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Strategies for imaging biliary neoplasms.

Biliary tract neoplasms are rare, develop in either intra- or extrahepatic locations, and are represented by a spectrum of imaging characteristics. These tumors may be imaged using a variety of traditional methods, such as ERCP, PTC, ultrasound, or CT, and some newer innovative cross-sectional techniques, such as MR- or CT-cholangiography. The choice of imaging technique depends on whether the study is for diagnostic, staging, or therapeutic purposes. Because these tumors are frequently small, secondary features such as intrahepatic ductal dilatation or even hepatic metastases, may be the initial finding on screening studies. Benign tumors, postsurgical strictures, or even biliary sludge may mimic features of malignant tumors, and the radiologist must be aware of these potential sources of interpretative error.

Biliary Tract↗

Microsatellite instability in intraductal papillary neoplasms of the biliary tract.

Intraductal papillary neoplasms of the biliary tree are unusual lesions characterized by solitary or diffuse growth along the intra- and/or extrahepatic biliary tract. Biliary papillary neoplasms bear some clinicopathologic similarity to intraductal papillary mucinous neoplasms of the pancreas. Like intraductal papillary mucinous neoplasms of the pancreas, biliary papillary neoplasms can be purely intraductal lesions or can give rise to invasive adenocarcinomas. We recently studied the genetic alterations present in a series of biliary papillary neoplasms and noted the presence of allelic shifts in some biliary tumors during allelic loss assays on chromosomes 5q and 18q. This suggested that microsatellite instability might play a role in the molecular pathogenesis of biliary papillary neoplasms. Genomic DNA was extracted from 17 intraductal papillary neoplasms, 6 associated invasive cholangiocarcinomas, and corresponding normal tissues, and microsatellite instability testing was performed using the 5 microsatellite loci recommended by the 1997 National Cancer Institute-sponsored consensus conference (D2S123, D5S346, D17S250, Bat-25, and Bat-26). High-level microsatellite instability was considered to be present when at least two of five microsatellite loci showed allelic shifts, and low-level microsatellite instability, when only one locus was shifted, as per the National Cancer Institute criteria. We also determined the methylation status of the DNA mismatch repair gene hMLH1 by bisulfite treatment of genomic DNA, followed by methylation-specific PCR. High-level microsatellite instability was present in 2 of 17 (11.8%) biliary papillary neoplasms, including 1 case of purely intraductal tumor and 1 case with both intraductal and invasive cholangiocarcinoma components. In both cases there was extensive microsatellite instability, with allelic shifts in five of five and four of five microsatellite markers, respectively. Low-level microsatellite instability was present in 6 of 17 (35.3%) biliary papillary neoplasms, including 2 cases of purely intraductal tumor and 4 cases with both intraductal and invasive cholangiocarcinoma components. Interestingly, the pattern of allelic shifts was frequently not identical between the intraductal and invasive cholangiocarcinoma components; although the same microsatellite markers were shifted, alleles of differing lengths were generated in the intraductal and invasive components of the neoplasms with high-level microsatellite instability and of two neoplasms with low-level microsatellite instability. None of the biliary papillary neoplasms (0 of 10 cases with adequate DNA for evaluation) showed methylation of hMLH1. These results indicate that microsatellite instability is a relatively frequent event in papillary neoplasms of the biliary tree but is not associated with hMLH1 promoter hypermethylation. The finding that alleles of differing lengths were frequently generated between the intraductal and invasive components of those tumors with microsatellite instability suggests that there is significant genetic heterogeneity within these neoplasms.

Adaptor Proteins, Signal Transducing↗

Molecular and immunohistochemical analysis of intraductal papillary neoplasms of the biliary tract.

Intraductal papillary neoplasms (IPNs) of the biliary tract are uncommon lesions that may be solitary or may spread extensively along the biliary tree. Some biliary IPNs are histologically and radiologically similar to intraductal papillary mucinous tumors (IPMNs) of the pancreas and present a risk for progression to invasive cholangiocarcinoma. Unlike pancreatic IPMNs, little is known about their molecular pathogenesis. We studied 14 biliary IPNs (including 5 cases with associated invasive cholangiocarcinoma) for genetic alterations in the APC/beta-catenin pathway, K-ras oncogene mutations, p53/chromosome 17p alterations, and Dpc4/18q alterations. Immunohistochemistry was performed for beta-catenin, p53, and Dpc4, and microdissected tissue was analyzed using direct DNA sequencing for exon 1 of K-ras and exon 3 of beta-catenin and allelic loss assays on chromosomes 5q, 17p, and 18q. Activating mutations in codon 12 of the K-ras oncogene were present in 4 of 14 (29%) biliary IPNs. Of these 4 cases, 2 patients had associated invasive cholangiocarcinoma, and identical K-ras mutations were present in both the intraductal and invasive components. Allelic loss on chromosome 18q was present in 4 of 13 informative cases (31%); however, no loss of normal Dpc4 expression was detected by immunohistochemistry. Nuclear accumulation of beta-catenin protein was demonstrated in 3 of 12 cases (25%); however, there were no beta-catenin gene mutations, and allelic loss on 5q was present in only 1 of 10 informative cases (10%). Both immunohistochemistry for p53 and 17p allelic loss assays were negative. Biliary IPNs therefore demonstrate a K-ras gene mutation frequency that is lower than that previously reported for pancreatic IPMNs, but similar to that reported for hepatic cholangiocarcinomas. The presence of K-ras mutations in 2 purely intraductal neoplasms, and identical K-ras mutations in 2 cases with both intraductal and invasive components, suggests that these mutations arise early in tumorigenesis. Finally, the frequency of allelic loss on 18q suggests that a locus on 18q is involved in the molecular pathogenesis of biliary IPNs, but this locus is not DPC4.

Adult↗

[Surgical treatment of cancer of the biliary tract and gall bladder].

With the advances in various kinds of diagnostic methods and improvement of operative technique, operations for cancer in biliary tract have recently increased, however, the prognosis has been unsatisfied. During the past 25 years, 495 cases with carcinoma of biliary tract (ca of gall bladder 175 cases, ca of bile duct 201, and ca of papilla vater 105) were operated. The resectability rate was 66% (62% in gall bladder, 62% in bile duct, 84% in papilla vater). Among the lesions in bile duct, the resectable rate in lower bile duct was better than the other site in bile duct. The late results in ca of bile duct, especially in the lesion of upper bile duct were still poor, however, the 5-years survival rate in ca of gallbladder or papilla vater carcinoma was 61% or 56%, respectively. For the further improvement of the surgical results, the sufficient resection of the intrahepatic bile duct in ca of bile duct should be performed, and in gall bladder carcinoma when tumor extends into the neck of gall bladder, bile duct should be resected. In advanced carcinoma, the appropriate hepatectomy or bile duct resection should be considered in proportion to the operative influence and the extension of the tumor.

Biliary Tract Neoplasms↗

Current attitudes in the management of obstructive biliary tract disease.

The current attitudes of surgeons towards the management of obstructive biliary tract disease were assessed by analyzing the responses of general surgeons to a 20-item questionnaire. The responses indicate that ultrasound is the most favored initial diagnostic test for suspected choledocolithiasis. Ninety-nine per cent of the respondents always or almost always insert a T-tube following exploration of the common bile duct for stones. For patients with stone impacted at the ampulla of Vater, sphincterotomy with or without sphincteroplasty is recommended by 86 per cent of surgeons. However, differences are noted in the approach to management of malignant lesions in the biliary tract. For carcinoma of the head of the pancreas, at laparotomy, if the lesion is resectable, 59 per cent of the surgeons will perform a Whipple procedure, nine per cent a total pancreatectomy, and 28 per cent recommend bypass only. For unresectable carcinoma of the head of the pancreas, 73 per cent perform cholecystojejunostomy, and 26 per cent prefer choledocojejunostomy. In addition to the biliary bypass, only 57 per cent perform a gastric bypass routinely. The favored treatment (62%) for unresectable common bile duct tumors is an internal bypass. However, following bypass, only 45 per cent recommend further treatment with radiation and/or chemotherapy. Therefore, it appears that there is agreement on the treatment of biliary obstruction due to stones. Differences are noted, however, in the approach to the management of malignant disease.

Attitude of Health Personnel↗

[Trends of management of carcinoma of the biliary tract].

Trends of management of carcinoma of the biliary tract are described. Ultrasonography has made it possible to perform non-invasive and routine examination for biliary disorders and to find early cancer of the gallbladder. Moreover, endoscopic ultrasonography has enabled to make a differential diagnosis and a staging diagnosis. Percutaneous transhepatic cholangioscopy has been used as the most precise diagnostic procedure and peroral cholangioscopy has been introduced as a more convenient endoscopy. Although percutaneous transhepatic biliary drainage is considered to be hazardous and disadvantageous procedure in Western countries, it is essential in Japan where radical and extended operation are frequently performed. In Japan, major hepatectomies, pancreatoduodenectomy and/or combined resections of major vessels are aggressively adopted for advanced gallbladder cancers. However, such operations are still much dangerous and long-term survivors are few. Therefore, application of these extended operation for this advanced disease should be carefully re-examined. Various hepatectomies with caudate loberesection have been performed for patients with carcinoma of the hepatic hilus. Liver transplantation is also attempted for this disease, however, not accepted generally. Pylolus preserving pancreatoduodenectomy is now being accepted for biliary malignancies, which brings excellent quality of life.

Biliary Tract Neoplasms↗

[Biliodigestive anastomoses].

Experience with biliodigestive anastomosis in biliary surgery is reported. About 40 operations, subdivided into hepatojejunostomy, choledochojejunostomy, choledochoduodenostomy, hepaticojejunostomy, cholecystoejunostomy, etc. were performed in the period between 1970 and 1978. Indications for these operations are reported and the techniques adopted described. Complications and results are reviewed for each. A choledochoplasty operation using the serosa of an ansa in Roux fashion and transhepatic drainage is reported.

Biliary Tract Diseases↗

[Endoscopic retrograde cholangiopancreatography and biliary prosthesis].

Endoscopic retrograde cholangio-pancreatography (ERCP) confirms the diagnosis of obstructive jaundice and sometimes provides the histological proof that the stenosis is due to cancer. Palliative treatment of biliary and pancreatic cancers is indicated when the extension of the tumour is such that it precludes any oncologically satisfactory excision, in patients at high operative risk, when jaundice recurs after surgery and in cases of biliary metastases from distant cancers. Cancers located below the hilum are usually easily treated by endoscopic insertion of a biliary stent, whereas hilar cancers extending to the bifurcation often require combined endoscopic and percutaneous techniques to drain all liver segments. The most frequent of early complications of biliary stents is cholangitis, notably in hilar cancers. Late complications, notably obstruction of the stent, can be reduced by using expandable metal stents.

Biliary Tract Neoplasms↗

Nutritional risk factors in major hepatobiliary surgery.

Preoperative nutritional assessment was performed for 32 patients undergoing surgery for malignant hepatobiliary and pancreatic disease. Weight, mid-arm circumference, total body potassium (TBK), and skin test reactivity were significantly reduced in the seven patients who died after operation (p less than .05, Student's t-test and Fisher's exact test). Analyses of major life-threatening complications indicated that those who had a complicated postoperative course (17 patients) had a significantly lower TBK (p less than .05, Fisher's exact test). Using linear discriminant analysis (SPSS computer program), correct prediction of postoperative death or survival was possible in 85% of patients if measured by TBK alone, and in 83% if weight loss and serum albumin were used. Seventy three percent were correctly classified as complicated or uncomplicated by TBK alone, but serum albumin and weight loss were not helpful in predicting patients with complications. This study shows that malnutrition and operative risk may be identified preoperatively in patients with malignant hepatobiliary and pancreatic disease. Objective improvement may be achieved by intensive nutritional support.

Adenocarcinoma↗

[The sunken drain for internal biliary tract drainage (author's transl)].

In over 4000 interventions on the biliary tract a sunken drain was inserted in 35 patients: 3 times because of carcinomatous infiltration from outside, 27 times because of a proximal hepatic carcinoma and 5 times because of Echinococcus multilocularis. The postoperative mortality was 8.5%. Follow-up examinations show that a little more than a quarter of carcinoma patients died of the primary disease within 6 months but also that 5 patients survived their serious cancer disease for up to 2 1/2 years after the removal of the drainage obstruction. The sunken drain gives better results in Echinococcus alveolaris. Trouble-free intervals of many years were observed.

Aged↗