MEN1 Surveillance Guidelines: Time to (re)Think?

Clinical Practice Guidelines for patients with Multiple Endocrine Neoplasia type 1 (MEN1) recommend a variety of surveillance options. Given progress over the past decade in this area, it is timely to evaluate their ongoing utility. MEN1 is characterized by the development of synchronous or asynchronous tumors affecting a multitude of endocrine and non-endocrine tissues, resulting in premature morbidity and mortality, such that the rationale for undertaking surveillance screening in at-risk individuals appears robust. Current guidelines recommend an intensive regimen of clinical, biochemical and radiological surveillance commencing in early childhood for those with a clinical or genetic diagnosis of MEN1, with the aim of early tumor detection and treatment. Although it is tempting to assume that such screening results in patient benefits and improved outcomes, the lack of a strong evidence base for several aspects of MEN1 care, and the potential for iatrogenic harms related to screening tests or interventions of unproven benefit, make such assumptions potentially unsound. Furthermore, the psychological, as well as economic burdens of intensive screening remain largely unstudied. Although screening undoubtedly constitutes an important component of MEN1 patient care, this perspective aims to highlight some of the current uncertainties and challenges related to existing MEN1 guidelines with a particular focus on the role of screening for pre-symptomatic tumors. Looking forward, a screening approach that acknowledges these limitations and uncertainties and places the patient at the heart of the decision-making process, is advocated.

Integrative Study of a High-Grade B-Cell Lymphoma Cohort of 45 Patients: A Single Institution Real Life Study

Background : High grade B cell lymphoma (HGBL) either Not Otherwise Specified (NOS) or either Double Hit (DH MYC/BCL2 or DH MYC/BCL6) or Triple Hit (TH) have been considered as separate entities from Diffuse Large B-Cell Lymphoma (DLBCL) NOS in the 2016 WHO classification. Until now, treatment of these particularly aggressive histological sybtypes remains unclear and most of patients (pts) still have a poor outcome because of chemoresistance or early relapse. Except IPI score, prognosis factors are not completely clarified. Since few years, treatment with Chimeric Antigen Receptor T (CAR-T) cells has changed the prognosis of relapsed refractory DLBCL and could represent a promising therapeutic approach - early in the course of the disease - to improve survival of HGBL. The aim of the present study is to describe a « real life » cohort of pts treated in our institution and to evaluate the prognostic impact of clinical, histological, genetic and imaging characteristics and treatment. Methods : We collected data of 45 pts diagnosed between January 2009 and October 2020. BCL2, BCL6 and MYC break were analyzed by Interphase Fluorescence In Situ Hybridization (FISH) with break-apart probes. When MYC was rearranged, MYC partner gene was analyzed with double fusion probes (MYC/IgH, MYC/IgL, MYC/IgK). Total metabolic tumor volume (TMTV) was calculated using fully automatic segmentation of lymphoma lesions by an artificial intelligence (P. Blanc-Durand, Eur J Nucl Med Mol Imaging, 2021). All pts were treated with rituximab R-CHOP/CHOP-like regimens. Treatment was reinforced (intensive regimen) with high dose methotrexate (14 pts treated with RCOPADM and one with R-ACVBP) when they were considered fit enough. Autologous stem cell transplantation at 1st relapse was performed in 3 pts and 5 pts were treated with CAR-T cells at 2 nd relapse. Results : Baseline characteristics were as follows: median age 60 y (28-80), IPI 3-5 : n=33 (73%), CNS localization : n=8/42 (19%), bone marrow involvement : n=10/34 (22%). Twenty-seven pts were DH lymphoma (MYC/BCL2: 18; MYC/BCL6: 9), 8 patients were TH-lymphoma and 10 were HGBL-NOS. MYC rearrangement was detected in 40 cases with an immunoglobulin partner gene (IgH, IgL or IgK) in 14 (52%) of 27 evaluable cases. TMTV was calculated for 29 pts with a median TMTV of 1019 ml (2-4536 ml). Fifteen pts were treated with an intensive regimen. With a median follow-up of alive pts of 17 months, 2-y progression-free survival (PFS) and overall survival (OS) were 42% [26.4 ; 56.8] and 62% [43.7 ; 75.5] respectively. PFS and OS were significantly affected by IPI 3-5 (PFS: p= 0.006, HR=3.37 ; OS: p= 0.01, HR=3.71) and CNS involvement (PFS : p=0.006, HR=6.93 ; OS: p=0.006, HR=7.44). TMTV>1000ml (PFS: p=0.051, HR 2.99 ; OS: p=0.033, HR=4.13) was associated with a significantly inferior OS. Prognosis of HGBL DH/TH and HGBL-NOS was similar (PFS: p= 0.89, HR=0.93 ; OS: p=0.64, HR=1.32). Immunoglobulin as MYC partner gene had no significant impact on prognosis (PFS: p=0.47, HR=1.48 ; OS: p=0.32, HR=1.73). Intensive regimens did not improve significantly prognosis (PFS: p=0.26, HR=1.71 ; OS: p=0.08, HR=2.86). Conclusion: This monocentric study confirms previous reports on the poor prognosis of HGBL (DH/TH and NOS) especially for patients for both high IPI or high TMTV and in case of initial CNS involvement. We confirm that intensive regimen don't improve prognosis supporting the need of alternative strategies incorporating bispecific monoclonal antibodies or consolidative CAR-T cells in very high risk pts. Disclosures Roulin: Janssen: Other: Travel and meetings. Lemonnier: Institut Roche: Research Funding; Gilead: Other: travel grant. Le Bras: Novartis: Honoraria; Takeda: Honoraria, Research Funding; Kite Gilead: Honoraria; Celgene BMS: Research Funding. Gaulard: Innate Pharma: Research Funding; Sanofi: Research Funding; Alderaan: Research Funding; Gilead: Consultancy; Takeda: Consultancy, Honoraria. Haioun: Miltenyi: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Servier: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding.

Statin Utilization among Patients with Acute Coronary Syndrome: Systematic Review

BACKGROUND: The early use of statin with intensive regimen has been recommended by the recent guidelines as the prevention of acute coronary syndrome (ACS) related events among the high-risk patients. Meanwhile, the inconsistent statin utilization for targeted patient in current practice is still an issue. AIM: This study aims to review the utilization rate of statin among patients with ACS. METHODS: A systematic search of relevant studies published between inceptions to June 2020 was conducted in PubMed. Patients and intervention domains were used to build up the searching formula. A study was eligible for inclusion if it was an original study of patients with ACS and it examined the utilization of statin. The risk of bias was assessed using Axis and NOS checklist. RESULTS: Among the 49 eligible studies, 38 were cohort studies while the others were cross-sectional studies. The utilization rate of statin at hospital admission ranged from 16% to 61% while 25% to 75% during the hospitalization. Of the total studies, 35 studies reported the statin rate at discharge ranging from 58% to 99%. Almost all studies revealed the reduction of statin utilization rate along the follow-up period. The number of statins prescribed was found to be lower among female and elderly patients. CONCLUSION: Despite the established benefits of statin among patients with ACS, our study revealed that statin was underutilized for secondary prevention after ACS. To improve patients’ clinical outcomes with ACS, efforts should be made to increase optimal treatment and compliance with a statin.

Does a less intensive surveillance protocol affect the survival of patients after treatment of a sarcoma of the limb?

Aims A single-centre prospective randomized trial was conducted to investigate whether a less intensive follow-up protocol would not be inferior to a conventional follow-up protocol, in terms of overall survival, in patients who have undergone surgery for sarcoma of the limb. Initial short-term results were published in 2014. Patients and Methods The primary objective was to show non-inferiority of a chest radiograph (CXR) group compared with a CT scan group, and of a less frequent (six-monthly) group than a more frequent (three-monthly) group, in two-by-two comparison. The primary outcome was overall survival and the secondary outcome was a recurrence-free survival. Five-year survival was compared between the CXR and CT scan groups and between the three-monthly and six-monthly groups. Of 500 patients who were enrolled, 476 were available for follow-up. Survival analyses were performed on a per-protocol basis (n = 412). Results The updated results recorded 12 (2.4%) local recurrences, 182 (36.8%) metastases, and 56 (11.3%) combined (local + metastases) recurrence at a median follow-up of 81 months (60 to 118). Of 68 local recurrences, 60 (88%) were identified by the patients themselves. The six-monthly regime (overall survival (OS) 54%, recurrence-free survival (RFS) 46%) did not lead to a worse survival and was not inferior to the three-monthly regime (OS 55%, RFS 47%) in terms of detecting recurrence. Although CT scans (OS 53%, RFS 54%) detected pulmonary metastasis earlier, it did not lead to a better survival compared with CXR (OS 56%, RFS 59%). Conclusion The overall survival of patients who are treated for a sarcoma of the limb is not inferior to those followed up with a less intensive regimen than a more intensive protocol, in terms of frequency of visits and mode of imaging. CXR at six-monthly intervals and patient education about examination of the site of the surgery will detect most recurrences without deleterious effects on the eventual outcome. Cite this article: Bone Joint J 2018;100-B:262–8.

Necrobiose lipoídica em adolescente com diabetes mellitus tipo 1: relato de caso

***Necrobiosis lipoidica in an adolescent with type 1 diabetes mellitus: case report***AIMS: To report a case of necrobiosis lipoidica, a rare chronic granulomatous dermatosis.CASE DESCRIPTION: We present the case of a 17-year-old male adolescent, with type 1 diabetes mellitus from the age of four, followed in the Pediatric-Diabetology clinics of a level II hospital, under intensive regimen with multiple insulin administrations and poor metabolic control. At the age of 15, he noticed the appearance of an asymptomatic, erythematous, infiltrated, oval-shaped plaque, with a waxy whitish center, well-defined borders, 5 cm in diameter and progressive growth, located on the left forearm. The histological examination confirmed the diagnosis of necrobiosis lipoidica. He was treated with topical corticosteroid and emollient, thus stabilizing and reducing lesion infiltration.CONCLUSIONS: The authors highlight a rare dermatosis, non-pathognomonic of diabetes mellitus but related to this diagnosis in most cases. Its challenging recognition, especially in the presence of recent onset lesions, with atypical clinical presentation or in unusual sites, is fundamental in order to avoid erroneous or late treatments and its progression to ulceration.

DOSE-INTENSIVE NEOADJUVANT CHEMOTHERAPY IN COMBINED TREATMENT FOR LOCALLY ADVANCED CERVICAL CANCER: THE EXPERIENCE AND PERSPECTIVES

In 24 patients (mean age 48 years) with locally advanced cervical cancer there were studied the efficacy and toxicity of 3 cycles of neoadjuvant dose-intensive chemotherapy with cisplatin (75 mg/m2) and doxorubicin (35 mg/m2) administered intravenously on the first day of a two- week cycle with the support of colony-stimulating factors. An important criterion for the inclusion in this study of patients with locally advanced cervical cancer (T1b2-2bN0-1M0) was the absence of infiltration of the anterior parameters according to the gynecological examination and MRI studies. An objective response to treatment was registered in 72.7 % of cases. Progression of the disease was not detected in any case. Conducting neoadjuvant drug therapy allowed performing radical surgical intervention in 95.4 % of patients. The pathomorphlogical response of tumor of varying severity was 40.9 %. In 9.1 % complete clinical regression of tumor was confirmed by a complete pathomor-phological response (CR). The dose-intensive regimen of chemotherapy did not lead to a significant increase of complications on the drug and surgical stages. An analysis showed that dose-intensive neoadjuvant chemotherapy is a highly effective method in treatment for locally advanced cervical cancer.