Stem Cell Origin of Cancer: Clinical Implications beyond Immunotherapy for Drug versus Therapy Development in Cancer Care.

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.

Aplastic Anemia Mimicking Myelofibrosis: A Diagnostic Dilemma.

Hematological disorders pose a diagnostic challenge due to overlapping clinical features, as demonstrated by the difficulty in differentiating between aplastic anemia (AA) and primary myelofibrosis (PM). Myeloproliferative disorders, characterized by aberrant proliferation of bone marrow stem cells, present complexities in diagnosis, often requiring a comprehensive evaluation to distinguish between disorders with similar manifestations. The distinctions between myelofibrosis and AA lie not only in clinical presentations but also in genetic and molecular markers, necessitating a nuanced diagnostic approach. We present a case of a 37-year-old male initially diagnosed with myelofibrosis based on a history of pancytopenia, warm submandibular and submental swelling, and negative BCR-ABL and JAK2 mutations. Further examination revealed empty fragmented cells, hypoplastic bone marrow, and suppressed erythropoiesis and myelopoiesis. Subsequent core biopsy showed increased megakaryocytes, prompting a revised diagnosis of AA. This case underscores the importance of a meticulous diagnostic journey, incorporating physical examination, genetic testing, and advanced imaging to unravel the complexities of hematological disorders. The intricacies of this case prompt a reevaluation of diagnostic paradigms, highlighting the limitations of relying solely on specific mutations for diagnosis. The absence of BCR-ABL and JAK2 mutations in AA raises questions about its genetic landscape, necessitating further exploration. Immunological considerations, given the immune-mediated nature of AA, provide a foundation for future research into immune dysregulation and potential therapeutic interventions. The clinical management challenges posed by AA underscore the need for personalized treatment strategies, guided by a deeper understanding of its underlying pathophysiology. Advanced imaging techniques, in conjunction with traditional diagnostic methods, emerge as crucial tools for enhancing diagnostic accuracy in hematological disorders. This case serves as a paradigm for ongoing medical education, multidisciplinary collaboration, and innovative approaches in the evolving landscape of hematology, emphasizing the imperative for continuous refinement in diagnostic strategies and patient care.

Coronary Artery Dissection and Myocarditis Caused by Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Case Report.

Eosinophilic granulomatosis with polyangiitis (EGPA) also referred to as Churg-Strauss syndrome is a rare vasculitis of the small to medium vessels. We present a rare case of acute coronary artery dissection brought on by EGPA, which generally has a poor prognosis. A 41-year-old male with history of bronchial asthma presented to the emergency room with a 2-week history of dyspnea, cough with clear phlegm, and fever. For the past eight months he had experienced episodes with similar symptoms relieved by steroids. CT chest showed bilateral upper lobe patchy opacities with extensive workup for infectious etiology being negative. He had peripheral eosinophilia with sinusitis. He had acute coronary syndrome and Coronary angiogram showed Right coronary artery dissection. After making a diagnosis of EGPA based on American college of Rheumatology criteria, he was successfully treated with high dose immunosuppression. Coronary artery dissection is a fatal and uncommon complication of EGPA which is usually diagnosed postmortem. Early recognition of this condition ante mortem and aggressive treatment can be lifesaving as demonstrated in our case.

A Case of Herpes Simplex Virus Meningitis in an Immunocompromised Individual: Avoiding Common Diagnostic Pitfalls.

Herpes simplex virus meningoencephalitis (HSV ME) is a severe viral infection that affects the brain and surrounding tissues. It is caused primarily by HSV type 1 (HSV-1) virus. This condition requires prompt recognition and treatment due to its potential for significant morbidity and mortality. We aim to highlight the importance of avoiding common diagnostic pitfalls in identifying HSV meningoencephalitis, especially in immunocompromised individuals. We present a case of a 34-year-old immunocompromised patient with HSV meningoencephalitis, emphasizing key clinical features and diagnostic strategies that helped us reach an accurate diagnosis. By sharing this case, we aim to enhance awareness and improve the management of HSV meningoencephalitis in similar patient populations, leading to better outcomes.

Phase I Study of Pazopanib and Ixabepilone in Patients With Solid Tumors.

OBJECTIVES: Pazopanib is a tyrosine kinase inhibitor predominantly acting on tumor endothelium, and ixabepilone is a semisynthetic analog of epothilone B that promotes microtubule stabilization inducing tumor and tumor endothelial cell apoptosis. The purpose of this study was to determine the optimal tolerated dose (OTD) of the combination of pazopanib and ixabepilone for the treatment of metastatic previously treated solid tumors. METHODS: Dose escalation started at 32 mg/m of ixabepilone and increased to 40 mg/m. Pazopanib was administered initially at 400 mg and escalated at 200 mg increments up to 800 mg. Pharmacokinetic analysis assessed effect of ixabepilone on pazopanib metabolism. Correlative studies evaluated changes in angiogenic cytokines. RESULTS: Thirty-one patients (20 male and 11 female; median age, 58 y) with ECOG PS of 0 or 1 were enrolled. Three patients had dose-limiting toxicities (fatigue and neutropenia) at dose level 2 (ixabepilone 40 mg/m and pazopanib 400 mg), and therefore the ixabepilone dose was decreased (32 mg/m) before escalating pazopanib to levels 3 and 4. One patient had a dose-limiting toxicity (thrombocytopenia) at dose level 4 (ixabepilone 32 mg/m and pazopanib 800 mg). Dose level 3 was determined to be the OTD (pazopanib 600 mg and ixabepilone 32 mg/m). The most common toxicities were cytopenias. A significant decrease in the level of sE-selectin was associated with improvement in progression free survival. CONCLUSIONS: The OTD for combination of pazopanib and ixabepilone was established. There was no impact of ixabepilone on pazopanib pharmacokinetics. The relationship between sE-selectin and progression free survival warrants further investigation.

Metanephric adenoma of the kidney: an unusual diagnostic challenge.

Although metanephric adenoma (MA) is a rare, benign neoplasm of epithelial cells, it is often difficult to distinguish this entity from other malignant neoplasms preoperatively. We report a case of a large renal mass for which preoperative diagnosis was indeterminate, with the differential diagnosis including Wilm's tumor, MA, and papillary renal cell carcinoma (PRCC). Accurate postoperative differentiation of MA from PRCC is critical because adjuvant therapy is considered after surgical resection of PRCC tumors.