Johji Hara

Osaka University, Suika, Ōsaka, Japan

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Publications (6)18.43 Total impact

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    ABSTRACT: The relationship between the epithelial-mesenchymal transition (EMT) and resistance to anticancer treatment has attracted attention in recent years. However, to date, there is no direct clinical evidence for a link between the mesenchymal phenotype and chemoresistance in human malignancies. The expression of EMT-related markers, including E-cadherin, Snail, vimentin, ZEB1, β-catenin and N-cadherin was examined immunohistochemically in 185 tissue samples from patients with esophageal cancer (including 93 patients who received preoperative chemotherapy followed by surgery and 92 patients who underwent surgery without preoperative therapy). The relationship between the expression of the above markers and clinical outcome including prognosis and response to chemotherapy was also examined. The expression of E-cadherin, a marker of epithelial cells, was significantly lower in residual tumors than chemo-naive tumors (P=0.003). The expression of Snail (P=0.028), ZEB1 (P<0.001) and N-cadherin (P=0.001), markers of mesenchymal cells, was higher in residual tumors than in chemonaive tumors. The expression of E-cadherin correlated inversely with that of Snail (P<0.001). Reduced expression of E-cadherin and increased expression of Snail in residual tumors from patients who received chemotherapy correlated significantly with poor response to chemotherapy and short survival time. Multivariate analysis identified Snail expression as an independent prognostic factor, along with tumor depth, in patients who received preoperative chemotherapy for esophageal cancer. The results suggest transition of residual esophageal cancer cells to mesenchymal phenotype after chemotherapy and this contributes to resistance to chemotherapy and poor prognosis in patients with esophageal cancer.
    Oncology Reports 11/2013; · 2.30 Impact Factor
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    ABSTRACT: A 5-cm gastric submucosal tumor was incidentally found through abdominal CT as a preoperative work-up for hysterectomy in a 62-year-old woman with uterine prolapse. NOTES using a flexible gastrointestinal endoscope via the transvaginal route was indicated to accomplish concomitant partial gastrectomy and hysterectomy. Perigastric dissection was performed, followed by stapled partial gastrectomy using transvaginal NOTES technique with two transabdominal ports. The specimen was delivered transvaginally by enlarging the initial vaginal entry site. Vaginal hysterectomy was then accomplished by utilizing the enlarged vaginal wound. The patient showed rapid and uneventful postoperative recovery without any narcotic need. No complication was noted, her cosmetic result was satisfactory, and there was complete resolution of preoperative gynecological symptoms. Female patients with concomitant gastrointestinal and gynecological conditions requiring large specimen retrieval would potentially be suitable candidates for the transvaginal NOTES approach.
    Asian Journal of Endoscopic Surgery 11/2012; 5(4):168-71.
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    ABSTRACT: BACKGROUND: It remains uncertain whether radical lymphadenectomy combined with total gastrectomy actually contributes to long-term survival for Siewert type II adenocarcinoma of the cardia. We identified the pattern of abdominal nodal spread in advanced type II adenocarcinoma and defined the optimal extent of abdominal lymphadenectomy. METHODS: Eighty-six patients undergoing R0 total gastrectomy for advanced type II adenocarcinoma were identified from the gastric cancer database of 4,884 patients. Prognostic factors were investigated by multivariate analysis. The therapeutic value of lymph node dissection for each station was estimated by multiplying the incidence of metastasis by the 5-year survival rate of patients with positive nodes in each station. RESULTS: The overall 5-year survival rate was 37.1 %. Age less than 65 years [hazard ratio, 0.455 (95 % confidence interval (CI), 0.261-0.793)] and nodal involvement with pN3 as referent [hazard ratio for pN0, 0.129 (95 % CI, 0.048-0.344); for pN1, 0.209 (95 % CI, 0.097-0.448); and for pN2, 0.376 (95 % CI, 0.189-0.746)] were identified as significant prognosticators for longer survival. Perigastric nodes of the lower half of the stomach in positions 4d-6 were considered not beneficial to dissect, whereas there were substantial therapeutic benefits to dissecting the perigastric nodes of the upper half of the stomach in positions 1-3 and the second-tier nodes in positions 7 and 11. CONCLUSIONS: Limited lymphadenectomy attained by proximal gastrectomy might suffice as an alternative to extended lymphadenectomy with total gastrectomy for obtaining potential therapeutic benefit in abdominal lymphadenectomy for advanced Siewert type II adenocarcinoma.
    Gastric Cancer 08/2012; · 3.99 Impact Factor
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    ABSTRACT: When the gastric submucosal tumor (SMT) locates adjacent to the esophagogastric junction (EGJ), it is difficult to preserve EGJ technically and oncologically. In this study, we describe our clinical experience with laparoscopic intragastric surgery (LIGS) and discuss its role for gastric SMTs adjacent to EGJ. A retrospective review was performed on patients who underwent surgical treatment of gastric SMTs adjacent to EGJ (April 1994 to May 2010). They were divided into 3 groups: laparoscopic partial gastrectomy (LAP, n=10), LIGS (n=10), and open laparotomy (OPEN, n=7), respectively. The completion rates were 50% in LAP and 90% in LIGS. Overall preservation rate of EGJ was 80% (LAP), 100% (LIGS), and 29% (OPEN), respectively. The patients who underwent total/proximal mastectomy showed significantly higher incidence of postoperative gastrointestinal symptoms, which required long-term medication. LIGS stays as a valuable alternative and would be an attractive option for gastric SMTs adjacent to EGJ.
    Surgical laparoscopy, endoscopy & percutaneous techniques 06/2012; 22(3):251-4. · 0.88 Impact Factor
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    ABSTRACT: To determine the relationship between resistance to chemotherapy and microRNA (miRNA) expression in esophageal cancer, we focused on miRNAs known to be associated with maintenance of stem cell function. Using 98 formalin-fixed, paraffin-embedded samples obtained from patients with esophageal cancer who had received preoperative chemotherapy followed by surgery, we measured expression levels of several miRNAs that are considered to be involved in the regulation of stem cell function (e.g., let-7a, let-7g, miR-21, miR-134, miR-145, miR-155, miR-200c, miR-203, and miR-296) by real-time reverse transcriptase PCR. Then, we examined the relationship between miRNA expression and prognosis or response to chemotherapy. To investigate the mechanism of miRNA-induced chemoresistance, in vitro assays were carried out using esophageal cancer cells. Analyses of the 9 miRNAs expression showed that overexpression of miR-200c (P = 0.037), underexpression of miR-145 (P = 0.023), and overexpression of miR-21 (P = 0.048) correlated significantly with shortened overall duration of survival. In particular, miR-200c expression correlated significantly with response to chemotherapy (P = 0.009 for clinical response; P = 0.007 for pathologic response). In vitro assay showed significantly increased miR-200c expression in cisplatin-resistant cells compared with their parent cells (∼1.7-fold). In anti-miR-200c-transfected cells, chemosensitivity to cisplatin and apoptosis after exposure to cisplatin was found to increase as compared with the negative control. Western blotting showed that knockdown of miR-200c expression was associated with increased expression of PPP2R1B, a subunit of protein phosphatase 2A, which resulted in reduced expression of phospho-Akt. Results of this study emphasized the involvement of miR-200c in resistance to chemotherapy among esophageal cancers and that this effect was mediated through the Akt pathway.
    Clinical Cancer Research 01/2011; 17(9):3029-38. · 7.84 Impact Factor
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    ABSTRACT: Transvaginal endoscopic gastric surgery is one of the cutting edge procedures in the field of natural orifice translumenal endoscopic surgery (NOTES). Its feasibility has been shown sporadically in bariatric cases but not in oncologic conditions. The authors report their early experience with hybrid transvaginal NOTES gastrectomy for gastric submucosal tumors (SMTs). Two female patients with SMTs in the distal stomach participated in this institutional review board (IRB)-approved study. Surgical indication was determined according to the National Comprehensive Cancer Network (NCCN) sarcoma guidelines, and the study adhered to the following oncologic principles: no direct handling of the lesion, full-thickness resection, and reasonable surgical margins. The study protocol required a minimum of two laparoscopic ports to ensure procedural safety and aforementioned oncologic appropriateness. Under laparoscopic guidance, a transvaginal route was created and secured with a 50-cm flexible overtube. A gastrointestinal endoscope was introduced, and the perigastric dissection was performed using an insulation-tipped diathermy knife (IT knife) and needle knife. This process was assisted with two laparoscopic graspers. After perigastric mobilization, the transvaginal endoscope was replaced with a digital stapling device, and partial gastrectomy was accomplished. The resected specimen was isolated and delivered through the vagina, and the vaginal wound was closed under direct vision. Outcomes measurements included surgical results, pain scoring, and clinical outcomes. Both operations were completed successfully in compliance with the aforementioned oncologic principles. The operating time was 365 and 170 min, respectively. The estimated blood loss was negligible. A minilaparotomy for specimen delivery was successfully avoided in both cases. A minimal vaginal incision was added for one patient at retrieval. Postoperatively, both patients reported no pain and recovered rapidly. The final diagnosis was hemorrhagic lipoma and gastrointestinal stromal tumor (GIST), respectively. Our initial experience with human transvaginal NOTES gastrectomy showed it to be feasible and safe for gastric SMTs. It is a complex but promising surgical alternative for female oncologic patients undergoing partial gastric resection.
    Surgical Endoscopy 05/2009; 23(12):2650-5. · 3.43 Impact Factor

Publication Stats

92 Citations
18.43 Total Impact Points

Institutions

  • 2012–2013
    • Osaka University
      • Division of Gastroenterological Surgery
      Suika, Ōsaka, Japan
    • Osaka National Hospital
      Ōsaka, Ōsaka, Japan
  • 2009–2012
    • Osaka City University
      • Department of Gastroenterological Surgery
      Ōsaka, Ōsaka, Japan