New-Onset Autoimmune Diabetes Mellitus Presenting As Diabetic Ketoacidosis in Association With Pembrolizumab Therapy and Long Term Follow-Up: Case Report.

Pembrolizumab, an immune checkpoint inhibitor (ICI) that acts against receptor programmed cell death-1 (PD-1), is currently being used in the treatment of a variety of cancers. As PD-1 is also present on other non-malignant tissues, this results in side effects involving a multitude of organ systems termed immune-related adverse effects (irAEs). Programmed cell death-1 is expressed on the beta cells of islets of the pancreas, and their destruction can result in hyperglycemia and the onset of new diabetes mellitus (DM). Thus, the anti-PD1 action of pembrolizumab can lead to autoimmune-related DM. We present a case of a 62-year-old male who developed new-onset DM after 12 cycles of pembrolizumab with a severe presentation in the form of diabetic ketoacidosis (DKA) and ICU stay. Our case underscores the importance of physician awareness, frequent lab monitoring and patient education about this rare but potentially fatal irAE of ICI. It also strengthens existing data in literature suggesting the association of irAEs with improved efficacy of ICI therapy.

Incidental Finding of Squamous Cell Carcinoma on a 68Ga-DOTATATE PET Scan.

Neuroendocrine tumors (NETs) are a relatively rare entity; however, the incidence and prevalence of these tumors are increasing, likely attributed to improved diagnostic accuracy. The diagnosis of suspected NETs is facilitated by clinical symptoms, laboratory test abnormalities such as elevated chromogranin-A, and other diagnostic modalities such as the use of computed tomography scans, magnetic resonance imaging scans, positron emission tomography (PET) scans, and biopsy. The expression of high levels of somatostatin receptors in NETs enables the use of a specialized PET scan using the radiolabeled somatostatin analogues 68Ga-DOTATATE. The sensitivity and specificity of 68Ga-DOTATATE PET is very high for the diagnosis of NETs, but the specificity decreases especially with no clear symptoms and with only borderline elevated tumor markers. We present a case of a suspected NET, which was initially diagnosed as a metastatic NET by virtue of a positive 68Ga-DOTATATE PET scan; however, on biopsy it was revealed to be a squamous cell carcinoma originating from the head and neck.

A Case of De Novo Psoriasis Secondary to Nivolumab in a Patient With Metastatic Renal Cell Carcinoma.

Immune-mediated adverse events are commonly seen with immune checkpoint inhibitors like nivolumab. Oncology specialists usually have to screen patients for risk factors for autoimmune diseases, since immune checkpoint inhibitors can potentially exacerbate these events. Some of the immune-mediated side effects include polyneuropathies, colitis, and cutaneous adverse effects. Non-specific maculopapular rash, pruritus, lichenoid reactions, eczema, and vitiligo are the most common dermatologic side effects. It is thought that these adverse events are due to the blocking of the programmed cell death protein-1 (PD-1) pathway and are mediated by the cytotoxic T cells. Psoriasis has been previously reported as a side effect in a few case reports and most commonly presented as an exacerbation of preexisting psoriasis. However, de novo psoriasis occurrence as a result of nivolumab is a rare entity, especially in a non-melanoma patient. Here, we present a case of renal cell carcinoma treated with immunotherapy with nivolumab, who developed de novo psoriasis with palmoplantar involvement.

Review of Bone Modifying Agents in Metastatic Breast Cancer.

Bone is the most common site for distant metastases in breast cancer and can cause significant morbidity and mortality. Bone modifying agents (BMAs) that include bisphosphonates (BPAs) and denosumab help in decreasing and delaying skeletal-related events (SREs) associated with metastatic breast cancer. BPAs approved for use by the Food and Drug Administration (FDA) in bone metastases (BM) in the United States are pamidronate and zolendronic acid, while clodronate and ibandronate are licensed for use in other countries. Current American Society of Clinical Oncology (ASCO) guidelines recommend denosumab 120 mg subcutaneously every four weeks, or zolendronic acid 4 mg every four weeks or every 12 weeks, or intravenous pamidronate 90 mg every four weeks. Current guidelines do not recommend one BMA over another, however, zolendronic acid and denosumab were the most commonly used BMAs in population-based studies. Side effects of BMAs include acute phase reactions, hypocalcemia, nephrotoxicity, osteonecrosis of jaw, etc. While other side effects are common with both BPAs and denosumab, the latter has less nephrotoxic potential and is preferred for use in patients with renal failure. Current ASCO guidelines recommend continuing BMAs indefinitely, however, in clinical practice, this decision needs to be individualized, especially since there is no data on the impact of long-term use of BMAs. Further studies would need to be developed to develop an algorithm of SRE risk assessment and to determine which patients would benefit from BMAs.

Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma.

Background Hepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade. Methods We derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors. Results A total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities. Conclusions In this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.