Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.

INTRODUCTION: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis. METHODS: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses. RESULTS: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells. CONCLUSION: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

Impact of the endoscopic surgical skill qualification system on conversion to laparotomy after low anterior resection for rectal cancer in Japan (a secondary analysis of the EnSSURE study).

BACKGROUND AND AIMS: Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for rectal cancer. METHODS: We performed a retrospective secondary analysis of data collected from patients undergoing laparoscopic surgery for cStage II and III rectal cancer from 2014 to 2016 across 56 institutions affiliated with the Japan Society of Laparoscopic Colorectal Surgery. Data from the original EnSSURE study were analyzed to investigate risk factors for conversion to laparotomy by performing univariate and multivariate analyses based on the reason for conversion. RESULTS: Data were collected for 3,168 cases, including 65 (2.1%) involving conversion to laparotomy. Indicated conversion accounted for 27 cases (0.9%), while technical conversion accounted for 35 cases (1.1%). The multivariate analysis identified the following independent risk factors for indicated conversion to laparotomy: tumor diameter [mm] (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.01-1.05, p = 0.0002), combined resection of adjacent organs [+/-] (OR 7.92, 95% CI 3.14-19.97, p < 0.0001), and surgical participation of an ESSQS-certified physician [-/+] (OR 4.46, 95% CI 2.01-9.90, p = 0.0002). The multivariate analysis identified the following risk factors for technical conversion to laparotomy: registered case number of institution (OR 0.99, 95% CI 0.99-1.00, p = 0.0029), institution type [non-university/university hospital] (OR 3.52, 95% CI 1.54-8.04, p = 0.0028), combined resection of adjacent organs [+/-] (OR 5.96, 95% CI 2.15-16.53, p = 0.0006), and surgical participation of an ESSQS-certified physician [-/+] (OR 6.26, 95% CI 3.01-13.05, p < 0.0001). CONCLUSIONS: Participation of ESSQS-certified physicians may reduce the risk of both indicated and technical conversion. Referral to specialized institutions, such as high-volume centers and university hospitals, especially for patients exhibiting relevant background risk factors, may reduce the risk of conversion to laparotomy and lead to better outcomes for patients. TRIAL REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000040645.

Risk factors for anastomotic leakage after low anterior resection for obese patients with rectal cancer.

PURPOSE: We aimed to analyze the risk factors for anastomotic leakage (AL) after low anterior resection (LAR) in obese patients (body mass index [BMI] ≥ 25 kg/m2) with rectal cancer. METHODS: Data were collected from four hundred two obese patients who underwent LAR for rectal cancer in 51 institutions. RESULTS: Forty-six (11.4%) patients had clinical AL. The median BMI (27 kg/m2) did not differ between the AL and non-AL groups. In the AL group, comorbid respiratory disease was more common (p = 0.025), and the median tumor size was larger (p = 0.002). The incidence of AL was 11.5% in the open surgery subgroup and 11.4% in the laparoscopic surgery subgroup. Among the patients who underwent open surgery, the AL group showed a male predominance (p = 0.04) in the univariate analysis, but it was not statistically significant in the multivariate analysis. Among the patients who underwent laparoscopic surgery, the AL group included a higher proportion of patients with comorbid respiratory disease (p = 0.003) and larger tumors (p = 0.007). CONCLUSION: Comorbid respiratory disease and tumor size were risk factors for AL in obese patients with rectal cancer. Careful perioperative respiratory management and appropriate selection of surgical procedures are required for obese rectal cancer patients with respiratory diseases.

Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG).

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain 'equipoise' between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

Success rate of acquiring informed consent and barriers to participation in a randomized controlled trial of laparoscopic versus open surgery for non-curative stage IV colon cancer in Japan (JCOG1107).

BACKGROUND: Successful achievement of randomized controlled trials (RCTs) is dependent on the acquisition of informed consent (IC) from patients. The aim of this study was to prospectively calculate the proportion of participation in a surgical RCT and to identify the reasons for failed acquisition of IC. METHODS: A 50-insitution RCT was conducted to evaluate oncological outcomes of open and laparoscopic surgery for stage IV colon cancer (JCOG1107: UMIN-CTR 000000105). The success rate of obtaining IC was evaluated in eight periods between January 2013 and January 2021. In addition, reasons for failed acquisition of IC were identified from questionnaires. RESULTS: In total, 391 patients were informed of their eligibility for the trial, and 168 (42%) were randomly assigned to either the laparoscopic surgery group (n = 84) or open surgery group (n = 84). The success rate of IC acquisition ranged from 33 to 58% in three periods. The most common reasons for failed IC acquisition were the patients' preference for one approach of surgery based on recommendations from referring doctors and family members, and anxiety/unhappiness about randomization. CONCLUSIONS: The success rate of acquiring IC from patients for an RCT of laparoscopic versus open surgery for stage IV colon cancer was lower than the expected rate planned in the protocol. To obtain the planned rate, investigators should make efforts to inform patients and their families about the medical contributions a surgical RCT can make and recognize that the period in equipoise may be limited.

Establishment and validation of a nomogram for predicting potential lateral pelvic lymph node metastasis in low rectal cancer.

BACKGROUND: Identifying lateral pelvic lymph node (LPN) metastasis in low rectal cancer is crucial before treatment. Several risk factors and prediction models for LPN metastasis have been reported. However, there is no useful tool to accurately predict LPN metastasis. Therefore, we aimed to construct a nomogram for predicting LPN metastasis in rectal cancer. METHODS: We analyzed the risk factors for potential LPN metastasis by logistic regression analysis in 705 patients who underwent primary resection of low rectal cancer. We included patients at 49 institutes of the Japan Society of Laparoscopic Colorectal Surgery between June 2010 and February 2012. Clinicopathological factors and magnetic resonance imaging findings were evaluated. The nomogram performance was assessed using the c-index and calibration plots, and the nomogram was validated using an external cohort. RESULTS: In the univariable logistic regression analysis, age, sex, carcinoembryonic antigen, tumor location, clinical T stage, tumor size, circumferential resection margin (CRM), extramural vascular invasion (EMVI), and the short and long axes of LPN and perirectal lymph node (PRLN) were nominated as risk factors for potential LPN metastasis. We identified a combination of the short axis of LPN, tumor location, EMVI, and short axis of PRLN as optimal for predicting potential LPN metastasis and developed a nomogram using these factors. This model had a c-index of 0.74 and was moderately calibrated and well-validated. CONCLUSIONS: This is the first study to construct a well-validated nomogram for predicting potential LPN metastasis in rectal cancer, and its performance was high.

Early response in phosphorylation of ribosomal protein S6 is associated with sensitivity to trametinib in colorectal cancer cells.

Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity.

Prognostic Impact of Lateral Pelvic Node Dissection on the Survival of Patients in Low Rectal Cancer Subgroups Based on Lymph Node Size.

BACKGROUND: Lateral pelvic node (LPN) dissection (LPND) is considered a promising technique for treating low rectal cancer; however, there is insufficient evidence of its prognostic value. Using centrally reviewed preoperative pelvic magnetic resonance (MR) images, this study aimed to find the patient population who has benefited from LPND. PATIENTS AND METHODS: MR images of patients from 69 institutes with stage II-III low rectal cancer were reviewed by experienced radiologists. Recurrence-free survival (RFS), overall survival (OS), and short-term outcomes were measured. RESULTS: In total, 731 preoperative MR images were reviewed (excluding patients with short-axis LPN ≥ 10 mm). Of these, 322 underwent total mesorectum excision (TME) without LPND (non-LPND group), and 409 underwent TME with LPND (LPND group). Preoperative treatment was performed for 40% and 25% of patients in the non-LPND and LPND groups, respectively. The incidence of postoperative complications was higher in the LPND group (44.5%) than in the non-LPND group (33.2%; P = 0.002). Among patients with LPNs < 5 mm, OS and RFS curves were not significantly different between the groups. Among patients with LPNs ≥ 5 mm, the LPND group had significantly higher 5-year OS and RFS than the non-LPND group (OS: 81.9% versus 67.3%; RFS: 69.4% versus 51.6%). On multivariate analysis of LPN ≥ 5 mm cases, LPND was independently associated with RFS. CONCLUSIONS: Despite the high incidence of postoperative complications, this study showed the prognostic impact of LPND on low rectal cancer patients with LPNs (≥ 5 mm, < 10 mm short axis) measured by experienced radiologists. Trial registration UMIN-ID: UMIN000013919.

Challenges of improving treatment outcomes for colorectal and anal cancers in Japan: the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG).

Colorectal cancer is a major public health concern in Japan. While early-stage colorectal adenocarcinoma treatment entails radical resection of the primary tumor, the importance of perioperative treatment is growing as physicians seek to further improve treatment outcomes. For anal squamous cell carcinoma, definitive chemoradiotherapy is superior to radical surgery in terms of improved patient quality of life. The Colorectal Cancer Study Group of the Japanese Clinical Oncology Group was established in 2001 and has worked to provide answers to common clinical questions and improve treatment outcomes for colorectal and anal cancers through 15 large-scale prospective clinical trials. Here, we discuss the current state of perioperative treatment for early-stage colon, rectal and anal cancers in Japan and approaches taken by the Colorectal Cancer Study Group/the Japanese Clinical Oncology Group to improve treatment outcomes for these cancers.

Short- and long-term outcomes of laparoscopic surgery for colorectal cancer in the elderly aged over 80 years old versus non-elderly: a retrospective cohort study.

BACKGROUND: Recently, colorectal cancer has increased in elderly patients worldwide, with laparoscopic colorectal surgery increasing in elderly patients with colorectal cancer. However, whether laparoscopic colorectal surgery is an optimal procedure for colorectal cancer in the elderly remains unclear. This study aimed to verify safety and curability of laparoscopic colorectal surgery in elderly patients ≥80 years old. METHODS: Patients undergoing curative colorectal surgery from 2006 to 2014 were enrolled and classified into the laparoscopic surgery in elderly patients aged ≥80 years (LAC-E) group, open surgery in elderly patients (OC-E) group, and laparoscopic surgery in non-elderly patients (LAC-NE) group. Short- and long-term outcomes were compared between these groups. RESULTS: The LAC-E, OC-E, and LAC-NE groups comprised 85, 25, and 358 patients, respectively. Intraoperative blood loss and incidence of postoperative complications were significantly lower in the LAC-E versus OC-E group (97 vs. 440 mL, p < .01 and 14% vs. 32%, p < .05, respectively). Long-term outcomes were not different between these two groups. Operation time was significantly shorter in the LAC-E versus LAC-NE group (249 vs. 288 min, p < .01). Intraoperative blood loss and postoperative complications were similar between the groups. Although the 5-year overall survival rate in the LAC-E group was lower than that in the LAC-NE group (64% vs. 80%, p < .01), there was no difference in 5-year disease-specific survival between the groups. CONCLUSION: Laparoscopic colorectal surgery is technically and oncologically safe for colorectal cancer in the elderly as well as the non-elderly and can be an optimal procedure for colorectal cancer in the elderly.

Preoperative chemoradiotherapy versus surgery alone for advanced low rectal cancer: a large multicenter cohort study in Japan.

PURPOSE: To clarify the usefulness of chemoradiotherapy (CRT) for low rectal cancer, we investigated the current status of CRT in Japan and its short- and long-term outcomes versus surgery alone for low rectal cancer in a large multicenter cohort study. METHODS: Between January 2010 and December 2011, data from 1608 patients with clinical Stage II-III rectal adenocarcinoma were collected from 69 specialized centers. Of these 1608 patients, 923 were diagnosed with clinical stage III low rectal cancer, 838 were enrolled in this study, divided into the surgery-alone group (n = 649) and preoperative CRT group (n = 189), and analyzed. RESULTS: The following parameters were significantly lower in the CRT versus surgery-alone group: blood loss (210 vs. 431.5 mL), postoperative complications (27.5% vs 39.0%), and the incidence of anastomotic leakage (3.7% vs. 8.8%). The 3-year overall survival, relapse-free and local recurrence-free survival rates did not between the two groups to a statistically significant extent (91.2% vs. 87.4%, 68.8% vs. 66.4%, and 88.2% vs. 88.4%, respectively). CONCLUSIONS: The present study revealed the current status of CRT for low rectal cancer in Japan. The results showed that CRT could be safely performed for advanced low rectal cancer in comparison to surgery alone.

Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.

It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of ERKs in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with an MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. In contrast, ERKs in the deep region were markedly hyperactivated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.

Open versus Laparoscopic Surgery for Advanced Low Rectal Cancer: A Large, Multicenter, Propensity Score Matched Cohort Study in Japan.

BACKGROUND: Laparoscopic surgery for rectal cancer is widely performed all over the world and several randomized controlled trials have been reported. However, the usefulness of laparoscopic surgery compared with open surgery has not been demonstrated sufficiently, especially for the low rectal area. OBJECTIVE: The aim of this study was to investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for locally advanced low rectal cancer. PATIENTS AND METHODS: Data from patients with clinical stage II to III low rectal cancer below the peritoneal reflection were collected and analyzed. The operations were performed from 2010 to 2011. Short-term outcomes and long-term prognosis were analyzed with propensity score matching. RESULTS: Of 1608 cases collated from 69 institutes, 1500 cases were eligible for analysis. The cases were matched into 482 laparoscopic and 482 open cases. The mean height of the tumor from the anal verge was 4.6 cm. Preoperative treatment was performed in 35% of the patients. The conversion rate from laparoscopic to open surgery was 5.2%. Estimated blood loss during laparoscopic surgery was significantly less than that during open surgery (90 vs 625 mL, P < 0.001). Overall, the occurrence of complications after laparoscopic surgeries was less than that after open surgeries (30.3% vs 39.2%, P = 0.005). Three-year overall survival rates were 89.9% [95% confidence interval (95% CI) 86.7-92.4] and 90.4% (95% CI 87.4-92.8) in the laparoscopic and open groups, respectively, and no significant difference was seen between the 2 groups. No significant difference was observed in recurrence-free survival (RFS) between the 2 groups (3-year RFS: 70.9%, 68.4 to 74.2 vs 71.8%, 67.5 to 75.7). CONCLUSION: Laparoscopic surgery could be considered as a treatment option for advanced, low rectal cancer below the peritoneal reflection, based on the short-term and long-term results of this large cohort study (UMIN-ID: UMIN000013919).

Current status of laparoscopic surgery for colorectal cancer based on the evidence of JCOG0404 trial.

The concept of optimal surgery for colorectal cancer in Japan includes D3 dissection, which preserves the mesocolic plane by sharp dissection off the parietal plane, with central vascular ligation. In recent 25 years, laparoscopic surgery for colorectal cancers has been widespread, and Japan Society for Endoscopic Surgery(JSES) demonstrated that a penetration rate of laparoscopic surgery for colorectal cancer was 58 % in 2013. To evaluate long and short-term outcomes of laparoscopic D3 resection for stage Il/III colorectal cancer, a randomized con- trolled trial was conducted in Japan (JCOG0404). The evidence based on JCOG0404 trial would contribute to the appropriate development of laparoscopic surgery with technical and oncological safety in Japan.

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.

A randomized controlled trial comparing laparoscopic surgery with open surgery in palliative resection of primary tumor in incurable Stage IV colorectal cancer: Japan Clinical Oncology Group Study JCOG 1107 (ENCORE trial).

A randomized controlled trial was started in Japan to evaluate the non-inferiority of overall survival of laparoscopic surgery to open surgery for palliative resection of primary tumor in incurable Stage IV colorectal cancer. Symptomatic, Stage IV colorectal cancer patients with non-curable metastasis are pre-operatively randomized to either open or laparoscopic colorectal resection. Surgeons in 56 specialized institutions will recruit 450 patients. The primary endpoint is overall survival. Secondary endpoints are progression-free survival, the proportion of conversion from laparoscopic surgery to open surgery, the proportion of patients who fulfill the criteria of starting chemotherapy by 6 weeks after operation, intraoperative and post-operative complications, adverse events during chemotherapy and serious adverse events.

Evaluation of 0.6% sodium alginate as a submucosal injection material in endoscopic submucosal dissection for early gastric cancer.

BACKGROUND AND AIM: We have focused on sodium alginate (SA) solution as a potential submucosal injection material for endoscopic submucosal dissection (ESD). A previous SA solution had high viscosity and problems such as difficult handling. After its properties were adjusted, SA solution was examined in vitro and its clinical safety was evaluated. METHODS: With 0.4% sodium hyaluronate (SH) solution as a control, catheter injectability and mucosa-elevating capacity of 0.3-0.8% SA solutions were evaluated. Next, 0.6% SA solution was used for ESD in 10 patients with early gastric cancer in a prospective clinical study. RESULTS: Compared with 0.4% SH solution, 0.6% SA solution exhibited no significant difference in catheter injectability but significant superiority in mucosa-elevating capacity. In the clinical study, no adverse events were observed in any patient. CONCLUSION: The safety of 0.6% SA solution as a submucosal injection material was confirmed and it is suggested that its efficacy should be investigated in a larger number of cases.

Risk factors of bleeding during rectal cancer surgery in obese patients in Japan.

BACKGROUND: According to several clinical trials for patients with rectal cancer, laparoscopic surgery significantly reduces intraoperative complications and bleeding compared with laparotomy and demonstrated comparable long-term results. However, obesity is considered one of the risk factors for increased surgical difficulty, including complication rate, prolonged operation time, and bleeding. METHODS: Patients with clinical pathological stage II/III rectal cancer and a body mass index of ≥25 kg/m2 who underwent laparotomy or laparoscopic surgery between January 2009 and December 2013 at 51 institutions participating in the Japan Society of Laparoscopic Colorectal Surgery were included. These patients were divided into major bleeding (>500 mL) group and minor bleeding (≤500 mL) group. The risk factors of major bleeding were evaluated by univariate and multivariate analyses. RESULTS: This study included 517 patients, of which 74 (19.9%) experienced major bleeding. Patient characteristics did not significantly differ between the two groups. The major bleeding group had a longer operative time (p < 0.001) and a larger tumor size than the minor bleeding group (p = 0.011). In the univariate analysis, age >65 years, laparotomy, operative time >300 min, and multivisceral resection were significantly associated with intraoperative massive bleeding. In the multivariate analysis, age >65 years (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.13-4.82), laparotomy (OR, 20.82; 95% CI, 11.56-39.75), operative time >300 min (OR, 5.39; 95% CI, 1.67-132), and multivisceral resection (OR, 10.72; 95% CI, 2.47-64.0) showed to be risk factors for massive bleeding. CONCLUSION: Age >65 years, laparotomy, operative time >300 min, and multivisceral resection were risk factors for massive bleeding during rectal cancer surgery in patients with obesity.

Evaluation of the advantage of surgeons certified by the endoscopic surgical skill qualification system participating in laparoscopic low anterior rectal resection.

Background: A technical qualification system was developed in 2004 by the Japan Society for Endoscopic Surgery. An analysis of the EnSSURE study on 3188 stage II-III rectal cancer patients, which was performed by including the participation of qualified surgeons as assistants and advisers without restricting their participation as operators, revealed that the participation of technically qualified surgeons in surgery improved the technical and oncological safety of laparoscopic rectal resection. Aim: This secondary retrospective analysis of the EnSSURE study examined the advantage of qualified surgeons participating in laparoscopic low anterior resection (LAR). Methods: The outcomes of low anterior resection were compared between groups with and without the participation of surgeons qualified by the Endoscopic Surgical Skill Qualification System (Q and non-Q groups, respectively). We used propensity score matching to generate paired cohorts at a one-to-one ratio. The postoperative complication rate, short-term results (hemorrhage volume, operative time, number of dissected lymph nodes, open conversion rate, intraoperative complication rate, and R0 resection rate), and long-term results (disease-free survival rate, local recurrence rate, and overall survival rate) were evaluated. Results: The frequencies of postoperative complications, anastomotic bleeding, and intraperitoneal abscess were significantly lower, the operative time was significantly shorter, the postoperative hospital stay was significantly shorter, and the number of dissected lymph nodes was higher in the Q group. No significant differences were observed in disease-free survival, local recurrence, or overall survival rate rates between the groups. Conclusion: The participation of qualified surgeons in LAR is technically advantageous.