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Gene fusions provide access to new therapeutic opportunities for patients treated for a colorectal cancer (CRC). However, they do not excess 1% of patients. A better identification of patients in whom gene fusions are highly prevalent is a major issue in a therapeutic and medico-economics perspective. This study assesses the rates of gene fusions in CRC patients with MSI/RAS-BRAF

Purpose: Treatment of pulmonary metastases (PM) from colorectal cancer (CRC) is the standard of care by several guidelines from Europe and the USA, but the validity of this strategy has been recently questioned, and the available evidence supporting this strategy is weak. We report the outcomes of a curative intent strategy in a very recent and homogenous series of patients. Methods: We did a retrospective review of all curative intent surgical or ablative treatment of PM from CRC performed consecutively in 3 French institutions from January 2015 to December 2019. Demographics, clinicopathological, and molecular characteristics were evaluated. Cox regression models were used to identify prognostic factors related to local recurrence and disease-free survival. Results: Records from 152 patients were reviewed. One-hundred thirty-five patients (88%) had surgical metastasectomy. Median age was 67years. Most of the patients had a single lesion (66%), and 16% had synchronous PM. Eighty-one patients (53%) experienced recurrence, and the thorax was the most common site of recurrence. Median disease-free survival and overall survival were 35months and 78months after PM treatment. At the end of the study, only 17% of the patients died. Pulmonary tumor burden was correlated with disease-free survival in univariate analysis, but multivariate analysis did not find any prognostic factor independently associated with local recurrence or survival. Conclusion: Our finds corroborate existing recommendation for the invasive treatment of PM from CRC in selected patients.

International audience; This document is a summary of the French intergroup guidelines regarding the nutrition and physical activity (PA) management in digestive oncology. This collaborative work was produced under the auspices of all French medical and surgical societies involved in digestive oncology, nutrition and supportive care. It is based on published guidelines, recent literature review and expert opinions. Recommendations are graded according to the level of evidence. Malnutrition affects more than half of patients with digestive cancers and is often underdiagnosed. It has multiple negative consequences on survival, quality of life and risk of treatment complications. Consequently, in addition to anticancer treatments, supportive care including nutritional support and PA plays a central role in the management of digestive cancers. It is crucial to detect malnutrition (diagnostic criteria updated in 2019) early, to prevent it and to act against it at all stages of the cancer and at all times of the care pathway. In this context, we proposed recommendations for the evaluation and management in nutrition and PA in digestive oncology for each stage of the disease (perioperative setting, during radiation therapy, during systemic treatments, at the palliative phase, after cancer). Guidelines for nutrition and PA management aim at increasing awareness about malnutrition in oncology. They are continuously evolving and need to be regularly updated.

BACKGROUND: Incisional hernia (IH) may occur in 20% of patients after laparotomy. The hernia sac volume may be of significance, with reintegration of visceral contents potentially leading to repair failure or abdominal compartment syndrome. The present study aimed to evaluate a two-step surgical strategy comprising right colectomy for hernia reduction with synchronous absorbable mesh repair followed by definitive non-absorbable mesh repair in recurrence. METHODS: Patients operated between 2012 and 2017 at two university centers were retrospectively included. Volumetric evaluation of the IH was performed by CT imaging. RESULTS: Eleven patients were included. The mean BMI was 43 kg/m(2) (23-52 kg/m(2)). Progressive preoperative pneumoperitoneum was performed in 82% of patients, with complications in 22%. The mean volumetric ratio of the volume of the hernia to the volume of the abdominal cavity was 70% (48-100%). The first parietal repair was performed using an synthetic absorbable mesh (36%), a biologic mesh (27%), or a slowly absorbable mesh (36%). No patients died as a result of the procedure. Seven (64%) patients developed grade III-IV complications, including one case of an anastomotic fistula. Recurrence occurred in eight (73%) patients after the first repair. Of these, four (50%) patients were reoperated using a non-absorbable mesh, leading to solid repair in 75% of cases. After 27 ± 18 months of follow-up, the residual IH rate was 46%. CONCLUSIONS: Right colectomy for volume reduction in IH with loss of domain potentially represents an appropriate salvage option, supporting bowel reintegration and temporary hernia repair with absorbable material.

International audience; Background: Chyle leak (CL) is a clinically relevant complication after pancreatectomy. Its incidence and the associated risk factors are ill defined, and various treatments options have been described. There is no consensus, however, regarding optimal management. The present study aims to systematically review the literature on CL after pancreatectomy. Methods: A systematic review from PubMed, Scopus and Embase database was performed. Studies using a clear definition for CL and published from January 2000 to January 2021 were included. The PRISMA guidelines were followed during all stages of this systematic review. The MINORS score was used to assess methodological quality. Results: Literature search found 361 reports, 99 of which were duplicates. The titles and abstracts of 262 articles were finally screened. The references from the remaining 181 articles were manually assessed. After the exclusions, 43 articles were thoroughly assessed. A total of 23 articles were ultimately included for this review. The number of patients varied from 54 to 3532. Incidence of post pancreatectomy CL varied from 1.3% to 22.1%. Main risk factors were the extent of the surgery and early oral or enteral feeding. CL dried up spontaneously or after conservative management within 14 days in 53% to 100% of the cases. Conclusions: The extent of surgery is the most common predictor of risk of CL. Conservative treatment has been shown to be effective in most cases and can be considered the treatment of choice. We propose a management algorithm based on the current available evidence.

Background Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. Methods In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. Results Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. Conclusions Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.

International audience; Importance: Available data comparing the long-term results of hybrid minimally invasive esophagectomy (HMIE) with that of open esophagectomy are conflicting, with similar or even better results reported for the minimally invasive esophagectomy group. Objective: To evaluate the long-term, 5-year outcomes of HMIE vs open esophagectomy, including overall survival (OS), disease-free survival (DFS), and pattern of disease recurrence, and the potential risk factors associated with these outcomes. Design, Setting, and Participants: This randomized clinical trial is a post hoc follow-up study that analyzes the results of the open-label Multicentre Randomized Controlled Phase III Trial, which enrolled patients from 13 different centers in France and was conducted from October 26, 2009, to April 4, 2012. Eligible patients were 18 to 75 years of age and were diagnosed with resectable cancer of the middle or lower third of the esophagus. After exclusions, patients were randomized to either the HMIE group or the open esophagectomy group. Data analysis was performed on an intention-to-treat basis from November 19, 2019, to December 4, 2020. Interventions: Hybrid minimally invasive esophagectomy (laparoscopic gastric mobilization with open right thoracotomy) was compared with open esophagectomy. Main Outcomes and Measures: The primary end points of this follow-up study were 5-year OS and DFS. The secondary end points were the site of disease recurrence and potential risk factors associated with DFS and OS. Results: A total of 207 patients were randomized, of whom 175 were men (85%), and the median (range) age was 61 (23-78) years. The median follow-up duration was 58.2 (95% CI, 56.5-63.8) months. The 5-year OS was 59% (95% CI, 48%-68%) in the HMIE group and 47% (95% CI, 37%-57%) in the open esophagectomy group (hazard ratio [HR], 0.71; 95% CI, 0.48-1.06). The 5-year DFS was 52% (95% CI, 42%-61%) in the HMIE group vs 44% (95% CI, 34%-53%) in the open esophagectomy group (HR, 0.81; 95% CI, 0.55-1.17). No statistically significant difference in recurrence rate or location was found between groups. In a multivariable analysis, major intraoperative and postoperative complications (HR, 2.21; 95% CI, 1.41-3.45; P

Multiple randomized controlled trials have demonstrated the short term benefits of (hybrid) minimally invasive esophagectomy (MIE) over open esophagectomy. Data regarding long term results are more conflicting with similar or even better results in the MIE arm. In this follow-up study of the MIRO-trial we evaluated the long-term 5-year outcomes including overall survival (OS), disease-free survival (DFS) as well as the pattern of disease recurrence, along with evaluation of potential prognostic factors affecting these outcomes. Methods From October 2009 till April 2012, we conducted a multicentre, open-label, prospective, randomized, controlled trial including patients who were diagnosed with thoracic esophageal cancer and eligible for curative surgical resection (Ivor-Lewis procedure). Patients were randomized between hybrid minimally invasive esophagectomy and open esophagectomy. The primary end-point of the initial MIRO trial was major intra- and postoperative complication (Clavien-Dindo ≥2) within 30 days after surgery. The primary end-points of this follow-up study were OS and DFS. Additional secondary end points were defined as site of disease recurrence and potential prognostic or mediating factors associated with DFS and OS. Results 207 patients underwent randomization. The median follow-up was 58,2 (95% CI, 56,5– 63,8) months. The 5y OS was 59% (95% CI, 48–68) and 47% (95% CI, 37–57) in the hybrid- and open-procedure group respectively (HR, 0,71, 95% CI, 0,48-1,06). The 5y DFS was 52% (95% CI, 42–61) in the hybrid-procedure group vs. 44% (95%CI, 34–53) in the open-procedure group. (HR 0.81 (95% CI, 0,55-1,17). There was no significant difference in recurrence rate (p = 0.519) or -location (p = 0.692) between groups. In a multivariate analysis, major postoperative and pulmonary complications were identified as prognostic factors of impaired OS (p Conclusion Besides a significant reduction in postoperative overall and pulmonary complication rate, minimally invasive (hybrid) esophagectomy offers long-term oncological results that are at least equivalent to open esophagectomy. Postoperative and pulmonary complications are independent prognostic factors for impaired overall- and disease-free survival, providing additional proof that minimally invasive esophagectomy could even be associated with better long-term oncological results compared to open esophagectomy mediated by a reduction in postoperative complications.

IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing Type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a Type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment. Here, we demonstrate that IL-36γ plays a similar role in driving a pro-inflammatory phenotype in human colorectal cancer. We analyzed a cohort of 33 primary colorectal carcinoma tumors using imaging, flow cytometry, and transcriptomics to determine the pattern and role of IL-36γ expression in this disease. In the colorectal tumor microenvironment, we observed IL-36γ to be predominantly expressed by M1 macrophages and cells of the vasculature, including smooth muscle cells and high endothelial venules. This pattern of IL-36γ expression is associated with a CD4(+) central memory T cell infiltrate and an increased density of B cells in tertiary lymphoid structures, as well as with markers of fibrosis. Conversely, expression of the antagonist to IL-36 signaling, IL-1F5, was associated with intratumoral expression of checkpoint molecules, including PD-1, PD-L1, and CTLA4, which can suppress the immune response. These data support a role for IL-36γ in the physiologic immune response to colorectal cancer by sustaining inflammation within the tumor microenvironment. PRECIS: This study reveals the association of intratumoral IL-36γ with established markers of cancer prognosis, indicating the translational relevance of investigating the IL-36 signaling pathway as a therapeutic target in colorectal cancer.

Background Several multicenter randomized controlled trials comparing laparoscopy and conventional open surgery for colon cancer have demonstrated that laparoscopic approach achieved the same oncological results while improving significantly early postoperative outcomes. These trials included few elderly patients, with a median age not exceeding 71 years. However, colon cancer is a disease of the elderly. More than 65% of patients operated on for colon cancer belong to this age group, and this proportion may become more pronounced in the coming years. In current practice, laparoscopy is underused in this population. Methods The CELL (Colectomy for cancer in the Elderly by Laparoscopy or Laparotomy) trial is a multicenter, open-label randomized, 2-arm phase III superiority trial. Patients aged 75 years or older with uncomplicated colonic adenocarcinoma or endoscopically unresectable colonic polyp will be randomized to either colectomy by laparoscopy or laparotomy. The primary endpoint of the study is overall postoperative morbidity, defined as any complication classification occurring up to 30 days after surgery. The secondary endpoints are: 30-day and 90-day postoperative mortality, 30-day readmission rate, quality of surgical resection, health-related quality of life and evolution of geriatric assessment. A 35 to 20% overall postoperative morbidity rate reduction is expected for patients operated on by laparoscopy compared with those who underwent surgery by laparotomy. With a two-sided α risk of 5% and a power of 80% (β = 0.20), 276 patients will be required in total. Discussion To date, no dedicated randomized controlled trial has been conducted to evaluate morbidity after colon cancer surgery by laparoscopy or laparotomy in the elderly and the benefits of laparoscopy is still debated in this context. Thus, a prospective multicenter randomized trial evaluating postoperative outcomes specifically in elderly patients operated on for colon cancer by laparoscopy or laparotomy with curative intent is warranted. If significant, such a study might change the current surgical practices and allow a significant improvement in the surgical management of this population, which will be the vast majority of patients treated for colon cancer in the coming years. Trial registration ClinicalTrials.gov NCT03033719 (January 27, 2017).

Resume But de l’etude La prise en charge oncologique optimale du cancer du rectum est problematique chez le sujet âge. L’objectif de ce travail etait d’etudier la faisabilite et les resultats du traitement multimodal du cancer du rectum chez le sujet de 75 ans et plus apres evaluation oncogeriatrique basee sur le score de Balducci. Patients et methode Les patients de 75 ans et plus pris en charge pour adenocarcinome du moyen et bas rectum etaient analyses en 3 groupes (Balducci 1 a 3) en fonction de leur reserve fonctionnelle, de leurs comorbidites, des syndromes geriatriques et de leur esperance de vie. Resultats Un traitement neoadjuvant etait indique chez 27 patients (47 %), mais administre chez 56 % d’entre eux, incluant 8, 7, et 1 patients des groupes Balducci 1, 2 et 3, respectivement. Cinquante-trois patients (93 %) ont eu une resection anterieure du rectum avec preservation sphincterienne et 4 une amputation abdominoperineale (7 %). Des complications postoperatoires etaient observees chez 21 patients (37 %). Le taux de complications postoperatoires etait non significativement correle avec l’âge ( p = 0,3) et le score de Balducci ( p = 0,64). Au total, 10 patients (18 %) ont eu une colostomie definitive, pour fistule anastomotique chez 5 patients (9 %) et incontinence chez 1 patient (2 %). Le taux de preservation sphincterienne etait de 82 % ( n = 47). Le risque de colostomie secondaire definitive n’etait pas correle au score de Balducci (groupe 1 : 14 % ; groupe 2/3 : 16 % ; p = 0,8). La survie globale estimee a 5 ans etait de 52 %. Conclusion Apres evaluation oncogeriatrique systematique, les sujets âges atteints de cancer du rectum ont un taux de conservation sphincterienne satisfaisant et une morbi-mortalite acceptable.

Few data are available on the management of elderly rectal cancer patients, and especially on the ability to provide optimal oncological treatment. The aim of this study was to determine the feasibility and results of multimodality treatment for rectal cancer in patients 75years and older after simplified comprehensive geriatric assessment (CGA) according to Balducci score.We reviewed the charts of elderly patients who underwent surgery for localized middle or low rectal cancer. Patients were classified into three CGA groups depending on their functional reserve, comorbidities, geriatric syndromes, and life expectancy.Neoadjuvant therapy was discussed for 27 patients (47%), but only 56% of them were treated, including 8, 7, and 1 patient from CGA groups 1, 2, and 3, respectively. Fifty-three patients (93%) underwent sphincter-preserving surgical resection and four patients underwent abdominoperineal resection (7%). Postoperative complications were observed in 21 patients (37%). The postoperative complication rate was correlated non-significantly with age (85years: 40.6%; ≥85years: 57.1%; P=0.3), and with the CGA (P=0.64). In total, 10 patients (18%) had definitive colostomy, including five anastomotic leakages (9%), and one incontinence (2%). The total rate of sphincter preservation was 82% (n=47). The risk of secondary definitive colonic stoma formation was not correlated with CGA (group 1: 14%; group 2/3: 16%; P=0.8). Estimated OS at five years was 52%.After routine geriatric assessment, elderly rectal cancer patients have good rates of sphincter conservation and acceptable morbidity/mortality.

The aim of this study was to report the 3-year survival results of the GRECCAR-6 trial.Current data on the effect of an extended interval between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0) is controversial. Furthermore, its effect on oncological outcomes is unknown.The GRECCAR-6 trial was a phase III, multicenter, randomized, open-label, parallel-group, controlled trial. Patients with cT3/T4 or TxN+ tumors of the mid or lower rectum who had received RCT (45-50 Gy with 5-fluorouracil or capecitabine) were included and randomized into a 7- or 11-week waiting period. Primary endpoint was the pCR rate. Secondary endpoints were 3-year overall (OS), disease-free survival (DFS), and recurrence rates.A total of 265 patients from 24 participating centers were enrolled. A total of 253 patients underwent a mesorectal excision. Overall pCR rate was 17% (43/253). Mean follow-up from surgical resection was 32 ± 8 months. Twenty-four deaths occurred with an 89% OS at 3 years. DFS was 68.7% at 3 years (75 recurrences). Three-year local and distant recurrences were 7.9% and 23.8%, respectively. The randomization group had no impact on the 3-year OS (P = 0.8868) or DFS (P = 0.9409). Distant (P = 0.7432) and local (P = 0.3944) recurrences were also not influenced by the waiting period. DFS was independently influenced by 3 factors: circumferential radial margin (CRM) ≤1 mm [hazard ratio (HR) = 2.03; 95% confidence interval (CI), 1.17-3.51], ypT3-T4 (HR = 2.69; 95% CI, 1.19-6.08) and positive lymph nodes (HR = 3.62; 95% CI, 1.89-6.91).Extending the waiting period by 4 weeks following RCT has no influence on the oncological outcomes of T3/T4 rectal cancers.

Obesity is a risk factor for the development of ventral hernia and increases the risk of recurrence and surgical site infection after hernia repair (HR).We tested the hypothesis that bariatric surgery (BS) before HR would decrease these risks in patients with morbid obesity.University hospital, France.We retrospectively compared 2 groups of patients with morbid obesity in a case-matched study; 1 underwent immediate HR surgery (control), and the other initially underwent BS and then HR after weight loss (case). Patients were individually matched at a 2:1 ratio according to defect size (7 or ≥7 cm), obesity grade (40 or ≥40 kg/m²), American Society of Anesthesiologists score, sex, smoker status, and presence of chronic obstructive pulmonary disease.From 2000 to 2017, 41 patients underwent BS, in association with herniorrhaphy in 14 cases (34%). Initial body mass index was higher in the BS group (46.7 ± 6.4 versus 42.4 ± 7.2, P.0001) but had decreased by the time of HR (34.1 ± 6.5 versus 42.3 ± 7.2, P.0001). Prosthetic HR was performed after 21.5 months (range, 7-87); however, 7 patients did not receive HR at this time due to insufficient weight loss. Postoperative morbidity was similar in the 2 groups. Hospital stay was shorter in the BS group (6.2 ± 2.6 versus 10.7 ± 9.3 d, P = .002). After a median follow-up of 4.6 ± 4.1 years, the recurrence rate was lower in the BS group (2/30, 6.7%) than in the control group (12/50, 24%; P = .048).For morbidly obese patients with ventral hernia, BS before HR surgery can decrease recurrence without increasing morbidity.

Postoperative complications, especially pulmonary complications, affect more than half the patients who undergo open esophagectomy for esophageal cancer. Whether hybrid minimally invasive esophagectomy results in lower morbidity than open esophagectomy is unclear.We performed a multicenter, open-label, randomized, controlled trial involving patients 18 to 75 years of age with resectable cancer of the middle or lower third of the esophagus. Patients were randomly assigned to undergo transthoracic open esophagectomy (open procedure) or hybrid minimally invasive esophagectomy (hybrid procedure). Surgical quality assurance was implemented by the credentialing of surgeons, standardization of technique, and monitoring of performance. Hybrid surgery comprised a two-field abdominal-thoracic operation (also called an Ivor-Lewis procedure) with laparoscopic gastric mobilization and open right thoracotomy. The primary end point was intraoperative or postoperative complication of grade II or higher according to the Clavien-Dindo classification (indicating major complication leading to intervention) within 30 days. Analyses were done according to the intention-to-treat principle.From October 2009 through April 2012, we randomly assigned 103 patients to the hybrid-procedure group and 104 to the open-procedure group. A total of 312 serious adverse events were recorded in 110 patients. A total of 37 patients (36%) in the hybrid-procedure group had a major intraoperative or postoperative complication, as compared with 67 (64%) in the open-procedure group (odds ratio, 0.31; 95% confidence interval [CI], 0.18 to 0.55; P0.001). A total of 18 of 102 patients (18%) in the hybrid-procedure group had a major pulmonary complication, as compared with 31 of 103 (30%) in the open-procedure group. At 3 years, overall survival was 67% (95% CI, 57 to 75) in the hybrid-procedure group, as compared with 55% (95% CI, 45 to 64) in the open-procedure group; disease-free survival was 57% (95% CI, 47 to 66) and 48% (95% CI, 38 to 57), respectively.We found that hybrid minimally invasive esophagectomy resulted in a lower incidence of intraoperative and postoperative major complications, specifically pulmonary complications, than open esophagectomy, without compromising overall and disease-free survival over a period of 3 years. (Funded by the French National Cancer Institute; ClinicalTrials.gov number, NCT00937456 .).

Colorectal cancer risk factors increase with age, comorbidities, delayed diagnosis, obstruction, emergency and frailty. Surgery is the standard treatment as the survival rate for this pathology is the same as in young patients. It would appear that there is an excess morbidity and mortality of colorectal cancer surgery in the elderly. Early rehabilitation is to be favoured during the postoperative period.

Pelvic floor disorders include urogenital and anorectal prolapse, urinary and faecal incontinence. These diseases affect 25% of patients. Most of time, treatment is primarily surgical with a high post-operative risk of recurrence, especially for pelvic organ prolapse. Vaginal delivery is the major risk factor for pelvic floor disorders through levator ani muscle injury or nerve damage. After vaginal delivery, 20% of patients experiment elevator ani trauma. These injuries are more common in case of instrumental delivery by forceps, prolonged second phase labor, increased neonatal head circumference and associated anal sphincter injuries. Moreover, 25% of patients have temporary perineal neuropathy. Recently, pelvic three-dimensional reconstructions from RMI data allowed a better understanding of detailed levator ani muscle morphology and gave birth to a clear new nomenclature describing this muscle complex to be developed. Radiologic and anatomic studies have allowed exploring levator ani innervation leading to speculate on the muscle and nerve damage mechanisms during delivery. We then reviewed the levator ani muscle anatomy and innervation to better understand pelvic floor dysfunction observed after vaginal delivery.

Rectal preservation has been proposed as an alternative to radical resection in patients with presumed complete or major response to chemoradiotherapy (CRT). The aim of this prospective study was to evaluate the accuracy of digital rectal examination (DRE) and magnetic resonance imaging (MRI) to predict major or complete rectal cancer response to CRT. Over 2 years, 61 patients underwent radical resection after CRT for rectal cancer. DRE and MRI were carried out before and 6 to 8 weeks after the end of CRT. Data from DRE and MRI post-CRT were compared with pathological examinations. At pathological examination, major/complete responses were recorded for tumors classified ypT1N0 and ypT0N0, respectively. DRE post-CRT showed major/complete response in 26 cases, of which 14 (54%) were confirmed by pathology. The positive (PPV) and negative (NPV) predictive values of DRE to predict major/complete response were 54 and 88 per cent, respectively. MRI post-CRT showed major/complete response in 12 cases, of which nine (75%) were confirmed by pathology. The PPV and NPV of MRI to predict major/complete response were 75 and 82 per cent, respectively. Data from DRE and RMI post-CRT were concordant in 45 patients. The PPV and NPV of concordant DRE and MRI to predict major/complete response were 82 and 91 per cent, respectively. DRE and MRI do not appear to be sufficiently accurate for safe selection of patients appropriate for a rectum-sparing strategy because the risk of leaving an invasive tumor untreated is 18 per cent.

Treatment of chronic mesh infections (CMI) after parietal repair is difficult and not standardized. Our objective was to present the results of a standardized surgical treatment including maximal infected mesh removal. Patients who were referred to our center for chronic mesh infection were analyzed according to CMI risk factors, initial hernia prosthetic cure, CMI characteristics and treatments they received to achieve a cure. Thirty-four patients (mean age 54 ± 13 years; range 23–72), were included. Initial prosthetic cure consisted of 26 incisional hernias and eight groin or umbilical hernias of which 21% were considered potentially contaminated because of three intestinal injuries, two stomas and two strangulated hernias. The mesh was synthetic in all cases. CMI appeared after a mean of 83 days (range 30–6740) and was characterized by chronic leaking in 52 cases (50%), an abscess in 22 cases (21%) and synchronous hernia recurrence in 17 cases (16.5%). Eighty-six reinterventions were necessary, including 36 mesh removals (42%), and 13 intestinal resections for entero-cutaneous fistula (15%). The CMI persistence rate was 81% (35 reinterventions out of 43) when mesh removal was voluntarily limited to infected and/or not incorporated material, but was 44% when mesh removal was voluntarily complete (19 reinterventions out of 43; p

Background The American College of surgical risk calculator (SRC) score has never been validated specifically for surgery in emergency. The objective was to evaluate the reliability of this calculator in patients with malignant colon obstruction. Materials and methods We retrospectively have analyzed the morbidity and mortality observed in operated patients. Risk factors for postoperative morbidity and mortality were analyzed by logistic regression model. We have compared the morbidity and mortality estimated by the SRC score with that observed using the Brier Score (BS). A BS of 0 indicated perfect prediction, whereas a BS of 1 indicated the poorest prediction. Results Sixty-nine patients aged 75 y (41-93) have been operated on emergency from November 2001 to August 2015. The tumor was localized in the sigmoid in 33 cases (48%), in the splenic flexure in nine cases (13%), and in the right colon in 17 cases (25%). The surgical procedures were as follows: right colectomy with anastomosis (29%), diverting proximal iliac colostomy (23%), and subtotal colectomy with anastomosis (19%). The SRC score indicated a good predictivity for mortality (9.8% predicted versus 8.7% observed, BS = 0.058), for morbidity (33.4% versus 40.6%, BS = 0.209), and for serious morbidity (25.5% versus 17.4%, BS = 0.131). In multivariate analysis, SRC was an independent risk factor for mortality (P = 0.030 odds ratio [OR] = 1.07 [1.01-1.15]) and morbidity (P = 0.001 OR = 1.16 [1.08-1.27]). Conclusions SRC score is a reliable tool for assessing the morbidity and mortality of obstructive colon cancer and could help with adapting the surgical gesture to the risks predicted.

Background Few data are available on management of very elderly colon cancer patients, especially concerning the parameters of therapeutic decisions and the role of geriatricians. Methods We retrospectively reviewed the charts of patients over 80 years of age who underwent surgery for a localised colon cancer in a French academic hospital. Results A total of 176 patients underwent surgery (postoperative morbidity and mortality rates: 25% and 6.7%). Adjuvant chemotherapy was discussed at a multidisciplinary team meeting for 91% of stage III patients, but only 13.5% of them were treated. Twenty-five patients relapsed: 19 were discussed at the multidisciplinary meeting and 16 were treated (5 had a metastasectomy). Despite their increase with time, geriatric assessments were infrequent, 17% (33% after 2006), and had no impact on postoperative morbi-mortality. Median overall survival and recurrence-free survival were 65.3 months and 65.1 months, respectively. Age, emergency surgery, and Charlson comorbidity index were independent prognostic factors. Conclusion Selected elderly colon cancer patients have significant access to surgery. However, postoperative morbi-mortality rates remain high and adjuvant chemotherapy rarely prescribed. Perioperative geriatric assessment, especially before surgery, should be routinely proposed to these patients to evaluate its impact on postoperative morbi-mortality and prescription of adjuvant treatment.

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate. Methods GRECCAR6 was a phase III, multicenter, randomized, open-label, parallel-group controlled trial. Patients with cT3/T4 or Tx N+ tumors of the mid or lower rectum who had received RCT (45 to 50 Gy with fluorouracil or capecitabine) were included. Patients were randomly included in the 7-week or the 11-week (11w) group. Primary end point was the pCR rate defined as a ypT0N0 specimen (NCT01648894). Results A total of 265 patients from 24 centers were enrolled between October 2012 and February 2015. The majority of the tumors were cT3 (82%). After RCT, surgery was not performed in nine patients (3.4%) because of the occurrence of distant metastasis (n = 5) or other reasons. Two patients underwent local resection of the tumor scar. A total of 47 (18.6%) specimens were classified as ypT0 (four had invaded lymph nodes [8.5%]). The primary end point (ypT0N0) was not different (7 weeks: 20 of 133, 15.0% v 11w: 23 of 132, 17.4%; P = .5983). Morbidity was significantly increased in the 11w group (44.5% v 32%; P = .0404) as a result of increased medical complications (32.8% v 19.2%; P = .0137). The 11w group had a worse quality of mesorectal resection (complete mesorectum [I] 78.7% v 90%; P = .0156). Conclusion Waiting 11 weeks after RCT did not increase the rate of pCR after surgical resection. A longer waiting period may be associated with higher morbidity and more difficult surgical resection.

Colorectal cancer risk factors increase with age, comorbidities, delayed diagnosis, obstruction, emergency and frailty. Surgery is the standard treatment as the survival rate for this pathology is the same as in young patients. It would appear that there is an excess morbidity and mortality of colorectal cancer surgery in the elderly. Early rehabilitation is to be favoured during the postoperative period.

TPS11630 Background: Nearly 50% of patients are older than 70 years at diagnosis of digestive cancer. Surgical resection is the first line strategy of treatment. Despite improvement in surgical techniques and development of rehabilitation programs, the rate of postoperative complications remains high. Peri-operative involvement of geriatricians may improve care management older cancer patients. Methods: During a 6 months run-up period (emerging project), we structured a multi-professional network (digestive surgeons, anesthetists, geriatricians, digestive oncologists, epidemiologists), we elaborated a innovative peri-operative geriatric intervention (Improved program) in digestive surgery setting based on evidence-based data. We build a dedicated evaluation plan by determinate the best design for assessing geriatric intervention in this complex context and choose the more appropriate endpoints. Results: We will include 554 patients aged 75 or more with resectable digestive cancer in a stepped wedge cluster randomized trial. The intervention is based on 1/ a preoperative geriatric assessment, focusing on frailty parameters and developing a coordinated program of tailored geriatric interventions 2/ a postoperative shared care with an integrated care model where both surgeon and geriatrician share responsibility for the patient management in surgical ward. This geriatric postoperative management will be focus on prevention and correction of complications, early mobilization, optimal nutritional support. The main endpoint Is is Grade II or higher post-surgical complications rate according Clavien-Dindo classification within 30 days after the surgical procedure. Conclusion: We expected to demonstrate a benefit of a peri-operative shared management model to decrease the risk of post-surgical complications In older patients with digestive cancer.

BRAF p.V600 mutation detection recently became necessary to treat metastatic melanoma patients with vemurafenib. This study compares different methods of detection of BRAF mutations. Melanoma samples from 111 patients were analyzed for BRAF mutations, and for 89 of them, results were obtained with the four following methods: Sanger sequencing, real-time PCR, immunohistochemistry, and pyrosequencing. All samples contained at least 60% of tumor cells. Directional Sanger sequencing of PCR products failed to detect 3 of 40 p.V600E-mutated cases (7.5%) (sensitivity, 92.5%; 95% CI, 78.5% to 98.0%). BRAF p.V600E-specific real-time PCR identified 39 of 40 p.V600E-mutated cases (97.6%) (sensitivity, 97.5%; 95% CI, 87.1% to 99.6%) and all 39 wild-type (WT) cases and surprisingly was also positive for 6/6 p.V600K (specificity, 87.8%; 95% CI, 75.8% to 94.3%). However, other mutations, p.V600R (n = 1), p.K601E (n = 2), and p.600_601delinsE (n = 1), were not detected. Immunohistochemistry with VE1, specific for p.V600E, identified all p.V600E and WT cases (sensitivity, 100%; 95% CI, 91.2% to 100%) but was negative for all other BRAF mutations. Pyrosequencing successfully identified all WT and mutated cases. Immunohistochemistry is highly specific for p.V600E, and could be used as a first-line method, as is currently performed for HER2 amplification detection. Pyrosequencing proved to be the most efficient method to detect BRAF mutations in melanomas and could be performed on VE1-negative or uninterpretable cases.

Patients with ypN0 rectal cancer who have received preoperative chemoradiotherapy can be divided into those who initially were node negative and those whose positive nodes have been sterilized by preoperative therapy. The long-term prognosis for ypN0 patients with sterilized lymph nodes (LNS) is unknown. This study aimed to assess the prognostic value of LNS after preoperative chemoradiotherapy for patients with ypN0 rectal cancer.From January 2007 to March 2014, 206 patients with ypN0 tumors of the mid or lower rectum treated by chemoradiotherapy and radical surgery were enrolled in the study. Of these 206 patients, 49 had ypN0 tumors with LNS (LNS+ group), and 157 had ypN0 tumors without LNS (LNS- group). The patients in both groups were comparable in terms of tumor characteristics, type of chemoradiotherapy, type of surgery, R0 resection rate, and postoperative complication rate.The mean follow-up period was 40.5 ± 27 months. The 1- and 3-year OS rates in the LNS+ group were respectively 100 and 95.5% versus 99.4 and 91.6% in the LNS- group (P = 0.549). The 1- and 3-year DFS rates in the LNS+ group were respectively 100 and 94.2% versus 94.7 and 87.1% in the LNS- group (P = 0.117). The multivariate analysis showed that the presence of LNS did not affect OS (P = 0.918) or DFS (P = 0.209).The prognosis is excellent for patients with ypN0 rectal cancer who have LNS after preoperative chemoradiotherapy. The presence of LNS in ypN0 rectal cancer patients after chemoradiotherapy should not be considered a factor for a poor prognosis.

Aim Whether or not nerve-sparing rectal-cancer surgery can effectively prevent removal of the pelvic autonomic nerves has not been substantiated microscopically. We aimed to analyse the quality of nerve preservation in female patients by quantifying residual nerve fibres in total mesorectal excision specimens, to analyse pro-erectile function of the nerve fibres removed and to determine risk factors for pelvic denervation. Method Serial transverse sections from female patients, 64 ± 18 years of age, were studied after the mesorectal fascia was inked and studied histologically [using anti-S100 and anti-neuronal nitric oxide synthase (nNOS) antibodies]. Nerve fibres located within 1 mm of the inked surface were counted and analysed according to type of surgery, tumour location, pT stage, circumferential resection margin and the necessity for a posterior colpectomy. Results Twelve specimens were analysed. Per specimen, the mean number of nerve-fibre sections outside the mesorectum was 5.3 ± 3.6 (range: 1–12). The mean number of fibres per specimen was 6.4 ± 4.1 in patients having a low-rectal tumour and 4.4 ± 2.9 in those with mid or higher rectal tumours (P = 0.42). The mean number of fibres was higher (9.2) for T4 tumours than for T2/T3 tumours (5.0 ± 3.5), but this difference was not statistically sigmificant (P = 0.25). Patients having abdominoperineal excision, a posterior colpectomy or a circumferential resection margin of less than 1 mm had significantly more nerve fibres in the specimen (10.6 ± 1.9 vs 4.4 ± 2.8; P = .041). Fibres localized at the anterolateral rectum corresponded to branches of the neurovascular bundle, expressing rich pro-erectile activity (positive anti-nNOS immunostaining). Conclusion The neurovascular bundle is a key risk zone for pelvic denervation during total mesorectal excision. Abdominoperineal excision, posterior colpectomy and an invaded circumferential resection margin are associated with perineal denervation.

Purpose BRAFV600 mutations are frequent in melanomas, and BRAFV600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ≥2 mm according to BRAFV600 mutations and other previously reported prognostic criteria.

Aim Optimal treatment of rectal adenocarcinoma involves total mesorectal excision with nerve-preserving dissection. Urinary and sexual dysfunction is still frequent following these procedures. Improved knowledge of pelvic nerve anatomy may help reduce this and define the key anatomical zones at risk. Method The MEDLINE database was searched for available literature on pelvic nerve anatomy and damage after rectal surgery using the key words ‘autonomic nerve’, ‘pelvic nerve’, ‘colorectal surgery’, and ‘genitourinary dysfunction’. All relevant French and English publications up to May 2010 were reviewed. Reviewed data were illustrated using 3D reconstruction of the foetal pelvis. Results The ligation of the inferior mesenteric artery and dissection of the retrorectal space can cause damage to the superior hypogastric plexus and/or hypogastric nerve. Anterolateral dissection in the ‘lateral ligament’ area and division of Denonvilliers’ fascia can damage the inferior hypogastric plexus and efferent pathways. Perineal dissection can indirectly damage the pudendal nerve. Conclusions In most cases, the pelvic nerves can be preserved during rectal surgery. Complete oncological resection may require dissection close to the nerves where the tumour is located anterolaterally where it is fixed and when the pelvis is narrow.

The aim of this retrospective study was to evaluate the survival impact of perioperative chemotherapy (PCT) in patients with gastric signet ring cell (SRC) adenocarcinoma.PCT is a standard treatment for advanced resectable gastric adenocarcinoma (GA). SRC has a worse prognosis compared to non-SRC and the chemosensitivity of SRC is uncertain.Among 3010 patients registered in 19 French centers between January 1997 and January 2010, 1050 (34.9%) were diagnosed with SRC. Of those treated with curative intent (n = 924), 171 (18.5%) received PCT with surgery (PCT group), whereas 753 (81.5%) were treated with primary surgery (S group). PCT was based mainly on a fluorouracil-platinum doublet or triplet regimen.The groups were comparable regarding age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, tumor location and cTNM stage. 60 patients did not undergo resection because of tumor progression (10) or metastases (50) found at operation. The R0 resection rates were 65.9% and 62.3% in the S and PCT groups, respectively (P = 0.308). Fewer patients received adjuvant chemotherapy in the S group than in the PCT group (35.2% vs. 66.5%, P0.001). At a median follow-up of 31.5 months, the median survival was shorter in the PCT group (12.8 vs. 14.0 months, P = 0.043). On multivariate analysis, PCT was found to be an independent predictor of poor survival (HR = 1.4, 95% CI 1.1-1.9, P = 0.042).PCT provides no survival benefit in patients with gastric SRC. Clinical Trial.gov record: ADCI001, Clinical Trial.gov identifier NCT01249859.

Sphincter continence and sexual function require co-ordinated activity of autonomic and somatic neural pathways, which communicate at several levels in the human pelvis. However, classical dissection approaches are only of limited value for the determination and examination of thin nerve fibres belonging to autonomic supralevator and somatic infralevator pathways. In this study, we aimed to identify the location and nature of communications between these two pathways by combining specific neuronal immunohistochemical staining and three-dimensional reconstruction imaging. We studied 14 normal human fetal pelvic specimens (seven male and seven female, 15–31 weeks’ gestation) by three-dimensional computer-assisted anatomic dissection (CAAD) with neural, nitrergic and myelin sheath markers. We determined the precise location and distribution of both the supra- and infralevator neural pathways, for which we provide a three-dimensional presentation. We found that the two pathways crossed each other distally in an X-shaped area in two spatial planes. They yielded dual innervation to five targets: the anal sphincter, levator ani muscles, urethral sphincter, corpus spongiosum and perineal muscles, and corpora cavernosa. The two pathways communicated at three levels: proximal supralevator, intermediary intralevator and distal infralevator. The dorsal penis/clitoris nerve (DN) had segmental nitrergic activity. The proximal DN was nNOS-negative, whereas the distal DN was nNOS-positive. Distal communication was found to involve interaction of the autonomic nitrergic cavernous nerves with somatic nitrergic branches of the DN, with nitrergic activity carried in the distal part of the nerve. In conclusion, the pelvic structures responsible for sphincter continence and sexual function receive dual innervation from the autonomic supralevator and the somatic infralevator pathways. These two pathways displayed proximal, intermediate and distal communication. The distal communication between the CN and branches of the DN extended nitrergic activity to the distal part of the cavernous bodies in fetuses of both sexes. These structures are important for erectile function, and care should therefore be taken to conserve this communication during reconstructive surgery.

Introduction Little detailed information is available concerning autonomic and somatic nerve supply to the clitoris, potentially causing difficulties for nerve preservation during pelvic and perineal surgery. Aim To identify the location and type (nitrergic, adrenergic, cholinergic and sensory) of nerve fibers in the clitoris and to provide a three‐dimensional (3D) representation of their structural relationship in the human female fetus. Methods Serial transverse sections were obtained from five human female fetuses (18–31 weeks of gestation) and subjected to histological and immunohistochemical investigations; digitized serial sections were used to construct a 3D representation of the pelvis. Main Outcome Measures Pelvic‐perineal nerve location and type were evaluated qualitatively. Results The female neurovascular bundle (NVB) is the anteroinferior terminal portion of the inferior hypogastric plexus that runs along the postero‐lateral then lateral face of the vagina and is rich in nNOS‐positive fibers. The cavernous nerve (CN) is a thin ventrocaudal collateral projection of the NVB, and this projection does not strictly follow the NVB course. The CN runs along the lateral surface of the vagina and urethra and penetrates the homolateral clitoral crus. The CN provides adrenergic, cholinergic, and nitrergic innervation to the clitoris, but not sensory innervation. The spongious nerve (SN) is the terminal and main projection of the NVB and provides nitrergic innervation to the vestibular bulbs. The dorsal clitoris nerve (DCN), somatic branche of the pudendal nerve, runs along the superior surface of the clitoral crus and body and has a segmental proerectile nitrergic activity related to communicating branches with the CN. Conclusions “Computer‐assisted anatomic dissection” allowed the identification of the precise location and distribution of the autonomic and somatic neural supply to female erectile bodies, providing an anatomical basis for nerve‐sparing surgical techniques, and participating to the understanding of neurogenic female sexual dysfunction. Moszkowicz D, Alsaid B, Bessede T, Zaitouna M, Penna C, Benoit G, and Peschaud F. Neural supply to the clitoris: Immunohistochemical study with 3D reconstruction of cavernous nerve, spongious nerve and dorsal clitoris nerve in human fetus.

To confront nerve dissection, tissue staining, nerve immunolabelling and Computer-Assisted Anatomic Dissection (CAAD) in identifying the precise location and origin of intrapelvic autonomic nerve fibers and to provide a three-dimensional (3D) representation of their relationship to other anatomical structures. Serial transverse sections of the pelvic portion of five human female fetuses (18–31 weeks of gestation) were studied histologically (with hematoxylin/eosin and Masson trichrome) and immunohistochemically (anti-protein S100 antibody) digitized and reconstructed three-dimensionally with Surf driver software for Windows (Winsurf 4.3). Three fresh female adult cadavers were macroscopically dissected to individualize the inferior hypogastric plexus afferences and efferences and their anatomical relationships. This combined investigation including the CAAD technique allowed identifying the precise location and distribution of the pelvic nerve elements and their relationships to female pelvic organs. Hypogastric nerves (HN) were located in the retrorectal multilaminar structure and joined the homolateral inferior hypogastric plexus (IHP) at the lateral border of the recto-uterine pouch. The intersection of the ureter with the posterior wall of the uterine artery precisely located the junction of HN and IHP. Antero-inferior branches supplying female sexual and continence organs originated from the antero-inferior angle of IHP and were bundled at the posterolateral vaginal wall. CAAD is an encouraging anatomical method for the development of anatomical and surgical research and teaching. Complementary to traditional anatomical studies, it may provide useful anatomical data for the comprehension of postoperative sexual and urinary dysfunction and the development of nerve-sparing surgical techniques.

102 Background: Radiofrequency ablation (RFA) efficiency of liver tumors is compromised by high rates of relapse. Death of cancer cells by hyperthermia induced tumor antigen releasing, expression of danger signals that activate a specific T-cell response. This effect is ineffective to avoid recurrence. We propose to combine RFA with priming of a strong immune antitumor response as curative treatment of an aggressive colorectal cancer (CRC) in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor as primary lesion. In two distinct clinical situations, macroscopic or microscopic distant tumors were established as secondary lesions. The immune response was modulated by the injection, in the treated area, of a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting recruitment and maturation of dendritic cells. In mice with far large lesions, this strategy was combined with PD1checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of tumoral lymphocyte infiltration TNF-α and IFN-y expression in peripheral T lymphocytes. Results: The in situ immunogel injection after RFA resulted in prolonged survival of mice. Regression of distant lesions was related to the induction of a strong systemic antitumor immune response and a great improvement of tumor infiltration by CD3+ T lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without another treatment. Immune escape of large secondary lesions was reversed by association of the RFA-immunogel vaccination with a systemic immune checkpoint inhibition, separately ineffective. Conclusions: Validation of this strategy, combining RFA of macroscopic lesions and activation of a strong immune response controlling the residual disease, could result in the design of a clinical assay including this approach within a standard treatment of colorectal liver metastases. The synergy between in situ immunomodulation as priming process and checkpoint blockade, ineffective alone in metastatic microsatellite stable CRC or after single RFA, allows reconsidering the use of checkpoint inhibitors in CRC.

Objective: The aim of the study was to evaluate the prognostic value of the ratio of metastatic to examined lymph nodes (LNR) in patients with rectal cancer. Summary Background Data: Lymph nodes ratio (LNR) has been shown to have prognostic value in patients with colon cancer. The impact of LNR on disease-free and overall survival in patients with rectal cancer is unknown. Patients and Methods: From 1998 to 2004, 307 patients underwent rectal resection for adenocarcinoma. The relationships between overall and disease-free survival at 3 years and 15 variables, including the presence or absence of metastatic lymph nodes, the total number of lymph nodes examined, and LNR, were analyzed by multivariate analysis. Patients were then assigned to 4 groups based on LNR: LNR = 0 (N0 patients), LNR = 0.01 to 0.07, LNR >0.07 to 0.2, LNR >0.2. Results: The mean number of lymph nodes examined was 22 ± 12. In the multivariate analysis, LNR was a significant prognostic factor for both disease-free (P = 0.006) and overall survival (P = 0.0003), whereas the presence or absence of metastatic lymph nodes was not. LNR remained a significant prognostic factor in the 59 patients in whom fewer than 12 lymph nodes were examined (P = 0.0058). According to LNR values, disease-free and overall survival decreased significantly with increasing LNR (P Conclusions: LNR is the most significant prognostic factor for both overall and disease-free survival in patients with rectal cancer, even in patients with fewer than 12 lymph nodes examined.

Any therapeutic decision in colorectal cancer must be taken by multidisciplinary coordination meeting. The treatment of non-metastatic colon cancer based on the first surgery with complete excision, dissection and respect distal margins. In case of node-adjuvant chemotherapy improves survival. For rectal cancer, surgery may be preceded by chemo radiotherapy for locally advanced cancers. The sphincter preservation rate in entrained teams can reach 90%. The abdominoperineal resection is indicated in cases of tumor invading the external sphincter. In colorectal cancer the most important prognostic factor is the histological stage (invasion of the intestinal wall and lymph node involvement). If the breach only affects the mucosal healing is 100%. If the entire wall is reached, node negative the survival is 60%. However, if the lymph nodes are affected survival drop 30-40%. Finally in the presence of synchronous liver metastases curative treatment options can be considered and must be defined in the multidisciplinary coordination meeting. Surgery of liver metastases can achieve cure rates of 30% at 5 years.

Background BRAF mutations are present in 40 % of human skin melanomas. Mutated tumors with an increased percentage of BRAF mutant alleles (BRAF-M%) may have a better response to RAF/MEK inhibitors. We evaluated the BRAF-M% in melanomas, and the genetic causes of its variation. Methods BRAF-M% was quantified by pyrosequencing, real-time PCR (rtPCR) and/or picoliter-droplet PCR (dPCR). BRAF mutant expression was detected by immunohistochemistry. Chromosomal alterations were analyzed with fluorescence in situ hybridization (FISH), and single nucleotide polymorphism (SNP) arrays. Results BRAF-M% quantification obtained with pyrosequencing was highly correlated (R = 0.94) with rtPCR, and with dPCR. BRAF-M% quantified from DNA and RNA were also highly correlated (R = 0.98). Among 368 samples with >80 % tumor cells, 38.6 % had a BRAFV600E mutation. Only 66.2 % cases were heterozygous (BRAF-M% 30 to 60 %). Increased BRAF-M% (>60 %) was observed in 19 % of cases. FISH showed a polysomy of chromosome 7 in 13.6 %, 35.3 % and 54.5 % of BRAF wild-type, heterozygous and non-heterozygous BRAF-mutated samples, respectively (P

In the pelvis, the rectogenital septum (RGS) separates the urogenital compartment from the digestive compartment. In men, it corresponds to Denonvilliers’ rectoprostatic fascia or rectovesical septum (RVS). Its purpose—and, indeed, its existence—are controversial in women. The purpose of this review was to update knowledge about the RGS in women and, in particular, to clarify its relationship to pelvic nerves in order to deduce practical consequences of pelvic surgery and compare it to the RVS in men. A review of the anatomical and surgical literature was undertaken. Evidence for embryological origin, composition, and surgical importance of the RGS in women and men is suggested. This manuscript presents evidence of the existence of the RGS in both women (rectovaginal septum, RVaS) and men (rectovesical septum, RVS). It originates from the genital structures and extends from the rectogenital pouch to the perineal body. It is composed of connective tissue associated with bundles of smooth muscle cells and has lateral expansions in close contact with neurovascular bundles originating from the inferior hypogastric plexus. During pelvic surgery for carcinoma, preservation of nerve fibers of erectile bodies is necessary if possible. The RGS is thus an important surgical landmark during urogenital sinus surgery, prolapse surgery, and proctectomy in women as well as during proctectomy and prostatectomy in men. The RGS is present in women as well as in men, with great similarities between the two sexes. It represents an important surgical landmark during pelvic nerve-sparing surgery.

International audience; Some autologous tissues can restore erectile function (EF) in rats after a resection of the cavernous nerve (CN). However, a cavernous nerve crush injury (CNCI) better reproduces ED occurring after a nerve-sparing radical prostatectomy (RP). The aim was to evaluate the effect on EF of an autologous vein graft after CNCI, compared with an artificial conduit. Five groups of rats were studied: those with CN exposure, exposure+vein, crush, crush+guide and crush+vein. Four weeks after surgery, the EF of rats was assessed by electrical stimulation of the CNs. The intracavernous pressure (ICP) and mean arterial pressure (MAP) were monitored during stimulations at various frequencies. The main outcome, that is, the rigidity of the erections, was defined as the ICP/MAP ratio. At 10 Hz, the ICP/MAP ratios were 41.8%, 34.7%, 20.9%, 33.9% and 20.5%, respectively. The EF was significantly lower in rats if the CNCI was treated with a vein graft instead of an artificial guide. Contrary to cases of CN resection, autologous vein grafts did not improve EF after CNCI. In terms of clinical use, the study suggests to limit an eventual use of autologous vein grafts to non-nerve-sparing RPs.

e14540 Background: Results of radiofrequency ablation (RFA), increasingly used to treat liver tumors, are compromised by local and systemic relapse. Hyperthermia related cancer cells death, release of tumor antigens and expression of danger signals activate a tumor-specific T-cells response. This effect remains ineffective to avoid recurrence. Therefore we propose to combine RFA with an activation of a solid immune antitumor response as curative treatment of a colorectal (CRC) metastatic disease in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor. In two distinct clinical situations, distant macroscopic or microscopic tumors were established as metastases before or at the time of RFA. Immune response was modulated by an injection in situof a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting dendritic cells. In the group of mice with large far lesions this strategy was combined with immune checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of lymphocyte infiltration in tumors and systemic immunity through specific TNF- α and IFN-y expression in spleen and draining lymph nodes. Results: The in situ immunogel injection after RFA resulted in a prolonged survival of mice. Regression of distant lesions was related to a strong systemic antitumor immune response and a great improvement of tumor infiltration by specific cytotoxic lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without any treatment. Immune escape of large secondary lesions was reversed by association of RFA-immunogel vaccination with a systemic check point blockade, separately ineffective. Conclusions: Validation of this strategy, combining RFA of liver metastases and activation of a strong immune response controlling the residual disease, could result in a clinical assay including this approach within the standard treatment of CRC. Furthermorethe powerful synergy between RFA-in situ immunomodulation as a starter treatment and checkpoint blockade ineffective alone in CRC or after single RFA, allows reconsidering the use of immune checkpoint inhibitors in metastatic microsatellite stable CRC.