GRECCAR 14 - a multicentric, randomized, phase II-III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol.

AIM: Total neoadjuvant treatment (TNT) is becoming standard in patients with locally advanced rectal carcinoma (LARC). Preoperative chemoradiotherapy (CRT) has proven side effects on bowel and genitourinary function. An early tumoral response to induction chemotherapy demonstrates its high prognostic value. Tailored management could be used as an alternative to systematic CRT. The GRECCAR 14 trial will attempt to personalize treatment strategy according to the patient's early tumour response to intensive chemotherapy with the aim of achieving the best toxicity-efficiency ratio. METHOD: GRECCAR 14 is a multicentric, randomized, two-arm, phase II-III noninferiority trial. Patients with mid or low LARC with a predictive circumferential resection margin ≤2 mm or T3c-d stage with extramural venous invasion will be included. Evaluation of the tumoral response will be performed after six courses of high-dose FOLFIRINOX chemotherapy. Good responders (GRs) will be defined by a 60% decrease in tumoral volume on magnetic resonance imaging. Patients will be randomized to CRT before surgery. The primary endpoints will be R0 resection for phase II and the 3-year disease-free survival (DFS) for phase III. RESULTS: Tailored management of LARC is becoming an exciting challenge for the modality of neoadjuvant treatment and for the type of surgery or its omission. Neoadjuvant FOLFIRINOX has established efficacy, with a significant increase in the 3-year DFS. Better control of systemic disease must be accompanied by the same locoregional control, with the lowest morbidity. Our previous GRECCAR 4 trial demonstrated the high value of the early tumoral response after induction chemotherapy and the long-term safety of tailored management for GRs. CONCLUSION: If GRECCAR 14 demonstrates the ability to tailor TNT for LARC, this could lead to changes in clinical practice.

Tailored Management with Highly-Selective Diversion for Low Colorectal Anastomosis: Biochemical Postoperative Follow-Up and Long-Term Results from a Single-Institution Cohort.

BACKGROUND: Defunctioning stoma (DS) can decrease the rate of symptomatic anastomotic leakage (AL). Since 2010, we have used tailored, highly selective DS management for low colorectal anastomosis (LCRA). METHODS: In total, 433 rectal cancer patients underwent the same standardized procedure. Non-stoma (NS) management was used in patients with no surgical difficulties as well as good colonic preparation and quality of anastomoses. In all other cases, DS was used. C-reactive protein was measured during postoperative follow-up. Imbalance in the initial population was adjusted using propensity-score matching according to sex, age, body mass index, tumor location, and American Society of Anesthesiologists score. Rate of AL within 30 days, 5-year overall survival, local relapse-free survival, and disease-free survival were recorded. RESULTS: Anastomosis was mostly ultra-low and was performed equally by laparoscopy or robotic surgery. The overall rate of AL was 13.4%, with no significant differences between groups (DS, 12.2%; NS, 14.6%; p = 0.575). Operative time, blood loss, and hospital stay were significantly lower for NS patients. The rate of secondary stoma was 11.4% overall. Pathological results were similar, with a 98% R0 resection rate. With a median follow-up of 5.5 years for the NS and DS groups, the overall survival was 84.9% and 73.4%, respectively (p = 0.064), disease-free survival was 67.0% and 55.8%, respectively (p = 0.095), and local relapse-free survival was 95.2% and 88.7%, respectively (p = 0.084). The long-term, stoma-free rate was 89.1% overall. CONCLUSIONS: Tailoring DS for LCRA seems safe and could provide potential benefits in postoperative morbidity with the same long-term oncological results in NS patients. Prospective, multicentric studies should validate this approach.

A multicentre, prospective cohort study of handsewn versus stapled intracorporeal anastomosis for robotic hemicolectomy.

AIM: Robotic right hemicolectomy is gaining in popularity due to the recognized technical benefits associated with the robotic platform. However, there is a lack of standardization regarding the optimal anastomotic technique in this cohort of patients, namely stapled or handsewn intra- or extra-corporeal anastomosis. The ergonomic benefit associated with the robotic platform lends itself to intracorporeal anastomosis (ICA). The aim of this study was to compare the short-term clinical outcomes of stapled versus handsewn ICA. METHOD: A multicentre prospective cohort study was undertaken across four high-volume robotic centres in France between September 2018 and December 2020. All adult patients undergoing an elective robotic right hemicolectomy with an ICA performed and a minimum postoperative follow-up of 30 days were included. The primary endpoint of our study was anastomotic leak within 30 days postoperatively. RESULTS: A total of 144 patients underwent robotic right hemicolectomy: 92 (63.8%) had a stapled ICA and 52 (36.1%) a handsewn ICA. The operative indication was adenocarcinoma in 90% with a stapled ICA compared with 62% in the handsewn ICA group (p < 0.001). The overall operating time was longer in the handsewn ICA group compared with the stapled ICA group (219 min vs. 193 min; p = 0.001). The anastomotic leak rate was 3.3% in stapled ICA and 3.8% in handsewn ICA (p = 1.00). There was no difference in the rate or severity of postoperative morbidity. CONCLUSION: ICA robotic hemicolectomy is technically safe and is associated with low rates of anastomotic leak overall and equivalent clinical outcomes between the two techniques.

Sphincter-saving surgery for ultra-low rectal carcinoma initially indicated for abdominoperineal resection: Is it safe on a long-term follow-up?

BACKGROUND: Rate of abdominoperineal resection (APR) varies from countries and surgeons. Surgical impact of preoperative treatment for ultra-low rectal carcinoma (ULRC) initially indicated for APR is debated. We report the 10-year oncological results from a prospective controlled trial (GRECCAR 1) which evaluate the sphincter saving surgery (SSR). METHODS: ULRC indicated for APR were included (n = 207). Randomization was between high-dose radiation (HDR, 45 + 18 Gy) and radiochemotherapy (RCT, 45 Gy + 5FU infusion). Surgical decision was based on tumour volume regression at surgery. SSR technique was standardized as mucosectomy (M) or partial (PISR)/complete (CISR) intersphincteric resection. RESULTS: Overall SSR rate was 85% (72% ISR), postoperative morbidity 27%, with no mortality. There were no significant differences between the HDR and RCT groups: 10-year overall survival (OS10) 70.1% versus 69.4%, respectively, 10.2% local recurrence (9.2%/14.5%) and 27.6% metastases (32.4%/27.7%). OS and disease-free survival were significantly longer for SSR (72.2% and 60.1%, respectively) versus APR (54.7% and 38.3%). No difference in OS10 between surgical approaches (M 78.9%, PISR 75.5%, CISR 65.5%) or tumour location (low 64.8%, ultralow 76.7%). CONCLUSION: GRECCAR 1 demonstrates the feasibility of safely changing an initial APR indication into an SSR procedure according to the preoperative treatment tumour response. Long-term oncologic follow-up validates this attitude.

Robotic Radical Hysterectomy for Cervical Adenocarcinoma after Preoperative Brachytherapy in 10 Steps.

STUDY OBJECTIVE: Minimally invasive surgery decreases postoperative morbidity after radical hysterectomy (RH) for early-stage cervical cancer. However, a randomized trial and large retrospective data question its safety after observing lower rates of survival than open surgery [1,2]. The causes of this higher recurrence rate are not definitely established but may result from cancer exposure to the peritoneum during vaginal section and cancerous cells' spillage enhanced by pneumoperitoneum or a uterine manipulator. The aim of this surgical video was to present a standardized step-by-step approach for robotic RH according to the recent recommendations from the ARCAGY -Group of National Investigators for the Study of Ovarian and Breast Cancers surgeon's group [3]. DESIGN: Step-by-step video demonstration of the technique. SETTING: Tertiary center specialized in gynecologic oncology and minimally invasive surgery. INTERVENTIONS: A 48-year-old woman was diagnosed with a stage IB2 endocervical adenocarcinoma (International Federation of Gynecology and Obstetrics 2018) with a tumor size of 27 mm. Surgery was planned after preoperative pulsed dose rate uterovaginal brachytherapy. Surgery was performed following 10 reproducible steps: • Pelvic sentinel node identification according to the SENTICOL-III trial • Right infundibulopelvic and round ligaments transection • Right uterine vessels transection • Parametrectomy • Right uterosacral ligament transection • Bladder mobilization • Identical left dissection • Rectovaginal space development • Colpectomy by vaginal route after complete pneumoperitoneum exsufflation • Robotic vaginal cuff closure and pelvic inspection Thorough robotically assisted vaginal cuff closure was carried out as a comparative study suggesting that abdominal closure may decrease vaginal complications and dehiscence [3]. CONCLUSION: No international recommendations for the RH approach have yet been endorsed. Patients must be clearly informed about the benefit-risk ratio of the surgical route. If a minimally invasive RH is still decided, the patient should be referred to experienced centers, and precautionary measures must be implemented [4]. Colpotomy by vaginal route without pneumoperitoneum is recommended. Uterine manipulators have to be strictly avoided. Preoperative brachytherapy has been reported in experienced centers in France with favorable histologic response with high rates of pathologic complete response (near 70%) and seems particularly worthwhile for tumor sizes ranging from 2 to 4 cm or presenting with lymphovascular invasion [5].

Robotic Versus Laparoscopic Total Mesorectal Excision for Sphincter-Saving Surgery: Results of a Single-Center Series of 400 Consecutive Patients and Perspectives.

OBJECTIVE: The aim of this study is to compare robotic total mesorectal excision (R-TME) with laparoscopic TME (L-TME) in a series of consecutive rectal cancer patients. BACKGROUND: R-TME and L-TME have drawn contradictory reports. A recent phase III trial (ROLARR) concluded that R-TME performed by surgeons with varying experience did not confer an advantage in rectal cancer resection. PATIENTS AND METHODS: In this retrospective single-center cohort study (8/2008 to 4/2015), data were prospectively registered. A total of 200 L-TME and 200 R-TME were operated consecutively without selection. The primary outcome was the conversion rate to open laparotomy or transanal TME. The secondary endpoints were type of anastomosis, operative time, postoperative morbidity, circumferential radial (CRM) and distal margins, quality of life, bladder and sexual dysfunction, and oncological outcomes. RESULTS: Baseline characteristics were well balanced. Type of anastomosis [colo-anal anastomosis (CAA) 40% vs 49%; p < 0.001], transanal TME (5% vs 13%; p = 0.005), and conversion rate (2% vs 9.5%; odd ratio (OR): 0.19 [95% confidence interval (CI): 0.05-0.60]) were significantly different. Intersphincteric resection (39% vs 47%), diverting stoma (66.5% vs 68%), CRM involvement, median operative time (243 vs 232 min), and R0 resection rate were similar. Conversion risk was lower for R-TME in male patients and those with small tumors (< 5 cm). The 3-year overall survival rate was 84.1% [77.3-88.9%] and 88.4% [82.9-92.2%] in the R-TME and L-TME group. No significant differences were reported in quality of life, and urinary or sexual function. CONCLUSIONS: R-TME is less likely to be converted to open surgery than L-TME; operative time and curative pathologic criteria are equivalent. Future prospective trial should compare standardized procedures performed by experienced surgeons for subgroups of high-risk patients.

Determination of biomarkers associated with neoadjuvant treatment response focusing on colibactin-producing Escherichia coli in patients with mid or low rectal cancer: a prospective clinical study protocol (MICARE).

INTRODUCTION: The management of mid and low rectal cancer is based on neoadjuvant chemoradiotherapy (CRT) followed by standardised surgery. There is no biomarker in rectal cancer to aid clinicians in foreseeing treatment response. The determination of factors associated with treatment response might allow the identification of patients who require tailored strategies (eg, therapeutic de-escalation or intensification). Colibactin-producing Escherichia coli (CoPEC) has been associated with aggressive colorectal cancer and could be a poor prognostic factor. Currently, no study has evaluated the potential association between intestinal microbiota composition and tumour response to CRT in mid and low rectal cancer. The aim of this study is to assess the association between response to neoadjuvant CRT and faecal intestinal microbiota composition and/or CoPEC prevalence in patients with mid or low rectal cancer. METHODS AND ANALYSIS: This is a non-randomised bicentric prospective clinical study with a recruitment capacity of 200 patients. Three stool samples will be collected from participants with histological-proven adenocarcinome of mid or low rectum who meet eligibility criteria of the study protocol: one before neoadjuvant treatment start, one in the period between CRT end and surgery and one the day before surgery. In each sample, CoPEC will be detected by culture in special media and molecular (PCR) approaches. The global microbiota composition will be also assessed by the bacterial 16S rRNA gene sequencing. Neoadjuvant CRT response and tumour regression grade will be described using the Dworak system at pathological examination. Clinical data and survival outcomes will also be collected and investigated. ETHICS AND DISSEMINATION: MICARE was approved by the local ethics committee (Comité de Protection des Personnes Sud-Est II, 18 December 2019. Reference number 2019-A02493-54 and the institutional review board. Patients will be required to provide written informed consent. Results will be published in a peer reviewed journal. TRIAL REGISTRATION NUMBER: NCT04103567.

Transrectal ultrasound image-based real-time augmented reality guidance in robot-assisted laparoscopic rectal surgery: a proof-of-concept study.

PURPOSE: Surgical treatments for low-rectal cancer require careful considerations due to the low location of cancer in rectums. Successful surgical outcomes highly depend on surgeons' ability to determine clear distal margins of rectal tumors. This is a challenge for surgeons in robot-assisted laparoscopic surgery, since tumors are often concealed in rectums and robotic surgical instruments do not provide tactile feedback for tissue diagnosis in real time. This paper presents the development and evaluation of an intraoperative ultrasound-based augmented reality framework for surgical guidance in robot-assisted rectal surgery. METHODS: Framework implementation consists in calibrating the transrectal ultrasound (TRUS) and the endoscopic camera (hand-eye calibration), generating a virtual model and registering it to the endoscopic image via optical tracking, and displaying the augmented view on a head-mounted display. An experimental validation setup is designed to evaluate the framework. RESULTS: The evaluation process yields a mean error of 0.9 mm for the TRUS calibration, a maximum error of 0.51 mm for the hand-eye calibration of endoscopic cameras, and a maximum RMS error of 0.8 mm for the whole framework. In the experiment with a rectum phantom, our framework guides the surgeon to accurately localize the simulated tumor and the distal resection margin. CONCLUSIONS: This framework is developed with our clinical partner, based on actual clinical conditions. The experimental protocol and the high level of accuracy show the feasibility of seamlessly integrating this framework within the surgical workflow.