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.

MRI features of spinal Fluorosis: Results of an endemic community screening.

OBJECTIVES: Fluorosis is endemic in many parts of the world. However community studies on MRI features of fluorosis are lacking. The aim of this study was to determine MRI features of spinal changes in a community with endemic fluorosis in the Thar Desert Pakistan. METHODOLOGY: Randomly selected adults from the Village Samorindh, district Tharparker, Sindh, Pakistan, with spinal fluorosis diagnosed on plain x-rays and raised serum fluoride levels were studied from June 2008 to January 2009. MRI was carried out on 0.5 T open magnet MRI system. Features of vertebral body, spinal ligaments, intervertebral disc, facet joints, iliac wings and other incidental findings were noted. Sclerosis was defined as low signal intensity on both T1 and T2 weighted images. RESULTS were described as mean and percentage values. RESULTS: All the studied 27 subjects complained of back ache without neurological signs. The average age was 43.33 ± 10.45 years; 21 being male (77.8%). The most frequent findings included generalized vertebral sclerosis (24, 88.8%), ligamentum flavum hypertrophy (23, 85%), anterior (20, 74%) and lateral (17, 62.9%) disc herniation, thickened longitudinal ligaments, and narrowing of spinal foramina. Hemangioma was seen in 04(14.8%). The most commonly involved level was L1-2, L4-5 and lower dorsal spine. CONCLUSION: Vertebral sclerosis, a combination of premature degeneration with anterior disc herniation and an unusually high frequency of vertebral hemangioma formed the spectrum of MRI findings in subjects with spinal fluorosis having back ache but no neurological findings.

The use of bone-modifying agents in multiple myeloma.

Multiple myeloma is a hematological neoplasm characterized by abnormal proliferation of plasma cells in the bone marrow and is usually associated with increased bone pain and skeletal-related events such as pathological fracture and/or spinal cord compression. Myeloma bone disease results in changes in the bone-marrow microenvironment evidenced by increased osteoclastic activity and/or decreased osteoblastic activity, which negatively affect quality of life. Treatment of myeloma bone disease includes bisphosphonates or denosumab (bone-modifying agents). These agents do not induce the formation of new bone or repair existing bone damage, but they can decrease bone pain and the risk of pathological fracture. While these agents improve quality of life, it is not known whether they improve overall survival. This review focuses on different classes of bone-modifying agents, their mechanisms of action, time of initiation, duration of therapy, and potential survival benefits.

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.

Sixth Nerve Palsy From Multiple Myeloma in Central Nervous System: Case Series and Review of Current Literature.

We reported two cases of the central nervous system (CNS) multiple myeloma (MM) with unusual presentation of sixth nerve palsy. The first patient developed in the setting of newly diagnosed MM and the second patient in the relapsed refractory setting. One underwent surgery, and the other received radiation. Both patients received systemic chemotherapy and noted improvement. We also performed a comprehensive literature review of previously published cases of sixth nerve palsy from MM. This review highlights the importance of recognizing this presentation of CNS multiple myeloma to avoid delays in diagnosis and to get appropriate management in time.

Feasibility of Outpatient Stem Cell Transplantation in Multiple Myeloma and Risk Factors Predictive of Hospital Admission.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. Although outpatient ASCT has been shown to be safe and feasible, the procedure is overall rare with most patients in the US undergoing inpatient ASCT. Furthermore, hospitalization rates for patients that undergo outpatient ASCT remain high. Adequate markers that predict hospitalization during outpatient ASCT are lacking, yet would be of great clinical value to select patients that are suited to outpatient ASCT. In this study we aimed to elucidate differences between planned outpatient and inpatient ASCT and further evaluated clinical characteristics that are significantly associated with hospitalization during planned outpatient hospitalization. Factors that were significantly associated with a planned inpatient ASCT included an advanced MM disease stage, worse performance status as well as non-Caucasian race, while low albumin levels and female gender were significantly associated with hospitalization during outpatient ASCT. The results of this analysis provide crucial knowledge of factors that are associated with planned inpatient ASCT and hospitalization during outpatient ASCT and could guide the treating physician in decision-making and further facilitate outpatient transplantation.