Evaluation of MGMT Gene Methylation in Neuroendocrine Neoplasms.

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

Is immunotherapy in the future of therapeutic management of sarcomas?

Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25-50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12-18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.

Intestinal ischemia secondary to Covid-19.

With the wide spread of the current SARS-Cov (Covid-19), It was found that about 2% of children was affected according to several studies, it should be mentioned that Those children are most often asymptomatic, but the current concern is about a vascular inflammatory disease which is similar to Kawasaki disease observed in children with Covid-19. we report a case of a 9-year-old girl, known to have idiopathic medullar aplasia, admitted to the emergency department for a pseudo appendicular syndrome with shock, neurological abnormalities and skin lesions. She underwent an emergency surgery; the peroperative exploration suggested an ischemic bowel lesion of the ileal loop and a healthy appendix. The link involving a Covid-19 infection was well established (RT-PCR +). We shared in common our clinical, radiological, biological and pathological data to draw attention towards the intestinal vasculitis that can be a part in the MIS-C related to Covid 19. To our best knowledge, this is the first case encountered of combination between Covid-19 with intestinal ischemic in children.