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Biomedical subjects

S Isaji

Publications and source records attributed to S Isaji.

At least 19 recordsLinked to original sources

Are the results of surgical treatment of hepatocellular carcinoma poor if the tumor has spontaneously ruptured?

BACKGROUND: The aim of this study was to clarify whether the results of surgical treatment of ruptured hepatocellular carcinoma (HCC) are poorer than the results of surgical treatment of non-ruptured HCC. METHODS: Out of a total of 224 HCC patients, the 6 patients with ruptured HCC were compared with 15 patients with non-ruptured HCC based on TNM stage IVA and having a Cancer of the Liver Italian Program (CLIP) score of 1 or 2. RESULTS: There were no significant differences in clinical and pathological features between the two groups. The 1-year and 3-year overall survival rates were 69.3% and 21.2%, respectively, in the ruptured HCC group and 51.3% and 20.5%, respectively, in the non-ruptured HCC group. The 1-year and 3-year disease-free survival rates were 33.0% and 0%, respectively, in the ruptured HCC group and 38.9% and 15.6%, respectively, in the non-ruptured HCC group. The differences in survival rates between these two groups did not reach statistical significance. CONCLUSION: Hepatic resection as definitive treatment after recovery from the initial insult of the rupture of HCC yields results similar to those obtained by surgical treatment of non-ruptured HCC at the same tumor stage and with the same degree of liver damage.

Adult↗

Analysis of 100 consecutive hepatectomies: risk factors in patients with liver cirrhosis or obstructive jaundice.

We analyzed various pre-, intra-, and postoperative variables in 100 consecutive patients treated by hepatectomy for various malignant and benign liver diseases to identify patients at risk of developing postoperative complications. Patients were divided into three groups: those with normal liver (NL, n = 53); those with liver cirrhosis (LC, n = 32); and those with obstructive jaundice (OJ, n = 15). The overall postoperative morbidity and mortality rates were 14% and 4% (due to liver failure), respectively. In the LC group the combined presence of abnormal levels of serum hyaluronic acid (HA, > 200 ng/ml), indocyanine green retention rate at 15 minutes (ICGR15, > 15%), and hepatic uptake ratio of (99m)Tc-galactosyl human serum albumin (GSA) at 15 minutes (LHL15, < 0.9) preoperatively was found to be a risk factor with a 100% morbidity rate. Operative blood loss of more than 1000 ml in LC patients was associated with high morbidity. In the OJ group preoperative parameters were almost normal after biliary drainage, but the extent of liver resection, blood loss > 2000 ml, and high serum interleukin-6 12 hours after hepatectomy correlated with high postoperative morbidity. No morbidity or mortality was reported in the NL group, except in a single patient who received long-term intraarterial chemotherapy preoperatively. Consequently, the extent of hepatectomy should be carefully determined according to the preoperative risk factors in LC patients; and in OJ patients hepatectomy, which tends to become extensive, should be carefully performed to minimize surgical stress because preoperative factors do not help predict outcome. Furthermore, the present study revealed that a serum HA level higher than 500 ng/ml on postoperative day 1 or day 7 (or both) was a useful marker for hepatic failure.

Adult↗

Surgical treatment of pancreatic cancer. Does extended lymphadenectomy provide a better outcome?

The rate of curative resection of pancreatic cancer has increased as a result of extended operations, but this has not led to any significant improvement in postoperative outcome. No definite conclusions were drawn in retrospective studies comparing outcome after standard and extended operations, and there was almost no difference in outcome between the two groups in a recent prospective randomized study. In addition, extended procedures are very stressful operations that, in most instances, impair the patient's quality of life (QOL). As a result, the need for performing extended surgery to treat pancreatic cancer has come into question. The outcome of advanced cancer in patients in whom curative resection cannot be achieved by extended operations is extremely poor, and we believe that, in such patients, priority should be given to QOL, by selecting bypass or limited operations instead. It is hoped that the value of extended surgery will be clarified by a very carefully planned multicenter prospective randomized study in the future.

Adenocarcinoma↗

Pancreatic head resection with second-portion duodenectomy for benign lesions, low-grade malignancies, and early stage carcinomas involving the pancreatic head region.

BACKGROUND: Preservation of arterial blood supply to the duodenum and common bile duct during duodenum-preserving total resection of the pancreatic head is a major problem. We describe here a new procedure comprising pancreatic head resection with second-portion duodenectomy to overcome it. METHODS: The procedure was performed in 18 patients with benign lesions, low-grade malignancies, or early stage carcinomas involving the pancreatic head and with carcinoma of the middle bile duct or the gallbladder. The technique preserves the third portion of the duodenum by conserving the anterior inferior pancreaticoduodenal artery. The second portion of the duodenum is divided, followed by division of the lower bile duct and pancreatic neck. After resection followed by duodenoduodenostomy, there is a choice of two procedures: type A, pancreaticoduodenostomy and choledochoduodenostomy; or type B, pancreaticojejunostomy and hepatodochojejunostomy. RESULTS: There were no operative or hospital deaths (type A, 6; type B, 12). Postoperative complications occurred in 2 patients, but the others had an uneventful postoperative course. The quality of life of all patients has been satisfactory up to 36 months postoperatively. CONCLUSION: This procedure is a reliable option as an organ-preserving procedure for benign lesions, low-grade malignancies, and early stage carcinomas involving the pancreatic head.

Bile Duct Neoplasms↗

Role of PAF in acute liver injury after extended hepatectomy: overexpression of PAF receptor mRNA in Kupffer cells.

To clarify the pathophysiology of acute liver injury after extended hepatectomy, we investigated the relationship between the site and levels of expression of platelet activating factor (PAF) receptor mRNA, and the blood levels of endotoxin, cytokines, and prostaglandin E2 (PGE2), using a rat model of 70% hepatectomy. After hepatectomy, a significant rise in serum tumor necrosis factor-alpha (TNF-alpha) was observed at 1 hr, the interleukin-6 (IL-6) levels had increased at 3 hr, and PGE2 levels had increased at 6 hr, but there were no significant increases in endotoxin levels in portal vein blood. Overexpression of PAF receptor mRNA in liver tissue was observed as early as 1 hr after hepatectomy, with peak expression occurring at 6 hr, and PAF receptor mRNA was significantly overexpressed in Kupffer cells. The PAF produced in the vicinity of Kupffer cells appears to play a very important role as one of the initial mediators of the acute liver injury that occurs after major hepatectomy.

Acute Disease↗

Liver injury in acute pancreatitis and mitigation by continuous arterial infusion of an antibiotic via the superior mesenteric artery.

Macrophage-derived inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), have been shown to play a central role in aggravation of acute pancreatitis (AP), but little is known about their roles in liver injury. We investigated the pathogenesis of the liver injury in AP and assessed the efficacy of arterial infusion of an antibiotic via the superior mesenteric artery (SMA). Infusion of saline (group A) or imipenem (group B) was started 6 hours after induction of AP in dogs by intraductal administration of autologous gallbladder bile. The survival rate in group B was significantly improved compared with group A. Serum alanine aminotransferase levels in peripheral blood and endotoxin levels in portal vein blood were both significantly higher at 18 hours in group A than in group B. When hepatocytes and Kupffer cells were isolated at 18 hours and cultured for 24 hours thereafter, there was significant exacerbation of the hepatocyte injury and significantly greater production of TNF-alpha in the coculture of hepatocytes and Kupffer cells in group A, indicating that the Kupffer cells had been activated. By contrast, both of these manifestations were significantly mitigated in group B. These findings suggest that TNF-alpha secreted by endotoxin-activated Kupffer cells contributes to liver injury in AP, and that SMA infusion of an antibiotic mitigates the liver injury by controlling endotoxin translocation.

Alanine Transaminase↗

Portal venous stent placement in patients with pancreatic and biliary neoplasms invading portal veins and causing portal hypertension: initial experience.

PURPOSE: To evaluate the clinical usefulness of portal venous stent placement in patients with pancreatic or biliary neoplasms invading portal veins and causing portal hypertension. MATERIALS AND METHODS: Thirteen patients underwent portal venous stent placement because of gastrointestinal bleeding (n = 8), risk of gastroesophageal varix rupture (n = 4), ascites (n = 4), thrombocytopenia (n = 3), and/or portal venous thrombosis (n = 3). The main portal vein or both the intrahepatic and main portal veins were invaded in six patients (group A). The main portal vein and splanchnic veins were involved in seven patients (group B). Stents were placed across the stenotic (n = 8) or occluded (n = 5) lesions after percutaneous transhepatic portography. Changes in portal venous pressure, stent patency, and survival were evaluated. RESULTS: Mean portal venous pressure decreased significantly immediately after stent placement, from 24.9 mm Hg +/- 5.9 (SD) to 15.8 mm Hg +/- 4.6 (P <.001). In group A, blood flow through the stent was maintained and the symptoms had subsided at follow-up (mean, 12.5 months). In group B, symptoms were improved in five patients, but the stents were occluded in all but one patient at a mean follow-up of 1.5 months. There was a significant difference in stent patency between the patients with (14%) and those without (100%) splanchnic venous involvement (P <.01). CONCLUSION: Stent placement helped to relieve portal hypertension symptoms. Splanchnic venous involvement was associated with worse stent patency.

Adult↗

Surgical treatment for hilar cholangiocarcinoma.

From September 1976 to February 1998, we experienced 75 resected patients with hilar cholangiocarcinoma. Curative resection was performed in 45 patients (60.0%), with a cumulative 5-year survival rate of 39.8%. In this retrospective study, we compared therapeutic outcomes in these 75 patients according to the period during which they were treated; (1) 12 patients in the early period (September 1976 to August 1981) chiefly treated by bile duct resection, (2) 50 patients in the middle period, September 1981 to August 1994, chiefly treated by aggressive surgical procedures with extensive hepatectomy plus caudate lobe resection, and (3) 13 patients in the late period, September 1994 to February 1998, during which percutaneous transhepatic portal embolization was introduced to increase the safety and curability of extended hepatectomy, and limited hepatectomy was selected according to tumor spread. In the late period, total resection of the caudate lobe was done in all patients, with the aim being thorough resection of cancer cells in the caudate lobe. The curative resection rates were 16.7% in the early period, 64.0% in the middle period, and 84.6% in the late period, showing an improvement year-by-year (P<0.05; early period vs middle period and late period). All patients in the early period died within 2 years of resection, whereas the 5-year survival rate in the middle period was 24.4%, significantly improved (P<0.05) compared with the early period. The 1- and 3-year survival rates of 84.6% and 58.0%, respectively, in the late period, show an even greater improvement in outcome.

Adult↗

Comparative clinicopathological study of resected intrahepatic cholangiocarcinoma in northeast Thailand and Japan.

Northeast Thailand has a very high incidence of intrahepatic cholangiocarcinoma (ICC), which is closely linked to infestation by the liver fluke, whereas the etiology of ICC in Japan remains to be clarified. This study compared the clinicopathological features, the expression of p53 and c-erbB-2 proteins, and the proliferative activity of ICC in 19 Thai and 23 Japanese patients with ICC who were treated by hepatic resection. The average age of the Thai patients (55.8 years) was lower than that of the Japanese (61.3 years). All Thai patients presented with symptoms, whereas 8 Japanese patients were asymptomatic. There were no significant differences in preoperative liver function test values. Tumors were less likely to be located in the right lobe in the Japanese (34.8%) than in the Thai patients (63.2%). Peribiliary fibrosis and adenomatous hyperplasia in noncancerous hepatic tissues were much more frequently found in the Thai patients (P = 0.0010; P<0.0001). No significant differences in the expression of p53 protein or c-erbB-2 protein were found between the two series of patients, but proliferative activity, evaluated on the basis of mean MIB1 labeling index, was significantly higher in the Thai patients (P<0.001). The present study suggested a higher proliferative activity of ICC in Thai patients than in Japanese patients.

Aged↗

Surgical anatomy of the bile duct branches of the medial segment (B4) of the liver in relation to hilar carcinoma.

In some patients, hilar bile duct carcinoma can easily spread to the bile duct branches of the caudate lobe (B1) as well as to the bile duct branches of the medial segment (B4), and resection of the inferior portion of the medial segment (S4a) is then required. It is therefore important to understand the detailed anatomy of the B4, its confluence patterns, and its relation to the B1 in order to be able to identify such patients. The confluence pattern of the B4 was studied in 141 specimens (68 adult cadavers and 73 liver casts) and the distance between the left bile duct branches of the caudate lobe (B11) and the B4 was measured in 56 of the 73 casts in which both B11 and B4 were present. Two main gross types of B4 were recognized: type I, in which B4 joined the left hepatic duct (LHD) close to the hilar confluence (35.5%), and type II, in which B4 joined the LHD far from the hilar confluence (54.6%). Analysis of the relationship between B11 and B4 revealed a mean distance between B11 and B4 of 8 mm in type 1, and 17 mm in type II. When the distance is less than 10 mm, B11 and B4 are considered to be located very close to each other, and in such individuals hilar bile duct carcinoma can infiltrate the B4 easily, thereby necessitating the resection of S4a, together with a caudate lobectomy for curative resection. Also, the confluence pattern of the B4 often creates a problem when the LHD is divided and reconstructed during hepatectomy, because of the numerous anatomical variations of the B4 itself. We therefore concluded that a good anatomical knowledge of the B4 and its relation to the B11 is essential in making the decision to perform S4a resection in selected patients with hilar bile duct carcinoma with the aim of curative resection.

Adult↗

Comparative study of perioperative management of hepatic resection.

In an attempt to identify the factors that influence outcome after hepatic resection, patient background was reviewed and operative morbidity and mortality rates were assessed during two periods: 1985-1988 (group I: N = 96) and 1995-1998 (group II: N = 109). There were no differences in patient background factors between the two groups, but intraoperative blood loss, operative morbidity, and mortality were significantly reduced in group II compared to group I. There has been a significant reduction in postoperative complications, even in cases complicated by liver cirrhosis or obstructive jaundice. As a result of appropriate surgical procedures, postoperative complications in cirrhosis have been markedly decreased. After preoperative percutaneous biliary drainage in obstructive jaundice, attempts have been made to reduce the volume of blood loss even in extensive hepatectomy, the extent of liver resection in poor risk cases has been reduced without sacrificing radicality, and, by minimizing surgical stress, perioperative management has been greatly improved.

Adult↗

Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas.

We analyzed K-ras and p53 mutations, microsatellite instability (MSI), and loss of heterozygosity (LOH) using the polymerase chain reaction (PCR) methods, as well as p53 expression and the Ki-67 labeling index (LI) using immunohistochemistry in 10 duodenal and 10 jejunal/ileal carcinomas. K-ras mutations were detected in two duodenal (20%) and three jejunal/ileal (30%) carcinomas and p53 mutations in one (10%) and three (30%), respectively. LOH of 17p was detected in two duodenal (20%) and two jejunal/ileal (20%) carcinomas and p53 expression in four duodenal (40%) and four jejunal/ileal (40%). One duodenal (10%) and two jejunal/ileal (20%) carcinomas demonstrated MSI. LOH of APC was detected in three jejunal/ileal (30%), but none of the duodenal carcinomas. The Ki-67 LI was 44% in duodenal and 52.6% in jejunal/ileal carcinomas. A subset of small intestinal carcinomas showed involvement of K-ras and p53 mutations, LOH of APC, and MSI. A difference was also apparent for LOH of APC between duodenal and jejunal/ileal carcinomas.

Adult↗

Transcriptional and post-transcriptional regulation of monocyte chemoattractant protein-3 gene expression in human endothelial cells by phorbol ester and cAMP signalling.

Monocyte chemoattractant protein-3 (MCP-3) is one of the most broadly active chemokines, potentially inducing chemotaxis of all leucocytic cells. In the present study, we examined the regulation of MCP-3 mRNA and protein production in endothelial cells by protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and cAMP signalling. On stimulation of endothelial cells with 10 nM PMA, MCP-3 mRNA increased to 300-fold the basal level at 3 hr and rapidly declined to 0.2-fold the basal level at 24 hr. PMA-induced MCP-3 mRNA and protein production of human endothelial cells were partially inhibited by pretreatment with the adenylate cyclase activator, forskolin, or membrane-permeable cAMP derivative. The PMA-induced MCP-3 mRNA increase was almost abrogated when cells were pretreated with cycloheximide (CHX). Forskolin inhibited the transcription of PMA-induced MCP-3 gene expression. Following PMA stimulation for 3 hr, subsequent addition of actinomycin D suppressed the rapid decay of PMA-induced MCP-3 mRNA. These results suggest that PMA induces the transcriptional activation of the MCP-3 gene through de novo protein synthesis and the rapid decay of PMA-induced MCP-3 mRNA through de novo synthesis of adenosine/uridine (AU)-rich element binding proteins and cAMP signalling inhibits the PMA-induced transcriptional activation of the MCP-3 gene expression.

Adenylyl Cyclases↗