(249/250 words) Background: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in pre-clinical and early-phase trials, but these were limited by small sample sizes. We sought to compare the efficacy of combined therapy and immunotherapy alone in patients with advanced hepatocellular carcinoma (HCC). Methods: The National Cancer Database was used to identify patients with advanced HCC diagnosed between 1/1/2017 and 12/31/2019. We included patients who received combined therapy or immunotherapy alone as first-line treatment. Multivariable logistic regression was conducted to determine predictors of combined therapy. Kaplan-Meier and Cox regression approaches were used to identify predictors of overall survival and to compare hazards of mortality between the patients who received combined therapy and immunotherapy alone. Results: Of 1,664 eligible patients with advanced-stage HCC, 142 received combined TARE/immunotherapy and 1522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanics and Blacks). Median overall survival was significantly higher in the combination group than in the immunotherapy alone group (19.8 vs. 9.5 months). In multivariable analysis, combined therapy was independently associated with reduced mortality (adjusted HR 0.50, 95%CI: 0.36-0.68, p<0.001). Results were consistent across subgroups and in sensitivity analyses using propensity score matching and inverse probability of treatment weighting. Conclusion: The combination of TARE and immunotherapy was associated with improved survival compared to immunotherapy alone in patients with advanced stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

Upper gastrointestinal (GI) malignancy is a leading cause of cancer-related morbidity and mortality. Upper endoscopy has an established role in diagnosing and staging upper GI cancers, screening for pre-malignant lesions, and providing palliation in cases of advanced malignancy. New advances in endoscopic techniques and technology have improved diagnostic accuracy and increased the therapeutic potential of upper endoscopy. We aim to describe the different types of endoscopic technology used in cancer diagnosis, summarize the current guidelines for endoscopic diagnosis and treatment of malignant and pre-malignant lesions, and explore new potential roles for endoscopy in cancer therapy.

Purpose: This study analyzes the characteristics and prognosis of patients with <i>de novo</i> and recurrent metastatic gastric cancers.Methods: This retrospective study included 301 advanced, pathologically confirmed gastric cancer patients who received palliative chemotherapy between 2012 and 2022. The <i>de novo</i> cohort included patients who presented with distant metastasis at diagnosis, and the recurrent metastatic cohort was composed of patients with metastasis after curative gastrectomy. We analyzed prognostic association by Cox regression and compared survival time of both cohorts using the Kaplan-Meier survival analysis.Results: The study included 167 <i>de novo</i> and 112 recurrent patients. No differences were noted among the patients with <i>de novo</i> disease and recurrent metastatic disease concerning age, sex, Eastern Cooperative Oncology Group scores, primary cancer location, and pathologic features. Patients in the recurrent group versus the <i>de novo</i> group had a longer duration of chemotherapy (1.16±1.18 years vs. 0.85±0.84 years, P= 0.01) and lower mean body mass index (20.22±2.78 kg/m² vs. 21.93±3.38 kg/m², P< 0.001). The median overall survival in the <i>de novo</i> group was 11.6 versus 14.4 months in the recurrent group (P= 0.02).Conclusion: <i>De novo</i> and recurrent metastatic gastric cancer are characterized by distinct subpopulations. Advanced gastric cancer patients with recurrence have significantly better survival versus those in the de novo cohort. The differences between de novo and recurrent gastric cancer patient outcomes could facilitate discussions about the selection of the clinical trial of each patient and help with their personalized treatment.

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INTRODUCTION: Chronic idiopathic constipation (CIC) and opioid-induced constipation (OIC) are disorders that negatively affect quality of life. We sought to assess the prevalence, symptom severity, and medication use among people with Rome IV CIC, OIC, and opioid-exacerbated constipation (OEC) using a nationally representative data set with nearly 89,000 people in the United States. METHODS: From May 3, 2020, to June 24, 2020, we recruited a representative sample of people in the United States ≥ 18 years to complete an online national health survey. The survey guided participants through the Rome IV CIC and OIC questionnaires, Patient-Reported Outcome Measurement Information System gastrointestinal scales (percentile 0–100; higher = more severe), and medication questions. Individuals with OEC were identified by asking those with OIC whether they experienced constipation before starting an opioid and whether their symptoms worsened afterward. RESULTS: Among the 88,607 participants, 5,334 (6.0%) had Rome IV CIC, and 1,548 (1.7%) and 335 (0.4%) had Rome IV OIC and OEC, respectively. When compared with people with CIC (Patient-Reported Outcome Measurement Information System score, 53.9 ± 26.5; reference), those with OIC (62.7 ± 28.0; adjusted P < 0.001) and OEC (61.1 ± 25.8, adjusted P = 0.048) had more severe constipation symptoms. People with OIC (odds ratio 2.72, 95% confidence interval 2.04–3.62) and OEC (odds ratio 3.52, 95% confidence interval 2.22–5.59) were also more likely to be taking a prescription medication for their constipation vs those with CIC. DISCUSSION: In this nationwide US survey, we found that Rome IV CIC is common (6.0%) while Rome IV OIC (1.7%) and OEC (0.4%) are less prevalent. Individuals with OIC and OEC have a higher burden of illness with respect to symptom severity and prescription constipation medication use.