[Diarrhea caused by systemic anti-cancer treatments]. / Diarrhées provoquées par les traitements systémiques anticancéreux.

Diarrhea is one of the most common complaints in oncologic patients. Causes are multiple including bowel resection, infections, radiation and systemic anti-cancer treatments. In the latter case, the pathophysiology is partially elucidated and requires the etiology to be precisely identified : chemotherapy, targeted therapy or immunotherapy. Loperamide remains central in uncomplicated cases. However, with development of immunotherapy, autoimmune mechanism should be recognized and requires different approach based mainly on corticosteroids. Physician taking care of patients with diarrhea should therefore identify possible causes in order to offer adapted treatments and therefore reduce morbidity and mortality.

Les diarrhées sont l'une des plaintes les plus fréquentes chez les patients oncologiques. On retrouve des étiologies multiples comme la résection digestive, les infections, la radiothérapie et les traitements anticancéreux systémiques. Dans ce dernier cas, la pathophysiologie est partiellement élucidée et nécessite d'en différencier l'étiologie : chimiothérapie, thérapie ciblée ou immunothérapie. Le lopéramide reste le traitement standard des cas non compliqués. Avec le développement de l'immunothérapie, un mécanisme auto-immun doit être reconnu car il nécessite une prise en charge différente reposant principalement sur l'utilisation des corticoïdes. Le médecin faisant face à un patient présentant une diarrhée doit de ce fait identifier la ou les causes possibles et ainsi adapter le traitement afin d'en réduire la morbidité et la mortalité.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort.

BACKGROUND AND AIMS: Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. METHODS: Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. RESULTS: Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. CONCLUSION: Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

The diagnostic value of abbreviated MRI protocol in the surveillance of Branch-Duct intraductal papillary mucinous neoplasm.

PURPOSE: To assess the diagnostic value of abbreviated protocol (AP) MRI to detect the degeneration signs in branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) in patients undergoing a routine MRI follow-up. METHODS: This dual-center retrospective study include patients with BD-IPMN diagnosed on initial comprehensive protocol (CP) MRI who underwent routine MRI follow-up. CP included axial and coronal T2-weighted images (T2WI), axial T1-weighted images (T1WI) before and after contrast administration, 3D MR cholangiopancreatography (MRCP) and diffusion-weighted images (DWI). Two APs, eliminating dynamic sequences ± DWI, were extracted from CP. Two radiologists evaluated the APs separately for IPMN degeneration signs according to Fukuoka criteria and compared the results to the follow-up CP. In patients who underwent EUS, imaging findings were correlated with pathological results. Per-patient and per-lesion sensitivity, specificity, PPV, NPV, and accuracy of APs were calculated. Additionally, the acquisition time for different protocols was calculated. RESULTS: One hundred-fourteen patients (56.1 % women, median age: 71 years) with 256 lesions were included. Degeneration signs were observed in 24.6 % and 12.1 % per-patient and per-lesion, respectively. Regarding APs, the per patient sensitivity, specificity, PPV, NPV, and accuracy in the detection of the degeneration signs were 100 %, 93.5 %, 83.3 %, 100 %, and 95.1 %, respectively. No additional role for DWI was detected. AP without DWI economized nearly half of CP acquisition time (388 versus 663 s, respectively). CONCLUSION: AP can confidently replace CP for BD-IPMN follow-up with high sensitivity and PPV while offering benefits such as patient comfort, improved MRI accessibility, and reduced dedicated time for image analysis. DWI necessitates special consideration. CLINICAL RELEVANCE STATEMENT: Our data suggest that APs safely detect all degeneration signs of IPMN. While there is an overestimation of mural nodules due to the lack of contrast injection, this occurs in a negligible number of patients.

Gastric Amphicrine Carcinoma Showing Neuroendocrine and Pancreatic Acinar Cell Differentiation. Lesson from a Challenging Case Opening New Perspectives in the Diagnostic Work-Up of Gastric Neuroendocrine Neoplasms.

Amphicrine carcinomas are epithelial neoplasms composed of cells with co-existing exocrine-neuroendocrine phenotype and are challenging lesions from both diagnostic and therapeutic perspectives.Here, we report the case of a 63-year-old male patient with a gastric nodule that was endoscopically biopsied, revealing histological features of a type 3 well-differentiated gastric neuroendocrine tumor (NET). At imaging, the lesion was single and limited to the stomach, but did not present In-111Octreotide uptake, despite SSTR2A immunohistochemical expression. The patient underwent a wedge resection of the gastric wall, with a final pathological diagnosis of amphicrine carcinoma with pancreatic acinar cell and neuroendocrine features (pT1b). Predictive immunohistochemistry showed microsatellite stability and negative HER2 status. Hotspot targeted deep sequencing of 57 genes showed no somatic mutation, in agreement with the low mutational burden reported for gastric amphicrine carcinomas. Due to a low stage of the tumor and the poor performance status of the patient, no additional oncological treatment was administered. The patient was disease-free after 18 months.This unusual case highlights the importance of considering amphicrine carcinoma in the diagnostic work-up of gastric type 3 NET. This can be done by including in the immunohistochemical panel non-neuroendocrine markers, such as the pancreatic acinar cell and glandular ones. Correct pathological diagnosis is pivotal to determine the appropriate staging (NET vs exocrine one) for surgical and oncological management.

[A primer on Wilson disease for the general practitioner]. / La maladie de Wilson: un caméléon clinique auquel il faut penser.

Wilson disease (WD) is an inherited disorder of hepatic copper excretion leading to toxic accumulation of copper in the liver as well as the brain, cornea, and other organs. The defect is due to mutations of the copper-transporting ATPase ATP7B. Clinical manifestations are highly variable and comprise acute liver failure, chronic hepatitis and cirrhosis as well as neurological or psychiatric symptoms. The Kayser-Fleischer corneal ring is pathognomonic but absent in about 50% of patients with hepatic manifestations alone. A high index of suspicion in clinically compatible situations is key, with a combination of laboratory tests allowing the diagnosis of WD. Treatment is based on the use of chelating agents, D-penicillamine or trientine. Liver transplantation should be considered for patients with acute liver failure or advanced cirrhosis.

Hepatic manifestations of Wilson's disease: 12-year experience in a Swiss tertiary referral centre.

BACKGROUND AND AIM: Wilson’s disease is an inherited disorder of hepatic copper metabolism, leading to the accumulation of copper in the liver as well as the brain, cornea and other organs. Here, we describe the adult cases of hepatic Wilson’s disease diagnosed at the Division of Gastroenterology and Hepatology of the University Hospital Lausanne, Switzerland between September 2004 and August 2016. METHODS: Clinical manifestations, results of diagnostic tests, management and outcomes of adult patients with hepatic Wilson’s disease were assessed based on standardised medical records. In addition, liver histology was reviewed and the lesional patterns were recorded. RESULTS: Ten new adult cases of hepatic Wilson’s disease were diagnosed in our centre between September 2004 and August 2016. Male to female ratio was 1:1 and median age at diagnosis was 26 (range 18–56) years. Four patients presented with acute liver failure, four with persistently elevated liver function tests, and two with decompensated cirrhosis; none had neurological manifestations. Only one patient had a Kayser-Fleischer corneal ring. Median ceruloplasmin level at diagnosis was 0.13 (range <0.03–0.30) g/l, median 24-hour urinary copper excretion was 2.8 (range 0.3–77.3) μmol, and median hepatic copper concentration was 789 (range 284–1677) μg/g. At least one mutation in the ATP7B gene was identified in eight patients. Allelic frequency of the common H1069Q mutation was 19%. Leipzig score was ≥5 in all patients. Three patients presenting with acute liver failure and the two with decompensated cirrhosis underwent successful liver transplantation. One patient with acute liver failure recovered under chelation therapy, as predicted by a Dhawan score <11. D-penicillamine was used as first-line chelator treatment, with a subsequent switch to trientine due to adverse effects in three out of six patients. CONCLUSIONS: The clinical presentation of hepatic Wilson’s disease is highly variable. Three out of 10 patients were diagnosed at an age >35 years. A high index of suspicion in clinically compatible situations is key.