Morphology of the proximal femur in our study population differed significantly from those in western populations, indicating regional variation. It could also be due to the younger age of our population.
Background: Metastatic pancreatic cancer (MPC) is associated with an extremely high mortality. Current NCCN guidelines recommend systemic therapy, as it is superior to best supportive care. Undertreatment of MPC continues to be an issue. Recent treatment and survival data of MPC in Veterans' Affairs' (VA) hospitals have not been published. The relationship between MPC treatment and survival and the American College of Surgeons' (ACS) Committee on Cancer (CoC) accreditation in VA hospitals has not been studied. Methods: Nationwide data from the National Veterans Affairs Cancer Cube Registry was analyzed. In total, 6,775 patients were diagnosed with MPC between 2000 and 2014. CoC accreditation of each VA hospital was obtained using the ACS website. Results: MPC constitutes 52.31% of all pancreatic cancer diagnosed (6,775/12,951 cases). The near totality was men (97.44%). The above 70 years age group and the 60-70 years age group were the most common ages at diagnosis with 39.39% and 38.02% respectively. The proportion of early-onset pancreatic cancer (EOPC) was 2.84%. When compared to all stages of pancreatic cancer, stage IV pancreatic cancer had a lower proportion of cancer originating from the head of the pancreas (39.33% versus 50.63%) and more originating from the tail (17.99% versus 13.39%). Tumors originating from head of the pancreas are more likely to cause biliary symptoms and thus are more likely to be caught at an earlier stage. Overall, treatment rate in the VA at the national level with first-line chemotherapy was 37.61%. The rate of treatment over the years has increased in a linear fashion from 33.01% in 2000 to 41.95% in 2014. This has corresponded with an increase of 1-5 years survival of 9.29% in 2000 to 22.99% in 2014 and 5-10 years survival from 0.96% in 2000 to 6.00% in 2012. Treatment rates in CoC-accredited and non-CoC accredited VA hospitals were similar (38.94% and 38.12%, respectively). Survival rates in CoC-accredited and non-COC accredited VAs were similar with a 1-5 years survival rate of 8.89% and 8.57%, respectively. Conclusions: Treatment and survival of MPC have risen significantly in the past decade at VA hospitals.CoC accreditation is not associated with a change in treatment or survival rates.
Mucosal melanoma is a rare variant of melanoma representing around 1% of total cases of melanoma diagnosed. The usual sites of mucosal involvement are the sino-nasal passages, the oral cavity, and less commonly the upper gastrointestinal (GI) tract. It also has been reported to occur in vulvovaginal and anorectal mucosa. We present a rare case of mucosal melanoma that presented as recurrent epistaxis, headache, and sinus pressure. CT maxillofacial imaging revealed a large mass right nasal cavity. This was biopsied by ENT and shown to be mucosal melanoma. This was treated with palliative radiation followed by immunotherapy with nivolumab. Along with details of the case, we also discuss current treatment options with a focus on the role of immunotherapy and its efficacy in cases of head and neck mucosal melanoma. Our review of literature supports use of combination immunotherapy (including both nivolumab and ipilimumab) as it shows greater efficacy than either therapy alone. When combined with radiation therapy (RT) the overall response rate is improved and RT induces an abscopal effect; where benefits of RT are also seen at nonirradiated locations. In our patient, the use of radiation was essentially palliative as the patient was deemed to not be a surgical candidate. We discuss in our literature review the optimum timing of radiation in relation to definitive surgery or immunotherapy.
Death-associated protein 1 (DAP1) is a highly conserved phosphoprotein involved in the regulation of autophagy. A previous clinical study by our group suggested an association between low DAP1 expression and clinicopathological parameters of human breast cancer. In the present study, we aimed to determine the role of DAP1 in cancer cell behaviour in the context of human breast cancer. We developed knockdown sublines of MCF7 and MDA-MB‑231, and performed growth, adhesion and invasion assays and electric cell-substrate impedance sensing (ECIS) studies of the post-wound migration of cells. In addition, we studied the mRNA expression of caspase 8 and 9, DELE, IPS1, cyclin D1 and p21 in the control and knockdown sublines. Knockdown was associated with increased adhesion and migration, significantly so in the MDA-MB-231DAP1kd cell subline (p=0.029 and p=0.001, respectively). Growth in MCF7 cells showed a significant suppression on day 3 (p=0.029), followed by an increase in growth matching the controls on day 5. While no change in the apoptotic response to serum starvation could be attributed to DAP1 knockdown, the expression of known components of the apoptosis pathway (caspase 8) and cell cycle (p21) was significantly reduced in the MCF7DAP1kd cell subline (p≤0.05), while in MDA-MB-231DAP1kd the expression of a pro-apoptotic molecule, IPS1, was suppressed (p≤0.05). DAP1 may have an important role in cell adhesion, migration and growth in the context of breast cancer and has significant associations with the apoptosis pathway. Furthermore, we believe that delayed increase in growth observed in the MCF7DAP1kd cell subline may indicate activation of a strongly pro-oncogenic pathway downstream of DAP1.
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