Local treatment of pancreatic cancer metastases: A multicenter French study of the AGEO group.

OBJECTIVE: This study reports the efficacy and safety of local treatment of metastases of pancreatic ductal adenocarcinoma (PDAC), with a curative intent. METHODS: We retrospectively included patients with histologically proven PDAC, who underwent a local treatment for metastases between January 1, 2000 and December 31, 2017, from 11 French hospitals. Complications of local treatment were reported. Univariate Cox models were performed to identify prognosis factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: We included 52 patients treated for 68 metastases; 33 (64%) of whom had metachronous metastases. Metastatic sites treated were: 39 (57%) hepatic, 18 (27%) pulmonary and 11 (16%) others. Metastases treatments were: 45 (66%) surgery, 9 (13%) radiofrequency and 14 (21%) other procedures. The rates of severe complications and mortality were respectively 10% and 4%. The median OS and DFS after local treatment were 36.5 months and 12.7 months, respectively. Prognosis factors associated with a shorter OS were: liver metastases when compared with lung metastases (HR 4.04; 95%CI: 1.18-13.81), N2 status of primary pancreatic tumor when compared to N0-N1 (HR 9.43; 95%CI: 2.44-36.36) and synchronous metastases when compared to metachronous metastases (HR 2.34; 95%CI: 1.05-5.23). N2 status of primary pancreatic tumor was associated with a shorter DFS when compared to N0-N1 (HR 2.82; 95%CI: 1.05-7.58). CONCLUSION: In this series of highly selected patients, local treatment of metastases from PDAC is associated with prolonged survival. The rate of severe complications was low. Factors associated with shorter OS were liver metastases, N2 status and synchronous metastases.

Lactose Sensitivity and Lactose Malabsorption: The 2 Faces of Lactose Intolerance.

BACKGROUND/AIMS: Self-reported lactose intolerance (LI) is frequent in patients with functional bowel disorders (FBD) that could be interpreted as irritable bowel syndrome (IBS). The present study aims to characterize the responses of patients with FBD, without small intestinal bacterial overgrowth (SIBO), and LI, in terms of lactose malabsorption (LM) and lactose sensitivity (LS) according to psychological and clinical features. METHODS: One hundred and fifty-eight consecutive FBD outpatients with LI, and no SIBO, were classified according to the Rome III questionnaire and filled Beck Depression Inventory, and State and Trait Anxiety questionnaires. They underwent a lactose tolerance test in which glycemia during 60 minutes and digestive symptoms for 3 hours were recorded. RESULTS: Abnormal lactose tolerance tests were found in 110 patients (70%), 44 (28%) with LM, 96 (61%) with LS, and 30 (19%) having both LM and LS. LM patients had a higher frequency of functional diarrhea (P = 0.040) and a lower frequency of dysphagia (P = 0.031). LS patients had a higher depression score (P = 0.007), higher frequency of globus (P = 0.042), irritable bowel syndrome (IBS) (P = 0.027) and mixed IBS (P = 0.049), and lower frequency of abdominal pain (P = 0.040). LS was significantly associated with a higher depression score (P = 0.002), and a higher frequency of globus (P = 0.046). CONCLUSIONS: Thirty percent of LI patients have normal lactose absorption and normal LS. In the other 70% of patients, LI could be associated with LM and/or LS.

Clinical, Physiological, and Psychological Correlates of the Improvement of Defecation during Menses in Women with Functional Gastrointestinal Disorders.

BACKGROUND/AIMS: Little is known about the improvement in defecation frequently reported by women around menses. We aimed to describe clinical, physiological, and psychological correlates of this improvement in those with functional bowel disorders. PATIENTS AND METHODS: We recruited 478 consecutive premenopausal adult females with no indication of gynecologic or psychiatric disease, who were attending an outpatient functional bowel disorders clinic. Patients completed a Rome III questionnaire, psychological evaluation stool form, and a 10-point Likert scale for constipation, diarrhea, bloating, and abdominal pain. These patients underwent physiological tests, anorectal manometry, and colonic transit time and were classified according to the presence or the absence of improvement in defecation during menses. The reverse selection procedure was used for model selection during multivariate logistic regression where statistically significant variables (p < 0.01) remained in the adjusted model. RESULTS: Ninety-seven patients (20%) reported easier defecation during menstruation. These patients were younger (p < 0.001) but had similar body mass indices and psychological profiles as the other patients. Clinically, they only reported more frequent irritable bowel syndrome (IBS) with constipation (p = 0.007), with harder stools (p = 0.005) and delayed left colon transit time (p = 0.002). No anorectal manometric parameter was different between the 2 groups. CONCLUSION: Improvement of constipation during menses is mainly associated with younger age and constipation-IBS phenotype and not with functional constipation.

Data Mining Approach for the Characterization of Functional Bowel Disorders According to Symptom Intensity Provides a Small Number of Homogenous Groups.

BACKGROUND/AIMS: The aim of the present study is to evaluate if the intensity of the cardinal symptoms of functional bowel disorders could be used to identify homogenous groups of patients defined by the Rome criteria. METHOD: In this observational study, 1,729 consecutive outpatients (73% females) filled out the Rome III questionnaire and 10-point Likert scales for constipation, diarrhea, bloating (BL)/distension, abdominal pain (AP) during the week before the medical consultation. A Gaussian mixture model was used for clustering the patients according to the intensity of symptoms without a priori information, and a classification tree was constructed from this clustering. Data were analyzed using analysis of variance and logistic regression analysis. RESULTS: According to the intensity of symptoms, the patients are divided into 8 groups named according to their main symptomatology: "painful constipation" (PFC), "mild pain constipation" (MPC), "painful diarrhea" (PFD), "mild pain diarrhea" (MPD), "mixed transit" (MT), "BL," "AP," and "nonspecific" (NS). The study of the relationship between the Rome III classification and this new grouping shows that irritable bowel syndrome (IBS)-constipation is associated with PFC, IBS-diarrhea with PFD and MPD, SII-mixed with MT, SII-unspecified with BL, functional constipation with PFC and MPC, functional diarrhea with MPD and NS, BL with "BL" and NS, nonspecific functional bowel disorders (FBD) with NS, and functional AP with "BL" and AP (p < 0.01 for all associations). CONCLUSION: A symptom intensity-based classification of FBD patients could simplify clinical phenotype, give homogeneous groups of patients, and could eventually be used by nongastroenterologists and in clinical research.

Late onset of nivolumab-induced severe gastroduodenitis and cholangitis in a patient with stage IV melanoma.

Antiprogramed cell death-1 protein agents represent a therapeutic approach based on stimulating the host's immune response through blockade of immune checkpoints, inhibitory pathways that dampen the physiological peripheral T-cell immune response and are essential for maintaining self-tolerance. We describe the late onset of severe gastroduodenitis and cholangitis in a nivolumab-treated, metastatic melanoma patient in complete remission. Positron-emission tomography with computed tomography scans showed diffuse fluorodeoxyglucose (FDG) uptake in the stomach preceding upper digestive tract symptoms. Hence, positron-emission tomography with computed tomography might as well be a useful tool for early diagnosis of subclinical gastric toxicity as recently shown for colitis. Furthermore, physicians must be aware and remain vigilant to antiprogramed cell death-1 protein-related digestive toxicity that may appear very late during treatment.

Influence of Age and Body Mass Index on Total and Segmental Colonic Transit Times in Constipated Subjects.

BACKGROUND/AIMS: Discordant data are found in the literature for the relationships between total and segmental colonic transit time (CTT) and demographic parameters. The aim of this study is to examine the influence of age, and body mass index (BMI) on total and segmental CTT in constipated subjects. METHODS: We included 354 constipated patients on this cross-sectional study. According to the Rome III criteria, patients were classified as having irritable bowel syndrome with constipation, or functional constipation. All patients filled the Bristol stool form, and reported the severity of constipation, bloating, and abdominal pain on a 10-point Likert scale. Total and segmental CTT were measured using radiopaque markers. RESULTS: Females were 84% of patients, with a mean age of 46.0 ± 15.9 years. The association between total and segmental CTT with age and BMI was significant after adjustment for gender, clinical phenotype, the presence of defecation disorders, and abdominal pain or bloating intensity despite the severity of symptoms, and the frequency of defecation disorders were higher in irritable bowel syndrome with constipation than in functional constipation patients. By comparison with subjects less than 30 years, rectosigmoid transit time (RSTT) was lower in patients between 30 and 60 years. Age was negatively associated with RSTT (P = 0.004). By comparison with patients with normal BMI, RSTT and total CTT were lower in patients of the overweight group. BMI was negatively associated with RSTT (P < 0.001). The severity of constipation was correlated with total (P < 0.001), right (P = 0.002), and left CTT (P = 0.049). CONCLUSION: Age and BMI are both associated with RSTT in constipated patients.

Resection of small bowel adenocarcinoma metastases: Results of the ARCAD-NADEGE cohort study.

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.

Clinical and psychological correlates of soiling in adult patients with functional gastrointestinal disorders.

BACKGROUND/AIMS: Fecal soiling (FS) is the staining of underwear without loss of significant amounts of fecal material. It is frequently associated with defecation disorders in children. The aim of this study was to search for psychological and clinical correlates of adult patients with soiling. Clinically, the complaint of staining is confused with that of fecal incontinence (FI) in the mind of both patients and attending physicians. DESIGN: Observational study PATIENTS AND METHOD: We included 1454 consecutive outpatients (71% females). They filled out the Rome III questionnaire for functional gastrointestinal disorders (FGIDs); Beck depression inventory, and state and trait anxiety questionnaires; and Likert scales for constipation, diarrhea, bloating, and abdominal pain. Data were analyzed using ANOVA and logistic regression analysis. RESULTS: Soiling was found in 123 patients (8.5%). They reported similar frequencies of esophageal, gastroduodenal, and abdominal pain as patients without soiling. In contrast, patients with soiling reported higher prevalence of IBS, such as IBS-Diarrhea, Mixed-IBS, functional diarrhea, functional constipation, and levator ani syndrome, and higher Likert scale for diarrhea, bloating, abdominal pain, and softer stools. The multivariable logistic regression analysis shows that patients with soiling have increased odds to report IBS (P = 0.019; OR = 1.958; 95% CI = [1.118-3.431]), functional diarrhea (P = 0.040; OR = 1.901; 95% CI = [1.028-3.513]), and high Diarrhea Likert scale (P < 0.001; OR = 1.215; 95% CI = [1.130-1.306]). No association was found with psychological evaluation. CONCLUSION: In FGID patients, soiling is not associated with psychological disorders and is mainly associated with IBS and functional diarrhea.