Collagenous Gastritis: An Atypical Presentation of a Rare Disease.

Collagenous gastritis is a rare inflammatory condition of unknown etiology defined histologically by subepithelial deposition of collagen bands ≥ 10 µm in the lamina propria. Adults typically present with diarrhea, often attributed to concurrent collagenous sprue or collagenous colitis. Children more commonly present with abdominal pain and anemia, with inflammation typically limited to the stomach. Herein, we present a case of collagenous gastritis in a 38-year-old female with a history of iron deficiency and hypothalamic amenorrhea who presented with a one-year history of microcytic anemia. Celiac disease panel, Helicobacter pylori testing, and anti-parietal cell and intrinsic factor antibodies were negative. Esophagogastroduodenoscopy revealed diffusely erythematous and nodular gastric mucosa in the antrum and pylorus. Biopsy from the gastric body showed complete loss of oxyntic glands and deposition of a thick band of collagen under the surface epithelium infiltrated by a few eosinophils, consistent with collagenous gastritis with severe atrophy. She was treated with omeprazole 40 mg daily for six weeks and iron supplementation. Our patient's symptoms and endoscopic findings are consistent with previously described pediatric, but not adult, cases of collagenous gastritis, yielding insight into the variable clinical presentation of this rare disease.

Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors.

PURPOSE OF REVIEW: To review the biology, drug development, and clinical data regarding the efficacy and safety of belzutifan (MK-6482), a small molecule inhibitor of HIF-2α. RECENT FINDINGS: Belzutifan, a second-generation HIF-2α inhibitor, was shown to provide clinically meaningful benefit in the treatment of VHL-associated tumors (including ccRCC, pancreatic lesions as well as neuroendocrine tumor, and CNS hemangioblastomas). The recommended dose of belzutifan is 120 mg orally daily and half-life is 14 h. In pretreated ccRCC, belzutifan achieved disease control rate of 80% in phase I trial. The most common side effects include anemia and hypoxia related symptoms. Investigation into the important role HIF-2α plays in the expression of genes associated with angiogenesis, erythropoiesis, carcinogenesis, and progression of tumors and the discovery of structural vulnerability within HIF-2α have resulted in the development of a new therapy that has demonstrated efficacy and safety in recent clinical trials. Further research is ongoing to optimize therapeutic benefits from this new exciting therapeutic modality and to improve the outcome of HIF-2α-driven tumors.

A Thrombotic Thrombocytopenic Purpura-Like Syndrome in HIV and Streptococcus pneumoniae Meningitis.

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by the formation of diffuse thromboses in small blood vessels, which can result in neurological and renal impairment, fever, and purpura, among additional sequelae. TTP-like syndromes are disease processes that have similar signs and symptoms as TTP but without a severe deficiency in ADAMTS13 levels. We present a case of a young male with advanced human immunodeficiency virus (HIV) and Streptococcus pneumoniae meningitis presenting with a thrombotic microangiopathy (TMA). Although his ADAMTS13 level was not suggestive of TTP, at 54.4% (normal low ADAMTS13: >66.8% activity; severe ADAMTS13 deficiency: ≤10% activity), he improved only after plasmapheresis was initiated, supporting a diagnosis of a TTP-like syndrome likely due to his streptococcal meningitis. We discuss the importance of treating patients with TTP-like syndromes and advanced HIV with highly active antiretroviral therapy (HAART). We also highlight the increased prevalence of TMA and TTP among HIV patients and that many of these patients do not have a severe deficiency in levels of serum ADAMTS13.

ONECUT2 as a key mediator of androgen receptor-independent cell growth and neuroendocrine differentiation in castration-resistant prostate cancer.

Despite androgen dependence in a majority of castration-resistant prostate cancers, some cancer cells are independent of androgen receptor (AR) function, a feature of heterogeneity in prostate cancer. One of the aggressive variants of prostate cancer that are AR independent is neuroendocrine prostate cancer (NEPC). This manuscript will focus on the new finding of human one cut domain family member 2 (ONECUT2) transcription factor and its role in castration resistance, especially in NEPC.

Gangrene of the Foot After Coronary Artery Bypass Graft Surgery.

Coronary artery bypass grafting (CABG) is the most common surgery performed by cardiothoracic surgeons worldwide. Risks of CABG include neurological outcomes, deep vein thrombosis, renal or gastrointestinal injury, and death. Perioperatively, some patients may need intra-aortic balloon pump (IABP) use to help assist with cardiac function. In this case, a 75-year-old man presented with multivessel myocardial infarction requiring IABP for cardiac assistance prior to undergoing CABG. Eighteen days after his CABG, his toes turned black at home. A CT angiogram showed aortic atherosclerosis, right tibioperoneal trunk stenosis, mild atherosclerotic right proximal anterior tibial artery stenosis, and multifocal occlusive lesions in the right and left infrapopliteal vessels. Vascular surgery performed balloon angioplasty of the right anterior tibial artery and podiatry performed a transmetatarsal amputation of the dry gangrene. The aim of this case report is to present a rare complication of CABG with peri-operative IABP use and to highlight the need for prompt diagnosis and treatment of dry gangrene.

Utility of serum CA-125 monitoring in patients with ovarian cancer undergoing immune checkpoint inhibitor therapy.

OBJECTIVE: This study aimed to evaluate the utility of serum cancer antigen-125 (CA-125) levels to monitor patients with epithelial ovarian cancer (EOC) undergoing immune checkpoint inhibitor (ICI) therapy. METHOD: This was a single-center retrospective review of all patients with EOC who were treated with ICI therapy from January 2013 to May 2017. This study compared the percentage change in baseline CA-125 in patients who had clinical benefit, defined as complete response, partial response, or stable disease by RECIST 1.1, with duration ≥24 weeks, versus those who did not. The groups were compared by Wilcoxon rank-sum test. RESULTS: Fifty-nine (66%) of 89 patients who underwent ICI therapy had CA-125 data at baseline and during treatment. Of those who derived clinical benefit, 11/15 (73%) experienced an increase in CA-125 from baseline to end of treatment. Of those who did not derive clinical benefit, 36/44 (82%) experienced a CA-125 increase (p = 0.48). The average % increase from baseline to within 12 weeks of treatment initiation for patients with and without clinical benefit was 34% and 195%, respectively (p = 0.008). CONCLUSION: Our analysis demonstrates a statistically significant difference in the magnitude of increase in CA-125 levels within the first 12 weeks of treatment between patients who achieved clinical benefit and those who did not. However, both groups of patients were equally likely to experience an increase in CA-125 within 12 weeks. These findings suggest that physicians should apply caution when using early CA-125 data to guide treatment decisions for patients with EOC undergoing ICI therapy.

Mixed Serous and Clear Cell Adenocarcinoma of the Ovary Presenting with Symptomatic Hypercalcemia: A Case Report and Clinical Considerations.

INTRODUCTION: Hypercalcemia is a common phenomenon in patients with cancer but is more common among certain cancer types. Hypercalcemia in ovarian cancer is the common presenting sign in small cell carcinoma of the ovary, hypercalcemic type; however, there are no known documented cases of hypercalcemia as the presenting sign for mixed serous and clear cell adenocarcinoma. This case report describes symptomatic hypercalcemia as the presenting sign of mixed serous and clear cell carcinoma of the ovary. CASE PRESENTATION: A 60-year-old woman with a medical history of hypertension and hyperlipidemia presented to the outpatient clinic with weakness, nausea, emesis, constipation, and an unintended 9-kg (20-lb) weight loss. Her calcium level was elevated at 15.7 mg/dL (reference range = 8.5-10.3 mg/dL). She was treated for hypercalcemia and subsequently admitted to the hospital 4 times because of recurrence of symptoms. On outpatient workup, she was noted to have an abnormal positron emission tomography scan showing intense activity in the uterus consistent with malignancy. An exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph node staging was performed, and pathologic findings demonstrated high-grade ovarian carcinoma with serous and clear cell features. DISCUSSION: Hypercalcemia is a rare but possible primary presenting symptom of ovarian cancer. In these patients, serum calcium measurements could possibly serve as a tumor marker for disease.

Early disease progression and treatment discontinuation in patients with advanced ovarian cancer receiving immune checkpoint blockade.

OBJECTIVE: Delayed responses observed with immune checkpoint blockade (ICB) present a challenge for patients with peritoneal malignancies, who risk early symptomatic disease progression requiring treatment discontinuation. While efforts are ongoing to define the biomarkers of response, it is equally important to identify patients at risk for early discontinuation. We sought to investigate the timing of disease progression in epithelial ovarian cancer (EOC) patients treated with ICB and to identify pre-treatment clinical parameters associated with early discontinuation. METHODS: Retrospective analysis was performed on EOC patients treated with ICB at MSKCC from January 2013 to May 2017. Cutoffs for early and very early discontinuation due to disease progression were defined at 12 and 8 weeks, respectively. Univariate and multivariate logistic regression models were built based on pre-treatment clinical variables. RESULTS: Of 108 identified patients, 89 were included in the analysis. Forty-six (51.7%) patients discontinued therapy early, 30 of which (33.7%) discontinued therapy very early. Eight patients (9.0%) died within 12 weeks of ICB initiation from disease progression. In multivariate analyses, bulky peritoneal disease (p = 0.009, OR: 4.94) and liver parenchymal metastases (p = 0.001, OR: 8.08) were associated with early discontinuation. Liver parenchymal metastases (p = 0.001, OR 6.64), and high neutrophil-to-lymphocyte ratio (p = 0.021, OR: 3.54), were associated with very early discontinuation. CONCLUSIONS: Over 50% of EOC patients suffer disease progression requiring early discontinuation of ICB. Pre-treatment prognostic clinical characteristics may identify patients at highest risk for early discontinuation due to disease progression and warrant caution in using these agents in late line patients with advanced disease.