Alpelisib-Induced Diabetic Ketoacidosis.

We present the third case of alpelisib-induced diabetic ketoacidosis. Alpelisib is an antineoplastic agent that inhibits phosphatidylinositol 3-kinase (PI3K), which plays a key role in multiple biological processes such as cell differentiation, proliferation, and survival. Thereby, the inhibition of this pathway should cause antitumor activity. Alpelisib was recently approved by the Food and Drug Administration (FDA) for use in PIK3CA-mutated breast cancer. This mutation is a common indicator of poor prognosis and is also the most commonly mutated gene in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. During its trial, ketoacidosis was reported in only 0.7% of patients, with the more common side effects (>20%) being diarrhea (58%), rash (52%), nausea (45%), fatigue (42%), decreased appetite (36%), stomatitis (30%), vomiting (27%), weight loss (27%), and alopecia (20%). As breast cancer is the second most common cancer in women and approximately 40% of HR+/HER2- advanced breast cancer patients have a PIK3CA mutation, alpelisib will be prescribed more by oncologists and, therefore, appropriate screening with fasting plasma glucose, hemoglobin A1c (HbA1C), and monitoring during drug administration is of utmost importance.

Percutaneous cryoablation of adrenal metastases: technical feasibility and safety.

PURPOSE: To assess the technical feasibility and outcomes of adrenal metastases cryoablation. MATERIALS AND METHODS: This is an IRB approved retrospective review of adrenal metastases cryoablation between April 2003 and October 2018. Forty percutaneous cryoablation procedures were performed on 40 adrenal metastases in 34 patients. Histology, tumor size, ablation zone size, major vessel proximity, local recurrences, complications, and anesthesia-managed hypertension monitoring was collected. Complications were graded according to the Common Terminology of Complications and Adverse Events (CTCAE). RESULTS: Mean tumor and ablation size was 3.2 cm and 5.2 cm, respectively. Local recurrence rate was 10.0% (N = 4/40) for a mean follow-up time of 1.8 years. Recurrences for tumors > 3 cm (21.0%, N = 4/19) was greater than for tumors ≤ 3 cm (0.0%, N = 0/21) (p = 0.027). Proximity of major vasculature (i.e., IVC & aorta) did not statistically effect recurrence rates (p = 0.52), however, those that recurred near vasculature were > 4 cm. Major complication (≥ grade 3) rate was 5.0% (N = 2/40), with one major complication attributable to the procedure. Immediate escalation of blood pressure during the passive stick phase (between freeze cycles) or post procedure thaw phase was greater in patients with residual adrenal tissue (N = 21/38) versus masses replacing the entire adrenal gland (N = 17/38), (p = 0.0020). Lower blood pressure elevation was noted in patients with residual adrenal tissue who were pre-treated with alpha blockade (p = 0.015). CONCLUSIONS: CT-guided percutaneous cryoablation is a safe, effective and low morbidity alternative for patients with adrenal metastases. Transient hypertension is related only to residual viable adrenal tissue but can be safely managed and prophylactically treated.

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer.

Involvement of the adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand biomarkers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative.Pathogenic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer.

Recurrence of Graves' disease in ectopic thyroid tissue.

A 40-year-old woman with a history of Graves' disease status postorbital decompression for severe ophthalmopathy underwent total thyroidectomy by a high volume thyroid surgeon in July 2013 with a benign final pathology. Eight months later, she presented with a mass on the right anterior neck that showed minimal growth over time. Her thyroid stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were consistently elevated and increasing. She underwent removal of the neck mass in September 2016. Final pathology showed benign thyroid tissue with diffuse hyperplasia and lymphoid follicles, consistent with Graves' disease. We present an unusual recurrence of Graves' disease post-total thyroidectomy that recurred secondary to ectopic thyroid tissue in the right upper anterior neck deep to the strap muscles.

Is this really just "fatigue"? A case series of immune-related central adrenal insufficiency secondary to immune checkpoint inhibitors.

While immunotherapy with programmed cell death protein 1 (PD1) checkpoint inhibition has shown promising activity against many tumor types, adverse events are common. Hypophysitis is a rare but serious immune-related event known to occur with anti-PD1 inhibition. It will become more prevalent as the usage of checkpoint inhibitors increases.

Sialendoscopy in the Management of Radioiodine Induced Sialadenitis: A Systematic Review.

OBJECTIVES: Salivary gland dysfunction as a consequence of radioiodide ablation is present in as many as two-thirds of patients, and unfortunately, many of these individuals do not respond to conservative measures. Sialendoscopy as a minimally invasive therapeutic modality may have utility in the treatment of radioiodide induced sialadenitis (RAIS). Our aim was to explore whether sialendoscopy resulted in clinical improvement in patients with RAIS. METHODS: A systematic review of studies on sialendoscopy for RAIS was conducted using MEDLINE database, Embase, and Cochrane Library. The outcomes of interest included the proportion of patients demonstrating clinical improvement after intervention, patient demographics, radiation dose, specific procedural variations, specific salivary gland, failure rate, and recurrence. RESULTS: Eight studies met inclusion criteria. Data reviewed showed an increased predilection of parotid sialadenitis relative to submandibular gland sialadenitis. All but 2 studies employed sialendoscopy only after failure of conservative measures. An overall rate of clinical improvement ranging from 75% to 100% was reported. CONCLUSION: This systematic review encompassing 122 patients represents the largest pooled sample to date of patients undergoing sialendoscopy for RAIS. Sialendoscopy represents an invaluable minimally invasive modality that may obviate the need for more invasive surgery as intervention was associated with a high success rate.

Glucose control and lipid metabolism in African American patients with type 2 diabetes mellitus and chronic hepatitis C viral infection.

OBJECTIVE: To compare lipid profiles and glucose control in African American patients with type 2 diabetes mellitus with and without chronic hepatitis C viral (HCV) infection. METHODS: This retrospective study conducted in an academic outpatient setting included African American patients with both type 2 diabetes and HCV, patients with HVC only, and patients with type 2 diabetes only. Serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride values were compared among all 3 patient groups. RESULTS: The study population included 283 patients, of whom 111 had type 2 diabetes and HCV, 68 had HCV only, and 104 had type 2 diabetes only. Chronic HCV was associated with lower total cholesterol and LDL-cholesterol levels in patients with or without type 2 diabetes. In contrast, elevated serum triglyceride levels associated with diabetes were not reduced in patients with chronic HCV, although diabetes control was better in the diabetes group with HCV than in the diabetes group without HCV (mean hemoglobin A1c [standard error of the mean]: 7.1% [1.8%]vs 8.8% [2.1%], P<.001). HDL cholesterol was higher in the patients with earlier stages of HCV when compared with HDL cholesterol in the other 2 groups. CONCLUSIONS: Chronic HCV infection in type 2 diabetic patients decreases serum levels of total and LDL cholesterol, but has no such protective effect on triglyceride levels. HCV infection may alter the cellular pathways of cholesterol and triglyceride metabolism in patients with type 2 diabetes.