Risk of anti-TNF therapy on pregnancy, breastfeeding, live vaccines and related information in patients with inflammatory bowel disease: Real-world data from a nationwide study.

BACKGROUND: Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them. AIMS: To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women. METHODS: We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year. RESULTS: Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %. CONCLUSION: In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

Olmesartan-associated enteropathy: results of a national survey.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare.

Liver metastases of digestive endocrine tumours: natural history and response to medical treatment.

BACKGROUND: Few data are available about the natural history of liver metastases of digestive endocrine tumours. Moreover, results of studies on treatment with intravenous chemotherapy, hepatic arterial chemoembolization and somatostatin analogues are conflicting. AIMS OF THE STUDY: To assess the progression of liver metastases of digestive endocrine tumours before antitumoral treatment, and to evaluate a stepwise therapeutic strategy in these patients. PATIENTS AND METHODS: 22 patients with histologically-confirmed liver metastases were studied. Primary tumours were carcinoids in nine, gastrinomas in five, non-functioning pancreatic tumours in six and calcitonin-secreting tumours in two patients. The progression of liver metastases was assessed according to the World Health Organization criteria in 10 patients before treatment, and during treatment in all patients. Intravenous (i.v.) chemotherapy with streptozotocin and 5-fluorouracil was used in patients with more than 25% progression in tumour size or with more than 50% liver involvement. Hepatic arterial chemoembolization was performed if i.v. chemotherapy failed, or as a first-choice treatment after 1993. The somatostatin analogues octreotide or lanreotide were used as a third-choice treatment. RESULTS: Progression (+90%, range 28-600%) of liver metastases was identified in the 10 patients studied before treatment, after a median follow-up of 11.5 months. Objective and minor responses were obtained in 2/10 patients (20%) and 1/10 patients (10%) receiving i.v. chemotherapy. Corresponding figures were 3/7 (43%) and 2/7 (29%) for hepatic arterial chemoembolization. No objective response was observed with somatostatin analogues, although 2 patients experienced a minor response. CONCLUSION: Untreated liver metastases of digestive endocrine tumours show an objective increase (their size approximately doubles after 1 year of follow-up). Among the currently available therapeutic modalities, hepatic arterial chemoembolization provides the highest response rates. An increase in patient survival as a result of this procedure remains to be determined.

[Does acute alcoholic pancreatitis always reveal chronic pancreatitis?]. / Les pancréatites aiguës alcooliques révèlent-elles toujours une pancréatite chronique?

OBJECTIVES: Whether acute alcoholic pancreatitis may occur without underlying alcoholic chronic pancreatitis is still a matter of debate. The aims of this study were to assess the frequency and delay of signs of alcoholic chronic pancreatitis in patients who had an alcoholic acute pancreatitis revealing a pancreatic disease. PATIENTS AND METHODS: From 1975 to 1993, all patients hospitalised for acute alcoholic pancreatitis as a first manifestation for a pancreatic disease and with follow-up > 2 years were included. Definite (pancreatic calcifications, mild to severe Wirsung duct abnormalities, histological or operative data) and probable (diabetes mellitus) diagnosis of chronic alcoholic pancreatitis was systematically searched for initially and during follow-up. RESULTS: Among 122 patients, 114 were included and 8 were excluded because of insufficient follow-up. A definite diagnosis of chronic pancreatitis was made in 101 patients (88.6%) (pancreatic calcifications: n = 71, mild to severe pancreatographic abnormalities: n = 19, histological data: n = 8, peroperative data: n = 3). In 61 patients, the diagnosis of chronic pancreatitis was made during the first year of follow-up and in 40 patients, the diagnosis was made after one year of follow-up. Diabetes mellitus occurred in 4 other patients (3.5%) in whom diagnosis of chronic pancreatitis was considered as probable. No signs of chronic pancreatitis were found in 9 patients (7.9%). CONCLUSION: Acute alcoholic pancreatitis is the hallmark of underlying chronic pancreatitis in 92.1% of patients. Acute alcoholic pancreatitis without underlying chronic pancreatitis either does not exist or is extremely rare.