Jun Higashijima

The University of Tokushima, Tokushima-shi, Tokushima-ken, Japan

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Publications (21)29.18 Total impact

  • Article: Impact of education with authorized technical experts on colorectal laparoscopic skills.
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    ABSTRACT: Laparoscopic skills training is becoming the standard for educating surgical residents. Because of the specific procedure which differs from that of open surgery, it is imperative to establish a unique training system to promote efficiency of learning laparoscopic skills. The aim of this study was to evaluate the efficiency of learning laparoscopic skills with or without authorized experts of JSES. Among 71 patients who underwent laparoscopic colectomy from 2004 to 2009, 30 patients who underwent operation in introduction era without a technical expert (2004-2006), 17 patients who underwent operation in late period of introduction era without a technical expert (2006-2008), 12 patients who underwent operation by resident with technical expert (2008-2009) and 12 patients who underwent operation by technical expert, were investigated. Operative time, amount of blood loss, intra- and post-operative complications and conversion to open surgery were investigated. Operative time: 477:333:262:220 minutes (early period:late period:resident:expert), amount of blood loss: 494:73:21:20mL and complications: ileus: 0:1:0:0, leakage: 1:1:3:0, neurological disturbance: 2:1:0:0. Instruction by authorized technical experts of JSES is helpful to avoid pitfalls which are not seen in open surgery without an expert.
    Hepato-gastroenterology 07/2012; 59(117):1412-4. · 0.66 Impact Factor
  • Article: Clinicopathological Analysis of Distal Margin for Rectal Cancer after Preoperative Chemoradiation Therapy.
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    ABSTRACT: Background/Aims: Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. Methodology: This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. Results: Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6mm to -9mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. Conclusions: This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins =1cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.
    Hepato-gastroenterology 02/2012; 59(119). · 0.66 Impact Factor
  • Article: Platelet-derived endothelial cell growth factor/thymidine phosphorylase inhibitor augments radiotherapeutic efficacy in experimental colorectal cancer.
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    ABSTRACT: A lot of radiosensitizers have been developed. However, there are few to be available in the clinical setting. Thymidine phosphorylase inhibitor (TPI) regulates the phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose-1-phosphate which is essential for tumor angiogenesis. The aim of this study is to evaluate whether TPI augments the radiotherapy for colorectal cancer in vitro and in vivo studies. The cytotoxicity of TPI with irradiation on HT29 and HCT116 cells was examined using MTT- and colony formation assay. At 10days post-inoculation, HT29 bearing orthotopic model mice (n=28) were divided into four groups and orally treated with TPI- (50mg/kg/day for 2weeks), radiation (RT, 2Gy×4: Total 8Gy), their combination or the vehicle. The mechanisms underlying the efficacy were assessed genomically and immunohistochemically. Compared to each single treatment, the combination of TPI and RT synergistically inhibited the cell viability in a time- and dose-dependent manner. In the HT-29 bearing mice, the combination of TPI and RT reduced the tumor growth compared with RT alone. Notably, the mRNA levels of VEGF, TGF-β and, Rad51 and the protein expressions of VEGF and CD34 were significantly lower in the combination than the others. Furthermore, the combination markedly increased the TUNEL-positive cells, suggesting that TPI augments the cancer cell death through inhibition of angiogenesis and DNA repair system in the radiotherapy. Our study first demonstrated that the combination of TPI and irradiation was effective in colon cancer. TPI would provide a promising therapeutic strategy as a radiosensitizer.
    Cancer letters 12/2011; 318(2):199-205. · 4.86 Impact Factor
  • Article: Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.
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    ABSTRACT: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05). DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.
    Surgery Today 11/2011; 42(1):60-7. · 1.22 Impact Factor
  • Article: Expression of histone deacetylase 1 and metastasis-associated protein 1 as prognostic factors in colon cancer.
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    ABSTRACT: Histone deacetylase 1 (HDAC1) and metastasis-associated protein 1 (MTA1) form the nucleosome remodeling and histone deacetylation (NuRD) complex and may possibly play a central role in cancer development. However, limited data has been reported regarding the expression of both HDAC1 and MTA1. The aim of the present study was to clarify the clinical role of HDAC1 and MTA1 expression in colon cancer. Seventy-four patients with colon cancer, who underwent colectomy at our institution, were enrolled in this study. Expression of HDAC1 and MTA1 was examined immunohistochemically. The patients were divided into four groups: HDAC1-positive group (n=58), HDAC1-negative group (n=16), MTA1-positive group (n=38) and MTA1-negative group (n=36). Clinicopathological factors and survival rates were compared between the groups. Regarding the clinicopathological factors, the depth of tumor invasion and stage correlated significantly with HDAC1 expression (p<0.05). Age, depth of tumor invasion and vascular invasion tended to correlate with MTA1 expression. The 5-year survival rate in the HDAC1-positive group (55.1%) was significantly worse compared to the HDAC1-negative group (86.5%) (p<0.05), and the 5-year survival rate of the MTA1-positive group (50.5%) was significantly worse than that of the MTA1-negative group (73.1%) (p=0.05). In patients with stages II-IV and curability A, B, the survival rate in those with HDAC1-positive expression was significantly worse than those with HDAC1-negative expression (p<0.05), and the survival rate of the MTA1-positive group tended to be worse than that of the MTA1-negative group (p=0.07). Overall survival in both the HDAC1 and MTA1-positive groups was significantly worse than overall survival of the other groups (p<0.05). Disease-free survival in both the HDAC1- and MTA1-positive groups, among patients with stages II-IV and curability A, B, was also significantly worse than that of the other groups (p<0.05). HDAC1 and MTA1 expression levels were significantly related to poorer prognosis. Therefore, HDAC1 and MTA1 expression levels are potential prognostic indicators for colon cancer.
    Oncology Reports 08/2011; 26(2):343-8. · 1.84 Impact Factor
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    Article: Intraperitoneal infusion of paclitaxel with S-1 for peritoneal metastasis of advanced gastric cancer: phase I study.
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    ABSTRACT: Intraperitoneal administration of taxanes revealed excellent anti-tumor effect for peritoneal metastasis of gastric cancer in some experimental models. The aim of this study is to determine maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended dose (RD) of intraperitoneally infused paclitaxel (PTX) with S-1 as a phase I study. Eighteen patients with advanced gastric cancer in addition to confirmed peritoneal metastasis using laparoscopy were enrolled in this study. The regimen consists of oral administration of S-1 (Dose 80 mg: BSA<1.25 m(2), 100 mg: 1.25<BSA<1.5 m(2), 120 mg: BSA>1.5 m(2)) for 14 days and intraperitoneal infusion of PTX (Dose escalation: level I: 40, II: 60, III: 80, level IV: 90, V: 100 mg/m(2)) at day 1 and 14. PTX concentrations in serum and ascites were determined at 4, 8, 12, 24, 48 hours after the infusion, which was repeated twice every 4 weeks. The number of patients were as follows: Level I: 3, Level II: 6, Level III: 3, Level IV: 3, Level V: 3. Grade 3 leukocytopenia was confirmed in 1 (Level II) and 2 (Level V). MTD is 90 mg/m(2), RD is 80 mg/m(2) and DLT is Grade 3 leukocytopenia. The average serum PTX concentrations remained in optimal range except for all 3 of level V patients. In all cohorts, the PTX concentrations in the ascites were approximately 1000 folds higher than those in serum for 48 hours after the infusion. MTD and RD were PTX 90 mg/m(2), 80 mg/m(2), respectively. These findings were supported by pharmocokinetics of PTX.
    The Journal of Medical Investigation 02/2011; 58(1-2):134-9.
  • Article: The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen.
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    ABSTRACT: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but its main dose-limiting toxicity is sensory neuropathy. The OPTIMOX (stop and go) approach offers a reasonable strategy, but the preventive agent is not established. It is reported that the Kampo medicine, Goshajinkigan (GJG), has recently been considered an effective agent for the neuropathy of taxanes and for vibration sensation in patients with diabetic neuropathy. The aim of this study was to clarify the efficacy of GJG for peripheral neuropathy associated with oxaliplatin therapy. From 2007, 45 patients treated with modified FOLFOX6 for non-resectable or recurrent colorectal cancer participated in the study. Twenty-two patients (GJG group) received oral administration of 7.5 g/day of GJG every day during mFOLFOX6 therapy and 23 patients (control group) did not receive GJG. Neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm). The median number of cycles per patient in the GJG group was 13 (range 4-32), and in the control group was 12 (range 4-28). The cumulative dose of oxaliplatin was 1105 mg/m(2) (GJG group) and 1120 mg/m(2) (control group). The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group (p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group, and after 20 courses was 33% in the GJG group and 75% in the control group. The percentage of grade 2 and 3 peripheral neuropathy in the GJG group was lower than that in the control group. There were no differences in adverse effects between the two groups except for peripheral neuropathy and influence on tumor response. The Kampo medicine, Goshajinkigan, is useful in preventing neuropathy in non-resectable or recurrent colorectal cancer patients treated with a FOLFOX regimen.
    International Journal of Clinical Oncology 01/2011; 16(4):322-7. · 1.41 Impact Factor
  • Article: Sonic hedgehog relates to colorectal carcinogenesis.
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    ABSTRACT: The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum. Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group. Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression. This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis.
    Journal of Gastroenterology 09/2009; 44(11):1113-7. · 4.16 Impact Factor
  • Article: Increased risk of lymph node metastasis in mucosal gastric cancer with extra indication for endoscopic mucosal resection.
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    ABSTRACT: Selected cases of clinical mucosal gastric cancer can be treated endoscopically. But mucosal gastric cancer, which has a higher incidence of lymph node metastasis, should be treated by gastrectomy with lymph node dissection. Laparoscopy-assisted gastrectomy is usually indicated for the surgical treatment of mucosal gastric cancer. From April 2005 to December 2007, 148 consecutive patients with clinical mucosal gastric cancer who underwent laparoscopy-assisted gastrectomy were investigated to clarify the clinicopathologic findings in this patient group. Of the patients who underwent gastrectomy, 93 (63%) had tumors>20 mm in diameter and 92 (62%) had undifferentiated cancer. The frequency of lymph node metastasis was 8% (12 patients). One patient had second-compartment lymph node metastasis (station 8a). In patients with lymph node metastasis, 11 (92%) had an ulcer scar and 11 (92%) had undifferentiated tumors. None of the patients met the criteria for extended endoscopic submucosal dissection. The incidence of lymph node metastasis in patients with mucosal gastric cancer in whom gastrectomy is indicated is higher than reported previously. More careful consideration is needed for the possibility of lymph node metastasis in this era of endoscopic submucosal dissection.
    Journal of the American College of Surgeons 06/2009; 208(6):1045-50. · 4.55 Impact Factor
  • Article: Laparoscopic removal of a foreign body in the pelvic cavity through one port using a flexible cholangioscope.
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    ABSTRACT: Background: More than two trocar ports 12 mm in diameter were usually used to remove a foreign body from the peritoneal cavity using laparoscopic surgery. We designed a method of laparoscopic removal through a single port 5 mm in diameter and a flexible cholangioscope. Patients and Methods: The patient had a ventriculoperitoneal shunt (V-P shunt) catheter implanted for hydrocephalus of unknown cause in his 40s. Endoscopic marsupialization of the third ventricle was performed because of functional failure of the V-P shunt catheter 7 years after the implantation. A falling off of the V-P shunt catheter into the pelvic space was detected, and laparoscopic removal of the V-P shunt catheter was performed. A laparoscope was inserted through a trocar port 5 mm in diameter to confirm the location of the V-P shunt catheter following replacement of the flexible cholangioscope to grasp the catheter. The catheter was held using a snare catheter through the cholangioscope. The V-P shunt catheter was removed by pulling through the trocar port with the flexible cholangioscope. Conclusion: Laparoscopic removal is a good technique for removal of a foreign body in the peritoneal cavity. It enables one-port laparoscopic removal using a flexible cholangioscope.
    Digestive surgery 06/2009; 26(3):205-8. · 1.37 Impact Factor
  • Article: Effect of splenectomy on antitumor immune system in mice.
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    ABSTRACT: The influence on the antitumor immune system after splenectomy in vivo are controversial. CD4+CD25+Foxp3+T-cells (regulatory T-cell: reg T) and natural killer (NK) cells play important roles in immunological tolerance and antitumor immunity. The influence of splenectomy on the antitumor immune system was evaluated in a metastasis induced mouse model. Experiment 1, splenectomy in a cancer-free model. The mice were divided into two groups, one control, and the other splenectomy group. At days 4, 7 and 10 after splenectomy, the mesenteric lymph node, the liver and the lung were harvested. The lymph nodes were analyzed by flow cytometric analysis and the number of reg T-cells and NK cells were calculated. Foxp3 mRNA in the liver and the lung was evaluated by reverse transcriptional polymerase chain reaction (RT-PCR). Experiment 2, splenectomy in a liver metastasis model. Colon 26 cells were injected into the spleen of mice and the mice were divided into two groups, a spleen preserved group, and a splenectomy group. Splenectomy was performed at day 4 after injection. At days 7 and 10 after injection, flow cytometric analysis, and at day 10 RT-PCR were performed. Ten days after injection, the number of liver metastases (>1 mm) was counted. Experiment 1, in the splenectomy group the flow cytometric analysis showed a significant decrease in the number of reg T and NK cells in the mesenteric lymph nodes compared with the control group. In the splenectomy group, the Foxp3 mRNA increased significantly in the liver at day 10, and in the lung at days 4 and 7. Experiment 2, liver metastasis was observed in the splenectomy group. Flow cytometric analysis showed that splenectomy did not affect the number of reg T at day 7 and day 10. The number of NK cells increased in the splenctomy group at day 7, but at day 10, there was no significant difference between the groups. RT-PCR showed that at day 10, the Foxp3 mRNA in liver increased in the splenectomy group. The spleen plays a very important role in the antitumor immune system and splenectomy enhances liver metastasis through the increase of Foxp3 mRNA in the liver.
    Anticancer research 02/2009; 29(1):385-93. · 1.73 Impact Factor
  • Article: Kampo medicine "Dai-kenchu-to" prevents bacterial translocation in rats.
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    ABSTRACT: Kampo medicine "Dai-kenchu-to" (DKT) has been used for treatment of ileus. The aim of this study was to evaluate the role of DKT on the bacterial translocation (BT) model in rats. Rats were divided into the following four groups: group 1, receiving only water, and groups 2, 3, and 4, receiving 100, 300, and 1,000 mg/kg/day of DKT. Rats were sacrificed 6 days after the beginning of the fast, and then the mesenteric lymph node was cultured. Inflammatory cytokines, intestinal integrity, and apoptosis were assessed. Incidence of BT in groups 3 (33%) and 4 (16%) was lower than in group 1 (66%). Interferon-gamma expression in groups 2, 3, and 4 was significantly lower than in group 1. Villous height and number of villus in groups 2, 3, and 4 were significantly taller and greater than in group 1. Apoptotic index in groups 2, 3, and 4 was significantly lower than in group 1. This is the first evidence that DKT prevents BT by reducing inflammatory reaction and maintaining intestinal integrity.
    Digestive Diseases and Sciences 08/2008; 53(7):1824-31. · 2.12 Impact Factor
  • Article: Pyrimidine nucleoside phosphorylase and dihydropyrimidine dihydrogenase activities as predictive factors for the efficacy of doxifluridine together with mitomycin C as adjuvant chemotherapy in primary colorectal cancer.
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    ABSTRACT: Pyrimidine Nucleoside Phosphorylase (PyNPase) converts 5'-deoxy-5-fluorouridine (5'-DFUR, doxifluridine) to 5-fluorouracil (5-FU). While this reaction is taking place Dihydropyrimidine Dihydrogenase (DPD) catalyzes 5-FU to inactive molecules. Mitomycin C (MMC) elevates the PyNPase level in tumor cells. We investigated 17 colorectal cancer patients' PyNPase and DPD activities in tumor and normal tissues using an enzyme-linked immunosorbent assay (ELISA) to assess their clinical significance as indicators for selecting colorectal cancer patients for 5'-DFUR together with MMC as adjuvant chemotherapy. Six of 17 patients developed experienced a recurrence. Tumor DPD activity of the 6 patients who had a recurrence were higher than those of the 11 patients with no recurrence (p = 0.047). On the other hand, there were no significant differences in both the PyNPase and the PyNPase/DPD (P/D) ratio between the group with recurrence and the group without recurrence. For survival analyses, we designed the cut-off value of tumor PyNPase, DPD and P/D ratio as their median value and classified patients into a higher group and a lower group, but there were no significant differences between the groups. The DPD activity in the tumor may be a useful indicator for selecting patients likely respond to 5'-DFUR together with MMC as adjuvant chemotherapy. If tumor DPD is high, we had better select a different anticancer drug.
    Hepato-gastroenterology 07/2007; 54(76):1089-93. · 0.66 Impact Factor
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    Article: Squamous cell carcinoma of the descending colon: report of a case and literature review.
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    ABSTRACT: It is very rare that squamous cell carcinoma (SCC) arises from colorectal epithelium. An 89-year-old man was treated in 2001 with chief complaints of anorexia, abdominal pain, and low grade fever. The histological diagnosis as SCC was determined by biopsy during a colonoscopy. We diagnosed primary SCC of the colon because except in the colon no malignant lesions were found by systemic CT. Surgical complete resection was performed. However, he died three months after surgical resection because of hepatic metastasis and cachexia. The prognosis of this disease seems to be worse than that of adenocarcinoma.
    Case Reports in Gastroenterology 01/2007; 1(1):77-83.
  • Article: Predictive factors of peritoneal metastasis in gastric cancer.
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    ABSTRACT: Preoperative radiological diagnosis of gastric cancer with peritoneal metastasis is still incomplete. Staging laparoscopy is performed for patients who are diagnosed T3 or T4 preoperatively. The aim of this study is to establish a method for predicting peritoneal metastasis. 236 gastric cancer patients who were determined histologically at the final staging were studied. We evaluated whether the parameters of preoperative evaluation such as maximum tumor size, circumferential involvement, macroscopic type, number of metastatic lymph nodes and histological differentiation could predict a peritoneal metastasis. The patients with maximum tumor size > 50 mm in diameter, all 4 cross-sectional parts in circumference involved, Type IV tumor, number of metastatic lymph nodes > 3 and histologically undifferentiated type had a significantly higher incidence of peritoneal metastasis, compared with those with other types. Maximum tumor size > 50 mm, all 4 cross-sectional parts involved and type IV were confirmed as independent risk factors by multivariate analysis. A predictive equation "y = 0.018+0.171 (Maximum tumor size > 50 mm)+0.387 (all 4 cross-sectional parts involved)+0.183 (type IV)" was established. When y value was set to 0.5, sensitivity and specificity were 78.3%, 88.5%, respectively. The predictive equation of peritoneal metastasis revealed satisfactory results and can be regarded as useful in diagnosing peritoneal metastasis.
    Hepato-gastroenterology 57(101):980-3. · 0.66 Impact Factor
  • Article: Gene expression profile can predict pathological response to preoperative chemoradiotherapy in rectal cancer.
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    ABSTRACT: Preoperative chemoradiotherapy (CRT) has been widely used to improve local control of disease and to preserve the anal sphincter in the treatment of rectal cancer. However, the response to CRT differs among individual tumors. Our purpose of this study was to identify a set of discriminating genes that can be used for characterization and prediction of response to CRT in rectal cancer. Seventeen rectal cancer patients who underwent preoperative CRT (40 Gy radiotherapy combined with S-1) were studied. Biopsy specimens were obtained from rectal cancer patients before preoperative CRT and were analyzed by focused DNA microarray (132 genes) and immunohistochemistry. Response to CRT was determined by histopathologic examination of surgically resected specimens and patients were classified as responders (grade 2 or 3) or non-responders (grade 0 or 1). Of the 17 samples, 10 were classified as responders and 7 as non-responders. Seventeen genes were differentially expressed at significant levels (p<0.05) between responders and non-responders. All genes showed higher expression in responders as compared with non-responders. The list of discriminating genes included matrix metalloproteinase- (MMP), apoptosis- (nuclear factor kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), transforming growth factor beta 1 (TGFB1)), DNA repair- (topoisomerase 1 (TOP1)), and cell proliferation (integrin, beta 1 (ITGB1))-related genes. In the immunohistochemistry of MMP7, 4 responders were judged as showing overexpression of MMP7. On the other hand, none of the non-responders were judged as showing overexpression of MMP7. Gene expression patterns of diagnostic biopsies can predict pathological response to preoperative CRT with S-1 in rectal cancer.
    Cancer genomics & proteomics. 8(2):87-92.
  • Article: Malignant potential of Barrett's esophagus: special reference to HDAC-1 and MTA-1 expression.
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    ABSTRACT: Barrett's esophagus is a major risk factor for esophageal adenocarcinoma. It is important to decide when and how to treat the patients with Barrett's esophagus (BE). It was reported that HDAC-1 (Histone Deacetylase-1) and MTA-1 (Metastasis-Associated Protein-1) were associated with initiation and progression of cancer. The aim of this study is to assess malignant potential of BE using the expression of HDAC-1 and MTA-1. Seven BE cases with pathological specialized columnar epithelium and CK7/20 in an immunohistochemically positive state were selected from resected specimens of 23 patients with gastro-esophageal junction cancer. The expression of HDAC-1 and MTA-1 protein was evaluated using an immunohistochemical method. All seven cases with Barrett's esophagus were diagnosed as low grade dysplasia. Positive expression of HDAC-1 and MTA-1 was found in 0 out of 7 cases (0%) with normal esophageal epithelium, and 0 out of 7 cases (0%) with normal gastric epithelium. On the other hand, positive expression of both HDAC-1 and MTA-1 was found in 6 out of 7 (85.7%) cases with Barrett's epithelium and 7 out of 7 (100%) cases with gastro-esophageal-junction-cancer, respectively. Positive expression of HDAC-1 and MTA-1 was found even in low grade dysplasia. Therefore, BE with HDAC-1 and MTA-1 expression is considered to be a precancerous lesion re quiring curative treatment.
    Hepato-gastroenterology 58(106):472-6. · 0.66 Impact Factor
  • Article: Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.
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    ABSTRACT: The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.
    Hepato-gastroenterology 59(116):1059-62. · 0.66 Impact Factor
  • Article: Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.
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    ABSTRACT: Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.
    Hepato-gastroenterology 59(116):990-3. · 0.66 Impact Factor
  • Article: Gastric emptying in Billroth-I and Roux-en-Y reconstruction after distal gastrectomy using C-acetate breath test.
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    ABSTRACT: Billroth-I and Roux-en-Y procedures have been applied generally as reconstruction techniques after distal gastrectomy. There have been few reports regarding the physiological differences of these two procedures. We compared gastric emptying after Roux-en-Y procedure with the Billroth-I procedure using the 13C-acetate breath test. Eleven patients who underwent distal gastrectomy, using reconstruction procedures of Billroth- I (B-I group: n=7) and Roux-en-Y (R-Y group: n=6), and 4 healthy volunteers (Control group) were studied. After ingestion of 200mL of liquid diet labelled with 100mg 13C-acetate, breath samples were collected every 5-15 minutes for 3 hours. The analysis of 13C-acetate enrichment was measured using infrared spectrometer. Mean breath-Tmax of B-I group (14.2min) and R-Y group (13.0min) were significantly shorter compared with that of the control group (42.5min). Mean breath-T1/2 of B-I group (76.8min) and R-Y group (80.2min) were significantly shorter compared with that of the control group (133.3min). Mean breath-Cmax of B-I group (60.1min) and R-Y group (59.3min) were significantly higher than that of the control group (27.6min). 13C-acetate breath test was useful to evaluate gastric emptying. There were no differences in gastric emptying for both Billroth-I and Roux-en-Y reconstruction.
    Hepato-gastroenterology 58(112):2020-3. · 0.66 Impact Factor