Expression Analysis of Early Metastatic Seeding of Colorectal Cancer.

BACKGROUND: Distant metastasis is the leading cause of death in patients with colorectal cancer (CRC). Tumor dissemination for metastasis formation occurs in advanced cancers and also during early stages of tumorigenesis. Here, we investigated the genes involved in early metastatic seeding of CRC using gene expression analysis. PATIENTS AND METHODS: We performed a cDNA microarray using specimens resected from stages I-II CRC with and without metachronous metastatic recurrence. For the candidate genes, we immunohistochemically validated protein expression using a tissue microarray of stages I-III CRC. RESULTS: The expression of TROP2, VWCE, and BMP7 was upregulated in the recurrence group rather than in the non-recurrence group. Protein expression analysis revealed significant association of these genes with distant metastatic recurrence. The specimens with high expression of BMP7 showed worse recurrence-free survival (RFS; p = 0.02). Those with high expression of TROP2 and VWCE showed worse overall survival (OS) and RFS (TROP2: p = 0.01 and p = 0.03; VWCE: p < 0.05 and p < 0.001, respectively). In the multivariate analysis, high expression of VWCE and BMP7 was an independent predictor of recurrence [VWCE: hazard ratio (HR) 3.41, p < 0.001; BMP7: HR 2.93, p = 0.005]. In contrast, TROP2 was an independent prognostic factor for OS (HR 4.58, p = 0.03). CONCLUSIONS: Gene expression analysis revealed that TROP2, VWCE, and BMP7 were involved in early metastatic seeding. The high expression of these genes may warrant careful surveillance or adjuvant therapy, even in stages I-II CRC cases.

Feasibility of Laparoscopic and Robotic Total Proctocolectomy for Ulcerative Colitis-related Colorectal Cancer.

BACKGROUND/AIM: To evaluate the feasibility of laparoscopic and robotic total proctocolectomy (TPC) for ulcerative colitis-associated colorectal cancer (UC-CRC). PATIENTS AND METHODS: We retrospectively analyzed the postoperative outcomes of TPC in 13 patients with UC-CRC between January 2011 and December 2021. Laparoscopic TPC was performed in 10 patients. TPC consisted of two procedures: ileal pouch-anal anastomosis (IAA) and TPC with end ileostomy. Using the da Vinci Xi platform with six ports, robotic TPC and abdominal perineal resection (APR) were performed in two and one patients, respectively. Transanal total mesorectal excision (TaTME) was performed using the perineal approach in five patients. RESULTS: UC-CRC was located in the transverse colon, sigmoid colon, rectum, and anal canal in 1, 1, 10, and 1 patients, respectively. IAA, TPC with end ileostomy, and APR were performed in nine, three, and one patients, respectively. Postoperative complications included colitis, portal vein thrombosis, and liver dysfunction, without mortality. The pathological stages were 0, I, IIa, IIIb, and IIIc in five, four, one, two, and one patients, respectively. The tumors were completely resected in all cases. Eleven patients with pStages 0, I, and II survived without recurrence; however, two patients with pStage III died of cancer recurrence. CONCLUSION: This study demonstrated the feasibility of laparoscopic and robotic TPC in patients with UC-CRC. However, long-term outcomes in terms of oncology and patient quality of life must be investigated in future large-scale studies.

A Study of risk factors of postoperative ileus after laparoscopic colorectal resection.

Aim: Postoperative ileus (POI) is a common complication after abdominal surgery. However, the risk factors for POI after laparoscopic colorectal resection are unclear. We therefore investigated the risk factors for POI after laparoscopic colorectal surgery. Methods: This retrospective study involved 484 patients who underwent laparoscopic surgery for primary colorectal cancer at Hokkaido University Hospital. We categorized the patients into a POI group (n = 19) and non-POI group (n = 465). We compared sex, age, smoking, chronic obstructive pulmonary disease (COPD), diabetes mellitus, body mass index (BMI), cardiac disorder, serum albumin, American Society of Anesthesiologists-physical status, tumor location, tumor stage, operative duration, stoma formation, lymph node dissection, operator, and bleeding as potential risk factors for POI between the POI group and non-POI group by univariate and multivariate analyses. Results: The univariate analysis results showed that the POI group had a higher incidence of male sex (P = 0.036), COPD (P = 0.029), and a BMI of <20 kg/m2 (P = 0.0487) as well as a higher bleeding volume (P = 0.014). The multivariate analysis results showed that male sex (odds ratio [OR], 0.2799; 95% confidence interval [CI], 0.089-0.993; P = 0.0298), COPD (0.2866; 0.095-0.862; P = 0.0262), and a BMI of <20 kg/m2 (0.2985; 0.112-0.794; P = 0.0154) were independent risk factors for POI after laparoscopic colorectal resection. Conclusion: Our findings suggest that male sex, COPD, and a BMI of <20 kg/m2 are independent risk factors for POI after laparoscopic colorectal surgery for treatment of colorectal cancer.

Endoscopic Surgical Skill Qualification System: propensity-score matched cohort analysis of accredited supervisors in laparoscopic rectal cancer surgery.

BACKGROUND: The Endoscopic Surgical Skill Qualification System (ESSQS) in Japan evaluates the surgical skills required for laparoscopic surgery as an operator as well as a supervisor. This study aimed to demonstrate the benefits of an ESSQS-certified surgeon's participation in laparoscopic rectal resections as a supervisor (assistant or advisor). METHODS: We retrospectively reviewed laparoscopic resection results for cStage II and III rectal cancer performed at 56 Japanese hospitals between 2014 and 2016. We used propensity score matching to generate paired cohorts with or without an ESSQS-certified supervisor at a one-to-one ratio. The impact of ESSQS-certified supervisors' participation on short-term outcomes was assessed. In the matched cohort, multivariable logistic regression analysis and multivariable regression analysis of postoperative complication rate and intraoperative blood loss were performed to further mitigate the impact of pathological factors. RESULTS: Two groups (n = 399 each) with or without an ESSQS-certified supervisor were well matched by clinical factors. The group with an ESSQS-certified supervisor had lower blood loss (68 mL vs. 98 mL, P = 0.036) and a lower incidence of severe morbidities of Clavien-Dindo grade ≥IIIa (8.0% vs. 13.3%, P = 0.016). Multivariable logistic regression analysis and multivariable regression analysis confirmed that the attendance of ESSQS-certified supervisors reduced postoperative complication occurrence (adjusted odds ratio: 2.28, 95% confidence interval: 1.38 - 3.80, P = 0.001) and intraoperative blood loss (estimated difference: -15.7 mL, P = 0.016). CONCLUSION: This study demonstrated the educational benefits of ESSQS-certified supervisors, including assistants and advisors, evidenced by their superior short-term outcomes.

Early-stage sigmoid colon cancer resection followed by liver metastasis recurrence 1 year later and mesenteric recurrence more than 5 years later: a case report.

BACKGROUND: Early-stage colorectal cancer (CRC) is often treated endoscopically, but additional surgical resection may be considered depending on pathological findings. CASE PRESENTATION: A 73-year-old man was found to have early-stage sigmoid colon cancer by colonoscopy during a medical examination, and endoscopic mucosal resection (EMR) was performed. The lesion was a 7-mm-sized sessile polyp, and the pathological diagnosis was well-differentiated tubular adenocarcinoma, pT1 (submucosal invasion of 400 µm), with no lymphovascular invasion, low budding grade, and negative horizontal and vertical margins. Therefore, the patient was observed without postoperative treatment. One year later, a computed tomography (CT) scan showed multiple liver metastases. After five courses of preoperative chemotherapy with folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX) and panitumumab, liver metastases were reduced. The patient underwent extended right hepatic lobectomy. The pathological finding was well-to-moderately differentiated tubular adenocarcinoma, and immunohistochemistry findings were consistent with liver metastases from sigmoid colon cancer. Postoperatively, the patient received five courses adjuvant chemotherapy with FOLFOX. Although the patient had been recurrence-free for 5 years after liver resection, a CT scan revealed a nodular lesion in the sigmoid mesentery. Positron emission tomography (PET) showed abnormal accumulation in the same lesion. Therefore, the mesenteric nodules diagnosed as lymph metastasis and recurrence of sigmoid colon cancer and performed laparoscopic sigmoid colon resection with lymph node dissection. The pathological findings showed that the recurrent lesion in the mesentery formed a nodular infiltrate with venous, lymphatic, and neural invasion, but lymph node structures were not found, and it was assumed to be metastasis or recurrence due to lymphovascular invasion. The pathologic specimen of the sigmoid colon had no neoplastic lesions, which are considered to be a local recurrence on the mucosal surface. After sigmoid colectomy, adjuvant chemotherapy with CapeOX was conducted, and the patient has been recurrence-free for 13 months at present. CONCLUSION: Even early-stage CRCs that have no pathological indications for additional resection have risks of metastases and recurrences, and we may need to consider that the criteria for additional resection should not be limited to pathological findings alone.

Preoperative mechanical bowel preparation using conventional versus hyperosmolar polyethylene glycol-electrolyte lavage solution before laparoscopic resection for colorectal cancer (TLUMP test): a phase III, multicenter randomized controlled non-inferiority trial.

BACKGROUND: A hyperosmolar ascorbic acid-enriched polyethylene glycol-electrolyte (ASC-PEG) lavage solution ensures excellent bowel preparation before colonoscopy; however, no study has demonstrated the efficacy of this lavage solution before surgery. This study aimed to establish the non-inferiority of ASC-PEG to the standard polyethylene glycol-electrolyte solution (PEG-ELS) in patients undergoing laparoscopic resection for colorectal cancer. METHODS: This was a prospective, single-blind, multicenter, randomized, controlled, non-inferiority clinical trial. Overall, 188 patients scheduled for laparoscopic colorectal resection for single colorectal adenocarcinomas were randomly assigned to undergo preparation with different PEG solutions between August 2017 and April 2020 at four hospitals in Japan. Participants received ASC-PEG (Group A) or PEG-ELS (Group B) preoperatively. The primary endpoint was the ratio of successful bowel preparations using the modified Aronchick scale, defined as "excellent" or "good." RESULTS: After exclusion, 86 and 87 patients in Groups A and B, respectively, completed the study, and their data were analyzed. ASC-PEG was not inferior to PEG-ELS in terms of effective bowel preparation prior to laparoscopic colorectal resection (0.93 vs. 0.92; 95% confidence interval, - 0.078 to 0.099, p = 0.007). The total volume of cleansing solution intake was lower in Group A than in Group B (1757.0 vs. 1970.1 mL). Two and three severe postoperative adverse events occurred in Groups A and B, respectively. Patient tolerance of the two solutions was almost equal. CONCLUSIONS: ASC-PEG is effective for preoperative bowel preparation in patients undergoing laparoscopic resection for colorectal cancer and is non-inferior to PEG-ELS.

Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells.

BACKGROUND: Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. METHODS: We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo. Living cell numbers and migration ability of CT26 cells were evaluated in the presence of ARG inhibitor in vitro. RESULTS: Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular L-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. CONCLUSION: Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy.

Effect of Continuous Box-trainer Training on Laparoscopic Skills of Surgical Residents: A Prospective, Observational Study.

BACKGROUND/AIM: As opportunities for hands-on surgical training during residency have decreased, off-the-job training before surgery is gaining importance. We developed a training program using a box-trainer for surgical residents. This study aimed to verify the effectiveness of the program. Using task-achievement time, we demonstrated the learning curve through continuous task training and verified the efficiency of our training tasks. In addition, we examined the circularity of the cut circle to evaluate the task accuracy and summarized the questionnaire results. PATIENTS AND METHODS: A prospective, observational study was conducted at a single center with five trainees from April 2019 to March 2020. The training consisted of four tasks based on the Fundamentals of Laparoscopic Surgery module. The trainees had to achieve expert proficiency time targets. The task-achievement time and circularity of the cut circle were used for objective assessment; subjective evaluation was done using a questionnaire. RESULTS: Although the learning curves of the task-achievement time seemed to reach a plateau between the third and the fifth skills lab, all the trainees achieved expert proficiency times for the three tasks. Circularity of the cut circle tended to be more accurate after training. All trainees perceived an improvement in their skills after the training program. The level of satisfaction of the training program was rated as 'very satisfied' or 'satisfied'. CONCLUSION: Continuous box-trainer training for 1 year may be effective for improvement in preoperative laparoscopic surgical skills of surgical residents.

[A Case of Pathological Complete Response of Advanced Rectal Cancer with Direct Invasion of the Prostate and Extra-Regional Lymph Node Metastasis after Chemotherapy].

A 62-year-old man was diagnosed as having advanced rectal cancer with an invasive carcinoma of the prostate and the right inguinal lymph node metastasis. He received chemotherapy consisting of combination of 5-FU, oxaliplatin, Leucovorin (mFOLFOX6)and bevacizumab. After 5 courses of the chemotherapy, CT and MRI findings revealed the tumor shrinkage. After 6 courses of the chemotherapy, a laparoscopic abdominoperineal resection, bilateral lymph node dissection and a resection of right inguinal lymph node were performed. The pathological findings showed a pCR. NAC with mFOLFOX6 and bevacizumab may contribute to the reduction of the surgical stress for the patients and be an effective treatment for advanced rectal cancer with distant lymph node metastasis.

Interischial Spine Distance Is a Simple Index of the Narrow Pelvis That Can Predict Difficulty During Laparoscopic Low Anterior Resection.

BACKGROUND: A narrow pelvis makes laparoscopic rectal resection difficult. This study aimed to evaluate whether a simple measurement on computed tomography can predict procedural difficulty. METHODS: A total of 62 patients with low rectal cancer underwent conventional laparoscopic low anterior resection. The interischial spine (IS) distance (ie, the distance between the ischial spines) was measured on an axial computed tomography slice. The operative time, blood loss, and time from the insertion of linear staplers to completion of clamping on the distal end of the rectum (clamp time) were compared between patients with narrow or wide pelvises. RESULTS: Overall, 42 men and 20 women with low rectal cancer were assessed. The mean tumor size was 34.5 mm. Total or tumor-specific mesorectal excisions were performed in all cases; high ligation and resection of the inferior mesenteric arteries were carried out in 92% of patients. The mean operative time and blood loss were 206 minutes and 15 mL, respectively. Four patients (6.5%) experienced postoperative complications, including 2 anastomotic leaks (3.2%). The mean IS distance was 93.3 mm. In simple linear regression analysis, a shorter IS distance correlated with a longer operative time ( R2 =0.08, P =0.030) and the clamp time ( R2 =0.07, P =0.046). Using a receiver operating characteristic curve, a narrow pelvis was defined as an IS distance <94.7 mm. Multivariate regression analysis revealed that an IS distance <94.7 mm (odds ratio: 3.51; P =0.04) was independently associated with a longer clamp time. CONCLUSIONS: The IS distance is a simple and useful measurement for predicting the difficulty of laparoscopic low anterior resection.

Exploration of the advantages of minimally invasive surgery for clinical T4 colorectal cancer compared with open surgery: A matched-pair analysis.

The indications of minimally invasive surgery (MIS) for T4 colorectal cancer are controversial because the advantages of MIS are unclear. Therefore, we compared overall survival (OS) and recurrence-free survival (RFS) as the primary endpoint, and short-term outcome, alteration in perioperative laboratory data, and the interval of postoperative chemotherapy from operation as secondary endpoints, between MIS and open surgery (OPEN) using a matched-pair analysis. We explored the advantages of MIS for T4 colorectal cancer. In this retrospective single-institution study, we included 125 patients with clinical T4 colorectal cancer who underwent curative-intent surgery of the primary tumor between October 2010 and September 2019. Conversion cases were excluded. MIS patients were matched to OPEN patients (ratio of 1:2) according to tumor location, clinical T stage, and preoperative treatment. We identified 25 and 50 patients who underwent OPEN and MIS, respectively, including 31 with distant metastasis. Both groups had similar background characteristics. The rate of major morbidities (Clavien-Dindo grade > III) was comparable between the 2 groups (P = .597), and there was no mortality in either group. MIS tended to result in shorter postoperative hospitalization than OPEN (P = .073). Perioperative alterations in laboratory data revealed that MIS suppressed surgical invasiveness better compared to OPEN. Postoperative chemotherapy, especially for patients with distant metastasis who underwent primary tumor resection, tended to be started earlier in the MIS group than in the OPEN group (P = .075). OS and RFS were comparable between the 2 groups (P = .996 and .870, respectively). In the multivariate analyses, MIS was not a significant prognostic factor for poor OS and RFS. MIS was surgically safe and showed similar oncological outcomes to OPEN-with the potential of reduced invasiveness and enhanced recovery from surgery. Therefore, patients undergoing MIS might receive subsequent postoperative treatments earlier.

STAT1-mediated induction of Ly6c-expressing macrophages are involved in the pathogenesis of an acute colitis model.

BACKGROUND: The development of inflammatory bowel diseases is thought to be multifactorial, but the exact steps in pathogenesis are poorly understood. In this study, we investigated involvement of the activation of STAT1 signal pathway in the pathogenesis of an acute colitis model. METHODS: A dextran sulfate sodium-induced acute colitis model was established by using wild-type C57BL/6 mice and STAT1-deficient mice. Disease indicators such as body weight loss and clinical score, induction of cytokines, chemokines, and inflammatory cells were evaluated in the acute colitis model. RESULTS: Disease state was significantly improved in the acute colitis model using STAT1-deficient mice compared with wild-type mice. The induction of Ly6c-highly expressing cells in colorectal tissues was attenuated in STAT1-deficient mice. IL-6, CCL2, and CCR2 gene expressions in Ly6c-highly expressing cells accumulated in the inflamed colon tissues and were significantly higher than in Ly6c-intermediate-expressing cells, whereas TNF-α and IFN-α/ß gene expression was higher in Ly6c-intermediate-expressing cells. Blockade of CCR2-mediated signaling significantly reduced the disease state in the acute colitis model. CONCLUSIONS: Two different types of Ly6c-expressing macrophages are induced in the inflamed tissues through the IFN-α/ß-STAT1-mediated CCL2/CCR2 cascade and this is associated with the pathogenesis such as onset, exacerbation, and subsequent chronicity of acute colitis.

The incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer in Japanese hospitals: A large-scale clinical study.

Aim: The aim of this retrospective study was to investigate the incidence of cardiovascular thrombotic complications after laparoscopic resection in colorectal cancer. Methods: This study involved 2017 patients with stages 0-III colorectal cancer who underwent laparoscopic surgery at 17 Japanese hospitals between January 2010 and December 2013. We assessed the incidence of postoperative cardiovascular thrombotic and haemorrhagic complications. Results: Laparoscopic surgeries were performed in 1152 men and 865 women with 1405 colon and 612 rectal cancers, respectively. Overall, 3%, 38%, 17%, 8%, and 9% of patients had comorbidities of heart failure, high blood pressure, diabetes, history of stroke, and vascular disease, respectively. Antithrombotic agents were being consumed by 17% of patients. The types (and perioperative rest periods) of the antithrombotic agents were aspirin in 58% (18.6 days), clopidogrel in 19% (21.1 days), cilostazol in 13% (13.3 days), and warfarin potassium in 21% (14.6 days) of cases with antithrombotic agents. Surgical time and blood loss in the total cohort were 234 minutes and 56 mL. Four cases (0.2%) had cardiovascular thrombotic complications, including one severe cardiac infarction and one stroke with major sequelae (CHADS2 scores were 2 points in both cases). Hemorrhagic complications occurred in 19 cases (0.9%). In particular, the incidence of the major gastroduodenal haemorrhagic ulcer was higher in cases with antithrombotic agents than without them (0.05% vs 0%, P = .02). Conclusion: The incidence of cardiovascular thrombotic complications was rare, although severe cardiac infarction and stroke could occur even after minimally invasive surgery in colorectal cancer.

Transabdominal Ultrasonography for Preoperative Diagnosis of Lymph Node Metastasis in Colon Cancer: A Retrospective Cohort Study.

Background/Aim: Although computed tomography (CT) is the standard modality for diagnosing lymph node metastasis (LNM), transabdominal ultrasonography (US) can be useful due to its high spatial resolution and use of Doppler signals to precisely analyse lymph nodes. This study aimed to evaluate the accuracy of US for lymph node assessment, establish US-based diagnostic criteria for LNM, and compare the capability of US with that of CT for the diagnosis of LNM. Patients and Methods: This retrospective, single-institution, cohort study included patients who underwent radical surgery for clinical stage 0-III colon cancer, between March 2012 and February 2019. Results: Overall, 34.9% (66/189) of patients had pathological LNM. The optimal US diagnostic criteria were 1) short axis ≥7 mm and short/long ratio ≥0.75 and 2) at least two of the following: the absence of hilar echoes, expansive appearance, or peripheral/mixed vascularity by the colour Doppler and/or contrast-enhanced method. Compared to CT, US showed a higher diagnostic sensitivity (54.5% vs. 43.9%; p=0.296), higher concordance with the number of pathological LNM (correlation coefficient: US, 0.42; CT, 0.27) and pathological N diagnosis (weighted ĸ: US, 0.35; CT, 0.18), and higher sensitivity for advanced LNM, including multiple LNMs (47.4% vs. 18.4%; p=0.014) and N2 stage (27.8% vs. 5.6%; p=0.177). Conclusion: US has higher sensitivity than CT for diagnosing LNM in colon cancer, along with a more accurate preoperative diagnosis of the N stage. Additionally, US may be more helpful than CT alone for preoperatively deciding the appropriateness of neoadjuvant treatment in colon cancer with advanced LNM.

Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Stable and Microsatellite Instability-High Locally Advanced Rectal Cancer.

PURPOSE: Preoperative chemoradiotherapy (CRT) and surgical resection are the standard treatment for locally advanced rectal cancer (LARC). Combining immune checkpoint inhibitors with radiation suggests a promising approach for enhancing efficacy. We investigated the efficacy of CRT followed by nivolumab and surgery in patients with LARC. PATIENTS AND METHODS: In phase I, we investigated the feasibility of sequentially combined CRT, 5 cycles of nivolumab, and radical surgery. In phase II, patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) LARC were evaluated. RESULTS: Three patients in phase I received full courses of CRT and nivolumab without dose modification; the schedule was recommended for phase II. A pathologic complete response (pCR) was centrally confirmed in 30% [11/37; 90% confidence interval (CI), 18%-44%] and 60% (3/5) of the MSS and exploratory MSI-H cohorts, respectively. While immune-related severe adverse events were observed in 3 patients, no treatment-related deaths were observed. In 38 patients with MSS who underwent surgery, pCR rates of 75% (6/8) and 17% (5/30; P = 0.004, Fisher exact test) were observed in those with programmed cell death ligand 1 (PD-L1) tumor proportion score ≥1% and <1%, respectively; IHC staining was performed using pre-CRT samples. In 24 patients with MSS, pre-CRT samples were analyzed by flow cytometry; pCR rates of 78% (7/9) and 13% (2/15; P = 0.003, Fisher exact test) were observed for CD8+ T cell/effector regulatory T cell (CD8/eTreg) ratios of ≥2.5 and <2.5, respectively, in tumor-infiltrating lymphocytes. CONCLUSIONS: CRT followed by consolidation nivolumab could increase pCR. PD-L1 expression and an elevated CD8/eTreg ratio were positive predictors in patients with MSS LARC.

The survival impact of preoperative FOLFOX for resectable locally advanced rectal cancer: the R-NAC-01 study.

PURPOSE: In this follow-up of the R-NAC-01 study, we assessed the long-term oncological benefit of four courses of modified leucovorin, 5-fluorouracil (FU), and oxaliplatin (mFOLFOX6) chemotherapy before rectal surgery. METHODS: In this prospective, multicenter study (UMIN 000012559) involving 11 hospitals in Japan, patients with lower rectal cancer underwent four cycles of mFOLFOX6 chemotherapy and subsequent surgery within four to six weeks. The 3-year recurrence-free survival and local recurrence rates were then reported. RESULTS: Of 41 patients (36 males, 5 females; mean age: 60.8 years old) who received 4 courses of chemotherapy, 40 underwent total mesorectal excision, and 1 underwent total pelvic exenteration. R0 resection was achieved in 40 patients, but none showed a pathological complete response. Twenty-nine patients received adjuvant chemotherapy for an average of 4 months. The 3 year recurrence-free survival and local recurrence rates in patients undergoing curable resection were 72.8% and 8.5%, respectively. cStage III patients with adjuvant chemotherapy had a significantly higher 3 year recurrence-free survival than those without adjuvant chemotherapy (76.6 vs. 40.0%, log-rank p = 0.03). CONCLUSION: Four courses of mFOLFOX6 chemotherapy before surgery may be a promising treatment strategy for locally advanced rectal cancer. Adjuvant chemotherapy might be needed for cStage III patients, even after four courses of neoadjuvant mFOLFOX6.

Impact of Endoscopic Surgical Skill Qualification on Laparoscopic Resections for Rectal Cancer in Japan: The EnSSURE Study.

Objective: This cohort study investigated short- and long-term postoperative outcomes of laparoscopic procedures for rectal cancer performed with versus without certified surgeons. Background: In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) evaluates surgical skills deemed essential for laparoscopic surgery; however, it is unknown whether this certification contributes to procedural safety. Methods: Outcomes of laparoscopic rectal resections for cStage II and III rectal cancer performed from 2014 to 2016 at 56 Japanese hospitals were retrospectively reviewed. The impact of having versus not having certified surgeons on postoperative complications and other short- and long-term outcomes were assessed. In cases with ESSQS-certified surgeons, surgeons attended surgery in the capacity of an operator, assistant, scope operator, or advisor. Results: Overall, 3188 procedures were analyzed, with 2644 procedures performed with and 544 without ESSQS-certified surgeons. A multivariate logistic regression model showed that the adjusted odds ratio of postoperative complications after procedures performed with ESSQS-certified surgeons was 0.68 (95% confidence interval, 0.51-0.91; P = 0.009). The adjusted odds ratios for conversion and pathological R0 resection rates with ESSQS-certified surgeons were 0.20 (P < 0.001) and 2.10 (P = 0.04), respectively. Multiple linear regression analyses showed significantly shorter surgical duration and more harvested lymph nodes for operations performed with ESSQS-certified surgeons. Multivariate Cox regression showed that the adjusted hazard ratios for poor overall and recurrence-free survival after operations performed with ESSQS-certified surgeons were 0.88 (P = 0.35) and 1.04 (P = 0.71), respectively. Conclusions: This study showed the superiority of the short-term postoperative results for laparoscopic rectal procedures performed with ESSQS-certified surgeons.

Lateral lymph node recurrence of rectal cancer with a pathological complete response to chemotherapy confirmed by laparoscopic lateral lymph node dissection: A case report.

Lateral lymph node (LLN) metastasis is one of the forms of local recurrence after surgery for lower rectal cancer. We here present a case of LLN recurrence of rectal cancer that was shown by laparoscopic lateral lymph node dissection (LLND) to have a complete pathological response to chemotherapy. A 58-year-old man underwent open low anterior resection for lower rectal cancer. After detection of right LLN recurrence 43 months after the operation, 11 cycles of capecitabine, oxaliplatin, and bevacizumab chemotherapy were administered. Laparoscopic right LLND was performed 55 months after the first operation. Pathological examination revealed no viable tumor cells in the dissected lymph nodes. The patient remains alive without recurrence 61 months after the first surgery and 6 months after laparoscopic LLND. Laparoscopic LLND for LLN recurrence of rectal cancer is feasible and should be considered a valid treatment option.

Modified complete mesocolic excision with central vascular ligation by the squeezing approach in laparoscopic right colectomy.

PURPOSE: Complete mesocolic excision (CME) and central vascular ligation (CVL) are becoming the standard procedure in laparoscopic right-sided colectomy. However, the approach to CME and CVL has not been established, although several useful approaches have been reported. The squeezing approach described herein is a novel procedure to perform modified CME and CVL in laparoscopic right colectomy. METHODS: The squeezing approach features retroperitoneal mobilization followed by cranial mesocolic mobilization and lymph node dissection using a cranial approach followed by a caudal approach. Dissection of the regional lymph nodes along with central vascular ligation was performed along the anterior wall of the superior mesenteric vein. In total, 177 patients (mean age, 70.6 years; male-to-female ratio, 90:87) who underwent laparoscopic right-sided colectomy were retrospectively assessed. Descriptive statistics for patient characteristics were calculated. RESULTS: The mean operative time and blood loss were 169 min and 37 mL, respectively. Seven patients (4.0%) required conversion to open surgery, and major postoperative complications occurred in five patients (2.8%) with no anastomotic leakage. Histological R0 resection was achieved in all cases of stages 0-III colon cancer. The 5-year recurrence-free survival rates were 100% (n = 19), 100% (n = 40), 87% (n = 46), and 81% (n = 43) in pathological stages 0, I, II, and III, respectively. Node recurrence occurred in one case near the root of the middle colic artery. CONCLUSION: The novel squeezing approach in laparoscopic right colectomy could be safely performed in terms of the technical and oncological aspects.

Preoperative Elemental Diet before Laparoscopic Anterior Resection in Patients with Advanced Stenotic Rectal Cancer.

OBJECTIVES: To evaluate the feasibility of our new preoperative enteral nutrition protocol using ElentalⓇ without mechanical bowel preparation (MBP) before laparoscopic anterior resection (LAR) in patients with advanced stenotic rectal cancer. METHODS: Among 74 patients with advanced rectal cancer (clinical stages T3 and T4) scheduled to undergo LAR, 42 patients with stenotic rectal cancer were administered ElentalⓇ (900 kcal/day) without MBP before LAR (group S). Thirty-two patients without stenosis (group NS) did not receive preoperative nutritional support but underwent MBP. RESULTS: Group S patients were maintained in a fasting state and received an elemental diet approximately 10 days preoperatively without severe adverse effects. The incidence of postoperative complications (Clavien-Dindo classification ≥ grade 2) was significantly lower in group S than that in group NS (adjusted odds ratio [OR]: 6.046, P = 0.008). Logistic regression analysis revealed that group NS exhibited higher risks of developing postoperative complications than those exhibited by group S (OR: 4.32, 95% confidence interval [CI]: 1.28-17.28, P = 0.018). Among preoperative characteristics, the clinical tumor stage indicated a significant intergroup difference. Thus, the clinical stage was selected as a covariate and adjusted in the logistic regression model to calculate a covariate-adjusted OR. Group NS exhibited a higher incidence of postoperative complications than group S (adjusted OR: 6.05, 95% CI: 1.58-28.35, P = 0.008). CONCLUSIONS: Administration of an elemental diet using ElentalⓇ without MBP before LAR is a feasible strategy in patients with advanced stenotic rectal cancer. Application of this research may encourage use of ElentalⓇ in the clinical setting.