Human colonic organoids for understanding early events of familial adenomatous polyposis pathogenesis.

Patients with familial adenomatous polyposis (FAP) harbor mutations in the APC gene and will develop adenoma and early colorectal cancer. There is no validated treatment, and animal models are not sufficient to study FAP. Our aim was to investigate the early events associated with FAP using the intestinal organoid model in a single-center study using biopsies from nonadenomatous and adenomatous colonic mucosa of FAP patients and from healthy controls (HCs).

Study of postoperative complications after the implementation of a multidisciplinary care pathway for patients with digestive endometriosis.

Purpose: To assess the quality of care following the establishment of a multidisciplinary care pathway for patient operated on for deep pelvic endometriosis with digestive impairment.

Methods: We conducted a retrospective monocentric study of patients suffering from deep infiltrating endometriosis, treated in Gynaecological Department at Toulouse University Hospital from January 2018 to December 2020. We compared our results to those of our previous study, Gornes et al.

Oncologic and Functional Outcomes of Pelvic Perineal Reconstruction by Perineal Colostomy and Malone Procedure After Abdominoperineal Resection.

Background: Abdominoperineal resection is the standard curative surgical technique for locally advanced adenocarcinoma of the lower rectum and squamous cell carcinoma of the anal canal after chemoradiotherapy. However, it requires a definitive abdominal colostomy that modifies the body appearance.

Objective: The study aim was to evaluate the combination of abdominoperineal resection with perineal colostomy reconstruction and Malone antegrade continence enema.

Randomised clinical trial for the cost-utility evaluation of two strategies of perineal reconstruction after abdominoperineal resection in the context of anorectal carcinoma: biological mesh repair versus primary perineal wound closure, study protocol for the GRECCAR 9 Study.

Introduction: Abdominoperineal resections performed for anorectal tumours leave a large pelvic and perineal defect causing a high rate of morbidity of the perineal wound (40%-60%). Biological meshes offer possibilities for new standards of perineal wound reconstruction. Perineal fillings with biological mesh are expected to increase quality of life by reducing perineal morbidity.

Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions.

Background And Aims: Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown.

Characterization of Human Colon Organoids From Inflammatory Bowel Disease Patients.

Inflammatory Bowel Diseases (IBD) are chronic inflammatory disorders, where epithelial defects drive, at least in part, some of the pathology. We reconstituted human intestinal epithelial organ, by using three-dimension culture of human colon organoids. Our aim was to characterize morphological and functional phenotypes of control (non-IBD) organoids, compared to inflamed organoids from IBD patients.

Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response.

Colonic macrophages are considered to be major effectors of inflammatory bowel diseases (IBDs) and the control of gut inflammation through C-type lectin receptors is an emerging concept. We show that during colitis, the loss of dectin-1 on myeloid cells prevents intestinal inflammation, while the lack of mannose receptor (MR) exacerbates it. A marked increase in dectin-1 expression in dextran sulfate sodium (DSS)-exposed MR-deficient mice supports the critical contribution of dectin-1 to colitis outcome.

Does A Longer Waiting Period After Neoadjuvant Radio-chemotherapy Improve the Oncological Prognosis of Rectal Cancer?: Three Years' Follow-up Results of the Greccar-6 Randomized Multicenter Trial.

Objective: The aim of this study was to report the 3-year survival results of the GRECCAR-6 trial.

Summary Background Data: Current data on the effect of an extended interval between radiochemotherapy (RCT) and resection for rectal cancer on the rate of complete pathological response (pCR = ypT0N0) is controversial. Furthermore, its effect on oncological outcomes is unknown.

Synchronous liver metastases and peritoneal carcinomatosis from colorectal cancer: different strategies for curative treatment?

Background: Management of patients with resectable hepatic metastases (HMs) and colorectal peritoneal carcinomatosis (CRPC) is not currently standardised.

Objective: The aims of this study were to evaluate the safety of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and hepatic surgery for patients with CRPC with synchronous hepatic metastases (HM), and its impact on survival rates.

Methods: A retrospective analysis was performed, including patients undergoing CRS/HIPEC for CRPC from 2007 to September 2016 in two groups, with (HM+) and without (HM-) synchronous hepatic metastases.

Thrombin modifies growth, proliferation and apoptosis of human colon organoids: a protease-activated receptor 1- and protease-activated receptor 4-dependent mechanism.

Background And Purpose: Thrombin is massively released upon tissue damage associated with bleeding or chronic inflammation. The effects of this thrombin on tissue regrowth and repair has been scarcely addressed and only in cancer cell lines. Hence, the purpose of the present study was to determine thrombin's pharmacological effects on human intestinal epithelium growth, proliferation and apoptosis, using three-dimensional cultures of human colon organoids.

Dose to organ at risk and dose prescription in liver SBRT.

Stereotactic body radiation therapy (SBRT) is delivered in a curative intent to many primary and secondary tumors. Concerning liver metastasis, SBRT can be safely delivered using one to five fractions. An excellent local control is obtained with doses from 20 to 60 Gy.

Comparative study of safety and efficacy of synthetic surgical glue for mesh fixation in ventral rectopexy.

Background: Ventral mesh rectopexy (VMR) is a surgical option to treat rectal prolapse with pelvic floor dysfunction (PFD). Using synthetic surgical glue to fix the mesh to the anterior rectal wall after ventral dissection could be advantageous in comparison with sutured or stapled fixation. This study aimed to evaluate the safety and efficacy of synthetic surgical glue for mesh fixation compared with suture mesh fixation in VMR.

Epithelial expression and function of trypsin-3 in irritable bowel syndrome.

Objectives: Proteases are key mediators of pain and altered enteric neuronal signalling, although the types and sources of these important intestinal mediators are unknown. We hypothesised that intestinal epithelium is a major source of trypsin-like activity in patients with IBS and this activity signals to primary afferent and enteric nerves and induces visceral hypersensitivity.

Design: Trypsin-like activity was determined in tissues from patients with IBS and in supernatants of Caco-2 cells stimulated or not.

To Drain or Not to Drain Infraperitoneal Anastomosis After Rectal Excision for Cancer: The GRECCAR 5 Randomized Trial.

Objective: To assess the effect of pelvic drainage after rectal surgery for cancer.

Background: Pelvic sepsis is one of the major complications after rectal excision for rectal cancer. Although many studies have confirmed infectiveness of drainage after colectomy, there is still a controversy after rectal surgery.

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6).

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the effect of increasing the interval between the end of RCT and surgery on the pCR rate.

PIK3CA mutations predict recurrence in localized microsatellite stable colon cancer.

PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently altered oncogenes in colon cancer (CC), but its prognostic value is still a matter of debate. Few reports have addressed the association between PIK3CA mutations and survival and their results are controversial. In the present study, we aimed to clarify the prognostic impact of PIK3CA mutations in stage I-III CC according to mismatch repair status.

Sporadic early-onset colorectal cancer is a specific sub-type of cancer: a morphological, molecular and genetics study.

Sporadic early onset colorectal carcinoma (EOCRC) which has by definition no identified hereditary predisposition is a growing problem that remains poorly understood. Molecular analysis could improve identification of distinct sub-types of colorectal cancers (CRC) with therapeutic implications and thus can help establish that sporadic EOCRC is a distinct entity. From 954 patients resected for CRC at our institution, 98 patients were selected.

Recurrence risk after Ivor Lewis oesophagectomy for cancer.

Objective: The aim of this study was to analyze the profile of tumor recurrence for patients operated on for cancer of oesophagogastric junction or oesophagus by Ivor-Lewis oesophagectomy.

Methods: Patients undergoing potentially curative Ivor-Lewis oesophageal resection between January 1999 to December 2008 at a single center institution were retrospectively analyzed. Their clinical records, details of surgical procedure, postoperative course, pathological findings, recurrence and long term survival were reviewed retrospectively.

Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value.

Background: Colon cancer (CC) pathological staging fails to accurately predict recurrence, and to date, no gene expression signature has proven reliable for prognosis stratification in clinical practice, perhaps because CC is a heterogeneous disease. The aim of this study was to establish a comprehensive molecular classification of CC based on mRNA expression profile analyses.

Methods And Findings: Fresh-frozen primary tumor samples from a large multicenter cohort of 750 patients with stage I to IV CC who underwent surgery between 1987 and 2007 in seven centers were characterized for common DNA alterations, including BRAF, KRAS, and TP53 mutations, CpG island methylator phenotype, mismatch repair status, and chromosomal instability status, and were screened with whole genome and transcriptome arrays.

Simplified identification of Lynch syndrome: a prospective, multicenter study.

Background: Recommended strategies to screen for Lynch syndrome in colorectal cancer are not applied in daily practice and most of Lynch cases remain undiagnosed.

Aims: We investigated in routine conditions a strategy that uses simplified clinical criteria plus detection of MisMatch Repair deficiency in tumours to identify Lynch carriers.

Methods: Colorectal cancer patients that met at least one of three clinical criteria were included: (1) colorectal cancer before 50 years, (2) personal history of colorectal or endometrial cancer, (3) first-degree relative history of colorectal or endometrial cancer.

Long-term clinical and imaging follow-up of nonoperated branch duct form of intraductal papillary mucinous neoplasms of the pancreas.

Objectives: The aim of our study was to perform a 10-year imaging and clinical prospective follow-up of patients with nonoperated branch duct (BD) intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.

Methods: Forty-nine patients with BD-IPMN who displayed a low probability for malignancy were followed up including a clinical component and a series of imaging techniques such as computed tomography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography.

Results: After a mean follow-up period of 77 months, 77.

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

Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested.

Is Crohn's creeping fat an adipose tissue?

Background: In human pathology, the "creeping fat" (CF) of the mesentery is unique to Crohn's disease (CD). CF is usually referred to as an ectopic extension of mesenteric adipose tissue (MAT). However, since no animal model developing CF has ever been established, very little is known about this type of fat-depot expansion and its role in the development of the disease.

BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas.

We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas.