ABSTRACT
Although immunotherapy has revolutionized cancer care, there is still an urgent need to enhance its efficacy and ensure its safety. A correct cancer theory and proper scientific method empower pertinent cancer research and enable effective and efficient drug versus therapy development for patient care. In this perspective, we revisit the concept of immune privilege in a cancer cell versus normal cell, as well as in a cancer stem cell versus normal stem cell. We re-examine whether effective immunotherapies are efficacious due to their anti-cancer and/or immune modulatory mechanisms. We reassess why checkpoint inhibitors (CPIs) are not equal. We reconsider whether one can attribute the utility of immunotherapy to specific cancer subtypes and its futility to certain tumor/immune compartments, components, and microenvironments. We propose ways and means to advance immunotherapy beyond CPIs by combining anti-PD1/L1 with various other treatment modalities according to an appropriate scientific theory, e.g., stem cell origin of cancer, and based on available clinical evidence, e.g., randomized clinical trials. We predict that a stem cell theory of cancer will facilitate the design of better and safer immunotherapy with improved selection of its use for the right patient with the right cancer type at the right time to optimize clinical benefits and minimize potential toxic effects and complications.
ABSTRACT
Background: Intracavernosal injection of phenylephrine is a commonly used therapy for ischemic priapism and is typically well tolerated with few severe adverse side effects. We report a case of intracranial hemorrhage related to hypertensive emergency due to intracavernosal phenylephrine. Case Report: A 43-year-old Caucasian man with history of hypertension, diabetes mellitus type I, end-stage renal disease status post a combination kidney-pancreas transplant, and recurrent idiopathic priapism presented to emergency department with an episode of priapism. His home medications were lisinopril, metoprolol tartrate, mycophenolate mofetil, prednisone, sulfamethoxazole-trimethoprim, and tacrolimus. After local injection of 2 rounds (1 hour apart) of 100 µg phenylephrine into each corpus cavernosa, priapism resolved. Within 5 minutes, the patient had headaches, dyspnea, and excruciating chest pain. His blood pressure (BP) was noted to be 240/130 mm Hg but normalized spontaneously within few minutes. During this period, he developed new-onset right arm and leg weakness and found to have intracranial hemorrhage in the midbrain. Conclusion: A careful review for pharmacologic interactions should be performed prior to intracavernosal phenylephrine administration, and close monitoring should occur after its administration.
