Ryohei Izumi

Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection

BACKGROUND/AIMS Prognostic analysis on hepatocellular carcinoma (HCC) in patients undergoing hepatectomy is necessary to determine the clinical value of hepatectomy on prognosis. METHODS Survival and disease-free survival were analyzed in 104 HCC patients undergoing hepatectomy using clinicopathologic factors by univariate and multivariate analyses. The value of the International Union Against Cancer (UICC) TNM classification on prognosis was assessed in the patients. RESULTS In multivariate analysis, portal vein invasion was the most influential factor. The difference between stage 1 and 2 or stage 3 and 4A using UICCs TNM classification was not significant with respect to survival or disease-free survival. The UICCs classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent to vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph nodal metastasis; and stage 4, tumor(s) with distant metastasis. The differences between each stage in the modified classification were significant with respect to disease-free survival. CONCLUSIONS The UICCs TNM classification was not of prognostic significance. Further studies on survival in patients with HCC are necessary to evaluate the value of the UICCs TNM classification; some modification may be necessary.

Hepatic resection using a water jet dissector.

A newly-designed water jet dissector was used for hepatic resections in humans. To evaluate its usefulness, the water jet dissector was compared toan ultrasonic surgical aspirator in terms of average blood loss and time of operation. In hepatectomies on patients associated with liver cirrhosis, the average blood loss during hepatic resection using the water jet dissector was significantly smaller (P<0.05) than that with the ultrasonic surgical aspirator. However, in hepatectomies on patients without cirrhosis, the average blood loss during hepatic resection did not significantly differ between the two groups. Neither did the time of operation significantly differ between the two procedures in hepatectomies on patients with and without liver cirrhosis. No serious complications attributable to the use of the water jet dissector were encountered. The water jet dissector is thus considered to be a useful new device for use in the transection of the liver during hepatic resections.

Imaging findings of mucinous type of cholangiocellular carcinoma

OBJECTIVE To demonstrate the imaging findings seen in two cases of mucinous type of cholangiocellular carcinoma of the liver. MATERIALS AND METHODS The CT and MR findings of two patients with pathologically proven mucinous type of cholangiocellular carcinoma were analyzed. RESULTS One of them showed calcification, both cases had no enhancing on the arterial dominant phase of dynamic CT, but showed enhancement in the periphery and internal septations on the equilibrium phase. The internal signal intensity was homogenous, and extremely hypo- and hyperintense on T1- and T2-weighted images, respectively. CONCLUSION Imaging findings were unique reflecting the characteristic pathological features that cancer cell nests are suspended in a large mucinous lake, and the specific diagnosis was considered to be possible by the integrated imaging diagnosis.

Clinical experience of intrahepatic cholangiocarcinoma associated with hepatolithiasis

Between 1960 and 1986, seven patients with intrahepatic cholangiocarcinoma and one patient with intrahepatic bile duct adenoma, related to hepatolithiasis, were seen among 112 cases of hepatolithiasis. Histopathologically, the tumors associated with hepatolithiasis arose from the periphery of the stone-containing bile duct, spread chiefly along the luminal surface, and invaded the ductal wall or periductal tissue. The tumors showed papillary to papillo-tubular proliferation and were diagnosed as the intraductal or periductal spreading type of cholangiocarcinoma. In addition, atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that chronic relapsing cholangitis in patients with hepatolithiasis can induce progressive changes to atypical epithelial hyperplasia which may develop into cholangiocarcinoma.

Angiomyolipoma of the liver: Its clinical and pathological diversity

Eighty cases (82 tumors) of hepatic angiomyolipoma (AML) from the world literature were reviewed, including our 8 cases. The tumors occurred predominantly in females (female: male ratio, 56∶24). Only six patients (7.5%) had associated tuberous sclerosis. The majority of the tumors (95%) occurred in non-cirrhotic, almost normal liver. The tumors usually presented as a hyperechoic mass on ultrasound (US) examination, a hypodense mass on computed tomography (CT) scan, and hyperintense mass on both T1- and T2-weighted magnetic resonance (MR) imagings. However, the imaging features of the tumor were occasionally variable according to the content of fat tissue component, and the tumors could not be clearly differentiated from other hepatic tumors, particularly hepatocellular carcinoma (HCC), based on the imaging features alone. Tumor location was recorded in 81 tumors; 44 were located in the right lobe, 30 in the left, 5 in the caudate, and 2 in both lobes of the liver. The tumor diameter ranged from 0.3 to 36cm (mean, 8.0±7.0cm). Macroscopically, the tumors usually had no fibrous capsule. The cut surface was yellow to dark brown depending on the amount of fat tissue or blood vessels. The histologic features were quite variable and occasionally included atypical and/or pleomorphic cells, which could lead to the erroneous diagnosis of a variety of benign and malignant tumors, including lipoma, leiomyoma, HCC, hepatoblastoma, leiomyosarcoma, and malignant fibrous histiocytoma. Extramedullary hematopoiesis was found in 33% of the tumors. Reactivity of the tumor cells of the liver with HMB-45, a melanoma-specific antibody, can accurately establish the diagnosis of AML.

PATHOLOGICAL AND IMMUNOHISTOCHEMICAL FINDINGS IN A CASE OF MUCINOUS CHOLANGIOCARCINOMA

A case of mucinous cholangiocarcinoma is reported. The patient was a 49 year old woman with the complaint of lumbago. Imaging examination disclosed a tumor 3.5 cm in diameter in the right hepatic lobe, which showed low density on computerized tomography scans and low signal intensity on T1–weighted magnetic resonance imaging (MRI) and high intensity on T2–weighted MRI. The hepatic tumor expanded rapidly and multiple pulmonary metastases and peritoneal dissemination developed. The patient died due to respiratory failure 5 months after the initial symptom. An autopsy, a massive tumor (9.5 cm in diameter) containing abundant mucus with several surrounding daughter nodules was found in the right hepatic lobe. Metastases were widespread. Histologically, the tumor was composed mainly of numerous lobulated mucus lakes in which ade‐nocarcinoma cells floated. Admixed signet ring cells were also noted. These gross and histologic features differ from those in other mucin‐producing hepatic tumors such as biliary papillomatosis and mucinous cystoadenocarcinoma. lmmunohistochemically, the adenocarcinoma cells were strongly positive for carcinoembryonic antigen, Lewis Y, Tn, and T antigens, and moderately positive for carbohydrate antigen 19–9, Lewis X, sialyl‐Lewis X and sialyl‐Tn antigen. Mature MUCl mucin and core protein of MUCl mucin were also expressed to varying degrees. The rapidly expanding, widespread metastases and poor prognosis found in the present case may be the clinicopathological features of mucinous cholangiocarcinoma.

Flow-Cytometric Analysis of Colorectal Cancer with Hepatic Metastases and Its Relationship to Metastatic Characteristics and Prognosis

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Cytochemical localization of glutaraldehyde-resistant NAD(P)H-oxidase in rat hepatocytes

SummaryNAD(P)H-oxidase activity was demonstrated in glutaraldehyde-fixed rat hepatocytes by a cerium technique. The activity was observed exclusively on the bile-canalicular plasma membrane of hepatocyte. No reaction product was formed in the absence of NAD(P)H as the substrate. The reaction was inhibited by pCMB (surface sulfhydryl group specific reagent), by heating, by anaerobic incubation and by catalase (H2O2 scavenger), but it was not inhibited by KCN or NaN3. The present results show that bile-canalicular plasma membrane produces H2O2 and the cerium technique for demonstration of H2O2 is therefore an useful method for the subcellular localization of NAD(P)H-oxidase activity in the glutaraldehyde-fixed hepatocyte.

A case of pheochromocytoma with severe paralytic ileus

We report herein a rare case of a 26 year old woman with pheochromocytoma complicated by paralytic ileus. She presented with remarkable abdominal distension and respiratory difficulty but was effectively treated by surgical removal of the tumor with preoperative and operative management using α and β adrenergic blocking agents. An excessive and persistent catecholamine production from large tumors or massive metastases characterizes this rare complication, and a review of the English and Japanese literature is given following this report.

The immunosuppressive effects of a leukotriene B4 receptor antagonist on liver allotransplantation in rats.

The immunosuppressive effects of a leukotriene B4 (LTB4) receptor antagonist, ONO4057, on liver allotransplantation in rats were evaluated, and the levels of prostaglandin E2 (PGE2) in the liver tissue during rejection of the allografts examined. The rats were divided into four groups: group 1: Lewis rats (LEW) given a sham operation with dimethyl sulfoxide (DMSO); group 2: LEW given syngenic orthotopic liver transplantation (OLT) from LEW, with DMSO; group 3: LEW given allogenic OLT from ACI rats (ACI), with DMSO; and group 4: LEW given allogenic OLT from ACI, with ONO4057 as 10, 30, or 100 mg/kg per day dissolved in DMSO to subgroups 4a, 4b, and 4c, respectively. Histological examinations were performed, survival times monitored, and liver tissue PGE2 levels 3, 5, 7, and 14 days after transplantation measured. The mean graft survival times in groups 4a, b, and c, at 37.5±10.4, 52.2±24.4, and 34.0±4.9 days (mean±SEM), respectively, were significantly longer than that in group 3 (at 13.0±3.2 days). Moreover, the levels of tissue PGE2 in the liver allografts in group 4a were significantly higher than those in group 3 on days 5 and 7. These results suggest that ONO4057 has an immunosuppressive effect on liver allotransplantation since it reduces the activities of LTB4 which augments immune responses, and also because it indirectly increases the PGE2 level.