Medicine and Pharmacology

Abstract: Objectives: This study aimed to evaluate very low HBV DNA viral load below the limit of quantification and to identify associated risk factors in different patient groups, including individuals with chronic hepatitis B, occult HBV infection (OBI) and others. Methods: We retrospectively analyzed 390 patients with very low-level viremia (VLLV). HBV DNA levels were measured in plasma samples using real-time RT-qPCR. Serological markers were evaluated in serum samples using chemiluminescence microparticle immunoassay (CMIA). Demographic variables, HBV serological markers (anti-HBs, anti-HBe, anti-HBc), and DNA results were evaluated. Results: The study included 193 patients in the sustained virological response (SVR) group and 197 patients in the other group; 60 of these patients had occult hepatitis B infection (HBV DNA positive, HBsAg negative) and 137 had no occult hepatitis B infection. Very low viral load was more common in men (53.3%) and in individuals aged ≥50 years (63.3%). In univariate analysis, OBI was associated with anti-HBe (odds ratio (OR)=2.874, 95%CI:1.256-6.172, p=0.012), anti-HBc seropositivity (OR=2.368; 95%CI:1.216-4.527, p=0.008), and being ≥50 years age (OR=1.845, 95% CI:0.963-3.473, p=0.077). In multivariate analysis, being ≥50 years of age, anti-HBe positivity, and anti-HBc positivity were independently associated with OBI. Among SVR patients, VLLV was associated with older age and anti-HBc positivity, but no significant association was observed with gender, anti-HBe, or anti-HBs status. Conclusions: In patients with VLLV, anti-HBc and anti-HBe seropositivity, along with older age, were independently associated with lower HBV DNA levels. Although anti-HBe positivity reflects reduced viral replication, it does not indicate complete viral suppression and may be detected at very low viremia levels, particularly in occult HBV infection. These findings highlight the complex interplay between viral replication dynamics and host immune responses across the VLLV spectrum, and emphasize the need for individualized monitoring strategies. Further validation through prospective studies is warranted.

Abstract: Background: Early detection of colorectal cancer (CRC) still relies mainly on invasive screening. Tumor hypoxia induces epigenetic, metabolic, and immune changes via hypoxia-inducible factor (HIF) signaling in experimental models. Building on these insights, this study evaluated whether hypoxia pathway biomarkers—plasma methylated SEPT9 (mSEPT9), urinary N¹, N¹² diacetylspermine (DiAcSpm), and systemic inflammatory indices (NLR, PLR, LMR)—could be combined into a noninvasive diagnostic panel compared with standard serum tumor markers. The study focused solely on diagnostic performance; it did not directly assess tumor hypoxia or HIF expression in patients. Methods: This prospective single-center study enrolled 382 participants: 142 with CRC, 62 with colorectal polyps, and 178 non-malignant controls. Plasma mSEPT9 was quantified by real-time PCR, urinary DiAcSpm by ELISA, and inflammatory indices from blood counts. Serum tumor markers (CEA, CA19-9, CA125, AFP) were measured by immunoassay. Diagnostic accuracy was assessed using ROC analysis and multivariable modeling. Results: mSEPT9 (AUC 0.843) and DiAcSpm (AUC 0.831) demonstrated significantly higher diagnostic accuracy than CEA (AUC 0.660) and CA19-9 (AUC 0.649). A combined panel including mSEPT9, DiAcSpm, NLR, PLR, and LMR achieved an AUC of 0.947, with 85.9% sensitivity and 92.9% specificity. This panel also showed strong performance for early-stage CRC (AUC 0.905).” Conclusions: A multimarker panel of previously reported hypoxia-associated biomarkers (mSEPT9, DiAcSpm, NLR, PLR, and LMR) provides a scalable, noninvasive approach for CRC detection with high diagnostic accuracy. These findings are associative; direct evidence that tumor hypoxia drives these biomarker changes in patients was not obtained and requires future investigation.

Abstract: Background and objectives: In Taiwan, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is the most common cause of hepatocellular carcinoma (HCC). However, an increasing number of non-HBV and non-HCV (NBNC) patient with HCC is noted in recent years. The connection between NBNC patient and HCC remains unknown etiology. We aim to explore the difference of clinical manifestation, pathological findings in HCC patients with HBV, HCV or NBNC. Methods: A retrospective study analyzed 521 HCC patients with completed hepatic virus profile in a single medical center in Taiwan between 2011 to 2020. Differential Expression Gene analysis, xCell stromal cell analysis, and Gene Set Enrichment Analysis were employed to explore the different HCC oncogenesis of viral and NBNC groups. Results: There are 38 non-HBV and non-HCV related HCC (NBNC-HCC) patients. NBNC-HCC patients have lower Fib-4 index than HCV-HCC patients (3.191 vs 6.077, P=0.0019). Less NBNC-HCC patients have cirrhosis than HBV-HCC patients (44.4% vs 68.1%, p=0.0057). Less NBNC-HCC patients have Ishak score 5-6 than HCV-HCC patients (31.3% vs 75.6%, p=0.0025). DEG analysis showed differential expression in oncogene OIT314, AKR1B1015 and liver fibrosis related genes like COLEC1016, CXCL1417, and LINC0109318. GSEA and stromal cell analysis also showed differential gene expression in stellate cells and vascular endothelial cells. Conclusion: NBNC-HCC patients have lower percentage of cirrhosis or fibrosis than HBV-HCC and HCV-HCC patients. Different gene expression and cell type enrichment features was shown between viral and NBNC groups. Which indicated a different pathogenesis in NBNC-HCC compared with hepatitis viruses induced hepatocellular carcinoma.

Abstract: Background: Liver abscesses represent an atypical yet potentially life-threatening complication of bacterial, fungal, protozoal, and helminthic infections. Frequently, the clinical findings associated with liver abscesses are nonspecific, necessitating a reliance on imaging for diagnosis. It is uncommon for a liver abscess to radiographically resemble a malignant liver tumor such as hepatocellular carcinoma (HCC). Here, we present the case of a 45-year-old male who was initially diagnosed with HCC (BCLC C) but was subse-quently found to have a liver abscess following biopsy. Case Presentation: A male patient, 45, presented with stiffness and pain in the right upper abdomen. He complained of nausea and vomiting since 10 days before admission as well. All supportive imaging suggested a diagnosis of HCC. A liver abscess was detected during a biopsy. A liver ultrasound-guided FNAB showcased chronic, suppurative in-flammation with negative acid-fast bacilli on Ziehl-Neelsen staining. The patient sub-sequently developed a complication of middle hepatic artery bleeding and underwent immediate embolization. Discussion: In fact, a liver abscess can be the initial manifestation of HCC. Patients tend to have a poorer prognosis because the diagnosis of a liver abscess often delays the discovery of the underlying HCC. Radiographically, liver abscesses range from well-circumscribed cystic lesions with an enhancing rim to heterogeneously enhancing mass-like lesions, which are sometimes indistinguishable from liver neoplasms. However, it is so scarce that a liver abscess may radiographically mimic HCC. Conclusion: Assessing liver abscess is somewhat complicated since the symptoms vary a lot. Therefore, a correct and exact diagnosis entail a combination of more comprehensive clinical and supporting examinations.

Abstract: Aim: This study aimed to investigate the effect of pancreatic ductal adenocarcinoma (PDAC) on the alterations in red blood cell aggregation related to angiogenesis and hypoxia markers. Material and Methods: We studied 32 patients with confirmed PDAC. The aggregation of red blood cells (RBCs) were evaluated using a Laser-assisted Optical Rotational Cell Analyzer (LORCA). Serum vascular endothelial gfowth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) levels were measured by an ELISA method. The following parameters specific to the aggregation process were estimated: the aggregation index (AI), the aggregation half-time (t1/2), and the threshold shear rate (γ_thr). Results: All measured RBC aggregation parameters among PDAC subjects differed from those in controls. The AI (P<0.05) and γ_thr (P<0.005) were significantly higher in the PDAC group, whereas t1/2 (P<0.01) and AMP (P<0.001) were significantly lower compared to the control group. The levels of VEGF (p<0.0001) and HIF-1α (p<0.0001) were significantly higher in the PDAC group than in the control group. There were significant correlations between RBC aggregation parameters and VEGF and HIF-1α. Conclusion: For the first time, we have demonstrated RBC aggregation disturbances in patients with pancreatic carcinoma. We also found that circulating levels of angiogenesis and hypoxia biomarkers are significantly elevated compared to the control group. Further studies are needed to explore the pathophysiological mechanisms linking PDAC to these aggregation indices.

Abstract:

Helicobacter pylori infection is a common gastrointestinal condition, more often seen in people living in crowded or less sanitary environments. In many cases, it is not detected until symptoms develop, rather than through routine screening. In this retrospective study, we reviewed patient records from a private laboratory to examine the relationship between gastrointestinal symptoms and H. pylori stool antigen (HpSAg) test results. Patients were also grouped by age to better understand how symptoms present across different life stages. The main aim of this study was to examine whether specific symptoms—particularly burning upper abdominal pain that worsens on an empty stomach—could help clinicians better identify patients who are more likely to benefit from testing. The idea was to support more targeted testing strategies, reduce unnecessary investigations, and ultimately help lower healthcare costs without compromising diagnostic accuracy. We assessed a range of gastrointestinal symptoms, including bloating, belching, nausea, vomiting, difficulty swallowing, early satiety, loss of appetite, weight loss, diarrhea, constipation, and melena, and compared them between infected and non-infected patients and across age groups. Burning epigastric pain was seen more often in patients with H. pylori, and overall, infected patients tended to report more symptoms, although this varies depending on age. It is important to emphasize that this study does not propose using symptoms as a replacement for diagnostic testing. Since the study was retrospective and did not include comparison with gold-standard methods such as the urea breath test or endoscopic biopsy, the findings should be interpreted as associations rather than definitive diagnostic conclusions. Still, the results suggest that certain symptom patterns—particularly burning epigastric pain on an empty stomach—may be useful for identifying patients more likely to benefit from testing. Further prospective studies are needed to confirm these observations. Materials and Methods: This retrospective observational study was conducted at Wilson Laboratory (Shush Square) in Tehran, Iran, using existing patient records. A total of 589 patients were included and classified as Helicobacter pylori–positive or Helicobacter pylori–negative based on stool antigen test (SAT) results. To better explore how symptoms differed across age groups, patients were divided into predefined age categories. These groups were selected to ensure a balanced distribution of cases and to make the comparisons clearer and easier to interpret. All stool antigen tests were performed using a commercially available enzyme immunoassay kit. Because the study was retrospective, detailed information about the assay characteristics—such as whether monoclonal or polyclonal antibodies were used, or the specific antigen targets (e.g., CagA or UreC) was not available. It is also recognized that test performance may vary depending on these factors, with monoclonal-based assays generally showing higher sensitivity and specificity. Gastrointestinal symptoms were extracted from patient records and compared between the H. pylori–positive and H. pylori–negative groups. The relationship between symptom patterns and infection status was then explored across different age groups using descriptive statistical analysis. Results: Of the 589 participants included in the study, 353 (59.9%) were Helicobacter pylori–positive and 236 (40.1%) were H. pylori–negative based on stool antigen test (SAT) results. H. pylori infection was significantly associated with burning epigastric pain that worsens on an empty stomach (p < 0.00001). Other gastrointestinal symptoms also showed significant associations with positive SAT results, including bloating (p = 0.012), persistent vomiting (p = 0.029), dysphagia (p < 0.00001), diarrhea (p = 0.0003), constipation (p = 0.0001), and melena (black, tarry stools) (p < 0.00001). The magnitude of these associations varied across age groups. Burning epigastric pain that worsens on an empty stomach demonstrated a sensitivity of 76.2% and a specificity of 95.8% for identifying H. pylori infection. The positive predictive value (PPV) was 96.4%, and the negative predictive value (NPV) was 72.9%. Conclusions: Overall, having at least one gastrointestinal symptom was strongly associated with Helicobacter pylori infection across all age groups. Among the symptoms studied, burning epigastric pain that worsens when the stomach is empty showed the strongest association with infection. Its relatively high specificity and positive predictive value suggests that it may be helpful in guiding clinicians when deciding which patients should be prioritized for testing. At the same time, because this was a retrospective study, these findings should be interpreted with caution. Further prospective studies are needed to better understand and confirm how useful symptom-based approaches can be in routine clinical practice.

Abstract:

Introduction Aspirin initially recognized for its anti-inflammatory, antipyretic and analgesic properties hold a prominent role in the treatment of cardiovascular disease. The utility of aspirin in cancer therapeutics has been explored and stratified into COX dependent and independent mechanisms. COX2 gene expression has been demonstrated to be significantly upregulated in colorectal cancer and various other gastrointestinal malignancies including pancreatic, esophageal, and gastric cancer. This study investigates the relationship of aspirin use and outcomes in patients with colorectal cancer. Methodology The Nationwide Inpatient Sample (NIS) database from 2017 to 2022 was analyzed for patients age >18 who were hospitalized for colorectal cancer and its decompensations using ICD-10 diagnostic codes. These patients were further stratified based on the long term use of aspirin. The principal outcome of this investigation is in-hospital mortality, with secondary outcomes including rates of pulmonary embolism, portal vein thrombosis, acute kidney injury and need for renal replacement therapy, septic shock and rates of hepatic, pulmonary, gastrointestinal and peritoneal or retroperitoneal metastatic disease. Multivariate logistic regression accounting for hospital and patient characteristics was implemented for analysis, with the Charlson Comorbidity Index used to adjust for coexisting comorbidity burden; a p-value (p) of <0.05 was considered statistically significant. Results In our analysis of the NIS, 569,306 patients were identified with colorectal cancer and 11.7% (66,608) of this population were identified with long term use of aspirin. Aspirin use was identified to have a significantly reduced odds of in-patient mortality (adjusted odds ratio) [aOR] 0.530, p value <0.001 95% CI (confidence interval): 0.460 – 0.617. Patients with aspirin use also demonstrated significantly reduced odds of gastrointestinal, hepatic, pulmonary and retroperitoneal/peritoneal metastasis; (aOR 0.606, 95% CI: 0.564-0.653, P<0.001), (aOR 0.628, 95% CI: 0.582 – 0.678, P<0.001), (aOR 0.676, 95% CI: 0.605 – 0.755, P<0.001) and (aOR 0.751, 95% CI: 0.685 – 0.825, P<0.001) respectively. Conclusion In recent years there has been an alarming increase in incidence of colorectal cancer, particularly amongst younger individuals with increased associated mortality. This mortality increase, albeit alarming, is a driving force for treatment innovation with continual examination of our repertoire of medications for possible repurposed applications. COX2 mediated signaling serves as a key promotor of tumorigenic molecular signaling that directly contribute to tumor cell proliferation, angiogenesis and metastasis in colorectal cancer. Aspirin use and its inhibitory action on COX2 demonstrated a significantly reduced risk of in-hospital mortality. Aspirin use is also linked to a significant reduction in odds of developing metastatic disease to the liver, gastrointestinal system, lungs and peritoneum in patients with colorectal cancer. These findings reveal that aspirin exerts shielding effects against in-hospital mortality and protects patients with colorectal cancer from the development of major comorbid conditions and metastatic disease as compared to those who do not use aspirin.

Abstract: Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) sharea characteristic depletion of bile acid-transforming bacteria, undermining intestinal mucosalimmune tolerance. These organisms convert lithocholic acid into immunomodulatory secondarybile acid species through distinct enzymatic pathways: 3-oxolithocholic acid and isolithocholicacid suppress Th17 differentiation through RORγt binding, while isoallolithocholic acidpromotes Foxp3⁺ regulatory T cell differentiation through mitochondrial reactive oxygen speciessignaling.This paper proposes that committed dietary patterns at either metabolic pole, verified nutritionalketosis or traditional Mediterranean diet, are hypothesized to restore coherent signaling acrossmultiple interdependent receptor and metabolic sensing networks (FXR, TGR5, S1PR2, RORγt,and an intersecting oxysterol-LXR axis) and thereby support mucosal immune tolerance. Bileacid signaling is the best-characterized candidate mechanism for one arm of this network and theprimary testable intermediate the experimental program interrogates. Under committed ketosis,lipoprotein remodeling is most directly attributable to malonyl-CoA depletion and CPT-1disinhibition; bile acid pool restructuring is a parallel candidate for immune effects.Mediterranean diet co-directional lipid and immune improvements are supported by IBD-specificrandomized controlled trials. The equivalent prediction for committed ketosis, that both domainsimprove simultaneously in the same subjects under BHB-verified conditions, has not beendemonstrated; IBD-specific clinical evidence for the ketogenic pole currently rests on a ten-patient case series, making it the primary hypothesis under experimental test rather than anestablished parallel. Intermediate carbohydrate restriction, defined by the absence of verifiedketosis, is hypothesized to produce oscillating rather than coherent receptor engagement,producing neither lipid nor immune improvement reliably.No study has simultaneously characterized dietary metabolic state, the bile acid metabolome, andTh17/Treg balance in the same IBD patients. A staged experimental program is proposed; across-sectional design in quiescent IBD patients constitutes the immediate test. The framework isdirectly falsified if committed and intermediate dietary groups do not differ in species-levelimmunomodulatory bile acid concentrations despite differing in lipid and immune outcomes;such a result would redirect Stage 3 design toward BHB-direct NLRP3 inhibition and Kbhb-mediated mTOR signaling as the primary mechanistic candidates. The Host-Microbe Counter-Regulation Index (HMCRI) — a candidate index requiring empirical validation, with nocurrently established reference ranges — is proposed as a systems-level index of signalingcoherence whose reference ranges and dietary responsiveness constitute primary Stage 1analytical objectives.

Abstract: Pancreatic cystic lesions (PCLs) represent a growing clinical challenge due to their diverse biological behaviors and the substantial overlap in imaging features between benign, premalignant, and malignant entities. Traditional diagnostic approaches relying on cross-sectional imaging or isolated morphologic criteria frequently fail to achieve adequate risk discrimination. Advances in endoscopic ultrasound (EUS) now permit detailed morphologic assessment complemented by cyst-fluid biochemical markers, proteomic signatures, and comprehensive genomic profiling using next-generation sequencing. Parallel progress in artificial intelligence (AI) further strengthens diagnostic precision by integrating EUS features with multimodal biomarker data to reduce subjectivity and support individualized clinical decision-making. This review introduces an EUS-based multimodal diagnostic framework of PCLs that integrates morphological evaluation, cyst-fluid biochemical testing, molecular profiling, and AI-assisted analysis. By synthesizing current evidence, we outline how the integrative approach enhances diagnostic accuracy, biological interpretability, and individualized risk stratification for PCLs.

Abstract: Background: Pepsin, a component of gastric refluxate, has been investigated as a potential salivary biomarker for gastro-esophageal reflux disease (GERD), although its diagnostic accuracy remains uncertain. This proof-of-concept study aimed to characterize the effects of pepsin on the human salivary peptidome using matrix-assisted laser desorption/ionization–time of flight (MALDI-ToF) mass spectrometry. Methods: Whole saliva samples were collected from ten healthy adult volunteers under fasting conditions and divided into untreated controls and aliquots digested with pepsin at acidic pH. MALDI-ToF MS was used to profile digestion-induced changes in peptide mass patterns. Spectral data were analyzed using multivariate statistical approaches, including principal component analysis (PCA), linear discriminant analysis (LDA), and hierarchical clustering. Results: Pepsin digestion increased peptide signal intensity and spectral complexity compared with controls. PCA demonstrated clear separation between native and digested samples along the first principal component. Ten peptide m/z features showed the strongest association with pepsin exposure based on PCA loadings. LDA and hierarchical clustering further supported this distinction, with the top 15 discriminative m/z features showing consistent enrichment in digested samples despite inter-individual variability. Conclusions: Pepsin exposure induces reproducible remodeling of the salivary peptidome detectable by MALDI‑ToF MS. Although this peptide‑level approach cannot resolve the full diversity of salivary proteoforms, the resulting signatures support the feasibility of identifying markers of reflux‑associated enzymatic activity and provide a basis for future validation in clinical GERD cohorts.

Abstract: Background/Objectives: Metabolic dysfunction–associated steatotic liver disease (MASLD) and its progressive inflammatory/fibrotic form, metabolic dysfunction–associated steatohepatitis (MASH), represent a growing global health burden. This progression is driven by complex mechanisms involving metabolic dysregulation, chronic inflammation, oxidative stress, and progressive fibrosis. To date, effective pharmacological therapies remain limited. Pentacyclic triterpenes have attracted increasing attention due to their broad biological activities and ability to modulate multiple molecular pathways implicated in chronic liver disease. This review aims to provide a mechanistic overview of the potential role of pentacyclic triterpenes in MASLD and MASH. Methods: A review of the literature was conducted using major scientific databases (PubMed, and Web of Science) to identify experimental studies investigating pentacyclic triterpenes in metabolic liver diseases. Selected studies were analyzed according to triterpene structural classification, reported bioactivities, molecular targets, and experimental evidence from in vitro and in vivo models of MASLD/MASH or related pathogenic processes. Results: Pentacyclic triterpenes, especially ursolic acid, oleanolic acid, and glycyrrhizin, exhibit hepatoprotective effects including regulation of lipid metabolism, attenuation of oxidative and endoplasmic reticulum stress, suppression of pro-inflammatory signaling, inhibition of inflammasome activation, and reduction of hepatic stellate cell activation and extracellular matrix deposition. These effects involve modulation of signaling pathways such as AMPK, NF-κB, NLRP3, TGF-β, FXR, and MAPK. Preclinical evidence demonstrates improvements in steatosis, inflammation, and fibrosis in experimental models. Conclusions: Pentacyclic triterpenes emerge as multitarget modulators of MASH pathophysiology. However, translation from preclinical evidence to well-designed clinical trials is necessary to validate their safety and efficacy in humans.

Abstract: Background: Drug-induced liver injury (DILI) is a leading cause of acute liver dysfunction and acute liver failure in the United States. Nitrofurantoin is a well-recognized cause of DILI and is associated with both acute and chronic hepatitis-like syndromes. Case Presentation: A 77-year-old male with hypertension, hyperlipidemia, and chronic obstructive pulmonary disease developed severe hepatocellular injury after two days of nitrofurantoin therapy for a suspected urinary tract infection. He presented with generalized weakness, difficulty ambulating, and mild abdominal discomfort. Laboratory evaluation revealed markedly elevated transaminases. Nitrofurantoin was discontinued, and supportive care was initiated, resulting in rapid biochemical improvement. Conclusion: Nitrofurantoin-induced hepatotoxicity may occur even after short-term exposure. Early recognition and prompt discontinuation are essential to prevent progression. This case highlights the need for vigilance when prescribing nitrofurantoin in elderly patients.

Abstract: Ulcerative colitis (UC) is a chronic, relapsing-remitting subtype of inflammatory bowel disease (IBD), featured by continuous mucosal inflammation restricted to the colon and rectum. Although the exact pathogenesis of UC has not been fully clarified, intestinal barrier impairment and disrupted mucosal homeostasis are recognized as the central mechanism. Therefore, restoring intestinal mucosal barrier function represents a core strategy for UC prevention and treatment, which aligns with the therapeutic goal of achieving mucosal healing and sustained remission. In this review, we outline the composition and functional significance of the intestinal barrier, explore key mechanisms underlying its disruption, and summarize recent advances in UC-related monitoring strategies. Finally, we explore novel therapeutic approaches aimed at epithelial barrier repair. The review aims to provide insights valuable for both basic research and clinical management of UC.

Abstract: Background: Open hilar resection has long been the standard for hilar cholangiocarcinoma (HCCA) due to the complex biliary anatomy, but its invasiveness remains a concern. We conducted a network meta-analysis to evaluate whether minimally invasive approaches, particularly robotic hilar resection, can improve perioperative outcomes without compromising oncological results.Methods: We performed a Bayesian network meta-analysis of 18 studies involving 2,216 patients. Due to limited reporting, formal subgroup network estimates were not feasible. Primary outcomes included estimated blood loss, R0 resection rate, and Clavien-Dindo grade ≥ III complications.Results: We included 18 studies reporting data on 2,216 patients in a Bayesian network meta-analysis. Robotic resection ranked highest for reducing estimated blood loss (SUCRA 89%). Open surgery remained the fastest (mean difference −84.2 min, 95% CrI −112 to −56.4), while robotic resection showed comparable R0 rates to open surgery (OR 1.04, 95% CrI 0.82–1.31). Major complications were similar across approaches. Trends favoring robotics appeared more pronounced in complex (Bismuth III/IV) tumors, although dedicated subgroup analyses were limited by available data. Conclusion: The optimal surgical approach for hilar cholangiocarcinoma should be individualized according to anatomical complexity, patient condition, and institutional expertise. In experienced centers, robotic resection offers a viable precisionv guided option that improves certain perioperative outcomes without apparent oncological detriment.

Abstract: Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn’s dis-ease, are associated with an increased risk of colorectal cancer through mechanisms driven by persistent mucosal inflammation. Chronic inflammatory signaling, recurrent epithelial injury, and altered tissue repair processes progressively reshape the intesti-nal microenvironment, promoting genomic instability and facilitating the development of colitis-associated colorectal cancer (CAC). Despite the well-established link between inflammation and tumorigenesis, only a subset of patients with long-standing IBD de-velops malignancy, highlighting the complexity of the regulatory effects of the ongoing inflammation on the tumor initiation and progression. This review discusses the multifaceted roles of innate and adaptive immune responses in CAC pathogenesis. Innate immune signaling mediated by pattern recognition recep-tors, particularly Toll-like receptors, integrates microbial and damage-associated sig-nals to activate inflammatory pathways that regulate epithelial proliferation, survival, and tumor-promoting cytokine networks. Tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells contribute to carcinogenesis by sustaining chronic inflammation, promoting immunosuppression, and remodeling the tumor mi-croenvironment, although under specific conditions these cells can also support anti-tumor immunity. Innate lymphocyte subsets participate in immune surveillance and epithelial homeostasis, yet may also amplify inflammatory circuits that influence tu-mor development. Adaptive immune populations further shape CAC evolution, as CD4⁺ T-helper subsets, CD8⁺ cytotoxic T lymphocytes, regulatory T cells, and B cells exert divergent effects depending on cytokine milieu, immune context, and disease stage. Understanding immune-cell plasticity and the molecular pathways governing these processes may facilitate the identification of predictive biomarkers and the de-velopment of targeted immunomodulatory strategies aimed at preventing CAC.

Abstract: High liver fat content is closely associated with hepatic disease and multiple comorbidities including cancer, diabetes and cardiovascular accidents. Therefore, accurate quantification of hepatic steatosis is essential for clinical management. Although MRI provides a non-invasive means for hepatic fat assessment, current approaches remain limited by variability introduced through region-of-interest based methodologies or by classification models that predict discrete fat grades without providing uncertainty estimates. This study proposes a novel approach for hepatic steatosis quantification based on a probabilistic neural network and Beta distribution with single in-phase MRI image inputs to provide estimates of the percentage of hepatic fat with corresponding prediction confidence intervals. The novel model achieved a low prediction error and demonstrated good generalization performance on the test set. By explicitly incorporating uncertainty quantification into the estimates of hepatic steatosis, this probabilistic framework represents a methodological advance that offers an accurate estimate that can be interpreted with greater confidence.

Abstract: Background: Organized colorectal cancer (CRC) screening programs have been widely implemented across Europe; however, robust population-level evaluations of their real-world effectiveness, particularly for programmes based exclusively on faecal immunochemical testing (FIT), remain limited. The Galician CRC screening programme was progressively implemented between 2013 and 2019. Methods: We conducted a population-based ecological time-series study using data from the Galician Tumour Registry (ICD-10 C18–C21) for 2015–2023. Age-standardized mortality (ASMR) and incidence (ASIR) rates were analyzed. Structural changes associated with program implementation were evaluated using interrupted time-series (ITS) models, estimating annual percent change (APC) before and after implementation and the net change in slope (ΔAPC). Absolute and relative changes in ASMR and ASIR were calculated by comparing 2015–2017 and 2019–2023. Analyses were performed for the overall population and for individuals aged 50–69 years. Results: Between 2015 and 2023, overall CRC mortality declined significantly (APC −3.00%; 95% CI −3.37 to −2.63). ITS analysis demonstrated a marked modification of mortality trajectories following program implementation. Mortality shifted from an increasing pre-implementation slope (APC +13.70%; 95% CI 10.12, 17.39) to a significant annual decline post-implementation (APC −3.62%; 95% CI −4.47, −2.76), yielding a ΔAPC of −17.32. In individuals aged 50–69 years, the structural change was more pronounced (ΔAPC −19.88), with post-implementation mortality decreasing by −8.08% annually (95% CI −10.43, −5.66). Incidence showed a comparable structural modification. Overall APC changed from +15.26% (95% CI 5.48, 25.95) before implementation to −2.48% (95% CI −5.29, 0.41) afterwards (ΔAPC −17.74). In the screening-eligible population, APC shifted from +21.32% (95% CI 4.60, 40.71) to −3.74% (95% CI −7.62, 0.30), corresponding to a ΔAPC of −25.06. Descriptively, ASMR declined from 41.92 to 35.91 per 100,000 (−14.33%), and ASIR from 98.37 to 85.16 per 100,000 (−13.42%) between 2015–2017 and 2019–2023. Relative reductions were larger in individuals aged 50–69 years and were more pronounced for colon cancer than for rectal cancer. Conclusions: Implementation of an organized FIT-based screening program was associated with a structural change in CRC mortality and incidence trends, particularly among individuals aged 50–69 years.

Abstract: Background: Discrepancies are frequently observed between liver steatosis grading assessed by conventional B-mode ultrasonography and vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP). This study aimed to identify factors associated with these differences and to evaluate whether the two imaging methods provide comparable steatosis classifications. Methods: We conducted a retrospective cross-sectional observational study including 130 hospitalized patients evaluated over a two-year period who underwent laboratory testing, abdominal ultrasonography, and transient elastography. The analyzed variables included demographic characteristics, nutritional status, comorbidities, and biochemical parameters such as alanine aminotransferase (ALAT), total cholesterol, triglycerides, gamma-glutamyl transferase (GGT), and the fibrosis-4 index (FIB-4). Patients were classified into two groups: concordant steatosis grading between the two methods (n = 61) and discordant results (n = 69). Results: Concordant steatosis grading was more frequently observed in patients with serum total cholesterol >200 mg/dL (45.9%) and FIB-4 values between 1.45–3.25 (44.2%). A trend toward higher concordance was also observed in patients with elevated triglycerides. In contrast, viral liver disease was significantly associated with discordant results (26.2%). Higher fibrosis stages assessed by VCTE (F ≥ 2) and FIB-4 values >3.25 showed a non-significant trend toward discordance. Conclusions: Several clinical and biochemical factors influence the agreement between ultrasound and VCTE-based CAP in the assessment of hepatic steatosis. Elevated cholesterol and intermediate FIB-4 values were associated with concordant results, whereas viral liver disease was associated with discordance between the two imaging modalities.

Abstract: Background/Objectives: This study aimed to develop and evaluate a prediction model for fatty liver (hepatic steatosis) using ultrasound-derived quantitative variables, with MRI DIXON-based fat fraction (MRI-FF) as the reference standard. Methods: Twenty-seven participants with above-normal BMI underwent ultrasound and MRI examinations con-currently. Ultrasound images of the liver, kidney, and spleen were acquired at dynamic range (DR) settings of 100, 150, and 200. Quantitative variables (signal intensity, linear slope, exponential attenuation coefficient, and R²) were extracted using ImageJ. Key varia-bles were selected via principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) with VIP scores ≥1.25. A support vector ma-chine (SVM) model was constructed using training (n=21) and validation (n=6) datasets. Results: PCA and OPLS-DA revealed that the liver-to-kidney attenuation ratio, liver at-tenuation R² (DR200), and linear slope R² (DR200) correlated most strongly with MRI-FF (r=0.814, 0.753, 0.724; all p < 0.001). Attenuation variables were significantly higher in fatty liver groups across all MRI-FF thresholds. The SVM model demonstrated excellent predic-tive performance (RMSE=2.1997, r=0.82, p < 0.001). Conclusions: Ultrasound-derived sig-nal attenuation characteristics correlate strongly with MRI-FF, enabling accurate quantita-tive assessment of hepatic steatosis through machine learning. This noninvasive, cost-effective approach shows significant potential for screening and longitudinal moni-toring of fatty liver disease.

Abstract: The traditional Japanese dietary pattern, characterized by extremely low fat intake (<15% of energy), has long been regarded as a paradigm of healthy eating. Paradoxically, Japan remains one of the developed countries with the highest gastric cancer incidence globally. Current explanations focusing on high salt intake and Helicobacter pylori infection fail to fully account for this elevated risk. We propose a novel hypothesis: long-term extreme low-fat diet is an independent synergistic risk factor for gastric diseases in Japan. Chronic inadequate dietary fat intake impairs gastrointestinal mucosal barrier integrity through multiple mechanisms—reduced phospholipid synthesis, diminished prostaglandin E2 production, and disrupted gut microbiota homeostasis. This compromised mucosal barrier creates a "vulnerable state" that amplifies the damaging effects of established risk factors such as high salt consumption and H. pylori infection. Supporting evidence includes: (1) animal studies demonstrating that essential fatty acid deficiency impairs gastric mucosal protection and increases susceptibility to injury; (2) the Japan Collaborative Cohort Study showing that a western-style breakfast pattern, characterized by higher fat intake, was significantly associated with lower stomach cancer risk in males (HR 0.49, 95% CI 0.35–0.70) compared with a traditional Japanese-style breakfast; (3) temporal trends showing that increased fat consumption in Japan over 50 years correlates inversely with declining gastric cancer mortality, though concurrent lifestyle changes preclude causal attribution. This hypothesis provides a mechanistic explanation for the Japanese diet paradox and suggests that dietary fat optimization (20–30% of energy) should be considered as a complementary gastric cancer prevention strategy.