Publications by authors named "Cécile Brigand"

59 Publications

CDX2 controls genes involved in the metabolism of 5-fluorouracil and is associated with reduced efficacy of chemotherapy in colorectal cancer.

Biomed Pharmacother 2022 Mar 17;147:112630. Epub 2022 Jan 17.

Strasbourg University, INSERM, IRFAC / UMR-S1113, FHU ARRIMAGE, FMTS, 3 avenue Molière, 67200 Strasbourg, France. Electronic address:

Most patients affected with colorectal cancers (CRC) are treated with 5-fluorouracil (5-FU)-based chemotherapy but its efficacy is often hampered by resistance mechanisms linked to tumor heterogeneity. A better understanding of the molecular determinants involved in chemoresistance is critical for precision medicine and therapeutic progress. Caudal type homeobox 2 (CDX2) is a master regulator of intestinal identity and acts as tumor suppressor in the colon. Here, using a translational approach, we examined the role of CDX2 in CRC chemoresistance. Unexpectedly, we discovered that the prognosis value of CDX2 for disease-free survival of patients affected with CRC is lost upon chemotherapy and that CDX2 expression enhances resistance of colon cancer cells towards 5-FU. At the molecular level, we found that CDX2 expression correlates with higher levels of genes regulating the bioavailability of 5-FU through efflux (ABCC11) and catabolism (DPYD) in patients affected with CRC and CRC cell lines. We further showed that CDX2 directly regulates the expression of ABCC11 and that the inhibition of ABCC11 improves 5-FU-sensitivity of CDX2-expressing colon cancer cells. Thus, this study illustrates how biological functions are hijacked in CRC cells and reveals the therapeutic interest of CDX2/ABCC11/DPYD to improve systemic chemotherapy in CRC.
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http://dx.doi.org/10.1016/j.biopha.2022.112630DOI Listing
March 2022

Does baseline quality of life predict the occurrence of complications in resectable esophageal cancer?

Surg Oncol 2022 Mar 30;40:101707. Epub 2021 Dec 30.

Epidemiology and Quality of Life Unit, Georges-François Leclerc Cancer Centre-UNICANCER, Dijon, France; National Quality of Life and Cancer Clinical Research Platform, Dijon, France. Electronic address:

Background: The aim of this study was to assess the impact of baseline health related quality of life (HRQOL) on the occurrence of postoperative complications and death in patients with resectable esophageal cancer.

Methods: Existing data from a prospective, multicenter, open label, randomized, controlled phase III trial comparing hybrid versus open esophagectomy in patients with resectable esophageal cancer from 2009 to 2012 in France were used. A Cox regression model was used to assess the prognostic value of the baseline HRQOL score on the occurrence of major complications (MC), and major pulmonary complications (MPC) at 30 days post-surgery, as well as on 1-year postoperative overall survival (OS).

Results: Every 10-point increase in the baseline role functioning score was associated with a 14% reduction in the risk of MC, while every 10-point increase in fatigue or pain score was associated with an 18% increase in the risk of MC. Similarly, higher scores on fatigue and pain were associated with a higher risk of MPC. Compared with the hybrid procedure, patients undergoing open esophagectomy had a significantly higher risk of MC and MPC. Patients diagnosed with esophageal adenocarcinoma were at significantly lower risk of MC or MPC compared to patients with esophageal squamous cell carcinoma. Higher pain (HR = 1.23, p = 0.035) and insomnia (HR = 1.16, P = 0.031) scores were associated with increased 1-year OS.

Conclusion: Fatigue, pain, insomnia, and squamous cell pathology were indicators of poor prognosis, and that the presence of these findings might possibly change the management plan towards other forms of treatment and warrant close attention.
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http://dx.doi.org/10.1016/j.suronc.2021.101707DOI Listing
March 2022

What Is the Optimal Elective Colectomy for Splenic Flexure Cancer: End of the Debate? A Multicenter Study From the GRECCAR Group With a Propensity Score Analysis.

Dis Colon Rectum 2022 01;65(1):55-65

Université de Paris, Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Digestive and Oncologic Surgery, Paris, France.

Background: The optimal elective colectomy in patients with splenic flexure tumor is debated.

Objective: This study aimed to compare splenic flexure colectomy, left hemicolectomy, and subtotal colectomy for perioperative, histological, and survival outcomes in this setting.

Design: This is a multicenter retrospective cohort study.

Setting: Patients diagnosed with nonmetastatic splenic flexure tumor who underwent elective colectomy were included.

Patients: Between 2006 and 2014, 313 consecutive patients were operated on in 15 French Research Group of Rectal Cancer Surgery centers.

Interventions: Propensity score weighting was performed to compare short- and long-term outcomes.

Main Outcome Measures: The primary end point was disease-free survival. Secondary end points included overall survival, quality of surgical resection, overall postoperative morbidity, surgical postoperative morbidity, and rate of anastomotic leakage.

Results: The most performed surgery was splenic flexure colectomy (59%), followed by subtotal colectomy (23%) and left hemicolectomy (18%). Subtotal colectomy was more often performed by laparotomy compared with splenic flexure colectomy and left hemicolectomy (93% vs 61% vs 56%, p < 0.0001), and was associated with a longer operative time (260 minutes (120-460) vs 180 minutes (68-440) vs 217 minutes (149-480), p < 0.0001). Postoperative morbidity was similar between the 3 groups, but the median length of hospital stay was significantly longer after subtotal colectomy (13 days (5-56) vs 10 (4-175) vs 9 (4-55), p = 0.0007). The median number of harvested lymph nodes was significantly higher after subtotal colectomy compared with splenic flexure colectomy and left hemicolectomy (24 (8-90) vs 15 (1-81) vs 16 (3-52), p < 0.0001). The rate of stage III disease and the number of patients treated by adjuvant chemotherapy were similar between the 3 groups. There was no difference in terms of disease-free survival and overall survival between the 3 procedures.

Limitations: The study was limited by its retrospective design.

Conclusions: In the elective setting, splenic flexure colectomy is safe and oncologically adequate for patients with nonmetastatic splenic flexure tumor. However, given the oncological clearance after splenic flexure colectomy, it seems that the debate is not completely closed. See Video Abstract at http://links.lww.com/DCR/B703.

Cul Es La Colectoma Electiva Ptima Para El Cncer De Ngulo Esplnico Fin Del Debate Un Estudio Multicntrico Del Grupo Greccar Con Un Anlisis De Puntaje De Propensin: ANTECEDENTES:La colectomía electiva óptima en pacientes con tumores del ángulo esplénico continua en debate.OBJETIVO:Comparar la colectomía de ángulo esplénico, hemicolectomía izquierda y colectomía subtotal para los resultados perioperatorios, histológicos y de supervivencia en este escenario.DISEÑO:Estudio de cohorte retrospectivo multicéntrico.ESCENARIO:Se incluyeron pacientes diagnosticados de tumores del ángulo esplénico no metastásicos que se sometieron a colectomía electiva.PACIENTES:Entre 2006 y 2014, 313 pacientes consecutivos fueron intervenidos en 15 centros GRECCAR.INTERVENCIONES:Se realizó una ponderación del puntaje de propensión para comparar los resultados a corto y largo plazo.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la supervivencia libre de enfermedad. Los criterios de valoración secundarios incluyeron la supervivencia general, la calidad de la resección quirúrgica, la morbilidad posoperatoria general, la morbilidad posoperatoria quirúrgica y la tasa de fuga anastomótica.RESULTADOS:La cirugía más realizada fue la colectomía del ángulo esplénico (59%), seguida de la colectomía subtotal (23%) y la hemicolectomía izquierda (18%). La colectomía subtotal se realizó con mayor frecuencia mediante laparotomía en comparación con la colectomía de ángulo esplénico y la hemicolectomía izquierda (93% frente a 61% frente a 56%, p <0.0001), y se asoció con un tiempo quirúrgico más prolongado (260 min [120-460] frente a 180 min [68-440] frente a 217 min [149-480], p <0.0001). La morbilidad posoperatoria fue similar entre los tres grupos, pero la duración media de la estancia hospitalaria fue significativamente más prolongada después de la colectomía subtotal (13 días [5-56] frente a 10 [4-175] frente a 9 [4-55], p = 0.0007). La mediana del número de ganglios linfáticos extraídos fue significativamente mayor después de la colectomía subtotal en comparación con la colectomía del ángulo esplénico y la hemicolectomía izquierda (24 [8-90] frente a 15 [1-81] frente a 16 [3-52], p <0.0001). La tasa de enfermedad en estadio III y el número de pacientes tratados con quimioterapia adyuvante fueron similares entre los 3 grupos. No hubo diferencias en términos de supervivencia libre de enfermedad y supervivencia general entre los 3 procedimientos.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:En un escenario electivo, la colectomía del ángulo esplénico es segura y oncológicamente adecuada para pacientes con tumores del ángulo esplénico no metastásicos. Sin embargo, dado el aclaramiento oncológico tras la colectomía del ángulo esplénico, parece que el debate no está completamente cerrado. Consulte Video Resumen en http://links.lww.com/DCR/B703.
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http://dx.doi.org/10.1097/DCR.0000000000001937DOI Listing
January 2022

Half of Postoperative Deaths After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Could be Preventable: A French Root Cause Analysis on 5562 Patients.

Ann Surg 2021 11;274(5):797-804

Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, F-59000 Lille, France.

Objective: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures.

Background: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality.

Methods: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram.

Results: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%).

Conclusion: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions.
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http://dx.doi.org/10.1097/SLA.0000000000005101DOI Listing
November 2021

Current practice and perceptions of safety protocols for the use of intraperitoneal chemotherapy in the operating room: results of the IP-OR international survey.

Pleura Peritoneum 2021 Mar 12;6(1):39-45. Epub 2021 Feb 12.

Department of Surgical Oncology, Cancer Institute of Montpellier (ICM), Montpellier, France.

Objectives: To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Methods: A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0-10 (maximum).

Results: Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p<0.05), with Anesth scoring the lowest (6.81). Perceived contamination risk was 4.19 for HIPEC vs. 3.5 for PIPAC (p<0.01). Information level was lower for CleanS and Anesth for HIPEC and PIPAC procedures compared to all other responders (6.48 vs. 4.86, and 6.48 vs. 5.67, p<0.01). Willingness to obtain more information was 86%, the highest among CleanS (94%).

Conclusions: Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.
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http://dx.doi.org/10.1515/pp-2020-0148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223803PMC
March 2021

Limited Resection Versus Pancreaticoduodenectomy for Duodenal Gastrointestinal Stromal Tumors? Enucleation Interferes in the Debate: A European Multicenter Retrospective Cohort Study.

Ann Surg Oncol 2021 Oct 10;28(11):6294-6306. Epub 2021 Apr 10.

Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, CHU de Lille, Lille, France.

Background: The optimal surgical procedure for duodenal gastrointestinal stromal tumors (D-GISTs) remains poorly defined. Pancreaticoduodenectomy (PD) allows for a wide resection but is associated with a high morbidity rate.

Objectives: The aim of this study was to compare the short- and long-term outcomes of PD versus limited resection (LR) for D-GISTs and to evaluate the role of tumor enucleation (EN).

Methods: In this retrospective European multicenter cohort study, 100 patients who underwent resection for D-GIST between 2001 and 2013 were compared between PD (n = 19) and LR (n = 81). LR included segmental duodenectomy (n = 47), wedge resection (n = 21), or EN (n = 13). The primary objective was to evaluate disease-free survival (DFS) between the groups, while the secondary objectives were to analyze the overall morbidity and mortality, radicality of resection, and 5-year overall survival (OS) and recurrence rates between groups. Furthermore, the short- and long-term outcomes of EN were evaluated.

Results: Baseline characteristics were comparable between the PD and LR groups, except for a more frequent D2 tumor location in the PD group (68.3% vs. 29.6%; p = 0.016). Postoperative morbidity was higher after PD (68.4% vs. 23.5%; p < 0.001). OS (p = 0.70) and DFS (p = 0.64) were comparable after adjustment for D2 location and adjuvant therapy rate. EN was performed more in American Society of Anesthesiologists (ASA) stage III/IV patients with tumors < 5 cm and was associated with a 5-year OS rate of 84.6%, without any disease recurrences.

Conclusions: For D-GISTs, LR should be the procedure of choice due to lower morbidity and similar oncological outcomes compared with PD. In selected patients, EN appears to be associated with equivalent short- and long-term outcomes. Based on these results, a surgical treatment algorithm is proposed.
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http://dx.doi.org/10.1245/s10434-021-09862-7DOI Listing
October 2021

Five-Year Survival Outcomes of Hybrid Minimally Invasive Esophagectomy in Esophageal Cancer: Results of the MIRO Randomized Clinical Trial.

JAMA Surg 2021 04;156(4):323-332

Department of Digestive and Oncological Surgery, Hôpital Claude Huriez, Centre Hospitalier Universitaire (CHU) de Lille, Lille, France.

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 < .001) and major pulmonary complications (HR, 1.94; 95% CI, 1.21-3.10; P = .005) were identified as risk factors associated with decreased OS. Similarly, multivariable analysis of DFS identified overall intraoperative and postoperative complications (HR, 1.93; 95% CI, 1.28-2.90; P = .002) and major pulmonary complications (HR, 1.85; 95% CI, 1.19-2.86; P = .006) as risk factors.

Conclusions And Relevance: This study found no difference in long-term survival between the HMIE and open esophagectomy groups. Major postoperative overall complications and pulmonary complications appeared to be independent risk factors in decreased OS and DFS, providing additional evidence that HMIE may be associated with improved oncological results compared with open esophagectomy primarily because of a reduction in postoperative complications.

Trial Registration: ClinicalTrials.gov Identifier: NCT00937456.
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http://dx.doi.org/10.1001/jamasurg.2020.7081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890455PMC
April 2021

Is nonanatomic rectal resection a valid therapeutic option for rectal gastrointestinal stromal tumors? A proposed decision algorithm.

J Surg Oncol 2020 Dec 16;122(8):1639-1646. Epub 2020 Sep 16.

Department of Digestive Surgery, Strasbourg University, Strasbourg, France.

Background And Objectives: The best surgical approach to rectal gastrointestinal stromal tumors (GISTs) is still debated, and both nonanatomic rectal resection (NARR) and anatomic rectal resection (ARR) are applied. The aim of this study was to evaluate the feasibility and oncological outcomes of NARR and ARR for rectal GISTs (R-GISTs).

Methods: Through a large French multicentre retrospective study, 35 patients were treated for R-GIST between 2001 and 2013. Patients who underwent NARR and ARR were compared.

Results: There were 23 (65.7%) patients in group ARR and 12 (34.3%) in group NARR. Significantly more patients in the group with ARR had a neoadjuvant treatment (86%) with tyrosine kinase inhibitor (TKI) (imatinib) compared to those with NARR (25%) (p < .01). The median preoperative tumor size was significantly different between the groups without and with neoadjuvant TKI: 30 ± 23 mm versus 64 ± 44.4 mm, respectively (p < .001). Overall postoperative morbidity was 20% (n = 7) (26% for ARR vs. 8% for NARR; p = .4). After a median follow-up of 60.2 (3.2-164.3) months, the 5-year disease-free survival rates were 79.5% (confidence interval [CI] 95%: 54-100) for the NARR group and 68% (CI 95%: 46.4-89.7) for the ARR group (p = .697), respectively.

Conclusion: The use of NARR for small R-GIST's does not seem to impair the oncological prognosis.
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http://dx.doi.org/10.1002/jso.26215DOI Listing
December 2020

Is Lanreotide Really Useful in High Output Stoma? Comparison between Lanreotide to Conventional Antidiarrheal Treatment Alone.

J Invest Surg 2021 Dec 4;34(12):1312-1316. Epub 2020 Aug 4.

Department of Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.

Background: The incidence of high-output stoma (HOS) was reported to be approximately 3 to 16% in the literature, and HOS can cause dehydration. This complication is often severe enough to warrant hospital readmission and may result in renal failure. The aim of this study was to show a decrease of 50% in ileostomy output in the experimental arm using lanreotide treatment.

Methods: Patients with an ileostomy output ≥ 1.5 l/24 hours were included in this prospective, open, multicentre randomized trial. Patients were randomly allocated between treatment arms with either lanreotide (LAN) and antidiarrhoeal treatments (TAD) (LAN-TAD group) or antidiarrhoeal treatments only (TADS group). The primary outcome was ileostomy output after 72 days. The secondary endpoints were ileostomy output during the first 6 days, blood urea and creatinine values, hospital length of stay and serious adverse events.

Results: In the per-protocol analysis, there were nine patients in the control group (TADS) and six patients in the experimental group (TAD-LAN group). The stoma outputs at Day 3 (D3) in the experimental and control groups were 1,900 ± 855.7 mL and 1,728.6 ± 845.5 mL, respectively ( = 0.2). No differences were found concerning stoma output at D6, renal function, or hospital length of stay between the two groups.

Conclusion: The trial was prematurely stopped due to the low number of patients included. The question of the usefulness of somatostatin analogues in HOS persists, especially as the cost of this treatment is high, and there is a lack of evidence of its effectiveness.
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http://dx.doi.org/10.1080/08941939.2020.1800871DOI Listing
December 2021

Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.

Lancet Oncol 2020 09 24;21(9):1147-1154. Epub 2020 Jul 24.

Department of Surgical Oncology, University Hospital Gustave Roussy, Villejuif, France.

Background: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases.

Methods: We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m, or oxaliplatin 300 mg/m plus irinotecan 200 mg/m, plus intravenous fluorouracil 400 mg/m), or mitomycin-HIPEC (mitomycin 35 mg/m) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394.

Findings: Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0-54·8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61-1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients.

Interpretation: Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes.

Funding: French National Cancer Institute.
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http://dx.doi.org/10.1016/S1470-2045(20)30322-3DOI Listing
September 2020

Evaluating the Surgeon's Experience as a Risk Factor for Post-Esophagectomy Chylothorax on a Four-Year Cohort.

Cureus 2020 Jun 19;12(6):e8696. Epub 2020 Jun 19.

Visceral and Digestive Surgery, Hautepierre University Hospital, Strasbourg, FRA.

Background: Chylothorax (CHT) is a known post-operative complication after esophageal surgery with vaguely defined risk factors.

Methods: This is a retrospective chart review of 70 consecutive patients with operable cancer over a period of four years (January 2013 to December 2016). Ivor Lewis and McKeown interventions were performed. Thoracic duct is identified and ligated routinely. Factors related to the patient, the tumor, and the operating surgeon were analyzed.

Results: Incidence of CHT was 10%. Surgeons with less than five years of esophageal surgery experience had the most CHT, 71% (p=0.001). No association was found between tumor location, type, body mass index (BMI), neoadjuvant therapy, response to neoadjuvant therapy or male sex, and CHT. The odds of developing CHT were 17 times higher in patients operated by a junior surgeon (odds ratio, OR=17.67, confidence interval, CI 2.68-116.34, p=0.003). Four patients (5.7%) had anastomotic leaks, none of them had CHT. Senior surgeons had less operative time and harvested more lymph nodes (p=0.0002 and p=0.1086 respectively).

Conclusion: Surgeon's experience might be considered a major risk factor to develop CHT. This finding needs to be confirmed by a larger multicentric series taking into consideration the human factor.
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http://dx.doi.org/10.7759/cureus.8696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370582PMC
June 2020

How to Prevent Sarcopenia Occurrence during Neoadjuvant Chemotherapy for Oesogastric Adenocarcinoma?

Nutr Cancer 2021 25;73(5):802-808. Epub 2020 May 25.

Department of Digestive Surgery, Strasbourg University Hospital, Strasbourg, France.

The aim of this study was to evaluate the impact of a preoperative feeding jejunostomy (FJ) on the occurrence of sarcopenia before and after preoperative chemotherapy for patients with an oesogastric adenocarcinoma (OGA). Forty-six patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. Sarcopenia was evaluated by measuring muscle surfaces (psoas, paraspinal and abdominal wall muscles) on abdominal CT images at the level of the 3rd lumbar vertebra. A FJ was placed in 31 patients (67.4%) before the neoadjuvant treatment (FJ group), while 15 patients (32.6%) started neoadjuvant treatments without FJ (control group). After preoperative chemotherapy, there were significantly more sarcopenic patients in the control group, compared to the FJ group. In the FJ group, 13% of the patients ( = 4) were sarcopenic before treatment and 22.6% of them ( = 7) became sarcopenic after preoperative chemotherapy ( = 0.3). In the control group, if initially only 6.7% ( = 1) of patients were sarcopenic, the majority of the patients (60%,  = 9) became sarcopenic after chemotherapy ( = 0.012). The FJ was an independent risk factor of sarcopenia after neoadjuvant chemotherapy. FJ with enteral nutritional support during the preoperative management of OGA seemed to efficiently counteract sarcopenia occurrence during preoperative chemotherapy.
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http://dx.doi.org/10.1080/01635581.2020.1770813DOI Listing
August 2021

Multicystic and diffuse malignant peritoneal mesothelioma in children.

Pediatr Blood Cancer 2020 06 11;67(6):e28286. Epub 2020 Apr 11.

Department of Pediatric Surgery, University Hospital of Saint-Etienne, Saint-Priest-en-Jarez, France.

Background: Malignant and multicystic peritoneal mesotheliomas are extremely rare tumors in children, developing from mesothelial cells. No specific guidelines are available at this age.

Methods: We performed a retrospective analysis of all identified children (< 18-year-old) treated in France from 1987 to 2017 for a diffuse malignant peritoneal mesothelioma (DMPM) or a multicystic peritoneal mesothelioma (MCPM).

Results: Fourteen patients (5 males and nine females), aged 2.2 to 17.5 years, were included. The most frequent presenting symptoms were abdominal pain, ascitis, and alteration in the general condition. Eight patients had epithelioid mesothelioma, three had biphasic mesothelioma, and three had MCPM. Eight patients with DMPM diagnosis received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Among them, six patients had neoadjuvant systemic chemotherapy, one patient, post-operative chemotherapy, and one patient CRS and HIPEC only. Three patients received only systemic chemotherapy. All patients with MCPM had only surgery. After a median follow-up of seven years (2-15), six patients (6/11; one death) with DMPM and two patients (two/three) with MCPM had a local and distant recurrences.

Conclusion: Peritoneal mesothelioma in children is a rare condition with difficult diagnosis and high risk of recurrence. Worldwide interdisciplinary collaboration and networking are mandatory to help diagnosis and provide harmonious treatment guidelines.
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http://dx.doi.org/10.1002/pbc.28286DOI Listing
June 2020

Ovarian and peritoneal psammocarcinoma: Results of a multicenter study on 25 patients.

Eur J Surg Oncol 2020 05 9;46(5):862-867. Epub 2019 Dec 9.

Department of Surgical Oncology, Gustave Roussy Cancer Campus, 114, rue Edouard vaillant, 94800, Villejuif, France.

Purpose: Psammocarcinoma (PK) is a rare disease of unknown origin. We aimed to report the characteristics, management and survival of patients operated on for PK within the French Network for Rare Peritoneal Malignancies (RENAPE) expert centers.

Patients And Methods: All consecutive cases of PK operated within all 26 RENAPE centers between 1997 and 2018 were retrospectively analyzed.

Results: Twenty-five patients were identified. The median age was 53 years [range 17-78]. None of the patients had extra peritoneal metastases at diagnosis. A median of 6 cycles of carboplatin-based systemic chemotherapy was delivered in 52% preoperatively (n = 13) and 56% postoperatively (n = 14); associated with placlitaxel for 12 patients. All patients were operated on. The median PCI was 23 [0-33]. Eighty-four percent had a complete cytoreductive surgery through digestive (n = 7), spleen (n = 3), pancreas (n = 1) resections and/or multiple peritonectomies (n = 11). Five patients (20%) had intraperitoneal chemotherapy. Morbidity (Dindo-Clavien ≥3) was 12%. No postoperative death occurred. After a median follow-up of 42 months (range [2-194]), the median overall (OS) and progression-free (DFS) survival times were respectively 128 months and 31 months. Eighteen patients recurred (72%), mainly in the peritoneum (n = 16). Four of them (22%) were reoperated. The 5 and 10-year DFS rates were both 20.3%. The 5 and 10-year OS rates were 62% and 51.7%, respectively. A complete cytoreductive surgery was associated with a better OS and DFS in a univariate analysis.

Conclusion: Complete cytoreductive surgery is the cornerstone of the PK's management as a primary treatment. Recurrence remains common and new adjuvant strategies seem needed.
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http://dx.doi.org/10.1016/j.ejso.2019.12.005DOI Listing
May 2020

Health-related Quality of Life Following Hybrid Minimally Invasive Versus Open Esophagectomy for Patients With Esophageal Cancer, Analysis of a Multicenter, Open-label, Randomized Phase III Controlled Trial: The MIRO Trial.

Ann Surg 2020 06;271(6):1023-1029

Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, University Lille, Lille, France.

Background: Hybrid minimally invasive esophagectomy (HMIE) has been shown to reduce major postoperative complications compared with open esophagectomy (OE) for esophageal cancer.

Objectives: The aim of this study was to compare short- and long-term health-related quality of life (HRQOL) following HMIE and OE within a randomized controlled trial.

Methods: We performed a multicenter, open-label, randomized controlled trial at 13 study centers between 2009 and 2012. Patients aged 18 to 75 years with resectable cancers of the middle or lower third of the esophagus were randomized to undergo either transthoracic OE or HMIE. Patients were followed-up every 6 months for 3 years postoperatively and global health assessed with EORTC-QLQC30 and esophageal symptoms assessed with EORTC-OES18.

Results: The short-term reduction in global HRQOL at 30 days specifically role functioning [-33.33 (HMIE) vs -46.3 (OE); P = 0.0407] and social functioning [-16.88 (HMIE) vs -35.74 (OE); P = 0.0003] was less substantial in the HMIE group. At 2 years, social functioning had improved following HMIE to beyond baseline (+5.37) but remained reduced in the OE group (-8.33) (P = 0.0303). At 2 years, increases in pain were similarly reduced in the HMIE compared with the OE group [+6.94 (HMIE) vs +14.05 (OE); P = 0.018]. Postoperative complications in multivariate analysis were associated with role functioning, pain, and dysphagia.

Conclusions: Esophagectomy has substantial effects upon short-term HRQOL. These effects for some specific parameters are, however, reduced with HMIE, with persistent differences up to 2 years, and maybe mediated by a reduction in postoperative complications.
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http://dx.doi.org/10.1097/SLA.0000000000003559DOI Listing
June 2020

Strangulated recurrent rectal prolapse after a Delorme intervention, a case report.

Clin Case Rep 2019 Apr 6;7(4):770-772. Epub 2019 Mar 6.

Department of General and Digestive Surgery Hautepierre University Hospital Strasbourg France.

A surgeon must be aware of indications of rectal prolapse surgery with proper preoperative evaluation and have the ability to recognize complications. Sigmoid redundancy might lead to early recurrence, which itself could complicate into strangulation. Complications per say might require more drastic measures, as Hartmann's procedure in this case.
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http://dx.doi.org/10.1002/ccr3.2087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452528PMC
April 2019

Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer.

N Engl J Med 2019 01;380(2):152-162

From the Department of Digestive and Oncologic Surgery, Claude Huriez University Hospital, and INSERM, Centre Hospitalier Universitaire (CHU) Lille, Unité Mixte de Recherche 1172-JPARC Jean-Pierre Aubert Research Center, Team "Mucins, epithelial differentiation, and carcinogenesis," Université de Lille, Lille (C.M., G.P.), the Epidemiology and Quality of Life Unit, INSERM Unité 1231, Centre Georges François Leclerc, Dijon (T.S.D.-Y.), the Department of Hepatobiliary and Digestive Surgery, CHU Rennes, University of Rennes 1, Rennes (B.M.), Université Clermont Auvergne, INSERM, CHU Clermont-Ferrand, Service de Chirurgie Digestive, Clermont-Ferrand (D.P.), the Department of Digestive Surgery, Haut Lévèque University Hospital, Bordeaux (D.C.), the Department of Thoracic Surgery, Hôpital Nord, Aix-Marseille Université, Assistance Publique-Hôpitaux de Marseille, Marseille (X.B.D.), the Department of Digestive Surgery, Strasbourg University, Strasbourg (C.B.), the Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris (T.P.), the Department of Digestive Surgery, Purpan Hospital, CHU Toulouse, Université Toulouse III, Toulouse (N.C.), the Department of General Surgery and Liver Transplantation, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Equipe Mixte de Recherche 3738, Université Lyon 1, Lyon (J.-Y.M.), the Department of Digestive and General Surgery, CHU Louis Mourier, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris 7, Denis Diderot, PRES Sorbonne Paris Cité, Colombes (S.M.), the Department of Surgery and Oncology, Centre Hospitalier Universitaire Ambroise Paré, AP-HP, Université de Versailles, Boulogne-Billancourt (F.P.), the Department of Digestive Surgery, CHU Nîmes, Nîmes (M.P.), and the Methodology and Quality of Life Unit in Cancer, INSERM Unité Mixte de Recherche 1098, University Hospital of Besançon, Besançon (F.B.) - all in France; and the Department of Surgery and Cancer, Imperial College, London (S.R.M.).

Background: 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.

Methods: 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.

Results: 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; P<0.001). 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.

Conclusions: 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 .).
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http://dx.doi.org/10.1056/NEJMoa1805101DOI Listing
January 2019

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

J Surg Oncol 2019 Mar 16;119(3):336-346. Epub 2018 Dec 16.

St. George Hospital & University of New South Wales, Department of Surgery, Sydney, NSW, Australia.

Background And Objectives: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival.

Methods: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases.

Results: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001).

Conclusion: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.
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http://dx.doi.org/10.1002/jso.25277DOI Listing
March 2019

Biliary pancreatitis in a duplicate gallbladder: a case report and review of literature.

J Surg Case Rep 2018 May 29;2018(5):rjy112. Epub 2018 May 29.

Department of General and Digestive Surgery, University Hospital of Strasbourg, Strasbourg, France.

Duplicated gallbladder is a rare congenital anomaly that require special attentions due to its clinical, surgical and diagnostic difficulties. We present a case of a 39-year-old female patient with a duplicated gallbladder who presented with an acute biliary pancreatitis, a case to our knowledge is the first in the literature. A double gallbladder in an abdominal ultrasonography was doubtful, thus a computed tomography scan, a magnetic resonance cholangiopancreatography and an endoscopic retrograde cholangiopancreatography were done that confirmed the double gallbladder. A laparoscopic cholecystectomy with an intraoperative cholangiography was performed safely two months after the acute attack. The histopathological report revealed a Y-shaped type 1 double gallbladder according to the Harlaftis classification.
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http://dx.doi.org/10.1093/jscr/rjy112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007220PMC
May 2018

Cytoreductive surgery and hyperthermic intraperitoneal perfusion with chemotherapy in children with peritoneal tumor spread: A French nationwide study over 14 years.

Pediatr Blood Cancer 2018 Apr 29;65(4). Epub 2017 Dec 29.

Department of Pediatric Surgery, Paris Descartes University, Hôpital Necker Enfants-Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.

Background: Efficacy and role of cytoreductive surgery (CRS) and hyperthermic peritoneal perfusion with chemotherapy (HIPEC) remain poorly documented in pediatric tumors.

Methods: This retrospective national study analyzed all pediatric patients with peritoneal tumor spread treated by CRS and HIPEC as part of a multimodal therapy in France from 2001 to 2015.

Results: Twenty-two patients (nine males and 13 females) were selected. The median age at diagnosis was 14.8 years (4.2-17.6). Seven had peritoneal mesotheliomas; seven, desmoplastic small round cells tumors (DSRCT); and eight, other histologic types. A complete macroscopic resection (CC-0, where CC is completeness of cytoreduction) was achieved in 16 (73%) cases. Incomplete resections were classified as CC-1 in four (18%) cases and CC-2 in two (9%) cases. Fourteen (64%) patients had complications within 30 days from HIPEC, requiring an urgent laparotomy in eight (36%) cases. Thirteen (59%) patients received adjuvant chemotherapy and four (18%) received total abdominal radiotherapy after surgery. Sixteen (72%) patients had relapse after a median time of 9.6 months (1.4-86.4) and nine (41%) eventually died after a median time of 5.3 months (0.1-36.1) from relapse. Six (27%) patients (four mesotheliomas, one pseudopapillary pancreatic tumor, and one DSRCT) were alive and in complete remission after a median follow-up of 25.0 months (5.3-78.2). The mean overall survival (OS) and disease-free survival (DFS) were 57.5 months (95% CI [38.59-76.32]) and 30.9 months (95% CI [14.96-46.77]). Patients with a peritoneal mesothelioma had a significantly better OS (p = 0.015) and DFS (p = 0.028) than other histologic type.

Conclusions: In this national series, outcomes of HIPEC are encouraging for the treatment of peritoneal mesothelioma in children.
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http://dx.doi.org/10.1002/pbc.26934DOI Listing
April 2018

Proposal of a new preliminary scoring tool for early identification of significant blunt bowel and mesenteric injuries in patients at risk after road traffic crashes.

Eur J Trauma Emerg Surg 2018 Oct 14;44(5):779-785. Epub 2017 Dec 14.

Department of Digestive Surgery, Strasbourg University, 1 Avenue Moliere, 67000, Strasbourg, France.

Purpose: Blunt bowel and mesenteric injuries (BBMI) are regularly missed by abdominal computed tomography (CT) scans. The aim of this study was to develop a risk assessment tool for BBMI to help clinicians in decision-making for blunt trauma after road traffic crashes (RTCs).

Methods: Single-center retrospective study of trauma patients from January 2010 to April 2015. All patients admitted to our hospital after blunt trauma following RTCs and CT scan at admission were assessed.

Results: Of the 394 patients included, 78 (19.8%) required surgical exploration and 34 (43.6%) of these had a significant BBMI. A univariate and multivariate analysis were performed comparing patients with BBMI (n = 34) and patients without BBMI (n = 360). A score with a range from 0 to 13 was created. Scores from 8 to 9 were associated with 5-25% BBMI risk. The power of this new score ≥ 8 to predict a surgically significant BBMI had a sensitivity of 96%, specificity of 86.4%, positive predictive value (PPV) of 48% and negative predictive value (NPV) of 99.4%.

Conclusion: This score could be a valuable tool for the management of blunt trauma patients after RTA without a clear indication for laparotomy but at risk for BBMI. The outcome of this study suggests selective diagnostic laparoscopy for a score ≥ 8 in obtunded patients and ≥ 10 in all other. To assess the value and accuracy of this new score, a prospective validation of these retrospective findings is due.
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http://dx.doi.org/10.1007/s00068-017-0893-4DOI Listing
October 2018

The Added Diagnostic Value of F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

J Gastrointest Surg 2018 04 12;22(4):722-730. Epub 2017 Dec 12.

Department of Biophysics and Nuclear Medicine, Hautepierre University Hospital, University Hospitals of Strasbourg, University of Strasbourg, 1, Avenue Molière, 67098, Strasbourg Cedex 09, France.

Background: The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of F-fluorodihydroxyphenylalanine (F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.

Methods: Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology.

Results: There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003).

Conclusion: F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.
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http://dx.doi.org/10.1007/s11605-017-3645-1DOI Listing
April 2018

Discrepancy Between Clinical and Pathologic Nodal Status of Esophageal Cancer and Impact on Prognosis and Therapeutic Strategy.

Ann Surg Oncol 2017 Dec 25;24(13):3911-3920. Epub 2017 Sep 25.

Department of Digestive and Oncological Surgery, Univ.Lille, Claude Huriez University Hospital, Lille, France.

Background: The impact of discrepancies between clinical (c) and pathologic (p) stages of esophageal cancer remains a poorly understood issue. This study aimed to compare the prognosis of patient groups treated by primary surgery including clinical N0/pathologic N0 (cN0pN0), clinical N0/pathologic N+ (cN0pN+), clinical N+/pathologic N0 (cN+pN0), and clinical N+/pathologic N+ (cN+pN+).

Methods: Data were collected from 30 European centers during the years 2000 to 2010. Among 2944 recruited patients, 1554 patients receiving primary surgery met the inclusion criteria including 613 cN0pN0, 403 cN0pN+, 220 cN+pN0, and 318 cN+pN+ patients. Analyses with adjustment of the propensity score were used to compensate for differences in baseline characteristics.

Results: Clinical T stages 3 and 4 were increased in cN+pN+ (73.0%), cN0pN+ (49.6%), and cN+pN0 (51.8%) compared with cN0pN0 (32.8%). Compared with cN0pN0, cN+pN+ and cN0pN+ showed an increase in the proportion of adenocarcinoma histologic subtype, poor tumor differentiation, pathologic T3 and T4 stages, and R1/2 resection margin. Adjusted 5-year overall survival (hazard ratio [HR] 3.12; 95% confidence interval [CI] 2.57-3.78; P < 0.001) and event-free survival (HR 2.87; 95% CI 2.39-3.45; P < 0.001) were significantly reduced in cN0pN+ compared with cN0pN0. No significant differences in 5-year overall survival or event-free survival between cN0pN+ and cN+pN+ were observed. Regression analysis identified an association of distal tumor location, advanced clinical T stage, and poor tumor differentiation with pN+ disease.

Conclusions: This large multicenter study showed that cN0pN+ has a prognosis similar to that of cN+pN+ and worse than that of cN0pN0. Patients with clinical N0 disease but risk factors for pathologic N+ disease may benefit from neoadjuvant therapy before surgery.
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http://dx.doi.org/10.1245/s10434-017-6088-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670185PMC
December 2017

Surgical management of a De Garengeot's hernia using a biologic mesh: A case report and review of literature.

Int J Surg Case Rep 2017 18;39:273-275. Epub 2017 Aug 18.

Department of Digestive Surgery, Strasbourg University, 1 Avenue Moliere, 67000 Strasbourg, France. Electronic address:

Introduction: A De Garengeot hernia is a rare form of femoral hernia, where the appendix is found in the herniated sac. This feature is important to report, as both the diagnosis and the treatment are quite challenging in this particular condition.

Presentation Of Case: We report the case of a 77-year-old female presenting with a femoral hernia, containing an incarcerated necrotic vermiform appendix (De Garengeot hernia). A laparoscopic appendectomy was performed and the herniated defect was repaired according to Rives technique, using a biological mesh.

Discussion: The De Garengeot hernia is often unexpected and diagnosed intra-operatively. A pre-operative diagnosis is quite difficult, as it often presents clinically as a strangled femoral hernia. In patients without peritoneal signs, a contrast-enhanced Computed Tomography (CT) of the abdomen is useful for the diagnosis. Many surgical techniques have been discussed in literature, but there is no consensus. We show the feasibility and safety of the hernia repair according to Rives technique, through an inguinotomy with a biologic mesh. A laparoscopic approach was used to remove the necrotic appendix.

Conclusion: The De Garengeot hernia is an uncommon differential diagnosis for patients presenting with clinical signs of strangled femoral hernia. Although hernia repairs with a synthetic mesh in the presence of appendicitis have been reported, we describe a case of femoral hernia repair using a biologic mesh, in a patient with a De Garengot hernia.
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http://dx.doi.org/10.1016/j.ijscr.2017.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587892PMC
August 2017

Survival Benefit of Neoadjuvant Treatment in Clinical T3N0M0 Esophageal Cancer: Results From a Retrospective Multicenter European Study.

Ann Surg 2017 11;266(5):805-813

*Department of Visceral Surgery, Lausanne University Hospital, Lausanne, Switzerland †UniversityLille, Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France ‡Department of Digestive Surgery, Haut-Lévêque University Hospital, Bordeaux, France §UniversityLille, Department of Pathology, University Hospital, Lille, France ¶UniversityLille, UMR-S 1172 - JPARC - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille, France ||Inserm, UMR-S 1172, Lille, France **UniversityLille, Department of Biostatistics, University Hospital, Lille, France ††SIRIC (Site de Recherche Intégrée en Cancérologie) OncoLille, France ‡‡Department of Digestive Surgery, Cavale Blanche University Hospital, Brest, France §§Department of General and Digestive Surgery, Hautepierre University Hospital, Strasbourg, France ¶¶Department of General and Digestive Surgery, Purpan University Hospital, Toulouse, France ||||Department of Digestive Surgery, Saint-Antoine University Hospital, Paris, France ***Department of Digestive Surgery, Edouard Herriot University Hospital, Lyon, France †††Department of Digestive and Hepatobiliary Surgery, Pontchaillou University Hospital, Rennes, France.

Background: Based on current guidelines, clinical T3N0M0 esophageal tumors may or may not receive neoadjuvant treatment, according to their perception as locally advanced (cT3) or early-stage tumors (stage II). The study aim was to assess the impact of neoadjuvant treatment upon survival for cT3N0M0 esophageal cancer patients, with subgroup analyses by histological type (squamous cell carcinoma vs adenocarcinoma) and type of neoadjuvant treatment (chemotherapy vs radiochemotherapy).

Methods: Data from patients operated on for esophageal cancer in 30 European centers were collected. Among the 382 of 2944 patients with clinical T3N0M0 stage at initial diagnosis (13.0%), we compared those treated with primary surgery (S, n = 193) versus with neoadjuvant treatment plus surgery (NS, n = 189).

Results: The S and NS groups were similar regarding their demographic and surgical characteristics. In-hospital postoperative morbidity and mortality rates were comparable between groups. Patients were found to be pN+ in 64.2% versus 42.9% in the S and NS groups respectively (P < 0.001), pN2/N3 in 35.2% versus 21.2% (P < 0.001), stage 0 in 0% versus 16.4% (P < 0.001), and R0 in 81.3% versus 89.4% of cases (P = 0.026). Median overall and disease-free survivals were significantly better in the NS group, 38.4 versus 27.9 months (P = 0.007) and 31.6 versus 27.5 months (P = 0.040), respectively, and this difference remained for both histological types. Radiotherapy did not offer a benefit compared with chemotherapy alone (P = 0.687). In multivariable analysis, neoadjuvant treatment was an independent favorable prognostic factor (HR 0.76, 95% CI 0.58-0.99, P = 0.044).

Conclusion: Neoadjuvant treatment offers a significant survival benefit for clinical T3N0M0 esophageal cancer.
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http://dx.doi.org/10.1097/SLA.0000000000002402DOI Listing
November 2017

Could a Feeding Jejunostomy be Integrated into a Standardized Preoperative Management of Oeso-gastric Junction Adenocarcinoma?

Ann Surg Oncol 2017 Oct 26;24(11):3324-3330. Epub 2017 Jun 26.

Department of Digestive Surgery, Strasbourg University Hospital, 1 Avenue Moliere, 67000, Strasbourg, France.

Purpose: To evaluate the impact of a feeding jejunostomy (FJ) on the preoperative management of patients with an oesogastric adenocarcinoma (OGA).

Methods: From January 2007 to December 2014, patients with potentially resectable OGA were enrolled in a perioperative chemotherapy protocol. FJ was performed before starting perioperative treatments in patients presenting with dysphagia or with a nutritional risk index (NRI) <97.5. The patients who did not require a FJ served as a control group.

Results: Among the 114 patients with OGA consecutively admitted in our surgical department, 88 (77.2%) were enrolled for neoadjuvant treatment. A FJ was placed in 50 patients (56.8%) before the neoadjuvant treatment (FJ group), whereas 38 patients (43.2%) started neoadjuvant treatments without FJ (control group). Ninety-six percent of patients (n = 48) in the FJ group successfully completed the neoadjuvant treatment but only 81.6% of patients without FJ (n = 31; p = 0.004). The FJ group was divided between responders: 37 patients with a weight response (74%), and nonresponders: 13 patients without weight response (26%). In the FJ group, the nutritional response during preoperative chemotherapy was a significant predictive factor for the achievement of second stage oesogastric resection (p = 0.002).

Conclusions: FJ with enteral nutritional support during the preoperative management of OGA is a safe and effective support for the completion of the preoperative chemotherapy. The weight response to the enteral support is a predictor factor for a completion of the preoperative chemotherapy and could identify a group of patients who would have a better chance of reaching radical surgery.
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http://dx.doi.org/10.1245/s10434-017-5945-9DOI Listing
October 2017

Surgery Is an Effective Option after Failure of Chemoradiation in Cancers of the Anal Canal and Anal Margin.

Oncology 2017 2;93(3):183-190. Epub 2017 Jun 2.

Service de chirurgie générale et digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France.

Background: Surgery for anal canal cancer (ACC) and anal margin cancer (AMC) is the only curative option after failure of chemoradiotherapy (CRT). This study aimed to determine the efficacy of surgery for ACC or AMC after failed CRT.

Methods: This was a single-centre, retrospective study of 161 patients initially treated with CRT. We compared the survival rates of patients successfully treated by CRT with those of patients whose CRT failed (both surgically salvaged and treated palliatively).

Results: Thirty-one patients underwent surgery with curative intent, 20 received palliative treatment after failure of CRT, and 110 had effective CRT. The 5-year overall survival (OS) rate was significantly higher among patients with successful CRT than among patients who underwent surgery with curative intent (86 vs. 66%, p < 0.001). On the other hand, the 5-year OS of patients treated with curative surgery was significantly better than that of patients who underwent palliative treatment (66 vs. 13.5%, p < 0.001). The postoperative morbidity and mortality rates were 32 and 3%, respectively. Considering patients with failed CRT, curative surgery was the only factor prognostic of favourable OS in the multivariate analysis.

Conclusion: Curative surgery after failure of CRT for ACC or AMC remains an effective treatment to improve survival in two-thirds of cases, resulting in high but manageable morbidity.
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http://dx.doi.org/10.1159/000475758DOI Listing
December 2017

Management of rectal squamous cell carcinoma.

Clin Res Hepatol Gastroenterol 2017 10 5;41(5):e71-e73. Epub 2017 May 5.

Service de chirurgie générale et digestive, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, 2, avenue Molière, 67200 Strasbourg, France.

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http://dx.doi.org/10.1016/j.clinre.2017.03.012DOI Listing
October 2017

Surgically treated oesophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes.

Eur J Cancer 2017 04 23;75:179-189. Epub 2017 Feb 23.

Univ. Lille, Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, F-59000 Lille, France; Univ. Lille, UMR-S 1172 - JPARC - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France; Inserm, UMR-S 1172, F-59000 Lille, France; SIRIC OncoLille, France. Electronic address:

Background: The objectives of this study were to compare peri-operative and long-term outcomes from oesophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary (PEC) and among ECRF patients and (ii) radiotherapy-induced (RIEC) versus non-radiotherapy-induced EC (NRIEC).

Methods: Data were collected from 30 European centres from 2000 to 2010. Two thousand four hundred eighty nine EC patients surgically treated were included in the PEC group and 136 in the ECRF group, NRIEC group (n = 61) and RIEC group (n = 75). Propensity score matching analyses were used to compensate for differences in baseline characteristics.

Results: Compared to the PEC group, the ECRF group was characterised by less use of neoadjuvant chemoradiotherapy (0% versus 29.5%; P < 0.001), less pathological stage III/IV (31.6% versus 39.2%, P = 0.036), greater incidence of R1/2 margins (21.3% versus 10.9%; P < 0.001), increased in-hospital mortality (14.0% versus 7.1%; P = 0.003) and overall morbidity (68.4% versus 56.4%, P = 0.006). After matching, 5-year overall (28.8% versus 50.5%; hazard ratio [HR] = 1.53, 95% confidence interval [CI]: 1.15-2.04; P = 0.003) and event-free (32.2% versus 42.5%; HR = 1.56, 95% CI: 1.18-2.05; P = 0.002) survivals were significantly reduced in the ECRF group. There were no significant differences in incidence or pattern of tumour recurrence. Comparing RIEC and NRIEC groups, there were no significant differences in short- or long-term outcomes before and after matching.

Conclusions: ECRF is associated with poorer long-term survival related to a reduced utilisation of neoadjuvant chemoradiotherapy and an increased incidence of tumour margin involvement at surgery. Outcomes appear to be dictated by the limitations related to previous radiotherapy administration more than the radiotherapy-induced carcinogenesis.
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http://dx.doi.org/10.1016/j.ejca.2016.12.036DOI Listing
April 2017

Perioperative bevacizumab improves survival following lung metastasectomy for colorectal cancer in patients harbouring v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue exon 2 codon 12 mutations†.

Eur J Cardiothorac Surg 2017 02;51(2):255-262

Department of Thoracic Surgery, Strasbourg University Hospital, Strasbourg, France.

Objectives: The role of perioperative chemotherapy (POC) and targeted therapies in lung metastasectomy for colorectal cancer (CRC) is still subject to debate. We aimed to evaluate whether POC and targeted therapies were associated with different outcomes according to the mutational status.

Methods: We reviewed data from 223 patients who underwent pulmonary metastasectomy for CRC from 1998 to 2015 and for whom the V-Ki-ras2 Kirsten sarcoma viral oncogene homologue (KRAS) and V-raf Murine sarcoma viral oncogene homologue B1 (BRAF) mutational statuses were known.

Results: A total of 167 patients (74%) underwent POC: 62 (37%) received neoadjuvant therapy, 59 (35%) were in the adjuvant setting and 46 (28%) were in both the neoadjuvant and adjuvant settings. POC did not significantly influence either the loco-regional recurrence free survival (LRRFS) (P = 0.21) or the overall survival (OS) (P = 0.29). Furthermore, in cases of adjuvant chemotherapy, outcomes were not significantly different in cases of neoadjuvant chemotherapy or both neoadjuvant and adjuvant treatment (P = 0.26 for OS, P = 0.14 for LRRFS). For patients with KRAS mutation, perioperative bevacizumab was associated with a significant improvement in both LRRFS [70 months (41.58–98.42) vs 24 months (1.15–46.86), P = 0.001] and OS [101 vs 55 months (49.77–60.23), P = 0.004]. However, this benefit was only significant in cases of KRAS exon 2 codon 12 mutations [median OS: 101 months (83.97–118.02) vs 60 months (53–66.99), P < 0.001; median LRRFS: 76 months (64.62–87.38) vs 44 months (35.27–52.73), P < 0.001].

Conclusion: Perioperative bevacizumab appears to be beneficial in patients with exon 2 codon 12 KRAS mutations who have undergone lung metastasectomy for CRC.
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http://dx.doi.org/10.1093/ejcts/ezw304DOI Listing
February 2017
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