholecystectomy: effect of incidental appendicectomy.

The records of a consecutive series of 224 patients were analysed to discover the effect of incidental appendicectomy on the wound sepsis rate after cholecystectomy. One hundred and five patients had had a cholecystectomy alone and 119 cholecystectomy with incidental appendicectomy. The incidence of wound sepsis in patients not given adequate antibiotic prophylaxis was significantly lower (16-1%) when cholecystectomy alone was carried out than when the appendix was removed as well (41-1%).

Adult

Biliary lipid secretion in cholesterol gallstone disease. The effect of cholecystectomy and obesity.

Cholesterol gallstone disease is initiated in a liver which produces abnormal bile with excess cholesterol relative to bile salts and phospholipid. To define the responsible secretory mechanism(s), the rate of biliary lipid secretion was measured by a duodenal marker perfusion technique, while the bile salt pool was simultaneously estimated by isotope dilution. Two groups of control patients expected to have normal biliary lipid composition--14 subjects without hepatobiliary disease and 6 patients with pigment gallstones, were compared to two experimental groups expected to have abnormal bile--10 nonobese patients with cholesterol gallstones and 7 obese subjects without gallstones. Both control groups had nearly identical biliary lipid secretion rates, and a corresponding low relative molar concentration of cholesterol. Two different secretory mechanisms were found to be responsible for the abnormal bile in the experimental groups. In the nonobese patients with cholesterol gallstones, bile salt and phospholipid secretion rates were both significantly reduced. Conversely, the grossly obese subjects had an increased cholesterol secretion. To determine how cholecystectomy improves biliary lipid composition, three groups of gallstone patients --6 with pigment stones, 4 grossly obese with cholesterol stones, and 13 nonobese with cholesterol stones --were all examined after full recovery from surgery. In the nonobese patients with cholesterol gallstones, both bile salt and phospholipid secretion significantly increased, causing a definite improvement in bile composition. Cholecystectomy produced a similar but less marked trend in the obese patients with cholesterol stones, and in the patients with pigment stones. Cholesterol secretion, however, was unaffected by surgery. The bile salt pool was definitely small in the nonobese patients with cholesterol gallstones and became slightly smaller after cholecystectomy. The pool was significantly reduced by cholecystectomyin the patients with cholesterol gallstones. Removal of the gallbladder in all three groups caused a greater fraction of the pool to cycle around the enterohepatic circulation each hour. This more rapid cycling produced the increase in bile salt and phospolipid secretion, and was responsible for the improved composition found after cholecystectomy.

Adult

Cholecystectomy during pregnancy.

While cholecystitis has definitely been associated with pregnancy, performance of cholecystectomy during pregnancy seem to be a rare occurrence. To document this observation we reviewed the records of all cholecystectomies performed during a 10-year period on women between the ages of 16 and 45 in a university hospital and a busy community hospital. Six of the 749 cholecystectomies performed at the university hospital occurred during pregnancies of from four to 26 weeks' gestation. Four of the patients were operated on emergently after an average of one week of conservation management. In no instance did the operation induce premature labor or abortion. Operative cholangiography was performed in four of the patients without detriment to the fetus. This review indicates that the need to perform cholecystectomy during pregnancy is rare, but that it can be performed with minimal risk to the fetus regardless of gestation.

Acute Disease

A controlled trial of drainage after cholecystectomy.

A prospective controlled trial of drainage after cholecystectomy has been carried out. In a consecutive series of 143 patients undergoing cholecystectomy, 50 patients were randomly allocated to a drainage group and a further 50 patients to a non-drainage group. The remaining 43 patients were drained electively because the common bile duct was explored or because of infection or incomplete haemostasis. There was no significant difference in the incidence of wound infection or other complications between the drainage and the non-drainage groups. The duration of postoperative pyrexia, the number of analgesic injections and the length of postoperative hospital stay were the same in both the randomized groups. One patient in the randomized drainage group had a reactionary haemorrhage from the drain site requiring transfusion. There was no mortality but one patient in the elective drainage group had to be re-explored for a subhepatic abscess. Three patients in this group drained bile from the drain for 3-9 days but all had a T tube in place. This trial fails to demonstrate any advantage or disadvantage in draining the gallbladder bed after cholecystectomy.

Adult

Cholecystectomy with and without surgical drainage.

Thirty-seven patients who met specific criteria had cholecystectomy without drainage, and thirty-seven matched control patients had cholecystectomy with drainage. This study suggests that surgical drainage after every uncomplicated cholecystectomy is unnecessary and may be unwise. Such drainage may result in an increased incidence of postoperative morbidity and prolonged hospital stay.

Adolescent

Carl Langenbuch and the first cholecystectomy.

Cholecystectomy is the second most common operation performed today, but its founder, Carl Langenbuch, has received little recognition. The evolution of biliary surgery to the first cholecystectomy is traced. Contributions of von der Wiel, Petit, and Thudicum are reviewed. The cases of the first cholecystotomy by John Stough Bobbs, the first cholecystostomy by Marion Sims, and the first cholecystectomy of Carl Langenbuch are described.

Berlin

Prolonged secretion of lithogenic bile after cholecystectomy.

Hepatic bile samples were obtained from 8 subjects 1 1/2 to 23 years after cholecystectomy for presumed cholesterol gallstones. The content of cholesterol, bile acids and lecithin was determined for each bile sample and compared to the values found in gallbladder bile in 15 control subjects undergoing cholecystectomy for pure and mixed cholesterol stones. Plot of the data on triangular coordinates and subsequent determination of lithogenic index showed that bile was supersaturated with cholesterol in both groups of patients. The cholesterol content of bile remained at supersaturated levels following cholecystectomy and showed no tendency to return toward normal levels with the passage of time.

Adult

Abdominal drainage following appendectomy and cholecystectomy.

Consecutive patients undergoing emergency appendectomy (283) or urgent cholecystectomy (51) were prospectively studied for the development of post-operative incisional or peritoneal sepsis. Severity of the original peritoneal infection was carefully recorded, while use of a Penrose dam to drain the peritoneum was randomized according to pre-assigned hospital number. Both aerobic and anaerobic cultures were taken from the abdomen at the time of operation as well as from all postoperative infectious foci. Results demonstrated no essential differences in incidence of wound and peritoneal infection following appendectomy for simple or suppurative appendicitis (187) or following cholecystectomy for acute cholecystitis (51). However, with gangrenous or perforative appendicitis (94), incisional and intra-abdominal infection rates were 43% and 45%, respectively, when a drain was used; yet only 29 and 13%, respectively, without a drain. These latter differences were significant (p < 0.001). In addition, intra-abdominal abscesses were three times as likely to drain through the incision than along any tract provided by the rubber conduit. Cultures revealed that hospital pathogens accounted for a greater proportion of wound and peritoneal sepsis after cholecystectomy and appendectomy for simple or suppurative appendicitis if a drain had been inserted than if managed otherwise. By contrast, a mixed bacterial flora was responsible for most infections following appendectomy for gangrenous or perforated appendicitis, irrespective as to use of a drain.

Abdomen

Enterohepatic circulation of bile acids after cholecystectomy.

Bile acid metabolism was investigated in 10 patients after cholecystectomy, 10 gallstone patients, and 10 control subjects. Diurnal variations of serum levels of cholic and chenodeoxycholic acid conjugates were not abolished by cholecystectomy. Cholic acid pool size was significantly reduced in cholecystectomised patients and the fractional turnover rate and the rate of intestinal degradation of bile acid showed a significant increase. In cholecystectomised patients fasting bile was supersaturated in cholesterol, though less than in gallstone patients, but, in both, feeding resulted in improvement of cholesterol solubility in bile. These data suggest that after cholecystectomy the small intestine alone acts as a pump in regulating the dynamics of the enterohepatic circulation of bile acids and that the improvement of cholesterol solubility in bile is due to a more rapid circulation of the bile acid pool in fasting cholecystectomised patients.

Bile Acids and Salts

Metagenomic profiling of gut microbiome in post-cholecystectomy patients with diarrhea: a nested case-control study.

BACKGROUND: Cholecystectomy can cause diarrhea, with an incidence as high as 57.2%, seriously impacting patient prognosis. To investigate the gut dysbiosis following cholecystectomy and identify microbial biomarkers and functional genomics associated with post-cholecystectomy diarrhea (PCD), we conducted a nested case-control study within a prospective cohort. METHODS: We enrolled a cohort of 160 patients. At follow-up completion, 30 patients who developed PCD were matched with 30 non-PCD (NPCD) controls. 16&#xa0;S rRNA sequencing was used to analyze gut microbiota structure and diversity (mainly at genus level). Representative fecal samples underwent metagenomic sequencing for species level and genetic differential analysis. RESULTS: The potentially pathogenic bacterial species Coprococcus comes and Blautia sp. were significantly enriched in the gut microbiota of PCD patients, with their abundance positively correlated with the degree of intestinal inflammation. In contrast, the potentially beneficial bacterial species Bacteroides intestinalis and Prevotella copri, known to contribute to lipid metabolism and play a role in modulating gut immunity and suppressing inflammatory responses, were found to be significantly depleted in PCD patients. Further metagenomic functional analysis revealed significant enrichment of pathways related to cell motility, membrane transport, and sulfur metabolism in PCD patients. CONCLUSIONS: This work identified potential beneficial and pathogenic bacterial species associated with the onset of PCD, as well as significantly enriched functional pathways within the intestinal microbiota. These findings provide a scientific basis for elucidating the relationship between PCD and gut microbiota, and provide candidate microbial signatures and functional pathways that may inform future microbiota-targeted strategies, pending external and mechanistic validation.

Humans

Flow through the bile duct after cholecystectomy.

The human bile duct has no intrinsic motility, but following cholecystectomy, flow through the bile duct is governed by the intraductal pressure generated by the liver, by the resistance to flow through the duct and sphincter at the terminal end of bile duct and by intraduodenal pressure. Pressure-flow experiments were performed upon 50 patients with biliary T-tube drainage following cholecystectomy and choledochostomy; nine patients had also undergone transduodenal sphincterotomy. Saline solution was introduced into the bile duct at controlled pressures, ranging from zero to 30 centimeters of water, while recordings were made of the flow rate of saline solution, intraduodenal pressure and respiratory movements. Although the flow rate of saline solution increased as its perfusion pressure was increased, three types of variation in flow were also recorded: rhythmic arrests of flow, occurring four to eight times per minute, believed to be due sphincteric contractions; nonrhythmic arrests of flow, lasting up to one minute, believed to be due to sphincteric contraction, and variations in flow associated with changes in intraduodenal pressure. The resistance to the flow of saline solution and the variations in flow rate were also similar in the patients who had undergone sphincterotomy. This study supports the view that sphincteric activity is present followingcholecystectomy, that the choledochal sphincter has rhythmic activity which differs from that of duodenal motility and that sphincter probably opens and closes continuously in a rhythmic manner during fasting periods in patients who have undergone cholecystectomy.

Bile Ducts