Search PubMed⌕ Search

Biomedical subjects

S Ohwada

Publications and source records attributed to S Ohwada.

At least 73 records · Page 4Linked to original sources

Left colon substitution with His' angle following total gastrectomy. Surgical technique using stapling devices.

To resolve the disadvantages of jejunal Roux-en-Y reconstruction following total gastrectomy, we attempted the use of left colon substitution with all anastomoses conducted using mechanical stapling devices. A His' angle was formed to reduce regurgitation esophagitis. About 25 cm of the left colon with the ascending branch of the left colic artery with an adequate blood supply was brought up to the remnant esophagus without tension on the mesentery. The colon graft was interposed between the esophagus and duodenum in an isoperistaltic fashion. Three anastomoses, esophagocolic, duodenocolic and colocolic, were completed with a circular stapling device. An end-to-side esophagocolonostomy was positioned about 3 cm distal from the blind end of the proximal colon stump. The proximal end of the left colon was pexied to the esophagus using 3-4 stitches to make a new His' angle. Gastrointestinal continuity was restored by a side-to-end colonoduodenostomy and an end-to-end colonocolonostomy. Fifteen gastric cancer patients underwent left colon substitution following total gastrectomy. The circular staple used for esophagocolonostomy and colonoduodenostomy was 25 mm in all patients, and for colonocolonostomy was 29 mm in 9 patients and 33 mm in 6 patients. No problems were encountered in any steps of the procedure, and faulty stapling was avoided. Neither anastomotic leakage nor necrosis of the interposed colon segment was seen, nor was late anastomotic stricture, in any patient. Barium radiograms of the interposed colon segment showed that the capacity and passage of the interposed colon were adequate, and regurgitation did not occur. Diet volume was satisfactory and weight loss minimal.

Adult↗

Effects of a phosphate buffered extracellular (Ep4) solution in preservation and reperfusion injury in the canine liver.

The Ep4 solution, a phosphate buffered extracellular-type solution, is effective in canine lung transplantation following a 96-hour hypothermic (4 degrees C) preservation. In this experiment, we used this solution for liver preservation followed by transplantation. We compared the Ep4 solution with the lactated Ringer's (LR) and the Collins' M (CM) solution (a phosphate buffered intracellular-type solution) in two studies, 1) 48-hour liver preservation, and 2) orthotopic liver transplantation after 5-hour preservation. In the preservation study, purine nucleoside phosphorylase (PNP) levels as a marker of endothelial damage, and alanine aminotransferase (ALT) levels were significantly lower in the livers immersed into the Ep4 solution than in those immersed into other solutions at 36 and 48 hours after preservation. Microscopically, the endothelial injury occurred 24 hours after preservation in the CM solution, and 36 hours after preservation in the LR and Ep4 solutions. In the transplantation study, serum PNP and ALT levels in the livers immersed in Ep4 solution showed a lower tendency compared with those in other solutions at the time of reperfusion, but the histological differences among three groups were not apparent. The present study suggests that the liver can be stored better for a longer time using Ep4 solution than using LR and CM solutions.

Alanine Transaminase↗

Mutation analysis of transforming growth factor beta type II receptor, Smad2, and Smad4 in hepatocellular carcinoma.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII), Smad2, and Smad4 genes have been detected in several human cancers. However, there are no reports of mutation analysis of the entire coding regions in these genes in hepatocellular carcinoma, and the roles of these genes in hepatocarcinogenesis remain unknown. We screened 30 hepatocellular carcinomas for mutations of these genes using polymerase chain reaction single-strand conformation polymorphism. We detected no mutations, but did find 3 cases of loss of heterozygosity of chromosome 17p13.1. These results suggest that mutations of the TGFbetaRII, Smad2, and Smad4 genes are rare, and that genetic instability is uncommon in human hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

The effect of Lazaroid U-74389G on extended liver resection with ischemia in dogs.

BACKGROUND: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and it sometimes causes liver failure. This study was designed to evaluate the effect of Lazaroid U-74389G (LAZ-G), which inhibits iron-dependent lipid peroxidation, on ischemia-reperfusion injury during liver resection in dogs. METHODS: The experiment animals were divided into 2 groups. The control group was subjected to 60 minutes of warm ischemia by partial inflow occlusion. The LAZ-G-treated group received LAZ-G before ischemia and then underwent liver ischemia. After reperfusion, the nonischemic lobes were resected, and the remnant liver function was evaluated. RESULTS: The LAZ-G-treated group showed a significantly improved animal survival rate. Biochemical analysis and morphologic evaluation by electron microscopy suggest that LAZ-G pretreatment protects both hepatic parenchymal cells and sinusoidal endothelial cells from ischemia-reperfusion injury. Expression of IL-1 beta messenger RNA in hepatic venous blood was measured by a reverse transcriptase-polymerase chain reaction; it was shown to be inhibited in the LAZ-G-treated group after reperfusion. This suggests that LAZ-G decreases the activation of proinflammatory cytokine expression. CONCLUSIONS: Lazaroid U-74389G ameliorates ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may therefore be clinically applicable for extended liver surgery involving vascular isolation.

Animals↗

Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer.

The serum concentration of hepatocyte growth factor (HGF) was examined in 34 patients with metastatic breast cancer. Although no significant difference was observed between HGF concentration and the site of metastasis, serum HGF levels were slightly higher in patients with liver metastasis and in patients with multiple metastatic sites than in patients with other lesions. Significantly higher levels of serum HGF were observed in patients with progressive metastasis of breast cancer compared with those with stable metastasis. The patients with high HGF levels exhibited a significantly shorter survival rate than those with low HGF levels. Circulating HGF levels may be a useful indicator for the progression of metastatic lesions and the prognosis of patients with metastatic breast cancer.

Adult↗

Growth dependency of a new human pancreatic cancer cell line, YAPC, on autocrine interleukin-1alpha stimulation.

We established a new human pancreatic cancer cell line from the malignant ascites of a patient with pancreatic cancer and called it YAPC. Cytogenetic and morphological analysis indicated that this cell line is monoclonal and of human origin. YAPC cells grow in nude mice, resulting in the formation of a tumor with some functional characteristics of the original tumor. The cells secreted a large amount of inflammatory cytokines including interleukin-1alpha(IL-1alpha), IL-6 and IL-8 in the culture medium. Removal of serum from the culture medium did not change the growth rate of YAPC cells, but the removal of the conditioned medium arrested their proliferation under the serum-free conditions. Exogenous IL-1alpha but neither IL-6 nor IL-8 stimulated DNA synthesis of the cells and accelerated the progress of cell cycle from G1 to the S phase. Anti-IL-1alpha antibody prevented growth of the cells in a dose-dependent fashion. In this pancreatic cancer cell line cell growth is dependent on IL-1alpha in an autocrine fashion. This line may be a useful model for studying growth regulation mechanisms of pancreatic cancer.

Adult↗

Association of CDKN2A(p16)/CDKN2B(p15) alterations and homozygous chromosome arm 9p deletions in human lung carcinoma.

To elucidate the possibility of the existence of multiple tumor suppressor genes on chromosome arm 9p, we performed genetic and epigenetic analyses of the CDKN2A/p16/MTS1 and CDKN2B/p15/MTS2 genes as well as homozygous deletion mapping of 9p in human lung carcinoma. To avoid overlooking genetic alterations due to contamination of noncancerous cells, we examined 32 non-small cell lung carcinoma (NSCLC) and 16 cell small cell lung carcinoma (SCLC) cell lines. (CDKN2A was mutated or homozygously deleted in 20 (63%) of 32 NSCLC cell lines, and methylation of the CpG island in the CDKN2A gene was detected in six of the 12 cell lines carrying the wild-type CDKN2A gene. Although homozygous deletions of the CDKN2B gene were also detected in NSCLC cell lines with CDKN2A deletions, mutation and methylation in the CDKN2B gene were infrequent. Thus, it was indicated that the CDKN2A gene rather than the CDKN2B gene plays a critical role as a tumor suppressor gene in NSCLC. Homozygous deletions on 9p were detected in 14 (44%) NSCLC cell lines. It is of note that two common regions of homozygous deletions were mapped proximal to the CDKN2A and CDKN2B loci, suggesting that tumor suppressor genes other than CDKN2A are present on 9p. In contrast to NSCLC, homozygous deletions on 9p as well as CDKN2A and CDKN2B alterations were infrequent in SCLC. Therefore, the pathogenetic significance of 9p alterations is likely to differ between SCLC and NSCLC.

Carcinoma, Small Cell↗

The effects of FR167653 in extended liver resection with ischemia in dogs.

Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are cytokines commonly associated with inflammatory conditions such as hepatic injury after ischemia-reperfusion. FR167653 has been characterized as a potent suppressant of IL-1beta and TNF-alpha production. In this study, we evaluated the effect of FR167653 in an extended liver resection with ischemia in a dog model. The right portal pedicle was clamped for 60 minutes, while the left portal branch was patent to avoid portal congestion. Following reperfusion, 75% of the liver (including the right central, quadrate, left central, left lateral, and papillary lobes) were resected. Animals were divided into two groups: a control group (n = 10), and a FR-treated group (n = 6) in which FR167653 was administered via the portal vein. Hepatic venous blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), purine nucleoside phosphorylase (PNP), and hyaluronic acid (HA) levels, and IL-1beta expression was also measured by reverse-transcriptase polymerase chain reaction (RT-PCR). ALT, AST, LDH, PNP, and HA levels after reperfusion were significantly lower (P < .05) in the FR-treated group than in the control group, and the FR-treated group showed inhibited IL-1beta expression. Liver tissue blood flow, measured by a laser Doppler flow meter, was kept higher in the FR-treated group than in the control group. Histologically, tissue damage was mild in the FR-treated group. The 2-day survival rate was statistically better (P < .05) in the FR-treated group than in the control group. We conclude that FR167653 provides a protective effect for liver parenchyma and sinusoidal endothelial cells in extended liver resection with ischemia.

Alanine Transaminase↗

Intramucosal pH and intestinal mucosal damage in ischemia-reperfusion injury.

Small bowel transplantation (SBT) has become an increasingly promising treatment for short bowel syndrome. The evaluation of graft viability after SBT, however, has not been established, except by mucosal biopsy. We monitored intestinal mucosal acidity in order to detect small intestinal ischemia-reperfusion injury. Mongrel dogs were used in this study. After laparotomy, the small bowel was isolated with a vascular pedicle. A tonometer to measure intramucosal pH (pHi) was then positioned in the terminal ileum. The superior mesenteric artery was occluded with or without concomitant superior mesenteric vein occlusion for 60 or 120 min. The value of pHi was determined from laparotomy (baseline) to 12 h after reperfusion. Whole-thickness specimens of the ileum were taken before ischemia, just before reperfusion, and 1 h afterward. Mucosal injury was graded histopathologically. pHi decreased from baseline in relation to the degree of histopathological mucosal injury. There was a significant correlation between histological findings and the change in pHi. We conclude that monitoring intestinal mucosal acidity is a reliable way of determining graft viability after SBT.

Animals↗

Fibrin glue sandwich prevents pancreatic fistula following distal pancreatectomy.

Pancreatic fistula is a major form of morbidity following pancreatic resection. We conducted a nonrandomized clinical trial comparing the sealing and sandwich techniques of spraying fibrin glue to prevent pancreatic fistula following distal pancreatectomy. The pancreas was transected with a scalpel to identify and suture the main pancreatic duct and its small branches. In the sealing group, fibrin glue was sprayed over the closed pancreatic stump and sutures. Alternatively, in the sandwich group fibrin glue was sprayed so as to cover and join the cut surface of the pancreatic remnant, which was then held closed with sutures. Altogether 111 patients were included in the study (90 with gastric cancer, 10 with esophageal cancer, and 11 with pancreatic cancer). Patients were nonrandomly assigned to the sandwich or the sealing group. Morbidity was 21.8% for the patients in the sandwich group versus 33.9% in the sealing group. Pancreatic fistulas occurred in 9.0% of the sandwich group versus 26.8% of the sealing group. The incidence of fistula was thus significantly lower in the sandwich group. The incidence of fistula was also significantly lower in the sandwich group for gastric malignancy patients undergoing extended radical lymphadenectomy down to the paraaortic lymph nodes combined with left adrenalectomy. Of the patients with gastric malignancy, pancreatic fistulas occurred in 9.3% of the sandwich group versus 25.5% of the sealing group. The fibrin glue sandwich technique is simple and reliable and should be valuable for complementing other prophylactic methods of preventing pancreatic fistula.

Adult↗

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗

Efficacy of hypothermic perfusion using University of Wisconsin solution in extended hepatectomy with hepatic inflow occlusion in a canine model.

This study was designed to elucidate the efficacy of University of Wisconsin (UW) solution for preventing liver injury, when used as a hypothermic perfusate infused into the systemic circulation during extended hepatectomy with hepatic inflow occlusion. Adult mongrel dogs (9.5-17.5 kg, n = 14) were subjected to 75% hepatectomy under 60 min hepatic inflow occlusion. The animals were divided into two groups. The UW group (n = 7) underwent hypothermic perfusion using 4 degrees C UW solution (core temperature of the liver: 12.3 +/- 0.2 degrees C). The control group designated as the Ringer's lactate (LR) group (n = 7) underwent hypothermic perfusion using 4 degrees C LR solution. The perfusate was introduced into the systemic circulation via the hepatic vein. Blood from the hepatic vein was sampled, and alanine aminotransferase, purine nucleoside phosphorylase activities and the ammonia concentration were measured. The 7 day survival rate was higher in the UW group than in the LR group. The parameters of liver function were less significantly altered in the UW group than in the LR group. The plasma ammonia concentration was significantly (P < 0.05) lower 6 h after reperfusion in the UW group than in the LR group. A small volume of hypothermic perfusion of the liver using UW solution was safe if it returned to systemic circulation. Hypothermic perfusion of the liver using UW solution may be effective for preventing hepatic tissue injury during extended hepatectomy with hepatic vascular occlusion.

Adenosine↗