Kentaro Nakajima

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.

Quality Control by Photo Documentation for Evaluation of Laparoscopic and Open Colectomy with D3 Resection for Stage II/III Colorectal Cancer: Japan Clinical Oncology Group Study JCOG 0404

OBJECTIVE The quality of surgery with D3 resection in randomized controlled clinical trial [Japan Clinical Oncology Group study (JCOG0404)] was assessed by evaluation of the photo documentation of both open and laparoscopic surgeries. METHODS A multi-institutional randomized-controlled trial (JCOG0404) was conducted to evaluate open and laparoscopic D3 resection (complete mesocolic excision + ligation and dissection at the root of the main vessels) for Stage II/III colon cancer (UMIN-CTR number C000000105). A total of 1057 (open, 528; laparoscopic, 529) eligible patients were enrolled. For quality control, it was ensured that the surgeries were performed by accredited surgeons, and a central committee reviewed each surgery on the basis of the submitted photographs of the resected field, specimen and skin incision. RESULTS For right-sided tumors, the rate of D3 resection was 98.5% (131/133) in the open arm and 100% (136/136) in the laparoscopic arm, and for left-sided tumors, they were 97.9% (322/329) and 98.2% (320/326), respectively. Sufficient length of the resected longitudinal margin was ensured in all cases. The skin incisions made in all the cases were <8 cm as defined in the protocol in laparoscopic arm. CONCLUSIONS Completion of high quality surgery with D3 resection was confirmed in JCOG0404 by central peer review of photographs of the surgical procedures in addition to operator regulations. This study suggests that the central review of the photo documentation is one of the important tools to assure a quality control of surgical technique in the Phase III randomized-controlled study.

Prospective Feasibility Study to Evaluate Neoadjuvant-synchronous S-1 + RT for Locally Advanced Rectal Cancer: A Multicenter Phase II Trial (UMIN ID: 03396)

In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. However, in Japan, the treatment results without preoperative chemoradiotherapy are by no means inferior; therefore, extrapolation of the results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative chemoradiotherapy with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy using S-1 in patients with locally advanced rectal cancer. The primary endpoint is the rate of complete treatment of neoadjuvant chemoradiotherapy. Secondary endpoints are the response rate of neoadjuvant chemoradiotherapy, short-term clinical outcomes, rate of curative resection and pathological evaluation. The short-term clinical outcomes are adverse events of neoadjuvant chemoradiotherapy and surgery-related complications. Thirty-five patients are required for this study.

Decreased expression of Bauhinia purpurea lectin is a predictor of gastric cancer recurrence

PurposeMolecular markers as indicators for gastric cancer recurrence are urgently required. The aim of this study was to identify lectins that can be used to predict gastric cancer recurrence after gastrectomy.MethodsWe created lectin expression profiles by microarray analysis for 60 patients, who underwent surgery for gastric cancer at the Oita University Hospital between January, 2005 and December, 2007. Lectin expression and clinicopathological factors in patients who suffered gastric cancer recurrence and those who did not were compared by univariate and multivariate analyses.ResultsThirteen lectins showed a significant increase in binding to cancer tissues, whereas 11 lectins showed a significant decrease in binding to cancer tissues, when compared with binding to normal epithelia. Multivariate analysis revealed that lymph node metastasis and low Bauhinia purpurea lectin (BPL)-binding signals were independent predictive factors for recurrence. All patients with low BPL expression had significantly worse relapse-free survival than those with high BPL expression.ConclusionsOur results using a novel lectin microarray system provide the first solid evidence that BPL expression is a predictor of gastric cancer recurrence.

Rectoseminal vesicle fistula as a rare complication after low anterior resection: a report of three cases

A rectoseminal vesicle fistula is a rare complication after a low anterior resection for rectal cancer, usually developing in the outpatient postoperative period with pneumaturia, fever, scrotal swelling or testicular pain. A diagnostic water-soluble contrast enema, cystography and computed tomography reveal a tract from the rectum to the seminal vesicle. Anastomotic leakage is thought to be partially responsible for the formation of such tracts. This report presents three cases of rectoseminal vesicle fistula, and the presumed course of the disease and optimal treatment options are discussed.

Secondary myelodysplastic syndrome after small cell lung cancer and esophageal cancer

Abstract  A 50‐year‐old man was referred to our department with esophageal cancer. He had past history of small cell lung cancer treated with chemoradiation therapy 10 years prior. The disease was evaluated as complete remission after chemoradiation therapy and no recurrence had been observed. Esophagectomy accompanying postoperative chemotherapy was applied, but he died of secondary myelodysplastic syndrome with its acute myeloblastic transformation. Risk evaluation revealed a high incidence of esophageal cancer after radiation therapy and hematological malignancies after chemoradiation therapy in usual regimen with topoisomerase inhibitor or alkylating agents. Chemoradiation therapy is thought to be one of a few highly effective therapeutic alternatives and many complete remission cases have been reported in small cell lung cancer or esophageal cancer. In post‐therapeutic follow up of patients with such past therapeutic histories, we should be cautious about secondary malignancies even if primary malignant disease was evaluated as complete remission in long past history.

Perforated duodenal ulcer associated with an incarcerated hiatal hernia: Report of a case

Abstract.We report the case of a perforated duodenal ulcer and diffuse peritonitis associated with an incarcerated hiatal hernia. A 77-year-old woman with a 17-year history of rheumatoid arthritis treated with nonsteroidal anti-inflammatory drugs, who had also been receiving treatment for non-Hodgkins lymphoma over 4 years, was referred to us for investigation of nausea and vomiting. An abdominal compute tomography (CT) scan showed an incarcerated hiatal hernia and free air in the hernia sac. Emergency laparotomy revealed an incarcerated hiatal hernia involving the stomach, transverse colon, and omentum. A perforated ulcer was also found in the posterior wall of the first portion of the duodenum. The combination of these disorders is thought to be rare in patients with a hiatal hernia and free air in its sac. As the reported mortality of perforated gastric ulcer associated with a hiatal hernia is high, early elective surgery should be performed in patients with a duodenal ulcer associated with a hiatal hernia.

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.

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 ...