Second primary cancers and recurrence in patients after resection of colorectal cancer: An integrated analysis of trials by Japan Clinical Oncology Group: JCOG1702A.

BACKGROUND: Improvements in early detection and treatment have resulted in an increasing number of long-term survivors of colorectal cancer (CRC). For the survivors, second primary cancer and recurrence are important issues; however, evidence for an appropriate surveillance strategy remains limited.This study aimed to investigate the frequency and timing of second primary cancer in patients after surgery for exploring an appropriate surveillance strategy by using an integrated analysis of three large-scale randomized controlled trials in Japan. METHODS: The eligibility criteria of three trials included histologically confirmed CRC and having received surgery. The timing, site and frequency of second primary cancers and recurrence were investigated. Risk factors associated with second primary cancers were also examined. The standardized incidence ratio (SIR) of second primary cancers compared with the national database of the Japan Cancer Registry was estimated. RESULTS: A total of 2824 patients were included in this study. The cumulative incidence of second primary cancer increased over time. The SIR of any second primary cancer was 1.07 (95% CI: 0.94-1.21). The SIR for second primary cancers of colon was 1.09 (95% CI: 0.79-1.47). The cumulative incidence of recurrence almost reached plateau at 3 years. CONCLUSIONS: A common surveillance strategy for the general population can be applied even for curatively resected CRC patients, as the risk of second primary cancers was almost the same as that of the general population.

Development of Endoscopic Surgery Navigated by Artificial Intelligence.

Endoscopic surgery, which was first introduced in the late 1980s, has rapidly become widespread. However, despite its popularity, the occurrence of intraoperative organ damage has not necessarily decreased. To avoid intraoperative bile duct injury in laparoscopic cholecystectomy, which is one of the most popular procedures in endoscopic surgery, we are developing a laparoscopic surgical system that uses Artificial Intelligence (AI) to identify four anatomical landmarks (cystic duct of the gallbladder, common bile duct, lower surface of hepatic S4, and Rouviere's sulcus, related to "Calot's triangle") in real time during surgery. The development process consists of 5 steps: 1) identification of anatomical landmarks, 2) collection and creation of teaching data, 3) annotation and deep learning, 4) validation of development model, and 5) actual clinical performance evaluation. At present, anatomical landmarks can be identified with high accuracy in an actual clinical performance test in laparoscopic cholecystectomy, whereas issues for practical clinical use, such as a need to recognize the scene of surgical steps and surgical difficulties related to inflammation of the gallbladder, have also been clarified. The development of an AI-navigation system for endoscopic surgery, which could identify anatomical landmarks in real time during surgery, could be expected to support surgeons' decisions, reduce surgical complications, and contribute to improving the quality of surgical treatments.

Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements).

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.

The utility of DHL-HisZnNa, a novel antioxidant, against anticancer agent-induced alopecia in breast cancer patients: a multicenter phase II clinical trial.

PURPOSE: Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of anticancer drugs; however, there are currently no mechanisms to completely prevent CIA. In this study, we performed a clinical trial to examine whether sodium N-(dihydrolipoyl)-l-histidinate zinc complex (DHL-HisZnNa), an alpha-lipoic acid derivative, prevents CIA in patients with breast cancer. METHODS: Between July 2014 and May 2015, we performed a multi-center, single arm, clinical trial involving 103 breast cancer patients who received adjuvant chemotherapy at three medical institutions in Japan. During chemotherapy, a lotion containing 1% DHL-HisZnNa was applied daily to the patients' scalps. The primary endpoint was the incidence of grade 2 alopecia; the secondary endpoints were the duration of grade 2 alopecia, alopecia-related symptoms, and drug-related adverse events. Alopecia was evaluated by three independent reviewers using head photographs taken from four angles. RESULTS: Safety analysis was performed for 101 patients who started the protocol therapy. After excluding one patient who experienced disease progression during treatment, 100 patients who received at least two courses of chemotherapy underwent efficacy analysis. All original 101 patients developed grade 2 alopecia, the median durations of which were 119 days (112-133 days) and 203 days (196-212 days) in the groups treated with four and eight courses of chemotherapy, respectively. Mild or moderate adverse events potentially related to DHL-HisZnNa were observed in 11 patients. Alopecia-related symptoms were observed in 53 patients (52%). CONCLUSIONS: The application of 1% DHL-HisZnNa to the scalp did not prevent CIA. However, this drug may promote recovery from CIA. TRIAL REGISTRATION NUMBER: UMIN000014840.

Introducing laparoscopic total gastrectomy for gastric cancer in general practice: a retrospective cohort study based on a nationwide registry database in Japan.

BACKGROUND: Although laparoscopic total gastrectomy (LTG) is considered a technically demanding procedure with safety issues, it has been performed in several hospitals in Japan. Data from a nationwide web-based data entry system for surgical procedures (NCD) that started enrollment in 2011 are now available for analysis. METHODS: A retrospective cohort study was conducted using data from 32,144 patients who underwent total gastrectomy and were registered in the NCD database between January 2012 and December 2013. Mortality and morbidities were compared between patients who received LTG and those who underwent open total gastrectomy (OTG) in the propensity score-matched Stage I cohort and Stage II-IV cohort. RESULTS: There was no significant difference in mortality rate between LTG and OTG in both cohorts. Operating time was significantly longer in LTG while the blood loss was smaller. In the Stage I cohort, LTG, performed in 33.6% of the patients, was associated with significantly shorter hospital stay but significantly higher incidence of readmission, reoperation, and anastomotic leakage (5.4% vs. 3.6%, p < 0.01). In the Stage II-IV cohort, LTG was performed in only 8.8% of the patients and was associated with significantly higher incidence of leakage (5.7% vs. 3.6%, p < 0.02) although the hospital stay was shorter (15 days vs. 17 days, p < 0.001). CONCLUSION: LTG was more discreetly introduced than distal gastrectomy, but remained a technically demanding procedure as of 2013. This procedure should be performed only among the well-trained and informed laparoscopic team.

Surgical risk and benefits of laparoscopic surgery for elderly patients with gastric cancer: a multicenter prospective cohort study.

BACKGROUND: Laparoscopic gastrectomy (LG) might have greater clinical benefits for elderly patients as less invasive surgery; however, there is still little evidence to support its benefit. We evaluated the surgical outcomes of elderly patients in a nationwide prospective cohort study. METHODS: One hundred and sixty-nine participating institutions were identified by stratified random sampling, and were adjusted for hospital volume, type and location. During 1 year from 2014 to 2015, consecutive patients who underwent gastrectomy for gastric cancer were prospectively enrolled. 'Elderly' was defined as ≥ 75 years of age, based on the prevalence of comorbidities and the activities of daily living of patients of this age. We compared the surgical outcomes of LG to those of open gastrectomy (OG) in non-elderly and elderly patients. The primary outcome was the incidence of severe morbidities (Grade ≥ 3). RESULTS: Eight thousand nine hundred and twenty-seven patients were enrolled [non-elderly, n = 6090 (OG, n = 2602; LG, n = 3488); elderly, n = 2837 (OG, n = 1471; LG, n = 1366)]. Grade ≥ 3 complications occurred in 161 (10.9%) patients who underwent OG and 98 (7.2%) who underwent LG (p < 0.001). After adjusting for confounding factors, we confirmed that laparoscopic surgery was not an independent risk factor (odds ratio = 0.81, 0.60-1.09). OG was associated with a significantly longer median length of postoperative stay in comparison to LG (16 versus 12 days, p < 0.001). There were no significant differences in the incidence of other postoperative comorbidities. CONCLUSION: The safety of LG in elderly patients was demonstrated. LG shortened the length of postoperative hospital stay.

Efficacy and safety of 0.6% sodium alginate solution in endoscopic submucosal dissection for esophageal and gastric neoplastic lesion: A randomized controlled study.

OBJECTIVES: Sodium alginate (SA) solution has characteristic viscoelasticity. We aimed to determine efficacy and safety of 0.6% SA for submucosal injection during endoscopic submucosal dissection (ESD) in patients with localized neoplastic lesion in the esophageal and gastric mucosa. METHODS: We conducted a randomized controlled study at six major hospitals in Japan including 130 patients with endoscopically localized neoplastic lesion in the esophageal and gastric mucosa and eligible for ESD. Patients were randomly assigned to SA or 0.4% sodium hyaluronate (SH) group (control); ESD was performed using a submucosal injection of SA/SH. As a primary outcome measure, non-inferiority of SA against SH was investigated using en bloc complete resection in ESD and formation and maintenance of mucosal elevation upon injection as an efficacy index. Adverse events during the study were evaluated as safety outcome measures. This study was registered with Pharmaceuticals and Medical Devices Agency (clinical trial no. 28-277/2016-18; clinical trial identification no. KP2013-009_C001). RESULTS: Efficacy rate of submucosal injection during ESD was 91.7% (55/60) and 88.7% (55/62) in the SA and SH groups, respectively, demonstrating non-inferiority of SA against SH. Adverse events for which a causal relationship with submucosal injection solution could not be eliminated were noted in 8.2% (5/61) and 4.7% (3/64) in the SA and SH groups, respectively, but symptoms disappeared without treatment/after drug administration in both groups. CONCLUSIONS: In Japan, 0.4% SH is the only commercially approved formulation for submucosal injection during ESD. The study results may expand submucosal injection solution options in clinical practice.

Long-term outcomes of laparoscopy-assisted distal gastrectomy with suprapancreatic nodal dissection for clinical stage I gastric cancer: a multicenter phase II trial (JCOG0703).

BACKGROUND: Laparoscopic gastrectomy has become a common surgical treatment for gastric cancer in eastern Asian countries. However, a large-scale prospective study to investigate the benefit of laparoscopy-assisted distal gastrectomy (LADG) regarding long-term outcomes has never been reported. We have already reported the short-term outcomes of this study. Here we report long-term outcomes as the secondary endpoints of this study after a 5-year follow-up period. METHODS: This study comprised patients with clinical stage I gastric cancer who were able to undergo a distal gastrectomy. LADG with D1 plus suprapancreatic lymph node dissection was performed by credentialed gastric surgeons who had each conducted at least 30 LADG and 30 open gastrectomy procedures. The primary endpoint was the proportion of patients who developed either anastomotic leakage or pancreatic fistula. The secondary endpoints included overall survival and relapse-free survival. RESULTS: From November 2007 to September 2008, 176 eligible patients were enrolled, comprising 140 patients with pathological stage IA disease, 23 patients with pathological stage IB disease, 9 patients with pathological stage II disease, and 4 patients with pathological stage IIIA disease. No patients had recurrent disease, and three of the patients died within the follow-up period. The 5-year overall survival was 98.2% (95% confidence interval 94.4-99.4%) and the 5-year relapse-free survival was 98.2% (95% confidence interval 94.4-99.4%). CONCLUSIONS: The long-term outcomes of stage I gastric cancer patients undergoing LADG seem comparable to those of patients undergoing an open procedure, although this result should be confirmed by a randomized control trial. We have already completed accrual of 921 patients for a multicenter randomized phase III trial (JCOG0912) to confirm the noninferiority of LADG compared with open gastrectomy in terms of relapse-free survival.

Higher incidence of pancreatic fistula in laparoscopic gastrectomy. Real-world evidence from a nationwide prospective cohort study.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) is becoming the standard procedure for gastric cancer. However, supporting evidence thus far has been derived primarily from randomized control trials conducted by centers of excellence. In the present study we used the National Clinical Database (NCD) in Japan to prospectively accumulate data from diverse types of hospitals and examine whether LDG is a safe and valid standard procedure. METHODS: From the NCD, 169 institutions were selected to form a cohort that was considered to be representative of Japan. From August 2014 to July 2015, 5288 patients who underwent LDG were registered prospectively, and clinical data were acquired through the NCD. To compare surgical outcomes between open distal gastrectomy (ODG) and LDG, we adjusted for confounding factors using propensity score matching, ultimately retrieving data from 1067 patients in each group. RESULTS: There were no significant differences in the number of in-hospital deaths in the ODG and LDG groups (3/1067 vs. 6/1067; P = 0.51) or in the number of reoperations (20/1067 vs. 29/1067; P = 0.19). However, the length of hospital stay was significantly shorter in the LDG. Although wound infection and dehiscence were more common in the ODG group, LDG was more often associated with grade B or higher pancreatic fistulas. CONCLUSION: The safety and minimal invasiveness of LDG were confirmed in the present Japanese nationwide survey. However, care must be taken to prevent the formation of pancreatic fistulas with LDG, and further improvements in surgical quality are warranted in this regard.

Morbidity and mortality from a propensity score-matched, prospective cohort study of laparoscopic versus open total gastrectomy for gastric cancer: data from a nationwide web-based database.

BACKGROUND: Controversy persists regarding the technical feasibility of laparoscopic total gastrectomy (LTG), and to our knowledge, no prospective study with a sample size sufficient to investigate its safety has been reported. We aimed to compare the postoperative morbidity and mortality rates in patients undergoing LTG and open total gastrectomy (OTG) for gastric cancer in prospectively enrolled cohort using nationwide web-based registry. METHODS: From August 2014 to July 2015, consecutive patients undergoing LTG or OTG (925 and 1569 patients, respectively) at the participating institutions were enrolled prospectively into the National Clinical Database registration system. We constructed propensity score (PS) models separately in four facility yearly case-volume groups, and evaluated the postoperative morbidity and mortality in PS-matched 1024 patients undergoing LTG or OTG. RESULTS: The incidence of overall morbidity were 84 (16.4%) in the OTG and 54 (10.3%) in the LTG groups (p = 0.01).The incidence of anastomotic leakage and pancreatic fistula grade B or above were not significantly different between the two groups (LTG 5.3% vs. OTG 6.1%, p = 0.59, LTG 2.7% vs. OTG 3.7%, p = 0.38, respectively). There were also no significant differences in the 30-day and in-hospital mortality rates between the two groups (LTG 0.2% vs. OTG 0.4%, p = 0.56; LTG 0.4% vs. OTG 0.4%, p = 1.00, respectively). CONCLUSION: The results from our nationally representative data analysis showed that LTG could be a safe procedure to treat gastric cancer compared to OTG. The indication for LTG should be considered carefully in a clinical setting.

Clinical practice guidelines for peroral endoscopic myotomy.

Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in Japan used to treat esophageal achalasia and esophageal motility disorders. This technique has been rapidly accepted and widely disseminated throughout our clinical practice because of its low invasiveness, technical novelty, and high efficacy. Since the advent of POEM, there have been no clinical guidelines that clearly indicated its standard of care, and these guidelines have been anticipated both nationally and internationally by clinicians who engage in POEM practice. In 2017, to meet these needs, the Japan Gastroenterological Endoscopy Society (JGES) launched the guideline committee for POEM. Based on the guideline development process proposed by the Medical Information Network Distribution Service (MINDS), the guideline committee initially created research questions on POEM and conducted a systematic review and meta-analysis on each topic. The clinical research extracted from databases for these clinical questions and the systematic review mainly comprised a few retrospective studies with a small number of participants and short trial periods; hence, the strength of the evidence and recommendations derived from these results was low. Throughout this process, the guideline committee met thrice: once on May 13, 2017, and again on September 17, 2017, to formulate the draft. A consensus meeting was then held on January 14, 2018, in Tokyo to establish the guideline statements and finalize the recommendations using the modified Delphi method. This manuscript presents clinical guidelines regarding current standards of practice and recommendations in terms of the nine chief topics in POEM.

Laparoscopic sentinel node navigation surgery for early gastric cancer: a prospective multicenter trial.

BACKGROUND: Prospective multicenter trials have shown the feasibility of sentinel node (SN) navigation surgery using a dual tracer of dye and radioisotope for early gastric cancer. However, comparable trials using the indocyanine green (ICG) and the infrared ray laparoscopic system (IRLS) have not been reported. On the basis of our cohort studies, we assumed that the ICG imaging with the IRLS is as effective as the dual tracer in detecting SNs. Therefore, we conducted a prospective multicenter trial to assess the effectiveness and generalizability of the infrared ICG technique in patients with early gastric cancer. PATIENTS AND METHODS: Patients with previously untreated cT1 gastric adenocarcinomas less than 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using ICG combined with IRLS technique. Following biopsy of the identified SNs, D2 or modified D2 laparoscopic gastrectomy was performed according to the current Japanese Gastric Cancer Association guidelines. RESULTS: Among the 47 patients who gave written informed consent, 44 were eligible from the surgical findings, for whom SN biopsy was performed. The detection rate of the lymphatic basin by the ICG with IRLS was 100% (44/44). The accuracy was also 100% (7/7) for detecting metastatic lymph node, which was verified on the permanent pathologic examination. Following the median follow-up of 114 months (range, 60 to 120 months), no recurrence (0/40) was observed. Although the number of patients was unequally distributed among the hospitals participating in the trial, the detection rates of SNs in low-volume hospitals were comparable to those in high-volume hospitals. Consequently, there was no learning curve in this trial. CONCLUSION: The infrared ICG imaging accurately detected the lymphatic basin and SNs with occult metastasis in SN-navigated gastrectomy for gastric cancer. This method was feasible even for low-volume surgeons and hospitals.

[NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY].

The clinical application of natural orifice translumenal endoscopic surgery (NOTES) began in 2007, and several thousand patients worldwide have undergone the technique. In this review, we summarize and highlight the current status and future directions of NOTES. The most common procedures are cholecystectomy and appendectomy, mainly performed as hybrid NOTES through the transvaginal route. In addition, direct-target NOTES such as per oral endoscopic myotomy (POEM) or transanal total mesorectal excision has spread rapidly, because it allows access to the operative field without injuring healthy visceral organs. In Japan, a clinical registration system was established, and clinical applications are carried out safely. NOTES performed in Japan is characterized by procedures requiring extensive techniques of endoscopic treatment such as endoscopic full-thickness resection, POEM, and the submucosal tunnel method. It will be necessary to develop instruments and determine social needs to achieve pure NOTES. It will also be necessary to determine the significance of reducing surgical wounds on the body surface. Although much work is still needed to refine the techniques for NOTES, it appears to be developing as a new minimally invasive form of surgical and endoscopic treatment.

A Multi-institutional, Prospective, Phase II Feasibility Study of Laparoscopy-Assisted Distal Gastrectomy with D2 Lymph Node Dissection for Locally Advanced Gastric Cancer (JLSSG0901).

BACKGROUND: The efficacy and safety outcomes of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection for locally advanced gastric cancer remain unclear. Therefore, we conducted a randomized, controlled phase II trial to confirm the feasibility of LADG in terms of technical safety, and short-term surgical outcomes were investigated. METHODS: Eligibility criteria included pre-operatively diagnosed advanced gastric cancer that could be treated by distal gastrectomy with D2 lymph node dissection; MP, SS, and SE without involvement of other organs; and N0-2 and M0. Patients aged 20-80 years were pre-operatively randomized. RESULTS: In total, 180 patients were registered and randomized to the open (89 patients) and laparoscopic arms (91 patients). Among 91 patients in the laparoscopic arm, 86 underwent laparoscopic gastrectomy according to the study protocol. Regarding the primary endpoint of the phase II trial, the proportion of patients with either anastomotic leakage or pancreatic fistula was 4.7 % (4/86). The grade 3 or higher morbidity rate, including systemic and local complications, was 5.8 %. Conversion to open surgery was required for 1 patient (1.2 %), without any intra-operative complication. The post-operative mortality rate was 0, and no patient required readmission for surgical complications within 6 months after initial discharge. CONCLUSIONS: The technical safety of LADG with D2 lymph node dissection for locally advanced gastric cancer was demonstrated. A phase III trial to confirm the non-inferiority of this procedure to open gastrectomy in terms of long-term outcomes is ongoing. Registered Number: UMIN 000003420 ( www.umin.ac.jp/ctr/).

Effects of sleeve gastrectomy and gastric banding on the hypothalamic feeding center in an obese rat model.

PURPOSE: Laparoscopic sleeve gastrectomy (SG) and gastric banding (GB) are popular bariatric procedures for treating morbid obesity. This study aimed to investigate changes in the hypothalamic feeding center after these surgeries in a diet-induced obese rat model. METHODS: Obesity was induced in 60 Sprague-Dawley rats using a high-energy diet for 6 weeks. These rats were divided into four groups: the sham-operated (SO) control, pair-fed (PF) control, SG and GB groups. Six weeks after the surgery, metabolic parameters, the plasma levels of leptin, ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) and the hypothalamic mRNA expressions of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) were measured. RESULTS: Compared with those observed in the SO group, the body and fat tissue weights were significantly decreased and the metabolic parameters were significantly improved in the PF, SG and GB groups 6 weeks after surgery. The plasma ghrelin levels were significantly lower and the PYY and GLP-1 levels were significantly higher in the SG group than in the PF, GB and SO groups. Compared with that seen in the PF and GB groups, the hypothalamic mRNA expression of NPY was significantly lower and the expression of POMC was significantly higher in the SG group. CONCLUSIONS: SG may affect the neurological pathway associated with appetite in the hypothalamus and thereby control ingestive behavior.

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

PURPOSE: Molecular 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. METHODS: We 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. RESULTS: Thirteen 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. CONCLUSIONS: Our results using a novel lectin microarray system provide the first solid evidence that BPL expression is a predictor of gastric cancer recurrence.

Short-term surgical outcomes from a randomized controlled trial to evaluate laparoscopic and open D3 dissection for stage II/III colon cancer: Japan Clinical Oncology Group Study JCOG 0404.

OBJECTIVE: A randomized controlled trial to confirm the non-inferiority of laparoscopic surgery to open surgery in terms of overall survival was conducted, and short-term surgical outcomes are demonstrated. BACKGROUND: The efficacy and safety outcome of laparoscopic surgery for clinical stages II/III colon cancer undergoing Japanese D3 dissection are still unclear. METHODS: Eligibility criteria included colon cancer; tumor located in the cecum, ascending, sigmoid, or rectosigmoid colon; T3 or T4 without involvement of other organs; N0-2; and M0. Patients were randomized preoperatively and underwent tumor resection with D3 dissection. Safety analyses were conducted by per-protocol set. RESULTS: A total of 1057 patients were randomized between October 2004 and March 2009. By per-protocol set, 524 patients who underwent open surgery and 533 patients who underwent laparoscopic surgery were analyzed. D3 dissection was performed in 521 (99.4%) patients in the open surgery arm and 529 (99.2%) patients in the laparoscopic surgery arm. Conversion to open surgery was needed for 29 (5.4%) patients. Patients assigned to laparoscopic surgery had less blood loss (P < 0.001), although laparoscopic surgery lasted 52 minutes longer (P < 0.001). Laparoscopic surgery was associated with a shorter time to pass first flatus, decreased use of analgesics after 5 postoperative days, and a shorter hospital stay. Morbidity [14.3% (76/533) vs 22.3% (117/524), P < 0.001] was lower in the laparoscopic surgery arm. CONCLUSIONS: Short-term surgical safety and clinical benefits of laparoscopic D3 dissection were demonstrated. The primary endpoint will be reported after the primary analysis, planned for 2014.

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

BACKGROUND AND AIM: 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. METHODS: Mice were divided into four equal groups: Control, DSS, DSS + light low (LL), and DSS + light high (LH) groups. Normal fluorescent light intensity in the Control and DSS groups was 200 lux. Artificial light intensities were as follows: DSS + LL group, 1000 lux; DSS + LH group, 2500 lux. After administering phototherapy for 7 days, we evaluated disease activity index (DAI), histological score, colon length/weight, serum 1,25-dihydroxyvitamin D(3) level, and serum and colonic cytokines in the mice. RESULTS: DAI and histological scores were significantly lower in the DSS + LL group than in the DSS group (both, P < 0.05). Colon length and weight were significantly higher in the DSS + LL group than in the DSS group (both, P < 0.05). Serum interleukin (IL)-6, TNF-α, and IL-17 in the DSS + LL group were significantly lower, and serum and colonic IL-10 were significantly higher in the DSS + LL group than in the DSS group (all, P < 0.05). Serum 1,25-dihydroxyvitamin D(3) levels in the DSS + LH group were significantly increased compared with those in the DSS + LL and DSS groups. CONCLUSION: Artificial light phototherapy suppressed DSS-induced colitis in mice by suppression of pro-inflammatory cytokines and promotion of anti-inflammatory cytokines.

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.

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.