A Diagnosis of Gastric Inflammatory Myofibroblast Tumor: A Challenge Like No Other!

Inflammatory myofibroblastic tumors (IMTs) are mesenchymal tumors of intermediate malignant potential. Gastric IMTs are rare and commonly affect young adults. They are typically confused with gastrointestinal stromal tumors, inflammatory fibroid polyps, and leiomyosarcomas. The etiology of IMTs remains unclear, but is theorized to be due to hyperinflammatory response to chronic infections. We present a middle-aged woman found to have a gastric mass positive for Helicobacter pylori, underwent multiple endoscopies with endoscopic ultrasound, and a definitive diagnosis of gastric IMT was only made after a partial gastrectomy with immunohistochemistry negative for CD-117, S-100, ALK-1, and positive for vimentin and SMA.

Adrenocortical Carcinomas: Molecular Pathogenesis, Treatment Options, and Emerging Immunotherapy and Targeted Therapy Approaches.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy in the advanced setting with poor prognosis. This narrative review provides an overview of the epidemiology of ACC and its molecular pathogenesis with a summary of the main involved signaling pathways. We then provide an update on the clinical presentation, diagnosis, and current management strategies of both localized and metastatic disease from a multidisciplinary perspective. We highlight the debate around the use of mitotane in the adjuvant setting and review the use of combination chemotherapy with etoposide, doxorubicin, and cisplatin. The review also focuses on emerging data providing hope for the use of immune checkpoint inhibitors and targeted therapies in ACC with a summary of ongoing trials.

Genomic determinants in advanced endometrial cancer patients with sustained response to hormonal therapy- case series and review of literature.

The incidence of endometrial cancer is increasing, however treatment options for advanced disease are limited. Hormonal therapy has demonstrated positive outcomes for Stage IV EC. Next generation sequencing (NGS) has increased our understanding of molecular mechanisms driving EC. In this case series, we selected six patients at our institution with Stage IV, hormone receptor positive, endometrial cancer currently being treated with hormonal therapy. All patients achieved SD for at least ≥ 1.5 years. We studied NGS data on all six patients to assess for any common genomic marker which could predict the SD of at least 1.5 years achieved in this group. Institutional Review Board (IRB) approval was obtained from Staten Island University Hospital and Northwell Health, New York. PTEN, PIK3CA, PIK3R1, and ARID1A mutations were found in 83%, 67% 50%, and 67% of patients respectively. TP53 and FGFR2 were both found in 50% of patients. All patients were positive for estrogen and/or progesterone receptor (ER+ and/or PR+). We did not find any one common mutation that could have predicted the observed response (or SD of ≥1.5 years) to hormone therapy. However, our data reflects the prevalence of various mutations reported in literature: (1) Hormone Receptor status is a positive prognostic indicator (2) PTEN/PIK3CA mutations can occur concurrently in EC (3) ARID1A coexists with PTEN (4) FGFR and PTEN pathways may be interlinked. We suggest NGS be employed frequently in patients with endometrial cancer to identify targetable mutations. Additional larger studies are needed to characterize the interplay between mutations.

The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Management of acute chest syndrome in patients with sickle cell disease: a systematic review of randomized clinical trials.

INTRODUCTION: Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established. AREAS COVERED: To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed. EXPERT OPINION: 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

Babesiosis and the human immune system.

Immunological phenomena have been described in infections such as infective endocarditis. However, none has been reported in the context of Babesiosis. Babesiosis is a tick-borne illness caused by the protozoa of the genus Babesia and causes infections that range from asymptomatic to severe and sometimes are fatal. This report presents the first case of ANCA/ANA positive severe babesiosis in an asplenic patient treated with repeated red blood cell exchange transfusion.

Acute promyelocytic leukemia presenting as recurrent venous and arterial thrombotic events: a case report and review of the literature.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a translocation of chromosomes 15 and 17, creating an alternation in the retinoic acid receptor-alpha (RAR-alpha) gene. This leads to excessive medullary production of promyelocytic blasts, which are frequently associated with the hemorrhagic complications seen in APL. In contrast, APL-associated thrombosis occurs much less frequently and is an underappreciated life-threatening manifestation of the disease. Most thrombotic events occur during induction chemotherapy with all-transretinoic acid and are rarely seen as the initial presentation on APL. Here we report an exceedingly rare case of a patient with recurrent venous and arterial thrombotic events, including deep vein thrombosis, bilateral segmental pulmonary embolism, an ischemic stroke, splenic infarcts, and renal infarcts, later found to have APL. We aim to discuss the most recent understanding of the pathogenesis of APL-associated thrombosis and to summarize the literature of this rare presentation of APL.