Laparoscopic adrenalectomy of pheochromocytoma following management of severe aortic stenosis with transcatheter aortic valve replacement under monitored anesthesia care sedation: a case report.

BACKGROUND: Management of a patient with an active pheochromocytoma and severe aortic stenosis remains controversial. Adrenalectomy for a pheochromocytoma poses a high risk for stroke, hypertensive emergency, and mortality, compounded by the cardiovascular instability of severe aortic stenosis. In this case report, successful management of an active pheochromocytoma with concomitant severe aortic stenosis was accomplished by performing transcatheter aortic valve replacement under monitored anesthesia care prior to laparoscopic adrenalectomy. CASE PRESENTATION: An 84-year-old woman with severe aortic stenosis (valve area 0.53 cm2) presented with a symptomatic pheochromocytoma. Transcatheter aortic valve replacement was performed under monitored anesthesia care using a judicious approach of 100 mcg fentanyl total, 4 mg total of midazolam, and a background dexmedetomidine infusion. Alpha-blockade was maintained with 10 mg total of phentolamine mesylate. Laparoscopic adrenalectomy was performed after an uncomplicated postoperative course. The perioperative course for the adrenalectomy was unremarkable and the patient was hemodynamically stable. Postoperative course was uncomplicated and the patient was discharged from the hospital after 5 days. CONCLUSION: This case report demonstrated the successful approach of managing severe aortic stenosis through a transcatheter aortic valve replacement using monitored anesthesia care sedation prior to laparoscopic adrenalectomy of a symptomatic pheochromocytoma.

Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has an exceedingly low median overall survival of only 15 months. Current standard-of-care for GBM consists of gross total surgical resection followed by radiation with concurrent and adjuvant chemotherapy. Temozolomide (TMZ) is the first-choice chemotherapeutic agent in GBM; however, the development of resistance to TMZ often becomes the limiting factor in effective treatment. While O6-methylguanine-DNA methyltransferase repair activity and uniquely resistant populations of glioma stem cells are the most well-known contributors to TMZ resistance, many other molecular mechanisms have come to light in recent years. Key emerging mechanisms include the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. This review aims to provide a comprehensive overview of the clinically relevant molecular mechanisms and their extensive interconnections to better inform efforts to combat TMZ resistance.