Colorectal cancer (CRC) is a rising health concern in Lebanon and across the Arab world, concomitant with dietary and lifestyle transitions. The gut microbiome may contribute to CRC progression and treatment response, and it remains understudied in Arab populations. This pilot study investigates gut microbiome dynamics in a cohort of stage IV CRC patients and cancer-free individuals from Lebanon, benchmarking computational tools for 16S rRNA sequencing and analyzing microbial and functional shifts associated with cancer development and therapy. Stool samples were collected from cancer-free individuals (n = 32) and newly diagnosed stage IV CRC patients before therapy (n = 17). A subset of CRC patients (n = 10) provided follow-up samples 3–6 months after therapy. 16S rRNA microbial profiling was conducted using the Illumina MiSeq platform. Computational tools were benchmarked using a mock community, with a defined microbial composition. Microbiome and functional analyses included diversity metrics, differential abundance testing, and pathway prediction, with adjustments for age and sex, followed by sensitivity analyses accounting for antibiotic use and immunotherapy. Among the evaluated computational tools, USEARCH was selected for downstream CRC microbiome analyses based on its performance. CRC patients exhibited progressive dysbiosis, characterised by distinct beta diversity profiles, reduced alpha diversity and a declining Firmicutes/Bacteroidota ratio from cancer-free controls to baseline CRC and post-therapy samples. Differential abundance analysis identified taxa associated with CRC development and therapy response, including Fusobacterium, Muribaculaceae, Intestinimonas, Intestinimonas butyriciproducens and Lactobacillus fermentum. Notably, some potentially beneficial taxa increased progressively across the disease and treatment continuum, suggesting that therapy may promote specific favorable microorganisms while coinciding with broader microbiome dysregulation. Functional pathway analysis revealed widespread alterations in microbial functional capacity, including potential therapy-associated shifts. This study represents a pioneering effort in gut microbiome profiling of Lebanese population with advanced CRC, establishing a molecular reference map during a period of rising CRC incidence and dietary transition. Computational benchmarking using a mock community supported the robustness of the analytical workflow. The results may facilitate the discovery of microbial signatures associated with CRC development and therapy response, providing insights into cancer prevention and clinical intervention.

BACKGROUND:Prostate cancer in the Middle East and North Africa (MENA) region is shaped by a complex interplay of behavioral and environmental risk factors, yet comprehensive estimates of preventable cases remain scarce. To address this gap, we estimated population-attributable fractions (PAFs) for a range of modifiable exposures among men aged 50 years and older and assessed potential reductions in incidence under feasible intervention scenarios. METHODS:Regional prevalence data were combined with relative risks from meta-analyses to compute closed-form PAFs for tobacco smoking, obesity, physical inactivity, high dairy and calcium intake, heavy alcohol use, drinking water nitrates, trihalomethanes, arsenic, lead, selenium status, ambient PM2.5 and NO2, and occupational diesel exhaust, covering an estimated 47 million men. Estimates were validated using a synthetic cohort simulation of 100,000 individuals, with uncertainty quantified through Monte Carlo sampling. RESULTS:Results showed that drinking water nitrate exposure accounted for the largest single fraction (17.4%), followed by tobacco smoking (9.5%), physical inactivity (6.7%), and trihalomethane exposure (5.0%), while other exposures contributed smaller but meaningful shares. Joint elimination of all exposures projected a 45.5% reduction in incidence, and simultaneous feasible reductions in four targeted exposures yielded a combined potential impact fraction of 12.1%. CONCLUSIONS:These findings suggest that integrated water quality management, tobacco control, lifestyle interventions, and targeted environmental surveillance should be prioritized to reduce prostate cancer burden in the MENA region. However, estimates of drinking-water nitrate exposure rely on limited evidence from a single case-control study with a relatively small sample size, and should therefore be considered exploratory and primarily hypothesis-generating.

Evidence on the impact of ultra-processed food (UPF) intake on diet quality among cancer survivors remains limited. This study examined UPF consumption and nutrient intake adequacy among cancer survivors in Lebanon. In this cross-sectional study, adult cancer survivors in remission for at least three months were recruited from two medical centers. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and food items were categorized according to the NOVA classification. Nutrient adequacy ratio (NAR) and mean adequacy ratio (MAR) were calculated. Participant characteristics, nutrient adequacy, and macronutrient intakes were compared across UPF quartiles using Chi-square tests, and ANOVA. Logistic regression was performed to identify predictors of nutrient inadequacy. The study included 268 participants (mean age: 59 years; 83

Advanced pancreatic adenocarcinoma lacks a universally accepted second-line chemotherapy regimen following progression on FOLFIRINOX or Gemzar/Abraxane. In a previous retrospective study at AUBMC, the modified GTX regimen showed good tolerability and a 33

ABSTRACT Background Pancreatic ductal adenocarcinoma (PDAC) is the sixth leading cause of global cancer death. The process of epithelial‐to‐mesenchymal transition (EMT) is a key driver of early progression and metastasis in PDAC. Aim Our study aimed to explore the correlation between the expression of EMT markers and survival outcomes. Methods and Results We conducted a retrospective longitudinal study on patients diagnosed with resectable PDAC between January 2005 and June 2019, with a 5‐year follow‐up for survival analysis. Immunohistochemical staining was performed to assess E‐cadherin and vimentin expression. EMT was defined as the presence of high Vimentin (mesenchymal) expression combined with low E‐cadherin (epithelial) expression. The study cohort included 135 patients with resectable PDAC, with 86 males (63.7%) and a mean age of 63.5 years (SD 10.1); most tumors were grade 2 (84, 64.6%). Cox regression analysis revealed that Vimentin expression (p = 0.005), positive margin (p = 0.008), and absence of metformin intake (p = 0.023) were independent predictors of poor OS. High Vimentin was associated with lower median OS (17.0 ± 4.4 vs. 25.8 ± 2.3 months, p = 0.037) and DFS (8.6 ± 1.2 vs. 13.0 ± 2.3 months, p = 0.014), compared to low Vimentin, and it was correlated with higher tumor grade (p = 0.028) and metastasis rate (p = 0.032). The poorest outcomes were observed when high Vimentin was coupled with low E‐cadherin (median OS of 12.6 ± 4.7 vs. 24.5 ± 2.1 months, p = 0.038; median DFS of 9.5 ± 0.5 vs. 10.8 ± 2.1 months, p = 0.029), compared to the rest of the population. Conclusion Our findings showed that Vimentin overexpression and the EMT phenomenon are strongly associated with poor OS and DFS in resectable PDAC, underscoring their potential as prognostic biomarkers and therapeutic targets.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare and distinct histologic subtype of hepatocellular carcinoma that typically arises in non-cirrhotic livers of adolescents and young adults without underlying viral hepatitis or chronic liver disease. Accounting for less than 1% of all primary liver cancers, FLC is characterized by unique clinical, radiologic, and molecular features, most notably the highly characteristic DNAJB1-PRKACA fusion. Due to its rarity and frequently nonspecific presentation, diagnosis is often delayed or misinterpreted as by benign hepatic lesions such as focal nodular hyperplasia or adenoma. This report presents a rare case of metastatic FLC in a young adult who initially presented with right upper quadrant pain, anemia, and preserved hepatic function. Imaging revealed a large hepatic mass with a central non-enhancing area suggestive of necrosis, and histopathologic evaluation aided in the diagnosis based on characteristic lamellar fibrosis, polygonal eosinophilic cells, and positive CK7 and HepPar-1 staining. Confirmatory molecular testing through DNAJB1-PRKACA fusion was not performed. Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. Through this case and accompanying review, we aim to highlight the diagnostic complexity, molecular underpinnings, and current therapeutic approaches of FLC. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy.

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival outcomes in various malignancies, including renal cell carcinoma (RCC). Pembrolizumab, an anti-PD-1 monoclonal antibody, is an established adjuvant therapy for high-risk localized RCC. However, ICIs are associated with a unique spectrum of immune-related adverse events (irAEs). Cutaneous irAEs are common, but eosinophilic fasciitis (EF), a rare scleroderma-like disorder characterized by symmetrical painful swelling, progressive induration of the skin and soft tissues, and peripheral eosinophilia, remains an infrequent and often under-recognized complication. A particularly challenging aspect is the occurrence of delayed immune-related events (DIRE), which manifest after the cessation of immunotherapy. Case Presentation: We report the case of a 61-year-old male who developed progressive diffuse muscle stiffness, cutaneous tightness, and marked peripheral eosinophilia five months after completing adjuvant pembrolizumab for high-risk localized clear cell RCC. The patient had previously experienced grade 3 immune-mediated hepatotoxicity near the end of his adjuvant treatment, leading to pembrolizumab discontinuation. Despite initial differential diagnoses including parasitic infection, a full-thickness skin and fascia biopsy confirmed eosinophilic fasciitis, revealing characteristic inflammatory infiltrates in the deep fascia with sparing of the epidermis and superficial dermis The patient was successfully managed with systemic corticosteroids and rituximab. Conclusions: This case highlights a rare instance of delayed-onset eosinophilic fasciitis following adjuvant pembrolizumab therapy for RCC, emphasizing the importance of long-term monitoring for irAEs even after immunotherapy cessation. Clinicians should maintain a high index of suspicion for late-onset musculoskeletal and cutaneous toxicities in patients with a history of ICI exposure. Early recognition and a multidisciplinary approach, including rheumatologic evaluation and histopathological confirmation, are essential for the timely diagnosis and management of these complex and potentially debilitating complications.

INTRODUCTION:Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening complication whose association with COVID-19 is controversial. Understanding this connection is essential due to its significant impact on patient outcomes, and timely diagnosis and intervention are critical in managing this condition effectively. AREAS COVERED:This paper presents a case of TTP triggered by COVID-19 infection in a 48-year-old female. Additionally, a comprehensive literature review was conducted using PubMed and Google Scholar databases, from inception through August 2024, to identify all published cases of COVID-19-associated TTP. The literature search focused on adult cases of TTP secondary to COVID-19 infection, highlighting the treatments used and patient outcomes. EXPERT OPINION:In this report, we highlight the importance of recognizing TTP as a possible complication of COVID-19. While the standard treatment for TTP - plasma exchange and corticosteroids - remains the primary approach, we note that COVID-19-related cases exhibit a high risk of early relapse, as seen in our patient. The literature review suggests that TTP triggered by COVID-19 may have unique characteristics, such as a persistent low ADAMTS13 activity and increased relapse rates. Larger studies are necessary to develop optimal treatment guidelines and understand whether the presence of COVID-19 alters the typical clinical course of TTP.

Colorectal cancer (CRC) has a complex etiology involving genetic, lifestyle, and environmental factors. This study investigates the association between exposure to water contaminants and the risk of developing CRC in Lebanon. Population Attributable Fraction (PAF) was calculated using exposure prevalence from environmental reports and water quality assessments. Relative risks (RR) were obtained from multiple meta-analyses and epidemiological studies to quantify the contribution of five water contaminants to CRC incidence: nitrates, mercury, arsenic, trihalomethanes (THMs), and microbial pollutants (E. coli). A synthetic cohort was simulated using national exposure data and probabilistic techniques, employing multivariate logistic regression models to ensure precise CRC risk and controlling for lifestyle covariates. Adjusted PAF values were calculated using regression data to determine the proportion of CRC cases attributable to each water contaminant. THMs and E. coli showed the strongest association with CRC, with adjusted PAF values of 25.76% and 23.65%, respectively. Exposure to nitrates, arsenic, and mercury contributed less to CRC risk (1.02%, 0.52% and 2.20%, respectively). Multivariate regression confirmed that THMs and E. coli remained the strongest independent predictors of CRC risk (OR = 1.37, p = 0.001) and (OR = 1.79, p < 0.0001) among water contaminants, respectively. Our model-based approach carries limitations due to reliance on indirect exposure and risk estimates, which may introduce uncertainty stemming from data gaps and underlying assumptions. This study highlights the importance of water quality management in CRC prevention as exposure to drinking water contaminants contributes meaningfully to disease burden.

Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and radiologic neoadjuvant rectal (NAR) scores in predicting pathologic complete response (pCRs). Methods: The scores were assessed for patients with LARC enrolled in the Averectal study (NCT03503630), who received five fractions of short-course radiotherapy, followed by six cycles of mFOLFOX-6 plus avelumab, and total mesorectal excision. The IS was calculated using the mean density percentiles of CD3- and CD8-positive T-cells on baseline biopsy samples. Baseline and post-treatment MRIs were reviewed to measure the mrTRG. NAR scores were calculated using the pre-treatment T stage and post-treatment pathologic and radiologic N and T stages. Results: Fifteen out of thirty-five patients whose data were available achieved pCR (42.8%), and seven out of fourteen patients with mrTRG = 1 (complete response) attained pCR. In patients with both a mrTRG = 1 and high IS, the pCR rate was 66.7% (6/9). All of the patients who achieved pCR had a low or intermediate pathologic NAR score with a significant correlation between pCR and pathologic NAR scores (p < 0.0001). Both pathologic and radiologic NAR scores were correlated with overall survival and disease-free survival. Conclusions: The IS can supplement the mrTRG to better predict TNT outcomes, along with the use of the NAR score. This combination could potentially help with patient selection for non-operative management and guide treatment strategies for those with different recurrence risks.

BACKGROUND:Total neoadjuvant therapy(TNT) has improved complete pathologic response (pCR) rate and disease-free survival (DFS) in locally advanced rectal cancer (LARC), though an increased local recurrence rate (LRR) with short-course radiotherapy (SCRT) is concerning. Synergism between immunotherapy and radiotherapy may improve outcomes in LARC, even where microsatellite stable (MSS) tumours exist. The Averectal trial evaluated SCRT, followed by chemotherapy and immunotherapy with avelumab and total mesorectal excision (TME) in these patients. METHODS:Patients with LARC received SCRT (5 Gy x5 fractions), 6 cycles of mFOLFOX-6 plus avelumab every 2 weeks, followed by TME in an investigator-initiated, open-label, single-arm, multicentre, phase II study. The primary outcome was pCR vs. historical control. Secondary outcomes were 3-year DFS, local recurrence rate (LR) and the association of the ImmunoScore (IS) with outcomes including pCR, safety, and quality of life (QoL). RESULTS:Out Of 44 MSS patients enrolled from 3 centres (July 2018 -October 2020), 40 completed treatment and analysed (65 % male, median age 58.5 [31.0, 74.0] years). Median follow-up was 44 months (11.4, 51.4). Fifteen patients (37.5 %) achieved pCR; and 67.5 % had a major pathologic response. Mean DFS was 42 months (37.9, 46.1). Mean OS was 46.3 months (44.4, 48.2). Median DFS and OS were not reached. Three-year DFS was 85 %. LRR was 2.5 %. Patients with vs. without pCR had higher mean IS (68 vs. 52, p = 0.036). Serious adverse events occurred in 23.5 % (one was related to avelumab). Three patients died (7.5 %), due to disease progression. QOL was similar between baseline and last follow-up. CONCLUSION:Adding avelumab to neoadjuvant chemotherapy mFOLFOX6 after SCRT, followed by TME, improved pCR without increasing LRR, with acceptable toxicity and QOL.

Treatment of locally advanced rectal cancer (LARC), clinical stages II–III, typically involves multimodal treatment options. Over the past decade, the role of radiation therapy as a neoadjuvant treatment for LARC has evolved and is currently a part of total neoadjuvant therapy (TNT). Some recently published studies advocate for the omission of radiation therapy entirely, while others report on a non-operative approach that emphasizes the use of higher radiation therapy doses. This review aims to evaluate the latest literature on the current role of radiation therapy in the management of LARC, with a discussion of how to best select the most appropriate treatment protocol based on individual patient and tumor characteristics, comorbidities, and personal needs and preferences.

BACKGROUND/AIMS:Muscle-invasive bladder cancer (MIBC) has a 5-year survival rate of 40-60% following traditional treatment with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), which significantly impacts quality of life. Bladder preservation strategies, including maximal transurethral resection of the bladder tumor (TURBT), NAC, and radiation therapy, offer similar survival rates with better quality of life. Immune checkpoint inhibitors like avelumab show potential benefits when combined with bladder preservation modalities. This phase II randomized, non-comparative, double-arm, open-label, multicenter trial evaluates the efficacy and safety of two tetra-modality bladder preservation strategies in MIBC patients (T2-T4N0M0). The primary endpoint is the 2-year proportion of bladder-preserved participants. Secondary endpoints include response rates post-induction, quality of life, and safety evaluations. METHODS:Eighty participants will be randomized 1:1 into Arm A or Arm B. All participants will first receive induction chemotherapy (DDMVAC or GC) combined with avelumab, followed by disease evaluation using imaging and TURBT. Those achieving a complete or near-complete response will proceed to hypofractionated radiation therapy (55 Grays in 20 fractions). After radiation, Arm A will receive maintenance avelumab for 1 year, while Arm B will follow a watch-and-wait approach. Non-responders in both arms will be referred for salvage RC. CLINICAL TRIAL REGISTRATION:NCT06686381 (ClinicalTrials.gov).

PURPOSE:Pancreatic cancer remains a deadly disease with a low survival rate specifically if diagnosed at later stages. Surgery is one of the mainstay treatments for early stage disease but is accompanied by significant mortality and morbidity even in high volume centers. In the present study we wanted to determine the influence of pre-operative weight loss, BMI and liver function tests on postoperative outcomes. METHODS:Data for patients who underwent pancreatic surgery at the American University of Beirut Medical Center between 1998 and 2017 were analyzed. The data included patient demographics, pathologic diagnosis, stage, nodal involvement, tumor grade, surgical margin, type of adjuvant therapy, liver function tests and post-operative complications. The correlation and p-value were determined by the chi-square test with p-value < 0.05 considered statistically significant. RESULTS:The analysis included 236 patients. 63% were males and mean age was 60 years. A total of 96 (41%) patients had significant weight loss prior to surgery and 173 (31%) had a BMI > 30 kg/m2 which were considered obese. Obesity and significant weight loss were associated with increased risk of post-operative complications (P = 0.013 and P = 0.004, respectively). Transaminases and cholestatic liver enzymes were not associated with post-operative complications. CONCLUSIONS:Assessment and management of nutritional status particularly weight loss and BMI prior to pancreatic cancer surgery may influence postoperative outcomes in this patient population.

In this editorial, we discuss the article by Agatsuma et al. We concentrate specifically on the current routinely used screening tests recommended by society guidelines and delve into the significance of early diagnosis of colorectal cancer (CRC) and its substantial impact on both incidence and mortality rates. Screening is highly recommended, and an early diagnosis stands out as the most crucial predictor of survival for CRC patients. Therefore, it is essential to identify and address the barriers hindering adherence to screening measures, as these barriers can vary among different populations. Furthermore, we focus on screening strategy optimization by selecting high-risk groups. Patients with comorbidities who regularly visit hospitals have been diagnosed at an early stage, showing no significant difference compared to patients undergoing regular screening. This finding highlights the importance of extending screening measures to include patients with comorbidities who do not routinely visit the hospital.

The etiology of colon cancer is either genetic in nature or results from inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease; nevertheless, dietary habits play a crucial role in the disease. Wheatgrass is a dietary supplement that is rich in vitamins, minerals, and antioxidants which contribute to health promotion in cardiovascular diseases, liver disease, blood diseases, diabetes, and inflammatory bowel diseases, as well as in several types of cancers, such as oral squamous cell cancer, cervical cancer, and breast cancer. In colorectal cancer (CRC), the prospect that wheatgrass possesses anti-inflammatory, antioxidant, and anticancer properties, and its use as an adjunctive therapy, have been minimally investigated and evidence is still limited. In this review, we compiled the available evidence pertaining to wheatgrass and its likely impact on CRC, described the pathways of inflammation in which wheatgrass could possibly play a role, and identified future research needs on the subject.

Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy; they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.

Background A high neutrophil-lymphocyte ratio (NLR) may be associated with worse survival in esophageal cancer (EC). Our aims were to describe the demographic and clinical data of EC in a tertiary referral center in Lebanon and to determine the prognostic value of NLR. Methods A retrospective cohort study based on chart review of patients diagnosed with EC was conducted at the American University of Beirut Medical Center (AUBMC). The demographic characteristics, clinical presentation and outcomes were described and compared between squamous cell carcinomas (ESCC) and adenocarcinomas (EAC). Data about esophageal cancer incidence were obtained from the National Cancer Registry, the Ministry of Public Health and GLOBOCAN 2020. Cox regression analysis was performed to determine whether the NLR is an independent predictor of survival, using variables based on clinical knowledge and previously established data. Results 110 patients were diagnosed with EC, which was the least common among other gastrointestinal malignancies. Our follow up rates reached 86.4%. The median survival was 9 months (IQR 3–25.5.) and was comparable between ESCC (median of 7 months, IQR 2–25) and EAC (median of 9 months, IQR 3–26.3), p = 0.803. Advanced stage was associated with a worse prognosis ( p = 0.037). The mean NLR(±SD) was 5.20 ± 6.8, with no significant difference between EAC and ESCC (4.5 ± 3.4 vs. 5.9 ± 9.2, p = 0.420) or between early or advanced stages (5.4 ± 8.1 vs. 4.7 ± 6.8, p = 0.732). The area under the curve for the NLR was 0.560 (95% CI: 0.374–0.746, p = 0.488). After adjusting for age, gender, TNM staging and grading, cox regression analysis showed that an increased NLR was a significant predictor of mortality, with an adjusted hazard ratio of 1.095 ( p = 0.011). Conclusion EC is quite uncommon in Lebanon despite a high prevalence of smoking and obesity. Advanced stage and high NLR were associated with a negative prognostic value.