Prevalence and Burden of Illness of Rome IV Chronic Idiopathic Constipation, Opioid-Induced Constipation, and Opioid-Exacerbated Constipation in the United States.

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.

Immunotherapy and Transarterial Radioembolization Combination Treatment for Advanced Hepatocellular Carcinoma.

INTRODUCTION: The efficacy and safety of combined immunotherapy and transarterial radioembolization (TARE) were suggested in preclinical 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 January 1, 2017, and December 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 1,522 received immunotherapy alone. Receipt of combination therapy was associated with care at an academic center and inversely associated with racial/ethnic minority status (Hispanic and Black individuals). The 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 hazard ratio 0.50, 95% confidence interval: 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. DISCUSSION: The combination of TARE and immunotherapy was associated with improved survival compared with immunotherapy alone in patients with advanced-stage HCC. Our findings underly the importance of large clinical trials evaluating combination therapy in these patients.

Impact of the Early COVID-19 Pandemic on Incidence and Outcomes of Hepatocellular Carcinoma in the United States.

INTRODUCTION: Access to hepatocellular carcinoma (HCC) surveillance and treatments were disrupted during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to characterize the impact of the pandemic on HCC incidence and mortality rates, treatment, and outcomes in the United States. METHODS: Two nationwide databases, the United States Cancer Statistics and the National Vital Statistics System, were used to investigate HCC incidence and mortality between 2001 and 2020. Trends in age-adjusted incidence rate (aIR) and adjusted mortality rate (aMR) were assessed using joinpoint analysis. The 2020 aIR and aMR were projected based on the prepandemic data and compared with actual values to assess the extent of underdiagnosis. We assessed differences in HCC characteristics, treatment, and overall survival between 2020 and 2018-2019. RESULTS: The aIR of HCC in 2020 was significantly reduced compared with 2019 (5.22 vs 6.03/100K person-years [PY]), representing a 12.2% decrease compared with the predicted aIR in 2020 (5.94/100K PY). The greatest extent of underdiagnosis was observed in Black (-14.87%) and Hispanic (-14.51%) individuals and those with localized HCC (-15.12%). Individuals staged as regional or distant HCC were also less likely to receive treatment in 2020. However, there was no significant difference in short-term overall survival in 2020 compared with 2018-2019, with HCC mortality rates remaining stable (aMR: 2.76 vs 2.73/100K PY in 2020 vs 2019). DISCUSSION: The COVID-19 pandemic resulted in underdiagnosis of HCC, particularly early stage disease and racial ethnic minorities, and underuse of HCC-directed treatment. Longer follow-up is needed to determine the impact of the COVID-19 pandemic on HCC-related mortality.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

Development and validation of a biomarker index for HCC treatment response.

BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927. CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.

Ethnic disparities in the epidemiology, treatment, and outcome of patients with hepatocellular carcinoma in the United States.

There are significant ethnic disparities in incidence, tumor stage, curative therapy receipt, and survival among patients with hepatocellular carcinoma (HCC) in the US. While previous models had predicted an increasing trend in the incidence rate of HCC until 2030 in the US, recent studies have shown that HCC incidence plateaued in 2013 and then started to decline in 2015. The decreasing trend has been observed in all ethnicities except for American Indians/Alaska Natives, whose incidence rates of HCC continue to rise. Current evidence shows that African-Americans and Hispanics are two groups that are more likely to be diagnosed with late-stage HCC, and this finding has been consistent in different socioeconomic statuses of the patients. These two ethnic minority groups are also among those who are less likely to have curative therapy for early-stage HCC. Finally, advances in early diagnosis and treatment approaches have led to an improvement in HCC survival for all ethnicities; however, African-Americans continue to have the worst survival. More studies to find the causes of these disparities and interventions to eliminate them are urgently needed.

Role of Endoscopy in Management of Upper Gastrointestinal Cancers.

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.

Detection of inflammation using cardiac positron emission tomography for evaluation of ventricular arrhythmias: An institutional experience.

BACKGROUND: The use of cardiac positron emission tomography-computed tomography (PET-CT) is increasingly used for the detection of underlying inflammation in patients with ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]), but the role of PET-CT remains undefined, particularly for patients who do not meet Task Force criteria for sarcoidosis. OBJECTIVE: The purpose of this study was to determine the utility of PET-CT for clinical evaluation of VT/VF in patients with nonischemic cardiomyopathy. METHODS: Consecutive patients with nonischemic cardiomyopathy and VT/VF who underwent cardiac PET-CT to detect inflammation between 2012 and 2019 were analyzed for baseline demographic characteristics, imaging results, and outcomes. Patients with known sarcoidosis or other conditions requiring immunosuppressive therapy were excluded. RESULTS: PET-CT was performed in 133 patients with mean age 56.3 ± 13.5 years and left ventricular ejection fraction 43% ± 16.1%, with evidence of myocardial inflammation detected in 32 (23.5%). Patients with myocardial inflammation were managed conservatively with medical therapy including immunosuppressive agents. Ten patients with myocardial inflammation ultimately required catheter ablation for ongoing arrhythmias. There was no significant difference in arrhythmia recurrence between PET-positive and PET-negative groups (37.5% vs 32.4%; P = .43) or in time to recurrence (P = .26), in spite of the disparate management strategies. Gadolinium-enhanced cardiac magnetic resonance imaging was performed in 96 patients (72%); however, magnetic resonance imaging did not detect 31% of cases with active inflammation that were otherwise detected on PET-CT. CONCLUSION: The use of PET-CT significantly improves the detection of underlying myocardial inflammation contributing to ventricular arrhythmias. Management of these patients with immunosuppressive medical therapy is effective for arrhythmia control and may obviate the need for invasive ablation procedures in some patients.

Endovascular repair of a complex renal artery aneurysm using PipelineTM Embolization Device (PED) assisted coil embolization.

Background: We describe the treatment of a renal artery aneurysm with complex anatomy using coils and the PipelineTM Embolization Device (Medtronic, Irvine, CA), a flow-diverting stent typically used for the treatment of intracranial aneurysms. Methods: A 62-year-old female with history of an asymptomatic right renal artery aneurysm that was discovered incidentally 10 years ago was found to have enlargement of the aneurysm (1.9cm to 2.7cm) on a repeat surveillance CT scan. She was successfully treated with combined Pipeline Embolization Device and coil embolization of the aneurysm sac. Results: Post-procedural angiography showed complete occlusion of the aneurysm with maintenance of perfusion to the entire kidney. Conclusion: PipelineTM assisted coil embolization may be an option for parenchyma-sparing treatment of renal artery aneurysms with complex anatomy.