Pulmonary large cell neuroendocrine carcinoma (LCNEC): a population-based study addressing recent molecular-genetic advances and emerging therapeutic approaches.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. METHODS: Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000-2018. RESULTS: In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2 years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3-18.8) and 21.9% (95% CI 20.5-23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27-43). Age > 60 years, male gender, size > 7 cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. CONCLUSION: Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2 years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer.

Pain Management in Oncology Patients Amidst the Opioid Epidemic: How To Minimize Non-Medical Opioid Use.

The opioid epidemic continues to be a significant public health concern. On the surface, it appears difficult to understate the profound consequences and unnecessary loss of life at the hands of the opioid crisis throughout the 2010s. This reality should not dissuade rigorous attention toward those who have suffered unnecessarily due to an overreaching backlash toward the opioid crisis. Oncology patients have been significantly impacted on both ends of the opioid crisis. Like other populations, cancer patients were first affected during the initial surge of opioid availability, prescription, and use at the beginning of the crisis, where opioid abuse and overdose negatively impacted cancer patient populations at similar rates as the general population. Yet, cancer patients were perhaps even more heavily affected during secondary events after the initial crisis, as opioid restrictions and the stigmatization, undoubtedly beneficial in many spaces, of opioid use became prevalent across the American society. During this second period of the opioid crisis (loosely from 2013 to the present day after the Veterans Health Administration Opioid Safety Initiative started), restrictions on opioids have significantly decreased the use and access of opioids for cancer patients. Management of pain, in general, is a complex topic, and cancer pain is no exception. Cancer patients may experience pain related to the disease itself, its treatment, or other comorbidities. This review aims to clarify the impact of reducing opioid use on cancer patients over the past eight years. We summarize the challenges facing providers as they attempt to manage cancer-related pain. Additionally, we propose tools for best practices to reduce the unnecessary suffering of cancer patients and protect against the overuse and abuse of opioids.

Validation of a New North American Islet Donor Score for Donor Pancreas Selection and Successful Islet Isolation in a Medium-Volume Islet Transplant Center.

The selection of optimal pancreas donors is one of the key factors in determining the ultimate outcome of clinical islet isolation. North American Islet Donor Score (NAIDS) allows for estimating the chance of the success of islet isolation. It was developed based on the data from over 1000 donors from 11 islet isolation centers and validated in the University of Alberta, Edmonton, on the cohort from the most active islet transplant center. Now we aimed to also validate it in our much less active program. Areas under the receiver operating characteristic curves (AUROCs) and logistic regression analyses were obtained to test if NAIDS would better predict successful islet isolation (defined as post-purification islet yield >400,000 islet equivalents (IEQ)) than previously described Edmonton islet donor score (IDS) and our modified version of IDS. We analyzed the donor scores with reference to 82 of our islet isolation outcomes. The success rate increased proportionally as NAIDS increased, from 0% success in NAIDS < 50 points to 40% success in NAIDS ≥ 80 points. AUROCs were 0.67 (95% confidence interval (CI) 0.55-0.79) for NAIDS, 0.58 (95% CI 0.44-0.71) for modified IDS, and 0.51 (95% CI 0.37-0.65) for IDS and did not differ significantly. However, based on logistic regression analyses, NAIDS was the only statistically significant predictor of successful isolation (p = 0.01). The main advantage of NAIDS is an enhanced ability to discriminate poor-quality donors than previously used scoring systems at University of Chicago, with 0% chance for success when NAIDS was <50 as compared with 40% success rate for IDS <50. NAIDS was found to be the most useful available tool for donor pancreas selection in clinical and research practice in our center, allowing for identification and rejection of poor-quality donors, saving time and resources.

Utilization of leukapheresis and CD4 positive selection in Treg isolation and the ex-vivo expansion for a clinical application in transplantation and autoimmune disorders.

Adoptive transfer of T regulatory cells (Tregs) is of great interest as a novel immunosuppressive therapy in autoimmune disorders and transplantation. Obtaining a sufficient number of stable and functional Tregs generated according to current Good Manufacturing Practice (cGMP) requirements has been a major challenge in introducing Tregs as a clinical therapy. Here, we present a protocol involving leukapheresis and CD4+ cell pre-enrichment prior to Treg sorting, which allows a sufficient number of Tregs for a clinical application to be obtained. With this method there is a decreased requirement for ex- vivo expansion. The protocol was validated in cGMP conditions. Our final Treg product passed all release criteria set for clinical applications. Moreover, during expansion Tregs presented their stable phenotype: percentage of CD4+CD25hiCD127- and CD4+FoxP3+ Tregs was > 95% and > 80%, respectively, and Tregs maintained proper immune suppressive function in vitro. Our results suggest that utilization of leukapheresis and CD4 positive selection during Treg isolation improves the likelihood of obtaining a sufficient number of high quality Treg cells during subsequent ex-vivo expansion and they can be applied clinically.