Kazuo Miura

Ultrasonographic evidence of association of polyps and stones with gallbladder cancer

Objective:The purpose of this study was to evaluate the level of gallbladder cancer risk associated with polyps and stones of the gallbladder by ultrasound examinations.Methods:We investigated abdominal ultrasonographic findings for gallstones and polyps of the gallbladder and the relationship of these findings to malignancy in 194,767 asymptomatic participants in health screening examinations.Results:Gallstones were detected in 7,985 participants (4.1%), at a prevalence of 5.3% in male and 4.5% in female participants. The prevalence was highest in the participants’ seventh decade, followed by the sixth and the fifth decades, in both male and female participants. Polyps were found in 10,926 (5.6%), at a prevalence of 6.9% in the male and 4.5% in the female participants. In the male participants, prevalence was highest in the fourth decade, followed by the third and the fifth decades, whereas in the female participants it was highest in the fifth decade, followed by the fourth and third. High prevalence of polyps ≥10 mm in diameter was found in the fifth to seventh decades in both sexes. Nineteen participants (0.01%) were diagnosed as having gallbladder cancer, and many of them were in the sixth or seventh decade in both sexes. Patients with stones showed a higher prevalence of gallbladder cancer. This difference was shown to be statistically significant by age-adjusted analysis (p < 0.01). The age distribution of the participants with polyps ≥10 mm in diameter was correlated with that of patients diagnosed with gallbladder cancer. Furthermore, polyp incidence was significantly related to cancer by statistical analysis (p < 0.01).Conclusion:These results suggest an association between gallstone or polyp of the gallbladder and increased risk of malignancy, implying that an etiological association may also exist.

Invasive Ductal Carcinoma of the Breast Associated with Poland's Syndrome: Report of a Case

Abstract We report herein a rare case of invasive ductal carcinoma of the breast associated with Polands syndrome. The patient was a 59-year-old woman who was referred to our department after a nodule had been found in the upper outer portion of the left breast by a breast cancer screening program. On physical examination, marked hypoplasia of the right breast and upper limb was noted. Preoperative computed tomography also revealed a defect in the right pectoralis muscles. A quadrantectomy of the left breast with lymphadenectomy was subsequently performed and pathological examination of the resected specimen showed invasive ductal carcinoma. Her medical history revealed that her mother had attempted to abort the pregnancy around the fifth week of her gestation. The present case suggests that such an event during gestational development may be associated with congenital anomalies predisposing to malignant disorders.

Hepatic Arterial Infusion of Interleukin-2 in Advanced Hepatocellular Carcinoma

From August 1988 to February 1991, we performed hepatic arterial cannulation after tumor mass reduction in 17 patients with advanced hepatocellular carcinoma. By a subcutaneous infusion pump the patient received a continuous infusion of interleukin-2 (IL-2) (0.35 x 10(6) Japanese Reference Unit/day) and intermittent chemoembolization with 10 mg doxorubicin emulsion. The longest period of IL-2 infusion was 32 months. In 3 patients, the IL-2 dose could not be increased to the planned level due to fever or jaundice. Eight patients received the infusion for more than 10 months. NK and LAK activity in the peripheral blood, which had been reduced after partial liver resection, arterial embolization, or ethanol injection, was enhanced significantly by the IL-2 infusion, and the levels remained high for about 8 to 10 months. During periods of high NK and LAK activity, direct effects on the liver tumors were observed. In 11 patients who received IL-2 infusion for more than 6 months there was CR in 4, PR in 2, NC in 3 and PD in 2. Thereafter, however, the levels of NK and LAK activity decreased despite increase in the IL-2 dose, and sudden appearance of metastatic tumors caused deterioration of the patients. The 1-year and 2-year cumulative survival rates were 41% and 16% respectively. Further studies are required to explore ways for longer-lasting enhancement of NK and LAK activity.

Bile flow analysis by hepatobiliary scintigraphy in the terminal bile duct in patients with congenital malformations of the pancreatico-biliary ductal system

SummaryThe authers employed hepatobiliary scintigraphy (HBS), to study a dynamic state of bile stasis in the common bile duct and bile flow through the papilla of Vater in patients with congenital malformations of the pancreatico-biliary ductal system, such as congenital cystic dilatation of the common bile duct (CCDB) and anomalous arrangement of the pancreatico-biliary ductal system (AAPB). The HBS data were evaluated by a cholestatic index (CI), as an indicator of bile stasis in the common bile duct, and passage time (PT), as an indicator of bile flow through the papilla of Vater. CI was significantly higher in CCDB (3.67±0.92), in AAPB (2.87±0.28) and in both CCDB and AAPB with symptoms (2.86±0.59), compared with patients without CCDB or AAPB (0.96±0.41). PT was prolonged only in patients with AAPB with/without CCDB (>30 minutes) compared to patients without AAPB (<12 minutes). This result suggested that bile stasis in the common bile duct was caused by a pooling of bile in the dilated common bile duct in CCDB, and by a disturbance of bile flow through the papilla of Vater in AAPB.

Clinicopathologic differentiation of atrophy of the pancreatic body and tail aplasia

SummaryConclusionCongenital aplasia of the body and tail of the pancreas is derived from a defect of the dorsal pancreatic anlage and should not be considered a type of acquired atrophy of these structures.BackgroundCongenital aplasia of the body and tail of the pancreas radiologically mimics acquired atrophy of the pancreatic body and tail.MethodsTwo patients with radiologically identified aplasia of the body and tail of the pancreas were studied clinicopathologically.ResultsAn 82-yr-old man was diagnosed radiologically as having both carcinoma of the head of the pancreas and aplasia of the body and tail of the pancreas and underwent pancreatoduodenectomy. Pathologically the carcinoma was distributed in the anterosuperior part of the head of the pancreas, and spread into the duct of Santorini and intraductally to a portion of the main pancreatic duct beyond the junction of the ducts of Santorini and Wirsung. Consequently, obstructive pancreatitis of the body and tail of the pancreas developed, resulting in marked atrophy that mimicked aplasia of the body and tail of the pancreas. A 74-yr-old woman was diagnosed radiologically as having two carcinomas, one of the gallbladder and one of the stomach, and aplasia of the body and tail of the pancreas. During surgery, suspected parenchymal disappearance and fatty replacement in the body and tail of the pancreas were noted. Histologic examination of biopsy specimens from the body portion revealed atrophic pancreatic tissue surrounded by fat. Therefore, these patients had atrophy of the pancreatic body and tail.

Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer

AIM To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor.

Small-cell carcinoma manifesting systemic lymphadenopathy combined with adenocarcinoma in the gallbladder: aggressiveness and sensitivity to chemotherapy

Small-cell carcinoma of the gallbladder is a very rare tumor. In this report, we describe a patient with small-cell carcinoma combined with adenocarcinoma in the gallbladder. The patient was a 70-year-old man, who clinically manifested systemic lymphadenopathy. An incisional biopsy of Virchows lymph node revealed small-cell carcinoma. Abdominal computed tomography (CT) showed massive multiple paraaortic lymph node swelling and a round mass in the gallbladder, although chest CT did not show any abnormal masses in the lung. After two courses of chemotherapy (PVP therapy; cisplatin [CDDP], 80 mg/m2, day 1, intravenous injection; and etoposide [VP-16], 50 mg/m2, every day, per oral intake; given every 3 weeks) were performed, the systemic lymphadenopathy had completely diminished and only the gallbladder tumor remained on clinical examinations. Endoscopic retrograde cholangiopancreatography (ERCP) revealed nodular tumors in the gallbladder fundus. Cholecystectomy with partial resection of the liver was performed. Pathological examination revealed small-cell carcinoma combined with adenocarcinoma of the gallbladder. We discuss the characteristics and the treatment of this rare tumor.

Glucagon responses in rabbits with obstructive jaundice and a low energy status in the liver

Glucagon has a choleretic effect and also stimulates energy-consuming reactions, such as gluconeogenesis and ureogenesis in the liver. The effect of glucagon on energy metabolism in the liver was analyzed in rabbits with obstructive jaundice that had severe liver damage, indicated by significantly lower hepatic energy charge levels. The gluconeogenetic responses to glucagon administration, as shown by increases in the plasma glucose levels, were usually observed in normal rabbits, but these responses were completely depressed after glucagon administration in rabbits with obstructive jaundice. The energy charge levels in the latter animals decreased even further after glucagon administration. Even though the energy consumption for gluconeogenesis after glucagon administration was limited in the jaundiced rabbits, it was sufficient to cause a deterioration in the hepatic energy balance. The above findings show that the administration of glucagon increases the amount of energy expended in the liver following a reduction in the hepatic energy charge in rabbits with obstructive jaundice. Therefore, even though glucagon has a choleretic effect, it should be administered carefully to patients with obstructive jaundice, especially in those with severe liver damage, such as in patients with cholangitis.

Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats

The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.

Disease-free Survival for 9 Years After Liver Resection for Stage IV Gallbladder Cancer : Report of a Case

We report herein the case of a 66-year-old woman who has survived for more than 9 years without recurrence since undergoing a right trisegmentectomy of the liver with biliary reconstruction using the jejunum for stage IV (T1, N1a, M0, UICC) gallbladder cancer. The resected tumor, which was histologically diagnosed as moderately to poorly differentiated adenocarcinoma, was approximately 8cm in diameter and infiltrated from the gallbladder to the medial, anterior, and posterior segments of the liver, involving the right hepatic and common hepatic ducts and the right hepatic artery; no intrahepatic distant metastasis was found. Although preoperative imaging diagnosis showed swollen lymph nodes at the hepatoduodenal ligament and paraaortic region, histological analysis of the resected lymph nodes revealed only one metastasis, located at the cystic duct which was involved in the tumor. This case demonstrates that curative resection may be the appropriate surgical intervention for patients with a stage IV tumor and direct infiltration to the liver and surrounding organs but no distant metastases.