Masaki Fukasawa

Role of Preoperative Transcatheter Arterial Chemoembolization for Resectable Hepatocellular Carcinoma: Relation between Postoperative Course and the Pattern of Tumor Recurrence

The effects of preoperative transcatheter arterial chemoembolization (TACE) were retrospectively evaluated in patients with resectable hepatocellular carcinoma (HCC). A total of 227 patients who underwent hepatectomy for HCC were studied (146 underwent preoperative TACE and 81 did not). We compared operative outcome, mortality, and disease-free survival between TACE and non-TACE groups. We also compared the pattern of recurrence and postrecurrence survival between subgroups according to staging. Of the 227 patients, 105 with tumor stage I-II were assigned to group A (group A/TACE, n = 69; group A/non-TACE, n = 36), and the remaining 122 with tumor stage III-IV were assigned to group B (group B/TACE, n =77; group B/non-TACE, n =45). Complete necrosis was found to be more frequent in the TACE group (p < 0.01). Operating time, blood loss, and mortality did not differ between those who did and did not undergo preoperative TACE. TACE did not significantly improve disease-free survival within either the entire TACE group or group A/TACE. In contrast, in group B/TACE the disease-free survival rates were significantly higher than in group B/non-TACE. Furthermore, both extrahepatic metastasis and diffuse intrahepatic metastasis were significantly more frequent in group B/non-TACE than in group B/TACE. The preoperative TACE also improved the postrecurrence survival in group B. We speculate that preoperative TACE reduced tumor recurrence and that it might confer a survival advantage after surgery, particularly in patients with advanced HCC. In addition, it is expected that this procedure may improve the pattern of tumor recurrence when it does occur.

Clinical investigation of endothelin-1 and nitric oxide in patients with portal hypertension focusing on plasma levels and immunohistological staining of liver tissues

Plasma concentrations of endothelin-1 (ET-1) and nitrite/nitrate of patients with portal hypertension were measured. Sixteen patients with liver cirrhosis (the LC group) and 14 patients with idiopathic portal hypertension (the IPH group) and 12 healthy subjects (normal controls) were included in this study. The peripheral venous plasma concentration of ET-1 was significantly higher in the LC group (6.69+/-2.44 pg/ml) than in the IPH group (3.07+/-0.84 pg/ml) and normal controls (1.79+/-0.36 pg/ml), while the value in the IPH group was also significantly higher than that in normal controls. The peripheral venous plasma concentration of nitrite/nitrate was significantly higher in the LC group (67.7+/-38.9 &mgr;Mol/l) than in the IPH group (32.3+/-24.4 &mgr;Mol/l) and normal controls (26.1+/-9.8 &mgr;Mol/l). Hepatic venous plasma concentrations of ET-1 and nitrite/nitrate were measured in 8 patients from the LC group and 10 patients from the IPH group. The plasma concentration of ET-1 in the hepatic vein was significantly higher than that in the peripheral vein in both the LC and the IPH groups. The plasma concentration of nitrite/nitrate in the hepatic vein was significantly higher than that in the peripheral vein in the LC group. We also investigated the localization of ET-1, endothelin receptor (ET receptor) and nitric oxide synthase (NOS) in the liver tissue of LC patients (n=10), IPH patients (n=10) and normal controls (n=10). The expressions of ET-1, ET A receptors, ET B receptors, and inducive NOS (iNOS) were detected in patients with LC, and the labeling index (LI) was significantly higher than that in patients with IPH and normal controls. The expressions of ET-1, ET A receptors, and ET B receptors were found in patients with IPH, and the LI was significantly higher than that in normal controls. The expression of endothelial NOS (eNOS) was scarce in both LC and IPH patients. From these results, overproduction of ET-1 in the liver was regarded as one of the causes of the high plasma concentration of ET-1 in patients with LC and IPH. One of the causes of the high plasma concentration of nitrite/nitrate in LC was considered to be overproduction of nitric oxide (NO) in the liver. And we suggested that ET-1 is at a relatively higher density than NO in the hepatic sinusoid in LC and IPH.

Carcinosarcoma of the esophagus characterized by myoepithelial and ductal differentiations

We report a case of carcinosarcoma of the esophagus characterized by ductal and myoepithelial differentiation. A 61‐year‐old man was operated on for a polypoid tumor of the distal esophagus. Histologically, this tumor was composed of ductal structures and sarcomatous spindle cells surrounding the ducts at the central area of the tumor. The tumor was also composed of squamous cell and basaloid carcinoma in the periphery. Immunohistochemically, a few spindle cells surrounding the ductal structures showed immunopositivity for α‐smooth muscle actin and S‐100 protein. Electron microscopy revealed that the spindle cells had tonofilament and pinocytic vesicles in the cytoplasm, and basal lamina adjacent to the cytoplasmic membrane. Both of the results strongly supported the suggestion that the spindle cells may be myoepithelial cells. Basaloid carcinoma showed a gradual transition to chondrosarcomatous cells producing the matrix, which had both immunopositivities for S‐100 protein and cytokeratin. Therefore, chondrosarcomatous cells may be derived from carcinoma cells. The histogenesis of this tumor may be associated with a totipotential stem cell of esophageal mucosa, which has the potential to differentiate into squamous cells, ductal cells or myoepithelial cells.

Correlation of Thymidine Phosphorylase Staining and the Ki-67 Labeling Index to Clinicopathologic Factors and Hepatic Metastasis in Patients with Colorectal Cancer

AbstractPurpose. Our aim was to investigate the thymidine phosphorylase (TdRPase) expression and Ki-67 labeling index (LI) of primary tumors of colorectal cancer and hepatic metastases immunochemically and to evaluate the relationship of these parameters to various clinicopathologic factors and hepatic metastasis. Methods. We performed immunochemical studies in 74 patients with colorectal cancer, using anti-TdRPase antibody and MIB-1 antibody. Results. TdRPase expression and a Ki-67 LI ≧30% in primary lesions were significantly more common in patients with lymphatic invasion (ly), venous invasion (v), lymph node involvement (n), and hepatic metastasis. A Ki-67 LI ≧ 30% of the primary tumor was associated with a significantly higher frequency of metachronous liver metastasis. In the same patients, the mean Ki-67 LI was 24.3 ± 17.9 for primary lesions and 5.0 ± 4.2 for hepatic metastases, this difference being significant. Conclusions. These results indicate that TdRPase expression and the Ki-67 LI are related to various clinicopathologic factors, suggesting their usefulness as indices of tumor malignancy. We suggest that the Ki-67 LI of primary colorectal cancer could be an important predictor of the future development of metachronous liver metastasis.

Hemodynamics in extrahepatic portal vein obstruction and its changes during long-term follow-ups

Thirty-six patients with extrahepatic portal vein obstruction (EHO) were studied. Twenty-one patients, whose age at onset was under 20 years old, were thought to be primary EHO. Ten of 15 patients over 21 years old, had a history of abdominal diseases, and were thus considered to be secondary EHO; only 5 were primary EHO. EHO was classified into three categories, based on selective celiac-superior mesenteric arteriography, and intraoperative trans-splenic and superior mesenteric venography: the hilar obstruction of portal vein, the portal trunk obstruction, and the portal trunk-splenic vein obstruction. Both primary and secondary EHO cases were found to have extended their obstructed region over time by progressing from hepatic hilum to portal trunk obstruction followed by splenic vein obstruction. On the other hand, based on retrograde portography, EHO was classified into the absence of intrahepatic portal obstruction (portal trunk type) and the intrahepatic obstruction (portal branch type) and the portal branch type tended to predominate. Changes of intra- and extra-hepatic portal obstruction were examined by comparing various angiographies of the 14 patients available for between 1 and 26 years of long-term follow-up. While EHO tended to progress with time, no patient showed progress of a intrahepatic portal vein obstruction. From these results, EHO patients are expected to show continuous progression of EHOs during long-term follow-ups, and to have high recurrence rates of gastrointestinal varices after various treatments due to the persistent portal hypertension. However, effective hepatic flow is likely to be maintained because collateral circulation to the liver develops, and intrahepatic portal vein obstruction does not progress, resulting in a good prognosis for EHO.

Numerical chromosomal abnormality in gastric MALT lymphoma and diffuse large B-cell lymphoma.

Background: We investigated numerical chromosomal abnormalities, using the fluorescence in situ hybridization (FISH) method, in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). We also compared the histopathological findings, including the presence or absence of Helicobacter pylori infection, with the analytical results. Methods: Sixteen patients who underwent operation for malignant gastric lymphoma in our department were divided into three groups: patients with low-grade gastric MALT lymphoma (l-MALT; n = 5), those with high-grade gastric MALT lymphoma (h-MALT; n = 8), and those with DLBL (n = 3). Numerical abnormalities of chromosomes 8, 9, 12, and 17 were investigated by the FISH method, and the presence or absence of H. pylori infection was microscopically examined. Results: Numerical abnormality was observed in chromosome 12 in 11 patients (68.8%), in chromosome 8 in 10 (62.5%), and in chromosome 17 in 5 (31.3%), showing a high frequency. H. pylori infection was detected in 80% and 50% of patients with l-MALT and h-MALT, respectively, but no H. pylori infection was observed in patients with DLBL. Conclusions: A new biological characteristic of gastric MALT lymphoma was obtained, i.e., a high frequency of numerical abnormalities of chromosomes 12, 8, and 17. There was no correlation between the numerical chromosomal abnormalities and the clinicopathological findings.

Evaluation of a non-shunting operation by measurement of the blood flow velocity using transendoscopic microvascular Doppler sonography for esophageal and gastric varices

The purpose of this study was to evaluate whether transendoscopic microvascular Doppler sonography (EMDS) is useful to analyze Hassabs operation and esophageal transection (non-shunting operation) which are effective for patients with esophagogastric varices. Twenty patients with esophagogastric varices were examined. Before the operation, we examined the conditions of the esophagogastric varices and measured the velocity of the varices with EMDS. The blood flow velocity in the largest varices (F3) was significantly higher than that in the straight varices (F1). After the operation, the esophageal and gastric variceal blood flow velocities were markedly decreased in 15 patients. In five of the patients who received Hassabs operation, the esophageal variceal form and blood flow velocity still remained. After endoscopic injection sclerotherapy, the velocity and form were completely resolved. The non-shunting operation is effective therapy in the esophageal and gastric varices. It is concluded that EMDS is a non-invasive method and it appears to be very useful for the evaluation of the non-shunting operation.

Serum Bile Acid Concentration for Detection of the Connection Site of Portal-Systemic Shunt-A case report with Cruveilhiel-Baumgarten syndrome-

肝性脳症を呈したCruveilhier-Baumgarten症候群の1例で,肝静脈および大静脈各部位の血清総胆汁酸濃度を測定した.血清総胆汁酸濃度は,肝静脈血で最も低値を示した.右心房混合静脈血が肝静脈血より高濃度である事は,肝外シャントによる門脈血の大静脈系への流入の結果と考えられた.大静脈系は,混合静脈血濃度より更に高値を示した.大静脈各部位で胆汁酸濃度差がみられた事から門脈血の混入部位を推定したが,血管造影により,血清胆汁酸濃度の上昇部で門脈側副血行路の存在が証明された.以上から,血清胆汁酸は,門脈大循環シャントの存在または存在部位を示す生化学的指標として有用と考えられた.