The effect of FK409 on small bowel ischemia-reperfusion injury in dogs.
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Biomedical subjects
Publications and source records attributed to S Ohwada.
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Cell proliferation was evaluated in 167 tissue specimens obtained from primary breast cancer patients who had undergone radical surgery between 1984 and 1988. Formalin-fixed and paraffin-embedded tissue specimens were used in the immunohistochemical study. The immunohistochemical method was carried out using the avidin-biotin immunoperoxidase technique, and anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used for primary antibody. Based upon the PCNA labeling index (LI), the patients were divided into two groups: low PCNA, <25% and high PCNA, >/= 25%. The PCNA LI ranged from 1% to 76% (mean, 23.9%). Patients aged </= 50 showed significantly higher PCNA LI than those of > 50 years. There was no relationship between the PCNA LI and tumor size, lymph node involvement and hormone receptors. The survival curves of 146 invasive breast cancer patients showed that the high PCNA group had poor overall survival compared with the low PCNA group. A significant difference in the overall survival between the high and low PCNA groups was observed in lymph node-positive patients, however, no significant difference was found between the two groups in lymph node-negative patients. PCNA LI was identified as an independent predictor in primary breast cancer patients.
We analyzed the results of local re-excision after radiation therapy on seven patients with positive surgical margins at the initial breast-conserving surgery. The age of the patients ranged from 30 to 55 years, and the tumor sizes from 1.1 to 4.7 cm. Both estrogen receptor and progesterone receptor status were positive in two patients, negative in four, and unknown in one. Pathological examination revealed residual carcinoma in one (14.3%) of seven patients. The immunohistochemical results of the initial specimen were estrogen receptor-positive, c-erbB-2-positive, and Bax-negative. We performed local re-excision after radiation therapy and found only one incidence of residual carcinoma in the conserved breast.
One hundred and seventy patients received breast-conserving therapy in the Second Department of Surgery, Gunma University School of Medicine. Six (3.5%) out of the 170 patients showed breast recurrence. We investigated the breast recurrent cases clinicopathologically. The age at the initial operation ranged from 38 to 78 (mean 57) years. One patient was clinical stage I and the others were clinical stage II. Surgical margin at the initial operation was negative in two patients and positive in four. Histological type was invasive ductal cancer in all cases. Three patients had lymph node involvement. The interval from the initial operation to breast recurrence ranged from 19 to 68 months. Five cases were nodular type and one was diffuse type of breast recurrence. Histological type of breast recurrence was the same as the initial one. We performed salvage surgery for all breast recurrent patients, mastectomy for four patients and local resection for two. One patient who showed diffuse type of recurrence could not be controlled with any surgical treatment, and later died of breast cancer. We investigated the expression of estrogen receptor, progesterone receptor, pS2, c-erbB-2 and p53 on both initial and recurrent specimens of the six patients. The expression of each protein on the recurrent specimens was the same as the initial one. We conclude that breast recurrence after breast-conserving therapy has its origin in the residue of cancer cells at the initial operation, even if surgical margins are histopathologically negative.
The serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was examined in 83 patients with metastatic breast cancer. ICTP levels were significantly higher in patients with bone metastases than in those without bone metastasis. In patients with bone metastasis, significantly higher ICTP levels were observed in those with multiple lesions than in those with a solitary lesion and these levels reflected therapeutic response. Sequential monitoring of ICTP revealed that this elevation was correlated with disease progression. Combined with imaging studies, monitoring of ICTP appears to offer additional information for detection of bone metastasis and evaluation of therapeutic response to bone metastasis.
We examined the potent inhibitory effects of interferon-alpha (IFN-alpha) on both cellular adhesion and cell proliferation of MCF-7 breast carcinoma cells. When MCF-7 cells were exposed to IFN-alpha at a concentration of 5x10(3) IU/ml for 5 days, cell proliferation was markedly inhibited. Cell attachment assay demonstrated that incubation with IFN-alpha for up to 48 h reduced alpha2beta1 integrin-mediated cellular adhesion. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with IFN-alpha for 24 h had no effect upon the cell surface expressions of either alpha2 and beta1 integrin on MCF-7 cells. These antiproliferative and antiadhesive actions of IFN-alpha may be applied to treatment for patients with metastatic breast carcinoma.
Pyrimidine nucleoside phosphorylase (PyNPase) is an enzyme which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU), and is induced by various cytokines in tumor cells. We evaluated a combination of 5'-DFUR and lentinan which is widely used as a biological response modifier (BRM), to verify antitumor effects, the induction of cytokines such as tumor necrosis factor (TNF)-alpha and latent transforming growth factor (TGF)-beta, and PyNPase activity against AH66 ascites hepatoma cells in rats. AH66 ascites hepatoma cells were subcutaneously injected into the backs of Donryu rats. Rats were randomly assigned to a group receiving either 5'-DFUR or lentinan alone, to a group receiving both 5'-DFUR and lentinan, or to a control group. 5'-DFUR was administered orally, and lentinan was administered intraperitoneally. The tumor size, PyNPase activity in the tumor and spleen, and TNF-alpha and TGF-beta in the tumor were examined. The results were as follows. a) Tumor growth was significantly (P < 0.05) inhibited in both the 5'-DFUR group and the 5'-DFUR + Lentinan group when compared to the control group. Tumor growth in the 5'-DFUR + Lentinan group was significantly (P < 0.01) inhibited compared to that in both the 5'-DFUR group and the Lentinan group. b) PyNPase activity in the tumor was significantly (P < 0.01) higher in each group than in the spleen. In the tumor, PyNPase activity was significantly (P < 0.01) higher in the Lentinan group compared to the control group. In the 5'-DFUR + Lentinan group PyNPase activity in the tumor was significantly (P < 0.01) lower compared to the Lentinan group. c) Levels of TNF-alpha and TGF-beta production in the tumor were significantly (P < 0.05) lower in the 5'-DFUR + Lentinan group compared to the control group. These findings suggested that PyNPase activity in the tumor was induced by lentinan but not so in the spleen, and lentinan increased the susceptibility of tumor cells to 5'-DFUR.
BACKGROUND/AIMS: Nitric oxide (NO) plays an important role in the regulation of systemic hemodynamics in various shock status. The effect of NO on shock induced by hepatic inflow occlusion has not been previously investigated. METHODOLOGY: We examined the effects of NO on systemic hemodynamics and oxygen metabolism in shock caused by temporary hepatic inflow occlusion without bypass in pigs using NO synthase inhibitor, NG-nitro-L-arginine methyl ester (NAME group) and the substrate for NO synthesis, L-arginine (ARG group). RESULTS: All animals in the control and ARG group tolerated the surgery, while 2 of 5 animals in the NAME group died during the occlusion period. Cardiac output and mixed venous oxygen saturation (SvO2) in the NAME group was significantly reduced compared with the other two groups during and after hepatic inflow occlusion. In contrast, SvO2 in the ARG group was maintained at higher levels throughout the study period, and the recovery time of cardiac output following reperfusion was earlier than that of the other two groups. CONCLUSIONS: Endogenous NO inhibition exacerbates the shock status induced by hepatic inflow occlusion. Exogenous administration of NO donor may improve the shock status induced by hepatic inflow occlusion.
BACKGROUND/AIMS: Glutaraldehyde-fixed heterologous pericardium has been widely used for grafts in cardiac surgery. We applied it for inferior vena cava (IVC) patch grafting following combined resection of the liver and the IVC. METHODOLOGY: IVC grafting using a glutaraldehyde-fixed horse pericardium following combined resection of the liver and the IVC was performed in 2 patients--one with hepatocellular carcinoma and the other with hepatic metastasis following rectal cancer. The retrohepatic vena cava defect was closed with a 10 x 5 cm patch in one patient and a 7 x 4 cm patch in the other. RESULTS: Hepatic vascular exclusion was avoided in both patients. The IVC exclusion period was 40 min for the first patient and 25 min for the second. One patient required a veno-venous bypass with an active centrifugal pump of 153 min. There was no complication and no graft infection. The microscopic extension to the IVC was evident in one patient, and fibrous adhesive was evident in the IVC wall of the other. One patient died of hepatic failure 3 years and 6 months after surgery, and the other died of hepatic recurrence 7 months after surgery. Both grafts were patent, without calcification and stricture, until the patients' death. CONCLUSIONS: Glutaraldehyde-fixed heterologous pericardium is an option for IVC grafting.
BACKGROUND/AIMS: The aim of this study was to identify factors that might affect the results of treating benign anastomotic stricture of the esophagus with balloon dilation. METHODOLOGY: Balloon dilation was performed on 35 patients with benign esophageal anastomotic stricture of the upper (esophageal cancer: 18) or lower (gastric cancer: 15, esophageal varices: 2) esophagus. The procedure was considered effective when patients were able to maintain a solid diet more than 12 months after the last dilation. The follow-up period ranged from 15-130 months (mean: 51 months). RESULTS: A total of 245 dilations were performed, with an average of 6.6 dilations per patient. Treatment was effective in 29 patients (83%). Balloon dilation was successful when treating strictures shorter than 12 mm in length. The strictures were significantly shorter in patients treated effectively (5.6 vs. 30.8 mm). The diameter of the stricture did not affect the results. All the strictures in the lower esophagus and all those resulting from stapled anastomoses were treated successfully, while the effectiveness of treating strictures in the upper esophagus or those resulting from hand-sewn anastomoses was 67% and 57%, respectively. Strictures without prior leakage were treated effectively 92% of the time, while the success rate fell to 56% if there was a preceding leak. An average of 4.4 dilations were performed in effective cases, while the average was 17.5 dilations in ineffective cases. The number of repeat dilations was correlated with the length of the stricture. CONCLUSIONS: Balloon dilation can successfully treat strictures shorter than 12 mm long. The correlation equation may be used to predict the number of repeat dilations and treatment results, and is useful for deciding when to use an alternative method to balloon dilation.
A 69 year-old man with a history of thoracoplastic surgery for pulmonary tuberculosis, who required a blood transfusion and subsequently tested positive for hepatitis C virus, developed a right hypochondrial mass, swelling of the lower extremities and malaise. A huge hepatocellular carcinoma invading the suprahepatic vena cava with tumor thrombi was diagnosed radiographically. An extended right hepatectomy with supra- to retrohepatic IVC resection was performed in an en bloc fashion using a centrifugal pump for hepatic vascular exclusion (HVE). The supra- to retrohepatic IVC was replaced with an expanded polytetrafluoroethylene (ePTFE) graft, 20 mm x 10 cm in size, and the left hepatic venous confluence was reconstructed. Twenty-one months after surgery, the patient is in good condition without recurrence of tumor.
BACKGROUND/AIMS: We modified the surgical procedure for segmental gastrectomy, which is normally used for peptic ulcers, to treat early gastric cancer of the mid-stomach. In this paper, we describe the surgical technique and its results. METHODOLOGY: The location of the tumor was confirmed by intra-operative endoscopic examination. An area 2 cm proximal and distal to the tumor was marked with sutures. Firstly, the lymph nodes were dissected from around the perigastric and along the left gastric and common hepatic arteries. Then, a segmental gastrectomy was performed. The greater omentum, omental sac, and vagal nerve, including the hepatic, pyloric and celiac rami, were left intact. An end-to-end gastrogastrostomy was performed using Gambee's sutures and 4-0 monofilament polydioxanone. Gastric drainage was not necessary. RESULTS: We performed segmental gastrectomies on 30 patients. Tumors less than 1 cm in diameter were found in 4 patients; 1.1-2 cm in 14, 2.1-5 cm in 11, and a tumor exceeding 5.1 cm in one patient. The cancer was confined to the mucosa in 23 patients; in the other 7, it had penetrated the submucosa. No lymph node metastases were found but 2 patients had microscopic invasion or permeation of the lymphatic vessels. One patient required post-operative balloon dilation of the pyloric sphincter for delayed gastric emptying. The remaining patients had no post-operative complications. To date, 29 patients, excluding one who died in a traffic accident, have survived disease-free for a mean of 30 months (range: 7-51). Their body weight and dietary volume returned to pre-operative levels within 12 months of surgery. CONCLUSIONS: Patients who underwent segmental gastrectomy have had a reasonably good quality of life in the post-operative follow-up to date.
A 79 year-old man was admitted to our hospital because of upper abdominal pain and nausea. A mobile tumor was palpable in the right upper abdomen. Abdominal ultrasonography, computed tomography and celiac angiography revealed a gallbladder tumor. Endoscopic retrograde cholangiopancreatography revealed a fistula 1.5 cm oral to the orifice of the papilla of Vater, dilatation of the common bile duct, and a filling defect in the gallbladder. Pancreatoduodenectomy associated with reconstruction using Imanaga's method was performed under a pre-operative diagnosis of gallbladder carcinoma with choledochoduodenal fistula. The gallbladder contained a tumor and two bilirubin stones impacted in the orifice of the duodenal papilla. Histological studies confirmed that the gallbladder tumor was a mucinous adenocarcinoma and had not infiltrated the bile duct. We speculated that choledochoduodenal fistula stimulated the development of cancer due to chronic irritation from pancreatic juice reflux.
BACKGROUND/AIMS: Resection of hepatic arteries is often obligatory on resecting pancreatic, gastric and hepatobiliary malignancies. Hepatic artery reconstruction is required to preserve liver function and blood flow to the bile duct. We applied the gonadal vein to hepatic artery reconstruction. METHODOLOGY: Hepatic artery reconstruction using a gonadal vein graft was performed in two patients: one with gallbladder cancer and the other with recurrent gastric cancer. RESULTS: The right ovarian vein, 2 mm in diameter and 4 cm in length, was grafted for reconstruction between the proper hepatic and the posterior hepatic artery in one patient who underwent modified central hepatic bisegmetectomy and common bile duct resection. The left spermatic vein, 3 mm in diameter and 6 cm in length, was grafted for reconstruction between the celiac artery and the right hepatic artery in the other, who underwent upper abdominal exenteration. The former graft was occluded due to tumor invasion at 4 months after surgery, the latter one was patent at 8 weeks after surgery. CONCLUSIONS: The gonadal vein had an ideal diameter and sufficient length to accomplish hepatic arterial reconstruction. The gonadal vein graft will be a new and preferable addition to the selection of an optimal graft for hepatic arterial reconstruction.
BACKGROUND/AIMS: We evaluated the quality of life and gastric emptying in patients who had undergone a segmental gastrectomy to treat early gastric cancer in the middle part of the stomach. METHODOLOGY: Thirty patients were considered in this study. Their mean age was 65.5 years (range: 44-83). All of the patients were free from recurrence of their cancer in the follow-up period. This ranged from 5 to 50 months (mean 30). Patients were interviewed at regular intervals to assess their quality of life and to note particular complaints. The upper gastrointestinal tract was assessed endoscopically. A gastric emptying study was performed at 3, 6, and 12 months after surgery. The meal used in this dual-phase study had solid and liquid phases. For the solid phase, 74 MBq of 99mTc sulfur colloid was injected into an egg, which was then hard-boiled. For the liquid phase, 18.5 MBq of (111)In-diethyltriaminopenta acetic acid (DTPA) were mixed into 150 ml of a commercial, elentary liquid diet. RESULTS: Three months after surgery, the patients' main complaints were gastric stasis (25%), heartburn (8%) and belching (8%). The patients gradually became asymptomatic following surgery. Fifty-nine percent were asymptomatic at the 3-month follow-up, 84% at 6 months, and 92% at 12 months. There was no evidence of reflux esophagitis or gastritis after the 3-month follow-up. One patient developed a complicated duodenal ulcer. Initially, the patients all had prolonged gastric emptying of the dual phase meal, compared to normal individuals. The T1/2 for liquid meal emptying was 87+/-18 min at 3 months, 77+/-20 min at 6 months and 50+/-5 min at 1 year after surgery. The last value is the same as for healthy individuals. Solid meal emptying was still prolonged, with an emptying rate of 36+/-9.7% at 2 hours, one year after surgery. CONCLUSIONS: Segmental gastrectomy patients experienced prolonged gastric emptying in the early post-operative period. This improved in the first year after surgery. The quality of life for patients who underwent segmental gastrectomy has been reasonably good in the follow-up period to date.
An 83 year-old man was admitted because of abdominal pain and distention. A mass measuring 20x10 cm and associated with tenderness and guarding was palpable in the right lower abdomen. Ultrasonography and computed tomography showed a tumor with solid and multiple cystic areas. Celiac angiography showed slight tumor vascularity fed by the right gastroepiploic artery. A malignant tumor of the omentum was suspected. At laparotomy, torsion of the omental pedicle of the tumor was found. Histological examination of the resected tumor revealed characteristics of round-cell liposarcoma, which usually has a poor prognosis. The patient has been alive and well for 2 years. Primary liposarcoma of the omentum has been reported in only seven previous cases. None of these patients presented with torsion, and no report has thus far included a documented survival.
Renal cell carcinoma (RCC) is often associated with an extension of tumor thrombi into the inferior vena cava (IVC) and occasionally up to the right atrium. RCC with IVC involvement has a relatively favorable prognosis when it is completely resected. We present a successfully resected case of RCC with tumor thrombi extending into the right atrium. We performed radical right nephrectomy with lymph node dissection and removed the tumor thrombi en bloc under total hepatic vascular exclusion with the veno-venous bypass between the IVC and the right atrium using an active centrifugal force pump. The patient has been in good condition for 3 years since surgery with no evidence of recurrence.
BACKGROUND/AIMS: Segmental pancreatectomy for benign tumors of the neck of the pancreas was reported in 1993. Mucin-producing carcinomas are generally regarded as low-grade malignancies as compared with ductal cell carcinomas of the pancreas. We report herein our experience with a segmental pancreatectomy for mucin-producing pancreatic tumors. METHODOLOGY: Three patients with mucin-producing tumors of the pancreatic body underwent a segmental pancreatectomy. After the pancreatic tumor had been located with intra-operative ultrasonography (US), the medial pancreas centered on the tumor was resected. The margin of the retained pancreas was submitted for histopathologic inspection intra-operatively to prevent retained disease. A conduit for draining the pancreatic juice consisted of a jejunal Roux-en-Y loop between the left and cephalic portions of the pancreas. Histologically, the 3 tumors were identified as a cystadenocarcinoma, an intraductal papillary adenocarcinoma, and a cystadenoma with a focus of borderline malignancy. The functional result was evaluated with oral glucose tolerance and pancreatic function diagnostic (PFD) testing. Pancreatic juice drainage was confirmed using magnetic resonance cholangiopancreatography (MRCP). RESULTS: Neither technical failure nor operative death occurred in any of the patients. The patients have been followed-up for between 33 months and 77 months after surgery and all are disease free. The oral glucose tolerance test and PFD test results were all within the normal range. MRCP showed good pancreatic juice drainage in the 2 patients examined. CONCLUSIONS: Segmental pancreatectomy may be an appropriate surgical procedure for mucin-producing pancreatic tumors, to prolong survival and to preserve endocrine and exocrine function.