Takahiro Hiratsuka

Establishment of new predictive markers for distant recurrence of colorectal cancer using lectin microarray analysis

We evaluated the clinical benefits of novel predictive markers for distant recurrence with colorectal cancer using lectin microarray analysis of cell surface glycan modifications. Glycoproteins were extracted from formalin‐fixed, paraffin‐embedded tumor specimens and normal epithelium from 53 consecutive curatively resected stage I–III colorectal cancer cases and then subjected to lectin microarray to obtain lectin–glycan interaction (LGI) values. In addition, clinicopathological factors associated with distant recurrence were identified. LGI values that were associated with distant recurrence were validated with an additional 55 curatively resected stage II colorectal cancer cases. LGI values for Agaricus bisporus (ABA) lectin, prominent in cancer tissues, were statistically associated with distant recurrence. ABA lectin staining exhibited strikingly intense signals in the cytoplasm and apical surfaces of cancer cells, while weak staining was observed in the supranuclear regions of normal epithelium. This ABA tumor/normal LGI ratio may be a new predictive biomarker for distant recurrence of curatively resected colorectal cancer.

Phototherapy with artificial light suppresses dextran sulfate sodium‐induced colitis in a mouse model

Medical treatment for inflammatory bowel disease (IBD) requires chronic administration and causes side effects. Recently, anti‐inflammatory effects of phototherapy were reported in animal models. The present study evaluated whether phototherapy improves dextran sulfate sodium (DSS)‐induced colitis in a mouse model of IBD.

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.

A Comparison of Laparoscopic and Open Surgery Following Pre-operative Chemoradiation Therapy for Locally Advanced Lower Rectal Cancer

OBJECTIVE Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination. METHODS We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses. RESULTS In total, 33 patients were enrolled (open surgery group, n = 14; laparoscopic surgery group, n = 19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra--operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group. CONCLUSIONS This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery.

Anti-proliferation effect of blue light-emitting diodes against antibiotic-resistant Helicobacter pylori : Blue LED against H. pylori

Infection by Helicobacter pylori is implicated in a wide range of upper gastrointestinal diseases. Owing to the rapid emergence of antibiotic‐resistant strains of H. pylori, the development of novel treatment modalities for antibiotic‐resistant H. pylori infection is a key priority. Blue light‐emitting diodes (LED) may represent a unique option owing to their antimicrobial effect. In this study, we aimed to evaluate the anti‐proliferative effect of blue LED against antibiotic‐resistant H. pylori.

Serosal and muscular layers incision technique in laparoscopic surgery for gastric gastrointestinal stromal tumors.

To minimize the resection of stomach tissue, especially for lesions close to the esophagogastric junction or pyloric ring, we developed laparoscopic wedge resection with the serosal and muscular layers incision technique (SAMIT) for gastric gastrointestinal stromal tumors.

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.

Long-term outcomes of neoadjuvant-synchronous S-1 plus radiotherapy for locally advanced rectal cancer: a multi-institutional prospective phase II study

Objectives: This study aimed to evaluate the long-term outcomes of neoadjuvant chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. Methods: A multi-institutional, prospective, phase II trial was conducted between April 2009 and August 2011. The study enrolled 37 patients with histologically proven rectal carcinoma (T3-4 N0-3 M0) who underwent neoadjuvant chemoradiotherapy with S-1. Total mesorectal excision with D3 lymphadenectomy was performed 4-8 weeks after completion of neoadjuvant chemoradiotherapy with S-1 in 36 patients. We then analyzed late adverse events, overall survival, and disease-free survival. Results: The median patient age was 59 years (range: 32-79 years); there were 24 men and 13 women. Ten patients had Stage II disease, and 27 had Stage III disease. Severe late adverse events occurred in 7 patients (18.9%). The 5-year disease-free survival was 66.7%, and the 5-year overall survival was 74.7%. The median follow-up period was 57 months. Local recurrences developed in 5 patients (13.5%), and distant metastases developed in 8 (21.6%). Conclusion: Neoadjuvant-synchronous chemoradiotherapy with S-1 for locally advanced rectal cancer is feasible in terms of adverse events and long-term outcomes. (UMIN Clinical Trial Registry: UMIN000003396)

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.

Short- and long-term outcomes of neoadjuvant-synchronus S-1+radiotherapy for locally advanced rectal cancer: Multicenter phase II study.

720 Background: Fluorouracil-based chemoradiotherapy (CRT) is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug S-1. Methods: A multi-institutional (17 specialized centers), interventional phase II trial, was conducted from April 2009 to August 2011. For inclusion, patients must fulfill the following requirements before neoadjuvant CRT: (i) histologically proven rectal carcinoma; (ii) tumor located in the rectum (upper, lower); (iii) cancer classified as T3-4, N0–3 and M0; Two cycles of neoadjuvant CRT with S-1 (100 mg/m2 on days 1-5, 8-12, 22-26, and 29-33) was administered, and irradiation (total 45Gy/25fr, 1.8Gy/day, on days 1-5, 8-12, 15-19, 22-26, and 29-33) was performed. Total mesorectal excision was performed during the 4th and 8th week after the end of the neoadjuvant CRT. The primary endpoint is rate of complete treatment of neoadjuvant CRT. Secondary endpoints are response ...