Unique Considerations for Females Undergoing Esophagectomy.

OBJECTIVE: To improve understanding of sex differences in clinicopathologic characteristics, treatment and outcomes between male and female patients undergoing esophagectomy for esophageal cancer. SUMMARY BACKGROUND DATA: Esophageal cancer is a male predominant disease, and sex has not been considered in previous studies as an important factor in diagnosis or management. Sex differences in demographics, clinicopathologic characteristics, and postoperative outcomes remain largely undefined. METHODS: Retrospective review of 1958 patients (21% female) with esophageal cancer who underwent esophagectomy at a single institution between 1995 and 2017. RESULTS: Most patients had adenocarcinoma (83%); however, the rate of squamous cell carcinoma was significantly higher in females (35% vs 11%, respectively; P < .0001). Females had a lower rate of smoking (62 vs 73%) and heavy alcohol use (12 vs 19%) but a higher rate of previous mediastinal radiation (8.4 vs 1.8%) (P < 0.001). Postoperative mortality and overall survival (OS) were similar between sexes. However, subanalysis of patients with locoregional disease (clinical stage II/III) demonstrated that females received neoadjuvant therapy less frequently than males and had worse OS (median OS 2.56 yrs vs 2.08; P = 0.034). This difference remained significant on adjusted analysis (HR 1.24, 95% CI 1.06-1.46). CONCLUSIONS: Female patients had higher incidence of squamous cell carcinoma despite lower prevalence of behavioral risk factors. Among patients with locoregional disease, undertreatment in females may reflect treatment bias and history of previous mediastinal radiation. Esophageal cancer in females should be considered a unique entity as compared with the presentation and treatment of males.

Comparing Symmetric Dimethylarginine and Amyloid-ß42 as Predictors of Alzheimer's Disease Development.

Background: Physicians may soon be able to diagnose Alzheimer's disease (AD) in its early stages using fluid biomarkers like amyloid. However, it is acknowledged that additional biomarkers need to be characterized which would facilitate earlier monitoring of AD pathogenesis. Objective: To determine if a potential novel inflammation biomarker for AD, symmetric dimethylarginine, has utility as a baseline serum biomarker for discriminating prodromal AD from cognitively unimpaired controls in comparison to cerebrospinal fluid amyloid-ß42 (Aß42). Methods: Data including demographics, magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography scans, Mini-Mental State Examination and Functional Activities Questionnaire scores, and biomarker concentrations were obtained from the Alzheimer's Disease Neuroimaging Initiative for a total of 146 prodromal AD participants and 108 cognitively unimpaired controls. Results: Aß42 (p = 0.65) and symmetric dimethylarginine (p = 0.45) were unable to predict age-matched cognitively unimpaired controls and prodromal AD participants. Aß42 was negatively associated with regional brain atrophy and hypometabolism as well as cognitive and functional decline in cognitively unimpaired control participants (p < 0.05) that generally decreased in time. There were no significant associations between Aß42 and symmetric dimethylarginine with imaging or neurocognitive biomarkers in prodromal AD patients. Conclusions: Correlations were smaller between Aß42 and neuropathological biomarkers over time and were absent in prodromal AD participants, suggesting a plateau effect dependent on age and disease stage. Evidence supporting symmetric dimethylarginine as a novel biomarker for AD as a single measurement was not found.

Long-term Quality of Life After Parathyroidectomy for Primary Hyperparathyroidism: A Systematic Review.

Importance: Definitive treatment of primary hyperparathyroidism (pHPT) with curative parathyroidectomy has been shown to improve nonspecific neurocognitive symptoms and may improve long-term quality of life (QOL). However, QOL is not currently routinely assessed preoperatively, and as a result, diminished QOL may be overlooked as an indication for surgery. Objective: To examine results for measures of long-term QOL after parathyroidectomy in patients with pHPT. Evidence Review: A systematic, English-language literature review was performed to assess the long-term association of parathyroidectomy, defined as a minimum of 1-year postoperative follow-up, with QOL in patients with pHPT. We conducted a search of PubMed and Scopus using Medical Subject Heading (MeSH) terms for hyperparathyroidism, parathyroid hormone, parathyroidectomy, hypercalcemia, and quality of life. All relevant literature published between June 1998 and February 15, 2021, was included. Study selection was guided by the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) strategy. Findings: Thirty-one studies conducted in 14 countries with a minimum of 1 year of follow-up were included, comprising 3298 patients with pHPT (2975 underwent parathyroidectomy; 323 were observed), 5445 age- and sex-matched control participants, and 386 control patients with benign thyroid disease. To assess QOL, 21 studies (68%) used a general tool, the 36-item Short Form Survey (SF-36), and 8 (26%) used the disease-specific tool Parathyroidectomy Assessment of Symptoms (PAS). The remaining studies used a combination of 10 additional QOL tools. The median follow-up period was 1 year (range, 1-10 years). Of the 31 studies, 27 (87%) demonstrated significant score improvement in long-term QOL after parathyroidectomy, including 1 study that showed continued improvement in QOL 10 years after parathyroidectomy. The remaining 4 studies (13%) reported mixed results. Conclusions and Relevance: This systematic review suggests that parathyroidectomy is associated with improved and sustained QOL in patients with pHPT. Patients with pHPT should be screened with a validated QOL tool such as the SF-36 or PAS at the time of diagnosis to guide discussion of these symptoms in the preoperative setting and the potential for long-term improvement after curative parathyroidectomy.

Image-guided interventional radiological delivery of chimeric antigen receptor (CAR) T cells for pleural malignancies in a phase I/II clinical trial.

OBJECTIVES: We describe techniques and results of image-guided delivery of mesothelin-targeted chimeric antigen receptor (CAR) T cells in patients with pleural malignancies in a phase I/II trial (ClinicalTrials.gov: NCT02414269). MATERIALS AND METHODS: Patients without a pleural catheter or who lack effusion for insertion of a catheter (31 of 41) were administered intrapleural CAR T cells by interventional radiologists under image guidance by computed tomography or ultrasound. CAR T cells were administered through a needle in an accessible pleural loculation (intracavitary) or following an induced loculated artificial pneumothorax. In patients where intracavitary infusion was not feasible, CAR T cells were injected via percutaneous approach either surrounding and/or in the pleural nodule/thickening (intratumoral). Pre- and post-procedural clinical, laboratory, and imaging findings were assessed. RESULTS: CAR T cells were administered intrapleurally in 31 patients (33 procedures, 2 patients were administered a second dose) with successful delivery of planned dose (10-186 mL); 14/33 (42%) intracavitary and 19/33 (58%) intratumoral. All procedures were completed within 2 h of T-cell thawing. There were no procedure-related adverse events greater than grade 1 (1 in 3 patients had prior ipsilateral pleural fusion procedures). The most common imaging finding was ground glass opacities with interlobular septal thickening and/or consolidation, observed in 12/33 (36%) procedures. There was no difference in the incidence of fever, CRP, IL-6, and peak vector copy number in the peripheral blood between infusion methods. CONCLUSION: Image-guided intrapleural delivery of CAR T cells using intracavitary or intratumoral routes is feasible, repeatable and safe across anatomically variable pleural cancers.

How Effective Is Neoadjuvant Therapy Followed by Surgery for Pathologic Single-Station N2 Non-Small Cell Lung Cancer?

The optimal treatment strategy for pathologic single-station N2 (pN2a1) non-small cell lung cancer (NSCLC)-surgery first followed by adjuvant treatment (SF) or neoadjuvant therapy followed by surgery (NS)-remains unclear. We compared disease-free survival (DFS) and overall survival (OS) after NS versus SF for pN2a1 NSCLC. We retrospectively identified patients with pN2a1 NSCLC resected between 2000 and 2018. Patients in the SF group had cN0 disease and were treated with surgery before adjuvant chemotherapy; patients in the NS group had known preoperative nodal disease, cN2 disease, and were treated with neoadjuvant therapy before surgery. The matching-weights procedure was applied to generate a cohort with similar characteristics between groups. DFS and OS were calculated using the Kaplan-Meier approach and compared between groups using weighted log-rank test and Cox proportional hazards models. We identified 227 patients with pN2a1 disease: 121 treated with SF and 106 with NS. After the matching-weights procedure, 5- and 10-year DFS were 45% and 27% for SF versus 26% and 21% for NS (log-rank P = 0.056; hazard ratio [HR], 1.61; 95% confidence interval [CI], 0.98-2.65); 5- and 10-year OS were 49% and 30% for SF versus 43% and 20% for NS (log-rank P = 0.428; HR, 1.24; 95% CI, 0.67-2.28). SF and NS for pN2a1 NSCLC resulted in similar survival. A study comparing SF for known preresectional pN2a1 with occult pN2a1 disease could be a next step. Further investigation of SF for known N2a1 versus occult pN2a1 disease could power a clinical trial focused on N2a NSCLC.

Primary lung cancer in women after previous breast cancer.

BACKGROUND: Breast cancer is the most common malignancy among women in the USA. Improved survival has resulted in increasing incidence of second primary malignancies, of which lung cancer is the most common. The United States Preventive Services Task Force (USPSTF) guidelines for lung-cancer screening do not include previous malignancy as a high-risk feature requiring evaluation. The aim of this study was to compare women undergoing resection for lung cancer with and without a history of breast cancer and to assess whether there were differences in stage at diagnosis, survival and eligibility for lung-cancer screening between the two groups. METHODS: Women who underwent lung-cancer resection between 2000 and 2017 were identified. Demographic, clinicopathological, treatment and outcomes data were compared between patients with a history of breast cancer (BC-Lung) and patients without a history of breast cancer (P-Lung) before lung cancer. RESULTS: Of 2192 patients included, 331 (15.1 per cent) were in the BC-Lung group. The most common method of lung-cancer diagnosis in the BC-Lung group was breast-cancer surveillance or work-up imaging. Patients in the BC-Lung group had an earlier stage of lung cancer at the time of diagnosis. Five-year overall survival was not statistically significantly different between groups (73.3 per cent for both). Overall, 58.4 per cent of patients (1281 patients) had a history of smoking, and 33.3 per cent (731 patients) met the current criteria for lung-cancer screening. CONCLUSION: Differences in stage at diagnosis of lung cancer and treatment selection were observed between patients with and without a history of breast cancer. Overall, there were no statistically significant differences in genomic or oncogenic pathway alterations between the two groups, which suggests that lung cancer in patients who previously had breast cancer may not be affected at the genomic level by the previous breast cancer. The most important finding of the study was that a high percentage of women with lung cancer, regardless of breast-cancer history, did not meet the current USPSTF criteria for lung-cancer screening.

Surveillance Implications of Recurrence Patterns in Early Node-Negative Esophageal Adenocarcinoma.

BACKGROUND: There are limited data regarding optimal surveillance after curative resection for esophageal cancer. Once disease recurrence is diagnosed, the prognosis is poor. The purpose of this article was to characterize disease recurrence in patients with early esophageal adenocarcinoma. METHODS: Two hundred sixty patients were identified from a prospective institutional database with pathologic T1 and T2 node-negative disease therapy treated with curative esophagectomy alone for esophageal adenocarcinoma between 1995 and 2017. Competing risk analysis was used to analyze factors associated with recurrence. RESULTS: The 5-year cumulative incidence of recurrence was 12%. Predictive factors for increased risk of recurrence included increasing tumor size, poor differentiation, and pathologic T2 disease (P < .05), whereas presence of Barrett's esophagus on pathology was protective. Recurrence within 2 years was 2.5%, 6.1%, and 12% for T1a, T1b, and T2 disease, respectively. At 5 years cumulative incidence of recurrence was 8.2%, 11.5% and 22.2%, respectively. Median overall survival after recurrence was 1.04 years (95% confidence interval, 0.7-2.4). There were 14 subclinical and 13 symptomatic recurrences; patients with symptomatic recurrence had a significantly shorter overall survival after recurrence occurred (0.31 vs 0.71 years, P = .018). CONCLUSIONS: Among early node-negative patients with esophageal cancer undergoing curative resection, 5-year recurrence was 12%. Survival after recurrence was poor, and only a few patients had isolated locoregional recurrence at time of diagnosis, suggesting that scheduled surveillance may have an important role.