[Rectal cancer: Towards personalized medicine]. / Cancer du rectum : vers une prise en charge personnalisée.

The standard of care for patients with locally advanced rectal cancer has recently changed and is now based on the concept of total neoadjuvant therapy with the association of radiotherapy and systemic chemotherapy before radical surgery. The addition of noeadjuvant systemic chemotherapy before or after radiotherapy during preoperative course significantly decreased the risk of distant metastases and prolonged disease-free survival after surgery. The risk of recurrence varies among patients and the standard management associating chemotherapy, radiotherapy and surgery may expose many patients to overtreatment and can negatively affect quality of life. In this setting, several ongoing trials evaluate the possibility of less aggressive individually tailored approach based on omission of one of three treatments. In particular, NORAD and PROSPECT trials evaluate whether irradiation could be safely omitted in patients who are good responders to induction chemotherapy and have locally advanced primarily resectable tumor with large predictive circumferential resection margin. In the other hand, the total neoadjuvant therapy had significantly improved the pathological complete response rate, up to 30%, leading the concept of non-operative management and organ-preserving strategies. The phase III GRECCAR 12 study has therefore evaluated the potential benefit of intensification of neoadjuvant chemotherapy whereas OPERA and MORPHEUS trials assessed radiotherapy dose escalation by contact X-ray or brachytherapy for organ-preserving strategies. To date, total neoadjuvant therapy following by radical surgery remains the standard of care but probably less aggressive approach with omission of radiotherapy or surgery will become a new standard in selected patients in next future.

New treatment strategies for non-metastatic rectal cancer.

The most widely practiced (standard) treatment of non-metastatic rectal cancer is based on proctectomy with mesorectal excision (partial or total according to the location of the tumor and commonly called TME). Surgery is preceded by CAP50-type chemoradiotherapy (capecitabineand 50 Grays radiation) and performed 6-8 weeks after the end of chemoradiotherapy. The development of new endoscopic, surgical, radiation-based and chemotherapeutic modalities leads surgeons to envisage customized treatment to find the best compromise between functional and oncologic results according to the locoregional extension of the tumor. Superficial lesions are amenable to transanal excision. T2-3 tumors<4cm are amenable to rectal preservation when neoadjuvant treatment obtains a complete response, allowing local excision or close surveillance. Intensification endocavitary radiotherapy and induction and consolidation chemotherapy regimens to avoid recourse to salvage abdomino-perineal resection (APR) are under investigation. For locally advanced rectal cancers (T3-4 and all N+ irrespective of T), the following scenarios can be envisaged: for initially resectable tumors (T3N0, T1-T3N+, circumferential resection margin>2mm), neoadjuvant chemotherapy alone aims to minimize the risk of local recurrence while avoiding the sequelae of radiotherapy. In case of initially non-resectable tumors (T4, circumferential resection margin<1mm), induction chemotherapy before chemoradiotherapy and consolidation chemotherapy after short course radiotherapy provide better results than standard treatment in terms of complete response and recurrence-free survival, and should be routinely proposed in this indication.

A Reappraisal of Outcome of Elective Surgery After Successful Non-Operative Management of an Intra-Abdominal Abscess Complicating Ileocolonic Crohn's Disease: A Subgroup Analysis of a Nationwide Prospective Cohort.

BACKGROUND AND AIMS: Few prospective data exist on outcomes of surgery in Crohn's disease [CD] complicated by an intra-abdominal abscess after resolution of this abscess by antibiotics optionally combined with drainage. METHODS: From 2013 to 2015, all patients undergoing elective surgery for CD after successful non-operative management of an intra-abdominal abscess [Abscess-CD group] were selected from a nationwide multicentre prospective cohort. Resolution of the abscess had to be computed tomography/magnetic resonance-proven prior to surgery. Abscess-CD group patients were 1:1 matched to uncomplicated CD [Non-Penetrating-CD group] using a propensity score. Postoperative results and long-term outcomes were compared between the two groups. RESULTS: Among 592 patients included in the registry, 63 [11%] fulfilled the inclusion criteria. The abscess measured 37 ±â€…20 mm and was primarily managed with antibiotics combined with drainage in 14 patients and nutritional support in 45 patients. At surgery, a residual fluid collection was found in 16 patients [25%]. Systemic steroids within 3 months before surgery [p = 0.013] and the absence of preoperative enteral support [p = 0.001] were identified as the two significant risk factors for the persistence of a fluid collection. After propensity score matching, there was no significant difference between the Abscess-CD and Non-Penetrating-CD groups in the rates of primary anastomosis [84% vs 90% respectively, p = 0.283], overall [28% vs 15% respectively, p = 0.077] and severe postoperative morbidity [7% vs 7% respectively, p = 1.000]. One-year recurrence rates for endoscopic recurrence were 41% in the Abscess-CD and 51% in the Non-Penetrating-CD group [p = 0.159]. CONCLUSIONS: Surgery after successful non-operative management of intra-abdominal abscess complicating CD provides good early and long-term outcomes.

Colon sparing resection versus extended colectomy for left-sided obstructing colon cancer with caecal ischaemia or perforation: a nationwide study from the French Surgical Association.

AIM: It is not known whether patients with obstructive left colon cancer (OLCC) with caecal ischaemia or diastatic perforation (defined as a blowout of the caecal wall related to colonic overdistension) should undergo a (sub)total colectomy (STC) or an ileo-caecal resection with double-barrelled ileo-colostomy. We aimed to compare the results of these two strategies. METHOD: From 2000 to 2015, 1220 patients with OLCC underwent surgery by clinicians who were members of the French Surgical Association. Of these cases, 201 (16%) were found to have caecal ischaemia or diastatic perforation intra-operatively: 174 patients (87%) underwent a STC (extended colectomy group) and 27 (13%) an ileo-caecal resection with double-end stoma (colon-sparing group). Outcomes were compared retrospectively. RESULTS: In the extended colectomy group, 95 patients (55%) had primary anastomosis and 79 (45%) had a STC with an end ileostomy. In the colon-sparing group, 10 patients (37%) had simultaneous resection of their primary tumour with segmental colectomy and an anastomosis which was protected by a double-barrelled ileo-colostomy. The demographic data for the two groups were comparable. Median operative time was longer in the STC group (P = 0.0044). There was a decrease in postoperative mortality (7% vs 12%, P = 0.75) and overall morbidity (56% vs 67%, P = 0.37) including surgical (30% vs 40%, P = 0.29) and severe complications (17% vs 27%, P = 0.29) in the colon-sparing group, although these differences did not reach statistical significance. Cumulative morbidity included all surgical stages and the rate of permanent stoma was 66% and 37%, respectively, with no significant difference between the two groups. Overall survival and disease-free survival were similar between the two groups. CONCLUSION: The colon-sparing strategy may represent a valid and safe alternative to STC in OLCC patients with caecal ischaemia or diastatic perforation.

Elective surgery for tumours of the splenic flexure: a French inter-group (AFC, SFCD, FRENCH, GRECCAR) survey.

BACKGROUND: In an elective setting, there is no consensus regarding the type of colectomy that is best for patients with tumors of the splenic flexure: segmental left colectomy (or splenic flexure colectomy), left hemicolectomy or subtotal colectomy (or extended right hemicolectomy). In the United Kingdom, extended right hemicolectomy is preferred by surgeons. The aim of the present survey was to report on the practices in France for this particular tumor location. METHODS: Between 15/07/17 and 15/10/17, members of two French surgical societies [the French Association of Surgery (AFC) and the French Society of Digestive Surgery (SFCD)] and two French surgical cooperative groups [the French Federation of Surgical Research (FRENCH) and the French Research Group of Rectal Cancer Surgery (GRECCAR)] were solicited by email to answer an online anonymous questionnaire. RESULTS: A total of 190 out of 420 surgeons participated in this study (response rate 45%). The preferred procedure was splenic flexure colectomy (70%), followed by left hemicolectomy (17%) and subtotal colectomy (13%). The most used surgical approach was laparoscopy (63%), followed by laparotomy (31%) and hand-assisted laparoscopy (6%). Lymph node dissection was extended to the middle colic artery in 29% of splenic flexure colectomies and in 33% of left hemicolectomies. Twenty-nine percent of responders thought that tumors of the splenic flexure had a worse prognosis in comparison with other colonic sites, because of insufficient lymph node dissection (73%) or a more advanced stage (50%) at diagnosis. However, this opinion did not change the type of colectomy performed. CONCLUSIONS: There is a strong consensus in France to operate tumors of the splenic flexure with a splenic flexure colectomy and lymph node dissection limited to the left colic artery.

BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases.

BACKGROUND: BRAF mutation is associated with a poor prognosis in patients with metastatic colorectal cancer. For patients with resectable colorectal liver metastases (CRLMs), the prognostic impact of BRAF mutation is unknown and the benefit of surgery debated. This nationwide intergroup (ACHBT, FRENCH, AGEO) study aimed to evaluate the oncological outcome of patients undergoing liver resection for BRAF-mutated CRLMs. METHODS: The study included patients who underwent resection for BRAF-mutated CRLMs in 24 centres between 2012 and 2016. A case-matched comparison was made with 183 patients who underwent resection of CRLMs with wild-type BRAF during the same interval. RESULTS: Sixty-six patients who underwent resection for BRAF-mutated CRLMs in 24 centres were compared with 183 patients with wild-type BRAF. The 1- and 3-year disease-free survival (DFS) rates were 46 and 19 per cent for the BRAF-mutated group, and 55·4 and 27·8 per cent for the group with wild-type BRAF (P = 0·430). In multivariable analysis, BRAF mutation was not associated with worse DFS (hazard ratio 1·16, 95 per cent c.i. 0·72 to 1·85; P = 0·547). The 1- and 3-year overall survival rates after surgery were 94 and 54 per cent respectively among patients with BRAF mutation, and 95·8 and 82·9 per cent in those with wild-type BRAF (P = 0·004). Median survival after disease progression was 23·0 (95 per cent c.i. 11·0 to 35·0) months among patients with mutated BRAF and 44·3 (35·9 to 52·6) months in those with wild-type BRAF (P = 0·050). Multisite disease progression was more common in the BRAF-mutated group (48 versus 29·8 per cent; P = 0·034). CONCLUSION: These results support surgical treatment for resectable BRAF-mutated CRLM, as BRAF mutation by itself does not increase the risk of relapse after resection. BRAF mutation is associated with worse survival in patients whose disease relapses after resection of CRLM, as for non-metastatic colorectal cancer.

The accuracy of preoperative imaging in measuring the length of the ileocolic segment affected by Crohn's disease: a prospective cohort study.

AIM: The study aimed to evaluate the accuracy of imaging for measurement of the length of the ileocolic segment affected by Crohn's disease. METHOD: Fifty-four consecutive patients who underwent resection between 2011 and 2014 for ileocolic Crohn's disease were prospectively studied. All had preoperative MR or CT enterography. Two independent radiologists measured the length of the diseased intestinal segment. The measurements were compared with the length of disease assessed on pathology of the non-fixed surgical specimen. RESULTS: The median preoperative length of the Crohn's disease segment on imaging was 20.5 (2-73) cm and 20 (3-90) cm, as measured by the two radiologists. Interobserver agreement was substantial (κ = 0.69) with a correlation coefficient (r) of 0.82 (P < 0.001). The median length of the Crohn's disease segment on pathological examination was 16.5 (2-75) cm and was closely correlated with the radiological measurement (r = 0.76, P < 0.001). The length of the Crohn's disease segment on imaging was correct to within 5 cm of the value on pathology. It was correct in 30 (55%) patients and was underestimated and overestimated in 6 (11.1%) and 18 (33.3%). A length of disease of less than 20 cm found on imaging in 26 patients was confirmed in 25 (96%) on pathology, whereas a length of more than 20 cm found on imaging in 28 patients was confirmed in 18 (64%) on pathology. The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of imaging for predicting a length of less than 20 cm were 71%, 95%, 96%, 64% and 79%. CONCLUSION: Imaging accurately identifies the length of the ileocolic segment of Crohn's disease when it is 20 cm or less on pathological examination. In patients with more extensive disease, imaging tends to overestimate the length and should be interpreted with caution.

Practice patterns for complex situations in the management of rectal cancer: A multidisciplinary inter-group national survey.

GOAL: To report the current clinical practice of French physicians for rectal cancer in various complex settings. METHODS: Nineteen clinical situations and four surveillance modalities were proposed to a panel of experts via 11 learned societies. The answers of 48 experts and the impact of colorectal specialists on therapeutic options were compared to those of other participants. RESULTS: A total of 722 physicians [surgeons=319 (44%), gastro-intestinal oncologists=305 (42%), radiotherapists=98 (14%)] participated in this study. The mean number of answers per question was 500. A consensus was reached in 19 clinical situations. Approaches according to specialty were similar in most situations. In seven settings, the therapeutic strategy differed significantly (interval between the end of chemo-radiation and surgery, attitude based on response of neo-adjuvant therapy, treatment of usT1N0 or pT1sm2 tumors after endoscopic resection, adjuvant therapy for pT3N1 tumors, interval to protective stoma closure, and schedule of follow-up surveillance). There was disagreement between experts and non-experts with regard to three management plans (contra-indications for neo-adjuvant chemo-radiation therapy, strategy according to response to neo-adjuvant therapy, and date of protective stoma closure). CONCLUSION: This survey provides an overview of current practice of a selected group of French physicians. Sound knowledge of the current literature and case-by-case discussion with a group of experts from each involved specialty during a multidisciplinary conference are essential. Certain complex cases should be presented to expert centers to validate the therapeutic approach.

Outcome of emergency surgery for severe neuroleptic-induced colitis: results of a prospective cohort.

AIM: The study evaluated the outcome of severe acute antipsychotic (neuroleptic) drug related colitis requiring emergency surgery. METHOD: From 2009 to 2014, 20 patients underwent emergency surgery for acute and severe neuroleptic-related ischaemic colitis. Neuroleptic-induced colitis was defined as another cause besides inflammatory, infectious or ischaemic colitis with a relationship to treatment by antipsychotic drugs. RESULTS: The main drugs involved were cyamemazine (n = 9, 45%), loxapine (n = 5, 25%), haloperidol (n = 4, 20%) and alimemazine (n = 4, 20%). Most (n = 14, 70%) patients presented with haemodynamic instability requiring massive resuscitation and vasopressive drugs. CT signs of digestive impairment were found in 13 (65%) patients having emergency surgery. The lesions were pancolonic in 40%; transparietal necrosis was found in 45% and 15% had colonic perforation. Twelve (60%) patients had total or subtotal colectomy and eight (40%) a segmental colectomy with colostomy or ileostomy in all cases. The postoperative mortality was 15% and morbidity was 70%, necessitating surgical reintervention in two (10%) patients. Of the 17 surviving patients, 11 (64.7%) had restoration of intestinal continuity after a median delay of 103 days, with a postoperative morbidity rate of 36.3%. In the intent-to-treat population, the permanent stoma rate was 30%. CONCLUSION: The morbidity and mortality of surgery for neuroleptic-drug-induced colitis is higher than for colitis due to other causes. A better knowledge of this condition should lead to early diagnosis.

Cardiophrenic angle lymph node is an indicator of metastatic spread but not specifically peritoneal carcinomatosis in colorectal cancer patients: Results of a prospective validation study in 91 patients.

BACKGROUND: The presence of cardiophrenic angle lymph node (CPALN) has been associated with the risk of peritoneal carcinomatosis (PC) in high risk colon cancer patients. Its accuracy to predict PC and its prognostic value in non-selected CRC patients has not been validated prospectively. METHODS: From 2011 to 2013, all patients undergoing colectomy for colon cancer were included prospectively. Presence of CPALN was assessed on preoperative computed tomography scan by two radiologists. Surgical exploration was used as reference for the diagnosis of PC. Factors associated with presence of CPALN and progression-free survival were analyzed. RESULTS: Ninety one patients fulfilled inclusion criteria. CPALN was detected in 36 patients (39.5%) on CT scan. At surgical exploration, PC was found in 6 patients (6.5%). Sensitivity, specificity, negative predictive value, positive predictive value and overall accuracy of CPALN on CT scan for predicting PC were 67%, 62%, 96%, 11% and 63% respectively. In multivariate analysis, the presence of distant metastases whatever the site was associated with the presence of CPALN (p = 0.03; hazard ratio HR = 3.8; confidence interval CI 95% = 1.1-13.3). In the multivariate analysis, only vascular involvement (p = 0.034, HR = 3.574, CI 95% = 1.10-11.60) was associated with progression-free survival whereas CPALN was not found to predict outcome (p = 0.893). CONCLUSION: CPALN is a common finding in non-selected colon cancer patients. Although in the absence of CPALN, PC can almost be excluded, its value for the diagnosis of PC is limited. Our findings support that CPALN is mainly an indicator of metastatic spread of the tumor.

Nutritional assessment and screening for malnutrition.

Malnutrition can be detected in up to 50% of patients with gastrointestinal cancer. Although malnutrition reflects the severity of cancer, it is important to underline that anticancer treatments including surgery likely increase the severity of malnutrition. Additionally, malnutrition is associated with an increased risk of perioperative morbidity and mortality. Nutritional assessment should be a part of pre-treatment work up of gastrointestinal cancer patients because nutritional support has been shown to limit the negative impact of malnutrition on perioperative outcome. The objective of these practice guidelines is to address the following questions regarding nutritional screening in gastrointestinal cancer patients: who should benefit from nutritional assessment, when nutritional assessment should be proposed, how nutritional assessment should be carried out and why nutritional assessment is indicated.

Pathological response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation.

AIM: Pathological response to chemotherapy without pelvic irradiation is not well defined in rectal cancer. This study aimed to evaluate the objective pathological response to preoperative chemotherapy without pelvic irradiation in middle or low locally advanced rectal cancer (LARC). METHODS: Between 2008 and 2013, 22 patients with middle or low LARC (T3/4 and/or N+ and circumferential resection margin < 2 mm) and synchronous metastatic disease or a contraindication to pelvic irradiation underwent rectal resection after preoperative chemotherapy. The pathological response of rectal tumour was analysed according to the Rödel tumour regression grading (TRG) system. Predictive factors of objective pathological response (TRG 2-4) were analysed. RESULTS: All patients underwent rectal surgery after a median of six cycles of preoperative chemotherapy. Of these, 20 (91%) had sphincter saving surgery and an R0 resection. Twelve (55%) patients had an objective pathological response (TRG 2-4), including one complete response. Poor response (TRG 0-1) to chemotherapy was noted in 10 (45%) patients. In univariate analyses, none of the factors examined was found to be predictive of an objective pathological response to chemotherapy. At a median follow-up of 37.2 months, none of the 22 patients experienced local recurrence. Of the 19 patients with Stage IV rectal cancer, 15 (79%) had liver surgery with curative intent. CONCLUSION: Preoperative chemotherapy without pelvic irradiation is associated with objective pathological response and adequate local control in selected patients with LARC. Further prospective controlled studies will address the question of whether it can be used as a valuable alternative to radiochemotherapy in LARC.

Anastomotic leakage after gastrointestinal surgery: diagnosis and management.

Anastomotic leakage represents a major complication of gastrointestinal surgery, leading to increased postoperative morbidity; it the foremost cause of mortality after intestinal resection. Identification of risk factors is essential for the prevention of AL. AL can present with various clinical pictures, ranging from the absence of symptoms to life-threatening septic shock. Contrast-enhanced CT scan is the most complete investigation to define AL and its consequences. Early and optimal multidisciplinary management is based on three options: medical management, radiologic or endoscopic intervention, or surgical re-intervention. Prompt treatment should help decrease postoperative morbidity and mortality, with the choice depending on the septic status of the patient. If the patient is asymptomatic, treatment can be medical only, coupled with close surveillance. Interventional management is indicated when the fistula is symptomatic but not life-threatening. On the other hand, when the vital prognosis is engaged, surgery is indicated, emergently, associated with intensive care. Even more than their prevention, early and appropriate management counts most to decrease their consequences.

What is the fate of the abstracts submitted at the French Congress of Digestive and Hepato-biliary Surgery?

GOAL: The aim of this study was to objectively analyze the characteristics of abstracts submitted to the annual joint congress of the SFCD (French Society of Digestive Surgery) and the ACBHT (Association of Hepato-biliary Surgery and Transplantation), in order to identify factors associated with acceptance for presentation at the Congress and of subsequent publication in a scientific journal. MATERIAL AND METHODS: All abstracts submitted between 2005 and 2012 were retrospectively reviewed. Univariate and multivariate analysis were perfomed to determine the factors associated with acceptance for presentation at the Congress and/or for subsequent publication in the medical literature (based on PubMed). RESULTS: The number of submissions increased from 128 in 2005 to 223 in 2012, i.e., an increase of 74.2%. Among the 1352 abstracts, 1106 (81.8%) were retrospective studies while only 15 (1.1%) were randomized controlled trials. The two principal themes were hepato-bilio-pancreatic surgery in 606 studies (44.8%) and colorectal surgery in 364 studies (26.9%). The overall rate of acceptance for the Congress was 49.9%, of which 21.0% were accepted for oral presentation. In multivariate analysis, the factors associated with acceptance for oral presentation were the geographic origin of the study (P<0.001), studies including >100 patients (P=0.01), and the prospective nature of the study (P=0.045). The rate of subsequent publication was 61.9% for studies accepted for oral presentation, 39.7% for studies accepted for poster presentation, and 25.9% for studies that were not accepted (P<0.001). In multivariate analysis, the factors associated with subsequent publication were geographic origin of the study (P=0.003), the experimental character of the study (P<0.001), and acceptance for presentation at the Congress (P<0.001). CONCLUSION: Only half of the studies submitted for presentation at the annual Congress of the SFCD/ACBHT are accepted; this nevertheless constitutes a quality measure associated with nearly a 50% chance of subsequent publication in the medical literature.

Practice patterns in complex ventral hernia repair and place of biological grafts: a national survey among French digestive academic surgeons.

BACKGROUND: Despite the prevalence of complex ventral hernias, there is little agreement on the most appropriate technique or prosthetic to repair these defects, especially in contaminated fields. Our objective was to determine French surgical practice patterns among academic surgeons in complex ventral hernia repair (CVHR) with regard to indications, most appropriate techniques, choice of prosthesis, and experience with complications. METHODS: A survey consisting of 21 questions and 6 case-scenarios was e-mailed to French practicing academic surgeons performing CVHR, representing all French University Hospitals. RESULTS: Forty over 54 surgeons (74%) responded to the survey, representing 29 French University Hospitals. Regarding the techniques used for CVHR, primary closure without reinforcement was provided in 31.6% of cases, primary closure using the component separation technique without mesh use in 43.7% of cases, mesh positioned as a bridge in 16.5% of cases, size reduction of the defect by using aponeurotomy incisions without mesh use in 8.2% of cases. Among the 40 respondents, 36 had experience with biologic mesh. There was a strong consensus among surveyed surgeons for not using synthetic mesh in contaminated or dirty fields (100%), but for using it in clean settings (100%). There was also a strong consensus between respondents for using biologic mesh in contaminated (82.5%) or infected (77.5%) fields and for not using it in clean setting (95%). In clean-contaminated surgery, there was no consensus for defining the optimal therapeutic strategy in CVHR. Infection was the most common complication reported after biologic mesh used (58%). The most commonly reported influences for the use of biologic grafts included literature, conferences and discussion with colleagues (85.0%), personal experience (45.0%) and cost (40.0%). CONCLUSIONS: Despite a lack of level I evidence, biologic meshes are being used by 90% of surveyed surgeons for CVHR. Importantly, there was a strong consensus for using them in contaminated or infected fields and for not using them in clean setting. To better guide surgeons, prospective, randomized trials should be undertaken to evaluate the short- and long-term outcomes associated with these materials in various surgical wound classifications.