Geographical Variations in Early Onset Colorectal Cancer in the United States between 2001 and 2020.

BACKGROUND: Colorectal cancer remains the second leading cause of cancer-related death in the US. As early-onset colorectal cancer (EO-CRC) becomes more prevalent in the US, research attention has shifted towards identifying at-risk populations. Previous studies have highlighted the rising rate of early-onset adenocarcinoma (ADC) and neuroendocrine tumors (NET) in the US. However, data on geographical variations of EO-CRC are scarce. Hence, our study aims to analyze time trends in EO-CRC incidence rates across various US regions and to assess these trends by sex and histopathological subtypes (ADC and NET). METHODS: We analyze data spanning from 2001 to 2020 from the United States Cancer Statistics (USCS) database, covering nearly 98% of the US population. Using SEER*Stat software version (8.4.2, NCI), we calculated EO-CRC incidence rates among adults aged 20-54 years, adjusting for the age standard 2000 US population. The rates were categorized by sex and US geographical regions into west, midwest, northeast, and south. Time trends, reported as annual percentage change (APC) and average APC (AAPC), were generated via Joinpoint Regression software (v.5.0.2, NCI) utilizing the weighted Bayesian Information Criteria "BIC" method to generate the best-fit trends with a two-sided p-value cutoff at 0.05. The rates were also stratified by histopathology into ADC and NET. RESULTS: Between 2001 and 2020, a total of 514,875 individuals were diagnosed with early-onset CRC in the US, with 54.78% being men. Incidence rates and trends varied across geographical regions. In the western region (comprising 106,685 patients, 54.85% men), incidence rates significantly increased in both women (AAPC = 1.37, p < 0.001) and men (AAPC = 1.34, p < 0.001). Similarly, in the midwestern region (with 110,380 patients, 55.46% men), there were significant increases in incidence rates among women (AAPC = 1.06, p < 0.001) and men (AAPC = 1.35, p < 0.001). The northeastern region (with 94,758 patients, 54.53% men) also witnessed significant increases in incidence rates for both women (AAPC = 0.71, p < 0.001) and men (AAPC = 0.84, p < 0.001). In contrast, the southern region (with 203,052 patients, 54.48% men) experienced slower increases in incidence rates among both women and men (AAPC = 0.25, p < 0.05 in women; AAPC = 0.66, p < 0.05 in men). When stratified by histopathology, incidence rates for adenocarcinomas (ADC) increased in all regions, most notably in the west (AAPC = 1.45, p < 0.05), and least in the south (AAPC = 0.46, p < 0.05). Conversely, for neuroendocrine tumors (NET), while incidence rates increased similarly across all regions, the pace was notably faster compared to ADC, particularly in the west (AAPC = 3.26, p < 0.05) and slower in the south (AAPC = 2.24, p < 0.05) Discussion: Our analysis of nationwide US data spanning two decades and encompassing over half a million early-onset CRC patients, representing nearly 98% of the US population, highlights significant temporal variation in incidence rates across various geographical regions. The most substantial increases in incidence rates were observed in the west, while the least pronounced changes were noted in the south, affecting both men and women. These trends persisted across the main CRC histopathological subtypes, with NET exhibiting a notably swifter pace of increase compared with ADC. These findings hold important implications for public health strategies and underscore the need for targeted interventions to address the rising burden of early-onset CRC across different regions in the US.

Hypertriglyceridemia-induced acute necrotizing pancreatitis: Poor clinical outcomes requiring revisiting management modalities.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is the third most common cause of AP after gallstones and alcohol. Supportive measures, intravenous insulin, and plasmapheresis are possible treatment modalities for HTG-AP; however, definitive guidelines evaluating the best therapeutic approach are not clearly established. We present a rare case of a 42-year-old male without known comorbidities who was found to have HTG-AP. Despite early initiation of intravenous insulin and plasmapheresis and the initial decline in his triglycerides level, his condition was complicated by necrotizing pancreatitis and subsequent multi-organ failure. Future studies are warranted to evaluate the role of plasmapheresis in HTG-AP and its efficacy.

Early-Onset Colorectal Cancer: Are Neuroendocrine Tumors or Adenocarcinomas the Culprit? Analysis of the Largest U.S. Cancer Incidence Database, 2001-2020.

(1) Background: While prior data showed an increasing incidence of colorectal cancer (CRC) in young adults, the contribution of adenocarcinoma (ADC) and neuroendocrine tumors (NETs) to this trend is not well studied. Therefore, we conducted a comparative analysis of the incidence rates and time trends of colorectal ADC and NETs in young adults (aged 24-54) using the United States Cancer Statistics (USCS) database. (2) Methods: Age-adjusted CRC incidence rates between 2001 and 2020 were calculated and categorized by sex, histopathology, and stage at diagnosis. Annual percentage change (APC) and average APC (AAPC) were computed via joinpoint regression utilizing weighted Bayesian information criteria to generate the simplest trend. Pairwise comparative analysis of ADC and NETs was conducted using tests of identicalness and parallelism. (3) Results: In this study, 514,875 patients were diagnosed with early-onset-CRC between 2001 and 2020 (54.8% men). While CRC incidence was significantly increased, including both ADC (448,670 patients) and NETs (36,205 patients), a significantly greater increase was seen for NETs (AAPC = 2.65) compared to ADC (AAPC = 0.91), with AAPC difference = 1.73 (p = 0.01) and non-identical non-parallel trends (p-values < 0.001). This was most notable in males (AAPC difference = 1.81, p = 0.03) and for early-stage tumors (AAPC difference = 3.56, p < 0.001). (4) Conclusions: Our study, covering ~98% of the U.S. population provides the first comparative analysis of early-onset CRC histopathological subtypes, showing that the rate of increase of NETs in young adults is much greater than that of ADC. Given that patients with NETs with malignant behavior can experience significant mortality, our findings are importance, highlighting the rapidly increasing NET incidence in young adults and encouraging early screening that can improve outcomes.

Locally Advanced Gastric Cancer Management: A Cost-Effectiveness Analysis.

Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US) and perioperative chemotherapy (PCT). Preoperative therapies have demonstrated survival benefits over US and thus long-term outcomes are expected to vary between the options. However, as these 2 modalities continue to be regularly employed, we sought to perform a decision analysis comparing the costs and quality-of-life associated with the treatment of patients with LAGC to identify the most cost-effective option. We designed a decision tree model to investigate the survival and costs associated with the most commonly utilized management modalities for LAGC in the United States: US and PCT. The tree described costs and treatment strategies over a 6-month time horizon. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life-years (QALYs). One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. PCT was the most cost-effective treatment modality for patients with LAGC over US with a cost of $40,792.16 yielding 3.11 QALYs. US has a cost of $55,575.57 while yielding 3.15 QALYs; the incremental cost-effectiveness ratio (ICER) was $369,585.25. One-way and two-way sensitivity analyses favored PCT in all variations of variables across their standard deviations. Across 100,000 Monte Carlo simulations, 100% of trials favored PCT. In our model simulating patients with LAGC, the most cost-effective treatment strategy was PCT. While US demonstrated improved QALYs over PCT, the associated cost was too great to justify its use.

Liver Severity Score-Based Modeling to Predict Six-Week Mortality Risk Among Hospitalized Cirrhosis Patients With Upper Gastrointestinal Bleeding.

Background: Patients with cirrhosis who have gastrointestinal bleeding have high short-term mortality, but the best modality for risk calculation remains in debate. Liver severity indices, such as Child-Turcotte-Pugh (CTP) and Model-for-End-Stage-Liver Disease (MELD) score, are well-studied in portal hypertensive bleeding, but there is a paucity of data confirming their accuracy in non-portal hypertensive bleeding and overall acute upper gastrointestinal bleeding (UGIB), unrelated to portal hypertension. Aims: This study aims to better understand the accuracy of current mortality risk calculators in predicting mortality for patients with any type of UGIB, which could allow for earlier risk stratification and targeted intervention prior to endoscopy to identify the bleeding source. Methods: In a large US single-center cohort, we investigated and recalibrated the model performance of CTP and MELD scores to predict six-week mortality risk for both sources of UGIB (portal hypertensive and non-portal hypertensive). Results: Both CTP- and MELD-based models have excellent discrimination in predicting six-week mortality for all types of bleeding sources. However, only a CTP-based model demonstrates calibration for all bleeding, regardless of bleeding etiology. Median predicted 6-week mortality by CTP class A, B, and C estimates a risk of 1%, 7%, and 35% respectively. Conclusions: Our study corroborates findings in the literature that CTP- and MELD-based models have similar discriminative abilities for predicting 6-week mortality in hospitalized cirrhosis patients presenting with either portal hypertensive or non-portal hypertensive UGIB. CTP class is an effective clinical decision tool that can be used, even prior to endoscopy, to accurately risk stratify a patient with known cirrhosis presenting with any UGIB into low, moderate, and severe risk groupings.

The Incidence of Rectal Neuroendocrine Tumors Is Increasing in Younger Adults in the US, 2001-2020.

Prior non-comparative data showed increasing incidence of rectal neuroendocrine tumors (RNET) in the US. We aimed to evaluate age-specific RNET incidence rates and time-trends in demographic- and tumor-specific populations. The RNET age-adjusted incidence rates were calculated from the United States Cancer Statistics (USCS) database between 2001 and 2020. The population was stratified by age into older (≥55 years) and younger adults (<55 years), as well as by sex and race. The tumors were categorized by their stage at diagnosis into early and late. The annual percentage change (APC) and average APC (AAPC) were estimated using joinpoint regression and Monte Carlo permutation analysis. Pairwise comparison assessed for parallelism and coincidence. There were 59,846 patients diagnosed with RNET between 2001 and 2020 (50.3% women). Overall, the RNET incidence rates during this period were increasing in younger but not older adults (AAPC = 3.12 vs. -1.10; AAPC difference = 4.22, p < 0.001), with non-identical non-parallel data (p-values < 0.001). While similar results were seen in men, a greater age-specific difference was noted in women (AAPC = 3.31 vs. -1.10; AAPC difference = 4.41, p = 0.003). The difference between younger and older adults was seen in non-Hispanic White (AAPC-difference = 4.89; p < 0.001) and non-Hispanic Black (AAPC-difference = 3.33; p = 0.03) patients, and, in most years, among Hispanic and Non-Hispanic Asian/Pacific Islander patients, and it was mostly driven by early-stage tumors (AAPC-difference = 3.93; p < 0.001). The nationwide data show a significantly increasing RNET incidence in younger adults, most notably in younger women and in early-stage tumors, seen in various races. Future studies should evaluate RNET risk factors and outcomes in demographic-specific populations.

Rare Manifestation of Pancreaticobiliary Cancer With Extrahepatic Lesions.

Pancreaticobiliary cancers are uncommon neoplasms, frequently diagnosed at an advanced stage with metastasis to the liver, lung, or peritoneum. Here, we report an extraordinary case of a patient presenting with both hepatic and extrahepatic lesions, including bone involvement, but without discernible disease in the biliary system or pancreas. Eventual pathological evidence supports the origin of primary pancreaticobiliary carcinoma. This case report aims to stimulate discourse regarding the consideration of pancreaticobiliary cancers as a potential cause of extrahepatic metastatic lesions. Increased awareness of such atypical presentations is crucial for early diagnosis and optimal patient management.

A case of cryptococcoma in an immunocompetent man with polysubstance use.

Cryptococcus most commonly affects the pulmonary and central nervous systems in patients who are immunocompromised. It is most likely to present as meningitis. However, it can affect immunocompetent patients in the cerebral parenchyma. Here we describe a rare case of cryptococcoma in an immunocompetent male patient who originally presented with headache and possible seizure-like activity and had IV drug use as a risk factor. Cryptococcomas are a rare manifestation of the disease, and can present due to Cryptococcus gatti. Definite diagnosis is dependent on culture of the organism and treatment includes a long course of anti-fungals.

Efficacy of endoscopic resuturing versus pharmacotherapy to treat weight recidivism after endoscopic sleeve gastroplasty.

BACKGROUND AND AIMS: A subset of patients experience weight recidivism after primary endoscopic sleeve gastroplasty (P-ESG). Available options for management of weight regain include initiation of antiobesity medications (AOMs) or redo ESG (R-ESG). The comparative effectiveness of these options is not clear. METHODS: This was a retrospective analysis of a prospectively maintained database of patients undergoing ESG. From 2013 to 2021, 79 patients who were started on AOM or underwent R-ESG for management of weight recidivism after P-ESG were included. The primary outcome of this study was final total body weight loss (TBWL) at the end of follow-up. RESULTS: Fifty-five patients were started on AOM and 24 patients underwent R-ESG. Age, gender distribution, and baseline body mass index did not differ significantly between groups. The proportion of noncompliant patients (defined as patients who missed their first post-ESG follow-up visit) was significantly higher in the AOM group compared with the R-ESG group (67% vs 35%, P = .012). The additional TBWL after R-ESG was significantly (both clinically and statistically) better than after initiation of AOM (9.5% ± 7.2% vs 2.1% ± 8.6%, respectively; P = .001). Final TBWL clearly favored R-ESG over AOM for treatment of weight recidivism (19.9% ± 10.4% vs 13.6% ± 9.2%, P = .028). CONCLUSIONS: R-ESG is an effective treatment to induce weight loss after experiencing weight recidivism. These results highlight an important advantage of ESG as a repeatable minimally invasive procedure.

Impact of Adjunctive Pharmacotherapy With Intragastric Balloons for the Treatment of Obesity.

BACKGROUND: We conducted this study to compare the weight loss outcome of intragastric balloons (IGBs) in conjunction with pharmacotherapy vs IGB and intensive lifestyle changes alone. METHODS: This was a multicenter, non-randomized, retrospective study involving 4 academic hospitals. Patients underwent IGB placement with or without concomitant anti-obesity pharmacotherapy. The primary outcome was percent total weight loss (TBWL) after IGB placement at 6 and 12 months. RESULTS: This study included 102 patients, with 23 patients (mean age 46.6 years, 82.6% female) treated with IGB/pharmacotherapy and 79 patients (mean age 46.0 years, 88.6% female) treated with IGB/lifestyle modifications. Patients had a 100% follow-up rate at 6 and 12 months. At 6 months following IGB placement, both groups achieved a similar %TBWL. At 12 months, %TBWL was greater in the IGB/pharmacotherapy group (12.6% ± 1.2 vs 9.7% ± 0.7, P = .04). 65.2% of patients achieved ≥10% TBWL at 12 months in the IGB/pharmacotherapy group, compared to 38.0% in the IGB/lifestyle group (P < .05). The proportion of patients that achieved ≥15% weight loss at 12 months was also significantly different between the IGB/pharmacotherapy and IGB/lifestyle groups (30.4% vs 20.3%, P < .05). DISCUSSION: IGB with concomitant use of pharmacotherapy did not improve weight loss while the IGB was in place compared to IGB and lifestyle changes. However, patients receiving IGB with pharmacotherapy did have greater weight loss and diminished weight regain after balloon removal compared to those receiving just IGB and lifestyle changes.

Successful minimally invasive management of adverse events following EUS-guided gallbladder drainage in a suboptimal surgical patient.

Video 1Successful minimally invasive management of adverse events following EUS-guided gallbladder drainage in a suboptimal surgical patient.

Endoscopic ultrasound-guided ileosigmoidostomy using a lumen-apposing metal stent for palliation of malignant small-bowel obstruction.

Video 1Endoscopic ultrasound-guided ileosigmoidostomy for relief of small bowel obstruction.

Effect of Statin Use on Cancer-related Mortality in Nonalcoholic Fatty Liver Disease: A Prospective United States Cohort Study.

BACKGROUND: Indications for use of statins are common among patients with nonalcoholic fatty liver disease (NAFLD). Epidemiologic studies have suggested a possible association between statins and decreased risk of malignancies. We hypothesized that statin use has a protective effect on cancer mortality in patients with NAFLD. METHODS: Participants with NAFLD in 8 rounds of National Health and Nutrition Examination Survey (NHANES) were included in this study. Mortality data were obtained by linking the NHANES data to National Death Index. NAFLD was defined using the previously validated Hepatic Steatosis Index model. RESULTS: A total of 10,821 participants with NAFLD were included and 23% were statin users (n=2523). Statin use was associated with a 43% lower risk of cancer mortality [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.43-0.75, P<0.001] in multivariable analysis. Statin use under 1 year did not show a significant effect on cancer mortality (HR=0.72, 95% CI: 0.46-1.12), while statin use for 1 to 5 years decreased cancer mortality by 35% (HR=0.65, 95% CI: 0.42-0.99, P=0.46), and statin use >5 years decreased cancer mortality by 56% (HR=0.44, 95% CI: 0.29-0.66, P<0.001). Statin use was associated with a significant decrease in the risk of cancer mortality in NAFLD patients with both low and high risk of liver fibrosis (HR=0.55, 95% CI: 0.38-0.81; and HR=0.53, 95% CI: 0.31-0.89, respectively). CONCLUSION: Using a large US prospective cohort, we showed statin use is associated with a considerable decrease in cancer-related mortality among patients with NAFLD. These results are important for clinical decision making, as statin indications are prevalent among NAFLD patients, but many do not receive benefit in the event that the statin is discontinued due to liver test abnormalities.

Simultaneous EUS-guided portosystemic pressure measurement and liver biopsy sampling correlate with clinically meaningful outcomes.

BACKGROUND AND AIMS: The measurement of the portosystemic pressure gradient (PSG) in patients with advanced liver disease is helpful to assess the severity of portal hypertension (PH) and predict adverse clinical outcomes. EUS-guided PSG (EUS-PSG) measurement is a novel tool to assess PSG in all patients with advanced liver disease. We sought to assess the safety, feasibility, and technical success of simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling using a single-center experience. METHODS: Patients with suspected liver disease or cirrhosis were enrolled prospectively from 2020 to 2021. EUS-PSG was measured by calculating the difference between the mean portal pressure and the mean hepatic vein pressure. PH was defined as PSG >5 mm Hg and clinically significant PH as PSG ≥10 mm Hg. The primary outcomes were procedural technical success rate and correlation of EUS-PSG with fibrosis stage obtained from concurrent EUS-guided liver biopsy sampling and the correlation of EUS-PSG with patients' imaging, clinical, and laboratory findings. The secondary outcome was occurrence of procedural adverse events (AEs). RESULTS: Twenty-four patients were included in the study. PSG measurement and EUS-guided liver biopsy sampling were successful in 23 patients (technical success rate of 96%) and 24 patients (100% success), respectively. Analysis revealed a significant association between both PSG and liver stiffness measured on transient elastography (P = .011) and fibrosis-4 score (P = .026). No significant correlation was found between the fibrosis stage on histology and measured PSG (P = .559). One mild AE of abdominal pain was noted. Additionally, EUS-PSG was predictive of clinically evident PH. CONCLUSIONS: Simultaneous EUS-PSG measurement and EUS-guided liver biopsy sampling were both feasible and safe and correlated with clinically evident PH and noninvasive markers of fibrosis.

Observed risk of recurrent bleeding and thromboembolic disease in COVID-19 patients with gastrointestinal bleeding.

Background and study aim COVID-19 patients are at increased risk for venous thromboembolism (VTE) requiring the use of anticoagulation. Gastrointestinal bleeding (GIB) is increasingly being reported, complicating the decision to initiate or resume anticoagulation as providers balance the risk of thrombotic disease with the risk of bleeding. Our study aimed to assess rebleeding rates in COVID-19 patients with GIB and determine whether endoscopy reduces these rebleeding events. We also report 30-day VTE and mortality rates. Methods This was a retrospective study evaluating 56 COVID-19 patients with GIB for the following outcomes: 30-day rebleeding rate, 30-day VTE rate, effects of endoscopic intervention on the rate of rebleeding, and 30-day mortality. Results The overall rates of VTE and rebleeding events were 27 % and 41 %, respectively. Rebleeding rates in patients managed conservatively was 42 % compared with 40 % in the endoscopy group. Overall, 87 % of those who underwent invasive intervention resumed anticoagulation vs. 55 % of those managed medically ( P  = 0.02). The all-cause 30-day mortality and GIB-related deaths were 32 % and 9 %, respectively. Mortality rates between the endoscopic and conservative management groups were not statistically different (25 % vs. 39 %; P  = 0.30). Conclusions Although rebleeding rates were similar between the endoscopic and conservative management groups, patients who underwent intervention were more likely to restart anticoagulation. While endoscopy appeared to limit the duration that anticoagulation was withheld, larger studies are needed to further characterize its direct effect on mortality outcomes in these complex patients.

Dynamic α-Fetoprotein Response and Outcomes After Liver Transplant for Hepatocellular Carcinoma.

Importance: Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. Objective: To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated score with currently accepted HCC selection tools, namely, the Milan Criteria (MC), the French-AFP (F-AFP), and Metroticket 2.0 models. Design, Setting, and Participants: A retrospective, multicenter prognostic analysis of prospectively collected databases of 2236 adults undergoing liver transplant for HCC was conducted at 3 US, 1 Canadian, and 4 European centers from January 1, 2001, to December 31, 2013. The AFP-R was measured as the difference between maximum and final pre-liver transplant AFP level. Cox proportional hazards regression and competing risk regression analyses examined recurrence-free and overall survival. Receiver operating characteristic analyses and net reclassification index were used to compare NYCA with MC, F-AFP, and Metroticket 2.0. Data analysis was performed from June 2019 to April 2020. Main Outcomes and Measures: The primary study outcome was 5-year recurrence-free survival; overall survival was the secondary outcome. Results: Of 2236 patients, 1808 (80.9%) were men; mean (SD) age was 58.3 (7.96) years. A total of 545 patients (24.4%) did not meet the MC. The NYCA score proved valid on competing risk regression analysis, accurately predicting recurrence-free and overall survival (5-year cumulative incidence of recurrence risk in NYCA risk categories was 9.5% for low-, 20.5%, for acceptable-, and 40.5% for high-risk categories; P < .001 for all). The NYCA also predicted recurrence-free survival on a center-specific level: 453 of 545 patients (83.1%) who did not meet MC, 213 of 308 (69.2%) who did not meet the French-AFP, 292 of 384 (76.1%) who did not meet Metroticket 2.0 would be recategorized into NYCA low- and acceptable-risk groups (>75% 5-year recurrence-free survival). The Harrell C statistic for the validated NYCA score was 0.66 compared with 0.59 for the MC and 0.57 for the F-AFP models (P < .001). The net reclassification index for NYCA was 8.1 vs MC, 12.9 vs F-AFP, and 10.1 vs Metroticket 2.0. Conclusions and Relevance: This study appears to externally validate the importance of AFP-R in the selection of patients with HCC for liver transplant. The AFP-R represents one of the truly objective measures of biological characteristics available before transplantation. Incorporation of AFP-R into selection criteria allows safe expansion of MC and other models, offering liver transplant to patients with acceptable tumor biological characteristics who would otherwise be denied potential cure.