[Orbital mantle cell lymphoma succesfully treated by Bcl-2 inhibitor: Report of a case]. / Lymphome du manteau orbitaire traité avec succès par un inhibiteur de Bcl-2 : à propos d'un cas.

Lymphoma is the most common orbital malignancy in adults. Among the types of lymphoma, mantle cell lymphoma is a particularly aggressive form, often discovered through systemic involvement, with a dismal prognosis due to frequent recurrences. It is secondary to a t (11 ; 14) (q13; q32) chromosomal translocation resulting in an anti-apoptotic signal via overexpression of Bcl-2. Treatment is based on R-CHOP poly-chemotherapy. We describe the case of a patient with an orbital recurrence of mantle cell lymphoma successfully treated with oral Bcl-2 inhibitor monotherapy. A 58-year-old man who was treated with R-CHOP 8 years ago for mantle cell lymphoma, in remission for 5 years, presented with progressive decreased visual acuity in the left eye, along with binocular diplopia. Clinical examination revealed a decrease in visual acuity in the left eye to 1/20 Parinaud 20 and a relative afferent pupillary defect on the left. External examination revealed a left cranial nerve VI palsy, 2mm of painless proptosis, and hypesthesia of the left V1 territory, leading to a diagnosis of left orbital apex syndrome. The disc and macular OCT were normal. The visual field showed enlargement of the left blind spot. An emergency CT scan and MRI revealed an apical extraconal tissue mass infiltrating the medial rectus muscle, extending to the superior orbital fissure, optic canal and left cavernous sinus, hyperintense on T2 weighted images and isointense on T1. The morphological appearance was strongly suggestive of an infiltrative lymphomatous process. An 18 FDG PET-scan identified the orbital lesion as well as enhancing lesions in the axilla and colon; given the clinical features and test results, the diagnosis of recurrent mantle cell lymphoma was made without biopsy. Treatment with Venetoclax (Bcl-2 inhibitor) was initiated. At one month of treatment, the orbital apex syndrome had entirely resolved, with visual acuity increased to 8/10 Parinaud 4 and a metabolic return to normal on PET scan. The PET scanner and clinical examination at 3 months were entirely normal. At the one-year follow-up visit, the patient was still on Venetoclax, the clinical examination was unchanged, and the PET-scan still showed a complete metabolic response.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

[COV IMPACT: Stress exposure analysis among hospital staff in 2 hospitals in France during the COVID-19 pandemic]. / COV IMPACT : analyse des différents facteurs de stress du personnel hospitalier dans 2 centres hospitaliers en France lors de la pandémie COVID-19.

The COVID-19 pandemic has swept through our hospitals which have had to adapt as a matter of urgency. We are aware that a health crisis of this magnitude is likely to generate mental disorders particularly affecting exposed healthcare workers. Being so brutal and global, this one-of the kind pandemic has been impacting the staff in their professional sphere but also within their private circle. The COV IMPACT study is an early assessment survey conducted for 2 weeks in May 2020, of the perception by all hospital workers of the changes induced in their professional activity by the pandemic. The study was carried out by a survey sent to the hospital staff of Béziers and Montfermeil. The readjusted working conditions were source of increased physical fatigue for 62 % of the respondents. Moral exhaustion was reported by 36 %. It was related to the stress of contracting the infection (72 %) but above all of transmitting it to relatives (89 %) with a broad perception of a vital risk (41 %). This stress affected all socio-professional categories (CSP) and was independent of exposure to COVID. Change in organisation, lack of information and protective gear and equipment were major factors of insecurity at the start of the epidemic. Work on supportive measures is necessary. It should focus on the spread of information, particularly towards the youngest, as well as bringing more psychological support and a larger amount of medical equipment, beyond healthcare workers and the COVID sectors.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Peptic ulcer disease: one in five is related to neither Helicobacter pylori nor aspirin/NSAID intake.

BACKGROUND: The proportion (and even the reality) of peptic ulcer disease (PUD) not related to H. pylori or NSAID/aspirin is debated. AIM: To analyse the current epidemiological and clinical characteristics of peptic ulcer disease in French general hospitals. METHODS: Prospective multicentre study of patients with peptic ulcer disease in 32 French general hospitals over 1 year. H. pylori status was assessed by histology, and/or serology and/or C13-urea breath test. NSAID/aspirin intake (obtained by direct interview) and data about concomitant diseases were collected on the day of endoscopy. RESULTS: Nine hundred and thirty-three patients were selected during the year 2009. After exclusion of 118 patients with only erosive duodenitis, 24 with major missing data, 13 with other causes of ulcer and 65 negative for H. pylori by only one test, 713 patients were classified into four groups: 285 (40.0%) had only H. pylori infection; 133 (18.7%) only gastrotoxic drugs; 141 (19.8%) had both and 154 (21.6%) neither H. pylori infection nor gastrotoxic drug intake ('idiopathic ulcers'). Patients with idiopathic ulcers differed in many ways both from H. pylori and NSAID/aspirin groups. However, multivariate analysis identified only three independent predictors: age, French metropolitan origin and the presence of comorbidities. CONCLUSION: In a general hospital-based population in France, peptic ulcer disease appears idiopathic in a fifth of cases.

Epidemiological and prognostic factors involved in upper gastrointestinal bleeding: results of a French prospective multicenter study.

BACKGROUND AND STUDY AIMS: The mortality rate from upper gastrointestinal bleeding (UGIB) remains high, at 5 % - 10 %. The aim of the current study was to describe the epidemiological characteristics, prognostic factors, and actual practice in a cohort of patients with UGIB admitted to French general hospitals. METHODS: From March 2005 to February 2006, a prospective multicenter study was conducted at 53 French hospitals. A total of 3298 patients admitted for UGIB were enrolled consecutively. Patient data were collected up to the date of discharge from hospital. RESULTS: Data were available for 2130 men and 1073 women (mean age 63 ± 18 years), one-third of whom were taking drugs that would increase the risk of UGIB. The two main causes of bleeding were peptic ulcers (38 %) and esophagogastric varices (EGV) or portal hypertensive gastropathy (24.5 %). Mean Rockall score was 5.0 ± 2.3. Endoscopy was performed on 96 % of patients (within 24 hours in 79 %), and 66 % of those with ulcers and 62.5 % of the EGV patients underwent hemostatic therapy when indicated. Rebleeding occurred in 9.9 % of the patients, and 8.3 % died. Independent predictors of rebleeding were: need for transfusion (odds ratio [OR] 19.1; 95 % confidence interval [95 %CI] 10.1 - 35.9); hemoglobin < 10 g/dL (OR: 1.7; 95 %CI 1.1 - 3.3); Rockall score (OR: 1.4 for each 1 point score increase; 95 %CI 1.0 - 1.9), systolic blood pressure < 100 mmHg (OR: 1.9; 95 %CI 1.4 - 2.5), and signs of recent bleeding (OR: 2.4; 95 %CI 1.7 - 3.5). Independent predictors of mortality were: Rockall score (OR: 2.8; 95 %CI 2.0 - 4.0), co-morbidities (OR: 3.6 for each additional co-morbidity; 95 %CI 2.0 - 6.3), and systolic blood pressure < 100 mmHg (OR: 2.1; 95 %CI 1.8 - 2.8). Rockall score, blood pressure and co-morbidities were taken as continuous variables meaning that the OR was 1.4 for every point increase, it was the same for blood pressure. CONCLUSION: UGIB still occurs mainly as a result of peptic ulcers and portal hypertension in France, and causes significant rates of mortality. There is scope for improvement via better prevention (better use of UGIB-facilitating drugs), endoscopic therapy, and management of co-morbidities.

Liver and inflammatory bowel disease.

Liver disease is exceptional in patients with inflammatory bowel disease. The most common manifestation, sclerosing cholangitis, characterized by inflammation and fibrosis of the intra- and\or extrahepatic bile ducts, is unusual in patients with inflammatory bowel disease. Conversely, inflammatory bowel disease (mainly chronic ulcerative colitis) is not infrequent in patients with sclerosing cholangitis. Gallstone disease, portal vein thrombosis, and hepatic abscesses are complications directly related to inflammatory bowel disease. Drugs prescribed for the treatment of inflammatory bowel disease can be the cause of rare but potentially serious hepatic manifestations which must be recognized and detected early. Recent studies have demonstrated the role of purine analogues in the development of nodular regenerative hyperplasia. Because of the poor prognosis, patients taking purine analogues should be monitored regularly to search for inaugural signs such as an elevation of serum alkaline phosphatase or low platelet counts (which may not necessarily reach thrombopenia). The risk of methotrexate-induced fibrosis is exceptional in inflammatory bowel disease. Patients should be monitored with non-invasive tests to recognize the development of fibrosis. Finally, because of the risk of viral reactivation, patients should be screened for hepatitis B virus surface antigen before introducing infliximab; chronic carriers should be given preventive treatment with nucleoside or nucleotide analogues.

Duodenal intraepithelial lymphocytosis during Helicobacter pylori infection is reduced by antibiotic treatment.

AIM: To evaluate clinical, biological and immunological features of patients with increased duodenal intraepithelial lymphocytes (IELs), and its relation to Helicobacter pylori (HP) and coeliac disease (CD). METHODS: We have studied all patients accrued over a 4-year period with increased duodenal IELs. Those patients were recalled for biological and immunological evaluation and a second endoscopy. RESULTS: Twenty-three from a total of 639 patients were identified and 17 of them were included in the study. The median duodenal IEL count was 59 per 100 epithelial cells. Twelve (71%) patients were HP+; eight of them received HP eradication. At the second endoscopy the duodenal IEL count was significantly lower 2 months after HP eradication (73 versus 28), while the IEL count was unchanged in those patients seronegative for HP (n = 5) or those in whom it was not eradicated (n = 4) (55 versus 55). No patient had coeliac antibodies, four expressed HLA-DQ2, lower than in the general population, and the prevalence of CD was 2% (12/639 patients). CONCLUSION: In some cases an increased duodenal IEL count may be due to an inappropriate host response to HP. HP screening and eradication should be considered before recommending a gluten-free diet.

[Isolated carcinoid tumor of the ovary disclosed by tricuspid insufficiency]. / Une tumeur carcinoïde isolée de l'ovaire révélée par une insuffisance tricuspide.

A 68-year old woman was hospitalised because of isolated right heart failure. Doppler echocardiography revealed severe tricuspid regurgitation with thickened, shortened, hypomobile leaflets. Pulmonary valve was thickened with mild pulmonary regurgitation. Mitral and aortic valves were normal. The patient was finally diagnosed with carcinoid heart disease from an isolated ovarian carcinoid cancer without hepatic metastases. Ovarectomy was performed and the patient was considered cured of her cancer. Because of refractory right heart failure, she underwent tricuspid valve replacement with a bioprosthesis. Such cardiovascular manifestations are rarely the presenting symptoms of carcinoid disease. Carcinoid heart disease from ovarian primary cancer is exceptional. In this circumstance, carcinoid cardiac lesions may develop in the absence of hepatic metastases because the venous blood from the ovaries drains into the inferior vena cava without hepatic first past effect. Surgical resection of primary ovarian carcinoid tumor is often curative and the prognosis depends mainly on the cardiac condition. The diagnosis of carcinoid syndrome should be discussed in patients with organic tricuspid regurgitation without left valvular disease.

[Axillary lymph node and bone marrow micrometastases of breast cancer]. / Les micrométastases ganglionnaires et osseuses des cancers du sein.

Micrometastatic disease from breast cancer is a major concern both for clinicians and pathologists. Histologically, they can be defined as potentially invasive microfoci of tumoral cancer cells located in the vicinity of blood vessels and are a distinct entity from residual disease. They are mainly looked for in bone marrow and lymph nodes specimens and their diagnosis is currently easier thanks to immunohistochemistry. Provided a standard definition of micrometastatic disease and standard screening procedures can be met, the presence of micrometastases at the time of diagnosis could represent a major parameter in therapeutic decision-making. Although controversial, the presence of medullary and axillary lymph node micrometastases appears to be a major prognostic factor in terms of survival. Recognition of this entity could help in better defining the high-risk subset of patients who would potentially benefit from adjuvant chemotherapy.

[Portal vein thrombosis associated with a myeloproliferative disorder, prothrombin G20210A mutation, antiphospholipid syndrome, with repermeation during anticoagulant therapy]. / Thrombose portale récente régressive sous anticoagulants secondaire à un syndrome myéloprolifératif latent, une mutation G20210A du gène de la prothrombine et un syndrome des antiphospholipides.

Portal vein thrombosis, except in hepatocellular carcinoma and severe cirrhosis, is due to one or several prothrombotic disorders with or without a local precipitating factor. We report a case of a portal and splenic vein thrombosis, without cavernoma and varices which occurred in a 72-year-old man with abdominal pain and weakness. Three prothrombotic states including latent myeloproliferative disorder, antiphospholipid syndrome, and factor II G202101 mutation, were observed. Anticoagulant treatment resulted in complete repermeation of the portal and splenic veins without a hemorrhagic event. This illustrates that several prothrombotic states may occur in a single patient with portal vein thrombosis. Early anticoagulant therapy, in recent portal vein thrombosis, can result in repermeation.

[Achalasia mimicking psychiatric eating disorders]. / Achalasie mimant des troubles du comportement alimentaire.

Anorexia nervosa and psychogen vomiting are psychiatric eating disorders characterized by unexplained weight loss and induced vomiting. These diagnoses require absence of somatic disease. Achalasia is a primary disorder of the esophagus that can be responsible for the same symptoms. This may occult the real diagnosis, especially as dysphagia is not constant and variable in time. We report four cases of achalasia mistakenly diagnosed and treated as anorexia nervosa or psychogen vomiting. Achalasia was unrecognized because specific symptoms, such as dysphagia, were overlooked or misinterpreted by the patients' physicians and psychiatrists, or by the patients themselves. In patients with such eating disorders considered to be psychiatric, physicians should inquire about signs suggestive of achalasia. The diagnosis of achalasia is suspected by imaging and endoscopy, and confirmed or ruled out by manometry.