Biomedical subjects

Masato Kusunoki

Publications and source records attributed to Masato Kusunoki.

At least 37 records · Page 2Linked to original sources

PubMed2006

Genomic instability and tissue expression of angiogenic growth factors in sporadic colorectal cancer.

BACKGROUND: Chromosomal instability evidenced by a loss of heterozygosity (LOH) is implicated as a predictor of poor survival in patients with colorectal cancer, whereas microsatellite instability (MSI) is associated with improved survival rates. We investigated the relationship between tumor expression of angiogenic growth factors and genomic alterations in colorectal cancer. METHODS: Two genotypes, LOH and MSI, determined by microsatellite markers in the 4 cancer-related chromosomes 2p, 3p, 17p, and 18q, were analyzed in 73 patients with colorectal cancer. The tumor-specific expression of vascular endothelial growth factor and hepatocyte growth factor (HGF) were quantified, and the interleukin-6 network also was evaluated. RESULTS: MSI-positive neoplasms showed a lesser expression of both tumor growth factors and interleukin-6. In contrast, LOH-positive neoplasms showed a greater expression of HGF and a lesser expression of interleukin-1-receptor antagonist. MSI neoplasms were correlated with favorable prognosis in agreement with previous findings. CONCLUSIONS: The suppressed production of angiogenic growth factors in MSI cancers partly might explain the better prognosis in MSI-positive patients. The interleukin-6 network, which upregulates production of vascular endothelial growth factor and HGF, might be involved in this mechanism.

Adult↗

PubMed2006

Laparoscopic intragastric surgery using GelPort.

In laparoscopic intragastric surgery for early gastric cancer and submucosal tumors, three trocars are routinely inserted in the gastric lumen. We placed a GelPort hand assist device through a 5-cm transverse incision in the upper abdomen, and inserted the trocars into the gastric lumen through the gel seal cap, snapping the gel seal cap on and off during the operation. This makes it possible to use an open technique in which trocars are inserted into the gastric lumen, and to close the trocar sites in the gastric wall. We believe that the technique described here is easier and saves time compared with inserting trocars and closing trocar sites laparoscopically.

Aged, 80 and over↗

PubMed2006

Hemidouble stapling for esophagogastrostomy during laparoscopically assisted proximal gastrectomy.

In esophagogastrostomy during laparoscopically assisted proximal gastrectomy, some problems have occurred; the main ones being reflux esophagitis and the technical difficulty in anastomosis. We have had good results with a hemidouble stapling technique; the center rod of circular stapler is pierced through the left end of the staple line of the stomach. The longest distance from the pylorus to the esophagogastrostomy can be fired in this position. The distance is longer, so alkaline esophagitis is rarer. When the center rod is pierced through the anterior or posterior gastric wall, the operator may be worried about ischemia of the area surrounded by the linear stapler and circular stapler. In hemidouble stapling, an ischemic area is not created at all structurally. Any surgeon can perform a reproducible anastomosis because the place pierced with the center rod is fixed. This technique is easy and safety to operate via minilaparotomy.

Aged↗

PubMed2006

A case of congenital jejunal atresia associated with bilateral athelia and choanal atresia: new syndrome spectrum.

We present a case of bilateral choanal atresia, cleft of the posterior palate. Cardiac, respiratory and central nervous system examinations were normal. An examination of the chest revealed aplasia of the bilateral absence of the bilateral nipple-areola complex. Skin, soft tissue and bilateral pectoral muscles of the chest wall were normal. The patient did not have scalp nodules or abnormal ears. Four hours after birth, an X-ray examination showed the distended intestinal loops, suggesting small bowel obstruction. Exploration was performed and congenital jejunal atresia was surgically identified. A primary anastomosis was performed. At 3 years of age, the patient had mild mental and growth retardation. Chromosome analysis was normal (46,XX). Magnetic resonance imaging showed no abnormal finding in the spinal cord; however, mild atrophy of the left cerebrum was pointed out. An abdominal echo examination showed no abnormal findings in the kidney. These associations may represent a previously undescribed syndrome spectrum.

Cerebellum↗

PubMed2006

in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer.

The combination of irinotecan and a fluoro-pyrimidine is widely accepted as a treatment for advanced colorectal cancer. However, evaluable data on the feasibility of these combinations has not been presented, and an optimal sequence for administration has not been experimentally and clinically determined. The sequential effect of a combination of 5-FU and CPT-11 in the human colon cancer cell line LoVo was evaluated by WST-8 colorimetric assay. The cytotoxicity and cell cycle distributions of each drug were analyzed by apoptosis assay and flow cytometry. Further, the potential mechanisms of the sequence-dependent effects were investigated by a microarray technique, and confirmed by Western blot analysis. The cytotoxicity of 5-FU (10, 100, 1000 microM) followed by CPT-11 (1 microM) was significantly greater than that of CPT-11 (1 microM) followed by 5-FU (10, 100, 1000 microM) (p<0.05). In cell cycle distribution, 5-FU exposure for 24 h increased the S phase fraction in a dose-dependent manner; though there was no significant difference in cell cycle distribution in 24 h CPT-11 (0.01-1 microM) exposure. Microarray analysis revealed that expressions of some apoptosis related genes such as Bcl-2 changed, and were correlated with sequence-dependent cytotoxicity of the 5-FU --> CPT-11 sequence. Western blot analysis confirmed that the Bcl-2/Bax ratio was lower after 5-FU --> CPT-11 sequence than before. The sequence-dependent cytotoxic effect may depend on the sensitizing effect of 5-FU pretreatment on CPT-11 cytotoxicity. 5-FU followed by CPT-11 administration may be an optimal sequence for IFL treatment of advanced colon cancer.

Antimetabolites, Antineoplastic↗

PubMed2006

Irinotecan cytotoxicity does not necessarily depend on the UGT1A1 polymorphism but on fluoropyrimidine: a molecular case report.

We have previously demonstrated that the combined use of doxifluridine and irinotecan shows a different molecular mechanism than that of the protracted venous infusion of 5-FU and irinotecan. In this analysis, there is a suggestion that doxifluridine may enhance irinotecan and enable us to decrease the dose of irinotecan without losing the strong effect by using doxifluridine instead of 5-FU. We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28) as a known high risk for irinotecan, who was treated with a combination of doxifluridine and irinotecan for peritoneal dissemination resulting in stable disease for 2 years without adverse reactions, although the patient initially developed severe adverse effects to the combination of the protracted venous infusion of 5-FU and irinotecan. Even with the same ratios of fluoropyrimidine and irinotecan combinations, replacing 5-FU with doxifluridine or capecitabine could provide new strategies to obtain not only convenience but also better efficacy and safety at the molecular level.

Aged↗

PubMed2006

The optimal schedule for 5-fluorouracil radiosensitization in colon cancer cell lines.

To evaluate the optimal schedule of 5-fluorouracil (5-FU) radiosensitization in rectal cancer, we investigated the interaction between radiation and several doses of 5-FU on colon cancer cell lines based on pharmacokinetics of oral fluoropyrimidine. Cellular cytotoxicity in colon cancer cell lines, LoVo, WiDr and Caco-2 was determined, using a WST-8 colorimetric assay, after 24 h exposure to several concentrations of 5-FU and a radiation dose of 5 Gy. Cells were exposed to 5-FU 24 and 0 h before radiation. 5-FU doses were classified into three groups: uracil-tegafur (0.01-0.1 microM), S-1 (0.1-1.0 microM) and pharmacokinetic modulating chemotherapy (0.1-10 microM). In addition, the effect of 5-FU on the steady-state levels of a human excision repair cross-complementing 1 gene and cell cycle distribution were examined. Regardless of time of 5-FU exposure, all cell growth was significantly inhibited in a dose-dependent manner. In Caco-2 cells, the cytotoxicity of radiation followed by 5-FU was significantly greater than that of 5-FU followed by radiation, unlike in the other cell lines. The growth inhibitory effect of radiation followed by 5-FU increased in a dose-dependent manner to reach a plateau at S-1 doses in all cell lines. In cell cycle distribution, 5-FU exposure for 24 h increased the S phase fraction in a dose-dependent manner. RT-PCR showed that 5-FU post-treatment graduallly inhibited mRNA expression of ERCC1, which may affect recombination repair efficiency, accounting for the higher tumor sensitivity. Oral fluoropyrimidines, like S-1, that can maintain a constant level of 5-FU may be an acceptable alternative radiosensitizer to protracted 5-FU infusion, when the aim of neoadjuvant chemoradiotherapy for rectal cancer is locoregional control.

Antimetabolites, Antineoplastic↗

PubMed2005

Ingestion of multiple magnets: hazardous foreign bodies for children.

We report a case of perforation, fistula formation, and small bowel obstruction in a 2-year-old child who had ingested 32 small magnets. Multiple magnets will attract one another through the bowel wall and lead to pressure necrosis with complications. We recommend early surgical intervention before the onset of gastrointestinal complications if ingested multiple magnets have not moved on the follow-up radiograph. Both clinicians and the lay population need to be aware that multiple magnets can be hazardous foreign bodies for children.

Deglutition↗

PubMed2005

Secondary pouchitis in a post-operative patient with ulcerative colitis, successfully treated by salvage surgery.

We report a case of secondary pouchitis, defined as a mucosal inflammatory lesion in the ileal reservoir provoked by pouch-related complication following total colectomy and pouch anal anastomosis, which was successfully treated by salvage surgery. A 20-year-old woman with ulcerative colitis developed acute severe bloody diarrhea following proctocolectomy, ileal pouch-anal anastomosis and diverting ileostomy. She was diagnosed as having a secondary pouchitis mainly caused by a peripouch abscess and partly concerned with the abnormal pouch formation. The remnant rectum and ileal pouch were excised and ileal pouch-anal anastomosis and diverting ileostomy were constructed. The postoperative course was uneventful with no sign of pouchitis. Salvage surgery may be indicated to treat secondary pouchitis when caused by surgery-related complications.

Adult↗

PubMed2005

Persistence of gene expression changes in noninflamed and inflamed colonic mucosa in ulcerative colitis and their presence in colonic carcinoma.

AIM: A few studies have applied genomic-wide gene expression analysis in inflamed colon tissue sample in ulcerative colitis (UC). We reported the first study of non-inflamed mucosal gene expression in UC and explored its clinical implication. METHODS: Non-inflamed mucosa was obtained from 6 UC patients who received total colectomy. The gene expression of UC in noninflamed mucosa was monitored with a microarray. For a selected gene, RT-PCR was performed to verify array results and to further examine expression pattern in inflamed mucosa of UC, colorectal cancer tissue and normal mucosa using additional matched pairs. RESULTS: Two genes showing 2.5-fold decreased expression with significance set at in UC samples were homeo box a4 (HOXa4) and mads box transcription enhancer factor 2, polypeptide B (MEF2b). RT-PCR showed that MEF2b expression in non-inflamed mucosa was significantly downregulated, whereas the expression of MEF2b increased in accordance with the severity of mucosal inflammation. HOXa4 expression both in inflamed and non-inflamed mucosa in UC was consistently downregulated, and the downregulation of HOXa4 was also found in colorectal carcinoma. CONCLUSION: It is suggested that the MEF2b expression in UC which increase in accordance with inflammation may be induced by the inflammatory mediator. In contrast the downregulation of HOXa4 may be partly involved in the pathogenesis of disease including UC and UC-related carcinogenesis.

Adult↗

PubMed2005

Administration sequence-dependent antitumor effects of paclitaxel and 5-fluorouracil in the human gastric cancer cell line MKN45.

BACKGROUND: The clinical outcome of gastric cancer patients has been improved by combination of 5-fluorouracil (5-FU) and paclitaxel (PXL). However, the optimal schedule of this combination has not been determined. METHODS: The efficacies of sequential administrations of 5-FU and PXL on the gastric cancer cell line MKN45 were investigated using a WST-8 colorimetric assay. The cell cycle distribution of each drug was evaluated by flow-cytometry. Furthermore, the mechanism of antitumor activity enhancement by the administration sequence was investigated by western blotting. RESULTS: MKN45 cell growth was significantly inhibited by each drug in a dose- and time-dependent manner. The cytotoxicities of PXL followed by 5-FU were significantly greater than those of 5-FU followed by PXL. The flow-cytometric analysis revealed that PXL exposure caused viable cell accumulation in G2/M phase in a dose-dependent manner. Western blotting showed that PXL exposure followed by 5-FU up-regulated Chk1 and Wee1 protein expressions until PXL removal and 5-FU exposure, when these expressions gradually decreased to their basal levels. 14-3-3sigma protein expression was significantly up-regulated upon PXL treatment followed by 5-FU. Interestingly, Mad2 protein expression with PXL treatment followed by 5-FU gradually increased after the PXL removal and 5-FU exposure. CONCLUSIONS: PXL followed by 5-FU administration may be the optimal sequence for treatment of gastric cancer. The enhanced viable cell accumulation after PXL pretreatment may be related to G2 arrest. After PXL removal and 5-FU exposure, the cells progressing to M phase may undergo cell death by mitotic catastrophe due to DNA damage caused by 5-FU exposure.

14-3-3 Proteins↗

PubMed2005

Interleukin-1 receptor antagonist inhibits the expression of vascular endothelial growth factor in colorectal carcinoma.

OBJECTIVE: Interleukin (IL)-1 is known to act as a tumor growth factor by inducing angiogenic factors. We examined the significance of IL-1beta and IL-1 receptor antagonist (RA) for inducing the expression of vascular endothelial growth factor (VEGF) in colorectal cancers. METHODS: We investigated the expression of VEGF induced by IL-1beta in five colon cancer cell lines and the possible involvement of IL-1 RA. We also measured the tissue concentrations of IL-1beta, IL-1 RA and VEGF by ELISA in 65 colorectal cancer patients. RESULTS: IL-1beta induced VEGF secretion with a 19-fold increase in Caco-2 cells. A significant increase in VEGF secretion was also observed in SW480 and WiDr cells. IL-1 RA inhibited IL-1beta-induced VEGF secretion by 87%. Our data from the clinically obtained specimens showed that the IL-1 RA/IL-1beta ratio is significantly lower in cancer tissue. Regarding the clinicopathological parameters, the IL-1 RA/IL-1beta ratio was significantly lower in patients with vessel involvement than in those without involvement, and IL-1 RA/IL-1beta ratio was negatively correlated with the VEGF protein level in colorectal tumors. CONCLUSIONS: Our data suggest that IL-1beta induces VEGF expression and IL-1 RA acts as the competitive inhibitor, and that the IL-1 RA/IL-1beta ratio is significant for VEGF expression in the microenvironment of colorectal cancer tissue. We conclude that IL-1beta induces VEGF secretion in a certain population of colorectal cancer patients, and that IL-1 RA is the potential therapeutic agent for antiangiogenic therapy in colorectal cancer patients.

Adult↗

PubMed2005

Stapled gastroplasty for antral stricture after repair of neonatal gastric rupture: report of a case.

The patient was the second of twin girls born at 32 weeks' gestation, weighing 1736 g. Abdominal distention was noted the day after birth, and abdominal x-ray showed free air in the abdomen. An emergent laparotomy with debridement and primary closure were performed for spontaneous gastric rupture. From the age of 8 months, the infant sometimes vomited after meals and was unable to gain weight. She was diagnosed, by upper gastrointestinal series and gastroscopy, with antral stricture with a normal prepyloric area and pylorus. The presence of an antral web, ulcers, or ectopic pancreatic tissue was excluded. There was sufficient distance between the stricture area and the pylorus. Stapled gastroplasty using an Endopath linear cutter stapler and a Proximate linear stapler was performed safely and quickly without injury to the normal pylorus or branches of the vagal nerve at the lesser curvature. The child's postoperative course was uneventful.

Constriction, Pathologic↗

PubMed2005

Laparoscopic lymphatic mapping and sentinel node biopsies for early-stage gastric cancer: the cause of false negativity.

Sentinel node (SN) biopsies might be useful for performing minimally invasive surgery without interrupting surgical curability. This study examined the cause of false negativity during laparoscopic lymphatic mapping and SN biopsies for early-stage gastric cancer. Thirty-seven patients with gastric cancer (preoperative stage T1-2 or N0) who underwent laparoscopic lymph node mapping and SN biopsies between March 2001 and June 2004 were enrolled in this study. The tracer, patent blue and technecium-99m-labeled tin colloid, was injected endoscopically. Blue-stained or radioactive nodes were defined as SNs. Gastrectomy with lymphadenectomy was performed then the results of the SN biopsies were compared with the final diagnosis of the removed lymph nodes in permanent sections. Sentinel nodes were successfully identified in 35 patients (94.6%), and they were positive in 3 of 4 patients with metastatic lymph nodes; sensitivity was 75% and specificity was 100%. Sentinel node status could therefore be used to diagnose lymph node status with 97.1% accuracy. Of 6 SNs with metastasis, 5 showed radioactivity, and only 2 were blue stained. In the false negative case, a radioactive SN with metastasis in the right paracardial region was missed during laparoscopic mapping. An error in laparoscopic intracorporeal detection of the radioactive node with metastasis occurred because we could not eliminate the shine-through effect. We found that during laparoscopic SN mapping there is a high risk of false negativity with SNs located in the right paracardial region. To apply laparoscopic SN mapping to early-stage gastric cancer patients, the shine-through effect must be eliminated because radiotracers are essential for this method.

Aged↗

PubMed2005

Esophageal stricture with a pseudodiverticulum caused by the unrecognized ingestion of a small foreign body in a child: report of a case.

A 2-year-old boy with a long history of vomiting, dysphagia, and weight loss was found to have a rigid stricture in the proximal esophagus. We performed esophageal repair using a Livaditis circular myotomy technique. The removed section of esophagus contained the inflammatory stricture with a pseudodiverticulum, caused by the unrecognized ingestion of a small, hard plastic sticker.

Diagnosis, Differential↗

PubMed2005

Bioresorbable hyaluronate-carboxymethylcellulose membrane (Seprafilm) in surgery for rectal carcinoma: a prospective randomized clinical trial.

PURPOSE: To evaluate the effectiveness of Seprafilm in preventing abdominal adhesions after radical resection of rectal carcinoma, and to observe whether Seprafilm had any adverse effects in patients treated with radiotherapy and chemotherapy. METHODS: A total of 62 patients participated in this prospective randomized clinical study, which was conducted to compare the outcomes of patients operated on with Seprafilm (SEPRA+) with those operated on without Seprafilm (SEPRA-). All patients received preoperative radiotherapy, followed by a two-stage operation, and 5-fluorouracil (5-FU)-based systemic chemotherapy. The primary endpoint of severity and extent of adhesions were evaluated at the time of ileostomy closure. The secondary endpoint included the recurrence of tumors, late complications, and outcome. RESULTS: Seprafilm significantly reduced the adhesions in both the midline incision area and peristomal area. This in turn reduced the operation time, blood loss, and extent of the incision at ileostomy closure. Seprafilm was not associated with any postoperative complications or chemoradiation-related toxicity, nor did it affect recurrence or survival rates. CONCLUSION: Seprafilm effectively reduced abdominal adhesions in chemoradiated patients, and had no adverse effects on the oncologic results of fully introduced adjuvant therapy. Thus, Seprafilm is a safe and effective tool for use in rectal carcinoma surgery.

Absorbable Implants↗

PubMed2005

Seprafilm does not aggravate intraperitoneal septic conditions or evoke systemic inflammatory response.

PURPOSE: To determine whether Seprafilm aggravates the systemic inflammatory response and adversely affects the outcome of postoperative intraperitoneal septic conditions. METHODS: We retrospectively analyzed the relationship between the intraperitoneal placement of Seprafilm and the rate of intraperitoneal septic complications in 278 consecutive patients. Experimentally, 40 rats were subjected to laparotomy with or without the intraperitoneal placement of Seprafilm. Bacterial peritonitis was induced by cecal ligation and puncture (CLP) and the serum cytokine levels were measured. RESULTS: Seprafilm did not increase the rate of septic complications or aggravate inflammatory responses in patients with or without postoperative intraperitoneal inflammatory complications. Experimentally, there was no significant difference between the serum inflammatory cytokine levels after CLP with or without Seprafilm. CONCLUSIONS: Seprafilm did not adversely affect postoperative inflammatory response or clinical outcomes, even in patients with intraperitoneal septic complications.

Adult↗

PubMed2005

Usefulness of a single trocar for intrathoracic anastomosis during open thoracic surgery for esophageal cancer.

When patients with esophageal cancer undergo intrathoracic anastomosis after esophagectomy in our institution, we resect the lesser curvature in the thorax using a surgical instrument after circular-stapled esophagogastric anastomosis. We then place the trocar in the seventh intercostal space on the midaxillary line, except in fifth intercostal anterolateral thoracotomy. A linear stapler applied through the thoracotomy sometimes blocks the operator's view, and so it is not so easy to operate with a rather big head in the thorax. We operate a linear cutter for laparoscopic surgery through the trocar. With this method, the instrument is used in good position in respect to the operator's view, and access to the gastric tube is easy. Moreover, we can adjust the resectional angle with this instrument by using the bending mechanism in its shaft. Furthermore, we can reuse the trocar site for the chest tube.

Anastomosis, Surgical↗