Head and neck oncology management in the time of COVID-19: results of a head and neck cancer center

Purpose Given the concerns about the effects of the COVID-19 pandemic on cancer care, we analyzed the treatment quality of the head and neck cancer center Regensburg before and throughout 2 years of the pandemic. We included data of 3 years to reflect the extended pandemic period as new developments continued to influence its course. Methods This retrospective review included all patients diagnosed with head and neck cancer in 2019, 2020, and 2021 who had not started treatment elsewhere prior to being referred to the head and neck cancer center. We compared tumor characteristics and times to therapy of patients diagnosed before COVID-19 in 2019 (n = 253), during COVID-19 in 2020 (n = 206), and in a phase of partial normalization in a persistent pandemic situation in 2021 (n = 247). Results Our data revealed no decrease in diagnoses or drift in stages toward more advanced stages. There was an increased percentage of diagnoses confirmed at the head and neck cancer center from 2019 (57.3%) to 2020 (68.0%) and to 2021 (65.6%) compared to confirmation at other institutions (2019, 42.7%; 2020, 32.0%; 2021, 34.4%; P = 0.041). Surgery and radiotherapy were performed with the same frequency. The median days between diagnosis and surgery were decreased in 2020 (19.5 days; P = 0.049) and 2021 (20.0 days; P = 0.026) in comparison to 2019 (23 days). The days to radiotherapy were not affected. Conclusion The data indicate a consistent oncological performance for head and neck cancer patients in all waves of the pandemic and thereafter without a decrease in diagnoses or shift in stages

PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC)

Essays on Institutional and Macroeconomic Aspects of International Trade

Thesis (Ph.D.)--University of Washington, 2014The overarching theme of this dissertation is the analysis of institutional and macroeconomic factors that shape and interact with international trade. Chapters 1, 2 and 4 of this dissertation examine how institutional arrangements impact trade policy decisions and bilateral trade flows, while chapter 3 analyzes how the structural composition of trade affects macroeconomic development. Chapters 1 and 2 focus on the emergence of trade disputes in the World Trade Organization (WTO). Starting out in chapter 1 with a thorough stylized facts analysis of the usage pattern of the WTO dispute settlement mechanism, chapter 2 develops and empirically tests a model of members' selection into WTO disputes which can account for a number of key discoveries in the data. In particular, I extend the standard WTO theory by incorporating a link between endogenous trade policy formation and agreement violation and dispute filing decisions. I show that countries are more likely to engage in trade disputes as complainants or defendants when they have a small ``tariff overhang'', which represents the difference between bound tariffs (by WTO negotiations) and the actually applied tariffs. Chapter 3 considers the question whether the structure of a nation's trade flows has a clear-cut effect on economic growth. In the growth determinants literature, numerous alternative candidate regressors have been motivated by alternative theories but not one trade regressor has been robustly related to growth. Instead of relying on aggregate trade measures as previous studies, chapter 3 proposes a structured approach and examines the diversity of sectoral exports as a potential growth determinant. Controlling for model uncertainty and endogeneity, chapter 3 shows that export diversity serves as a crucial growth determinant for low income countries, an effect that weakens with the level of development. Chapter 4 examines to what extent underlying differences in the design of preferential trade agreements (PTAs) are responsible for the observed heterogeneity in PTA effects on bilateral trade flows. Controlling in the estimation framework for multilateral resistance terms and bilateral heterogeneity to reduce omitted variable and endogeneity biases, chapter 4 shows that PTAs focusing on goods trade liberalization and the legal enforceability of agreement provisions are most successful in raising trade flows. Moreover, countries' efforts to harmonize product standards and other regulations decrease bilateral trade flows, at least initially. The results also show that the underlying agreement dimension effects mostly operate through the intensive margin of trade