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Biomedical subjects

Masato Kusunoki

Publications and source records attributed to Masato Kusunoki.

At least 55 records · Page 3Linked to original sources
PubMed2005

Efficacy of Seprafilm for reducing reoperative risk in pediatric surgical patients undergoing abdominal surgery.

BACKGROUND: The safety and efficacy of Seprafilm (Genzyme Corporation, Cambridge, Mass) in adult surgery patients have been established. The aim of this study was to evaluate the safety and efficacy of Seprafilm in pediatric surgical patients. METHODS: One hundred twenty-two pediatric abdominal surgery patients were enrolled. Sixty-seven patients received Seprafilm application. Of these patients, 18 again received Seprafilm at abdominal closure during a second surgery, and of the 18, 4 received Seprafilm at closure after a third surgery. Of the 55 control patients who did not receive Seprafilm, 14 had a second surgery, and of these 14 patients, 4 had a third surgery. Adverse events, operation time, and blood loss were compared with assessed Seprafilm safety. Seprafilm efficacy evaluations included incidence and severity of adhesions in those patients who required relaparotomy. RESULTS: The incidence (Seprafilm, 40.9%; control, 82.4%) and severity (Seprafilm: 59.1%, grade 0; control: 17.6%, grade 0) of adhesions under the abdominal incision site were significantly reduced in the Seprafilm group (P = .007 and P = .0009, respectively). In addition, mean relaparotomy operation time was significantly shorter for Seprafilm patients (P = .004). At relaparotomy, blood loss/body weight ratio for Seprafilm patients compared with control patients showed a trend toward but did not reach significance (P = .09). CONCLUSIONS: Decreased incidence and severity of postsurgical adhesions with Seprafilm in pediatric patients may lead to reduction of the risks associated with subsequent operation.

Abdomen↗
PubMed2005

Deficiency in systemic interleukin-1 receptor antagonist production as an operative risk factor in malnourished elderly patients with colorectal carcinoma.

OBJECTIVE: Aging and tumor-related malnutrition are associated with increased inflammatory cytokine levels. However, it is unclear whether this influences the outcomes of surgery. We explored the relationships between cytokines and surgical complications among patients undergoing surgery for colorectal cancer. DESIGN: Laboratory experiment. SETTING: Surgery department of school of medicine. PATIENTS: One hundred patients with colorectal cancer. INTERVENTIONS: The perioperative circulating levels of interleukin (IL)-1beta, IL-6, and IL-1 receptor antagonist (Ra) were determined, and the numbers of circulating lymphocytes and neutrophils were counted. MEASUREMENTS AND MAIN RESULTS: Trends toward increasing postoperative infection were observed among patients who were older and had lower body mass index. Preoperative IL-1Ra and intraoperative blood loss, however, remained the only two independent predictors of postoperative infection. Clinically, patients with low preoperative IL-1Ra most frequently were the elderly with low body mass index. Postoperatively, elderly patients with low body mass index showed an exaggerated IL-6 response, followed by an exaggerated postoperative inflammatory response and increased postoperative loss of body weight. In contrast, normal immunoreactivity was preserved in well-nourished elderly patients. CONCLUSIONS: In colorectal cancer patients undergoing surgery, low preoperative IL-1Ra is associated with postoperative infection. In our patient population, lower IL-1Ra level is commonly observed in the elderly with low body mass index. These findings suggest that postoperative infection, frequently seen in the nutritionally deficient elderly, may be the result of defective immunoinflammatory adaptation system.

Age Factors↗
PubMed2005

Prospective study of arterial infusion chemotherapy followed by radiofrequency ablation for the treatment of liver metastasis of gastric cancer.

This prospective study was conducted to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) with use of an implanted port followed by radiofrequency (RF) ablation for the treatment of liver metastasis of gastric cancer. Seven patients without extrahepatic metastasis were enrolled. The maximum tumor size was less than 3 cm in one patient and 3.2-6.0 cm in the other six patients (mean, 4.4 cm +/- 1.5). Two patients had single lesions and the other five patients had two to six lesions each. The maximum tumor size was reduced to 3 cm or less (mean, 2.4 cm +/- 0.4; P < .03) after HAIC in all patients. The total number of tumors was reduced from 25 to 16. RF ablation was performed for all residual liver tumors, resulting in complete tumor necrosis. All but one patient are still living without intrahepatic recurrence, with a median survival time of 16.5 months.

Adult↗
PubMed2005

Methylthioadenosine phosphorylase gene is silenced by promoter hypermethylation in human lymphoma cell line DHL-9: another mechanism of enzyme deficiency.

Methylthioadenosine phosphorylase (MTAP) involved in the metabolism of purine and polyamine has been known to be deficient in a variety of tumors. Although this enzyme deficiency was reportedly caused by partial or total deletion of the MTAP gene, human MTAP-deficient lymphoma cell line DHL-9 has the intact MTAP gene. In order to determine the mechanism of MTAP deficiency in DHL-9, we carried out methylation-specific PCR analysis of sodium bisulfite-treated genomic DNA followed by DNA sequence analysis. Following incubation with various concentrations of 5-Aza-2'-deoxycytidine, DHL-9 cells were subjected to RT-PCR and an immunoblot analysis for MTAP expression. MTAP promoter in DHL-9 cells was methylated at cytosine of all CpG dinucleotides analyzed. Moreover, 5-Aza-2'-deoxycytidine treatment induced DHL-9 cells to express MTAP mRNA and protein. Taken together, MTAP deficiency in DHL-9 was caused by transcriptional silencing due to promoter methylation. Promoter methylation of the MTAP gene was also found in DNA samples from adult T-cell leukemia patients. These results indicated that promoter hypermethylation is another mechanism of MTAP deficiency in human malignancy. Thus, immunological diagnostics will be needed for an accurate evaluation of MTAP expression at the protein level.

Antimetabolites, Antineoplastic↗
PubMed2005

Improved survival using multi-modality therapy in patients with lung metastases from colorectal cancer: a preliminary study.

This retrospective study was conducted to assess the safety, efficacy, and long-term results of multi-modality therapy including radio-frequency thermal ablation (RFA) and radiotherapy as an additional cytoreductive method for eliciting the marked effects of chemotherapy in treating unresectable lung metastases from colorectal cancer. Total of 21 patients with lung metastasis from colorectal cancer were included. They were treated with modified pharmacokinetic modulating chemotherapy (PMC). Eleven were also treated with RFA and/or radiotherapy (multi-modality group), and 10 were treated with chemotherapy alone (chemotherapy group). Characteristics and survival of patients in the multi-modality group were compared with those of the chemotherapy group. The median survival of all patients was 38.6 months after the initial PMC. The cumulative 3-year survival rate of patients in the multi-modality group was 87.5% compared with 33.3% in the chemotherapy group (p=0.0041). The course of multi-modality therapy was uneventful except for pneumothorax in those who received RFA. Although pneumothorax developed in 4 of 11 patients (36.4%) treated with RFA, all were able to receive chemotherapy within 2 weeks after RFA. In conclusion, multi-modality therapy combined with modified PMC, radiation and RFA is a feasible choice of treatment associated with reasonable morbidity and mortality in patients with inoperable lung metastases from colorectal cancer.

Adult↗
PubMed2005

Hyaluronic acid-carboxycellulose membrane (Seprafilm) reduces early postoperative small bowel obstruction in gastrointestinal surgery.

This study aimed to evaluate the efficacy of sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) on early postoperative small bowel obstruction (EPSBO). It also examined whether using Seprafilm affected surgical site infection rates in gastrointestinal surgery. One hundred eighty-four patients who had Seprafilm placed during gastrointestinal surgery between October 2000 and December 2003 were included in the study (Seprafilm group) and were compared with a matched cohort (control group) of patients operated on without Seprafilm. All patients were retrospectively assessed for EPSBO and surgical site infections. The incidence of EPSBO was significantly lower (P < 0.05) in the Seprafilm group (12/184) than in the control group (26/183). The incidence of surgical site infection between the Seprafilm (15.2%) and control (13.7%) groups was not statistically significant. The placement of Seprafilm helped to prevent EPSBO and had no significant adverse affect on surgical site infections.

Adolescent↗
PubMed2004

Nutritional status and cytokine-related protein breakdown in elderly patients with gastrointestinal malignancies.

BACKGROUND: Age-related factors affecting cytokine-related whole-body protein breakdown and their relation to clinical outcomes in cancer patients were investigated. METHODS: For assessment of protein-calorie malnutrition and protein breakdown, the creatinine height index (CHI) and daily urinary excretion of 3-methylhistidine (3-MH) were measured in 70 patients with gastrointestinal malignancies. Perioperative cytokine profile was evaluated to assess its relation to perioperative protein catabolism. RESULTS: In elderly patients, daily 3-MH excretion during the stable preoperative period decreased with the increase of tumor interleukin (IL)-6 production, suggestive of the activation of a metabolic compensation mechanism. However, these patients showed significant increases in postoperative 3-MH excretion in accord with perioperative systemic IL-6 response, and this deterioration of the compensating mechanism seemed to be associated with poor clinical outcome. An increase in 3-MH excretion under surgical stress was positively correlated with postoperative consumption of IL-6 soluble receptor (sR) in elderly patients with nutritional depletion. CONCLUSIONS: In elderly cancer patients with protein-calorie malnutrition, metabolic compliance against intrinsic IL-6 may be compensated for in the preoperative stable period, but deteriorate from surgical insults. This mechanism might involve increased affinity of IL-6 with IL-6sR under surgical stress.

Adult↗
PubMed2004

Serum monocyte chemoattractant protein-1 in patients with postoperative infectious complications from gastrointestinal surgery for cancer.

We examined the kinetics of serum monocyte chemoattractant protein-1 (MCP-1) perioperatively and clarified its significance regarding the development of infectious complications. We studied 94 patients who underwent gastrointestinal surgery for gastric or colorectal cancer at Mie University Hospital from 1996 to 2000. Serum concentrations of MCP-1 and interleukin-6 (IL-6) were measured perioperatively. The number of circulating lymphocytes and neutrophils were counted to assess the apoptotic rate of neutrophils. Patients were divided into two groups at the median preoperative MCP-1 level obtained from 40 gender- and age-matched healthy volunteers. The rate of developing infectious complications was significantly higher and tumor size was significantly larger in the low MCP-1 group than in the high MCP-1 group. The increasing IL-6 ratio (postoperative/preoperative IL-6 level) in the low MCP-1 group was about twofold greater than that in the high MCP-1 group. The neutrophil level calculated for the low MCP-1 group was significantly higher than that in the high MCP-1 group on postoperative day 3. We concluded that a decreased level of serum MCP-1 reflected tumor-related immunosuppression. Low MCP-1 levels were associated with an exaggerated postoperative IL-6 response and delayed neutrophil apoptosis, which affected the incidence of postoperative infectious complications developing in patients with gastrointestinal malignancies.

Adult↗
PubMed2004

Trocar site hernia.

OBJECTIVE: To review the relationship between the pathogenesis and clinical manifestations of trocar site hernias seeking to confirm the definition of trocar site hernias by classification. DATA SOURCES: We searched this subject in English on MEDLINE by combining the words "trocar," "port," "hernia, and "laparoscopy."Data Extraction and STUDY SELECTION: We limited the main operations to cholecystectomy, colon and rectal surgery, fundoplication, and gastric surgery; finding 44 reports on these procedures. Of these, 19 were case reports, 18 were original articles (setting criteria; the incidence of the trocar site hernia was clarified, and involved >100 patients), and 7 technical notes on "how to do it" were collected. We obtained 19 additional reports using the references of those previously obtained. We, thus, reviewed 63 reports (24 case reports, 27 original articles, 7 technical notes, and 5 review articles). DATA SYNTHESIS: Trocar site hernia was classified into 3 types. The early-onset type that occurred immediately after the operation, with a small-bowel obstruction, especially the Richter hernia, frequently developing. The late-onset type that occurred several months after the operation, mostly with local abdominal bulging with no small-bowel obstruction developing. The special type that occurred indicated the protrusion of the intestine and/or omentum. Trocar site hernias with fascial defects of 10 mm or larger should be closed, including the peritoneum. Opinion varied if a 5-mm trocar site defect should be closed. CONCLUSION: It is useful to clearly classify trocar site hernias to improve management of laparoscopic procedures.

Digestive System Surgical Procedures↗
PubMed2004

Operative morbidity associated with groin dissections.

PURPOSE: Groin dissection remains the treatment of choice for malignant neoplasms of the skin in the lower extremities and perineum. We sought to quantify the hospital complications after groin dissection, and to identify the patient- and procedure-related factors affecting these complications. METHODS: We reviewed 20 consecutive patients who underwent a collective 25 groin dissections for malignant neoplasms of the skin between 1996 and 2002 to determine the incidence and degree of morbidity, and to analyze the clinical factors associated with morbidity. An S-shaped incision was used for the first 8 procedures, whereas a straight incision was used for the next 17. RESULTS: The overall incidences of complications were 24% for wound infection, 52% for skin flap problems, 32% for seromas, 40% for edema, and 4% for hemorrhage, whereas the incidences of moderate to severe complications were 16% for wound infection, 16% for skin flap problems, 12% for seromas, 4% for edema, and 4% for hemorrhage. The incidence of wound infection tended to be higher after S-shaped incisions than after straight incisions ( P = 0.059), and the incidence of leg edema was significantly higher after S-shaped incisions than after straight incisions ( P = 0.028). CONCLUSION: S-shaped incisions more often resulted in lymphatic collection and stagnation, with a higher incidence of wound infections and leg edema than straight incisions. Therefore, we now perform straight incisions to minimize the risk of wound infections and leg edema.

Adult↗
PubMed2004

Successful treatment of refractory hepatic lymphorrhea after gastrectomy for early gastric cancer, using surgical ligation and subsequent OK-432 (Picibanil) sclerotherapy.

Postoperative hepatic lymphorrhea is a very rare complication after abdominal surgery. Hepatic lymphorrhea, not containing chyle, involves an internal lymph fistula between the lymphatic channels toward the cisterna chyli and the peritoneal cavity. Over the past 20 years, 17 cases have been reported in Japan. Here, we report a further case, of a patient with successfully treated intractable hepatic lymphorrhea following gastrectomy for early gastric cancer. We review 18 cases, including the present case, with respect to the management of postoperative lymphorrhea refractory to conventional medical treatment.

Aged↗
PubMed2004

Predicting factor of quality of life in long-term jaundice-free survivors after the Kasai operation.

BACKGROUND/PURPOSE: The aim of this study was to determine simple predictors for quality of life (QOL) in long-term jaundice-free survivors after the Kasai operation. METHODS: Kasai's original portoenterostomy was performed on 55 patients with biliary atresia. Among them, records were reviewed retrospectively of 35 long-term (at least 5 years) and jaundice-free (clearance in bilirubin level less than 1.0 mg/dL after Kasai operation) survivors. The patients were divided into 2 groups based on QOL, and the differences in clinical and laboratory data were analyzed statistically. RESULTS: The ages at Kasai operation, histologic, fibrosis grade of liver biopsy specimen at operation, the first onset and frequency of postoperative cholangitis, and postoperative clearance speed of jaundice after Kasai operation were not significantly different between the 2 groups. The aspartate aminotransferase (AST) level at 1 year was significantly correlated with the serum concentration of hyaluronic acid and an independent predictor for QOL in long-term jaundice-free survivors of the Kasai operation. CONCLUSIONS: The serum AST level at 1 year was a simple, strong predicting factor of QOL and liver dysfunction in long-term jaundice-free survivors after Kasai operation and may prove useful in planning liver transplantation.

Aspartate Aminotransferases↗
PubMed2004

Terminal endbuds and acini as the respective major targets for chemical and sporadic carcinogenesis in the mammary glands of human c-Ha-ras protooncogene transgenic rats.

A rat strain carrying the human c-Ha-ras protooncogene, established by our laboratory, is highly susceptible to mammary chemical carcinogens. The transgenic rats exhibit increased number of terminal endbuds (TEBs) at the tips of developing ducts in the mammary gland compared to non-transgenic littermates. Confocal microscopy revealed the level of active mitogen-activated protein kinase to be elevated in these TEBs, and a close correlation between their numbers and tumorigenic response initiated by 7,12-dimethylbenz[a]anthracene was confirmed. Single injections of N-methyl-N-nitrosourea into the transgenic rats caused mutations in codon 12 of human c-Ha-ras transgene in TEBs before tumor development, supporting the conclusion that these structures are the major targets of chemical carcinogens. In contrast, with spontaneous development of lesions, alveolar hyperplasia with elevated expression levels of rat and human c-Ha-ras protooncogenes is the first morphological alteration which becomes apparent. Some but not all hyperplastic alveolar nodules were found to harbor mutations in the transgene. The results indicate that elevated expression of c-Ha-ras protooncogene is sufficient in itself to cause a highly proliferative phenotype of mammary alveoli. Our data suggest that TEBs and acini are the major targets for chemical and sporadic carcinogenesis, respectively, in the mammary glands of human c-Ha-ras protooncogene transgenic rats.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

C-reactive protein as a prognostic variable that reflects uncontrolled up-regulation of the IL-1-IL-6 network system in colorectal carcinoma.

Up-regulation of the IL-1-IL-6 network stimulates systemic expression of C-reactive protein (CRP). This cytokine network system plays a pivotal role in inducing angiogenic growth factors in intestinal mucosa. Serum CRP level and tissue concentrations of cytokines in colorectal cancer patients were determined and an in vitro model was employed to determine the time course of induction of IL-6 in Caco-2 cells. Increased serum CRP was associated with recurrent disease and shorter survival time. Intense surgical stress and the presence of an acute phase reactant were independently associated with overexpression of IL-6 in the tumor. Enhanced IL-6 protein expression in Caco-2 cells induced by the initial treatment with IL-1beta or lipopolysaccharide could be abrogated by additional presupplementation of IL-1ra. The presence of an acute phase reactant reflects uncontrolled up-regulation of the local IL-1-IL-6 network system in the tumor, which may enhance the survival and proliferation of remnant cancer cells after tumor resection.

Aged↗
PubMed2004

The clinical implication of 14-3-3 sigma expression in primary gastrointestinal malignancy.

14-3-3 Sigma is a checkpoint control gene that promotes G2 arrest following DNA damage. The inactivation of the 14-3-3 sigma gene, primarily by methylation-mediated silencing, has been reported in various human cancers. The loss of 14-3-3 sigma expression may contribute to malignant transformation by impairing the G2/M cell cycle checkpoint function, allowing an accumulation of genetic defects. In this report, we measured 14-3-3 sigma expression in 34 gastric and 35 colorectal cancers by using semi-quantitative reverse transcription-polymerase chain reaction and Western blot analysis. We also analyzed the association between 14-3-3 sigma expression and clinicopathological parameters including p53 status. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot analysis showed that 14-3-3 sigma was significantly overexpressed in gastric and colorectal cancer tissues compared with normal ones (P<0.01). The immunoreactive 14-3-3 sigma protein was mainly detected in cytoplasm of cancer cells. Sigma overexpression tended to be associated with lymph node metastasis (P=0.08) in colorectal cancer. There was significant correlation between 14-3-3 sigma protein expression and the Ki-67 labeling index in gastric cancer (P=0.001). No significant association was observed between 14-3-3 sigma expression and p53 status. These results suggest that overexpressed 14-3-3 sigma in cancer cells might be induced by the p53 independent pathway, and that increased 14-3-3 sigma expression could contribute to cancer cell proliferation and the development and/or progression of human gastrointestinal cancers.

14-3-3 Proteins↗
PubMed2004

Gene expression profiles of colorectal carcinoma in response to neo-adjuvant chemotherapy.

The combination of irinotecan and a fluoropyrimidine has been widely accepted as a treatment for advanced colorectal carcinoma. However, there have been no evaluable data on the feasibility of these combinations. To assess the significance of such combinations, we attempted to identify gene expression patterns in response to irinotecan and two different types of fluoropyrimidines. In 12 patients dispositioned to receive preoperative chemotherapy for colorectal carcinoma, pre-therapy tumor biopsies and final resected specimens were available for analysis. Patients were randomly assigned to receive one of the following four regimens: (I), oral doxifluridine; (II), intravenous infusion of 5-FU; (III), intravenous infusion of irinotecan; (IV), combination of doxifluridine and irinotecan (I+III). To identify genes whose expressions changed, we analyzed the gene expression profiles prior to and after these therapies using an oligonucleotide microarray consisting of 12,000 genes. Next, we focused on the genes that demonstrated similar kinetics of altered expression in all patients in each of the regimens. We identified two proto-oncogenes, nuclear receptor of T-cells (NOT) and c-fos, that were up-regulated in doxifluridine- and irinotecan-related regimens but unchanged in the 5-FU-related regimen. Moreover, group IV tumors showed the highest apoptotic rate and lowest proliferation activity following the combined chemotherapy. These results suggest that doxifluridine has a synergistic impact on the therapeutic effect of irinotecan by up-regulating proto-oncogenes such as NOT and c-fos, and thus justify the use of one of the irinotecan and fluoropyrimidine combinations.

Administration, Oral↗
PubMed2004

Laparoscopically assisted total gastrectomy with sentinel node biopsy for early gastric cancer: preliminary results.

This study sought to describe a procedure involving laparoscopically assisted total gastrectomy (LATG) with sentinel node biopsy (SNB) and to evaluate the results of the first three patients. LATG for early gastric cancer was performed with sentinel node (SN) identification using a combined patent blue-violet dye and 99mtechnetium-labeled tin colloid technique. Laparoscopically resected SNs were processed for frozen section examination by routine hematoxylin and eosin (H&E) and immunohistochemical cytokeratin (IHC-CK) stains. LATG consists of a four-surgical port technique, removal of the specimen through a small 5-cm laparotomy, and stapled Roux-en-Y esophagojejunostomy. Five patients were candidates for LATG with SNB between March 2001 and June 2003; two had open surgery because of a tumor extending the serosal surface and peritoneal dissemination, whereas in the remaining three, SNs were successfully identified and evaluated with no evidence of sentinel node (micro) metastases intraoperatively. Based on the results of SNB, three patients underwent LATG with adequate lymphadenectomy. Mean operative time and blood loss were 375 min and 219 mL, respectively. No dissected lymph nodes had evidence of metastasis by H&E and IHC-CK on permanent sections. LATG with SNB followed by adequate lymphadenectomy is technically feasible, and with its acceptable operative time and blood loss, presents an excellent therapeutic option for early gastric cancer; while SNB and subsequent frozen section analysis by H&E and IHC-CK staining is a rapid and reliable diagnostic method for intraoperative detection of SN (micro) metastasis. This combination treatment is a promising alternative to laparoscopic gastrectomy with conventional lymphadenectomy.

Adenocarcinoma↗