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Microsatellite instability (MSI) is a negative predictive factor for neoadjuvant chemotherapy in resectable oesogastric adenocarcinoma and a crucial determinant for immunotherapy. We aimed to evaluate reliability of dMMR/MSI status screening performed on preoperative endoscopic biopsies. Paired pathological samples from biopsies and surgical specimen of oesogastric adenocarcinoma were retrospectively collected between 2009 and 2019. We compared dMMR status obtained by immunohistochemistry (IHC) and MSI status by PCR. dMMR/MSI status on surgical specimen was considered as reference. PCR and IHC were conclusive on biopsies respectively for 53 (96.4%) and 47 (85.5%) of the 55 patients enrolled. IHC was not contributive for 1 surgical specimen. A third reading of IHC was carried out for 3 biopsies. MSI status was observed in 7 (12.5%) surgical specimens. When analyses were contributive, sensitivity and specificity of biopsies for dMMR/MSI were respectively 85% and 98% for PCR vs. 86% and 98% for IHC. Concordance rate between biopsies and surgical specimen was 96.2% for PCR and 97.8% for IHC. Endoscopic biopsies are a suitable source of tissue for dMMR/MSI status determination in oesogastric adenocarcinoma which should be routinely performed at diagnosis to better adapt neoadjuvant treatment. By comparison of dMMR phenotype obtained by immunohistochemistry and MSI status by PCR between match-paired samples of oesogastric cancer's endoscopic biopsies and surgical specimen, we observed that biopsies are a suitable source of tissue for dMMR/MSI status determination. [ABSTRACT FROM AUTHOR]

To examine the relationship between carcinoembryonic antigen (CEA) kinetics and prognosis in metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the PRODIGE9 trial. Associations between monthly CEA measurements within 6 months since baseline and progression-free survival (PFS) were evaluated using a joint-latent class-mixed model. A validation set was used to test our prognosis model. Correlations between CEA trajectories (classes) and baseline characteristics were also investigated. Three classes were identified. Class 1 had low baseline CEA with small variations. Class 2 had high baseline CEA with a rapid decrease reaching the same CEA level at 6 months as in class 1. Class 3 had high baseline CEA with a transient decrease followed by an increase to reach, at 6 months, the same CEA level as at baseline. Six-month PFS was significantly lower in class 3 than in classes 1 and 2 (57% vs. 91% and 93% respectively; p <0.01). Class 3 was significantly associated with ECOG 2 status, a high LDH level and non-resected primary tumor. Variations in CEA kinetics correlate with prognosis in patients receiving first-line chemotherapy for mCRC. We propose here a user-friendly application to classify CEA trajectory. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel diseases (IBD) are exposed to drug-related nephrotoxicity and kidney-related extra-intestinal manifestations (EIMs). Patients should be monitored but guidance is lacking in current international recommendations. The objective of the Kidney Function Monitoring in Inflammatory Bowel Disease (MONITORED) initiative was to achieve an expert consensus about monitoring kidney function in IBD. A literature review was first conducted. Then, an expert consensus meeting, involving 28 attendees representing French-speaking gastroenterologists and nephrologists, was held as part of an academic initiative on May 28, 2021. An anonymous Delphi process was used to discuss and vote on statements. Agreement was defined as at least 75% of participants voting for any one statement. Experts reached consensus on 11 criteria for referral to the nephrologist. Concerning kidney function monitoring, participants unanimously validated the use of serum creatinine with estimation of the glomerular filtration rate via the MDRD or CKD-EPI equations. A blood ionogram and a urine sample with measurement of a protein-to-creatinine ratio were also broadly agreed validated. Experts recommended performing this monitoring at IBD diagnosis, prior introducing a new treatment, and annually for EIMs screening and evaluation of treatment tolerance. An evaluation 3 months after starting mesalamine and then every 6 months was felt necessary, while for biologics an annually monitoring was deemed sufficient. The MONITORED consensus proposed guidelines on how to monitor kidney function in IBD. These recommendations should be considered in clinical practice to preserve kidney function and ensure the best approach to our patients. [ABSTRACT FROM AUTHOR]

This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed. [ABSTRACT FROM AUTHOR]

There are few data concerning patients with Crohn's disease (CD) complicated by a stricture of the upper gastrointestinal tract (UGT). We evaluated the outcome and management of CD patients complicated by a stricture of the UGT. We performed a retrospective multicenter study including all CD patients with a non-passable symptomatic UGT stricture on endoscopy. Primary outcome measure was surgery-free survival from diagnosis of stricture. Efficacy of medical, endoscopic, and surgical treatments, and identification of predictors of surgery were also evaluated. 60 CD patients with an UGT stricture were included. 60% of the strictures were located in the duodenum. With a median follow-up of 5.5 (IQR: 3.0–12.0) years since stricture diagnosis, surgical-free survival was 75% and 64% at 1 and 5 years, respectively. At the end of the follow up, 27 (45%) patients underwent surgery. 77 endoscopic procedures were performed in 30 patients with an immediate success of 81% and a clinical benefit in 84% of the procedures. In multivariate analysis, anti-TNF treatment initiation was associated with a reduced risk of surgery. CD UGT strictures are mainly located in the duodenum. Medical and endoscopic treatments allow to avoid surgery in half of the patients [ABSTRACT FROM AUTHOR]

Abstract Introduction Data are lacking with regard to curative resection of metastasis from small bowel adenocarcinoma (SBA). This study evaluated outcomes and prognostic factors in patients with curatively resected metastatic SBA. Methods A series of 34 patients undergoing resection of metastatic SBA from January 2009 to November 2014 at French centers were included into this cohort study. The primary endpoint was overall survival (OS). Secondary endpoints were recurrence-free survival (RFS) and prognostic factors. Univariate analyses were performed to determine prognostic risk factors. Results The sites of SBA metastases were peritoneal (29.4%), liver (26.5%), lymph nodes (11.8%), lung (2.9%), multiple (14.7%), and other (14.7%). Thirty (88.2%) patients received adjuvant or perioperative chemotherapy, mainly was oxaliplatin-based (76.5%). The median OS was 28.6 months and RFS was 18.7 months. Fourteen (41.2%) patients survived for more than 36 months. In univariate analysis, poor differentiation (P = 0.006), invaded margins (P = 0.003), and lymphatic invasion in the primary tumor (P = 0.039) were associated with decreased OS. Conclusion Overall survival of patients after resection of metastatic SBA remains poor, but long-term survivors are observed. Resection of metastatic SBA should be consider if patients are expected to be operated on with curative intent and have moderately or well-differentiated tumors. [ABSTRACT FROM AUTHOR]

Background Complete cytoreductive surgery (CCRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a validated treatment in selected patients with peritoneal metastases (PM) of intestinal origin. There is an increased risk of Colorectal Cancer (CRC) and Small Bowel Adenocarcinoma (SBA) in Inflammatory Bowel Disease (IBD). The feasibility and benefit of that surgical approach in IBD patients is unknown. Methods IBD patients with operated PM complicating CRC or SBA were extracted from a French national multicenter prospective database of patients who underwent surgery for PM in HIPEC expert centers from 1995 to 2016. IBD patients who underwent CCRS plus HIPEC were compared with a cohort of 234 patients who had the same surgery for sporadic colon cancer. Results 14 patients (male 57%, median age 40 years, 12 Crohn's disease) with CRC (n = 7) and SBA (n = 7) were included. CCRS followed by HIPEC (oxaliplatin 72.7%) was performed in 11 cases (median peritoneal cancer index 7; range 1–30). The control group had the same characteristics except an older age at HIPEC (56.52 vs 45.74; p = 0.003). Overall survival (HR = 4.47; 90% CI, 1.91 to 10.49), Relapse Free Survival (HR = 2.31; 90% CI, 1.17 to 4.56) and Peritoneal Recurrence Free Survival (HR = 3.30; 90% CI, 1.59 to 6.85) were significantly lower in IBD patients. Six of the 11 patients presented major surgical morbidity with no impact on post-operative treatment. Conclusion CCRS followed by HIPEC is less effective in IBD patients with resectable PM complicating CRC or SBA. More careful selection of those patients is needed. [ABSTRACT FROM AUTHOR]

Background & Aims Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated. Methods We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis. Results We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn’s disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3–6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5–20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03–0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25–33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6–217; P = .0029). Conclusions In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD. [ABSTRACT FROM AUTHOR]

Introduction Autoimmune cytopenias (AIC) including autoimmune hemolytic anemia (AIHA) and immunologic thrombocytopenia (ITP) are rare immunologic disorders, scarcely reported in inflammatory bowel diseases (IBD). We conducted a multicentric retrospective study, including a case-control analysis, that aimed to describe the characteristics and outcomes of patients affected by AIC and IBD. Method Forty cases were recruited from 4 IBD centers and 2 AIC tertiary centers. Controls were recruited from the MICISTA registry. Results From the MICISTA registry, incidences were estimated at 4.1/100,000 patient-years and 12.5/100,000 patient-years after IBD diagnosis for AIHA and ITP, respectively. All AIHA patients (n = 14) had colonic involvement (13/14 with UC), whereas CD (52%) and UC (48%) diagnoses were evenly distributed among ITP patients. Compared to control IBD patients, cases were characterized by a higher frequency of extra-intestinal manifestations (37.5% vs 17%, p < 0.001) and by the presence of IBD severity’s hallmark. AIHA and IBD ran mainly in parallel, and 12 out of 14 AIHA were warm AIHA. In isolated cases, rituximab and infliximab were efficient to treat IBD and AIC, respectively. IBD surgery may induce AIC remission in some cases. Conclusion Although low, incidence of AIC appears higher in IBD patients compared to the general population. The association seems to be mainly non-fortuitous, especially for colitis-associated AIHA. [ABSTRACT FROM AUTHOR]

Background After intestinal resection for Crohn's disease, the severity of endoscopic recurrence in the first year following surgery is predictive of clinical outcome. Aim of the study was to assess the impact on clinical recurrence of tailored therapy based on endoscopic findings in the first year following surgery for Crohn's disease. Methods All patients who underwent an intestinal resection for Crohn's disease between 1995 and 2005 at Saint-Louis Hospital were retrospectively included. Time-to-clinical recurrence was compared in two groups: patients who had systematic ileocolonoscopy 6–12 months after intestinal surgery with tailored treatment according to the severity of endoscopic lesions (group C) and patients without systematic endoscopic evaluation (group NC). Results 132 patients (group C = 90, group NC = 42) were included. Probabilities of clinical recurrence were significantly lower in group C (21% and 26% at 3 and 5 years, respectively) compared with group NC (31% and 52% at 3 and 5 years respectively, p = 0.01). Conclusion Tailored treatment according to endoscopic assessment after ileocolonic resection is significantly associated with reduced clinical recurrence rate. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and human immunodeficiency virus (HIV) both impact innate and adaptive immunity in the intestinal mucosa. As it is a rare situation, the intersection between HIV and IBD remains unclear, especially the impact of HIV infection on the course of IBD, and the drug safety profile is unknown. We conducted a multicenter retrospective cohort study between January 2019 and August 2020. All adult patients with IBD and concomitant HIV infection were included. Each IBD patient with HIV was matched to two HIV-uninfected IBD patients. Overall, 195 patients with IBD were included, including 65 HIV-infected patients and 130 without HIV infection. Of the 65 infected patients, 22 (33.8%) required immunosuppressants and 31 (47.7%) biologics. In the HIV-infected group, the need for immunosuppressants (p = 0.034 for CD and p = 0.012 for UC) and biologics (p = 0.004 for CD and p = 0.008 for UC) was significantly lower. The disease course, using a severity composite criterion, was not significantly different between the two groups for CD (hazard ration (HR) = 1.3 [0.7; 2.4], p = 0.45) and UC (HR, 1.1 [0.5; 2.7], p = 0.767). The overall drug safety profile was statistically similar between the two groups. Although HIV-infected patients receive less treatments, the course of their IBD did not differ than uninfected, suggesting that HIV infection might attenuate IBD. The drug safety profile is reassuring, allowing physician to treat these patients according to current recommendations. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: There is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME). METHODS: We followed and collected data from 19,486 patients with IBD (60.3% with Crohn's disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD. RESULTS: Thirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6-1.8; P = .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1-0.9; P = .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis. CONCLUSIONS: Patients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. Patients and methods: Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model. Results: Lymphoma complicated non clonal enteropathy, celiac disease (n =15) and type I refractory celiac disease (n =2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p =0.0007, p <0.0001, p <0.0001, p <0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p <0.002, p <0.03, p <0.03, respectively). Conclusions: Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival. [Copyright &y& Elsevier]

Abstract: Introduction: Enteropathy-associated T-cell lymphoma is a rare form of T-cell lymphoma associated with a poor prognosis and the relative ineffectiveness of standard chemotherapy. The occurrence of haemophagocytic lymphohistiocytosis has been reported only once with this entity. Patients and methods: A retrospective study of 15 patients with enteropathy-associated T-cell lymphoma (type 1 in 12), followed-up in our units, since 1985. Two patients died before starting chemotherapy. The remaining 13 patients were treated with standard chemotherapy (n =7) and purine nucleotide analogues (n =6). Results: Median follow-up was 8.7 (1–97) months. Surgery was required in 10 patients (66%) for intestinal complications (n =7) or elective small bowel resection (n =3). Survival probability was 40% and 20% at 1 and 5 years, respectively (Kaplan–Meier method). Survival was not significantly different between the two chemotherapy regimens. However, a slight decrease of febrile neutropenia was observed in the purine nucleotide analogues group (p =0.06). Haemophagocytic lymphohistiocytosis occurred in 6/15 (40%) cases. In these six patients, haemophagocytic lymphohistiocytosis was always fatal within 3 months. Conclusion: Enteropathy-associated T-cell lymphoma is associated with a poor outcome, independently of the chemotherapy regimens administered and frequent occurrence of haemophagocytic lymphohistiocytosis. The latter complication should be considered for urgent rescue therapy. [Copyright &y& Elsevier]

Abstract: Background: Total proctocolectomy with definitive ileostomy is the ultimate treatment for refractory colonic Crohn''s disease (CD). Aim of the study was to report the outcome of Crohn''s disease patients after total proctocolectomy with definitive ileostomy. Patients and methods: Between 1990 and 2005, 55 patients underwent total proctocolectomy with definitive ileostomy for Crohn''s disease in our institution. None of them received preventive post-operative treatment. We studied clinical recurrence, need for immunosuppressants (IS), anti-TNF therapy and re-operation in this retrospective cohort. Results: Median follow-up was 5.4 years. Probabilities of clinical Crohn''s disease recurrence were 4%, 27% and 39% at 1, 5 and 8 years, respectively. In multivariate analysis, clinical recurrence rate was significantly higher for patients with penetrating disease behaviour (RR 1.7 IC95% [1.5–19], p =0.05) and absence of perianal disease (RR=1.6, IC95% [1.4–10]; p =0.01). Clinical recurrences were located in terminal ileum in all cases and treated medically in 9 of 16 patients including IS or anti TNF agents in 7 cases. Probabilities of treatment with immunosuppressants or anti-TNF therapy were 4%, 15% and 15% at 1, 5 and 8 years, respectively. Nearly one third of the patients (29%) underwent surgery for mechanical complications (N=11) and/or CD recurrence (N=7). Probabilities of reoperation for Crohn''s disease recurrence were 0%, 10% and 18% at 1, 5 and 8 years, respectively. Conclusion: Recurrence after total proctocolectomy with definitive ileostomy for Crohn''s disease is not uncommon, and in our series often required immunosuppressants or surgical procedure. [Copyright &y& Elsevier]

Background & Aims: Crohn’s disease (CD) is an inflammatory bowel disease characterized by uncontrolled immune responses to bacterial flora, with excessive activation of T lymphocytes. MICA is a stress-induced major histocompatibility complex–related molecule expressed on normal intestinal epithelial cells (IECs) and recognized by the NKG2D-activating receptor on CD8+ T cells, γδ T cells, and natural killer cells. We examined the role of MICA-NKG2D interactions in the activation of T lymphocytes in CD. Methods: MICA expression was analyzed by flow cytometry on IECs isolated from patients with active inflammatory bowel disease and controls. NKG2D expression and function were analyzed on lamina propria and peripheral blood lymphocytes. Results: MICA expression was significantly increased on IECs in CD, with higher expression in macroscopically involved areas. A subset of CD4+ T cells expressing NKG2D was increased in the lamina propria from patients with CD compared with controls and patients with ulcerative colitis. CD4+NKG2D+ T cells with a Th1 cytokine profile and expressing perforin were increased in the periphery and in the mucosa in CD. CD4+NKG2D+ T-cell clones were functionally active through MICA-NKG2D interactions, producing interferon-γ and killing targets expressing MICA. IECs from patients with CD had the ability to expand this subset in vitro. CD4+NKG2D+ lamina propria lymphocytes from patients with CD highly expressed interleukin-15Rα, and interleukin-15 increased NKG2D and DAP10 expression in CD4+NKG2D+ T-cell clones. Conclusions: These findings highlight the role of MICA-NKG2D in the activation of a unique subset of CD4+ T cells with inflammatory and cytotoxic properties in CD. [Copyright &y& Elsevier]

B Background: b There is no therapeutic standard in the second line of gastric peritoneal metastases (GMP), survival is a few months. For two patients, disease control authorized a proposal for secondary cytoreduction surgery with HIPEC. [Extracted from the article]

Background & Aims Little is known about the efficacy and safety of thalidomide therapy for patients with refractory Crohn’s disease (CD), particularly in respect to long-term outcomes of patients. Methods We conducted a retrospective multicenter observational study to evaluate thalidomide efficacy and the probability of its withdrawal because of either toxicity or lack/loss of efficacy. We analyzed data from 77 patients with active intestinal and/or perineal CD, refractory to conventional immunosuppressive therapies, treated with thalidomide at 5 tertiary referral inflammatory bowel disease centers in France. We also analyzed the long-term efficacy of thalidomide. Results Fifty-four percent of the patients were in clinical remission after thalidomide treatment within the first year. The proportions of patients from whom thalidomide was withdrawn because of lack/loss of efficacy and/or toxicity were 35% at 3 months of treatment, 69% at 12 months, and 88% at 24 months. The proportions of patients from whom thalidomide was withdrawn because of toxicity alone were 22% at 3 months, 34% at 12 months, and 46% at 24 months. Overall, neuropathy occurred in 30 patients and was the main reason for thalidomide withdrawal. Conclusions On the basis of a retrospective multicenter observational study, thalidomide therapy is effective in most patients with refractory active intestinal and/or perineal CD. However, its toxicity limits its use as a maintenance therapy. [ABSTRACT FROM AUTHOR]

Background & Aims: The natural killer group 2 member D (NKG2D) is a stimulatory receptor expressed on a subset of mucosal and peripheral CD4+ T cells in patients with Crohn''s disease (CD) and other inflammatory diseases. Ligand activation of NKG2D in patients induces CD4+ T cells to release T-helper (Th) 1 cytokines and become cytotoxic. We investigated the Th17 cytokines produced by T cells that express NKG2D in blood and intestinal mucosa samples from patients with CD. Methods: We isolated CD4+ T cells from peripheral blood and lamina propria samples of patients with CD or ulcerative colitis (UC) and healthy individuals (controls). We analyzed the phenotype and functions of the CD4+NKG2D+ T cells and the cytokines they produce in response to NKG2D stimulation. Results: In patients with CD, CD4+ T cells that express NKG2D produced high levels of interleukin (IL)-17 and IL-22 and expressed high levels of CCR6, the IL-23 receptor, CD161, and RORC (a transcription factor that regulates expression of Th17 cytokines). CD4+ T cells that produced IL-17 expressed high levels of NKG2D and CD161. Costimulation of NKG2D and the T-cell receptor (TCR) significantly increased production of IL-17 and tumor necrosis factor α by CD4+ T cells, compared with activation of only the TCR. CD4+NKG2D+ T cells also responded to Th17 polarization. Conclusions: NKG2D is a functional marker of CD4+ T cells that produce IL-17 in patients with CD, via costimulation of the TCR and NKG2D. Reagents developed to block NKG2D might reduce gastrointestinal inflammation in patients with CD. [Copyright &y& Elsevier]

Few studies have explored the association between baseline characteristics and the occurrence of early toxicities in patients treated with first-line chemotherapy for metastatic colorectal cancer (mCRC). Individual patient data of 2190 patients enrolled in 10 prospective FFCD (Fédération Francophone de Cancérologie Digestive) trials were analysed. Severe early toxicity was defined as the occurrence of grade ≥III toxicity within 3 months after initiation of chemotherapy (ET3). Patients received monotherapy based on 5-FU (n = 1068), a cytotoxic doublet (n = 395) or tritherapy with a cytotoxic doublet plus anti-VEGF agent or a cytotoxic triplet (n = 727). The patients received 5-FU (100%), Irinotecan (39.6%), Oxaliplatin (13.4%), Bevacizumab (29.6%) or Aflibercept (1.8%). ET3 occurred in 244 patients (22.8%) with monotherapy, 248 patients (62.8%) with doublet and 392 patients (53.9%) with tritherapy. The most frequent ET3s were related to biological abnormalities and/or gastrointestinal, general and vascular disorders. The prognostic factors for the occurrence of an ET3 in multivariate analysis were a performance status of 2 rather than 0–1 (OR 2.57; 95% CI [1.16, 5.73]; p = 0.02), tritherapy versus monotherapy (OR 2.31; 95% CI [0.84, 6.33]; p = 0.02), alkaline phosphatase > 300 UI/l (OR 3.07; 95% CI [1.79, 5.27]; p < 0.001) and non-resected primary tumour versus resection (OR 1.59; 95% CI [1.06, 2.39]; p = 0.02). Median overall survival in patients without ET3 was significantly longer than that in patients with ET3 (HR 0.87; 95% CI [0.80–0.96]; p = 0.004). ET3 is frequent whatever the treatment regimen and is associated with certain baseline characteristics. The clinical impact of ET3 on prognosis in mCRC warrants further investigation. • Severe drug toxicity has a negative impact on prognosis in metastatic colorectal cancer. • Early toxicity within 3 months after first-line regimen initiation may be a key factor. • Early grade III or more toxicity is a new prognostic marker. • Some baseline characteristics are associated with ET3 occurrence. • Early grade III or more toxicity correlates with poorer overall survival. [ABSTRACT FROM AUTHOR]

Anal squamous cell carcinoma is associated with multiple risk factors, including infection with human papillomavirus and human immunodeficiency virus, immunosuppression, multiple sex partners, receptive anal sex and tobacco smoking. The aim of our study was to identify prognostic factors associated with poor outcomes after radiotherapy for anal cancer. We analysed retrospectively the medical records of 171 patients treated by (chemo)radiotherapy for non-metastatic anal cancer in our institution from 2000 to 2015. Patients and tumour characteristics, treatments (chemotherapy, radiotherapy [RT] and surgery) and outcomes were reported. Colostomy-free survival (CRF), disease-free survival and overall survival (OS) at 5 years were studied. Univariate and multivariate analyses were performed by logistic regression to determine factors associated with poor progression-free survival (PFS). Patients' characteristics were as follows: median age, 62 years (range = 36–89); gender, 45 men (26%) and 126 women (74%); HIV serology, positive: 21 patients (12%); tobacco smoking, 86 patients (50%), among whom 28 patients and 58 patients were current and former smokers, respectively. Tumours were classified as locally limited (T1–2, N0, M0) for 86 patients (50%) and locally advanced (T3–4 or N+, M0) for 85 patients (50%). The median total dose was 64.4 Gy (range = 54–76.6), and 146 patients were treated by concurrent chemoradiotherapy. Factors associated with poor PFS in univariate analysis were as follows: tumour size >4 cm, lymph node involvement, tobacco smoking, no initial surgical excision and anal warts at diagnosis. In multivariate analysis, only tobacco smoking status was significantly associated with poor PFS (hazard ratio = 2.85, 95% confidence interval [1.25–6.50], p = 0.013). Five-year PFS for non-smokers, former smokers and current smokers was 88.1%, 76.7% and 73.8%, respectively (p = 0.038). Tobacco smoking was also associated with poor overall survival (p = 0.03), locoregional relapse-free survival (LRFS; p = 0.05) and CFS (p = 0.02). Tobacco smoking status is associated with poor OS, LRFS, PFS and CFS in patients treated for anal cancer by high RT dose ± chemotherapy. • The patients's smoking status is associated with increased risk for anal cancer recurrence, colostomy and death. • The patient's smoking history (current smoker; ex-smoker; never smoker) is also associated with patient's outcome. • The patient's smoking status overcomes all prognostic factors in anal cancer treated by radiotherapy. [ABSTRACT FROM AUTHOR]

Baseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice. Chemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models. From July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31–0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001). ctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials. Trial registration: Clinicaltrials.gov, NCT02502656 • ctDNA at baseline was a strong prognostic biomarker. • An optimal mutated allelic frequency (MAF) cut-off of 20% was defined. • Prognostic value of ctDNA was found in all subgroups. • CEA and ctDNA MAF had an independent prognostic value and are not correlated. • CEA and MAF combination classified patients in three prognostic subgroups. [ABSTRACT FROM AUTHOR]

Purpose To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer. Methods and Materials We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5–7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume. Results Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (<10%) before salvage brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%). Conclusions Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control. [ABSTRACT FROM AUTHOR]