MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer.

BACKGROUND: MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/m2 46-h intravenous (i.v.) infusion day 1 q2 weeks plus leucovorin 400 mg/m2 2-h infusion i.v. day 1 q2 weeks or capecitabine 1000 mg/m2 b.i.d. orally days 1-14 every 21 days; bevacizumab 5 mg/kg 15-30-min i.v. infusion q2 weeks] or experimental treatment in one of four biomarker-driven cohorts. In patients with BRAF wild-type (BRAFwt) tumors (cohort 2), experimental treatment was FP/bevacizumab + atezolizumab (800 mg 60-min i.v. infusion q2 weeks). Primary efficacy endpoint was progression-free survival (PFS; intent-to-treat population). Enrollment is complete; efficacy and safety findings from cohort 2 are presented. RESULTS: Four hundred and forty-five patients with BRAFwt mCRC were randomized (2 : 1) to maintenance in cohort 2. At a median follow-up of 10.5 months, PFS outcome hypothesis was not met [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.72-1.17; P = 0.48]; overall survival (OS) was immature. At a median follow-up of 20.3 months (2-year survival follow-up), PFS benefit was also not met (HR 0.95; 95% CI 0.77-1.18; P = 0.666); OS HR with nearly two-thirds of patients with events was 0.83 (95% CI 0.65-1.05; P = 0.117). No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events (TEAEs) for experimental versus control arms were hypertension (6.1% versus 4.2%), diarrhea (3.1% versus 2.1%), and palmar-plantar erythrodysesthesia syndrome (1.0% versus 2.5%). Four patients experienced TEAEs with fatal outcome, two were study treatment-related: hepatic failure (experimental arm) and large intestine perforation (control arm; bevacizumab-related). CONCLUSIONS: Adding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAFwt mCRC did not improve efficacy outcomes.

[Cardiac hydatid cysts: report of 10 cases]. / Kyste hydatique du coeur. A propos de 10 cas.

Authors report 10 observations of cardiac hydatid cyst collected to cardiovascular unit of Ibn Rochd hospital in Casablanca during last 7 years. Clinical investigation included in all cases chest X ray, ECG and ultrasonography (US). A computed tomography (CT) scan was performed in 6 cases, magnetic resonance imaging in four cases, transoesophageal US in two cases. Examination for other hydatic sites was realized in all cases, and brain CT was performed in 5 cases. The hydatid cyst was variably localized in the left ventricle in 6 cases, the pericardium in 4 cases, the interventricular septum in 2 cases, the right auricle in 2 cases and multiple locations in one case. The existence of other cardiac hydatid sites was found in 7 cases. Seven patients have been operated (2 cases to closed heart). Outcome was favorable in 6 cases with a mean of three years survey. Two patients died and 2 others have been lost of view. The diagnosis of the cardiac hydatid cyst has benefits from the combination USCT scan that allowed a precise topographical inventory, reducing the need for MRI to the complicated cases and to the rare cases of inconclusive results by US-CT scan.

[Malignant non-Hodgkin's lymphoma presenting with cardiac tamponade]. / Tamponnade cardiaque révélatrice d'un lymphome malin non hodgkinien.

Malignant non-Hodgkin's lymphoma rarely involves the heart. However, all cardiac structures may be invaded, although the myocardium and pericardium are affected more often than the valvular structures. Diagnosis is important because treatment must be adapted. The cardiac signs are usually non-specific and lymphomas presenting in this way have only occasionally been reported. The authors report two cases in which malignant non-Hodgkin's lymphoma presented with cardiac tamponade.

[Obstructive left triatrial heart in the adult. Echocardiographic appearances]. / Coeur triatrial obstructif gauche chez l'adulte. Aspects échocardiographiques.

The authors report the case of a 23-year old man who presented with signs of pulmonary hypertension due to an obstructive left triatrial heart in adulthood. Transthoracic and transoesophageal echocardiography showed a partially calcified intra-left atrial membrane perforated in its centre. Doppler analysis of flow through the membrane showed continuous systolo-diastolic flow at high velocity indicating haemodynamic obstruction. The systolic pulmonary artery pressure was estimated at 80 mmHg. The patient was treated by surgical excision of the intra-left atrial membrane.

[Malignant mediastinal schwannoma in Recklinghausen's disease presenting as cardiac tamponade. Report of two cases]. / Tamponnade cardiaque révélatrice de schwannome malin médiastinal au cours de la maladie de Recklinghausen. A propos de deux observations.

The authors report two cases of Recklinghausen's disease admitted for cardiac tamponade. Two-dimensional echocardiography showed a pericardial tumour in addition to a compressive pericardial effusion. After pericardial drainage, the outcome was rapidly fatal. Histological examination confirmed the diagnosis of a malignant intrapericardial schwannoma. A review of the literature revealed the scarcity of mediastinal malignant schwannoma. Associated with Von Reckinghausen's disease in 2 to 13% of cases, the prognosis is poor. The presentation of malignant mediastinal schwannoma with cardiac tamponade remains very rare.

[Horton's disease presenting as a myocardial infarction]. / Infarctus du myocarde révélant une maladie de Horton.

The authors report the case of a 60-year-old man admitted for uncomplicated acute myocardial infarction. The history of persistent fronto-occipital headaches and palpation of bilateral tortuous temporal arteries with a decreased pulse suggested the diagnosis of temporal arteritis, particularly in the presence of marked laboratory signs of inflammation and the coronary angiograph findings. The diagnosis was confirmed by temporal artery biopsy. Treatment consisted of corticosteroid therapy, with a satisfactory outcome at three months. The diagnosis of temporal arteritis should be systematically suggested in patients over the age of 50 years, presenting with a marked inflammatory syndrome and recent-onset arterial disease. Similarly, any form of arterial disease occurring during treated temporal arteritis should initially be considered to be a secondary site of the arteritis, requiring intensification of corticosteroid therapy.

[Hypertension and Takayasu disease. Report of 8 cases]. / HTA et maladie de Takayasu. A propos de 8 cas.

In this paper, the authors report 8 cases of Takayasu disease presenting in the form of hypertension, observed in the Cardiology of Ibn Rochd University Hospital in Casablanca between 1983 and 1995. The majority of cases presented with renovascular HT, secondary to unilateral or bilateral renal artery stenosis. More rarely, the patients presented proximal hypertension secondary to coarctation of the aorta. Medical treatment was prescribed all 8 cases, associated with surgery in 8 cases.

Pericardial tamponade as the first manifestation of dermatopolymyositis.

Pericardial involvement in polymyositis and dermatomyositis (PM/DM) is rare, usually asymptomatic and exceptionally part of the initial presentation. We describe a 37-year-old patient hospitalized for overt acute pericarditis, revealing dermatomyositis, which to our knowledge has not been previously reported. Pericardial puncture relieved the patient. The pericardial fluid was citrine yellow, exsudative, and mainly contained lymphocytes. Search for LE cells and anti-DNA antibodies was negative, whereas the antinuclear antibodies and the rheumatoid factor were present in the pericardial fluid. A biopsy of the pericardium showed a non-specific chronic inflammatory state and the search for an etiology was negative. There was no sign of tuberculosis, systemic lupus, nor neoplasia. Moreover bacteriological cultures and HIV serology were negative. After pericardiostomy associated with corticosteroid therapy at the dose of 1 mg/kg/day, outcome was good with a resolution of the pericarditis confirmed at one-year follow-up. Since pericardial tamponade, even though rare, may be fatal in a patient with dermatomyositis, we emphasize that a two dimensional echocardiographic study should be performed in all patient presenting with dermatopolymyositis.

[Deep venous thromboses and occult cancers]. / Thromboses veineuses profondes et cancers occultes.

The association between venous thrombosis and cancer has been known for a long time. Thrombophlebitis often occurs during the course of a known cancer, but sometimes constitutes the presenting sign. Based on a series of 10 cases of deep venous thrombosis (DVT) revealing an underlying cancer, the authors analyse the various aspects of this association and the elements which help to guide the diagnosis towards a cancer. A simple assessment comprising clinical examination, full blood count and differential white cell count, erythrocyte sedimentation rate, protein electrophoresis, chest x-ray and abdomino-pelvic ultrasonography was performed on admission in 75 cases of presumably idiopathic DVT and revealed a cancer in 10 cases: 6 women and 4 men with a mean age of 53 years. Cancers were located in the urogenital tract in 5 cases, in the bronchi in 2 cases, in the stomach in one case, and there was one case of acute myeloblastic leukaemia (AML) and another case of liposarcoma of the left iliac fossa. The histological type most frequently encountered was adenocarcinoma in 6 cases. In 9 out of 10 cases, the cancer was discovered at the stage of metastases. However, a localized cancer was detected in one case, in which surgical treatment allowed cure of the patient. Comparison of the various characteristics of DVT between the group of DVT revealing a cancer and the group of DVT which remained idiopathic did not reveal any statistically significant difference. A simple, inexpensive assessment looking for a cancer must be systematically performed in all cases of idiopathic DVT in patients between the ages of 50 and 85 years. Other more elaborate examinations may be requested on the basis of the results of the preliminary assessment.

[Cardiac tamponade disclosing neoplasm: apropos of 23 cases]. / Tamponnades révélatrices de néoplasme; à propos de 23 cas.

The authors report a series of cardio-pericardial metastases presenting acutely with tamponade. There were 14 men and 9 women with an average age of 39 years. The primary tumour was mainly bronchial in the men (5 cases: 20.8%) and breast (3 cases: 16.6%) or uterine (4 cases: 16.6%) in the women. The other malignancies were blood dyscrasias (5 NHL and 1 MHL) one pericardial mesothelioma, one Schwannoma, one Ewing's sarcoma and one carcinoma of the larynx. The primary tumour was not found in one case. Echocardiography showed a large, circumferential pericardial effusion in all cases and compressing the right heart chambers (RA and/or RV) in half the cases. Rounded echogenic masses implanted on the pericardial membranes (2 cases) or images of false membranes (10 cases) were also demonstrated. The clinical emergency led to pericardiocentesis with surgical drainage in 5 cases. A pleuro-pericardial window was fashioned in 4 cases. The effusion was important in all cases and bloody in 75% of cases. Cytology of the pericardial liquid was positive for malignant cells in 1 out of 2 cases. The diagnosis was made after death in 3 cases. The other biopsies, bronchial, lymph node, pleural and bone marrow also provided valuable diagnostic information. Undifferentiated carcinoma was found in 75% of bronchial carcinomas. In all three breast tumours, the histology showed moderately well differentiated adenocarcinoma. The authors underline the paucity of therapeutic measures: at this stage, pericardiocentesis is almost the only procedure apart from the cases of haemopathy. Some authors have suggested radiotherapy of the precordial region and others, intrapericardial chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)