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Biomedical subjects

K Sugimachi

Publications and source records attributed to K Sugimachi.

At least 289 records · Page 16Linked to original sources

Significance of preoperative elevation of serum C-reactive protein as an indicator for prognosis in colorectal cancer.

BACKGROUND: C-reactive protein (CRP) is a product synthesized in hepatocytes and has been reported to be upregulated by such proinflammatory cytokines as interleukin-1, interleukin-6, and tumor necrosis factor. The significance of a preoperative serum elevation in CRP as a predictive indicator for the malignant potential and prognosis in colorectal cancer has not been elucidated. METHOD: One hundred and twenty consecutive patients with colorectal cancer, whose local lesions were resected in our department, were selected. Any patients with inflammatory diseases such as infection or collagen diseases were excluded from the current study. The preoperative serum CRP level was measured, and the relationship between the serum elevation of CRP and both the clinicopathologic factors and prognosis of the patients was investigated. RESULTS: The incidences of liver metastases, peritonitis carcinomatosa, histopathologic lymph nodes metastasis, and intravascular invasion in patients with a preoperatively elevated serum CRP level were significantly more frequent than in those with a negative serum protein level. The survival rates of the patients without a preoperative elevation of the serum CRP proved to be significantly more favorable than that of the patients with such an elevation (P <0.001). CONCLUSIONS: A preoperative serum elevation of CRP was thus found to be an indicator of the malignant potential of the tumor as well as a predictor of the prognosis of patients with colorectal cancer.

Adult↗

Hemagglutinating virus of Japan-liposome-mediated gene transfer of endothelial cell nitric oxide synthase inhibits intimal hyperplasia of canine vein grafts under conditions of poor runoff.

PURPOSE: Late graft failure is a critical problem, particularly in the presence of poor runoff vessels. Intimal hyperplasia is considered to be the main cause of graft failure. We have already reported that intimal thickening of experimental vein grafts in dogs with poor runoff vessels is more pronounced than that in dogs with normal vessels. We and others also have reported that production of nitric oxide (NO) in the endothelium of canine vein grafts is impaired. In the present study, we asked whether in vivo gene transfer of endothelial cell NO synthase (ecNOS) would inhibit intimal hyperplasia of autogenous vein grafts implanted in limbs with poor distal runoff in dogs. METHODS: After exposing femoral veins, the nuclear-targeted lac Zgene, bovine ecNOS cDNA, or control vector plasmid encapsulated in the hemagglutinating virus of Japan-liposomes was infused intraluminally, followed by incubation for 10 minutes at room temperature under a distending pressure of 100 mm Hg. Twenty reversed vein grafts were implanted under normal runoff conditions, and 4 days later these were used to confirm gene transfer to the vein grafts. Twelve reversed vein grafts were implanted under conditions of poor runoff, and 4 weeks after the operation intimal thickening was evident. RESULTS: In vein grafts under normal runoff conditions, lac Z gene transfer exhibited diffuse and frequent X-Gal-positive signals in both medial and adventitial layers 4 days after implantation (n = 3). In case of the ecNOS gene-transferred vein grafts, bovine ecNOS protein was mainly detected in medial smooth muscle cells and adventitial cells 4 days after implantation, determined using immunohistochemical techniques and bovine ecNOS specific antibody (n = 3). In addition, ecNOS-transferred vessels showed intense purple signals by reduced nicotinamide adenine dinucleotide phosphate diaphorase and nitroblue tetrazolium reaction, in both medial and adventitial layers, whereas weak NOS activity was recognized at the adventitial vasa vasorum of the untreated veins or control vector transferred veins (n = 3, respectively). In vein grafts under poor runoff conditions, the intimal thickness at 4 weeks after implantation was significantly reduced by ecNOS gene transfer (n = 4; 90.0 +/- 7.6 microns and 1.18 +/- 0.07 mm2) in comparison with buffer-treated vessels (n = 4; 195.8 +/- 25.7 microns and 2.62 +/- 0.48 mm2) or vector vehicle-treated vessels (n = 4; 193.0 +/- 15.8 microns and 2.65 +/- 0.22 mm2). CONCLUSIONS: Our findings show that gene transfer of ecNOS inhibited intimal hyperplasia of canine vein grafts caused by poor runoff conditions, as a result of an increased local production of NO. Thus ecNOS gene transfer warrants further study as a possible approach to prevent late graft failure.

Animals↗

Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients.

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.

Administration, Oral↗

Role of adhesion molecule expression and soluble fractions in hepatic resection.

BACKGROUND: Little has so far been documented about the relationship between liver injury and adhesion molecules. The aim of this study is to clarify the role of adhesion molecules in hepatic resection by studying both the expression of such adhesion molecules and the measurement of their soluble fractions in the blood. STUDY DESIGN: To study adhesion molecule expression in the liver, liver biopsies were obtained before and after hepatectomy in 14 patients. Using frozen sections, immunochemical staining for intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was then performed. To study the soluble fractions of adhesion molecules in the hepatic venous blood, the serum soluble fractions of ICAM-1 and VCAM-1 from another 17 patients were measured using an enzyme-linked immunosorbent assay. The plasma levels of polymorphonuclear leukocyte (PMN) elastase were also measured using an enzyme immunoassay. Both the preoperative and postoperative values of the serum soluble fractions of ICAM-1, VCAM-1, and PMN elastase were then compared. The correlation between their values and the perioperative variables was also investigated. RESULTS: Either ICAM-1 or VCAM-1 was stained on the sinusoidal endothelial cells and Kupffer cells or circulating PMNs in the sinusoid. The positive rate of either ICAM-1 or VCAM-1 staining in livers with more than 40 minutes of total ischemic time (80%) was significantly higher than that in livers with less than 40 minutes of total ischemic time (0%; p < 0.05). The incidence of postoperative complications in the ICAM-1 positive staining group tended to be higher than that in the ICAM-1 negative group. Both soluble fractions of ICAM-1 and VCAM-1 in patients with cirrhotic liver disease were also significantly higher than those in patients with a normal liver. The soluble VCAM-1 level in patients with a chronic active hepatitic liver tended to be higher than that in those with a nonactive hepatitic liver. The preoperative level of soluble ICAM-1 correlated with that ofVCAM- 1, PMN elastase, albumin, aspartate aminotransferease (AST), and the indocyanine green dye retention test at 15 minutes (ICG R15), while the preoperative level of VCAM-1 correlated with albumin, the hepaplastin test, AST, and ICG R15. Both the serum soluble ICAM-1 and VCAM-1 levels after hepatectomy were significantly lower than those before hepatectomy. By contrast, the posthepatectomy level of PMN elastase was significantly higher than its prehepatectomy level. The difference between the postoperative and preoperative values of soluble ICAM-1 correlated with the postoperative AST level, postoperative alanine aminotransferase level, and total ischemic time. CONCLUSIONS: Adhesion molecules were expressed in the liver after hepatic resection, and such expression correlated with a total ischemic time during hepatectomy. In addition, judging from the soluble forms of such molecules, these adhesion molecules play an important role in hepatic resection.

Aged↗

Laparoscopic gastric devascularization and splenectomy for sclerotherapy-resistant esophagogastric varices with hypersplenism.

BACKGROUND: The combination of sclerotherapy with surgical salvage for sclerotherapy-resistant esophagogastric varices has recently received much attention, however, the longterm results after such an operation have yet to be reported. This is a preliminary report of a laparoscopic adaptation of a previously described surgical procedure for the treatment of refractory esophagogastric varices. STUDY DESIGN: Laparoscopic gastric devascularization and splenectomy (Hassab's operation) was successfully performed to treat recurrent sclerotherapy-resistant giant esophageal varices (n=4) and recurrent rebleeding gastric varices (n=6). The patients included 8 men and 2 women who ranged in age from 35 to 67 years (average, 54.2 years). The procedure and clinical results were evaluated from various viewpoints. RESULTS: The duration of the operation ranged from 200 to 400 minutes (mean+/-standard deviation; 287.5+/-66.0 minutes) and blood loss from 10 to 1,500 mL (average, 515.5+/-507.9 mL). The weight of the spleen ranged from 500 to 850 g (average 608.0+/-126.6 g). Conversion to minimal open operation with a gasless lifting method was done in 1 patient because of uncontrolled bleeding from the splenic vein. There were no other major complications either intraoperatively or postoperatively. All patients had hypersplenism; preoperative platelet counts ranged from 1.6 to 6.8 x 10(4)/microL (average, 4.5+/-2.7 x 10(4) microL) and the postoperative count was from 5.9 to 36.0 x 10(4)/microL (average, 21.7+/-11.5 x 10(4) microL). Postoperative endoscopy revealed that varices disappeared, and no patient had recurrence of the varices after operation during the mean followup period of 12.8+/-4.1 months (average, 8 to 20 months). CONCLUSIONS: The combination of laparoscopic gastric devascularization and splenectomy for sclerotherapy-resistant esophagogastric varices is considered a feasible and relatively safe surgical method for patients with hypersplenism.

Adult↗

Induction of apoptosis in human tumour xenografts after oral administration of uracil and tegafur to nude mice bearing tumours.

Various types of anti-neoplastic agents induce apoptosis in vitro, but less is known of the role of this mode of cell death in tumours treated in vivo. We examined the induction of apoptosis by oral anti-neoplastic agents, tegafur and uracil (UFT, a combined preparation of 1 mol tegafur and 4 mol uracil), and the relationship of effects on tumour growth. Seven different human gastrointestinal tumour xenografts were transplanted into nude mice, including two colon adenocarcinomas (KM20C and Col-1), three gastric carcinomas (SC-6, St-40 and 4-1ST) and two pancreatic carcinomas (PAN-4 and PAN-12), followed by oral administration of UFT (24 mg kg(-1) day(-1)) for 9 days. The percentage of apoptotic cells in each tumour was scored in histological sections, chronologically, using a molecular biological-histochemical system and growth inhibition was examined in each tumour. A significant growth inhibition by UFT was observed for all tumours, except PAN-12. In KM20C and SC-6, growth inhibition rates were 61.7% and 60.6% respectively. Quantitative assay for apoptosis showed a remarkable induction of apoptosis in KM20C (4.2%) and SC-6 (3.5%), which were relatively sensitive to UFT. In addition, KM20C and SC-6 showed a higher incidence of spontaneous apoptosis. In five other tumours, which responded to a lesser extent than KM20C and SC-6, UFT altered little the changes in apoptosis (less than 2%) and spontaneous apoptosis was relatively low. Thus, tumours with a higher apoptosis induced by UFT had a higher response to UFT. Apoptosis observed in tumours might serve as a predictor of a preferable response to UFT.

Animals↗

Risk factors linked to postoperative morbidity in patients with hepatocellular carcinoma.

BACKGROUND: The aim of this study was to clarify the risk factors for morbidity as well as to establish an optimum surgical strategy for hepatocellular carcinoma (HCC). METHODS: The risk factors linked to postoperative complications were analysed in 388 patients over a 10-year period, according to the kind of operative procedure. RESULTS: Stepwise regression analysis revealed that the most important factors related to postoperative morbidity were: age, creatinine level and the histological grade of fibrosis for the bisegmentectomy; the presence of diabetes mellitus, blood urea nitrogen level, the indocyanine green dye retention rate at 15 min and blood loss for the segmentectomy; the presence of diabetes mellitus and blood loss for subsegmentectomy; the presence of diabetes mellitus, the aspartate aminotransferase level, and the total operating time for resection less than subsegmentectomy. CONCLUSION: The most important risk factors were not always related to liver function tests, but instead to other coexisting conditions such as diabetes mellitus and operation stress including operating time and blood loss. Therefore, any future treatment strategy of hepatic resection for HCC should make every effort both to evaluate coexisting conditions carefully and to reduce operative stress as far as possible.

Age Factors↗

Amelioration of liver injury by ischaemic preconditioning.

BACKGROUND: Ischaemic preconditioning, i.e. preparatory brief ischaemia before subsequent long ischaemia, can effectively protect the heart from ischaemia-reperfusion injury in animals. The purpose of this study was to demonstrate the same phenomenon in the liver. METHODS: Using warm ischaemia-reperfusion of 70 per cent of the liver followed by resection of the non-ischaemic portion in rats, livers with 10 min of ischaemic preconditioning, i.e. 10 min of warm ischaemia and reperfusion, were compared with those that had not been subjected to such a manoeuvre. RESULTS: At 120 min after reperfusion following 40 min of warm ischaemia, the livers with 10 min of ischaemic preconditioning had a significantly lower mean(s.d.) serum alanine aminotransferase level (492(217) versus 1236(695) units/l; P < 0005) and lactic dehydrogenase level (7905(4002) versus 15066(9201) units/l; P< 0.05), as well as a higher bile output (0.12(0.03) versus 0.09(0.04) ml per g liver; P < 0.05) and liver tissue adenosine 5'-triphosphate level (78(13) versus 61(11) per cent; P< 0.05) than the control livers. The necrosis rate, histologically defined as the percentage of necrotic area in given liver sections, was reduced significantly by this manoeuvre (mean(s.d.) 1.3(1.3) versus 5.3(1.7) per cent; P< 0.05). CONCLUSION: Ischaemic preconditioning exerts a protective effect on hepatic warm ischaemia-reperfusion injury. Such a manoeuvre may be useful for hepatic resection in the clinical setting.

Adenosine Triphosphate↗

Relationship between preoperative assessment of organ function and postoperative morbidity in patients with oesophageal cancer.

OBJECTIVE: To find out if strict assessment of organ function preoperatively predicted morbidity and mortality in patients being operated on for oesophageal carcinoma. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 178 patients operated on for oesophageal cancer 1989-1993. INTERVENTIONS: Oesophagectomy and reconstruction (using either stomach or colon) in one stage by a right thoracoabdominal approach in 173, and transhiatal resection in 5 with either poor pulmonary reserve or early lesions. MAIN OUTCOME MEASURES: Correlation between preoperative assessment of organ function and postoperative development of complications. RESULT: 79 patients (44%) developed complications and 6 died (3%). Pulmonary dysfunction preoperatively was significantly associated with the development of all complications (p=0.001) and of postoperative pulmonary complications (p=0.04). No other preoperative assessment correlated significantly with the development of postoperative complications. CONCLUSION: Accurate preoperative assessment of pulmonary function is a valuable indicator of postoperative morbidity.

Aged↗

Spontaneous pneumothorax complicating lung metastasis from lingual carcinoma.

We report a patient with pneumothorax caused by a metastatic tumour from carcinoma of the tongue, which had given rise to a bronchopleural fistula with subsequent induction of pneumothorax. Although rare, pulmonary metastasis should be considered in the aetiology of spontaneous pneumothorax. Despite advanced disease, surgical treatment may be feasible.

Carcinoma, Squamous Cell↗

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE: The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA: A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS: Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS: Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiner's Grade 1. CONCLUSIONS: The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Algorithms↗

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

Adult↗

Nm23-H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma.

AIMS/BACKGROUND: Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23-H1 expression in both intrahepatic and distant metastases of HCC. METHODS: Thirteen patients with single-nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23-H1 protein was immunohistochemically examined in both primary and metastatic nodules. RESULTS: Ten of 13 single-nodule HCCs were found to overexpress nm23-H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23-H protein, except for two HCCs, which only partially expressed nm23-H1 protein. Regarding the nm23-H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23-H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23-H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23-H1 protein. Nm23-H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. CONCLUSIONS: Our study demonstrated that nm23-H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23-H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.

Adrenal Gland Neoplasms↗

The clinical management and results of surgery for acute cholecystitis.

The laparoscopic approach to acute cholecystitis is not only feasible, but it is also a cost-effective, safe, and beneficial treatment option in selected patients. Patients undergoing laparoscopic surgery for acute cholecystitis seem to enjoy the same benefits of diminished pain and shorter hospitalization as those patients undergoing an elective laparoscopic cholecystectomy. The complication rates are also comparable with those for an open cholecystectomy. An early laparoscopic cholecystectomy within 4 days of the onset of symptoms has been shown to reduce the number of major complications and conversion rate, thus resulting in a decreased hospital stay. A low threshold for conversion to laparotomy also seems to be an important factor in maintaining a low incidence of operative complications. The conversion to laparotomy is therefore considered to be a good surgical option for experienced surgeons. Patients who are in the high-risk category or who have severe disease are best managed initially by gallbladder drainage unless they have perforated disease, which thus requires an emergency laparotomy.

Acute Disease↗

Clinical significance of molecular detection of carcinoma cells in lymph nodes and peripheral blood by reverse transcription-polymerase chain reaction in patients with gastrointestinal or breast carcinomas.

PURPOSE: This study evaluates the clinical significance of detection of carcinoembryonic antigen (CEA) mRNA in the dissected lymph nodes and peripheral blood samples of patients with gastrointestinal or breast carcinomas. PATIENTS AND METHODS: A total of 406 lymph nodes obtained from 65 patients were analyzed by both histologic and molecular examination of CEA-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Peripheral blood samples from another 102 patients were also analyzed by CEA-specific RT-PCR. Patients were followed up prospectively for 24 +/- 12 months. RESULTS: Of 406 lymph nodes, the positive detection rate increased from 20% by histologic examination to 60% by RT-PCR examination. The recurrence rate was 40% in 15 cases showing positive results in both examinations, 14% in 29 cases showing histologically negative but RT-PCR positive results, and none in 21 cases showing negative results in both examinations. The positive detection rate for CEA mRNA in peripheral blood samples increased with advancing stage of disease. With respect to 62 curatively operated cases, CEA mRNA was detected in 12 cases. Four of these 12 cases developed metastatic disease after surgery whereas none of 50 cases negative by RT-PCR developed metastasis. CONCLUSION: It has been shown that RT-PCR is a powerful tool to detect CEA mRNA in the lymph nodes or the peripheral blood. This is potentially very useful to determine high-risk patients for metastasis. Serial analysis is warranted to assess the long-term significance of this method and its therapeutic and prognostic implications.

Breast Neoplasms↗

HVJ (Sendai virus) liposome-mediated gene transfer: current status and future perspectives (review).

Haemagglutinating virus of Japan (HVJ; Sendai virus), a member of the mouse paramyxovirus family, has been combined with liposomes to produce a novel gene transfer system, namely HVJ liposomes. This vector system is defined as a , constructed with inactivated viral particles and non-viral (artificial) multi- or unilamellar liposomes containing gene expression cassettes and has several advantages in comparison with other viral or non-viral systems. Many studies have shown that this vector system can, not only produce efficient gene transfer using reporter genes, but also with resulting in vivo functional changes in several animal models of diseases. Despite these results, it is likely that the construct will need to be modified to improve gene transfer and expression efficiency and also to extend the potential disease targets. We review the present status of this hybrid vector system and also discuss possible modifications for future application to either in vivo analysis of specific gene expression or human gene therapy strategies for congenital or acquired diseases.

Forecasting↗