Faculty Bibliography

INTRODUCTION/UNASSIGNED:Brain metastases (BM) are the most common malignancy in the central nervous system (CNS) and observed in approximately 30% of cancer patients. Brainstem metastases (BSM) are challenging because of their location and the associated neurological risks. There are still no general therapeutic recommendations in this setting. Stereotactic radiosurgery (SRS) is one of few possible local therapy options but limited due to the tolerance dose of the brainstem. There is still no standard regarding the optimal dose und fractionation. METHODS/UNASSIGNED:We retrospectively analyzed 65 patients with fractionated stereotactic radiotherapy (fSRT) for 69 BSM. FSRT was delivered at a dose of 30 Gy in six fractions prescribed to the 70 % isodose performed with Cyberknife. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analyzed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. RESULTS/UNASSIGNED:Median follow-up was 27.3 months. One-year TIBC was 35.0 % and one-year LC was 84.1 %. Median OS was 8.9 months. In total, local progression occurred in 7.7 % and in 8.2 % symptomatic radiation-induced contrast enhancements (RICE) were diagnosed. In univariate analysis the Karnofsky performance scale index (KPI) (p = 0,001) was an independent prognostic factor for longer OS. Acute CTCAE grade 3 toxicities occurred in 18.4 %. CONCLUSION/UNASSIGNED:FSRT for BSM is as an effective and safe treatment approach with high LC rates and reasonable neurological toxicity despite the poor prognosis in this patient cohort is still very poor. Clinical and imaging follow-up is necessary to identify cerebral progression and adverse toxicity including RICE.

INTRODUCTION/BACKGROUND:Patients with congenital heart disease (CHD) are at increased risk of cancer. In patients with CHD and advanced heart failure, isolated heart transplantation (HT) can be considered. In the overall HT population, immunosuppression after HT increases the risk of post-transplant malignancy (PTM). However, cancer outcomes among adult HT patients with CHD have not been investigated. METHODS:Patients aged ≥ 18 years who received HT between January 1, 2010 and December 31, 2021 were identified using the United Network for Organ Sharing (UNOS) registry. Patients with CHD were compared to those without. T primary outcome was a composite outcome of PTM or death due to malignancy. Multivariable Fine-Gray competing-risk regression was used to estimate the subhazard ratio (SHR) of primary and secondary outcomes. RESULTS:Of the total of 29717 patients with HT were included, 1017 (3.4%) had CHD. Patients with CHD were younger, more likely to be female, and have had prior cardiac surgery. After multivariable competing-risk regression, CHD was associated with a higher risk of the primary outcome (SHR 1.43, 95% CI 1.15-1.80). Among patients who developed PTM, the median time to diagnosis of first PTM (median 36 vs. 46 months, p = 0.027) was shorter in patients with CHD. Among patients with CHD, survival after PTM was significantly lower compared with patients without malignancy (HR 3.32, 95% CI 2.03-5.43). CONCLUSIONS:Among adult patients with HT, CHD was associated with an increased risk of PTM. Further investigation is warranted to identify risk factors and screening strategies for malignancy in this patient population.

BACKGROUND:In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS:About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS:Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION/CONCLUSIONS:SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.

Internal herniation through the foramen of Winslow (FoW) is a rare, life-threatening diagnosis. We present a case of intestinal obstruction due to herniation of the ileum, cecum, appendix, and ascending colon through the FoW. We reduced the herniation using a small colotomy and preserved the entirety of the bowel. We closed the FoW and colotomy and secured the bowel to the lateral abdominal wall by suture cecopexy. Due to the rarity of this pathology, the literature remains unclear about the benefits of prophylactic measures, hence, we recommend continued reporting of cases and research on prophylactic measures. Further, our own treatment strategy outlined in this report may provide further insight into the misdiagnosis and management of FoW hernias.

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

BACKGROUND:RYGB consists of the Roux limb (RL), the biliopancreatic limb (BPL), and the common channel (CC). There is no consensus on the optimal limb lengths. METHODS:Using a mouse model of RYGB, 30 diet-induced obese mice were divided into two groups with varying BPL and CC lengths: a standard BPL with a long CC (RYGB S) and a long BPL with a short CC (RYGB L). Additionally, 9 age-matched, lean control mice (LC) were also included in this study. RESULTS:RYGB S had limb lengths of RL = 17%, BPL = 24%, and CC = 59%. RYGB L had limb lengths of RL = 17%, BPL = 32%, and CC = 51%. RYGB S and RYGB L had 67% and 40% survival, respectively. Mortality in RYGB L included more instances where the cause of death was not apparent. RYGB L demonstrated greater weight loss, lower energy expenditure, and lower heart mass as compared to RYGB S. Both RYGB groups had lower epidydimal fat mass, spleen mass, and bone mineral density compared to LC. RYGB L had a lower heart mass than RYGB S and LC. While the relative abundance of Eubacterium was lower in RYGB L than in RYGB S, no other gut microbiota differences were observed. CONCLUSIONS:A longer BPL with a shorter CC induces greater weight loss but may lead to adverse effects, including lower heart mass, reduced bone density, and deaths with unclear causes.

BACKGROUND:The existence of sociodemographic disparities in pancreatic cancer has been well-studied but how these disparities have changed over time is unclear. The purpose of this study was to longitudinally assess patient management in the context of sociodemographic factors to identify persisting disparities in pancreatic cancer care. METHODS:Using the National Cancer Database, patients diagnosed with pancreatic ductal adenocarcinoma from 2010 to 2017 were identified. The primary outcomes were surgical resection and/or receipt of chemotherapy. Outcome measures included changes in associations between sociodemographic factors (i.e., sex, age, race, comorbidity index, SES, and insurance type) and treatment-related factors (i.e., clinical stage at diagnosis, surgical resection, and receipt of chemotherapy). For each year, associations were assessed via univariate and multivariate analyses. RESULTS:Of 75,801 studied patients, the majority were female (51%), White (83%), and had government insurance (65%). Older age (range of OR 2010-2017 [range-OR]:0.19-0.29), Black race (range-OR: 0.61-0.78), lower SES (range-OR: 0.52-0.94), and uninsured status (range-OR: 0.46-0.71) were associated with lower odds of surgical resection (all p < 0.005), with minimal fluctuations over the study period. Older age (range-OR: 0.11-0.84), lower SES (range-OR: 0.41-0.63), and uninsured status (range-OR: 0.38-0.61) were associated with largely stable lower odds of receiving chemotherapy (all p < 0.005). CONCLUSIONS:Throughout the study period, age, SES, and insurance type were associated with stable lower odds for both surgery and chemotherapy. Black patients exhibited stable lower odds of resection underscoring the continued importance of mitigating racial disparities in surgery. Investigation of mechanisms driving sociodemographic disparities are needed to promote equitable care.

PURPOSE/OBJECTIVE:Cancer-related financial toxicity occurs frequently and is a key driver of inequities in access to care and disparities in treatment outcomes. Current practices to screen for financial toxicity are inconsistent because of the lack of a validated and clinically integrated screening tool. This analysis aimed to create and assess an abbreviated version of the validated Comprehensive Score for Financial Toxicity (COST) tool, a measure of financial toxicity used for research purposes, which could easily be added into often-lengthy clinical screening workflows. METHODS:At an urban comprehensive cancer center with suburban satellite locations, a financial toxicity screening quality improvement project was conducted from June 2022 to August 2023 as part of routine clinical care: 57,526 longitudinal COST surveys were completed by 38,249 patients with cancer. An iterative algorithm selected the items with highest correlation with the total score. Using a separate validation data set, positive and negative predictive values (PPV and NPV, respectively) of the abbreviated tool (two-item) were assessed against the full COST score, with varying risk thresholds. RESULTS:Inclusion of two COST questions (Q3: "I worry about the financial problems I will have in the future as a result of my illness or treatment"; Q6: "I am satisfied with my current financial situation") yielded a score that had a correlation of 0.922 with the full instrument score. For the two-item scale, PPV ranged from 74% to 91%, and NPV ranged from 91% to 98% when compared with the full COST tool. CONCLUSION/CONCLUSIONS:This analysis of a large data set finds that a simplified COST tool has high predictive value when compared with the full validated measure. An abbreviated COST measure of two questions is suitable for implementation into clinical screening workflows.

Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.