Tsutomu Tomioka

Primary hepatic carcinoid tumor.

Abstract: A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 × 12 × 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.

Early Carcinoma of the Extrahepatic Bile Duct

This study attempts to define early carcinoma of the extrahepatic bile duct through a study of 11 patients whose carcinomatous invasion did not extend to the outer layer of the bile duct. The patients were divided into the following 3 groups, namely; a mucosa group comprised of 3 patients, a fibromuscular layer group comprised of 5 patients, and an adventitia group comprised of 3 patients. None of the patients had any lymphnode metastases. Histological characteristics were determined according to infiltrative growth (INFα, β, γ), lymphatic invasion (ly), venous invasion (v) and perineural invasion (pn). In the mucosa group, INFα was observed in 2 patients, while ly, v, and pn factors were all negative. In the fibromuscular layer group, INFβ was seen in 3 patients, ly was positive in 2 patients, while v, and pn factors were negative in all patients. In the adventitia group, INFγ was found in 2 patients, and ly, v, and pn factors were positive in all patients except for 1 in whom v was negative. Death from recurrence occurred in all the adventitia group patients and in 1 other patient. Early carcinoma of the extrahepatic bile duct could therefore be defined at present, as being carcinoma confined to within the mucosa and fibromuscular layer.

The surgical treatment for carcinoma of the gallbladder: rationale of the second-look operation for inapparent carcinoma

Eighty-seven patients with carcinoma of the gallbladder treated in our hospital over a 15-year period were reviewed. Macroscopic curative resection was performed in 30 cases, 6 of which received second-look operations, and their cumulative five-year survival rate was 42.6 per cent. Histological and clinical analysis of our cases initially diagnosed by postoperative histologic examination revealed that the depth of carcinomatous invasion was the most important criterion for the indication of second-look operation, and that the second-look operation is mandatory for the inapparent carcinoma limited to the muscularis or subserosa. The surgical procedures of the second-look operation were: resection of the anterior inferior and medial inferior areas of the liver and dissection of the regional lymph-nodes. The presence of invasion of carcinoma to the cut end of the cystic duct or severe carcinomatous invasion to the lymphatic vessels were also important histopathologic findings for a second-look operation. Cases in which lymphatic invasions are remarkably observed, should receive an en bloc hepato-cholecystectomy plus a resection of the extrahepatic bile duct with neural tissues and soft fatty tissues in the hepatoduodenal ligament in a two-stage operation.

IN VITRO PANCREATIC DUCTAL CELL CARCINOGENESIS

Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA‐1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N‐nitorosobis(2‐oxopropyl)amine (BOP). These treated cells were designated TAKA‐1 + BOP. The growth of TAKA‐1 and TAKA‐1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA‐1 + BOP was re‐cultured in vitro and designated TAKA‐1 + BOP‐T. Mutation of c‐K‐ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF‐α) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA‐1 + BOP but not TAKA‐1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non‐transformed and transformed cells. TAKA‐1, TAKA‐1 + BOP and TAKA‐1 + BOP‐T cells all expressed mRNA of TGF‐α and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA‐1 nor TAKA‐1 + BOP cells has a mutation of c‐K‐ras or p53. Karyotype analysis demonstrated that TAKA‐1 + BOP cells had more chromosomal abnormalities compared with TAKA‐1 cells. Mutation of c‐K‐ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA‐1 cells caused expression of TGF‐α to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non‐transformed and BOP‐transformed cells. Int. J. Cancer 72:1095–1103, 1997.

Solid and cystic tumor of the pancreas occurring without cyst formation in an adult male

SummaryA solid and cystic tumor (SCT) of the pancreas occurring in a 35-yr-old male is reported. Cut sections of the specimen revealed a solid, ill-defined mass measuring 2.5×2.3×2.0 cm, without cystic or necrotic changes. Histologically, the solid tumor consisted of small, round acidophilic cells invading the surrounding pancreatic parenchyma. The tumor cells were positive for α-1-antitrypsin and neuron-specific-enolase. Ultrastructural studies revealed clear nuclei with no zymogen, but immature secretory granules in the cytoplasm of the tumor cells, which had a junctional complex-like structure. These findings were consistent with the so-called solid and cystic tumor of the pancreas. There was neither a capsule surrounding the tumor nor a papillary structure, known to be characteristic findings of the SCT tumor. The small tumor reported in the present article might represent an early-stage SCT of the pancreas.

CT of neural plexus invasion in common bile duct carcinoma.

PURPOSE Our purpose was to analyze the CT findings of neural plexus invasion in common bile duct carcinoma. METHOD We studied 16 patients with common bile duct carcinoma who underwent surgery. Of these, neural invasion was seen in 10 patients. CT findings were retrospectively reviewed and correlated with the surgical and pathological findings. RESULTS Irregular masses adjacent to the medial aspect of the uncinate process were observed in 4 of 14 patients with distal common bile duct carcinoma. These lesions extended medially and showed contiguity with the superior mesenteric artery and/or celiac axis, corresponding to neural plexus invasion with desmoplastic change. Increased attenuation of the fat between the common bile duct and the proper hepatic artery was seen in two of two patients with proximal common bile duct carcinoma, associated with neural plexus invasion in the hepatoduodenal ligament. CONCLUSION The location and spread of neural plexus invasion in common bile duct carcinoma are characteristic and can be diagnosed by CT.

Cystadenoma and cystadenocarcinoma of the liver: Localization of carcinoembryonic antigen

Cystadenomas and cystadenocarcinomas of the liver are rare tumors. The distribution of carcinoembryonic antigen (CEA) in two cystadenomas and a cystadenocarcinoma was examined immunohistochemically by the peroxidase-labeled antibody method, at the light microscopic level. In the cystadenomas and areas consisting of benign-appearing cells in the cystadenocarcinoma, CEA was localized to the luminal surfaces of the glandular cells appearing as thin linear stains. In malignant epithelial cells forming nests and daughter cysts of the cystadenocarcinoma, CEA was demonstrated throughout the cytoplasm, in a diffuse pattern. Thus, the immunohistochemical localization of CEA may be helpful in the diagnosis of borderline lesions and in determining the distribution of benign and malignant epithelium in cystadenocarcinomas. The etiology, clinical features, pathology and treatment of these rare tumors are discussed.

Case Report: Mucinous Cystadenocarcinoma of the Spleen Presenting a Point Mutation of the Kirsten-ras Oncogene at Codon 12

14. Albores-Saave dra J, Angele s-Ange les A, Nadji M, Henson DE, Alvarez L: Mucinous cystadenocarcinoma of the pancreas. Am J Surg Pathol 11:11± 20, 1987 15. Hirota M, Tomioka T, Ohshima H, Yamasaki K, Matsuo T, Atari E: Mucin-producing bile duct carcinoma originating at the hepatic hilus. J Hepat Bil Pancr Surg 4:135± 140, 1997 16. Nio Y, Sato Y, Song MM, Sumi S, Minari Y, Yano S, Tamura K: Ki-ras point mutation in codon 12 and expression of p53 in mucin-producing tumor of the pancreas. J Hepat Bil Pancr Surg 4:93± 90, 1997 HIROTA ET AL 774 Digestive Diseases and Sciences, Vol. 44, No. 4 (April 1999)

K-ras gene mutations in intrahepatic bile duct tumors of Syrian golden hamsters

In our laboratory, we have developed a new model of carcinoma of the bile duct in Syrian golden hamsters, using N‐nitrosobis(2‐oxopropyl)amine (BOP). Morphologic and biologic characteristics of the carcinoma induced in this model are similar to those seen in humans. In order to examine the gene‐related carcinogenesis of intrahepatic bile duct carcinoma, we investigated mutations in the K‐ras gene in various early hyperplastic and neoplastic lesions of these hamsters, according to the original sites of the lesions.

A case of a rare anomaly of the common bile duct associated with an abnormal arrangement of the pancreaticobiliary ductal union

A 39 year-old Japanese female patient with a duplication of the distal portion of the common bile duct is presented herein. Moreover, an abnormal arrangement of the pancreaticobiliary ductal union, congenital biliary dilatation and carcinoma of the gallbladder were all demonstrated by cholangiographic and endoscopical studies. The patient underwent radical surgery for advanced adenosquamous carcinoma of the gallbladder, and her postoperative course was satisfactory. A reflux of pancreatic juice into the bile duct was demonstrated, but it was eliminated and considered to be a contributory etiologic factor of the gallbladder carcinoma.