Immune Checkpoint Inhibitors and Their Cardiovascular Adverse Effects.

Immune checkpoint inhibitors (ICIs) have reshaped and have become a well-established treatment modality for multiple advanced-stage malignancies. ICIs block the immune system regulatory checkpoints, namely CTLA-4 and PD-1/PDL1, which provokes excess immune response against self-antigens. Immune modulation with ICIs can result in diverse immune-related adverse events targeting organ systems. Several cases of ICI-related cardiotoxicity were reported, while the actual incidence was likely underestimated due to heterogeneous clinical presentation. These include, but are not limited to, myocarditis, pericarditis, atherosclerosis, and arrhythmia. EKG, Troponin, Echocardiogram (TTE), and Cardiac MRI (CMRI) are indispensable diagnostic tools to aid in the management of cardiac adverse effects. Herein, we review the ICI-mediated cardiovascular adverse events, diagnosis, treatment strategies, and reintroduction of ICIs post-cardiotoxicity.

Advances in understanding and management of high-grade pancreatic neuroendocrine neoplasm: a comprehensive review.

High-grade (HG) pancreatic neuroendocrine neoplasms (PAN-NENs) are aggressive and have a poor prognosis. Yet, our understanding and treatment approaches for these tumors have rapidly evolved in the past decade, despite a lack of prospective and randomized trials. It is essential to differentiate grade 3 (G3) neuroendocrine tumors (NETs) from neuroendocrine carcinomas (NECs) due to their different prognostic and treatment implications. The molecular landscape of HG PAN-NENs is complex, with mutations in key cancer-related genes, extensive genomic rearrangements, and chromosomal instability. Advanced studies have provided insights into the significant genetic heterogeneity of HG PAN-NENs and potential therapeutic targets. Several therapeutic strategies have emerged from molecular characterization studies. These include agents targeting the mammalian target of rapamycin (mTOR) pathway, DNA repair pathways, and epigenetic modifiers. Moreover, high programmed cell death ligand 1 (PD-L1) expression in some tumors indicates potential for immunotherapy. However, many challenges remain, with a deeper understanding of the genetic and epigenetic alterations in these tumors necessary to develop novel therapeutic strategies and improve patient outcomes. Treatment strategies for HG PAN-NENs vary. Looking to the future, many clinical trials are exploring novel therapies or combinations of known therapies to improve outcomes. It is evident that understanding the molecular landscape of PAN-NECs, alongside personalized therapeutic strategies, is crucial to developing effective treatment options and improving patient outcomes. In this discourse, our emphasis will be on the molecular landscape and available treatment strategies for HG PAN-NECs.

Therapeutic options for ampullary carcinomas. A review.

Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.

Immune checkpoint inhibitors in the management of malignancies in transplant recipients.

Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.