Metformin is associated with improved clinical outcomes in patients with melanoma: a retrospective, multi-institutional study.

Background: Pre-clinical studies have shown that metformin reduces intratumoral hypoxia, improves T-cell function, and increases sensitivity to PD-1 blockade, and metformin exposure has been associated with improved clinical outcomes in various types of cancer. However, the impact of this drug in diabetic melanoma patients has not yet been fully elucidated. Methods: We reviewed 4,790 diabetic patients with stage I-IV cutaneous melanoma treated at the UPMC-Hillman Cancer Center and Memorial Sloan Kettering Cancer Center between 1996-2020. The primary endpoints included recurrence rates, progression free survival (PFS), and overall survival (OS) with and without metformin exposure. Tabulated variables included BRAF mutational status, immunotherapy (IMT) by type, and incidence of brain metastases. Results: The five-year incidence of recurrence in stage I/II patients was significantly reduced with metformin exposure (32.3% vs 47.7%, p=0.012). The five-year recurrence rate for stage III patients was also significantly reduced (58.3% vs 77.3%, p=0.013) in the metformin cohort. OS was numerically increased in nearly all stages exposed to metformin, though this did not reach statistical significance. The incidence of brain metastases was significantly lower in the metformin cohort (8.9% vs 14.6%, p=0.039). Conclusion: This is the first study to demonstrate significantly improved clinical outcomes in diabetic melanoma patients exposed to metformin. Overall, these results provide further rationale for ongoing clinical trials studying the potential augmentation of checkpoint blockade with metformin in advanced melanoma.

Paratesticular leiomyosarcoma with metastasis to the extremities and lungs.

Paratesticular leiomyosarcoma is a rare malignant tumor deriving from the smooth muscle of structures surrounding the testes, including the epididymis or scrotum. With few cases of genitourinary soft tissue sarcomas reported in the literature, little is known about progression, management, and treatment. Herein, we report a case of metastatic paratesticular leiomyosarcoma in a 47-year-old male with no past urological history. The patient initially presented with a firm, painless right scrotal mass, and ultimately developed soft tissue and pulmonary metastases.

Is Calcium Score in the Abdominal Aorta or Renal Arteries Predictive of Acute Kidney Injury After Cardiopulmonary Bypass: An Exploratory Study.

Introduction Acute kidney injury (AKI) remains a serious complication after surgery with cardiopulmonary bypass (CPB). A relationship similar to the one between coronary artery calcification and increased incidence of cardiac complications is hypothesized to exist for aortic calcification and the development of AKI. Elevated pulse pressure (PP) hypertension has been shown to be a predictor of AKI-CPB (AKI after CPB surgery), and calcium deposition and stiffening of the body's conduit arteries may be part of this process. We hypothesized that calcium scores obtained from non-contrast computed tomography (CT) scans of the infrarenal aorta and renal arteries would be independently and significantly associated with AKI-CPB. Methods We conducted a retrospective study of 65 subjects who underwent non-emergent open heart surgery with CPB in a tertiary healthcare center. AKI-CPB was diagnosed using the Acute Kidney Injury Network criteria. Aortic and renal artery calcium (Agatston) scores were obtained and entered into a multivariable logistic regression model alongside other significant predictors of AKI-CPB from a univariable analysis. Results Pulse pressure, body surface area, and pre-operative serum creatinine were significantly associated with the development of AKI-CPB, but the calcium scores were not. For PP, the odds ratio (OR) was 1.062, (95% Wald confidence interval {CI}=1.012 - 1.114). The OR for the calcium score in the aorta was 1.0000 (95% CI=1.0 - 1.0). Conclusions Agatston calcium scores in the renal arteries and infrarenal aorta were not independently associated with AKI-CPB, but arterial stiffening, as indicated by elevated pulse pressure, was predictive of AKI-CPB.

Demographics and Medical Comorbidities as Risk Factors for Increased Episode of Care Costs Following Lumbar Fusion in Medicare Patients.

The objective was to evaluate medical comorbidities and surgical variables as independent risk factors for increased health care costs in Medicare patients undergoing lumbar fusion. Care episodes limited to lumbar fusions were retrospectively reviewed on the Centers of Medicare and Medicaid Innovation (CMMI) Bundled Payment for Care Improvement (BPCI) reimbursement database at a single academic institution. Total episode of care cost was also collected. A multivariable linear regression model was developed to identify independent risk factors for increased total episode of care cost, and logistic models for surgical complications and readmission. A total of 500 Medicare patients were included. Risk factors associated with increased total episode of care cost included transforaminal interbody fusion (TLIF) and anterior lumbar interbody fusion (ALIF) (ß = $5,399, P < 0.001) and ALIF+PLF (AP) fusions (ß = $24,488, P < 0.001), levels fused (ß = $3,989, P < 0.001), congestive heart failure (ß = $6,161, P = 0.022), hypertension with end-organ damage (ß = $10,138, P < 0.001), liver disease (ß = $16,682, P < 0.001), inpatient complications (ß = $4,548, P = 0.001), 90-day complications (ß = $10,012, P = 0.001), and 90-day readmissions (ß = $15,677, P < 0.001). The most common surgical complication was postoperative anemia, which was associated with significantly increased costs (ß = $18,478, P < 0.001). Female sex (OR = 2.27, P = 0.001), AP fusion (OR = 2.59, P = 0.002), levels fused (OR = 1.45, P = 0.005), cerebrovascular disease (OR = 4.19, P = 0.003), cardiac arrhythmias (OR = 2.32, P = 0.002), and fluid electrolyte disorders (OR = 4.24, P = 0.002) were independent predictors of surgical complications. Body mass index (OR = 1.07, P = 0.029) and AP fusions (OR = 2.87, P = 0.049) were independent predictors of surgical readmission. Among medical comorbidities, congestive heart failure, hypertension with end-organ damage, and liver disease were independently associated with a significant increase in total episode of care cost. Interbody devices were associated with increased admission cost.

Carcinosarcoma of the parotid gland with mucoepidermoid carcinoma component.

Carcinosarcoma is a biphasic malignant tumor composed of both carcinomatous and sarcomatous components. First cited in 1951 [1], there have been few cases of this malignant mixed tumor described in the literature. The typical patient presentation is that of an enlarging facial mass in the area of the parotid gland. Systemic symptoms are often absent. Time to initial presentation ranges from months to years. Physical examination findings include swelling and enlargement in the area of the parotid gland, facial nerve deficits, and possible cervical lymphadenopathy. Routine laboratory values (eg, blood counts and electrolytes) usually remain normal, however, nonspecific inflammatory markers (eg, erythrocyte sedimentation rate) may be elevated. Often times the first step in diagnostic evaluation is computed tomography scan with intravenous contrast. Computed tomography of the head/neck can identify malignant features such as poorly defined margins and calcifications. Magnetic resonance imaging is often performed to better evaluate for soft tissue and perineural invasion. It is important to note that these tumors can be mistaken for abscesses on imaging [2]. Ultimately pathological evaluation with immunohistochemical analysis is required to confirm the diagnosis. We present a case of a 70-year-old male who initially presented with a painless neck mass. To the best of our knowledge, this is the first case of mucoepidermoid carcinoma associated with carcinosarcoma reported in the parotid gland.