Ali, Hassam

Atezolizumab-bevacizumab and durvalumab-tremelimumab have established immunotherapy as a first-line standard of care in advanced hepatocellular carcinoma (HCC). Yet, objective response rates (ORRs) remain confined to approximately 15-20%, and no validated predictive biomarker exists for patient selection. Unlike melanoma and lung cancer, conventional markers, including programmed death-ligand 1, microsatellite instability-high status, and tumor mutational burden, have not demonstrated reliable predictive value in HCC. Prior narrative reviews comprehensively catalogued the biomarker landscape through 2022 but predate a wave of clinically significant publications. This narrative review synthesizes evidence published between 2020 and 2026, with particular emphasis on 2023–2026 data, within a unified clinical framework not provided by prior reviews. We critically evaluate tissue-based biomarkers, including the AI-derived Atezolizumab-Bevacizumab Response Signature-Pathology model, spatial multiplex immunohistochemistry, and β-catenin mutational profiling; blood-based biomarkers encompassing circulating tumor DNA for minimal residual disease detection and peripheral immune phenotyping; and serum indices including the CRAFITY score and neutrophil-to-lymphocyte ratio. Hepatitis B virus etiology and non-alcoholic steatohepatitis are discussed as biological modifiers of biomarker performance. We propose an original biomarker-guided clinical algorithm, a comparative clinical readiness table, and a disease-continuum biomarker timeline as practical tools for clinicians and trialists. Prospective biomarker-enrichment trials represent the most critical next step toward clinical translation.

Background: Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, post-LT outcomes may differ depending on underlying disease etiology. Our study aimed to compare post-LT outcomes between alcoholic and non-alcoholic steatohepatitis (NASH)-related liver transplant recipients in the United States. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Adult liver transplant recipients (≥18 years) were categorized into two mutually exclusive cohorts: alcoholic liver disease and NASH-related liver disease. Propensity score matching (1:1) was performed to balance baseline characteristics. Clinical outcomes were assessed. Comparative analyses included risk ratios, risk differences, odds ratios, Kaplan–Meier survival analysis, and hazard ratios with log-rank testing. Results: Compared with NASH recipients, alcoholic LT recipients had a significantly higher risk of rejection (14.5% vs. 12.1%; RR 1.195, 95% CI 1.076–1.327; p = 0.001) and hepatic encephalopathy (14.3% vs. 8.3%; RR 1.720, 95% CI 1.526–1.938; p < 0.001). Acute kidney injury was also more frequent in the alcoholic cohort (47.3% vs. 43.6%; RR 1.084, 95% CI 1.036–1.133; p < 0.001). In contrast, sepsis (15.6% vs. 18.0%; RR 0.869, 95% CI 0.794–0.952; p = 0.003) and CKD (46.1% vs. 51.1%; RR 0.901, 95% CI 0.863–0.939; p < 0.001) occurred less frequently in alcoholic LT patients. No significant differences were observed for liver transplant failure or ascites. Kaplan–Meier analyses demonstrated significantly lower rejection-free survival (HR 1.241, p < 0.001), higher hepatic encephalopathy (HR 1.808, p < 0.001), increased AKI risk (HR 1.150, p < 0.001) and higher all-cause mortality in the alcoholic cohort (HR 1.106, p = 0.031). Conclusions: In this large real-world matched cohort study, alcoholic LT recipients demonstrated higher risks of complications and all-cause mortality compared with NASH LT recipients.

Colorectal cancer (CRC) is responsible for a high cancer burden and a high number of deaths all over the world, although effective screening can make it preventable to a significant extent. Stool-based tests, such as the fecal immunochemical test (FIT) and multitarget stool DNA (mt-sDNA) testing, are gaining considerable popularity as non-invasive procedures that can be a replacement for colonoscopies for people at an average risk for colon cancer. Despite evidence from several randomized controlled trials supporting the use of these tests for colorectal cancer screening, their external validity in a real-world setting is influenced by many factors such as adherence, timely follow-up post testing, the healthcare cost burden, accessibility and the capacity of the health system. In this article, we have performed an extensive narrative literature review of research published between 2020 and 2025 comparing FIT and the mt-sDNA test with reference to diagnostic accuracy, cost-effectiveness, adherence and outcomes of implementation. We discuss the issues of sensitivity and specificity, look at post-test requirements for colonoscopy and check if there is any discrimination in healthcare. These findings suggest that FIT and mt-sDNA tests should not be considered competing technologies but rather complementary screening methods, with their overall effectiveness contingent upon appropriate patient selection and widespread system-level implementation. It is crucial to combine strategic test selection with a robust follow-up infrastructure to ensure that the entire population benefits from the CRC prevention program.

Antibody–drug conjugates (ADCs) are reshaping the therapeutic approach to advanced gastrointestinal cancers by integrating tumor-specific monoclonal antibodies with potent cytotoxic payloads to improve targeted tumor cell destruction while minimizing systemic exposure. Compared to traditional chemotherapy, trastuzumab deruxtecan has significantly improved objective response rates and overall survival in HER2-positive gastric and gastroesophageal junction tumors after trastuzumab-based therapy. This supports its role as an important second-line or later treatment option. The ongoing advancement of ADCs targeting CLDN18.2, TROP2, and CEACAM5 indicates that this therapeutic category will continue to expand across gastrointestinal neoplasms. Nonetheless, these advancements are accompanied by a specific and clinically significant toxicity profile. Hematologic suppression, gastrointestinal side effects, hepatotoxicity, and notably interstitial lung disease (ILD) are essential consequences that may need inpatient assessment and care. Interstitial lung disease (ILD), although uncommon, may be severe or lethal if not identified immediately and treated swiftly with medication cessation and corticosteroids. In hospitalized patients, distinguishing ADC-related toxicity from infection or disease progression is often difficult owing to overlapping clinical manifestations, requiring meticulous evaluation and interdisciplinary cooperation. As ADCs are integrated into earlier treatment lines and across a broader patient population, hospital systems must evolve to ensure prompt identification, consistent management protocols, and efficient collaboration between oncology and inpatient teams. This study analyzes the mechanisms, clinical effectiveness, and safety profile of ADCs in gastrointestinal oncology, pointing out the importance of institutional preparedness to safely incorporate these medicines into standard clinical practice. These features also align ADC therapy with personalized medicine by emphasizing biomarker-guided patient selection and individualized toxicity monitoring.

800 Background: Primary squamous cell carcinoma (SCC) of the small intestine is exceedingly rare and associated with poor prognosis. Literature is currently limited to a few case reports, and, to our knowledge, this is the first population-based analysis of patients with small intestine SCC. This study aimed to identify patient demographics and predictors of survival outcomes. Methods: Patients with histologically confirmed primary SCC of the small intestine diagnosed between 2000 and 2022 were identified from the SEER database; autopsy-only cases were excluded. Patient demographics, tumor site, stage (SEER summary stage), and initial treatments were summarized. Overall survival (OS) was defined from diagnosis to death, with one-year OS estimated by Kaplan–Meier methods. Multivariate Cox proportional hazards models evaluated associations between patient variables (age, sex, race, residence, year of diagnosis, surgery, and chemotherapy) and mortality. All statistical analyses were performed using R version 4.4.2. Results: A total of 89 patients diagnosed with primary small intestine SCC were identified. The median age at diagnosis was 68 years; 43 % were female, and 67 % were non-Hispanic White. Most patients (82 %) resided in urban counties. Tumor site was mostly the duodenum (37 %), followed by ileum (16 %) and jejunum (10 %); 33 % were not otherwise specified. Among patients with a recorded stage, 45 % had localized disease, 38 % regional disease, and 17 % distant metastases. Initial treatment comprised surgery in 60 % of patients, chemotherapy in 25 %, and radiation in 10%. The median OS was approximately six months, and the one-year OS was 36.7 % (95 % CI 27.9–48.3). Women had a higher one-year OS (42 %) than men (33 %), although this difference was not statistically significant. In multivariable analysis, surgical resection was associated with a markedly lower hazard of death (HR = 0.43, 95 % CI 0.25–0.74). Chemotherapy was associated with an insignificantly improved survival (HR 0.54, 95 % CI 0.27–1.09). Additionally, rural residence (HR ≈ 2.9) and older age (HR ≈ 1.03) were independently associated with worse survival (p<0.05). Conclusions: This population-based study highlights the rarity and aggressiveness of primary small bowel SCC, with a median OS of six months. Surgical resection was strongly associated with improved survival (adjusted HR ≈ 0.43), reinforcing its role as the cornerstone of management. Chemotherapy showed a nonsignificant survival benefit, highlighting the need for prospective studies. The association of rural residence with higher mortality suggests disparities in access to care and underscores the need for strategies to improve early detection and referral. Overall, these findings support a multimodal approach centered on surgery and warrant further studies to elucidate pathogenesis and optimize systemic therapy.

ABSTRACTObjectiveAlcohol‐related liver disease (ALD) has emerged as a significant public health concern, particularly among younger populations. ALD remains the leading cause of alcohol‐attributable deaths. This study aims to forecast ALD mortality trends up to 2030, focusing on individuals under 55 years.MethodsWe utilized data from the CDC WONDER database (1999–2022) to examine ALD‐related deaths, identified by ICD‐10 codes (K70.0–K70.9). Crude mortality rates (CMRs) per 100 000 were analyzed and temporal trends were assessed using annual and average annual percent changes (APC/AAPC) with empirical quantile confidence intervals. An Autoregressive Integrated Moving Average (ARIMA) model was employed to project mortality rates until 2030, validated through time series cross‐validation.ResultsFrom 1999 to 2022, there were 181 862 ALD‐related deaths among individuals under 55, with mortality rates increasing from 3.9 per 100 000 in 1999 to 9.7 per 100 000 in 2022 (AAPC 4.66%, 95% CI: 3.90%–5.86%). Projections suggest rates will continue to rise, reaching 14.4 per 100 000 by 2030. From 1999 to 2022, the 25–34 age group experienced the highest increase, with an AAPC of 10.27% (95% CI: 9.19%–11.35%), while the 35–44 and 45–54 age groups showed more moderate increases, with AAPCs of 5.03% and 4.38%, respectively. Projections indicate an AAPC of 3.86% for ages 25–34, 3.90% for ages 35–44, and 6.17% for ages 45–54 by 2030.ConclusionForecasts indicate a continued rise in ALD mortality among individuals under 55, necessitating immediate public health strategies to mitigate this trend.

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). Study Question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? Data Sources: MEDLINE, Embase, Scopus, and Cochrane databases. Study Design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

Summary Stag Beetle Knife (SB Knife) is increasingly being utilized for Zenker’s Diverticulectomy (ZD). Our study assessed the effectiveness and safety of the SB Knife for the management of ZD. Ovid EBM reviews, Ovid Embase, Ovid Medline, ClinicalTrials.gov, Scopus, and Web of Science were searched to identify studies that utilized SB knife for ZD. Pooled proportions (PP) were calculated using the random-effects model. Heterogeneity was evaluated using I2 statistics. A total of 7 studies with 268 patients were included in the final analysis. Dysphagia and regurgitation were the most common clinical symptoms. The mean size of the ZD was 2.8 ± 0.7 cm and 28 (of 148) patients had undergone previous treatments. The PP of technical success was 98% (95% CI: 92.3–99.5; I20) with a mean procedure duration of 26.2 ± 8.3 minutes. The PP of clinical response at first follow-up and relapse after index procedure was 87.9% (95% CI: 81.6–92.3; I219) and 13.5% (95% CI: 9.6–18.6; I22), respectively. At final follow-up, the PP of clinical remission was 96.2% (95% CI: 91–98.4; I230.6) while the PP of procedure failure was 3.6% (95% CI: 1.6–8.1; I20). No severe adverse events (AEs) were noted while using the SB Knife. However, the PP of intraprocedural and postprocedural AEs was 13.2% (95% CI: 9.6–17.8; I20) and 9.3% (95% CI: 5.7–14.9; I2 &lt; 20.9), respectively. SB Knife is highly safe and effective for Zenker’s Diverticulectomy with a failure rate of only 3.6%.