Publications by authors named "Emilie Duchalais"

35 Publications

Systematic upper endoscopy concomitant with colonoscopy performed within the colorectal cancer screening program: Impact on the patients' management.

Clin Res Hepatol Gastroenterol 2021 Mar 11;45(3):101501. Epub 2021 Mar 11.

Institut des Maladies de l'appareil Digestif, Hépato-Gastroentérologie & Oncologie Digestive, Hôtel Dieu, Nantes University Hospital, 1 place Alexis Ricordeau, Nantes 44093, France.

Background And Aims: The French colorectal cancer screening program is based on a fecal immunochemical test, followed by colonoscopy in case of positivity. The benefit of adding a concomitant upper endoscopy to detect upper digestive lesions (precancerous or others) is still debated. Our aim was to evaluate the frequency of upper digestive lesions detected by upper endoscopy performed concomitantly with colonoscopy following a positive fecal immunochemical test, and their impact on the patients' management (i.e., surveillance, medical treatment, endoscopic or surgical procedure).

Methods: Data of all the patients who consulted for a positive test between May 2016 and May 2019 in our center, and for whom concomitant upper endoscopy and colonoscopy were performed, were analyzed retrospectively. Patients with significant history of upper gastrointestinal diseases or with current gastrointestinal symptoms were excluded.

Results: One hundred patients were included [median age (min-max): 62 (50-75), men 64%]. Macroscopic and/or microscopic upper digestive lesions were found in 58 of them (58%): Helicobacter pylori infection in 17 patients, gastric precancerous lesions in 9 patients (chronic atrophic gastritis with intestinal metaplasia, n=8, low grade dysplasia, n=1), Barrett's esophagus requiring surveillance in 4 patients, and 1 duodenal adenoma with low-grade dysplasia. In 44 patients (44%), the upper endoscopy findings had an impact on patients' management, with no significant difference between the groups with positive (CRC or advanced adenoma)- or negative (any other lesions or normal) colonoscopy.

Conclusion: A systematic upper endoscopy combined with colonoscopy for positive fecal immunochemical test could represent an efficient strategy for upper digestive lesions screening in France. Further studies are necessary to confirm these results and to evaluate cost-effectiveness of this approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinre.2020.07.006DOI Listing
March 2021

Are colorectal cancer patients at risk for COVID-19 infection during the postoperative period? The Covid-GRECCAR study.

Int J Colorectal Dis 2021 Mar 26;36(3):611-615. Epub 2021 Jan 26.

Department of Digestive Surgical Oncology, Department of Mini Invasive Interventions (DIMI), Paoli Calmettes Institute, Marseille, France.

Introduction: During the COVID-19 pandemic, cancer patients have been regarded as having a high risk of severe events if they are infected with SARS-CoV-2, particularly those under medical or surgical treatment. The aim of this study was to assess the posttreatment risk of infection by SARS-CoV-2 in a population of patients operated on for colorectal cancer 3 months before the COVID-19 outbreak and who after hospitalization returned to an environment where the virus was circulating.

Materials And Methods: This French, multicenter cohort study included consecutive patients undergoing elective surgery for colorectal cancer between January 1 and March 31, 2020, at 19 GRECCAR hospitals. The outcome was the rate of COVID-19 infection in this group of patients who were followed until June 15, 2020.

Results: This study included 448 patients, 262 male (58.5%) and 186 female (41.5%), who underwent surgery for colon cancer (n = 290, 64.7%), rectal cancer (n = 155, 34.6%), or anal cancer (n = 3, 0.7%). The median age was 68 years (19-95). Comorbidities were present in nearly half of the patients, 52% were at least overweight, and the median BMI was 25 (12-42). At the end of the study, 448 were alive. Six patients (1.3%) developed COVID-19 infection; among them, 3 were hospitalized in the conventional ward, and none of them died.

Conclusion: The results are reassuring, with only a 1.3% infection rate and no deaths related to COVID-19. We believe that we can operate on colorectal cancer patients without additional mortality from COVID-19, applying all measures aimed at reducing the risk of infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00384-021-03847-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835106PMC
March 2021

The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer.

Cancers (Basel) 2021 Jan 7;13(2). Epub 2021 Jan 7.

Inserm, CRCINA, Université de Nantes, 44000 Nantes, France.

In colorectal cancer (CRC), a high density of T lymphocytes represents a strong prognostic marker in subtypes of CRC. Optimized immunotherapy strategies to boost this T-cell response are still needed. A good candidate is the inflammasome pathway, an emerging player in cancer immunology that bridges innate and adaptive immunity. Its effector protein caspase-1 matures IL-18 that can promote a T-helper/cytotoxic (Th1/Tc1) response. It is still unknown whether tumor cells from CRC possess a functional caspase-1/IL-18 axis that could modulate the Th1/Tc1 response. We used two independent cohorts of CRC patients to assess IL-18 and caspase-1 expression by tumor cells in relation to the density of TILs and the microsatellite status of CRC. Functional and multiparametric approaches at the protein and mRNA levels were performed on an ex vivo CRC explant culture model. We show that, in the majority of CRCs, tumor cells display an activated and functional caspase-1/IL-18 axis that contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Rα. Furthermore, unsupervised clustering identified three clusters of CRCs according to the caspase-1/IL-18/TIL density/interferon gamma (IFNγ) axis and microsatellite status. Together, our results strongly suggest that targeting the caspase-1/IL-18 axis can improve the anti-tumor immune response in subgroups of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13020189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825767PMC
January 2021

GLP-2 Prevents Neuronal and Glial Changes in the Distal Colon of Mice Chronically Treated with Cisplatin.

Int J Mol Sci 2020 Nov 23;21(22). Epub 2020 Nov 23.

Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine, University of Florence, 50139 Florence, Italy.

Cisplatin is a chemotherapeutic agent widely used for the treatment of solid cancers. Its administration is commonly associated with acute and chronic gastrointestinal dysfunctions, likely related to mucosal and enteric nervous system (ENS) injuries, respectively. Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone exerting trophic/reparative activities on the intestine, via antiapoptotic and pro-proliferating pathways, to guarantee mucosal integrity, energy absorption and motility. Further, it possesses anti-inflammatory properties. Presently, cisplatin acute and chronic damages and GLP-2 protective effects were investigated in the mouse distal colon using histological, immunohistochemical and biochemical techniques. The mice received cisplatin and the degradation-resistant GLP-2 analog ([Gly2]GLP-2) for 4 weeks. Cisplatin-treated mice showed mucosal damage, inflammation, IL-1β and IL-10 increase; decreased number of total neurons, ChAT- and nNOS-immunoreactive (IR) neurons; loss of SOX-10-IR cells and reduced expression of GFAP- and S100β-glial markers in the myenteric plexus. [Gly2]GLP-2 co-treatment partially prevented mucosal damage and counteracted the increase in cytokines and the loss of nNOS-IR and SOX-10-IR cells but not that of ChAT-IR neurons. Our data demonstrate that cisplatin causes mucosal injuries, neuropathy and gliopathy and that [Gly2]GLP-2 prevents these injuries, partially reducing mucosal inflammation and inducing ENS remodeling. Hence, this analog could represent an effective strategy to overcome colonic injures induced by cisplatin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21228875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700273PMC
November 2020

Concomitant decrease of double-positive lymphocyte population CD4CD8αα and Faecalibacterium prausnitzii in patients with colorectal cancer.

Eur J Gastroenterol Hepatol 2021 Feb;32(2):149-156

Université de Nantes, Microbiotas Hosts Antibiotics and bacterial Resistances (MiHAR).

Introduction And Aims: Changes in the composition of the gut microbiota in patients with colorectal cancer (CRC) compatible with a contribution of the gut microbiota in carcinogenesis have been reported. In particular, a decrease Faecalibacterium prausnitzii has been identified. A CD4CD8αα, double-positive lymphocyte population (DP8α) has recently been demonstrated in the human colon and blood with regulatory functions and specificity for F. prausnitzii. Here, we aimed to detect dysbiosis in the fecal microbiome of patients with CRC by metagenomic analysis, and to look for changes in the levels of DP8α circulating T cells specific for F. prausnitzii in these patients.

Patients And Methods: Patients with CRC and control subjects were prospectively included. None had received antibiotics in the previous month or any anti-tumor treatment. A stool sample was collected for each participant, and analyzed by shotgun sequencing. The DP8α T cell population was identified and quantified on fresh whole blood by flow cytometry with anti-CD45, anti-CD3, anti-CD4 and anti-CD8α co-labeling.

Results: Twenty-one patients with CRC and 20 controls subjects were included. We found that mean relative abundance of five species was significantly decreased in CRC patients compared with controls, including F. prausnitzii, Barnesiella intestinihominis, Alistipes finegoldii, Bacteroides eggerthii and Eubacterium siraeum. We also found that the DP8α T cell population was significantly decreased in the blood of CRC patients compared with controls.

Conclusion: In our work, we showed that a reduced abundance of F. prausnitzii in CRC patients was associated to a significant decrease in the circulating DP8α Treg population, suggesting a potential involvement of reduced activity of DP8α T cells in colonic carcinogenesis. These findings open new diagnostic and therapeutic strategies for CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001842DOI Listing
February 2021

Tau accumulates in Crohn's disease gut.

FASEB J 2020 07 21;34(7):9285-9296. Epub 2020 May 21.

Inserm, TENS, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Université de Nantes, Nantes, France.

A sizeable body of evidence has recently emerged to suggest that gastrointestinal (GI) inflammation might be involved in the development of Parkinson's disease (PD). There is now strong epidemiological and genetical evidence linking PD to inflammatory bowel diseases and we recently demonstrated that the neuronal protein alpha-synuclein, which is critically involved in PD pathophysiology, is upregulated in inflamed segments of Crohn's colon. The microtubule associated protein tau is another neuronal protein critically involved in neurodegenerative disorders but, in contrast to alpha-synuclein, no data are available about its expression and phosphorylation patterns in inflammatory bowel diseases. Here, we examined the expression levels of tau isoforms, their phosphorylation profile and truncation in colon biopsy specimens from 16 Crohn's disease (CD) and 6 ulcerative colitis (UC) patients and compared them to samples from 16 controls. Additional experiments were performed in full thickness segments of colon of five CD and five control subjects, in primary cultures of rat enteric neurons and in nuclear factor erythroid 2-related factor (Nrf2) knockout mice. Our results show the upregulation of two main human tau isoforms in the enteric nervous system (ENS) in CD but not in UC. This upregulation was not transcriptionally regulated but instead likely resulted from a decrease in protein clearance via an Nrf2 pathway. Our findings, which provide the first detailed characterization of tau in CD, suggest that the key proteins involved in neurodegenerative disorders such as alpha-synuclein and tau, might also play a role in CD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202000414RDOI Listing
July 2020

Nationwide Analysis of Urinary Retention Following Inguinal Hernia Repair: Results from the National Prospective Hernia Registry.

World J Surg 2020 08;44(8):2638-2646

Clinique de Chirurgie Digestive et Endocrinienne (CCDE), Institut des Maladies de l'Appareil Digestif (IMAD), University Hospital of Nantes, 1, Place Alexis Ricordeau, 44093, Nantes, France.

Background: Urinary retention is one of the most common early postoperative complications following inguinal hernia repair (IHR). The aim of this study was to assess the incidence of postoperative urinary retention (POUR) and to identify associated risk factors.

Method: Data of consecutive patients undergoing IHR from 2011 to 2017 were collected from a national multicenter cohort. POUR was defined as the inability to void requiring urinary catheterization. A multivariate analysis was conducted to identify independent risk factors for POUR.

Results: Of 13,736 patients, 109 (0.8%) developed POUR. Patients with POUR had longer hospital length of stay (p < 0.001). IHR was performed by a laparoscopic or an open approach in 7012 (51.3%) and 6655 (48.7%) patients, respectively, and spinal anesthesia was realized in 591 (4.3%) patients. Ambulatory surgery was performed in 10,466 (76.6%) patients. Multivariate analysis identified preoperative dysuria (0R 3.73, p < 0.001), diabetes mellitus (OR 1.98, p = 0.029) and spinal anesthesia (OR 7.56, p < 0.001) as independent preoperative risk factors associated with POUR. POUR was the cause of ambulatory failure in 35 (10.2%) patients who required unanticipated admission.

Conclusion: The incidence of POUR following IHR remains low but impacts hospitalization settings. Preoperative risk factors for POUR should be considered for the choice of the anesthetic technique.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-020-05538-7DOI Listing
August 2020

Alterations of the Rectal Microbiome Are Associated with the Development of Postoperative Ileus in Patients Undergoing Colorectal Surgery.

J Gastrointest Surg 2020 07 22;24(7):1663-1672. Epub 2020 Apr 22.

Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA.

Background: The most common complications after colorectal surgery, postoperative ileus, surgical site infections, and anastomotic leaks continue to occur despite advances in surgical technique and enhanced recovery pathways. Preclinical studies have documented that intestinal bacteria play a role in the development of these complication, yet human data is lacking. Here we hypothesized that patients that develop ileus, surgical site infection, and/or anastomotic leak following colorectal surgery harbor a specific preoperative gut microbiome.

Methods: We performed a prospective cohort study on 101 patients undergoing colon or rectal resection at the Mayo Clinic. Rectal samples were collected preoperatively and on the ward on postoperative day two. The bacterial community from each sample was characterized by 16S rRNA and associated with the development of complications.

Results: The rectal microbiome collected from patients in the operating room (p = .003) and on postoperative day two (p = .001) was significantly difference in patients whom later developed postoperative ileus compared with patients that had a normal return of bowel function. Patients whom developed ileus showed increased abundance of Bacteroides spp., Parabacteroides spp., and Ruminococcus spp., bacteria that are associated with promoting intestinal inflammation. There were no differences in the microbiome in patients that developed surgical site infections or anastomotic leaks.

Conclusions: In this pilot study, patients that develop postoperative ileus harbor a specific gut microbiome during the perioperative period. These findings demonstrate that the preoperative bacterial composition may predispose patients to the development of ileus and that perioperative manipulation of the gut bacteria may provide a novel method to promote normal return of bowel function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-020-04593-8DOI Listing
July 2020

Predictive value of inflammatory markers for postoperative recovery following colorectal surgery.

Int J Colorectal Dis 2020 Jun 14;35(6):1125-1131. Epub 2020 Apr 14.

Department of Digestive and Endocrine Surgery, University Hospital of Nantes, 1, Place Alexis Ricordeau, 44093, Nantes, France.

Background: Using biological markers to predict serious complications and global postoperative recovery, to ensure safe and timely patient discharge after elective colorectal surgery represents a major challenge. The aim of this study was to demonstrate that C-reactive protein levels < 172 mg/l on postoperative day 3 were associated with postoperative recovery within 5 days.

Methods: This is a prospective study of a consecutive bicentric cohort. Successive patients scheduled for bowel resection with anastomosis, without stoma, were included. The main composite endpoint for overall postoperative recovery included absence of fever, absence of pain > 2 on the visual analog scale, intestinal gas transit, and patient autonomy for mobility and body care.

Results: One hundred sixty-height patients, with a mean age of 65 years old, were analyzed. Ninety patients (53%) underwent right colectomy and 131 (77%) were operated on by laparoscopy. Severe postoperative complications were observed in 11 patients (6%). One hundred twenty patients (71%) recovered within 5 days. C-reactive protein levels < 172 mg/L on postoperative day 3 had a negative predictive value of 80% to predict recovery within 5 days. Ninety-five percent of patients with C-reactive protein < 172 mg/L at postoperative day 3 had no severe postoperative complications.

Conclusion: Levels of C-reactive protein < 172 mg/L at postoperative day 3 corresponded with an early recovery in 80% of cases, thus allowing safe and early discharge without risk of serious complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00384-020-03594-yDOI Listing
June 2020

Long-term Oncological Outcomes Following Anastomotic Leak in Rectal Cancer Surgery.

Dis Colon Rectum 2020 06;63(6):769-777

Division of Colon & Rectal Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Anastomotic leak remains a critical complication after restorative rectal cancer surgery and is associated with significant morbidity and mortality rates, whereas reported rates range from 4% to 29%. Whether the occurrence of leak may have an impact on long-term oncological outcomes is under debate.

Objective: This study aimed to describe the oncological impact of anastomotic leak on patients undergoing sphincter-preserving surgery for rectal adenocarcinoma.

Design: This is a retrospective review of a prospectively maintained database.

Settings: The study was conducted at a high-volume colorectal center.

Patients: Data on patients who underwent restorative surgery for rectal adenocarcinoma from January 2000 until December 2013 were retrospectively analyzed.

Main Outcome Measures: The primary outcome measured was the impact of anastomotic leak, defined according to the classification proposed by the International Study Group of Rectal Cancer, on long-term overall survival, disease-free survival, disease-specific survival, and local recurrence.

Results: A total of 787 patients undergoing sphincter-preserving surgery for rectal cancer met the inclusion criteria. Forty-two (5.3%) patients presented a symptomatic anastomotic leak. The median follow-up period was 64 months. Fifty-one (6.5%) patients experienced a cancer-related death, 2 of 42 in the anastomotic leak group. Five-year overall survival, disease-specific survival, and disease-free survival were 88%, 94.7%, and 85.3%. Local recurrence rate was 2%. There was no difference in long-term overall survival, disease-specific survival, disease-free survival, and local recurrence rate between groups. On a multivariable analysis, anastomotic leak did not impact oncological outcomes.

Limitations: This study was limited by retrospective analysis.

Conclusions: The occurrence of anastomotic leak after restorative resection for rectal cancer did not impact long-term oncological outcomes in our cohort of patients. See Video Abstract at http://links.lww.com/DCR/B187. RESULTADOS ONCOLÓGICOS A LARGO PLAZO DESPUÉS DE UNA FUGA ANASTOMÓTICA EN CIRUGÍA DE CÁNCER RECTAL: La fuga anastomótica sigue siendo una complicación crítica después de la cirugía restauradora del cáncer rectal y se asocia con tasas significativas de morbilidad y mortalidad, mientras que las tasas reportadas varían del 4% al 29%. Se está debatiendo si la aparición de fugas puede tener un impacto en los resultados oncológicos a largo plazo.Describir el impacto oncológico de la fuga anastomótica en pacientes sometidos a cirugía de preservación del esfínter para adenocarcinoma rectal.Revisión retrospectiva de una base de datos mantenida prospectivamente.El estudio se realizó en un centro colorrectal de alto volumen.Se analizaron retrospectivamente los datos de pacientes que se sometieron a cirugía reparadora por adenocarcinoma rectal desde Enero de 2000 hasta Diciembre de 2013.Impacto de la fuga anastomótica, definida de acuerdo con la clasificación propuesta por el Grupo de Estudio Internacional del Cáncer Rectal (International Study Group of Rectal Cancer), sobre la supervivencia general a largo plazo, la supervivencia libre de enfermedad, la supervivencia específica de la enfermedad y la recurrencia local.Un total de 787 pacientes sometidos a cirugía para preservar el esfínter por cáncer rectal cumplieron con los criterios de inclusión. Cuarenta y dos (5.3%) pacientes presentaron una fuga anastomótica sintomática. El tiempo mediano del período de seguimiento fue de 64 meses. Cincuenta y un (6.5%) pacientes sufrieron muerte relacionada con el cáncer, 2 de 42 en el grupo de fuga anastomótica. La supervivencia global a cinco años, la supervivencia específica de la enfermedad y la supervivencia libre de enfermedad fueron del 88%, 94.7% y 85.3%, respectivamente. La tasa de recurrencia local fue del 2%. No hubo diferencias en la supervivencia global a largo plazo, la supervivencia específica de la enfermedad, la supervivencia libre de enfermedad y la tasa de recurrencia local entre los grupos. En un análisis multivariable, la fuga anastomótica no afectó los resultados oncológicos.Este estudio fue limitado por análisis retrospectivo.La aparición de fuga anastomótica después de la resección restauradora para el cáncer rectal no afectó los resultados oncológicos a largo plazo en nuestra cohorte de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B187. (Traducción-Dr. Yesenia Rojas-Kahlil).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DCR.0000000000001634DOI Listing
June 2020

Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome.

Front Immunol 2019 13;10:3000. Epub 2020 Jan 13.

Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, Nantes, France.

Because of a loss-of-function mutation in the GGTA1 gene, humans are unable to synthetize α1,3-Galactose (Gal) decorated glycans and develop high levels of circulating anti-α1,3-Galactose antibodies (anti-Gal Abs). Anti-Gal Abs have been identified as a major obstacle of organ xenotransplantation and play a role in several host-pathogen relationships including potential susceptibility to infection. Anti-Gal Abs are supposed to stem from immunization against the gut microbiota, an assumption derived from the observation that some pathogens display α1,3-Gal and that antibiotic treatment decreases the level of anti-Gal. However, there is little information to date concerning the microorganisms producing α1,3-Gal in the human gut microbiome. Here, available α1,3-Galactosyltransferase (GT) gene sequences from gut bacteria were selectively quantified for the first time in the gut microbiome shotgun sequences of 163 adult individuals from three published population-based metagenomics analyses. We showed that most of the gut microbiome of adult individuals contained a small set of bacteria bearing α1,3-GT genes. These bacteria belong mainly to the Enterobacteriaceae family, including , but also to Pasteurellaceae genera, and species. α1,3-Gal antigens and α1,3-GT activity were detected in healthy stools of individuals exhibiting α1,3-GT bacterial gene sequences in their shotgun data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.03000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970434PMC
November 2020

Impact of delay to surgery on survival in stage I-III colon cancer.

Eur J Surg Oncol 2020 03 28;46(3):455-461. Epub 2019 Nov 28.

Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Purpose: To assess the impact of delay from diagnosis to curative surgery on survival in patients with non-metastatic colon cancer.

Methods: National Cancer database (NCDB) analysis (2004-2013) including all consecutive patients diagnosed with stage I-III colon cancer and treated with primary elective curative surgery. Short and long delays were defined as lower and upper quartiles of time from diagnosis to treatment, respectively. Age-, sex-, race-, tumor stage and location-, adjuvant treatment-, comorbidity- and socioeconomic factors-adjusted overall survival (OS) was compared between the two groups (short vs. long delay). A multivariable Cox regression model was used to identify the independent impact of each factor on OS.

Results: Time to treatment was <16 days in the short delay group (31,171 patients) and ≥37 days in the long delay group (29,617 patients). OS was 75.4 vs. 71.9% at 5 years and 56.6 vs. 49.7% at 10 years in short and long delay groups, respectively (both p < 0.0001). Besides demographic (comorbidities, advanced age) and pathological factors (transverse and right-vs. left-sided location, advanced tumor stage, poor differentiation, positive microscopic margins), treatment delay had a significant impact on OS (HR 1.06, 95% CI 1.05-1.07 per 14 day-delay) upon multivariable analysis. The adjusted hazard ratio for death increased continuously with delay times of longer than 30 days, to become significant after a delay of 40 days.

Conclusion: This analysis using a national cancer database revealed a significant impact on OS when surgeries for resectable colon cancer were delayed beyond 40 days from time of diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejso.2019.11.513DOI Listing
March 2020

Tumor cells hijack enteric glia to activate colon cancer stem cells and stimulate tumorigenesis.

EBioMedicine 2019 Nov 26;49:172-188. Epub 2019 Oct 26.

Bretagne Loire University, Nantes University, INSERM 1235, IMAD, The Enteric Nervous System in Gut and Brain Disorders, Nantes, France; Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA. Electronic address:

Background: Colon cancer stem cells (CSCs), considered responsible for tumor initiation and cancer relapse, are constantly exposed to regulatory cues emanating from neighboring cells present in the tumor microenvironment. Among these cells are enteric glial cells (EGCs) that are potent regulators of the epithelium functions in a healthy intestine. However, whether EGCs impact CSC-driven tumorigenesis remains unknown.

Methods: Impact of human EGC primary cultures or a non-transformed EGC line on CSCs isolated from human primary colon adenocarcinomas or colon cancer cell lines with different p53, MMR system and stemness status was determined using murine xenograft models and 3D co-culture systems. Supernatants of patient-matched human primary colon adenocarcinomas and non-adjacent healthy mucosa were used to mimic tumor versus healthy mucosa secretomes and compare their effects on EGCs.

Findings: Our data show that EGCs stimulate CSC expansion and ability to give rise to tumors via paracrine signaling. Importantly, only EGCs that were pre-activated by tumor epithelial cell-derived soluble factors increased CSC tumorigenicity. Pharmacological inhibition of PGE2 biosynthesis in EGCs or IL-1 knockdown in tumor epithelial cells prevented EGC acquisition of a pro-tumorigenic phenotype. Inhibition of PGE2 receptor EP4 and EGFR in CSCs inhibited the effects of tumor-activated EGCs.

Interpretation: Altogether, our results show that EGCs, once activated by the tumor, acquire a pro-tumorigenic phenotype and stimulate CSC-driven tumorigenesis via a PGE2/EP4/EGFR-dependent pathway.

Funding: This work was supported by grants from the French National Cancer Institute, La Ligue contre le Cancer, the 'Région des Pays de la Loire' and the UNC Lineberger Comprehensive Cancer Center.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.09.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945247PMC
November 2019

Author's reply: Outcomes of first-line endoscopic management for patients with sigmoid volvulus.

Dig Liver Dis 2019 07 3;51(7):1066. Epub 2019 Jun 3.

Institut des Maladies de l'Appareil Digestif (IMAD), University Hospital of Nantes place Alexis Ricordeau, Nantes, 44000, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2019.05.021DOI Listing
July 2019

Hybrid minimally invasive/open approach versus total minimally invasive approach for rectal cancer resection: short- and long-term results.

Int J Colorectal Dis 2019 Jul 28;34(7):1251-1258. Epub 2019 May 28.

Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Objectives: To reduce the technical challenges of a totally minimally invasive approach (TMA) and to decrease the morbidity associated with open surgery, a hybrid minimally invasive/open approach (HMOA) has been introduced as a surgical technique for rectal cancer. The aim of this study was to compare postoperative results and long-term oncologic outcomes between hybrid minimally invasive/open approach and totally minimally invasive approach in patients who underwent rectal resection for cancer.

Methods: All patients with rectal cancer undergoing a totally minimally invasive approach or hybrid minimally invasive/open approach proctectomy between 2012 and 2016 were analyzed. Preoperative and postoperative outcomes were collected from a prospectively maintained institutional database.

Results: Among 283 patients, 138 (48.8%) underwent a hybrid minimally invasive/open approach and 145 (51.2%) a totally minimally invasive approach. Preoperative characteristics were similar between groups except for distance from the anal verge, which was lower in totally minimally invasive approach group (50.7% vs 29%; p = 0.0008). Length of stay (LOS) was significantly longer in the hybrid minimally invasive/open approach group (6.4 vs 4.3; p = < 0.0001). The median follow-up was 29.6 (14-40.6) months. Overall survival and disease-free survival were not significantly different between groups.

Conclusions: Compared with a hybrid minimally invasive/open approach, a totally minimally invasive approach has a shorter length of stay and may improve short-term outcomes in patients undergoing proctectomy for cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00384-019-03311-4DOI Listing
July 2019

The density of Tbet+ tumor-infiltrating T lymphocytes reflects an effective and druggable preexisting adaptive antitumor immune response in colorectal cancer, irrespective of the microsatellite status.

Oncoimmunology 2019;8(4):e1562834. Epub 2019 Jan 19.

Service d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire Hôtel Dieu, Nantes, France.

: The recent success of anti-PD1 antibody in metastatic colorectal cancer (CRC) patients with microsatellite instability (MSI), known to be associated with an upregulated Th1/Tc1 gene signature, provides new promising therapeutic strategies. However, the partial objective response highlights a crucial need for relevant, easily evaluable, predictive biomarkers. Here we explore whether assessment of Tbet+ tumor infiltrating lymphocytes (TILs) reflects a pre-existing functional antitumor Th1/Tc1/IFNγ response, in relation with clinicopathological features, microsatellite status and expression of immunoregulatory molecules (PD1, PDL1, IDO-1). : In two independent cohorts of CRC (retrospective n = 80; prospective n = 27) we assessed TILs density (CD3, Tbet, PD1) and expression profile of PDL1 and IDO-1 by immunohistochemistry/image analysis. Furthermore, the prospective cohort allowed to perform CRC explant cultures and measure by Elisa the IFNγ response, at baseline and upon anti-PD1 treatment. : The density of Tbet+ TILs was significantly higher in MSI CRC, especially in the medullary subtype but also in a subgroup of MSS (microsatellite stable), and positively correlated with PD1 and PDL1 expression, but not with IDO-1. Finally, a high number of Tbet+ TILs was associated with a favorable overall survival. These Tbet+ TILs were functional as their density positively correlated with basal IFNγ levels. In addition, the combined score of Tbet+ PD1+ TILs coupled with IDO-1 expression predicted the magnitude of the IFNγ response upon anti-PD1. : Altogether, immunohistochemical quantification of Tbet+ TILs is a reliable and accurate tool to recapitulate a preexisting Th1/Tc1/IFNγ antitumor response that can be reinvigorated by anti-PD1 treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/2162402X.2018.1562834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422378PMC
January 2019

Short-Term Outcomes with Robotic Right Colectomy.

Am Surg 2018 Nov;84(11):1768-1773

Few series have reported on the impact of robotic right colectomy compared with conventional laparoscopy. Even fewer have reported on the outcomes of intracorporeal anastomoses. The aim of our study was to determine the impact of robotic surgery on short-term operative outcomes in patients undergoing right colectomy with intracorporeal anastomosis. One hundred and fourteen consecutive patients who underwent a right colectomy by two colorectal surgeons between 2012 and 2017 were included. Patients were separated into two groups: laparoscopic technique with extracorporeal anastomosis (n = 87) and robotic technique with intracorporeal anastomosis (n = 27). Univariate analysis was performed to determine differences in outcomes. Differences between cohorts were only identified with regard to gender (62 37%, = 0.022) and year of surgery. In comparison with laparoscopy, robotic colectomy resulted in a shorter time of GI recovery (1.3 ± 0.6 3 ± 1.1, < 0.0001), lower rates of postoperative ileus (4 28%, = 0.007), lower overall morbidity (26 52%, = 0.019), less blood loss ( = 0.001), 50 per cent lower narcotic use, and longer operative time (255 ± 66 139 ± 49, < 0.001). Despite longer operative time, robotic surgery improved GI recovery, significantly lowered oral morphine equivalent usage, and decreased short-term complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
November 2018

Outcomes of first-line endoscopic management for patients with sigmoid volvulus.

Dig Liver Dis 2019 03 11;51(3):386-390. Epub 2018 Oct 11.

Institute of Digestive Diseases (IMAD), University Hospital of Nantes, Hôtel Dieu, Nantes, France.

Background: Sigmoid volvulus is a common cause of colonic obstruction in old and frail patients. Its standard management includes the endoscopic detorsion of the colonic loop, followed by an elective sigmoidectomy to prevent recurrence. However, these patients are often poor candidates for surgery.

Aim: The aim of this study was to compare death rate between elective sigmoidectomy and conservative management following endoscopic detorsion for sigmoid volvulus.

Methods: The medical records of 83 patients undergoing endoscopic detorsion of a sigmoid volvulus from 2008 to 2014 were retrospectively reviewed. Patients were divided into two groups: 'elective surgery' and 'no surgery'.

Results: Patients in the 'no surgery' group (n = 42) were older and had more loss of autonomy than in the 'elective surgery' group. Volvulus endoscopic detorsion was successful in 96% of patients with no complications. The median follow-up was 13 months (1 day-67 months). The death rate was 62% in the 'no surgery' group versus 32% in the 'elective surgery' group (p = 0.02). In the 'no surgery' group, 23/42 of patients had volvulus recurrence. No recurrence occurred after surgery.

Conclusion: Elective surgery must be planned as soon as possible after the first episode of sigmoid volvulus. In frail patients, other options must be developed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2018.10.003DOI Listing
March 2019

Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type.

Tumour Biol 2018 Sep;40(9):1010428318799028

1 Université Bretagne Loire, Université de Nantes, INSERMU1235, TENS, Institut des Maladies de l'Appareil Digestif du CHU, Nantes, France.

Gastric cancer is the third leading cause of cancer-related death worldwide, but the mechanisms of gastric carcinogenesis are not completely understood. Recently, the role of cholinergic neuronal pathways in promoting this process has been demonstrated. Our aim was to extend these studies and to evaluate, using an in vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer cells, and the role of acetylcholine receptors and of the nitric oxide pathway, in this effect. The gastric cancer cell line MKN-45 of the diffuse type of gastric cancer was cultured in the presence of acetylcholine, or different agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and size of tumorspheres were assessed. The expression of cancer stem cell markers (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and quantitative reverse transcription polymerase chain reaction. We showed that acetylcholine increased both the number and size of tumorspheres and that this effect was reproduced with both muscarinic and nicotinic acetylcholine receptors agonists and was inhibited by both receptor antagonists. The nitric oxide donor stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine increased the expression of stem cell markers on gastric cancer cells. These results indicate that acetylcholine induces the stem cell properties of gastric cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway might be involved in this effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1010428318799028DOI Listing
September 2018

Long-Term Outcome Following Implanted Pulse Generator Change in Patients Treated With Sacral Nerve Modulation for Fecal Incontinence.

Neuromodulation 2018 Oct 28;21(7):694-699. Epub 2018 Aug 28.

Clinique de Chirurgie Digestive et Endocrinienne, Institut des Maladies de l'Appareil Digestif, University Hospital of Nantes, Nantes, France.

Background: Long-term outcome of sacral nerve modulation (SNM) patients after implanted pulse generator (IPG) change for fecal incontinence (FI) is unknown. This study reported the outcome and long-term satisfaction after a change of an exhausted IPG, questioning the need to concurrently change the electrode and looking for factors involved in the maintenance of treatment efficiency.

Methods: Patients with fecal incontinence and with a Medtronic IPG implanted in a single center (2001-2016) were prospectively followed up. Satisfaction was graded according to a patient-reported outcome measure from 0 to 10. A pre- and postreplacement FI severity score (Cleveland Clinic Fecal Incontinence Score) and Fecal Incontinence Quality of Life questionnaire were also collected.

Results: In 170 patients with SNM, 39 had an IPG replacement. At a median of 29 month after replacement, 32 and 7 patients reported respectively a similar and reduced satisfaction (7.6 ± 1.62 vs. 5.5 ± 0.87), p < .001. Satisfied patients were younger (65 years vs. 76 years, p < .001). Cleveland Clinic Fecal Incontinence Scores were not significantly different, but the satisfied group had a significantly better Fecal Incontinence Quality of Life score (p = .047). Only 5 patients needed an electrode change at the time of the IPG replacement or later.

Conclusions: Patient satisfaction and efficiency remain high after IPG replacement. Older age has a negative impact on the outcome. Electrode replacement is rarely required and does not need to be performed routinely when an IPG is exhausted.

Conflict Of Interest: Paul-Antoine Lehur has a consulting agreement with Medtronic SA. This had no impact with the results of the study. The other authors have no conflict of interests to declare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.12806DOI Listing
October 2018

Characterisation of tau in the human and rodent enteric nervous system under physiological conditions and in tauopathy.

Acta Neuropathol Commun 2018 07 23;6(1):65. Epub 2018 Jul 23.

Inserm, U1235, 1 rue Gaston Veil, F-44035, Nantes, France.

Tau is normally a highly soluble phosphoprotein found predominantly in neurons. Six different isoforms of tau are expressed in the adult human CNS. Under pathological conditions, phosphorylated tau aggregates are a defining feature of neurodegenerative disorders called tauopathies. Recent findings have suggested a potential role of the gut-brain axis in CNS homeostasis, and therefore we set out to examine the isoform profile and phosphorylation state of tau in the enteric nervous system (ENS) under physiological conditions and in tauopathies. Surgical specimens of human colon from controls, Parkinson's disease (PD) and progressive supranuclear palsy (PSP) patients were analyzed by Western Blot and immunohistochemistry using a panel of anti-tau antibodies. We found that adult human ENS primarily expresses two tau isoforms, localized in the cell bodies and neuronal processes. We did not observe any difference in the enteric tau isoform profile and phosphorylation state between PSP, PD and control subjects. The htau mouse model of tauopathy also expressed two main isoforms of human tau in the ENS, and there were no apparent differences in ENS tau localization or phosphorylation between wild-type and htau mice. Tau in both human and mouse ENS was found to be phosphorylated but poorly susceptible to dephosphorylation with lambda phosphatase. To investigate ENS tau phosphorylation further, primary cultures from rat enteric neurons, which express four isoforms of tau, were pharmacologically manipulated to show that ENS tau phosphorylation state can be regulated, at least in vitro. Our study is the first to characterize tau in the rodent and human ENS. As a whole, our findings provide a basis to unravel the functions of tau in the ENS and to further investigate the possibility of pathological changes in enteric neuropathies and tauopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40478-018-0568-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055332PMC
July 2018

Revisional and Reconstructive Surgery for Failing IPAA is Associated with Good Function and Pouch Salvage in Highly Selected Patients.

Dis Colon Rectum 2018 08;61(8):920-930

Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, Minnesota.

Background: Revisional and reconstructive surgery for IPAA is rare given the high success of pouch surgery for chronic ulcerative colitis. Limited data exist on both surgical and functional outcomes in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction.

Objective: This study aimed to determine the surgical and functional outcome in patients with chronic ulcerative colitis who undergo IPAA revision or reconstruction.

Design: A prospectively collected surgical database was accessed for this study.

Setting: This study was conducted at an IBD referral center.

Patients: Patients with chronic ulcerative colitis who underwent IPAA revision or reconstruction were selected.

Main Outcome Measures: The primary outcomes measured were 30-day postoperative outcomes and long-term pouch function.

Results: Eighty-one patients were identified. Original IPAA was performed for chronic ulcerative colitis (n = 71; 88%) and indeterminate colitis (n = 11; 12.%), and the most common configuration was a J-pouch (n = 69; 86%) with handsewn anastomosis (n = 41;68%). No independent predictors of 30-day postoperative complications following reconstructive/revisional surgery were identified. Pelvic abscesses and Crohn's disease of the pouch were independently associated with ultimate pouch excision. Median follow-up following revision/reconstruction was 40 months (range, 1-292 months) during which 15 patients (23%) had pouch failure. The 5- and 10-year pouch survival rates following revision were 85 ± 5% and 65 ± 9% by Kaplan-Meier estimation; age <30 years was significantly associated with pouch survival. Long-term function (n = 30; 35%) compared with a matched control cohort of primary IPAA was characterized by significantly increased daytime bowel incontinence (p = 0.0119), liquid stool (p = 0.0062), and medication to thicken stools (p = 0.0452).

Limitations: This was a single-center series, and response rate for functional data was 35%.

Conclusions: In properly selected patients with a failing pouch, originally made for chronic ulcerative colitis or indeterminate colitis, revisional and reconstructive surgery is associated with low complication rates, high pouch salvage, and acceptable long-term pouch function. See Video Abstract at http://links.lww.com/DCR/A640.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DCR.0000000000001130DOI Listing
August 2018

Long-Term Oncologic Outcomes of Minimally Invasive Proctectomy for Rectal Adenocarcinoma.

J Gastrointest Surg 2018 08 28;22(8):1412-1417. Epub 2018 Mar 28.

Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA.

Background: Long-term oncologic outcomes after minimally invasive surgery (MIS) for rectal adenocarcinoma compared to open surgery continue to be debated. We aimed to review our high-volume single-institution outcomes in MIS rectal cancer surgery.

Methods: A retrospective review of a prospectively collected database was completed of all consecutive adult patients with rectal adenocarcinoma treated from January 2005 through December 2011. Stage IV or recurrent disease was excluded. Demographics and operative and pathologic details were reviewed and reported. Primary endpoints include survival and recurrence.

Results: A total of 324 patients were included and median follow-up was 54 months (IQR = 37.0, 78.8). The mean age was 58.2 ± 14.1 years. Tumors were in the upper rectum in 111 patients, mid-rectum in 113 patients, and lower rectum in 100 patients. Stage III disease was most common (49.4%). Overall conversion to open procedure rate was 13.9%. The circumferential radial margin was positive in only 1 patient (0.3%) and the mean lymph node yield was 24.7 ± 17.2. Cancer recurred in 42 patients (13%), 10 (2.5%) patients developed local recurrence, 32 (9.8%) developed distant metastasis, and 2 (0.6%) patients had both. The 5-year overall survival for stage 0, 1, 2, and 3 disease is 96, 91, 80, and 77%, respectively (p = 0.015).

Conclusion: In carefully selected rectal cancer patients treated with MIS, long-term outcomes of survival and recurrence appear to compare favorably to previously published series.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11605-018-3751-8DOI Listing
August 2018

Colorectal Cancer Cells Adhere to and Migrate Along the Neurons of the Enteric Nervous System.

Cell Mol Gastroenterol Hepatol 2018 14;5(1):31-49. Epub 2017 Oct 14.

Inserm U1235, Institut des Maladies de l'Appareil Digestif, Nantes, France.

Background & Aims: In several types of cancers, tumor cells invade adjacent tissues by migrating along the resident nerves of the tumor microenvironment. This process, called , typically occurs along extrinsic nerves, with Schwann cells providing physical guidance for the tumor cells. However, in the colorectal cancer microenvironment, the most abundant nervous structures belong to the nonmyelinated intrinsic enteric nervous system (ENS). In this study, we investigated whether colon cancer cells interact with the ENS.

Methods: Tumor epithelial cells (TECs) from human primary colon adenocarcinomas and cell lines were cocultured with primary cultures of ENS and cultures of human ENS plexus explants. By combining confocal and atomic force microscopy, as well as video microscopy, we assessed tumor cell adhesion and migration on the ENS. We identified the adhesion proteins involved using a proteomics approach based on biotin/streptavidin interaction, and their implication was confirmed further using selective blocking antibodies.

Results: TEC adhered preferentially and with stronger adhesion forces to enteric nervous structures than to mesenchymal cells. TEC adhesion to ENS involved direct interactions with enteric neurons. Enteric neuron removal from ENS cultures led to a significant decrease in tumor cell adhesion. TECs migrated significantly longer and further when adherent on ENS compared with on mesenchymal cells, and their trajectory faithfully followed ENS structures. Blocking N-cadherin and L1CAM decreased TEC migration along ENS structures.

Conclusions: Our data show that the enteric neuronal network guides tumor cell migration, partly via L1CAM and N-cadherin. These results open a new avenue of research on the underlying mechanisms and consequences of perineural invasion in colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2017.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696385PMC
October 2017

Robotic right colectomy with intracorporeal anastomosis for malignancy.

J Robot Surg 2018 Sep 25;12(3):461-466. Epub 2017 Oct 25.

Division of Colon and Rectal Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Techniques for robotic resection of the right colon have not been extensively published or adopted. We report our initial experience of robotic right colectomy with intracorporeal anastomosis and specimen extraction through a Pfannenstiel incision retrospectively. Twenty-one consecutive patients with a right colon cancer (n = 18) or polyp too large to remove endoscopically (n = 3) were treated at Mayo Clinic Rochester, Minnesota. Main outcomes measured were estimated blood loss, operative time, conversion rate, return of gastrointestinal function, length of stay, overall and severe complications, discharge status, and pathology. All 21 procedures were technically successful without the need for conversion. The mean total operative time was 250 ± 56 min, estimated blood loss was less than 100 mL in 19 (90%), only 1 (5%) ileus occurred, mean length of stay and return of gastrointestinal function was 4 ± 1.3 and 1 ± 0.6 days, respectively, only 1 (5%) patient experienced a Dindo grade ≥ 3 complication, and 20 (95%) were discharged to home. Mean number of nodes resected was 26 ± 12. Tumors were diagnosed as stage 0 in 3 (14%), stage I in 7 (33%), stage II in 4 (19%), stage III in 6 (28%), and stage IV in 1 (5%). Main limitations were nonrandomized nature, single institution experience, small patient sample size, and procedures only being performed by two surgeons. Finally, we conclude that robotic right colectomy with central mesocolic excision, intracorporeal anastomosis, and extraction through a Pfannenstiel incision is technically feasible, efficacious, oncologically acceptable, and safe to perform.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11701-017-0759-0DOI Listing
September 2018

Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery.

World J Surg 2018 04;42(4):953-964

TENS - The enteric nervous system in gut and brain disorders, INSERM U1235, 44093, Nantes, France.

Background: Postoperative ileus (POI) is observed in 20-30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle.

Methods: This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty-eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery.

Results: ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03).

Conclusion: The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00268-017-4266-2DOI Listing
April 2018

Is the Failure of Laparoscopic Peritoneal Lavage Predictable in Hinchey III Diverticulitis Management?

Dis Colon Rectum 2017 Sep;60(9):965-970

1 Department of Digestive and Endocrine Surgery, University Hospital of Nantes, Nantes, France 2 Department of Digestive Surgery, Vendée Medical Center, La-Roche-Sur-Yon, France 3 Department of Visceral Surgery, University Hospital of Angers, Angers, France.

Background: Laparoscopic peritoneal lavage is an alternative to sigmoid resection in Hinchey III diverticulitis (generalized purulent peritonitis). The main limitation of laparoscopic peritoneal lavage is the higher rate of reoperation for persistent sepsis in comparison with sigmoid resection.

Objective: The purpose of the current study was to identify risk factors for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis.

Design: This was a retrospective multicenter study.

Settings: The study was conducted in 3 clinical sites in France.

Patients: From 2006 to 2015, all consecutive patients undergoing emergent surgery for diverticulitis were reviewed. All patients operated on with laparoscopic peritoneal lavage for laparoscopically confirmed Hinchey III diverticulitis were included.

Main Outcome Measures: The main outcome was laparoscopic peritoneal lavage failure, defined as reoperation or death at 30 postoperative days.

Results: A series of 71 patients (43 men, mean age 58 ± 15 years) were operated on with laparoscopic peritoneal lavage for Hinchey III diverticulitis. Laparoscopic peritoneal lavage failed in 14 (20%) of them: 1 died and 13 underwent reoperations. No major complication (Dindo-Clavien score ≥3) occurred after reoperation. Immunosuppressive drugs (p = 0.01) and ASA grade ≥3 (p = 0.02) were associated with laparoscopic peritoneal lavage failure after univariate analysis. Multivariate analysis identified only immunosuppressive drug intake (steroids or chemotherapy for cancer) as an independent predictive factor. Mean length of stay was 14.9 days (5-67). At the end of the 30 first postoperative days, 12 (17%) patients had a stoma.

Limitations: The study was limited by its retrospective nature and the small size of the cohort.

Conclusion: Our results highlight immunosuppressive drug intake as a major risk factor for laparoscopic peritoneal lavage failure in patients who have Hinchey III diverticulitis. Immunosuppression and severe comorbidities (ASA ≥3) should be considered when selecting a surgical option in patients with Hinchey III diverticulitis. See Video Abstract at http://links.lww.com/DCR/A423.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/DCR.0000000000000891DOI Listing
September 2017

Participation of Colon and Rectal Fellows in Robotic Rectal Cancer Surgery: Effect on Surgical Outcomes.

J Surg Educ 2018 Mar - Apr;75(2):465-470. Epub 2017 Jul 15.

Division of Colon & Rectal Surgery, Mayo Clinic, Rochester, Minnesota. Electronic address:

Objectives: To determine whether involvement of colon and rectal fellows has an effect on short-term surgical and oncological outcomes in robotic rectal cancer surgery.

Patients And Methods: From a dataset of 263 robotic-assisted rectal cancer operations, 114 case-matched patients over a 5-year period (January 2010-December 2015) were included in the study. Patients who underwent resection with and without fellow involvement were compared. Cases were matched according to age, body mass index, neoadjuvant therapy, and tumor location. Intraoperative, postoperative, and pathological outcomes were compared between the 2 groups.

Results: There was no difference in tumor grade, type of surgical procedure, presence of an anastomosis, or diverting stoma between groups. In addition, there was no difference in the incidence of intraoperative or postoperative complications between the 2 groups. Estimated blood loss was higher in the fellow group compared to the consultant group (mean difference of 70mL, p = 0.007). For pathological outcomes, there was no difference in surrogate oncological quality indicators, specifically margin positivity and lymph node yield, between the 2 groups. Furthermore, fellow involvement did not adversely affect operative time.

Conclusion: This study demonstrates that equivalent short-term surgical and oncological outcomes can be achieved with colorectal fellow participation in the field of robotic-assisted rectal cancer surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsurg.2017.07.006DOI Listing
December 2018

Clinical, histological, and molecular risk factors for cancer recurrence in patients with stage II colon cancer.

Eur J Gastroenterol Hepatol 2016 Dec;28(12):1394-1399

aDepartment of Hepatogastroenterology, Digestive Oncology Unit, University Hospital, Nantes bDepartment of Hepatogastroenterology, University Hospital, Tours cIntegrated Center for Oncology, Angers dDepartment of Pathology & EA-4273 BIOMETADYS, University Hospital, Nantes eDepartment of Digestive Surgery, University Hospital, Nantes fInstitute of Histopathology, Nantes gDepartment of Pathology, University Hospital, Tours hDepartment of Medical Genetics, University Hospital, Nantes iIntegrated Center for Oncology, Saint Herblain, France.

Introduction: The assessment of risk factors of cancer recurrence in patients with stage II colon cancer (CC) is crucial. Our aim was to study the clinical, histological, and molecular features associated with 3-year disease-free survival in a series of consecutive patients with stage II CC treated in three regional digestive oncology centers.

Methods: Clinical and histological data of all patients after curative surgery for stage II CC, treated from 2001 until 2009, were collected retrospectively. Histological samples were obtained and tested prospectively for microsatellite instability using fluorescent PCR amplification. Cox proportional hazards regression models were used to calculate P values, hazard ratios (HRs), and 95% confidence intervals (CIs).

Results: Among 195 patients studied, 22 (11%) had disease recurrence during the 3-year period following diagnosis. On multivariate analysis, only low number of lymph nodes (HR=3.81, 95% CI: 1.19-12.19, P=0.02) and T4 status (HR=5.49, 95% CI: 1.06-28.43, P=0.04) were associated significantly with an increased risk of relapse.

Conclusion: In this series of stage II CC patients, only T4 status and low number of lymph nodes were independent risk factors for poor 3-year disease-free survival, suggesting that patients with these features should be considered for adjuvant chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000000725DOI Listing
December 2016

The arachidonic acid metabolite 11β-ProstaglandinF2α controls intestinal epithelial healing: deficiency in patients with Crohn's disease.

Sci Rep 2016 05 3;6:25203. Epub 2016 May 3.

INSERM, UMR913, Nantes, F-44093, France.

In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn's Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression of glial markers and EGC-derived soluble factors (IL6, TGF-β, proEGF, GSH) but CD EGC failed to increase IEB resistance and healing. Lipid profiling showed that CD EGC produced decreased amounts of 15-HETE, 18-HEPE, 15dPGJ2 and 11βPGF2α as compared to healthy EGC. They also had reduced expression of the L-PGDS and AKR1C3 enzymes. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep25203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4853710PMC
May 2016