Histologic examinations of specimens obtained by PTCS-guided biopsy can detect invasive carcinoma in only the superficial layers of the bile duct, such as the mucosa and the shallowest fibromuscular layer. Multiple specimens are needed for the diagnosis of invasive carcinoma because the sensitivity of examination of a single specimen for detecting invasive carcinoma is low. Vascular dilatation is characteristic of carcinoma that is invading the mucosa beyond the adventitia, so the diagnosis of intramural extension of bile duct carcinoma limited to the adventitia, particularly if it has spread to the deeper fibromuscular layer and the adventitia, is difficult to make by PTCS.

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Table S1. Segregation analysis in family 1 of three microsatellite markers flanking KRT1 and the pathogenic mutation p.Phe191Ile demonstrating germline mosaicism. REFERENCESAlbers K, Fuchs E (1989) Expression of mutant keratin cDNAs in epithelial cells reveals possible mechanisms for initiation and assembly of intermediate filaments.

Drugs containing the carboxylic functional group can be metabolized to form acylglucuronides believed to cause idiosyncratic drug toxicity when the acylglucuronide is unstable. Recent studies have shown that the half-life of an acylglucuronide in phosphate buffer is the best means for classifying acylglucuronides into safe, warning, and withdrawn drugs. However, it is difficult to halt the late stage development of new chemical entities due to the instability of their acylglucuronides. We report an optimized in vitro method for determining the half-lives of acylglucuronides in simple phosphate buffer without the need for authentic standards. The experiment was divided into two incubations. In the first incubation, acylglucuronide was synthesized by human liver microsomes, and in the second incubation, the degradation rate of acylglucuronide in phosphate buffer was determined. The degradation rate constants of acylglucuronides were determined from changes in the LC-MS/MS peak area and the half-lives were calculated. We evaluated the half-lives of 10 drugs: 3 safe drugs (telmisartan, gemfibrozil and flufenamic acid) and 7 withdrawn or warning drugs (zomepirac, diclofenac, furosemide, ibuprofen, S-naproxen, probenecid and tolmetin). The half-lives of the 3 safe drugs were 10.6 h or longer, whereas the half-lives of the 7 withdrawn or warning drugs were 4.0 h or shorter. Although authentic acylglucuronide standards were not used, we obtained half-lives of acylglucuronides in phosphate buffer similar to those reported previously. Using this method, the risk of reactivity caused by acylglucuronides can be evaluated in the early stages of drug discovery.

Percutaneous transhepatic cholecystic drainage (PTCCD) with percutaneous transhepatic cholecystoscopic lithotomy (PTCCSL) were performed in 53 patients with acute cholecystitis caused by gallbladder stones and studied stone removal rates, complications, endoscopic findings, and stone recurrence. The stones were successfully removed in 96% of the patients, and there were no serious complications. The coexistence of cancer was confirmed in three patients, and all cases were accurately diagnosed on the basis of uitrasonographic, endoscopic, and biopsy findings. The mean duration of follow-up after stone removal was 42 months, and the stone recurrence rate was 2.5%. Among the 39 patients followed up for at least 1 year, the gallbladder could be preserved with no evidence of sludge in patients in whom drainage was performed early after the onset of symptoms, those with a normal gallbladder after PTCCSL, and those with normal gallbladder contractility after PTCCSL. Sludge was present in patients with evidence of extensive areas of yellowish white fibers on percutaneous transhepatic cholecystoscopy. If instituted early after the onset of symptoms, PTCCD combined with PTCCSL was considered useful in the treatment of patients with acute cholecystitis associated with gallbladder stones.