Yoshihisa Marugami

Biliary carcinogenesis in pancreaticobiliary maljunction

The coexistence of bile duct carcinoma in choledochal cysts is well known. With large number of cases of congenital bile duct dilatation and pancreaticobiliary maljunction (PBM), it is now apparent that gallbladder carcinoma is more frequent in PBM without bile duct dilatation. The incidence of Gallbladder cancer in choledochal cyst and bile duct cancer in PBM, regardless of the presence of bile duct dilatation is significantly higher than that in control patients with biliary cancer but without PBM. A recent survey shows that the incidence of bile duct cancer in PBM without dilatation is equivalent to that of gallbladder cancer and bile duct cancer in patients with choledochal dilatation. Pathology in PBM is a result of reflux of pancreatic juice and stasis of the mixture in the biliary system. Carcinogenic factors thus present in the biliary contents induce epithelial changes in the biliary tract. In the biliary contents, activated pancreatic enzymes and secondary or deconjugated bile acids are markedly increased and they irritate the biliary mucosa. Mutagens are proven to form in the bile of PBM. In the epithelia of PBM, hyperplasia, metaplasia, and dysplasia are often found, and proliferative activity is increased; furthermore, K-ras gene mutation and overexpression of p53 protein are demonstrated. As for treatment of PBM, whether it is symptomatic or not, an operative procedure, is necessary, to prevent carcinogenic changes in the gallbladder and bile duct. Regardless of whether dilatation is present or not, total excision of the extrahepatic bile duct, along with gallbladder, is the treatment of choice, followed by hepaticojejunostomy or hepaticoduodenostomy.

Cardiac metastasis from squamous cell carcinoma of gallbladder

A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.

Some considerations on the biology of pancreatic serous cystadenoma.

SummaryFive cases of pancreatic serous cystadenoma were examined pathologically, and their nuclear DNA ploidy patterns were determined. Four were unifocal tumors, and one was a multifocal tumor. The four unifocal tumors were typical serous cystadenomas. However, the multifocal tumor exhibited an increased N/C ratio, irregular nuclear margins, various-sized nuclei, coarse nuclear chromatin, and neural invasion. All tumor cells were stained with antiCA19-9 but none with antiCEA. In the antiCA19-9 staining, the four unifocal tumors and the tumors of the pancreatic tail in the multifocal case were positive only on the apical membrane, whereas the tumor cells of the pancreatic head in the multifocal case were positive within the whole cytosol. The unifocal tumors were diploid with a DNA Index (DI) of 1.0 and proliferation indices (PI) from 4.9 to 20.9% with a mean of 14.4%. In the multifocal case, the tumor in the pancreatic head was aneuploid (DI = 1.9) and had a PI of 27.8%. The multifocal sites in the pancreatic body were aneuploid (DI = 1.9) with a PI of 22.4%. We suggest that the biological property of serous cystadenoma should be revisited.

End-to-side choledochoduodenostomy: A widely applicable procedure for biliary reconstruction

End-to-side choledochoduodenostomy was originally used for reconstruction between the duodenum and the biliary tree in iatrogenic bile duct stricture. However, we believe the procedure could be applied for various biliary disorders. We have recently shown the high carcinogenicity of biliary epithelium in patients with pancreaticobiliary maljunction, and consequently we recommend excision of the bile duct, along with appropriate reconstruction of the biliary system to divert the flow of pancreatic juice from bile fluid, to prevent carcinoma in biliary epithelium even in patients without dilatation of the bile duct. The conditions causing primary or recurrent bile duct stones must be removed. We employed this procedure for biliary reconstruction in 42 patients with pancreatico-biliary maljunction and in 30 patients with various benign biliary diseases, such as bile duct stones and benign biliary stenosis. We also used the procedure for palliation in 6 patients with malignant tumors around the head of the pancreas. Among these 78 patients over 20 years, we experienced 5 cases of reflux cholangitis with anastomotic stenosis, for which conservative dilatation was required. This procedure of end-to-side choledochoduodenostomy could be widely applicable for biliary reconstruction in terms of its being simplicity, minimal invasiveness and the establishment of a single physiological route for bile flow into the duodenum.

Effects of nafamostat mesilate, somatostatin, and glucagon on caerulein‐induced acute pancreatitis in rats

The inhibitory effects of somatostatin (SMS) and glucagon (Gn) on acute pancreatitis were evaluated in an experimental acute pancreatitis model in male Wistar rats. The effects of these agents were compared with those of nafamostat mesilate (NM). The acute pancreatitis was induced by four serial subcutaneous injections of caerulein. The rats were divided into four groups. The first group (n=28) received SMS daily, the second group (n=28) received Gn daily, and the third group (n=28) received NM daily after the first injection of caerulein. The fourth group (n=42) received caerulein alone and served as the control group. Animals were sacrificed 4, 6, 8, 12, and 24 h, and 3 and 7 days after the first administration of caerulein and the degree of severity of the acute pancreatitis was evaluated by serial morphological and histological examinations of pancreatic tissues, as well as in terms of the serum concentrations of amylase and lipase. The characteristic findings of acute pancreatitis in the animals of all groups treated with SMS, Gn, or NM were markedly attenuated at all time points after the treatments compared with findings in the controls (caerulein alone) in terms of wet weight of pancreas, serum concentrations of amylase and lipase, formation of intracellular vacuoles in acinar cells, interstitial edema, and infiltration of an inflammatory cell component. The inhibitory effects of SMS, Gn, and NM on acute pancreatitis were similar at the doses used. These results suggest that SMS and Gn are as useful as NM, they may be of value for the treatment of acute pancreatitis.

Case Report of Early Gastric Carcinoma after Surgery for Metastatic Ovarian Tumors.

胃癌の卵巣転移は臨床上しばしぼ経験するが, 早期胃癌の卵巣転移報告例はいまだ少なく, 本邦では現在まで6例を数えるのみである. 今回われわれは卵巣転移を契機に発見された早期胃癌の1例を経験したので報告する.症例は33歳の女性で, 検診にて卵巣腫瘍を発見され, 両側卵巣摘除を行いKruckenberg腫瘍と診断した. 術後の検査で胃角上部後壁のIIc型早期胃癌を認め, 幽門側胃亜全摘, R2の手術を施行した. 病理所見は印環細胞癌, sm, ly2, v0, n2 (+) であった. 2度にわたる開腹所見にてP0, H0であり, 後腹膜リンパ節の腫大は触知しなかった. 術後1年の現在, 再発の徴候を認めていない.胃癌の卵巣への転移経路については古くから検討されてきたが, 対象のほとんどが進行癌で複数の転移巣を有することが多いため解析が困難なことが少なくなかった. 早期癌で1この点で有利であると考え, 集計報告6例を合わせ転移経路についての考察を加えた.