Venous Thromboembolism in Hospitalized Melanoma Patients: Analysis from the National Inpatient Sample Database.

INTRODUCTION: The association between cancer and hyper-coagulability is well known. However, the association between melanoma and venous thromboembolism (VTE) has not been identified. METHODS: We studied the national inpatient sample (NIS) which compromise 20% of US hospitalization to better characterize melanoma and VTE. We analyzed the data between 2010 and 2014 using ICD-9 codes. RESULTS: Melanoma patients were grouped into presence/absence of VTE. Multiple logistic regression was used to obtain the odds ratio (OR) to compare the mortality of the inpatient, total charges, length of stay (LOS), and disability at discharge. A total of 61,812 melanoma patients were identified, of which 5.2% were hospitalized for VTE. The presence of VTE was associated with a remarkable higher rate of discharge with a moderate to severe disability (57.5% vs 41.4%, P<0.001), in-hospital stroke (7.6% vs 4.9%, P<0.001), and in-hospital mortality (8.8% vs 5.1%, P<0.001). Costs of hospitalization (64,720$ vs 46,606, P<0.001) and LOS (5 vs 3 days, P<0.001) were significantly higher as well in the VTE group. After adjusting for common confounder, VTE was found to be an independent predictor of mortality (OR = 1.596, 95% CI [1.399-1.821], P<0.001). CONCLUSION: In summary, melanoma patients with VTE had higher inpatient mortality, LOS, higher hospital cost, and a higher degree of disability upon discharge.

Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor.

Although genetic changes may be pivotal in the origin of cancer, cellular context is paramount. This is particularly relevant in a progenitor germ cell tumor and its differentiated mature teratoma counterpart when it concerns tumor heterogeneity and cancer dormancy in subsequent second malignancies (subsequent malignant neoplasms (SMNs)). From our tumor registry database, we identified 655 testicular germ cell tumor (TGCT) patients who developed SMNs between January 1990 and September 2018. Of the 113 solid organ SMNs, 42 had sufficient tumor tissue available for fluorescence in situ hybridization (FISH) analysis of isochromosome 12p [i(12p)]. We identified seven additional patients for targeted DNA and RNA sequencing of teratomas and adjacent somatic transformation. Finally, we established cell lines from freshly resected post-chemotherapy teratomas and evaluated the cells for stemness expression by flow cytometry and by the formation of teratomas in a xenograft model. In our cohort, SMNs comprising non-germ cell tumors occurred about 18 years after a diagnosis of TGCT. Of the 42 SMNs examined, 5 (12%) contained i(12p) and 16 (38%) had 12p gain. When comparing a teratoma and adjacent somatic transformation, targeted DNA and RNA sequencing demonstrated high concordance. Studies of post-chemotherapy teratoma-derived cell lines revealed cancer-initiating cells expressing multipotency as well as early differentiation markers. For the first time, we demonstrated the prevalence of i(12p) in SMNs and the presence of progenitor cells embedded within mature teratomas after chemotherapy. Our findings suggest a progenitor stem-like cell of origin in SMN and TGCT and highlight the importance of cellular context in this disease.