Faculty Bibliography

PURPOSE/OBJECTIVE:To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery. BACKGROUND:Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC. METHODS:International multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). Primary endpoint is OS from diagnosis. Time-dependent Cox regression analysis was performed to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at time of diagnosis. Adjusted OS probabilities were calculated. RESULTS:=0.96) involvement. CONCLUSIONS:Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared to upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

BACKGROUND:Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neuroendocrine tumors. PitNETs can be challenging to classify, and current recommendations include a large immunohistochemical panel to differentiate among 14 WHO-recognized categories. METHODS:In this study, we analyzed clinical, immunohistochemical and DNA methylation data of 118 PitNETs to develop a clinico-molecular approach to classifying PitNETs and identify epigenetic classes. RESULTS:CNS DNA methylation classifier has an excellent performance in recognizing PitNETs and distinguishing the three lineages when the calibrated score is ≥0.3. Unsupervised DNA methylation analysis separated PitNETs into two major clusters. The first was composed of silent gonadotrophs, which form a biologically distinct group of PitNETs characterized by clinical silencing, weak hormonal expression on immunohistochemistry, and simple copy number profile. The second major cluster was composed of corticotrophs and Pit1 lineage PitNETs, which could be further classified using DNA methylation into distinct subclusters that corresponded to clinically functioning and silent tumors and are consistent with transcription factor expression. Analysis of promoter methylation patterns correlated with lineage for corticotrophs and Pit1 lineage subtypes. However, the gonadotrophic genes did not show a distinct promoter methylation pattern in gonadotroph tumors compared to other lineages. Promoter of the NR5A1 gene, which encodes SF1, was hypermethylated across all PitNETs clinical and molecular subtypes including gonadotrophs with strong SF1 protein expression indicating alternative epigenetic regulation. CONCLUSION/CONCLUSIONS:Our findings suggest that classification of PitNETs may benefit from DNA methylation for clinicopathological stratification.

In patients with cancer, spontaneous renal bleeding can stem from a range of underlying factors, necessitating precise diagnostic tools for effective patient management. Benign and malignant renal tumors are among the primary culprits, with angiomyolipomas and renal cell carcinomas being the most common among them. Vascular anomalies, infections, ureteral obstructions, and coagulation disorders can also contribute to renal-related bleeding. Cross-sectional imaging techniques, particularly ultrasound and computed tomography (CT), play pivotal roles in the initial detection of renal bleeding. Magnetic resonance imaging and CT are preferred for follow-up evaluations and aid in detecting underlying enhancing masses. IV contrast-enhanced ultrasound can provide additional information for active bleeding detection and differentiation. This review article explores specific disorders associated with or resembling spontaneous acute renal bleeding in patients with renal tumors; it focuses on the significance of advanced imaging techniques in accurately identifying and characterizing renal bleeding in these individuals. It also provides insights into the clinical presentations, imaging findings, and treatment options for various causes of renal bleeding, aiming to enhance the understanding, diagnosis, and management of the issue.

BACKGROUND/OBJECTIVES/OBJECTIVE:Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is rapidly becoming the most prevalent form of chronic liver disease in both pediatric and adult populations. It encompasses a wide spectrum of liver abnormalities, ranging from simple fat accumulation to severe conditions such as inflammation, fibrosis, cirrhosis, and liver cancer. Major risk factors for MASLD include obesity, insulin resistance, type 2 diabetes, and hypertriglyceridemia. METHODS:This narrative review employed a comprehensive search of recent literature to identify the latest studies on the relationship between MAFLD and obesity, the health consequences and the latest treatment options to prevent long-term damage to the liver and other organs. Additionally, the article presents perspectives on diagnostic biomarkers. RESULTS:Childhood obesity is linked to a multitude of comorbid conditions and remains a primary risk factor for adult obesity. This abnormal fat accumulation is known to have long-term detrimental effects into adulthood. Scientific evidence unequivocally demonstrates the role of obesity-related conditions, such as insulin resistance, dyslipidemia, and hyperglycemia, in the development and progression of MASLD. Oxidative stress, stemming from mitochondrial dysfunction, is a leading factor in MASLD. This review discusses the interconnections between oxidative stress, obesity, dyslipidemia, and MASLD. CONCLUSIONS:Atherogenic dyslipidemia, oxidative stress, inflammation, insulin resistance, endothelial dysfunction, and cytokines collectively contribute to the development of MASLD. Potential treatment targets for MASLD are focused on prevention and the use of drugs to address obesity and elevated blood lipid levels.

While the advent of chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed or refractory DLBCL, it is unclear how survival has changed at the population level following its approval. Herein, we performed a population-based cohort study using the SEER-17 database. The primary exposure was a period of diagnosis (2014-2017 vs. 2018-2021), and these periods were selected based on the first FDA-approval of CAR-T in 2017. Study outcomes were relative survival (RS), overall survival (OS), lymphoma-specific survival (LSS), and the cumulative incidence of death from lymphoma (CIF). A total of 51,584 patients with DLBCL were included in the study with 24,861 patients diagnosed in time period-1 (2014-2017) and 26,723 patients diagnosed in time period-2 (2018-2021). The median age at diagnosis was 68 years (interquartile range, 57-77) and most patients were White (n = 42,190, 82%) with advanced stage at diagnosis (n = 28,203, 55%). In unadjusted analysis, the 5-year RS (95% CI) increased from 64% from 2014 to 2017 to 66% from 2018 to 2021, while 5-year OS increased from 54 to 55%, and 5-year LSS increased from 64 to 66%. On competing risks analysis, the 5-year probability of death from lymphoma decreased from 34 to 31%. The improvements in survival were observed across age, disease stage, and racial groups, and remained significant when adjusting for age, sex, race, stage, B symptoms and documented receipt of chemotherapy in multivariable survival models (adjusted OS HR = 0.97, 95%CI = 0.94-1.00, p = 0.04; adjusted LSS HR = 0.93, 95%CI = 0.90-0.96, p < 0.001). We found improved survival for patients with DLBCL diagnosed between 2018 and 2021 when compared to those diagnosed between 2014 and 2017. These findings will serve as the benchmark for future studies evaluating the impact of CAR-T administered earlier in their disease course.

PURPOSE/OBJECTIVE:The dermatological management of cancer patients with cutaneous adverse events occurring during and after oncologic treatment is known as supportive oncodermatology. This includes prevention, early identification, and mitigation of dermatologic toxicities. The aim of the international RESCUE (Residents' survey on training of dermatology residents in supportive oncodermatology) study was to ascertain the current level of expertise in supportive oncodermatology among dermatology residents. METHODS:The European Task Force "Dermatology for cancer patients" and the US Oncodermatology Society developed an online questionnaire with 30 multiple-choice items. Responses were collected using qualitative ordinal data (yes/no, 1-5 ratings) and multiple-choice options. Ordinal range results were analyzed by aggregating responses 1 + 2 + 3 versus 4 + 5, with 5 representing the highest grade ("extremely confident" or "full training"). RESULTS:A total of 442 dermatology residents from 20 countries replied. These participants reported receiving less comprehensive training in supportive oncodermatology (only 41% receiving complete training) compared to immunodermatology (75%), cutaneous oncology (75%), dermoscopy (64%), and dermatologic surgery (50%). Only 17% of the residents reported feeling confident in managing the dermatological toxicities associated with anticancer treatments. Residents also indicated receiving less education regarding toxicities related to endocrine therapies (28%). In particular, lower levels of competence were reported in managing nail, hair, and oral toxicities. A significant majority of residents (98%) deemed it essential to enhance training in dermatological toxicities associated with anticancer therapies during their oncology residency. CONCLUSION/CONCLUSIONS:The RESCUE study represents the first project assessing residents' education in supportive oncodermatology. To enable future generations of dermatologists to provide enhanced care for cancer patients, supportive oncodermatology training should be integrated in residency programs worldwide, corresponding to training in other subspecialties. A more practical approach should also be incorporated, including extended training in hair, nail, and oral toxicities, enhancing the competencies of dermatology residents in all countries.

BACKGROUND/UNASSIGNED:Patients with bicuspid aortic stenosis who receive transcatheter aortic valve replacement (TAVR) may require subsequent valve interventions in their lifetime; however, the feasibility of redo-TAVR in this population is uncertain. We aimed to assess redo-TAVR feasibility in bicuspid patients and develop a predictive virtual valve planning algorithm. METHODS/UNASSIGNED:We studied computed tomography scans of bicuspid patients who received a balloon-expandable transcatheter heart valve (THV) in the LRT trial (Low Risk TAVR). Redo-TAVR feasibility, determined by valve-to-coronary and valve-to-aorta measurements on 30-day computed tomography, was assessed according to raphe location and calcification. A virtual valve planning algorithm was developed using baseline and 30-day computed tomography scans. RESULTS/UNASSIGNED:<0.001) due to favorable shifting of the THV away from the coronary ostia. A bicuspid virtual planning algorithm accounting for 83.4% THV underexpansion, resulting in an 11.9% taller frame and translation of the THV away from the calcified raphe (mean valve shift 6.6 mm) achieved 86.7% sensitivity and 88.9% specificity for predicting redo-TAVR feasibility. CONCLUSIONS/UNASSIGNED:Calcified raphe in left/right cusp fusion shifts the THV away from the coronary ostia, reducing coronary obstruction risk during redo-TAVR. Underexpansion causing increased THV frame height and valve shifting is common in bicuspid patients; a virtual planning algorithm accounting for these aspects can accurately assess redo-TAVR risk. REGISTRATION/UNASSIGNED:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02628899.

OBJECTIVE:Social determinants of health (SDOH) may impact the incidence of Respiratory Syncytial Virus (RSV) infection and the uptake of vaccinations in pregnancy. The objective of this study is to identify contributors to disparities in RSV vaccination in pregnancy. DESIGN/METHODS:This is a retrospective cohort study of patients delivering at term within three hospitals during February and March 2024, comparing pregnant patients identified as receiving vs not receiving RSV vaccinations. This period and gestational age were chosen to include patients who would have qualified for RSV vaccination administration. Vaccination status was extracted from standardized admission templates where these variables were recorded as discrete fields. Patients without RSV vaccination information were excluded. Sociodemographic factors, COVID vaccination status, and delivery campus were evaluated. Outcomes were analyzed using chi-squared, t-test, and McNemar test. RESULT/RESULTS:2181 patients met inclusion criteria and RSV vaccination information was available for 1548 patients (71%) with a 14% vaccination rate. Compared to those not vaccinated (n=1332), RSV vaccinated patients (n=216) were more likely to be older (30.7 vs 34.8, p<0.001), have private insurance (42% vs 85%, p<0.001), speak English (82% vs 95%, p<0.001), and deliver at our regional perinatal center (26% vs 77%, p<0.001). 50% of RSV vaccinated patients had a history of COVID vaccination compared to 33% of those not vaccinated against RSV (p<0.001). CONCLUSIONS:SDOH were associated with differences in RSV vaccination status. In addition, patients without RSV vaccination were less likely to have had COVID vaccination. These findings highlight the need to address SDOH to increase vaccination rates for vulnerable populations.