Jeremie H. Lefevre

Career choices of medical students: a national survey of 1780 students.

Medical Education 2010: 44: 603–612

Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis.

Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorouracil, which are routinely prescribed in the adjuvant treatment of people with CRC. The survival and response to chemotherapy of subjects with MSI CRCs was associated with the tumor expression level of HSP110ΔE9. HSP110 may thus constitute a major determinant for both prognosis and treatment response in CRC.

Risk factors for development of desmoid tumours in familial adenomatous polyposis

Desmoid tumours (DTs) are the primary cause of death of patients with familial adenomatous polyposis (FAP) following restorative proctocolectomy. The aim of this study was to identify risk factors for DT in a French population.

Outcome of antegrade continence enema procedures for faecal incontinence in adults.

Faecal incontinence has major consequences. Colostomy has been the mainstay of therapy when other options fail. Operations such as the Malone procedure have been proposed as an alternative. The aim of this study was to evaluate the outcomes and quality of life of patients having a Malone procedure for the treatment of faecal incontinence.

Martius advancement flap for low rectovaginal fistula: short- and long-term results.

Aimu2002 Many surgical approaches have been described for the treatment of low rectovaginal fistulae (LRVF); however, all are associated with a high recurrence rate and a poor function. The Martius flap technique was first described in 1928 and has since been modified for the treatment of LRVF. The aims of this study were to evaluate the short‐ and long‐term results of the Martius flap procedure.

Screening for Lynch syndrome in colorectal cancer: are we doing enough?

PurposeThe purpose of this study was to assess the efficacy of screening for the detection of Lynch syndrome (LS) in an unselected population undergoing surgery for a colorectal cancer.MethodsA total of 1,040 patients were prospectively included between 2005 and 2009. LS screening modalities included the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and microsatellite instability (MSI) by using pentaplex markers. Promoter methylation was assessed in tumors with a loss of MLH1 expression. Gene sequencing was offered to patients with abnormal IHC or MSI status without promoter methylation.ResultsA total of 105 patients had an abnormal result: 102 (9.8%) exhibited a loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in 10 patients with eventual proven LS in 6 patients. Loss of MLH1 (nxa0=xa064) was due to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with a germ-line mutation. Loss of MSH2 on IHC was associated with a mutation in 78.3% (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did not meet the Bethesda criteria.ConclusionsStrict application of the Bethesda criteria does not lead to identification of all patients with LS. IHC and MSI testing are complementary methods and should be used in association to identify potential LS patients.

Laparoscopic 3-step restorative proctocolectomy: comparative study with open approach in 45 patients.

Background To compare the results of a total laparoscopic versus open approach 3-time ileal pouch anal anastomosis (IPAA) for patients with acute or severe colitis complicating inflammatory bowel disease. Methods Consecutive subtotal colectomy was followed by IPAA then by stoma closure. Between 2000 and 2006, 23 consecutive patients, operated through a total laparoscopic approach were well matched with 22 patients operated by open approach. Results Overall major complications rate was lower after laparoscopic than after open approach (5/23 vs. 9/22; NS). Mean hospital stay for the 3 consecutive procedures was significantly reduced after laparoscopic versus open approach (27±7u2009d vs. 39±27u2009d; P<0.05). Conclusions Our case-control study suggests that, in experienced centers, a total laparoscopic approach can be viewed as a viable alternative to conventional open 3-step IPAA for the treatment of acute or severe colitis complicating inflammatory bowel disease.

Abdominoperineal Resection for Squamous Cell Anal Carcinoma: Survival and Risk Factors for Recurrence

BackgroundDespite the results of combined chemoradiation therapy for anal canal squamous cell carcinoma (SCC), up to 30xa0% of patients will undergo abdominoperineal resection (APR). The aim of this study was to evaluate oncologic outcomes, survival, and recurrence, following APR for anal canal SCC performed in a single center over a 13-year period.MethodsAll patients who underwent APR for anal canal SCC between 1996 and 2009 were retrospectively included. Demographic data, details on treatments, pathological report, and follow-up were noted. Survival curves were plotted using the Kaplan–Meier method and potential prognostic factors were evaluated using Cox proportional hazards models.ResultsA total of 105 patients (77 women) were included. Indications for APR included tumor persistence (nxa0=xa042; 40xa0%), recurrence (nxa0=xa055; 52.4xa0%), or a contraindication to radiotherapy (nxa0=xa08; 7.6xa0%). Median follow-up was 33.3xa0months (range, 1.5–174.3xa0months). Overall survival and disease-free survival were, respectively, 61 and 48xa0% at 5xa0years. In multivariate analysis, tumor stage (T3 or T4), positive margin on pathologic examination and existence of distant metastases at the time of the surgery were associated with a poor prognosis. The indication for APR (persistent vs recurrent disease), gender, concurrent HIV infection, or performance of a VRAM flap did not influence OS or DFS. Overall recurrence rate was 42.6xa0% (nxa0=xa043 of 101). The type of recurrence did not exert a significant effect on survival (pxa0=xa0.4571).ConclusionThis study describes the largest single series of APR for anal carcinoma. Major prognostic factors for survival and recurrence were T status and involved margin. The 5-year overall survival was 60xa0%.

A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design

BackgroundNeoadjuvant radiochemotherapy (RCT) is now part of the armamentarium of cancer of the lower and middle rectum. It is recommended in current clinical practice prior to surgical excision if the lesion is classified T3/T4 or N+. Histological complete response, defined by the absence of persistent tumor cell invasion and lymph node (ypT0N0) after pathological examination of surgical specimen has been shown to be an independent prognostic factor of overall survival and disease-free survival. Surgical excision is usually performed between 6 and 8xa0weeks after completion of CRT and pathological complete response rate ranges around 12%. In retrospective studies, a lengthening of the interval after RCT beyond 10xa0weeks was found as an independent factor increasing the rate of pathological complete response (between 26% and 31%), with a longer disease-free survival and without increasing the operative morbidity. The aim of the present study is to evaluate in 264 patients the rate of pathological complete response rate of rectal cancer after RCT by lengthening the time between RCT and surgery.Methods/designThe current study is a multicenter randomized trial in two parallel groups comparing 7 and 11xa0weeks of delay between the end of RCT and cancer surgery of rectal tumors.At the end of the RCT, surgery is planified and randomization is performed after patient’s written consent for participation. The histological complete response (ypT0N0) will be determined with analysis of the complete residual tumor and double reading by two pathologists blinded of the group of inclusion. Patients will be followed in clinics for 5xa0years after surgery. Participation in this trial does not change patient’s management in terms of treatment, investigations or visits. Secondary endpoints will include overall and disease free survival, rate of sphincter conservation and quality of mesorectal excision. The number of patients needed is 264.Trial registrationClinicalTrial.gov: NCT01648894

ECCO-ESCP Consensus on Surgery for Crohn's Disease

Willem A. Bemelman, Janindra Warusavitarne, Gianluca M. Sampietro, Zuzana Serclova, Oded Zmora, Gaetano Luglio, Anthony de Buck van Overstraeten, John P. Burke, Christianne J. Buskens, Francesco Colombo, Jorge Amil Dias, Rami Eliakim, Tomás Elosua, I. Ethem Gecim, Sanja Kolacek, Jaroslaw Kierkus, Kaija-Leena Kolho, Jérémie H. Lefevre, Monica Millan, Yves Panis, Thomas Pinkney, Richard K. Russell , Chaya Shwaartz, Carolynne Vaizey, Nuha Yassin, André D’Hoore, On behalf of the European Crohns and Colitis Organisation (ECCO) and the European Society of Coloproctology (ESCP)