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Background Gastrointestinal (GI) cancers were responsible for 26.3% of cancer cases and 35.4% of deaths worldwide in 2018. This study aimed to analyze the global incidence, mortality, prevalence, and contributing risk factors of the 6 major GI cancer entities [esophageal cancer (EC), gastric cancer (GC), liver cancer (LC), pancreatic cancer (PC), colon cancer, and rectal cancer]. Methods Using the Global Cancer Observatory and the Global Health Observatory databases, we reviewed the current GI cancer incidence, prevalence, and mortality, analyzed the association of GI cancer prevalence with national human development indices (HDIs), identified the contributing risk factors, and estimated developing age‐ and sex‐specific trends in incidence and mortality. Results In 2020, the trend in age‐standardized rate of incidence of GI cancers closely mirrored that of mortality, with the highest rates of LC, EC, and GC in Asia and of colorectal cancer (CRC) and PC mainly in Europe. Incidence and mortality were positively, but the mortality‐to‐incidence ratio (MIR) was inversely correlated with the national HDI levels. High MIRs in developing countries likely reflected the lack of preventive strategies and effective treatments. GI cancer prevalence was highest in Europe and was also positively correlated with HDIs and lifestyle‐associated risk factors, such as alcohol consumption, smoking, obesity, insufficient physical activity, and high blood cholesterol level, but negatively correlated with hypertension and diabetes. Incidences of EC were consistently and those of GC mostly decreasing, whereas incidences of CRC were increasing in most countries/regions, especially in the younger populations. Incidences of LC and PC were also increasing in all age‐gender populations except for younger males. Mortalities were decreasing for EC, GC, and CRC in most countries/regions, and age‐specific trends were observed in PC and LC with a decrease in the younger but an increase in the older population. Conclusions On the global scale, higher GI cancer burden was accompanied, for the most part, by factors associated with the so‐called Western lifestyle reflected by high and very high national HDI levels. In countries/regions with very high HDI levels, patients survived longer, and increasing GI cancer cases were observed with increasing national HDI levels. Optimizing GI cancer prevention and improving therapies, especially for patients with comorbid metabolic diseases, are thus urgently recommended. Prevalence of gastrointestinal cancers was positively correlated with national human development index levels, but negatively with hypertension and diabetes rates. Age‐specific trends were observed in stomach cancer and esophagus cancer for incidence and in liver cancer and pancreatic cancer for mortality, as well as sex‐specific trends for stomach cancer and pancreatic cancer in the elder.These findings suggest that future research has to focus on the specific etiology of gastrointestinal cancers behind these epidemiologic transitions and improve therapeutic strategies for patients with comorbid metabolic diseases.

Background: Malignant bowel obstruction (MBO) is a common and distressing complication in advanced gastrointestinal cancers, significantly impacting patients’ quality of life. When conservative management fails, palliative decompression is essential to relieve symptoms such as nausea, vomiting, and abdominal distension. Venting gastrostomy is the most established method; however, anatomical challenges may necessitate alternative percutaneous approaches. Objective: This narrative review aims to provide a comprehensive overview of percutaneous gastrostomy techniques for palliative gastrointestinal decompression, including percutaneous endoscopic gastrostomy (PEG), interdisciplinary imaging-guided percutaneous or transhepatic gastrostomy, and percutaneous transesophageal gastrostomy (PTEG). Methods: A literature review was conducted to evaluate the indications, techniques, efficacy, and complications associated with these procedures. The role of a multidisciplinary approach, incorporating radiologic, endoscopic, and palliative care expertise, was also explored. Results: PEG remains the gold standard for venting gastrostomy, achieving symptom relief in up to 92% of cases, with a low complication rate. However, interdisciplinary imaging-guided percutaneous or transhepatic gastrostomy offers a viable alternative for patients with surgically altered anatomy or difficult percutaneous access. PTEG, a newer technique, has demonstrated high technical success and symptom improvement, particularly in patients with extensive peritoneal carcinomatosis or massive ascites, where transabdominal approaches are not feasible. Conclusions: Palliative percutaneous decompression provides effective symptom relief in advanced gastrointestinal cancer. The choice of technique should be individualized based on patient anatomy, clinical condition, and resource availability. A multidisciplinary approach remains crucial in tailoring decompression strategies to improve the quality of life in end-stage malignancies.

Significance Because obese people are at an increased risk of many age-related diseases, it is a plausible hypothesis that obesity increases the biological age of some tissues and cell types. However, it has been difficult to detect such an accelerated aging effect because it is unclear how to measure tissue age. Here we use a recently developed biomarker of aging (known as “epigenetic clock”) to study the relationship between epigenetic age and obesity in several human tissues. We report an unexpectedly strong correlation between high body mass index and the epigenetic age of liver tissue. This finding may explain why obese people suffer from the early onset of many age-related pathologies, including liver cancer. Because of the dearth of biomarkers of aging, it has been difficult to test the hypothesis that obesity increases tissue age. Here we use a novel epigenetic biomarker of aging (referred to as an “epigenetic clock”) to study the relationship between high body mass index (BMI) and the DNA methylation ages of human blood, liver, muscle, and adipose tissue. A significant correlation between BMI and epigenetic age acceleration could only be observed for liver ( r = 0.42, P = 6.8 × 10 ⁻⁴ in dataset 1 and r = 0.42, P = 1.2 × 10 ⁻⁴ in dataset 2). On average, epigenetic age increased by 3.3 y for each 10 BMI units. The detected age acceleration in liver is not associated with the Nonalcoholic Fatty Liver Disease Activity Score or any of its component traits after adjustment for BMI. The 279 genes that are underexpressed in older liver samples are highly enriched (1.2 × 10 ⁻⁹) with nuclear mitochondrial genes that play a role in oxidative phosphorylation and electron transport. The epigenetic age acceleration, which is not reversible in the short term after rapid weight loss induced by bariatric surgery, may play a role in liver-related comorbidities of obesity, such as insulin resistance and liver cancer.

ObjectiveThe rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD.DesignMice with hepatocyte-specific deletion of MBOAT7 (Mboat7Δhep) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics. We analysed the association of rs641738C>T genotype with liver inflammation and fibrosis in 846 NAFLD patients and obtained genotype-specific liver lipidomes from 280 human biopsies.ResultsAllelic imbalance analysis of heterozygous human liver samples pointed to lower expression of the MBOAT7 transcript on the rs641738C>T haplotype. Mboat7Δhep mice showed spontaneous steatosis characterised by increased hepatic cholesterol ester content after 10 weeks. After 6 weeks on a high fat, methionine-low, choline-deficient diet, mice developed increased hepatic fibrosis as measured by picrosirius staining (p<0.05), hydroxyproline content (p<0.05) and transcriptomics, while the inflammatory cell populations and inflammatory mediators were minimally affected. In a human biopsied NAFLD cohort, MBOAT7 rs641738C>T was associated with fibrosis (p=0.004) independent of the presence of histological inflammation. Liver lipidomes of Mboat7Δhep mice and human rs641738TT carriers with fibrosis showed increased total lysophosphatidylinositol levels. The altered lysophosphatidylinositol and phosphatidylinositol subspecies in MBOAT7Δhep livers and human rs641738TT carriers were similar.ConclusionMboat7 deficiency in mice and human points to an inflammation-independent pathway of liver fibrosis that may be mediated by lipid signalling and a potentially targetable treatment option in NAFLD.

Purpose: Aim of this study was to investigate the association between postdiagnosis body mass index (BMI) and all-cause mortality in colorectal cancer (CRC) survivors in a prospective study and meta-analysis. Methods: We conducted a prospective cohort study on 2,143 CRC survivors in Germany. Participants were recruited to the study on average 4 years after diagnosis, and postdiagnosis BMI was assessed at recruitment using a self-administered questionnaire. CRC survivors were followed up for a mean time of 3.5 years. The association between BMI and all-cause mortality was investigated using multivariable Cox proportional hazards models. Additionally, we performed a meta-analysis of studies on postdiagnosis BMI and all-cause mortality (n = 5, including this study) by applying random-effects models. Results: In the prospective analysis, 349 participants died. BMI was not statistically significantly associated with all-cause mortality. Compared to normal weight survivors, the hazard ratios (HRs) [95 % confidence interval (CI)] for all-cause mortality in underweight, overweight and obese survivors were 1.65 (0.79–3.45), 0.80 (0.62–1.03) and 0.84 (0.62–1.14), respectively. In the meta-analysis, individuals with underweight were at increased risk for all-cause mortality [HR (95 % CI) 1.72 (1.18–2.49)], whereas individuals with overweight had a lower risk [HR (95 % CI) 0.79 (0.71–0.88)], compared to normal weight subjects. For obesity, the risk of mortality was also reduced with only borderline significance [HR (95 % CI) 0.88 (0.77–1.00)]. Conclusions: While the present study as well as single previously published studies showed that overweight was associated with a non-significant reduced risk for all-cause mortality, our meta-analysis indicated a decreased mortality risk among overweight CRC survivors.

Background The group of colorectal cancer (CRC) survivors continues to grow worldwide. Understanding health-related quality of life (HRQOL) determinants and consequences of HRQOL impairments in long-term CRC survivors may help to individualize survivorship care plans. We aimed to i) examine the HRQOL status of CRC long-term survivors, ii) identify cross-sectional sociodemographic and clinical correlates of HRQOL, and iii) investigate the prospective association of HRQOL after CRC diagnosis with all-cause mortality. Methods We assessed HRQOL within a Northern German cohort of 1294 CRC survivors at a median of 6 years after CRC diagnosis using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Cross-sectional correlates of different HRQOL dimensions were analyzed using multivariable-adjusted logistic regression models with HRQOL as a binary variable. With multivariable-adjusted Cox proportional hazards regression models, hazard ratios (HR) of all-cause mortality were estimated per 10-point-increments of an HRQOL summary score, a global quality of life scale, and HRQOL functioning and symptom domains. Results The median HRQOL summary score was 87 (interquartile range: 75–94). Sex, age, education, tumor location, metastases, other cancers, type of therapy, and current stoma were identified as correlates of different HRQOL scales. After a median follow-up time of 7 years after HRQOL assessment, 175 participants had died. Nearly all HRQOL domains, except for cognitive functioning and diarrhea, were significantly associated with all-cause mortality. A 10-point-increment in the summary score decreased the risk of death by 24% (HR: 0.76; 95% CI: 0.70–0.82). Conclusions HRQOL in CRC survivors appeared to be relatively high in the long term. Various clinical and sociodemographic factors were cross-sectionally associated with HRQOL in long-term CRC survivors. Lower HRQOL was associated with increased all-cause mortality. Individualized healthcare programs for CRC survivors (including psychosocial screening and interventions) are needed to detect decreased HRQOL and to further improve long-term HRQOL and survival.

Early disease diagnosis is key to the effective treatment of diseases. Histopathological analysis of human biopsies is the gold standard to diagnose tissue alterations. However, this approach has low resolution and overlooks 3D (three-dimensional) structural changes resulting from functional alterations. Here, we applied multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD). We identified a set of morphometric cellular and tissue parameters correlated with disease progression, and discover profound topological defects in the 3D bile canalicular (BC) network. Personalized biliary fluid dynamic simulations predicted an increased pericentral biliary pressure and micro-cholestasis, consistent with elevated cholestatic biomarkers in patients’ sera. Our spatially resolved models of human liver tissue can contribute to high-definition medicine by identifying quantitative multiparametric cellular and tissue signatures to define disease progression and provide new insights into NAFLD pathophysiology. A combination of high-resolution imaging and modeling approaches facilitates the study of the mechanisms and clinical progression of non-alcoholic fatty liver disease in humans.

Background/Objectives: Pancreatic surgery has always been associated with a variety of complications. In the current study, we analyzed more than 800 consecutive pancreatic resections and tried to find clinically relevant routine parameters that could predict adverse outcomes at an early stage. We focused on hepato-pancreato-biliary routine parameters, especially on liver enzymes, because so far there are no studies showing any correlation between postoperatively elevated liver enzymes and postoperative complications. Methods: All pancreatic resections of a tertiary care center from 2003 until 2025 were documented prospectively and analyzed retrospectively. Data analysis comprised descriptive as well as inferential statistical analyses. Results: Laboratory values from 808 consecutive resections were analyzed for the first week after surgery. Elevated aspartate aminotransferase (AST) was associated with postoperative hemorrhage on POD 1, pulmonary insufficiency on POD 1 to 4, other complications on POD 1 to 5, MODS on POD 2 to 4, and development of pneumonia on POD 3 to 5. Elevated alanine aminotransferase (ALT) was associated with pulmonary insufficiency on POD 1 to 4 and POD 6, pneumonia, and other complications on POD 3. It was also associated with MODS on POD 1 to 6. Bilirubin elevated preoperatively and on POD 1 could not really predict any complication. In this study, we can also confirm that elevated amylase and lipase can predict complications. Conclusions: This is the first study that shows a correlation between postoperatively elevated AST and ALT and the development of postpancreatectomy complications. Elevated AST and ALT, especially in combination with postoperative pancreatitis or at least elevated pancreatic enzymes, can identify patients at risk for life-threatening conditions and might be useful to decrease failure-to-rescue patients.

Objectives: Thoracic endovascular aortic repair (TEVAR) is rarely indicated on an urgent or emergent basis soon after open surgical repair of type A aortic dissection (TAAD), and systematic data on clinical outcomes are therefore missing. In the present study, we analyze a contemporary case series regarding the outcome after urgent and emergent endovascular treatment of the downstream thoracic aorta, following open surgery for TAAD. Methods: The study was conducted as a retrospective observational analysis. From January 2024 until April 2025, seven patients (four male, aged 56.8 ± 5.6 years) were treated with TEVAR on an urgent or emergent basis within 48 h after open surgical repair of TAAD at our institution. In all seven patients, the initial dissection extended from the ascending to the abdominal aorta. All seven patients had previously received emergent open surgical repair by ascending aortic repair combined with hemiarch replacement (five patients) or total arch replacement, utilizing the frozen elephant trunk (FET) technique (two patients). Results: In four patients, the indication for urgent TEVAR was due to true lumen collapse (TLC) of the downstream aorta with resulting visceral or peripheral malperfusion symptoms. Three patients were treated on an emergent basis, due to rupture of the descending thoracic aorta with a resulting hemorrhage. Technical success of the TEVAR procedure was 100%. Thirty-day mortality was 0% in the TLC cases but 66% in the ruptured cases, where two of three patients died postoperatively due to the consequences of severe hemorrhagic shock. Within the surviving patients, no subsequent aortic events occurred during follow-up. Late mortality was 0%. The follow-up period was 15.7 ± 2.0 months. Conclusions: In our case series, mortality of urgent or emergent TEVAR soon after open surgical repair for TAAD is substantial, especially in patients that were treated due to acute rupture of the descending thoracic aorta and consecutive hemorrhagic shock. On the other hand, true lumen collapse with resulting malperfusion was successfully treated by instant TEVAR application in all patients without late aortic complications by the midterm follow-up.

A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver. Spatial mapping of genomic programs in tissue cells is an important step in the understanding of organ function and disease. Here, the authors provide a spatially resolved epigenomic and transcriptomic map of human liver and show porto-central gradients in metabolic and morphogen networks and transcription factor binding sites as a basis to better understand liver regeneration and function.