Myeloma Bone Disease: A Comprehensive Review.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells in the bone marrow microenvironment, characterized by overproduction of heavy- and light-chain monoclonal proteins (M-protein). These proteins are mainly found in the serum and/or urine. Reduction in normal gammaglobulins (immunoparesis) leads to an increased risk of infection. The primary site of origin is the bone marrow for nearly all patients affected by MM with disseminated marrow involvement in most cases. MM is known to involve bones and result in myeloma bone disease. Osteolytic lesions are seen in 80% of patients with MM which are complicated frequently by skeletal-related events (SRE) such as hypercalcemia, bone pain, pathological fractures, vertebral collapse, and spinal cord compression. These deteriorate the patient's quality of life and affect the overall survival of the patient. The underlying pathogenesis of myeloma bone disease involves uncoupling of the bone remodeling processes. Interaction of myeloma cells with the bone marrow microenvironment promotes the release of many biochemical markers including osteoclast activating factors and osteoblast inhibitory factors. Elevated levels of osteoclast activating factors such as RANK/RANKL/OPG, MIP-1-α., TNF-α, IL-3, IL-6, and IL-11 increase bone resorption by osteoclast stimulation, differentiation, and maturation, whereas osteoblast inhibitory factors such as the Wnt/DKK1 pathway, secreted frizzle related protein-2, and runt-related transcription factor 2 inhibit osteoblast differentiation and formation leading to decreased bone formation. These biochemical factors also help in development and utilization of appropriate anti-myeloma treatments in myeloma patients. This review article summarizes the pathophysiology and the recent developments of abnormal bone remodeling in MM, while reviewing various approved and potential treatments for myeloma bone disease.

Adequate lymph node evaluation in the elderly is associated with improved survival in patients with stage I-III colon cancer: A validation study using the National Cancer Data Base.

BACKGROUND: Lymph node involvement (LNI) is an important prognostic factor in colon cancer. But, variations in LNI among different age groups are less known. Adequate lymph node evaluation (LNE) requires assessment of ≥12 nodes. In our previous study, using Surveillance, Epidemiology and End Results (SEER) data, we demonstrated that older patients are less likely to have LNI (Khan et al. 2014). Our current study validates those findings using National Cancer Data Base (NCDB). METHODS: NCDB was queried for patients diagnosed with stages I-III colon adenocarcinoma from 2004 to 2008 who underwent surgical resections. Pearson Chi-square test and Cox proportional hazards regression model were utilized for statistical analysis. RESULTS: A cohort of 97,831 patients was identified for analysis. Among patients belonging to 18-64, 65-74 and >75 years age groups, frequency of adequate LNE was 73.6%, 69% and 67.4% respectively, with pathologically confirmed LNI rates being 44.7%, 37.8% and 29.3% respectively (p < 0.0001). Adequate LNE was associated with improved 5-year overall survival (OS) regardless of age, gender, race, comorbidity index, insurance, income, year of diagnosis, pathologic tumor status, stage, grade, type of colectomy, adjuvant chemotherapy or academic level of facility. Rates of adequate LNE increased from 2004 to 2008, with a corresponding increase in survival outcomes (p < 0.0001). CONCLUSION: Adequate LNE is very crucial for appropriate staging of colon cancer, and carries a high prognostic value. This study validates our previous findings of lower rates of LNI in elderly and reiterates the importance of adequate LNE, which is associated with improved survival. Also identified were increasing rates of adequate LNE over the years, with corresponding improvement in OS.

A case of Hodgkin's lymphoma with severely impaired liver function treated successfully with gemcitabine followed by ABVD.

Hodgkin's lymphoma (HL) originates from clonal B cells and is the most common malignancy in the second decade of life. Liver involvement is uncommon at presentation in patients with HL and there is a paucity of data for treatment of patients with severely impaired liver function. We present an unusual case of HL with severe hepatic impairment, splenomegaly and multiple chromosomal abnormalities that was treated initially with gemcitabine and steroids. Once liver function tests improved, six cycles of Adriamycin, bleomycin, vinblastine, and dacarbazine were administered. The patient remains in remission at 3.5 years of follow-up.