Yohei Kono

Transrectal peritoneal access with the submucosal tunnel technique in NOTES: a porcine survival study

BackgroundNatural orifice transluminal endoscopic surgery (NOTES) procedures have been performed via transgastric, transvaginal, or transcolonic approaches. However, the transcolonic approach has potential disadvantages including intraperitoneal infection. To avoid such disadvantages, we applied the submucosal tunnel technique to transrectal peritoneal access in this study. Study aims are to clarify the technical feasibility of a submucosal tunnel method for transrectal abdominal access and to assess the healing process of the submucosal tunnel histopathologically.MethodsThe study comprised six female pigs. The following procedures were performed: (1) The mucosa was cut after injection of sodium hyaluronate into the submucosa at the upper rectum. (2) Submucosal tunneling was performed by endoscopic submucosal dissection technique. (3) A small incision was made at the end of the tunnel. (4) After transrectal peritoneoscopy, the mucosal incision site was closed with endoclips.ResultsTransrectal peritoneoscopy was successfully performed in all pigs. Necropsy revealed no findings of peritonitis. Histopathologic examination showed good healing of the submucosal tunnel. The wound healing process of the submucosal tunnel on postoperative day 7 was mainly in the inflammatory phase at the mucosal incision site, the proliferative phase at the submucosal tract, and the proliferative/remodeling phase at the seromuscular incision site.ConclusionsThe submucosal tunnel technique appears to be useful and safe for transrectal peritoneal access because healing at the seromuscular incision site proceeded rapidly.

Long-term outcomes of laparoscopic wedge resection for gastrointestinal stromal tumors of the stomach of less than 5 cm in diameter.

Background Few long-term results of laparoscopic resection for gastrointestinal stromal tumors (GISTs) of the stomach have been established to evaluate technical safety and oncologic feasibility. Methods Between April, 1998 and October, 2008, data of 18 patients who underwent laparoscopic resection of GISTs of <5 cm in diameter were reviewed. Results There were 10 men and 8 women with average age of 66.5 years. Estimated blood loss was minimal, and average operation time was 99.2±30.5 minutes. There were no major intraoperative complications or conversions to open approach. Oral feeding started 2 to 4 days after operation, and the mean hospital stay was 10.1±5.5 days. There were no major postoperative complications except for 1 patient who suffered from aspiration pneumonia. Tumor size was 3.7±1.1 cm (range, 1.5 to 7.0 cm), and all patients had free surgical margins. During long-term follow-up (average 54.6 mo), no complications occurred except for liver metastasis in only 1 patient who was responding well to imatinib therapy. Conclusions Laparoscopic wedge resection of GISTs of <5 cm in diameter is a safe and oncologically feasible technique offering good long-term outcomes.

Antiproliferative effects of a new α-lipoic acid derivative, DHL-HisZnNa, in HT29 human colon cancer cells in vitro

Objective: α-Lipoic acid has been reported to induce apoptosis in several cancer cell lines. However, it is prone to oxidation, polymerization and desulfurization, and is insoluble in water. In this study an α-lipoic acid derivative, sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), was synthesized, which can eliminate active oxygen species. The antiproliferative effects of DHL-HisZnNa, on human colon cancer cell HT29 in vitro, were evaluated. Methods: Whether DHL-HisZnNa elicits its antiproliferative effects by inducing apoptosis and cell cycle arrest, was investigated. Expressions of cell-cycle-related proteins and their phosphorylation on HT-29 was also analyzed. Results: DHL-HisZnNa inhibited cancer cell growth in cultures. Cell cycle analysis by flow cytometry showed time-dependent accumulation of HT-29 cells in G1 phase after exposure to DHL-HisZnNa. Analysis of DNA fragmentation did not reveal evidence of apoptosis after exposure to DHL-HisZnNa. Cells treated with DHL-HisZnNa showed an increase in p53 phosphorylation with the Bio-Plex Phosphoprotein assay. DHL-HisZnNa increased protein levels of the cyclin-dependent kinase inhibitor p21 and decreased that of phosphorylated retinoblastoma protein (Rb) by western blot analysis. Results obtained with DHL-HisZnNa are on a single colon cancer cell line and not comparative experiments with α-lipoic acid. Conclusions: This is the first study, to our knowledge, to report the antiproliferative effects of DHL-HisZnNa and the molecular mechanisms by which it inhibits growth of HT29.

Surgical Outcomes of Laparoscopic Versus Open Abdominoperineal Resection for Anorectal Cancer: A Comparative Study

Introduction: There has been no large, randomized prospective trial and few retrospective studies to clarify the surgical outcomes of laparoscopic abdominoperineal resection (Lap-APR) for anorectal cancer. The aim of this study was to clarify the surgical outcomes of Lap-APR for anorectal cancer. Methods: A consecutive series of 39 patients who underwent abdominoperineal resection for anorectal cancer was studied: 24 underwent Lap-APR, and 15 open abdominoperineal resection (Open-APR). Patient characteristics, tumor characteristics and operative outcomes were compared between the groups. Results: There were no significant differences between the groups in patient and tumor characteristics.The mean number of harvested nodes in the Lap-APR group was significantly more than that in the Open-APR group (11.8 ± 8.7 vs.7.6 ± 3.6, p=0.046). Although the mean operation time was similar in the two groups (372.1 ± 79.0 vs.402.7 ± 118.4 min, N.S), the mean blood loss in the Lap-APR group was significantly less than that in the Open-APR group (244.6 ± 175.0 vs.795.3 ± 544.9 g, p=0.002). Additionally, time to start oral intake of solid foods and time to first education of stoma management were significantly less after Lap-APR than Open-APR. Conclusion: Lap-APR offered particular advantages to patients with anorectal cancer,including less blood loss, rapid oral intake of solid foods and education of stoma care.

Clinical impact of laparoscopic intersphincteric resection following neoadjuvant chemoradiotherapy for locally advanced rectal cancer: case-controlled study

Background: Recently, laparoscopic (Lap) intersphincteric resection (ISR) for low-lying rectal cancer is gradually permeating worldwide. However, the usefulness of Lap-ISR after neoadjuvant chemoradiotherapy (NCRT) has not been clarified. This retrospective study aimed to evaluate the feasibility of Lap-ISR after NCRT for locally advanced low-lying rectal cancer. Methods: Fourteen patients with primary locally low-lying rectal cancer were enrolled in this study and underwent curative Lap-ISR between January 2008 and December 2011. Seven patients underwent Lap-ISR after NCRT (NCRT group) and seven patients underwent Lap-ISR without NCRT (non-NCRT group). Patient characteristics, short-term outcomes, postoperative anal function, and long-term oncological outcomes were evaluated and compared between the groups. Results: The tumor diameter was significantly larger in the NCRT group than the non-NCRT group (38±7 and 28±9 mm, respectively; P=0.04) and cStage was significantly more advanced in the NCRT group than the non-NCRT group (P=0.02). There were no significant differences in operative data or postoperative course between the groups. The Wexner score measured 5 years after initial surgery was significantly higher the NCRT group than the non-NCRT group (8.8±4.1 and 4.6±1.9, respectively; P=0.04). There were no significant differences in local recurrence rate, distant recurrence rate, or cancer-specific death rate between the two groups (median follow-up period was 60 months). Conclusions: Lap-ISR after NCRT is a feasible treatment option based on short-term outcomes, long-term oncological outcomes, and postoperative anal function. These data suggest that Lap-ISR after NCRT may be an appropriate treatment option for locally advanced low-lying rectal cancer.

Effect of the new synthetic vitamin E derivative ETS-GS on radiation enterocolitis symptoms in a rat model

Radiation enterocolitis is a severe adverse event that occurs after radiotherapy for malignant abdominal tumors. In this study, the therapeutic effects of ETS-GS, a novel vitamin E derivative with antioxidative and anti-inflammatory abilities, were examined in a rat model of radiation enterocolitis. The radiation enterocolitis model was created by irradiation of male rats with a single dose of 10 Gy. ETS-GS was administered subcutaneously (10 mg/kg/day) for five consecutive days from two days prior to irradiation. The animals were sacrificed three days after irradiation; following which, ileal tissue samples were analyzed for macroscopic and histological findings, presence of apoptosis, degree of oxidative stress and inflammation. In the irradiated group, severe erosion was observed in the small intestine in addition to necrosis of the mucosal layer, swelling and invasion of inflammatory cells of the submucosal layer, and shortening of the crypts. In irradiated rats that received ETS-GS, mucosal injury in the small intestine was milder compared with that of irradiated rats that received no ETS-GS. In addition, ETS-GS decreased apoptosis in the small intestine and reduced the activity of myeloperoxidase and malondialdehyde, which are markers for inflammation and oxidative stress. ETS-GS with antioxidant activity has a therapeutic effect on the symptoms of radiation enterocolitis in a rat model.