Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer: The JLSSG0901 Randomized Clinical Trial.

Importance: Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years. More robust evidence is necessary to verify noninferiority of laparoscopic gastrectomy. Objective: To compare 5-year survival outcomes between laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 lymph node dissection for locally advanced gastric cancer. Design, Setting, and Participants: This was a multicenter, open-label, noninferiority, prospective randomized clinical trial. Between November 26, 2009, and July 29, 2016, eligible patients with histologically proven gastric carcinoma from 37 institutes in Japan were enrolled. Two interim analyses and final analysis were performed in October 2014, May 2018, and November 2021, respectively. Interventions: Patients were randomly assigned (1:1) to either the ODG or LADG group. The procedures were performed exclusively by qualified surgeons. Main Outcomes and Measures: The primary end point was 5-year relapse-free survival, and the noninferiority margin for the hazard ratio (HR) was set at 1.31. The secondary end points were 5-year overall survival and safety. Results: A total of 502 patients were included in the full-analysis set: 254 (50.6%) in the ODG group and 248 (49.4%) in the LADG group. Patients in the ODG group had a median (IQR) age of 67 (33-80) years and included 168 males (66.1%). Patients in the LADG group had a median (IQR) age of 64 (34-80) years and included 169 males (68.1%). No significant differences were observed in severe postoperative complications between the 2 groups in the safety analysis (ODG, 4.7% [11 of 233] vs LADG, 3.5% [8 of 227]; P = .64). The median (IQR) follow-up for all patients after randomization was 67.9 (60.3-92.0) months. The 5-year relapse-free survival was 73.9% (95% CI, 68.7%-79.5%) and 75.7% (95% CI, 70.5%-81.2%) for the ODG and LADG groups, respectively, and the HR was 0.96 (90% CI, 0.72-1.26; noninferiority 1-sided P = .03). Further, no significant difference was observed in overall survival time between the 2 groups, and the HR was 0.83 (95% CI, 0.57-1.21; P = .34). The pattern of recurrence was similar between the 2 groups. Conclusions and Relevance: Results of this study show that on the basis of 5-year follow-up data, LADG with D2 lymph node dissection for locally advanced gastric cancer, when performed by qualified surgeons, was proved noninferior to ODG. This laparoscopic approach could become a standard treatment for locally advanced gastric cancer. Trial Registration: UMIN Clinical Trial Registry: UMIN000003420.

A multicenter survey of effects and challenges of an 8K ultra-high-definition endoscopy system compared to existing endoscopy systems for endoscopic surgery.

INTRODUCTION: 8K ultra-high-definition (UHD) images enabling clearer recognition of anatomical structures could contribute to further development of surgical techniques and advanced applications in endoscopic surgery fields. This study aimed to clarify effects and challenges of endoscopic surgery with 8K UHD endoscopy compared to existing endoscopy systems. METHODS: In this multicenter, cross-sectional, questionnaire survey, data were collected from surgical participants who newly used and observed 8K UHD endoscopy in patients undergoing surgery from February 2020 to February 2021. Survey items included sense of presence, reality, depth perception, visibility of tissue, eyestrain, and degree of satisfaction for operators and observers, and weight, operability, focus adjustment, physical fatigue, eyestrain, and satisfaction for camera assistants. Participants rated each 8K UHD endoscopic surgery on a one-to-five scale (definitively inferior, relatively inferior, equivalent, relatively superior, definitively superior) compared to the existing endoscopy system of each facility. RESULTS: Overall, questionnaire responses from 139 participants assessing 8K UHD endoscopic surgery were collected from surgeries performed in 46 patients. Respective ratings of operators and observers included sense of presence: "superior or relatively superior", 97.8% and 91.5%; reality: "superior or relatively superior", 76.1% and 72.3%; and visibility of tissue: "superior or relatively superior", 93.5% and 87.2%. Weight was rated as "inferior or relatively inferior" by 73.9% of camera assistants and focus adjustment as "inferior" by 60.9% of them. CONCLUSIONS: 8K UHD endoscopic surgery enabled identification of surgical anatomies more clearly, provided a sense of presence and reality, and might improve educational effect. Technological development is expected to reduce the burden of camera assistants.

Encouraging Young Pediatric Surgeons and Evaluation of the Effectiveness of a Pediatric Endosurgery Workshop by Self-Assessment and an Objective Skill Validation System.

Background: Japanese pediatric endosurgery experts conducted a workshop for young pediatric surgeons in Russia in collaboration with Russian expert pediatric surgeons. This study was aimed to develop a contributive workshop program and evaluate its impact on young pediatric surgeons. Methods: A 2-day pediatric endosurgery workshop was held in Moscow in February 2020. After conducting a needs assessment survey, Japanese and Russian faculties developed the workshop contents, including pre- and postworkshop skills assessments, lectures, and hands-on training. Skills assessments were performed using the objective skill validation system, the "A-Lap Mini," mimicking intestinal anastomosis. The trainees self-evaluated their knowledge and skills using a five-point scale. Results: Fifteen novice trainee participated and 14 (93.3%) completed the workshop program. The completion rate for the suturing task before and after the workshop was 40.0% (6/15) and 85.7% (12/14), respectively. The following five skill evaluation criteria, which were objectively evaluated: performance time changed from 751.6 ± 247.1 seconds to 780.0 ± 313.3 seconds (P > .05), number of full-thickness sutures improved from 1.0 ± 1.41 to 2.64 ± 0.84 (P = .003), area of wound-opening changed from 0.42 ± 0.83 mm2 to 0.53 ± 1.13 mm2 (P > .05), suture tension improved from 55.48% ± 19.51% to 61.95% ± 23.91% (P > .05), and maximum air leakage pressure improved from 3.76 ± 2.11 kPa to 8.42 ± 7.68 kPa (P > .05). Regarding the self-assessed questionnaire administered before and after the workshop, the confidence in endosurgery skills significantly improved as follows: forceps manipulation ability improved from 2.7 to 3.7 (P < .05), and suturing performance improved from 2.5 to 3.6 (P < .05). The usefulness of the workshop for clinical surgery was scored at 4.3. Conclusions: Quantitative skill evaluation with an automatic feedback function was useful for endosurgery training. Delivering feedback concerning the assessment results to the trainee helps them to determine the specific training requirements needed for clinical endosurgery.

Current Status of Endoscopic Surgery in Japan: The 15th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every 2 years. In 2019, 291,792 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 15th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2018-2019.

Identification of patient subgroups with unfavorable long-term outcomes associated with laparoscopic surgery in a randomized controlled trial comparing open and laparoscopic surgery for colon cancer (Japan Clinical Oncology Group Study JCOG0404).

BACKGROUND: Previously, we conducted a randomized controlled trial (JCOG0404) for stage II/III colon cancer patients and reported that the long-term survival after open surgery (OP) and laparoscopic surgery (LAP) were almost identical; however, JCOG0404 suggested that survival of patients after LAP with tumors located in the rectosigmoid colon, cT4 or cN2 tumors, and high body mass index (BMI) might be unfavorable. AIM: To identify the patient subgroups associated with poor long-term survival in the LAP arm compared with the OP arm. METHODS: Patients aged 20-75, clinical T3 or deeper lesion without involvement of other organs, clinical N0-2 and M0 were included. The patients with pathological stage IV and R2 resection were excluded from the current analysis. In each subgroup, the hazard ratio for LAP (vs. OP) in overall survival (OS) from surgery was estimated using a multivariable Cox regression model adjusted for the clinical and pathological factors. RESULTS: In total, 1025 patients (OP, 511 and LAP, 514) were included in the current analysis. Adjusted hazards ratios for OS of patients with high BMI (>25 kg/m2), pT4, and pN2 in LAP were 3.37 (95% confidence interval [CI], 1.24-9.19), 1.33 (0.73-2.41), and 1.74 (0.76-3.97), respectively. In contrast, that of rectosigmoid colon tumors was 0.98 (0.46-2.09). CONCLUSIONS: Although LAP is an acceptable optional treatment for stage II/III colon cancer, the present subgroup analysis suggests that high BMI (>25 kg/m2), pT4, and pN2 except for RS were factors associated with unfavorable long-term outcomes of LAP in patients with colon cancer who underwent curative resection. (JCOG 0404: NCT00147134/UMIN-CTR: C000000105.).

Institutional variation in survival and morbidity in laparoscopic surgery for colon cancer: From the data of a randomized controlled trial comparing open and laparoscopic surgery (JCOG0404).

BACKGROUND: Institutional variation in outcomes is a key factor to ascertain the generalizability of results and reliability of the clinical trial. This study evaluated institutional variation in survival and postoperative complications using data from JCOG0404 comparing laparoscopic colectomy (LAP) with open colectomy (OP). METHODS: Institutions with fewer than 10 registered patients were excluded from this analysis. Institutional variation was evaluated in terms of early postoperative complications, overall survival, and relapse-free survival and estimated using a mixed-effect model with institution as a random effect after adjusting for background factors. RESULTS: This analysis included 1028 patients in the safety analysis and 1040 patients in the efficacy analysis from 26 institutions. In the safety analysis, there was no variation in grades 3-4 early postoperative complications (in OP, median 6.3% [range 6.3%-6.3%]; in LAP, median 2.6% [range 2.6%-2.6%]), but some variation in grades 1-4 early postoperative complications was observed (in OP, median 20.8% [range 13.2%-31.8%]; in LAP, median 11.9% [range 7.2%-28.7%]), and that in grades 2-4 was observed only in LAP (median 8.8% [range 4.7%-24.0%]; in OP, median 12.7% [range 12.7%-12.7%]). Two specific institutions showed especially high incidences of postoperative complications in LAP. In the efficacy analysis, there was no institutional variation in OP, although a certain variation was observed in LAP. CONCLUSIONS: Some institutional variations in safety and efficacy were observed, although only in LAP. We conclude that a qualification system, including training and education, is needed when new surgical techniques such as laparoscopic surgery are introduced in clinical practice.

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.

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.

Endoscopic intragastric balloon therapy for 15 years in Japan: Results of nationwide surveys.

INTRODUCTION: Endoscopic intragastric balloon (IGB) placement has been performed in Japan since 2004. The nationwide surveys were repeatedly carried out to confirm the effectiveness and safety of IGB in Japan. We herein present the accumulated results. METHODS: Twenty-six Japanese endoscopists personally imported products of the BioEnterics Intragastric Balloon (BIB)/Orbera system after completing the training courses in Japan. Mail surveys were posted to them every 2 years from 2010. This study included the accumulated data of the six surveys, and excluded data from non-Japanese patients and the Orbera365 data. RESULTS: Between 2004 and 2019, 399 obese Japanese patients underwent IGB treatment using the BIB/Orbera system. The incidence rates of early removal of IGB within 1 week and complications due to IGB were 4.8% and 6.1%, respectively. The average percent excess weight loss (%EWL) and percent total weight loss (%TWL) at IGB removal were 46.6% and 11.5%, and successful weight loss, defined as %EWL ≥ 25% or %TWL ≥ 10%, was achieved in 65.6% or 54.5% of the patients, respectively. Multivariate analyses revealed that older age and larger saline filling volume were independent predictors of successful weight loss. At 1 year after IGB removal, successful weight loss defined by the %EWL and %TWL was maintained in 44.7% and 34.1% of the patients, respectively. CONCLUSION: IGB therapy using the BIB/Orbera system has been safely and effectively performed in Japan. The successful weight loss may be associated with older age and larger saline filling volume.

Current status of laparoscopic bariatric/metabolic surgery in Japan: The sixth nationwide survey by the Japan Consortium of Obesity and Metabolic Surgery.

INTRODUCTION: Laparoscopic bariatric procedures have been performed in Japan since 2000. Laparoscopic sleeve gastrectomy (LSG) has been fully covered by National Health Insurance since 2014, and it has been increasingly performed recently. The Japan Consortium of Obesity and Metabolic Surgery conducts a nationwide survey on laparoscopic bariatric/metabolic surgery every 2 years. METHODS: The survey was sent by post or email to 97 Japanese institutions in January 2020. RESULTS: From 2000 to 2019, a total of 3669 laparoscopic bariatric/metabolic procedures were performed in 64 institutions. The most popular procedure was LSG (n = 2866), followed by LSG with duodenojejunal bypass (LSG-DJB, n = 337) and laparoscopic Roux-en-Y gastric bypass (LRYGB, n = 280). Morbidity and reoperation rates were, respectively, 29.8% and 11.8% for LRYGB, 16.8% and 2.8% for LSG, and 13.6% and 6.6% for LSG-DJB. At 5 years after the procedures, the percentage of excess weight loss was 78% for LRYGB, 66% for LSG, and 80% for LSG-DJB. CONCLUSION: This nationwide survey clearly showed that laparoscopic bariatric/metabolic surgery has been safely and effectively performed for 20 years in Japan.

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.

Evaluation of the representativeness and generalizability of Japanese clinical trials for localized rectal/colon cancer: Comparing participants in the Japan Clinical Oncology Group study with patients in Japanese registries.

INTRODUCTION: It is unclear if clinical trial results including patients who meet trial eligibility criteria, are applicable to actual patients in daily practice (generalizability). Moreover, the extent to which are trial participants different from patients seen in daily practice (representativeness) is also unclear. The aim of this study was to evaluate the representativeness of the patients registered in randomized clinical trials to patients in daily practice and examine the generalizability of trial results to daily practice. METHODS: We compared the results of surgical trials conducted by the Japan Clinical Oncology Group with data from two Japanese cancer registries, representing patients seen in daily practice. We compared overall survival (OS) between trial participants and registry patients to evaluate representativeness of trial participants. We then compared the OS of registry patients who received open surgery (OP) and laparoscopic surgery (LAP) to evaluate the generalizability of trial results. RESULTS: We analyzed 3051 patients (701 in JCOG0212, 2350 registry patients) with rectal cancer and 3116 patients (1057 in JCOG0404, 2059 registry patients) with colon cancer. Trial participants tended to possess lower clinical stages. Multivariable analyses revealed registry patients with significantly worse survival compared with trial participants. The hazard ratio of LAP to OP among registry patients was 0.305 (95% CI; 0.048-2.188), which did not meet the prespecified generalizability criteria of 0.9. CONCLUSIONS: Our results failed to ensure either the representativeness or generalizability of clinical trial results, compared to daily practice. Careful considerations are required when applying trial results to patients in daily practice.

Clinical impact of D3 lymph node dissection with left colic artery (LCA) preservation compared to D3 without LCA preservation: Exploratory subgroup analysis of data from JCOG0404.

AIM: We investigated the clinical impact of D3 lymph node dissection preserving left colic artery (LCA) compared to D3 without LCA preservation using data from JCOG0404. LCA preservation is expected to maintain adequate blood supply, which is effective in preventing anastomotic leakage, intestinal paralysis, and bowel obstruction. Whether D3 with LCA preservation (Group A) improves clinical outcomes following resection of sigmoid colon cancer compared to D3 without LCA preservation (Group B) is unclear. METHODS: Procedure type was identified from photographs of the surgical field collected for central surgical review in JCOG0404. Clinical outcomes were compared between each procedure. RESULTS: Among the 1057 randomized patients in JCOG0404, 631 patients receiving sigmoid colectomy or anterior resection were included in the subgroup analysis. Group A comprised of 135 patients and Group B of 496 patients. Patient backgrounds did not differ between groups. Median operative time, blood loss, anastomotic leakage, and intestinal paralysis were not remarkably different (Group A vs Group B: 185 vs 186 minutes, 60 vs 50 mL, 3.0% vs 5.0%, and 2.2% vs 3.8%). More overall postoperative complications occurred in Group B than Group A (21.6% vs 9.6%, P = .022). Five-year relapse-free survival (RFS) and overall survival (OS) tended to be better in Group A than Group B (RFS: 83.7% and 80.5%, HR 0.80 [95% CI 0.51-1.26], OS: 96.3% and 91.1%, HR 0.41 [95% CI 0.19-0.89]). CONCLUSIONS: Short- and long-term outcomes tend to be better in Group A than Group B, indicating that preservation of LCA could be an alternative treatment.

Current status of endoscopic surgery in Japan: The 14th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every two years to evaluate the status of endoscopic surgery over time. In 2017, 248 743 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 14th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2016-2017.

Transitional impact of short- and long-term outcomes of a randomized controlled trial to evaluate laparoscopic versus open surgery for colorectal cancer from Japan Clinical Oncology Group Study JCOG0404.

BACKGROUND: The JCOG0404 randomized controlled trial conducted to compare laparoscopic surgery (LAP) with open surgery (OP) for stage II/III colon cancer showed better short-term outcomes and equal long-term outcomes of LAP versus OP. Technical instrumentation of surgery and anticancer agents given during the registration period might have affected the outcomes. AIM: To evaluate outcomes according to the registration periods. METHODS: The overall registration period was divided into three periods (first: 2004-2005, second: 2006-2007 and third: 2008-2009). Short-term and long-term outcomes were compared between registration periods. RESULTS: In total, 1057 patients were registered. Numbers of patients undergoing each approach for each of the three periods (1st/2nd/3rd) were 528 for OP (106/244/178) and 529 for LAP (106/246/177). Operation time (minutes) did not change between the periods for OP (160/156/161) or LAP (205/211/219). Blood loss (mL) gradually decreased in the latter two periods: (119/80/75) for OP and (35/28/25) for LAP. Incidence of complications (%) decreased in the latter periods for OP (27.6/20.3/21.3), whereas that for LAP remained consistently low (14.3/14.8/13.6). There was no particular trend in 5-year overall survival and recurrence-free survival depending on the period regardless of treatment. D3 dissection rates were 95% or more for all periods in both groups. CONCLUSIONS: Operation time and survival rates did not change over time, whereas blood loss in OP improved in the latter periods. Quality control applied in this trial might have been effective in producing such safe endpoints. (ClinicalTrials.gov, number NCT00147134, UMIN Clinical Trials Registry, number C000000105.).

Risk factors for early postoperative complications after D3 dissection for stage II or III colon cancer: Supplementary analysis of a multicenter randomized controlled trial in Japan (JCOG0404).

OBJECTIVE: To determine risk factors for early postoperative complications after D3 dissection for stage II/III colon cancer. BACKGROUND: Identification of risk factors for postoperative complications is essential in patients surgically treated for colon cancer. The Japan Clinical Oncology Group (JCOG) conducted a randomized controlled trial, JCOG0404, to confirm the non-inferiority of laparoscopic surgery (LAP) to open surgery (OP) with D3 dissection for stage II/III colon cancer. This supplementary analysis was made to assess risk factors for surgery requiring D3 dissection using data from JCOG0404. METHODS: Proportion of postoperative complications of any grade (CTCAE ver. 3.0) until first discharge and risk factors for the most frequent complications were analyzed by univariable and multivariable analysis. RESULTS: Among 1057 randomized patients treated between October 2004 and March 2009, 520 patients with OP and 525 patients with LAP were analyzed. Overall postoperative complications of all grades occurred in 190 patients (18.2%). Multivariable analysis showed that the risk factors for overall early postoperative complications were OP itself (odds ratio [OR] 2.01, 95% confidence interval [CI]: 1.38-2.91, P = 0.0003) and operation time of >240 minutes (OR 1.94, 95% CI: 1.24-3.02, P = 0.0036). The most frequent adverse event was wound complication (50/1045, 4.8%). In the univariable analysis, reconstruction, greater blood loss, OP, and higher body mass index were significantly associated with wound complication. CONCLUSION: Open surgery and longer operation time of >240 minutes were significant risk factors for postoperative complications. LAP surgery and shorter operation time could contribute to fewer postoperative complications in patients undergoing colectomy with D3 dissection. (Japan Clinical Oncology Group study JCOG 0404: NCT00147134/UMIN-CTR: C000000105.).

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.

Endoscopic surgery in Japan: The 13th national survey (2014-2015) by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, the operative procedure has been standardized, and the safety and usefulness of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less-invasive surgery, the number of endoscopic procedures has been increasing in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. For example, JSES established a technical skills certification system for surgeons to train instructors how to teach safe endoscopic surgery, and the organization performs a national survey every 2 years. In 2015, a total of 211 953 patients underwent endoscopic surgery in all surgical domains, including abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The course of laparoscopic surgery's development and its current status are reported here based on the results of the most recent questionnaire survey conducted by JSES.

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.

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.