Biomedical subjects

Susumu Ohwada

Publications and source records attributed to Susumu Ohwada.

53 records · Page 3Linked to original sources

PubMed2002

Mutation and expression of the beta-catenin-interacting protein ICAT in human colorectal tumors.

BACKGROUND: Aberrant activation of Wnt signaling caused by mutations in the tumor suppressor adenomatous polyposis coli or beta-catenin is a critical event in the development of human colorectal tumors. We have recently identified the ICAT gene, which encodes a small protein that interacts with beta-catenin and represses Wnt signaling. METHODS: We examined the prevalence of mutations in the entire ICAT coding sequence and intronic splice donor and acceptor regions of ICAT by PCR-SSCP and also the expression of the ICAT gene by RT-PCR. RESULTS: The ICAT gene was mapped to chromosome 1p36.1-p36.2, which is implicated in the pathogenesis of various types of cancers. However, no mutations in ICAT were detected among 128 colorectal tumors. Instead, ICAT was found to be overexpressed in almost half of colorectal carcinomas. Cases exhibiting ICAT overexpression showed a significantly higher incidence of well-differentiated adenocarcinoma and positive lymphatic permeation. CONCLUSION: Our results suggest that ICAT is not the putative tumor suppressor on 1p36.1-p36.2, although aberrant overexpression of ICAT may play a role in the pathogenesis of colorectal carcinomas.

Adaptor Proteins, Signal Transducing↗

PubMed2002

[A case of pancreatic tail cancer with peritoneal carcinosis treated with gemcitabine hydrochloride].

This paper reports a case of pancreatic tail cancer with peritoneal carcinosis that showed a good response to gemcitabine hydrochloride. A 52-year-old man, who had undergone a gastrojejunostomy for pancreatic tail cancer with peritoneal carcinosis, was referred to our hospital for anticancer therapy. Laboratory data on admission disclosed hypoalbuminemia and a high level of serum CA19-9 (156 IU/ml). These findings indicated that the patient was in a cancer cachexic condition. Gemcitabine hydrochloride treatment (1,000 mg/m2/week x 3/4 weeks) was started. Ascites disappeared after 2 courses of treatment, and the tumor was reduced (62% of the reduction rate) after 5 courses of treatment. Furthermore, the serum CA19-9 level and serum albumin value returned to normal, and performance status was improved to grade 1. The patient has been well for 15 months after the diagnosis of pancreatic tail cancer with peritoneal carcinosis. Gemcitabine hydrochloride may have not only reduced the tumor volume and improved cancer cachexic condition, but also prolonged the survival time in this case.

Antimetabolites, Antineoplastic↗

PubMed2001

FR128998 (a PAF Receptor Antagonist) Counters the Increased Pulmonary Vascular Resistance Associated with Ischemia-Reperfusion Injury in the Canine Lung.

Ischemia-reperfusion injury induces deterioration of pulmonary function following lung transplantation. The spiro-thiazepin derivative FR128998 (FR) is a novel PAF receptor antagonist. The effect of FR on ischemia-reperfusion injury was investigated in an in situ warm ischemia model of canine lungs. Fifteen adult mongrel dogs, weighing 6 to 12 kg, were divided into two groups. FR (1 mg/kg/hr) was administered from prior to ischemia until 2 hours after reperfusion (FR-treated group; n = 8), or vehicle was injected using the same technique (Control group; n = 7). Following hilar stripping of the left lung, the left pulmonary artery and veins were clamped for 3 hours to induce warm ischemia. The left main bronchus was bisected at the same time and anastomosed 3 hours later. Arterial oxygen saturation (SaO(2)), left pulmonary vascular resistance (L-PVR), and cardiac output (CO) were measured 30 minutes after reperfusion. The lungs were harvested for pathological study, and polymorphonuclear neutrophils (PMNs) were counted. The 2-day survival rate was also investigated. After reperfusion, SaO(2) L-PVR, and CO were significantly (p < 0.05) better in the FR-treated group than in the control group. Histological findings after 30 minutes of reperfusion showed alveolar damage with interstitial edema and hyaline membranes localized along the alveolar ducts in the control group, while there was only slight localized interstitial edema in the FR group. PMN infiltration was less extensive in the FR group than in the control group. FR appears to have a protective effect against lung ischemia-reperfusion injury. This might result from inhibition of the local release of PAF. </hea

Journal Article↗

PubMedDate not supplied

Cell cycle arrest and the induction of apoptosis in pancreatic cancer cells exposed to adenosine triphosphate in vitro.

Adenosine triphosphate (ATP) has been shown to be an inhibitory or a stimulatory agent for cell growth in various types of cells. Here, we studied the effects of extracellular ATP on two pancreatic cancer cell lines, PK-1 and YAPC established by us. In both cell lines, ATP inhibited cell growth in a time- and dose-dependent manner, whereas the same doses of ATP stimulated DNA synthesis. Flow cytometric analysis of the cells incubated with or without ATP demonstrated the ATP-induced striking increase in cells at S-phase. The same analysis showed also the increase in sub-G0/G1 population in the same analysis and the electrophoretic pattern of DNA showed the occurrence of ATP-induced cell disintegration likely to be apoptosis. We suggest that extracellular ATP is cytotoxic for pancreatic cancer cells because of its induction of cell cycle arrest at S-phase and cell death, possibly apoptosis, overcoming the promotion of the entry into S-phase.

Adenosine Triphosphate↗

PubMedDate not supplied

Omentoplasty versus no omentoplasty for cervical esophagogastrostomy following radical esophagectomy.

BACKGROUND/AIMS: Omentoplasty--wrapping the omentum around the alimentary tract anastomosis is thought to lower the rate of anastomotic leakage. We evaluated the role of omentoplasty to reinforce cervical esophagogastrostomy after radical esophagectomy. METHODOLOGY: We compared anastomotic leakage, stricture formation, and related deaths in 63 patients who underwent radical esophagectomy and cervical esophagogastrostomy, with (n = 48) or without (n = 15) omentoplasty, between 1995 and 1999. RESULTS: An esophageal anastomotic leakage was diagnosed in 1 of the 48 patients (2.1%) with omentoplasty versus 3 of the 15 patients (20.0%) without omentoplasty (P < 0.01). Anastomotic stricture occurred in 2 (4.2%) of the omentoplasty group and 1 (6.7%) of the no omentoplasty group (P < 0.01). Death within 1 month was zero in the omentoplasty group and one (6.7%) in the no-omentoplasty group, despite no differences in lethal anastomotic leakage. CONCLUSIONS: Omentoplasty of cervical esophagogastrostomy reduced anastomotic leakage. Although promising, these observations require confirmation with a randomized prospective study.

Aged↗

PubMedDate not supplied

Prognostic significance of DNA topoisomerase IIalpha expression in human hepatocellular carcinoma. .

BACKGROUND: The biological significance of the nuclear enzyme DNA topoisomerase II in hepatocellular carcinoma (HCC) remains unclear. MATERIALS AND METHODS: Using immunohistochemical staining methods, we examined the clinical significance of topo IIalpha (8D2) in surgically resected HCC, comparing the expression of both Ki-67 and p53, as well as various clinicopathological factors and prognosis. RESULTS: The 70 HCC samples showed a positive, but heterogeneous pattern. The mean topo IIalpha labeling index (LI) was 14.1 +/- 15.1%, and ranged from 0.2 to 55.6, and the median topo IIalpha LI was 9.9%. The mean value of the topo IIalpha LI in p53-positive HCC cases (25.6 +/- 17.4) was significantly higher than that in p53-negative cases (10.3 +/- 12.3). HCC patients with lower topo IIalpha LI had significantly longer disease-free survival and exhibited a longer cumulative survival period than did those with higher topo lIalpha LI. CONCLUSION: Topo IIalpha over-expression appears to be linked with a potentially aggressive tumor phenotype and may indicate tumor recurrence and cancer-related death in HCC.

Adult↗

PubMedDate not supplied

Malignant gastrointestinal stromal tumor of the jejunum with liver metastasis.

Primary malignant tumors of the small intestine are rare. Malignant gastrointestinal stromal tumors are the third most common neoplasm among primary malignant small bowel tumors. A 56-year-old woman was admitted to our hospital because of appetite loss and dyspnea with movement. On admission, physical examination revealed severe anemia in her conjunctiva and a tumor in her left abdomen. Her hemoglobin level was 6.2 g/dL and other laboratory data were normal. Abdominal ultrasonograms and computed tomograms revealed a 55 x 70-mm heterogeneous mass and multiple low-density masses in the liver. Superior mesenteric arteriograms revealed a hypervascular tumor fed by the jejunal arteries. A malignant gastrointestinal stromal tumor arising from the jejunum with liver metastases was suspected. Partial resection of the affected jejunum and left trisegmentectomy of the liver were performed. The resected primary tumor was 120 x 45 x 65 mm. The tumor was mainly submucosal, but extended outside the jejunum; it was elastically firm and multiloculated. A small ulcer was seen on the mucosal side. The metastatic liver tumors were solid or cystic with diameters of 20 to 40 mm. Histopathological examination revealed that the tumors were characterized by fascicular proliferation of spindle-shaped cells. Immunohistochemical staining was positive for CD34 and c-kit, and negative for S-100 protein and smooth muscle actin. This case was a malignant gastrointestinal stromal tumor originating in the jejunum with liver metastases. The primary tumor and liver metastases were successfully resected simultaneously.

Female↗

PubMedDate not supplied

The effect of FR167653 in a canine total hepatic vascular exclusion model.

BACKGROUND/AIMS: Though liver grafts from non-heart-beating donors are now attracting much attention, these grafts inevitably suffer from severe warm ischemia. The aim of this study was to evaluate the effect of TNF-alpha and IL-1 suppression on warm ischemia-reperfusion injury in a canine total hepatic vascular exclusion model. METHODOLOGY: Warm ischemia was induced by 1-h total hepatic vascular exclusion with active splenofemuro-juglar bypass. Animals were divided into two groups. FR167653 (1 mg/kg/hr) was administered via the portal vein from 30 min prior to ischemia until 2 h after reperfusion to the FR group (n = 7), and a vehicle was administered to the control group (n = 7). The serum alanine aminotransferase, aspartate amino-transferase, lactate dehydrogenase, and hyaluronic acid levels were measured. Hepatic tissue blood flow was also measured. Liver specimens were harvested for histological study, and polymorphonuclear neutrophils were counted. RESULTS: Serum liver enzymes were significantly (p < 0.05) lower, and hepatic tissue blood flow was kept significantly (p < 0.05) better in the FR group than in the control. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p < 0.05) lower in the FR group than in the control group. CONCLUSIONS: FR167653 provides protective effects on hepatic warm ischemic injury in a canine total hepatic vascular exclusion model.

Animals↗

PubMedDate not supplied

Liver metastasis of rectal cancer with intraluminal growth in the extrahepatic bile duct.

Metastatic liver tumors are considered to have a tendency for expansive growth and rarely invade the bile duct. We recently encountered a resected case of liver metastasis from rectal cancer with intraluminal growth in the extrahepatic bile duct with a successful left trisegmentectomy of the liver. A 54-year-old woman underwent a posterior total pelvic exenteration for advanced rectal cancer. Ultrasonography and computed tomography four months after the first operation demonstrated a solitary occupied lesion in the liver with dilation of the left hepatic duct. Endoscopic retrograde cholangiopancreatography disclosed a filling defect in the intra- to extrahepatic bile duct. Liver metastasis from rectal cancer with intraluminal growth in the bile duct was suspected despite a consideration of primary bile duct cancer. A left trisegmentectomy of the liver and resection of the extrahepatic bile duct with a right hepatojejunostomy were performed. The tumor had invaded the intrahepatic bile duct and had developed intraluminally in the extrahepatic bile duct. Tumor thrombi were microscopically found in the bile duct of the left caudal lobe. Liver metastasis arising from colorectal cancer with intraluminal growth in the bile duct is rare, however we encountered such a case with a successful resection involving a left trisegmentectomy of the liver.

Bile Ducts, Extrahepatic↗

PubMedDate not supplied

The effects of a selective cyclooxygenase-2 inhibitor on small bowel ischemia-reperfusion injury.

BACKGROUND/AIMS: The purpose of this study was to investigate the effects of a selective COX-2 inhibitor, FK3311, on warm ischemia-reperfusion injury of the canine small intestine. METHODOLOGY: Ten adult mongrel dogs were used. FK (1 mg/kg) was administered intravenously 15 minutes prior to ischemia and 15 minutes prior to reperfusion in the FK group (n = 5), and only an inert vehicle was injected in the control group (n = 5). The superior mesenteric artery and vein were clamped closed for 2 hours and then unclamped for 12 hours of reperfusion. Arterial and intramucosal pH were measured, and samples were taken for histological examination at 1, 3, 6, and 12 hours after the start of reperfusion. Serum thromboxane B2 and 6-keto-prostaglandin F1 alpha (stable metabolites of TxA2 and PGI2) were measured 30 minutes after reperfusion began. RESULTS: Arterial and intramucosal pH changes were significantly (p < 0.05) smaller in the FK group than in the control group. Histological ischemia-reperfusion injury was significantly (p < 0.05) more severe in the control group than in the FK group. Serum thromboxane B2 and 6-keto-prostaglandin F1 alpha levels were significantly (p < 0.05) lower in the FK group compared to the control group. CONCLUSIONS: FK protects the small bowel from ischemia-reperfusion injury by suppression of prostanoid production.

6-Ketoprostaglandin F1 alpha↗

PubMedDate not supplied

Intraoperative massive pulmonary tumor embolism from clear cell sarcoma in the retroperitoneum: successful treatment using cardiopulmonary bypass.

Malignant neoplasms rarely extend into the inferior vena cava and up to the right side of the heart. Although massive pulmonary tumor embolism occurs relatively rarely, it can be a catastrophic problem. Intraoperative pulmonary tumor embolism and cardiac arrest occurred in a 68-year-old woman while dissecting the inferior vena cava to resect a pararenal tumor extending into the retrohepatic inferior vena cava. Abrupt arterial hypotension, tachycardia, and increased central venous pressure lead to the diagnosis of massive pulmonary tumor embolism. Emergency cardiopulmonary bypass was commenced under profound hypothermia and cardiac arrest. The tumors in the main pulmonary artery were extracted, and fragments of remnant tumor were retrieved by a vascular endoscope, a Fogarty catheter, and milking of the lung. Following embolectomy, the tumor in the retrohepatic to infrarenal inferior vena cava was removed and the primary tumor together with the infrarenal inferior vena cava was resected under hepatic vascular exclusion and partial cardiopulmonary bypass. The inferior vena cava below the renal veins was not reconstructed. The patient recovered with slight retrograde amnesia. A postoperative pulmonary perfusion scintigram showed no defect in the pulmonary circulation. She is well now 8 months after surgery. Safe prevention measures should be accomplished as a part of the perioperative management of patients with inferior vena cava tumor thrombus that may be fragile, and cardiopulmonary bypass should always be stand-by on surgery.

Aged↗

PubMedDate not supplied

The effects of a bradykinin B2 receptor antagonist in extended liver resection with ischemia in dogs.

BACKGROUND/AIMS: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and sometimes causes liver failure. This study evaluated the effects of a bradykinin B2 receptor antagonist, FR173657 (FR), on ischemia-reperfusion injury during liver resection in dogs. METHODOLOGY: Experimental animals were divided into two groups. In the FR group (n=6), FR (100 nmol/kg/hr) was administered continuously via the portal vein from 30 min before the onset of ischemia until 2 hr after reperfusion. In the control group (n=6), vehicle was injected in the same manner. The right portal pedicle was clamped for 60 min, while the left portal branch was left patent to avoid portal congestion. Following reperfusion, the non-ischemic lobes were resected, and remnant liver function was evaluated. RESULTS: AST and ALT were significantly (p<0.05) lower in the FR group than in the control group. Hepatic tissue blood flow 30 min after reperfusion was significantly (p<0.05) higher in the FR group than in the control group. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p<0.05) reduced in the FR group compared with the control group. CONCLUSIONS: A bradykinin B2 receptor antagonist ameliorated the ischemia-reperfusion injury caused by Pringle's procedure during extended liver resection.

Analysis of Variance↗

PubMedDate not supplied

Advanced gastric cancer with peritoneal dissemination successfully treated with paclitaxel and doxifluridine: a case report.

A 50-year-old female presenting with severe ascites and anemia and diagnosed with advanced gastric cancer was admitted to our hospital. Endoscopic examination revealed an edematous lesion with redness and a giant fold in the stomach with poor expansion. The histological examination of biopsy specimens from the edematous lesion revealed signet-ring-cell carcinoma. Computed tomography demonstrated a thickening of the gastric wall, severe ascites, and peritoneal dissemination in the Douglas pouch. Paclitaxel (70mg/m2) was administered to the patient on days 1, 8, and 15, with doxifluridine (533mg/m2) for five days per week, on a 28-day cycle. By completion of the first course of treatment, the ascites had disappeared, the tumor in the Douglas pouch had shrunk, and the thickening of the gastric wall had lessened. In addition, the fold in the stomach appeared by endoscopic examination to have resumed its normal thickness, no malignant cells were detected in a biopsy, and the thymidine phosphorylase activity in the tumor tissue was two-fold greater than that before chemotherapy. After three treatment courses, the number of apoptotic cells had apparently increased compared with the prechemotherapy number. The only adverse drug reactions that were observed were grade 2 alopecia and grade 1 myalgia. After thirteen courses of chemotherapy over the past one year, both primary and metastatic lesions seem to be regressing. This case study suggests that paclitaxel plus doxifluridine therapy is effective and well-tolerated in non-resectable gastric cancer patients.

Antimetabolites, Antineoplastic↗

PubMedDate not supplied

Ampullary carcinoma associated with protein-losing gastropathy due to diffuse varioliform gastritis.

Protein-losing gastropathy due to diffuse varioliform gastritis is a rare condition, and its occurrence accompanying ampullary carcinoma is particularly rare. We report here a case of ampullary carcinoma accompanied with protein-losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old Japanese woman was admitted to our hospital because of general fatigue and generalized edema. Her total protein level was 3.1g/dL, with an albumin level of 1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic examination showed diffuse varioliform gastritis and carcinoma of the papilla of Vater. A diagnosis of protein-losing gastropathy was made based on the results of scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from ampullary carcinoma caused anemia and deteriorated hypoproteinemia. Pancreaticoduodenectomy was performed for ampullary carcinoma prior to Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which had invaded the lamina muscularis propria over the sphincter of Oddi; the resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori were detected on microscopic analysis. Scintigraphy after surgery showed no accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse varioliform gastritis are improved 6 months after surgery and H. pylori eradication, and the patient is currently free from disease.

Adenocarcinoma, Papillary↗

PubMedDate not supplied

A case of metachronous cholangiocellular and hepatocellular carcinoma with good prognosis.

A 63-year-old man was treated for 6 months with interferon (IFN) for chronic hepatitis C but the treatment failed to eradicate hepatitis C virus. Six months after completion of IFN therapy, cholangiocellular carcinoma (CCC) was detected in the posterior inferior segment and was resected surgically. He had been in good condition except for diabetic nephropathy progressing to renal failure at 3 years after the resection of CCC. Seven years after the resection of CCC, hepatocellular carcinoma (HCC) was detected in the posterior superior segment of the liver. The tumor was pathologically confirmed by fine needle aspiration biopsy. The patient was successfully treated with two courses of percutaneous ethanol injection and has been well 1 year after the treatment. HCV status did not change as genotype 1b with moderate viral load (300 to 500 kilo copies/mL by amplicore monitoring) during the follow-up. Thus, even though the patient was treated with IFN, hepatitis C could progress to not only HCC but also CCC in the same patient. Our patient is still alive, 9.5 years after detection of the first tumor.

Antiviral Agents↗

PubMedDate not supplied

Effects of a free radical scavenger, MCI-186, on ischemia-reperfusion injury during extended liver resection in dogs.

BACKGROUND/AIMS: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and this sometimes causes liver failure. This study evaluated the effects of a free radical scavenger, MCI-186, on ischemia-reperfusion injury during liver resection in dogs. METHODOLOGY: The experimental animals were divided into two groups. In the MCI group (n = 6), MCI-186 (6mg/kg/h) was administered twice, through a catheter placed in the right hepatic vein: the first time was from 0.5 hours before the onset of ischemia until ischemia by partial inflow occlusion, and the second was from 0.5-hours before reperfusion until reperfusion. In the control group (n = 6), vehicle (physiological saline) was administered in the same manner. RESULTS: The serum AST, ALT, and LDH levels were significantly (P < 0.05) lower in the MCI group than in the control group. Hepatic tissue blood flow 0.5 hours after reperfusion was significantly (P < 0.05) higher in the MCI group than in the control group. Histological tissue damage was mild, and tissue MDA levels were significantly (P < 0.05) lower in the MCI group than in the control group. CONCLUSIONS: MCI-186 ameliorates the ischemia-reperfusion injury caused by Pringle's procedure during extended liver resection.

Animals↗

PubMedDate not supplied

Factors affecting the prognosis of anatomical liver resection for liver metastases from colorectal cancer.

BACKGROUND/AIMS: Liver resection has improved the survival of colorectal cancer patients with metastases. However, there are groups at high risk of recurrence after liver resection. This report reviews our results using anatomical liver resection and analyzes the prognostic factors. METHODOLOGY: We analyzed 78 patients who underwent anatomical liver resection of liver metastases from colorectal cancer between June 1988 and March 2002. RESULTS: Twenty-nine patients had synchronous metastases, and 49 had metachronous. The 5-year overall survival rate was 43%. Patients with more than three metastatic tumors had a significantly poorer 5-year recurrence-free survival rate. There was no statistical difference in the 5-year overall survival rate between patients with metachronous metastases (41%) and those with synchronous (44%) metastases. The 5-year overall survival rate was significantly poorer for patients with an interval of 1 year or less between colorectal and liver resections than for patients with a longer interval. Recurrence after liver resection occurred in 38 patients (49%). The recurrences occurred in the lung in 18 patients, in remnant liver in 15 patients, in lymph nodes in 7 patients, and in other organs in 6 patients. CONCLUSIONS: We conclude that anatomical liver resection of liver metastases from colorectal cancer improves survival. Liver metastases that occur within 1 year of colorectal resection may need an interval of observation before liver resection.

Adult↗