Tetsuji Akiyama

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

DETECTION OF KI-RAS AND P53 GENE MUTATIONS IN TISSUE AND PANCREATIC JUICE FROM PANCREATIC ADENOCARCINOMAS

Abstract: Pancreatic carcinomas have a high incidence of Ki-ras mutations, and the genetic change is thought to occur at an early stage in the carcinogenesis. The aim of this study was to evaluate the usefulness of detecting genetic mutations in pure pancreatic juice (PPJ). DNA was extracted from tissue specimens of pancreatic carcinomas and from cells in PPJ, and subjected to polymerase chain reaction-single-strand conformation polymorphism analysis. Two types of mobility shifts that indicate Ki-ras mutations were observed in 13 of the 20 (65%) tissue specimens obtained by operation or autopsy. Ten of 15 specimens (67%) of PPJ collected from patients with pancreatic carcinomas showed two types of mobility shifts. Conventional imaging techniques did not show two in 10 of these patients. PPJ from patients with non-cancerous pancreatic diseases showed no Ki-ras mutations. The p53 tumor suppressor gene, examined by PCR-SSCP analysis, was mutated in 8 of the 20 tissue specimens obtained by operation or autopsy (40%). The detection of Ki-ras and p53 mutations in PPJ could be useful for the early diagnosis of pancreatic carcinomas, especially for neoplastic lesions of the intraductal type.

p53 Mutations in Two Patients with Intraductal Papillary Adenoma of the Pancreas

There has been no report on p53 gene mutation in benign human pancreatic intraductal tumors. We examined pancreatic juice and tissue specimens from two patients with intraductal papillary adenoma of the pancreas by polymerase chain reaction‐single‐strand conformation polymorphism analysis and direct sequencing and found point mutations of p53 gene resulting in amino acid substitutions in exons 6 and 8. Thus, p53 gene mutation may be an early event in the neoplastic process of some pancreatic intraductal tumors and may play an important role in tumorigenesis.

Simple and sensitive detection of K-ras gene mutations in human pancreatic cancers by nonradioisotopic single-strand conformation polymorphism analysis.

In an attempt to determine the best indications for the classically adopted ileo-rectal anastomosis (IRA) and the new techniques of restorative proctocolectomy, namely, ileal J-pouch-anal anastomosis (IAA) ilea J-pouch-anal canal anastomosis (IACA), we retrospectively studied 72 surgically treated patients with ulcerative colitis (UC) followed in our surgical department in the period between 1963 and 1994. Compared to these new techniques, IRA had a lower incidence of postoperative fecal incontinence, and was one-stepped in the majority of the patients. No significant difference regarding postoperative bowel function, operation time, volume of bleeding, hospital stay, and the need for postoperative prednisolone was observed. We concluded that IRA is a good procedure that is indicated for patients receiving high-dose prednisolone, for those who need a quick return to social activity, and for those with poor anal function. IACA is a good indication for those patients with good anal function assessed preoperatively, who agree to receive a multi-step operation. For those patients with cancer or dysplasia, IAA should be the operation of first choice.

Clinical Experience with Prototype Pancreatoscopes

Abstract: Peroral pancreatoscopy (PPS) was introduced at our institute in 1982, with the aim of improving diagnostic accuracy in patients with pancveatic diseases, and as a preliminary, procedure for therapeutic interventions to the pancreas. However, limitations in instrumentation permitted us to observe only the main pancreatic duct. This is a report of our experience with 2 types of peroral Pancreatoscopes and our findings in patients with chronic pancreatitis and pancreatic cancer.

Aberration of the p53 gene in human pancreatic ductal adenocarcinomas

The p53 gene is considered one of the tumor suppressor genes which negatively regulate cell growth and division in the wild type, and its mutations in evolutionary conserved exons are common in diverse types of human malignancies(l). Pancreatic ductal adenocarcinoma is well known as a tumor carrying activated Ki-ras gene(2), but other genes that correlate to multistep carcinogenesis are not yet known. Therefore, we analyzed aberrations of exons 5 to 8 of the p53 gene in 8 cases of advanced pancreatic ductal adenocarcinomas by PCR-SSCP analysis. The method of PCR-SSCP analysis of the p53 gene was described previously by Murakami et al.(3). Genomic DNA were extracted from fresh surgical specimens and, as a noncancerous control tissue the lymphocytes of the same patients were used. The PCR products which were labeled with e_np dCTP were applied to 5% polyacrylamide gel containing 10% glycerol and, after electrophoresis, the gel was dried and subjected to autoradiography. As shown in Figure, mobility shifts which indicate structural abnormalities were observed in 3 of 8 cases, 2 cases in exon 5 and 1 case in exon 6, respectively. No extra-band was seen in noncancerous tissue of the same patients. These results suggest the involvement of the p53 gene aberration in human pancreatic ductal carcinogenesis.

Endoscopic Findings of Primary Sclerosing Cholangitis—‐Report of a Case—

Abstract: A case of primary sclerosing cholangitis in which an endoscopic inspection through the fistula produced by percutaneous transhepatic biliary drainage was performed for the treatment of progressive jaundice and supprative cholangitis is presented. These treatments benefited the patient to some degree. After 3 years from the onset, the patient died of multi‐organ failure caused by disseminated intravascular coagulopathy. An autopsy revealed primary sclerosing cholangitis. No evidence of ductal stricture due to malignancy or underlying cholelithiasis was noted.

Hepatocellular Carcinoma with Invasion of the Right Intrahepatic Bile Duct Observed by Peroral Cholangioscopy: a Case Report

A 48‐year‐old chronic alcoholic with previous hepatitis B virus infection presented with recurrent episodes of obstructive jaundice secondary to hepatocellular carcinoma. The obstructive nature of the jaundice was confirmed by the peroral cholangioscopic findings of a friable nodular mass partially obstructing the right hepatic duct, and by relief of obstructive signs and symptoms after endoscopic sphincterotomy freed the common bile duct of “dark greenish formed materials”.