PubMed Health⌕ Search

Biomedical subjects

Kazuhiro Kaneko

Publications and source records attributed to Kazuhiro Kaneko.

At least 19 recordsLinked to original sources
PubMed2006

Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: We retrospectively investigated long-term toxicity after concurrent chemoradiotherapy (CRT) for patients with esophageal squamous cell carcinoma (ESCC). METHODS: Concurrent chemoradiotherapy was performed in 110 patients with T1 to T4 disease containing M1 lymph node (LYM) disease. Chemotherapy consisted of protracted infusion of 5-fluorouracil 400 mg/m(2) per 24 h on days 1 to 5 and 8 to 12, combined with 2-h infusion of cisplatin 40 mg/m(2) on days 1 and 8. Radiation treatment of the mediastinum at a dose of 30 Gy in 15 fractions was administered concomitantly with chemotherapy. A course schedule with a 3-week treatment and a 2-week break was applied twice, with a total radiation dose of 60 Gy. For the assessment of toxicity, the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring schema was adopted. RESULTS: A total of 81 patients were recruited in patients with stage I to IVA. Of 34 patients with complete response, 1 patient died as a result of acute myocardial infarction. Grade 2, 3, and 4 late toxicities occurred with the following incidences: pericarditis in 3 patients, 1 patient, and 2 patients, respectively; heart failure in 0, 0, and 3 patients; pleural effusion in 2, 3, and 0 patients; and radiation pneumonitis in 0, 0, and 1 patient, respectively. CONCLUSIONS: Definitive chemoradiotherapy for ESCC is effective with substantial toxicities. Further investigation is warranted to minimize the normal tissue toxicities.

Aged↗
PubMed2005

A free radical scavenger but not FGF-2-mediated angiogenic therapy rescues myonephropathic metabolic syndrome in severe hindlimb ischemia.

The therapeutic use of angiogenic factors shows promise in the treatment of critical limb ischemia; however, its potential for myonephropathic metabolic syndrome (MNMS), a fatal complication caused by arterial reconstruction, has not been elucidated. The objective of this study was to evaluate the effectiveness of recombinant Sendai virus-mediated gene transfer of fibroblast growth factor-2 (FGF-2) directly compared with that of a radical scavenger, MCI-186, in a rat model of MNMS. MNMS was surgically induced by aortic occlusion below renal arteries for 4 h, followed by 6 h of reperfusion. Administration of MCI-186 (twice; iv 5 min before induced ischemia and ip 5 min before reperfusion; 10 mg/kg, respectively), but not FGF-2 gene transfer (once, 48 h before induced ischemia), dramatically prevented the increase of serum biochemical markers as well as the edema of the gastrocnemius muscle. The effect of MCI-186 was accompanied by the marked suppression of the neutrophilic infiltration into the local (muscle) and remote (lung) organs. Although serum and muscular levels of a neutrophil-chemoattractant (growth-related oncogene/cytokine-induced neutrophil chemoattractant-1) were not affected by any treatment, the serum level of soluble intercellular adhesion molecule-1 was decreased by treatment with MCI-186 but not by treatment with FGF-2. These results suggest the distinct mechanism of MNMS from critical limb ischemia without reperfusion. Therefore, radical scavenging should be paid more attention than therapeutic angiogenesis when arterial circulation is reconstructed.

Angiogenesis Inducing Agents↗
PubMed2005

Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma.

AIM: To assess the validity of our selection criteria for hepatectomy procedures based on indocyanine green disappearance rate (K(ICG)), and to unveil the factors affecting posthepatectomy mortality in patients with hepatocellular carcinoma (HCC). METHODS: A retrospective analysis of 198 consecutive patients with HCC who underwent partial hepatectomies in the past 14 years was conducted. The selection criteria for hepatectomy procedures during the study period were K(ICG)>or=0.12 for hemihepatectomy, K(ICG)>or=0.10 for bisegmentectomy, K(ICG)>or=0.08 for monosegmentectomy, and K(ICG)>or=0.06 for nonanatomic hepatectomy. The hepatectomies were categorized into three types: major hepatectomy (hemihepatectomy or a more extensive procedure), bisegmentectomy, and limited hepatectomy. Univariate (Fisher's exact test) and multivariate (the logistic regression model) analyses were used. RESULTS: Postoperative mortality was 5% after major hepatectomy, 3% after bisegmentectomy, and 3% after limited hepatectomy. The three percentages were comparable (P = 0.876). The platelet count of 7.3X10(4)/microL died of postoperative morbidity, whereas 25% (6/24 patients) of patients with a platelet count of <or=7.3X10(4)/microL died (P<0.001). CONCLUSION: The selection criteria for hepatectomy procedures based on K(ICG) are generally considered valid, because of the acceptable morbidity and mortality with these criteria. The preoperative platelet count independently affects morbidity and mortality after hepatectomy, suggesting that a combination of K(ICG) and platelet count would further reduce postoperative mortality.

Blood Loss, Surgical↗
PubMed2004

Molecular differences between sporadic serrated and conventional colorectal adenomas.

PURPOSE: The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs). EXPERIMENTAL DESIGN: We evaluated the proliferative activity and molecular alterations in 47 SAs (25 pure-type and 22 mixed-type), 71 CADs, and 23 HPs. RESULTS: The proliferative activity of SAs, as evaluated by Ki-67 expression, was intermediate between CADs and HPs. There was no significant difference in the incidence of KRAS or p53 mutations between the three histological groups. In the microsatellite instability (MSI) analysis, 21% of SAs (9 of 43) showed MSI at two or more loci (MSI-H); corresponding values were 5% of CADs (3 of 64) and 8% of HPs (1 of 13; SAs versus CADs, P = 0.0125). MSI-H was more likely to be found in pure-type SAs (36%; 8 of 22) than in mixed-type SAs (5%; 1 of 21; P = 0.0212). Loss of hMLH-1 expression was found in 8 of 9 SAs with MSI-H. The incidence of BRAF or KRAS mutations was 36 and 15% of SAs, respectively; the combined incidence of BRAF and KRAS mutations occurred in 49% of SAs. However, there was no significant difference in the incidence of BRAF or KRAS mutations between SAs with and without MSI-H. CONCLUSIONS: Genetic instability is more frequently implicated in the tumorigenesis of SAs, especially pure-type SAs, than in that of CADs. In contrast, activation of the Ras/Raf/MEK/MAP kinase cascade by BRAF or KRAS mutation, independently of the genetic instability, may be associated with the progression of about half of SAs.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Essential role of PDGFRalpha-p70S6K signaling in mesenchymal cells during therapeutic and tumor angiogenesis in vivo: role of PDGFRalpha during angiogenesis.

Discovery of the common and ubiquitous molecular targets for the disruption of angiogenesis, that are independent of the characteristics of malignant tumors, is desired to develop the more effective antitumor drugs. In this study, we propose that the platelet-derived growth factor receptor-alpha (PDGFRalpha)-p70S6K signal transduction pathway in mesenchymal cells, which is required for functional angiogenesis induced by fibroblast growth factor-2, is the potent candidate. Using murine limb ischemia as a tumor-free assay system, we demonstrated that p70S6K inhibitor rapamycin (RAPA) targets mesenchymal cells to shut down the sustained expression of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via silencing of the PDGFRalpha-p70S6K pathway. Irrespective of the varied expression profiles of angiogenic factors in each tumor tested, RAPA constantly led the tumors to dormancy and severe ischemia in the time course, even associated with upregulated expression of VEGF from tumors. Because RAPA showed only a minimal effect to hypoxia-related expression of VEGF in culture, these results suggest that RAPA targets the host-vasculature rather than tumor itself in vivo. Thus, our current study indicates that the PDGFRalpha-p70S6K pathway is an essential regulator for FGF-2-mediated therapeutic neovascularization, as well as for the host-derived vasculature but not tumors during tumor angiogenesis, via controlling continuity of expression of multiple angiogenic growth factors.

Animals↗
PubMed2004

LPS binding protein does not participate in the pharmacokinetics of E5564.

E5564, a lipid A analogue, is a potent antagonist of lipopolysaccharide (LPS). Clinically, E5564 was developed as a possible therapy for treatment of sepsis and septic shock. Surface plasmon resonance (SPR) analysis indicates that E5564 binds to LPS binding protein (LBP), in a manner similar to LPS. Gel-filtration radioactive chromatograms of [(14)C]-E5564 in plasma revealed that E5564 initially distributes to the lipoprotein fractions, separated from high-density lipoprotein (HDL); the bound fraction is then released and binds to HDL. Similar results were obtained by heparin-manganese precipitation. At doses of E5564 relevant to its clinical use (i.e. 6 microg/ml), antibodies against LBP did not influence either the distribution of E5564 to non-HDL lipoprotein fractions or the transfer of E5564 from non-HDLs to HDL. Under these conditions, transfer of E5564 to HDL occurs similarly in the plasma of LBP knockout (KO) mice as in the plasma from wild-type mice. In addition, plasma clearance of E5564 in LBP KO mice is similar to that of wildtype mice. Thus, LBP binds E5564 in a manner similar to LPS, but does not play a role in E5564 redistribution/binding to lipoprotein and plasma clearance.

Acute-Phase Proteins↗
PubMed2004

[A case of advanced gastric cancer with multiple liver metastases successfully treated with TS-1 and CDDP].

A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old advanced gastric cancer patient with liver and lymph node metastases was treated by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS-1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80 mg/body on day 8. At the end of 2 courses, the primary tumor showed a hypertrophic wall, but a partial response of the liver metastases (reduction ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases.

Adenocarcinoma↗
PubMed2003

Hemangiopericytoma arising in the greater omentum: report of a case.

Although hemangiopericytoma may arise in any anatomic site, it rarely develops in the greater omentum. To our knowledge, only ten cases have been reported to date in the English-language literature. We report herein an additional case of hemangiopericytoma arising in the greater omentum. A review of the reported cases suggests that surgical resection provides the only chance of cure and that a high mitotic index (>4/10 high-power fields) and a tumor size of > or =20 cm predict an unfavorable prognosis after resection.

Aged↗
PubMed2003

Primary small cell carcinoma of the stomach.

We report on an 80-year-old man with primary gastric small cell carcinoma (SmCC). He was admitted to hospital with hematemesis. An upper gastrointestinal examination revealed an irregularly ulcerated tumor, 60 mm in diameter, on the lesser curvature of the stomach body extending to the cardia. An endoscopic biopsy revealed a solid proliferation of intermediate-sized tumor cells with hyperchromatic nuclei and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for neuron-specific enolase and chromogranin A, but negative for carcinoembryonic antigen. No tumor was detected on examination of the chest. Therefore, primary gastric SmCC was diagnosed preoperatively. To date, only 38 cases of primary gastric SmCC, including our case, have been reported. By using endoscopic biopsy, approximately two-thirds of cases have been diagnosed incorrectly. In the reported cases of gastric SmCC, the endoscopic findings frequently indicated a submucosal tumor. Gastric SmCC is clinically aggressive and has an extremely poor prognosis, even when discovered at an early stage. Most patients with gastric SmCC die within 1 year of diagnosis. Although a standard treatment for gastric SmCC has not been established, intensive chemotherapy should be considered to promote long-term survival. We believe that careful examination, including immunohistochemical investigation, is necessary for determining the therapeutic strategy whenever gastric SmCC is suspected during endoscopy.

Aged↗
PubMed2003

Discordant lymphoma: MALT lymphoma of the stomach and follicular lymphoma of the parotid gland.

More than one histological type of malignant lymphoma can occur simultaneously in an individual. The entity is classified as either composite or discordant lymphoma. Both types of lymphoma, particularly discordant lymphoma comprised of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue lymphoma (MALT-L) and follicular lymphoma (FL), are rare. We report a case of discordant lymphoma comprising MALT-L in the stomach and FL in the parotid gland. The patient was a 50-year-old Japanese woman who visited the University Hospital of Showa (Tokyo, Japan) because a barium study showed erosive gastric lesions. A gastro-intestinal endoscopy was performed 2 months after the barium study, which showed irregular erosions throughout the stomach body. A gastric biopsy showed MALT-L, and Helicobacter pylori (H. pylori) infection was confirmed. The patient had noticed a painless and elastic hard tumor mass of about 2 cm in diameter in the area of the left parotid gland 6 months before the barium study. We removed the parotid gland tumor and diagnosed it as FL 6 months after the barium study. We were able to diagnose the MALT-L and FL by morphological, immunohistochemical and molecular analyses of paraffin-embedded sections. This appears to be the first reported case of MALT-L and FL occurring together as a discordant lymphoma.

Female↗
PubMed2003

A comparison of magnifying and nonmagnifying colonoscopy for diagnosis of colorectal polyps: A prospective study.

BACKGROUND: Discrimination between neoplastic and non-neoplastic colorectal polyps is essential for determining appropriate treatment. The mucosal crypt pattern of polyps can be observed with a nonmagnifying colonoscope; however, mucosal crypt patterns are better seen by magnifying colonoscopy, which can also be a noninvasive means for predicting histopathology. This study prospectively compared the ability to distinguish between neoplastic and non-neoplastic lesions by magnifying and nonmagnifying colonoscopy. METHODS: Six hundred sixty patients were randomly assigned to undergo magnifying or nonmagnifying colonoscopy (2 groups each of 330 patients). The mucosal crypt pattern of colorectal lesions was classified into types I through V after spraying with 0.2% Indigo carmine dye. The histopathology of all lesions was confirmed by evaluation of endoscopic resection specimens or biopsy specimens. Only lesions 10 mm or less in diameter were included in the study. RESULTS: The accuracy of magnifying colonoscopy in distinguishing neoplastic from non-neoplastic lesions (92%, 372/405) was significantly higher than for nonmagnifying colonoscopy (68%, 278/407). Insertion of magnifying and nonmagnifying colonoscopes to the cecum was successful in, respectively, 321 patients (97%) and 317 patients (96%), with no significant differences in the average time to reach the cecum or average total procedure time. No serious complication was observed during or immediately after the examinations. CONCLUSIONS: Observation of mucosal crypt pattern with magnifying colonoscopy is superior to nonmagnifying colonoscopy for distinguishing between neoplastic and non-neoplastic colorectal lesions.

Colonic Polyps↗
PubMed2002

Evaluation of endoscopic ultrasonography in colorectal villous lesions.

BACKGROUND AND AIMS: The choice of therapeutic procedure for colorectal neoplasias depends largely on the depth of tumor invasion. This study examined the value of endoscopic ultrasonography (EUS) in determining whether local resection is applicable for colorectal villous lesions. MATERIALS AND METHODS: We performed EUS on 125 colorectal neoplasias classified into two categories, villous ( n=35) and nonvillous lesions ( n=90), according to their colonoscopic morphological features. We compared the EUS and clinicopathological findings for each lesion. RESULTS: The overall accuracy of EUS-based evaluation of tumor invasion depth was 60% in villous lesions and 91% in nonvillous lesions. In villous lesions 37% were overstaged and 3% understaged, and in of nonvillous lesions 6% were overstaged and 3% understaged. In differentiating mucosal neoplasias (M)/submucosal cancers with slight invasion (SM-s) from non-M/SM-s, the values in villous and nonvillous lesions were, respectively: sensitivity 60% and 86%, specificity 100% and 99%, and accuracy 66% and 96%. Large (>/=20 mm wide, >/=5 mm high) or rectal villous lesions were more likely than nonvillous lesions to be misjudged with regard to the differentiation between M/SM-s and non-M/SM-s. CONCLUSION: It is difficult to determine the depth of invasion in villous lesions, especially large or rectal lesions, using only EUS. EUS-based evaluation alone cannot determine the appropriate treatment for colorectal villous lesions.

Adenoma, Villous↗
PubMed2002

Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter region.

E-cadherin is a tumor suppressor involved in epithelial cell-cell interactions. Some of the nucleotide variation in the 5'-promoter region of the gene influences transcriptional efficiency. We investigated single nucleotide polymorphisms (SNPs) in the promoter-exon 1 region of the E-cadherin gene (CDH1) using fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP) analysis. We detected four kinds of polymorphisms between nucleotides -516 and +12, numbering from the translation initiation site. SNPs were localized at -472G-->GA, -288T-->deltaT, -285C-->A, and -54G-->C. Variants -472GA and -285A were frequently found in controls, but the -288deltaT and -54C are rare variants. We examined the effects of these variants on transcription. The activity of promoters containing the variants -288deltaT, -285A, or -54C was lower than the activity of promoters with the major variants, as assayed by a luciferase reporter gene. Variants -472G and -472GA displayed the same promoter activity. The decreased transcriptional activity from variant promoters affects the expression of E-cadherin.

Alleles↗
PubMed2002

Colorectal carcinoma with special reference to growth pattern classifications: clinicopathologic characteristics and genetic changes.

BACKGROUND: Many colorectal carcinomas are known to develop from preexisting polypoid adenomas; however, they can also develop from so-called "flat adenomas". To elucidate the growth patterns of flat- or depressed-derived colorectal carcinomas, we investigated the clinicopathologic characteristics and genetic changes of invasive carcinomas. METHODS: Seventy-five colorectal carcinomas were classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG) type, and 7 lateral growth (LG) type. All of them had histologically infiltrated the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by polymerase chain reaction-single-strand conformation polymorphism analysis, and overexpression of p53 protein was analyzed by immunohistochemistry. RESULTS: No DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors existing in the right colon was significantly higher in LG carcinomas (71%) than in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was significantly higher in the UG carcinomas than in the DG and LG carcinomas (52% vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of 7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG (57%), and DG (50%) carcinomas. CONCLUSIONS: These results suggest that UG carcinomas develop on the basis of the adenoma-carcinoma sequence, while the development of DG and LG carcinomas is different from that of UG carcinomas.

Adenoma↗
PubMedDate not supplied

Implantation of self-expanding metallic stent for patients with malignant stricture after failure of definitive chemoradiotherapy for T3 or T4 esophageal squamous cell carcinomas.

BACKGROUND/AIMS: Definitive chemoradiotherapy can have curative potential in unresectable patients with malignant stricture due to locally advanced esophageal carcinoma, however, dysphagia is the principal problem in patients who had recurrence or who did not respond to chemoradiotherapy. In this prospective study, we investigated the efficacy and feasibility of metallic stent implantation for patients with dysphagia after chemoradiotherapy failed. METHODOLOGY: Concurrent chemoradiotherapy was performed in 40 patients with severe dysphagia due to esophageal squamous cell carcinomas accompanied by T3 or T4 disease containing M1 lymph node (LYM) disease. A self-expanding metallic stent was inserted for patients with malignant stricture of the thoracic esophagus after failure of chemoradiotherapy using identical protocols. RESULTS: Of 40 patients, 13 (33%) achieved a complete response. However, 12 patients complained of severe dysphagia again after chemoradiotherapy despite a good performance status. Esophageal stricture of these 12 patients was caused by stable disease (n = 4), local progression (n = 5), and compression of metastatic lymph node (n = 3). Metallic stents were successfully inserted for all 12 patients, and dysphagia improved in 10 (83%) of these 12 patients. Life-threatening complication (17%) of sepsis in two patients was found in an early phase after stent insertion, although approximately 200 days had passed in a dysphagia-free state after chemoradiotherapy. CONCLUSIONS: Implantation of self-expanding metallic stent for patients with malignant stricture after failure of chemoradiotherapy is effective, however, serious complication can occur in the early phase.

Aged↗