Lillian G. Dawes

Learning sentinel node biopsy: Results of a prospective randomized trial of two techniques

BACKGROUND Evidence indicates that sentinel node (SN) biopsy can accurately predict axillary nodal status. Debate exists as to the optimal method of SN identification. METHODS Patients with clinical T1 or T2 tumors and negative axillae were randomized to SN localization with blue dye (B) alone (n = 50) or blue dye plus radioactivity (B+R) (n = 42). Patients undergoing needle localization (n = 47) were assigned to blue dye. RESULTS The SN was identified in 110 patients (79%) and contained metastases in 28. The SN predicted the axillary nodal status in 96% of cases. The SN identification rate did not differ between B (88%) or B+R (86%) but was significantly lower in patients requiring localization (64%). The time to SN identification also did not differ between B and B+R. The number of cases done by an individual surgeon was a significant predictor of SN identification. A stepwise logistic regression analysis of factors influencing the success of SN identification identified tumor location, needle localization, number of operations, and body mass index as significant predictors. CONCLUSIONS Our study does not identify any advantage for the use of the more expensive and complex method of SN identification using B+R compared with B alone, even for surgeons learning the techniques.

Gangrenous cholecystitis: Analysis of risk factors and experience with laparoscopic cholecystectomy

BACKGROUND Gangrenous cholecystitis occurs in up to 30% of patients admitted with acute cholecystitis. Factors predicting gangrenous disease in patients with acute cholecystitis remain poorly defined, making preoperative diagnosis difficult. Identification of these factors and early diagnosis of gangrenous cholecystitis will indicate more aggressive treatment, earlier operation, and a lower threshold for conversion of laparoscopic to open cholecystectomy. METHODS We reviewed our experience with acute cholecystitis during the 2-year period of 1995 to 1996. Admitting history, physical examination, operative report, laboratory and radiology data, and pathology report were analyzed for each patient. Acute cholecystitis and its gangrenous complication were diagnosed by both gross and microscopic examination. RESULTS One hundred fifty-four patients were admitted to the hospital with acute cholecystitis and underwent cholecystectomy; gallbladder gangrene was found in 27 (18%) of these patients. Four patients with gallbladder gangrene underwent open cholecystectomy and 23 patients underwent laparoscopic cholecystectomy, of which 15 (65%) were completed laparoscopically and 8 (35%) had open conversion as a result of severe inflammation. Risk factors for gallbladder gangrene included male gender, age older than 50 years, history of cardiovascular disease, and leukocytosis greater than 17,000 white blood cells/mL. CONCLUSIONS Older male patients (age older than 50 years) with history of cardiovascular disease, leukocytosis greater than 17,000 white blood cells/mL, and acute cholecystitis have increased risk of gallbladder gangrene and conversion of laparoscopic cholecystectomy to open cholecystectomy. Urgent laparoscopic cholecystectomy with low threshold for conversion to open cholecystectomy should be considered in these patients at high risk for gallbladder gangrene.

Isolation of an acidic protein from cholesterol gallstones, which inhibits the precipitation of calcium carbonate in vitro.

In seeking to identify nucleating/antinucleating proteins involved in the pathogenesis of cholesterol gallstones, a major acidic protein was isolated from each of 13 samples of cholesterol gallstones. After the stones were extracted with methyl t-butyl ether to remove cholesterol, and methanol to remove bile salts and other lipids, they were demineralized with EDTA. The extracts were desalted with Sephadex-G25, and the proteins separated by PAGE. A protein was isolated, of molecular weight below 10 kD, which included firmly-bound diazo-positive yellow pigments and contained 24% acidic, but only 7% basic amino acid residues. The presence of N-acetyl glucosamine suggested that this was a glycoprotein. This protein at concentrations as low as 2 micrograms/ml, but neither human serum albumin nor its complex with bilirubin, inhibited calcium carbonate precipitation from a supersaturated solution in vitro. This protein could be precipitated from 0.15 M NaCl solution by the addition of 0.5 M calcium chloride. Considering that cholesterol gallstones contain calcium and pigment at their centers, and that small acidic proteins are important regulators in other biomineralization systems, this protein seems likely to play a role in the pathogenesis of cholesterol gallstones.

Resistant pathogens in biliary obstruction: Importance of cultures to guide antibiotic therapy

BACKGROUND Cholangitis, infection of the bile ducts, is a serious condition that necessitates prompt and efficacious treatment for a good clinical outcome. A single center retrospective study of cholangitis was conducted to better define the spectrum of responsible pathogens and their antibiotic sensitivities. METHODS We studied all patients at our hospital who had cholangitis from January 1998 to June 2004. Patients were identified by ICD-9 codes and the cause of the cholangitis, the treatment and culture data were noted by review of the medical record. RESULTS Thirty patients presented with cholangitis as noted by the clinical symptoms of jaundice, fever and abdominal pain. The cause of the biliary obstruction was gallstones in 18 patients, benign biliary strictures in 5 and malignant obstruction in 7. All the patients with malignant obstruction with cholangitis had stents; there were no cases of cholangitis in malignant obstruction unless prior instrumentation had been performed. The most common isolates were Enterococcus>E. coli>Enterobacter>Klebsiella. Sixty-four percent of blood cultures and all but one of the bile cultures grew organisms. Seventy-two percent of patients had positive blood cultures with at least one resistant organism present and 36% had organisms resistant to multiple antibiotics. Fifty percent of patients with benign biliary disease and positive blood cultures had multiple organisms growing in their blood. Three-quarters of the isolates were resistant to one or more antibiotics and one-quarter of isolates were resistant to three or more antibiotics. Resistant organisms were found regardless of the cause of the biliary obstruction. DISCUSSION For all causes of cholangitis, there is a high incidence of positive blood cultures and a high rate of antibiotic resistance. For optimal treatment, blood and/or bile cultures should be routinely performed to optimize antibiotic therapy.

Supersaturation of canine gallbladder bile with calcium bilirubinate during formation of pigment gallstones

Analogous to cholesterol gallstones forming in bile supersaturated with cholesterol, pigment gallstones may form in bile supersaturated with calcium bilirubinate. We tested this hypothesis in a dietary model of pigment gallstones. The concentration of ionized calcium (Ca++) and unconjugated bilirubin (UCB) was measured in 15 normal dogs and in 15 dogs with pigment gallstones induced by 6 weeks of a methionine-deficient diet. Although there was minimal change in the gallbladders ability to acidify or concentrate bile, both [Ca++] and [UCB] markedly increased. These values were compared with equilibrium concentrations in model bile solutions. In all normal bile, the [UCB] was equal to or lower than the mean [UCB] concentration of model bile solutions with comparable [Ca++]. However, in all but one bile sample from dogs with pigment gallstones, the [UCB] exceeded this concentration and was therefore supersaturated with calcium bilirubinate. This supports the hypothesis that calcium bilirubinate precipitation is important in the formation and growth of pigment gallstones.

The influence of splenic weight and function on survival after experimental pneumococcal infection.

Splenectomy impairs survival after pneumococcal challenge in rats, while preservation of sufficient splenic tissue can be protective. This study investigated the effects of methylcellulose on stimulation of splenic weight, splenic histology, reticuloendothelial (RE) activity, and survival after pneumococcal infection. Methylcellulose increased spleen weight four- to five-fold but did not improve RE function or survival after infection. These parameters correlated best with the weight of the remnant in animals that did not receive methylcellulose. The functional limitations of splenic autotransplants were not corrected by methylcellulose stimulation of splenic weight. Preservation of a splenic remnant with intact blood supply is preferable to autotransplantation of the spleen to conserve RE capability.

Secretion of biliary calcium is increased in dogs with pigment gallstones

We have previously demonstrated that gallbladder bile is supersaturated with calcium bilirubinate in a canine dietary model of pigment gallstones. Supersaturation resulted from combined increases in the concentrations of both biliary calcium and unconjugated bilirubin. The elevations in biliary calcium and unconjugated bilirubin concentrations remain unexplained but could possibly be due to increases in hepatic or ductular secretion, alterations in bile composition with respect to calcium- or bilirubin-binding affinity, decreases in absorption from the gallbladder lumen, or, in the case of unconjugated bilirubin, production within the lumen by hydrolysis of conjugated bilirubin. Here, we study a single possible cause for the observed increase in biliary calcium concentration during pigment gallstone formation in dogs. Secretion of calcium into bile in dogs with pigment gallstones before and after infusion of the bile salt, taurocholate, was compared to normal dogs. A significant increase in bile acid-independent bile flow and calcium output (CaO) was observed at any given bile acid output. Thus, plots of bile flow and CaO versus bile acid output yielded two separate functions in normal dogs and dogs with pigment gallstones. The slopes of these functions were similar, but intercepts extrapolated to zero bile acid output were markedly different, indicating that bile acid-independent, but not bile acid-dependent, bile flow and CaO was increased. The increase in CaO was not due to secretion of bile with increased concentrations of calcium but rather to the increases in the rate of bile flow. These findings might, in part, explain elevated calcium concentrations since increased amounts of calcium would be presented to the gallbladder in these animals during gallstone formation.

42 – Gallbladder and Biliary Diseases: More Common in Women, More Severe in Men

Although differences in the sex distribution of gallbladder and biliary tree diseases are well established, the understanding of these differences is limited. With the presence of anatomic and physiologic differences, hormones may play an important role in these diseases. Much knowledge is needed to fully understand how sex influences the gallbladder and bile ducts. Better understanding of the origin of these gender differences will lead to strategies to improve the treatment and prevention of these disorders. Gallstones, gallbladder cancer, and choledochocysts are more frequent in women, while sclerosing cholangitis and acalculous cholecystitis are proportionately more often seen in men. This chapter reviews the current knowledge regarding the sex differences of gallbladder and biliary diseases and promotes further investigation into such differences.