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Associations between psychiatric disorders and digestive tract cancers have been proposed. However, the causal link between these factors remains unclear. This study pioneers Mendelian randomization (MR) analysis to explore the genetic link between psychiatric disorders and digestive tract cancers risk. We analysed data on six psychiatric disorders [schizophrenia, bipolar disorder, major depressive disorder (MDD), attention deficit hyperactivity disorder, autism spectrum disorder, and panic disorder (PD)] and digestive tract cancers [esophagus cancer (EC), gastric cancer (GC), and colorectal cancer (CRC)] from genome-wide association studies databases. Using instrumental variables identified from significant single nucleotide polymorphism associations, we employed the inverse variance weighted (IVW) method alongside the weighted median (WM) method and MR-Egger regression. The results revealed no causal link between psychiatric disorders and the risk of EC or GC. Psychiatric disorders were not identified as risk factors for CRC. Notably, PD demonstrated a lower CRC risk (OR = 0.79, 95% CI 0.66-0.93, P = 0.01). This MR analysis underscores the lack of a causal association between psychiatric disorders and digestive tract cancers risk while suggesting a potential protective effect of PD against CRC., (© 2024. The Author(s).)

Purpose: Previous observational studies have shown that green tea consumption is associated with a reduced incidence of digestive system cancers (DSCs). However, the observed association could be due to confounding factors. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the causal effect of green tea intake on the risk of five common DSCs., Methods: Independent genetic variants strongly associated with green tea consumption in European and East Asian populations were selected as instrumental variables in genome-wide association studies involving up to 64,949 European individuals and 152,653 East Asian individuals, respectively. The associations between genetic variants and DSCs were extracted from the FinnGen study and the Japan Biobank. The primary analysis was performed using random-effects inverse variance weighting (IVW). Other MR analyses, including weighted mode-based estimate, weighted-median, MR-Egger regression, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis, were used for sensitivity analyses. In addition, a multivariate MR design was performed to adjust for smoking and alcohol consumption., Results: The IVW results showed no causal relationship between tea intake and DSCs risk in European population (esophagus cancer: odds ratio (OR) = 1.044, 95% confidence interval (CI) 0.992-1.099, p = 0.096; stomach cancer: OR = 0.988, 95% CI 0.963-1.014, p = 0.368; colorectal cancer: OR = 1.003, 95% CI 0.992-1.015, p = 0.588; liver cancer: OR = 0.996, 95% CI 0.960-1.032, p = 0.808; pancreatic cancer: OR = 0.990, 95% CI 0.965-1.015, p = 0.432). The MR-Egger regression, MR-PRESSO analysis and other methods also confirmed the reliability of the conclusion. Similarly, no significant association was found between green tea consumption and the incidence of DSCs among East Asians. This relationship is not significant even after adjusting for smoking and alcohol consumption (P > 0.05)., Conclusion: Our study provides evidence that genetically predicted green tea intake is not causally associated with the development of DSCs in the European and East Asian population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

To investigate whether early-life exposure to the Great Famine of 1959-1961 in China was associated with the risk of digestive system cancer. The prospective cohort study involved 17 997 participants from the Kailuan Study (Tangshan, China) that began in 2006. All participants were divided into three groups based on their date of birth. The unexposed group (born from 1 October 1962 to 30 September 1964), fetal-exposed group (born from 1 October 1959 to 30 December 1961), and early-childhood-exposed group (born from 1 October 1956 to 30 December 1958). The Cox proportional hazards model was used to analyze the association between early famine exposure and digestive system cancer. During the mean follow-up period of (10.4 ± 2.2) years, a total of 223 digestive system cancer events occurred. Including 54 cases in the unexposed group (62.14/100 000 person-years), 57 cases in the fetal-exposed group (114.8/100 000 person-years), and 112 cases in the early-childhood-exposure group (122.2/100 000 person-years). After adjusting covariates, compared with the unexposed group, the HR and 95% CI were 1.85 (1.28, 2.69) for participants in the fetal-exposed group and 1.92 (1.38, 2.66) for participants in the early-childhood-exposed group. No interactions were observed in our study. After classifying digestive system cancers, the HR and 95% CI were 2.02 (1.03, 3.97) for colorectal cancer for participants in the fetal-exposed group and 2.55 (1.43, 4.55) for participants in the early-childhood-exposed group. The HR and 95% CI were (1.13, 3.83) of liver cancer for participants in the fetal-exposed group and 1.15 (0.63, 2.10) for participants in the early-childhood-exposed group. Early-life famine exposure was associated with a higher risk of digestive system cancer in adulthood. Fetal-exposed individuals might increase the risk of colorectal cancer and liver cancer, and early childhood-exposed might increase the risk of colorectal cancer., Competing Interests: We declare that we have no conflict of finical and commercial interest.

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs., (© 2024. The Author(s).)

Background: The diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database., Methods: PubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess  study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg's and Egger's tests., Results: A total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method., Conclusions: There was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference., (© 2023. The Author(s).)

Little is known about the relation between plant-based dietary patterns and digestive system cancers. This study investigated the prospective association between 3 pre-defined indices of plant-based dietary pattern and risk of digestive system cancers, as a whole or individually. We utilized data from 3 prospective cohorts, the Nurses' Health Study (1984-2018, 74,496 women aged 65 ± 10.9 years), Nurses' Health Study II (1991-2017, 91,705 women aged 49.3 ± 8.3 years), and Health Professionals Follow up Study (1986-2016, 45,472 men aged 65.4 ± 11.0 years). We used Cox proportional hazards regression models to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) of digestive system cancers across 3 plant-based diet index scores: overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). During a follow-up of 4,914,985 person-years, we identified 6,518 cases of digestive system cancers. In the pooled analysis of 3 cohorts, the HRs (95% CIs) per 10-point increase in hPDI score were 0.93 (0.89, 0.97) for total digestive system cancer, 0.94 (0.89, 0.99) for gastrointestinal tract cancer, 0.89 (0.81, 0.98) for accessory organ cancer, and 0.68 (0.52, 0.91) for liver cancer. In contrast, the HRs (95% CIs) per 10-point increase in uPDI score was 1.06 (1.01, 1.11) for gastrointestinal tract cancer and 1.07 (1.01, 1.13) for colorectal cancer. A healthy plant-based dietary pattern was associated with reduced risks of total digestive system cancers as well as individual cancers in the gastrointestinal tract and the accessory organs. Emphasizing the healthiness and quality of plant-based diets may be important for the prevention of developing cancers in the digestive system., (© 2023. Springer Nature B.V.)

Introduction: Immunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein-Barr virus (EBV) is considered to be involved in the etiology of this neoplasm., Case Report: A 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions., Conclusion: Although the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors., (© 2021. The Author(s).)

This meta-analysis was aimed to estimate the diagnostic performance of volatile organic compounds (VOCs) as a potential novel tool to screen for the neoplasm of the digestive system. An integrated literature search was performed by two independent investigators to identify all relevant studies investigating VOCs in diagnosing neoplasm of the digestive system from inception to 7th December 2020. STATA and Revman software were used for data analysis. The methodological quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A bivariate mixed model was used and meta-regression and subgroup analysis were performed to identify possible sources of heterogeneity. A total of 36 studies comprised of 1712 cases of neoplasm and 3215 controls were included in our meta-analysis. Bivariate analysis showed a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.83-0.90), specificity of 0.86 (95% CI 0.82-0.89), a positive likelihood ratio of 6.18 (95% CI 4.68-8.17), and a negative likelihood ratio of 0.15 (95% CI 0.12-0.20). The diagnostic odds ratio and the area under the summary ROC curve for diagnosing neoplasm of the digestive system were 40.61 (95% CI 24.77-66.57) and 0.93 (95% CI 0.90-0.95), respectively. Our analyses revealed that VOCs analysis could be considered as a potential novel tool to screen for malignant diseases of the digestive system., (© 2021. The Author(s).)

Background: Unrestrained eating behavior, as a potential proxy for diet frequency, timing, and caloric intake, has been questioned as a plausible risk factor for digestive system cancers, but epidemiological evidence remains sparse., Objectives: We investigated prospectively the associations between unrestrained eating behavior and digestive system cancer risk., Methods: Participants in the Nurses' Health Study who were free of cancer and reported dietary information in 1994 were followed for ≤18 y. Cox models were used to estimate HRs and 95% CIs for unrestrained eating (eating anything at any time, no concern with figure change, or both) and risk of digestive system cancers., Results: During follow-up, 2064 digestive system cancer cases were documented among 70,450 eligible participants in analyses of eating anything at any time, In total, 2081 digestive system cancer cases were documented among 72,468 eligible participants in analyses of no concern with figure change. In fully adjusted analyses, women with the behavior of eating anything at any time had a higher risk of overall digestive system cancer (HR: 1.22; 95% CI: 1.10, 1.35), overall gastrointestinal tract cancer ((HR: 1.33; 95% CI: 1.18, 1.50), buccal cavity and pharynx cancer (HR: 1.50; 95% CI: 1.02, 2.21), esophageal cancer (HR: 1.62; 95% CI: 1.01, 2.62), small intestine cancer (HR: 1.92; 95% CI: 1.02,3. 59), and colorectal cancer (HR: 1.20; 95% CI: 1.04, 1.38), and a non-statistically significant increased risk of stomach cancer (HR: 1.54; 95% CI: 0.96,2.48), compared with women without this behavior. No statistically significant association was observed for pancreatic cancer and liver and gallbladder cancer. The combined effect of eating anything at any time and having no concern with figure change was associated with a significantly increased risk of overall digestive system cancer (HR: 1.27; 95% CI: 1.10, 1.46), overall gastrointestinal tract cancer (HR: 1.45; 95% CI: 1.23, 1.71), and colorectal cancer (HR: 1.34; 95% CI: 1.11, 1.63), compared with women exhibiting the opposite., Conclusions: Unrestrained eating behavior was independently associated with increased risk of gastrointestinal tract cancers. The potential importance of unrestrained eating behavior modification in preventing gastrointestinal tract cancers should be noted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: This case-control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers., Methods: The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check-up registry, and cancer-free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications., Results: Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05-1.85), and anti-HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61-0.85), colonic (aOR = 0.73, 95% CI: 0.60-0.89), rectal (aOR = 0.73, 95% CI: 0.63-0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42-0.82) cancers. Compared to subgroups with non-infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03-1.93). However, no clear association was found between HBV infection and other cancers., Conclusions: HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV-associated gastric cancer needs to investigate further., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cancers evolve as a result of the accelerated proliferation of cancer cells in a complicated, enriched, and active microenvironment. Tumor microenvironment (TME) components are the master regulators of any step of cancer development. The tumor microenvironment is composed of many cellular and noncellular components that contribute to the evolution of cancer cells. Cancer-associated fibroblasts (CAFs) are activated fibroblasts in the TME that implicate in tumor progression and metastasis dissemination through secretion of oncogenic factors which are carried to the secondary metastatic sites through exosomes. In this review, we aimed to assess the role of CAF-derived exosomes in TME construction and pre-metastatic niche formation in different cancers of the digestive system in order to better understand some important mechanisms of metastasis and provide possible targets for clinical intervention. This review article is divided into two thematic parts explaining the general mechanisms of pre-metastatic niche formation and metastasis and the role of CAF-derived exosomes in different digestive system cancers including colorectal, gastric, esophageal, pancreatic, and liver cancers.

The aim of the present study was to identify novel antibody markers for the early diagnosis of atherosclerosis in order to improve the prognosis of patients at risk for acute ischemic stroke (AIS) and acute myocardial infarction (AMI). A first screening involved the serological identification of antigens by recombinant cDNA expression cloning and identified additional sex combs‑like 2 (ASXL2) as a target antigen recognized by serum IgG antibodies in the sera of patients with atherosclerosis. Antigens, including the recombinant glutathione S‑transferase‑fused ASXL2 protein and its synthetic peptide were then prepared to examine serum antibody levels. Amplified luminescence proximity homogeneous assay‑linked immunosorbent assay, which incorporates glutathione‑donor beads and anti‑human‑IgG‑acceptor beads, revealed significantly higher serum antibody levels against the ASXL2 protein and its peptide in the patients with AIS, diabetes mellitus, AMI, chronic kidney disease, esophageal squamous cell carcinoma, or colorectal carcinoma compared with those in healthy donors. The ASXL2 antibody levels were well associated with hypertension complication, but not with sex, body mass index, habitual smoking, or alcohol intake. These results suggest that the serum ASXL2 antibody marker can discriminate between hypertension‑induced atherosclerotic AIS and AMI, as well as a number of digestive organ cancers.

Pteridium arachnoideum , a fern of the Pteridium aquilinum species complex found in South America, is responsible for several different syndromes of poisoning. Cases of bovine enzootic hematuria and upper alimentary squamous cell carcinoma are both frequent occurrences in Brazil, whereas only bovine enzootic hematuria is noted with any frequency around the world. The reason for the high frequency of upper alimentary squamous cell carcinoma in Brazil is not currently known. One possible explanation may be the higher levels of ptaquiloside and pterosin B in Brazilian Pteridium than those present in the plant in other countries. However, these levels have not yet been determined in P. arachnoideum . Thus, the present study aimed to measure and compare ptaquiloside and pterosin B levels in mature green fronds and sprouts of P. arachnoideum collected from different locations in Brazil. Samples of P. arachnoideum were collected from the states of Minas Gerais and Rio Grande do Sul. A total of 28 mature leaf samples and 23 sprout samples were used. The mean concentrations of ptaquiloside and pterosin B present in the mature green fronds of P. arachnoideum ranged from 2.49 to 2.75 mg/g and 0.68 to 0.88 mg/g, respectively; in P. arachnoideum sprouts, mean concentrations of ptaquiloside and pterosin B ranged from 12.47 to 18.81 mg/g, and 4.03 to 10.42 mg/g for ptaquiloside and pterosin B, respectively. Thus, ptaquiloside and pterosin B levels in P. arachnoideum samples collected in Brazil were higher in sprouts than in mature green fronds, as observed in other countries. However, there was no variation in ptaquiloside levels among plants collected from different cities in Brazil. The high frequency of upper alimentary squamous cell carcinoma in Brazilian cattle may not be attributed to greater levels of ptaquiloside and pterosin B in P. arachnoideum than in other Pteridium species in other countries.

Background: The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies., Methods: The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis., Results: The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses., Conclusions: This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

Introduction: Introduction: the diet plays an important role in the origin and prevention of multiple chronic degenerative diseases, such as cardiovascular diseases or cancer. Objective: the main objective of this paper is to analyze the studies that are focused on researching the relationship between the consumption of the particular groups of foods and its importance on the increase and for prevention of the risk of cancer appearance. Methods: a bibliographical review was carried out in the main international databases (PubMed, Scopus and Nutrition Reference). The results were structured in two main sections: those related with the increase of cancer risk and food related with the increase of cancer risk. In the present review, 104 scientific articles have been evaluated. Results: the results have shown a positive association between red meat and colon cancer, alcoholic drinks and liver cancer, and salt and gastric cancer. The Mediterranean diet was associated in a preventive way with digestive and respiratory tract cancer. Conversely, no statistically significant association was found between dairy products and ovarian cancer, carbohydrates and sugars and pancreatic cancer, and tae and breast cancer. Conclusions: as a result, healthy eating guidelines, such as the Mediterranean diet, based on lower consumption of red meat, alcoholic drinks and salt, might contribute to reducing the incidence of colon cancer, liver cancer and gastric cancer.

Primary sclerosing cholangitis (PSC) is a chronic progressive inflammatory disease of the bile ducts that leads to multifocal bile duct fibrosis, strictures, cholestasis, liver parenchymal changes, and ultimately cirrhosis. It more commonly occurs in young adults, with a variety of clinical and imaging manifestations. The cause of the disease is not known, but it has a strong association with inflammatory bowel disease and can overlap with other autoimmune diseases, including autoimmune hepatitis and immunoglobulin G4-related disease. Patients are predisposed to various hepatic and extrahepatic deteriorating complications, such as bile duct and gallbladder calculi, acute bacterial cholangitis, liver abscess, and portal hypertension, as well as malignancies including cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Imaging has an essential role in diagnosis, surveillance, and detection of complications. MR cholangiopancreatography and endoscopic retrograde cholangiopancreatography have high specificity and sensitivity for detection of primary disease and assessment of disease progression. However, many patients with PSC are still diagnosed incidentally at US or CT. Novel imaging techniques such as transient elastography and MR elastography are used to survey the grade of liver fibrosis. Annual cancer surveillance is necessary in all PSC patients to screen for CCA and gallbladder cancer. Familiarity with PSC pathogenesis and imaging features across various classic imaging modalities and novel imaging techniques can aid in correct imaging diagnosis and guide appropriate management. The imaging features of the biliary system and liver parenchyma in PSC across various imaging modalities are reviewed. Imaging characteristics of the differential diagnosis of PSC, clinical associations, and complications are described. Finally, the role of imaging in evaluation of PSC progression, pre-liver transplant assessment, and post-liver transplant disease recurrence are discussed. © RSNA, 2019.

Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.

Several studies analysed the associations between dietary carbohydrate intake, glycaemic index (GI) and glycaemic load (GL) and digestive system cancers; however, the results remain controversial. This study was to perform a meta-analysis evaluating the quantitative and dose-response associations between carbohydrate intake, GI and GL, and risk of digestive system cancers. We searched medical and biological databases up to June 2018 and identified twenty-six cohort studies and eighteen case-control studies. Meta-analytic fixed or random effects models were applied to process data. We also performed dose-response analysis, meta-regression and subgroup analyses. We found that high levels of GI were significantly associated with the risk of digestive system cancers at the highest compared with the lowest categories from cohort studies (summary relative risk (RR)=1·10, 95 % CI 1·05, 1·15). Similar effects were observed from case-control studies of the comparison between the extreme categories, but the difference did not reach statistical significance (summary OR=1·28, 95 % CI 0·97, 1·69). We also observed significant dose-response association between GI and digestive system cancers, with every 10-unit increase in GI (summary RR=1·003; 95 % CI 1·000, 1·012 for cohort studies; summary OR=1·09; 95 % CI 1·06, 1·11 for case-control studies). In addition, both cohort studies and case-control studies indicated that neither dietary carbohydrate intake nor GL bore any statistical relationship to digestive system cancers from the results of the highest compared with the lowest categories analyses and dose-response analyses. The results suggest a moderate association between high-GI diets and the risk of digestive system cancers.

Background: Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28-year follow-up period (1991-2018) in a tertiary single institution., Material and Methods: Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs., Results: Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy-related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months)., Conclusions: Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Background/objectives: To assess the association between processed meat and the risk of selected digestive tract and laryngeal cancers., Subjects/methods: We conducted a series of case-control studies between 1985 and 2007 in Italy. The studies included a total of 1475 cases of cancer of the oral cavity and pharynx, 1077 of the larynx, 716 of the esophagus, 999 of the stomach, 684 of the liver, 159 of the biliary tract, 688 of the pancreas, and a total of 9720 controls. Odds ratios (ORs), and the corresponding 95% confidence intervals (CIs), were estimated by unconditional logistic regression models, including terms for socio-demographic factors, tobacco smoking, and alcohol intake., Results: Compared to the lowest tertile of processed meat consumption, the ORs for subjects in the highest one were 1.18 (95% CI 0.98-1.43) for oral cavity and pharyngeal, 1.51 (95% CI 1.18-1.91) for esophageal, 1.19 (95% CI 0.96-1.47) for laryngeal, 0.98 (95% CI 0.81-1.18) for stomach, 0.85 (95% CI 0.51-1.40) for biliary tract, 1.20 (95% CI 0.94-1.54) for liver, and 1.46 (95% CI 1.15-1.85) for pancreatic cancers., Conclusions: Our findings support the hypothesis that high processed meat consumption increases esophageal and pancreatic cancers risk. Residual confounding by socio-demographic factors, tobacco smoking, and alcohol intake may, partly or largely, account for these associations. We found no overall association with other digestive tract and laryngeal cancers.

In the last decade, a barge body of scientific literature has suggested that specific alterations of the gut microbiota may be associated with ther development and clinical course of several gastrointestinal diseases, including irritable bowel syndrome, inflammatory bowel disease, celiac disease, gastrointestinal cancer and Clostridium difficile infection. These alterations are often referred to as "dysbiosis", a generic term designing reduction of gut microbiota biodiversity and alterations in its composition. Here, we provide a synthetic overview of the key concepts on the relationship between intestinal microbiota and gastrointestinal diseases, focusing on the translation of these concepts into clinical practice.

Oxidative stress has been implicated as an important factor in tumorigenesis and tumor progression. The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (NOX4), a substrate of NADPH that can generate H 2 O 2 reactive oxygen species, has been reported to be highly expressed in gastrointestinal tumors. In this review we summarize the available evidence on the biological function of NOX4 in digestive system tumors by focusing on its correlation with classical cell signaling pathways, including VEGF, MAPK and PI3K/AKT, and with biochemical mediators, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein (AP)-1 and transforming growth factor (TGF)-β. According to the clinical and database studies on tumors of the digestive system, such as colorectal, gastric and pancreatic cancer, there are significant associations between NOX4 expression and tumor prognosis as well as patient's survival. Animal studies using NOX4 inhibitors such as diphenylene iodonium and GKT137831, which selectively block NOX4, indicate their potential as therapeutic agents for targeting cancer cells., (© 2018 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Upper digestive tract (UDT) cancer is rare in cattle, however in Southern Brazil, the UDT squamous cell carcinomas (SCCs) are relatively common and have been associated with bracken fern consumption and the presence of papillomas. Although a theory of pathogenesis considers bovine papillomavirus type 4 (BPV-4) as a cofactor in the development of these SCCs, some aspects of the etiopathogenesis of this disease need to be more investigated. In fact, detection of BPV-4 in UDT papillomas is scarce in other regions of the world and has not been performed in Brazil. Therefore, this study had two aims: 1) to analyze the epidemiological, clinical and pathological aspects of 100 natural cases of SCCs in the UDT of cattle grazing on bracken fern (Pteridium arachnoideum) highly contaminated areas, investigating the associations between these parameters; and 2) to investigate the presence of papillomavirus DNA by polymerase chain reaction (PCR) in the UDT papillomas (n = 47) from 30 cattle that also had UDT SCCs. There were statistically significant associations between clinical signs and tumor localization in the UDT; between histological grade of differentiation and tumor localization; and a trend towards significant association between histological grade of differentiation and presence of metastases. The average age of cattle with oropharyngeal SCCs was 7.39 years, with statistically significant difference comparing to cattle with esophageal SCCs (8.6 years). No statistical association was observed among other clinical-pathological parameters (growth pattern and primary site of the tumor) analyzed. No BPV DNA was detected in papillomas by PCR. Therefore, these results suggest the possibility that papillomas of the UDT are not necessarily associated with BPV infection., Competing Interests: The authors have declared that no competing interests exist.

Olfactomedin-4 (OLFM4, GW112, hGC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori ( H. pylori )-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Down-regulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advanced-stage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori -specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest.

Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.

Background: Tobacco use is a major risk factor for increasing the burden of upper aero digestive tract (UADT) cancer in the population of Northeast India., Objective: The objective of this study was to investigate the pattern of tobacco use in different UADT cancer., Materials and Methods: This was a retrospective study of electronically recorded data of the Hospital Cancer Registry for the period of May 2014 to December 2014. The UADT cancers were evaluated for gender and age-group distribution, their relative proportion, and association with tobacco use and tobacco-associated risk in males to develop UADT cancers. The type of tobacco usage was clustered as chewable, smoking, and both. Relative risk (RR) of UADT with tobacco usage was identified for males., Results: A total of 1965 (n) UADT cancer patients were identified, male:female was 2.9, tobacco habits was in 1608 (81.8%) patients, both forms of tobacco use in 705 (43.8%), chewable tobacco use in 588 (36.6%) and smoking in 315 (19.6%) patients, tobacco habits in males ranges from 67.3% to 94.3% and in females range from 5.7% to 32.7%, RR of UADT cancer in males for tongue cancer was 1.5 (confidence interval [CI] =1.2-1.9), oropharynx was 1.4 (CI = 1.0-1.8), hypopharynx 1.4 (CI = 1.1-1.7), esophageal cancer was 1.4 (CI = 1.3-1.7), and for laryngeal cancer RR was 1.7 (CI = 1.0-3.0)., Conclusion: Consumption of chewable tobacco is the major form of tobacco use alone or in combination in UADT cancer patients of our population., Competing Interests: There are no conflicts of interest.

Malignancy represents substantial morbidity and mortality in patients with primary sclerosing cholangitis (PSC). This subset of patients has been proven to be at increased risk for developing cholangiocarcinoma, gallbladder carcinoma and colorectal cancer in those with overlapping inflammatory bowel disease. Herein, we review the prevalence of these malignancies and recommend screening tools and current knowledge to reduce the disease burden in this population. Cholangiocarcinoma is the most dominant malignancy affecting PSC patients, with a lifetime risk ranging from 5% to 20%. We advocate for serial US or MRI/MRCP and CA 19-9 to screen for cholangiocarcinoma. Gallbladder cancer has a lifetime risk around 2% in this population and we agree with annual imaging for lesions as recommended by national guidelines. Patients with PSC and concomitant IBD are at increased risk of colorectal carcinoma from time of diagnosis and therefore should likely undergo annual surveillance. The low rates of hepatocellular cancer and pancreatic cancer indicate surveillance for these malignancies is less advantageous., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This article reviews the significance of the microbiome in cancer epidemiology, mechanistic and technical challenges in the field, and characterization of the microbiome in different tumor types to identify biomarkers of risk, progression, and prognosis. Publications on the microbiome and cancer epidemiology were reviewed to analyze sample collection and processing, microbiome taxa characterization by 16S ribosomal RNA sequencing, and microbiome metabolite characterization (metabotyping) by nuclear magnetic resonance and mass spectrometry. The analysis identified methodology types, research design, sample types, and issues in integrating data from different platforms. Aerodigestive cancer epidemiology studies conducted by different groups demonstrated the significance of microbiome information in developing approaches to improve health. Challenges exist in sample preparation and processing (eg, standardization of methods for collection and analysis). These challenges relate to technology, data integration from "omics" studies, inherent bias in primer selection during 16S ribosomal RNA sequencing, the need for large consortia with well-characterized biospecimens, cause and effect issues, resilience of microbiota to exposure events (requires longitudinal studies), and expanding studies for fungal and viral diversity (most studies used bacterial 16S ribosomal RNA sequencing for microbiota characterization). Despite these challenges, microbiome and cancer epidemiology studies are significant and may facilitate cancer risk assessment, diagnosis, and prognosis. In the future, clinical trials likely will use microbiota modifications to improve the efficacy of existing treatments.

The prevalence of obesity has steadily increased over the past few decades. Previous studies suggest that obesity is an oncogenic factor and that over 20% of all cancers are obesity-related. Among such cancers, digestive system malignancies (including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia, liver, and pancreas) are reported most frequently. While the 5-year survival rates of cancers of the breast and prostate are 90%, that rate is only 45% for digestive cancers. In this review, the mechanisms of obesity-associated digestive cancers are discussed, with an emphasis on obesity-related gene mutations, insulin and insulin-like growth factor signaling pathways, chronic inflammation, and altered adipokine levels. Evidence that these factors often function interdependently rather than independently in carcinogenesis is presented. Recommended interventions that may reduce the burden of obesity-associated digestive cancers, such as participation in physical activity, diet modulation, and calorie restriction, are also described.

Background: Various dietary components have been studied in relation to overall mortality; however, little is known about the relationship between the inflammatory potential of overall diet and mortality., Materials and Methods: We examined the association between the dietary inflammatory index (DII) and mortality in the National Health and Nutrition Examination Survey III follow-up study. The DII was computed from baseline dietary intake assessed using 24-h dietary recalls (1988-1994). Mortality was determined from the National Death Index records through 2006. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence interval (95 % CI). During the follow-up, 2795 deaths were identified, including 1233 due to cardiovascular disease (CVD), and 615 due to cancer, 158 of which were due to digestive-tract cancers., Results: Multivariate Cox proportional hazards regression analyses, adjusting for age, race, diabetes status, hypertension, physical activity, body mass index, poverty index, and smoking, revealed positive associations between higher DII scores and mortality. Comparing subjects in DII tertile 3 versus tertile 1, significant associations were noted for all-cause mortality (HR Tertile3vs1 1.34; 95 % CI 1.19-1.51, P trend  < 0.0001), CVD mortality (HR Tertile3vs1 1.46; 95 % CI 1.18-1.81, P trend  = 0.0006), cancer mortality (HR Tertile3vs1 1.46; 95 % CI 1.10-1.96, P trend  = 0.01), and digestive-tract cancer mortality (HR Tertile3vs1 2.10; 95 % CI 1.15-3.84, P trend  = 0.03)., Conclusion: These results indicate that a pro-inflammatory diet, as indicated by higher DII scores, was associated with higher risk of all-cause, CVD, and cancer mortality.

Objective: It has been reported by some prospective studies that C-reactive protein (CRP) is associated with cancer risk. However, the correlation between CRP and digestive system cancers has not been evaluated in Chinese females. We conducted a large population-based cohort study to investigate whether elevated level of CRP in serum is associated with an increased risk of digestive system cancers in Chinese women. Methods: From the Chinese Kailuan Female Cohort, 19, 437 women were enrolled in this study in July 2006, and all of the subjects were followed up through 2014. At the baseline investigation, the serum levels of high-sensitivity CRP (hsCRP) were tested for all subjects, and demographic information and risk factor data were collected. Multivariable Cox proportional hazards regression model was used to calculate the hazard ratios ( HR ) and 95% confidence intervals (95% CI ) for the baseline levels of hsCRP after adjusting for age, marital status, smoking, drinking, body mass index (BMI), diabetes and physical activity, and risk of digestive system tumors (including colorectal cancer, stomach cancer, pancreas cancer, liver and gallbladder cancer, and other cancers). Results: By Dec 31, 2014, a total of 100 incident cancer cases were observed, including 47 colorectal cancers, 17 stomach cancers, and altogether 29 pancreas, liver and gallbladder cancers. All the subjects investigated were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The 8-year cumulative incidence of digestive system cancers were 405/100 000, 520/100 000 and 787/100 000 in these 3 groups, respectively (Log rank test χ 2 = 8.37, P =0.015). Compared to those with lower hsCRP levels (<1 mg/L), the women with higher hsCRP (>3 mg/L) had a significantly increased risk of pancreas, liver and gallbladder cancers ( HR = 2.70, 95% CI = 1.06-6.91; P trend = 0.036). Conclusions: Elevated levels of hsCRP at baseline may be associated with increased risk of certain digestive system cancers.

Current knowledge about the overall and site-specific risk of malignancy associated with ankylosing spondylitis (AS) is inconsistent. We conducted a systematic review and meta-analysis to address this knowledge gap. Five databases (PubMed, EMBASE, Web of Science, the Cochrane library and the virtual health library) were systematically searched. A manual search of publications within the last 2 years in key journals in the field (Annals of the Rheumatic Diseases, Rheumatology and Arthritis &rheumatology) was also performed. STATA 11.2 software was used to conduct the meta-analysis. After screening, twenty-three studies, of different designs, were eligible for meta-analysis. AS is associated with a 14% (pooled RR 1.14; 95% CI 1.03-1.25) increase in the overall risk for malignancy. Compared to controls, patients with AS are at a specific increased risk for malignancy of the digestive system (pooled RR 1.20; 95% CI 1.01 to 1.42), multiple myelomas (pooled RR 1.92; 95% CI 1.37 to 3.69) and lymphomas (pooled RR 1.32; 95% CI 1.11 to 1.57). On subgroup analysis, evidence from high quality cohort studies indicated that AS patients from Asia are at highest risk for malignancy overall. Confirmation of findings from large-scale longitudinal studies is needed to identify specific risk factors and to evaluate treatment effects.

Alcoholic liver disease (ALD) is implicated in gut disturbances, both functionally and structurally. It has been noticed that the gut-liver interaction is an important feature in the prevention of systemic inflammation as well as liver health. The optimal functioning of the gut-liver axis depends on gut health. Therefore, gut problems may be important for estimating liver inflammation, while our knowledge of ALD could also provide an insight into gut health. Gut problems accompanied by ALD include gut motility and absorption problems, mucosal damage and the dysbiosis of gut microbiota and gastrointestinal carcinogenesis. Moreover, there is emerging evidence that besides direct inflammatory injury caused by alcohol, gut problems related to ALD play a crucial role in the pathogenesis of cardiovascular and immunological disorders. In this regard, we should consider ALD in relation to both gut health and chronic systemic low-grade inflammation. Accordingly, integrative therapeutic strategies are warranted for treating and preventing ALD and systemic inflammation as well as alcohol-related gut problems., (© 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

The beta genus of human papillomaviruses (ß-HPV) includes approximately 50 different viral types that are subdivided into five species (ß-1 through ß-5). Nonmelanoma cancers may involve some ß-1 and ß-2 HPV types, but the biology of most ß-HPV types and their possible connections to human disease are still little characterized. In this study, we studied the effects of ß-3 type HPV49 in a novel transgenic (Tg) mouse model, using a cytokeratin K14 promoter to drive expression of the E6 and E7 genes from this virus in the basal skin epidermis and the mucosal epithelia of the digestive tract (K14 HPV49 E6/E7-Tg mice). Viral oncogene expression only marginally increased cellular proliferation in the epidermis of Tg animals, compared with wild-type littermates, and we observed no spontaneous tumor formation during their entire lifespan. However, we found that K14 HPV49 E6/E7-Tg mice were highly susceptible to upper digestive tract carcinogenesis upon initiation with 4-nitroquinoline 1-oxide (4NQO). This was a selective effect, as the same mice did not exhibit any skin lesions after chronic UV irradiation. Opposite results were observed in an analogous Tg model expressing the ß-2 HPV38 E6 and E7 oncogenes at the same anatomic sites. While these mice were highly susceptible to UV-induced skin carcinogenesis, as previously shown, they were little affected by 4NQO treatment. Overall, our findings highlight important differences in the biologic properties of certain ß-type HPV that affect their impact on carcinogenesis in an anatomic site-specific manner. Cancer Res; 76(14); 4216-25. ©2016 AACR., (©2016 American Association for Cancer Research.)

The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04-2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In patients with inflammatory bowel disease (IBD), chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. The pathogenesis of colitis-associated cancer is distinct from sporadic colorectal carcinoma and the critical molecular mechanisms underlying this process have yet to be elucidated. Patients with IBD have also been shown to be at increased risk of developing extra-intestinal malignancies. Medical therapies that diminish the mucosal inflammatory response represent the foundation of treatment in IBD, and recent evidence supports their introduction earlier in the disease course. However, therapies that alter the immune system, often used for long durations, may also promote carcinogenesis. As the population of patients with IBD grows older, with longer duration of chronic inflammation and longer exposure to immunosuppression, there is an increasing risk of cancer development. Many of these patients will require cancer treatment, including chemotherapy, radiation, hormonal therapy, and surgery. Many patients will require further treatment for their IBD. This review seeks to explore the characteristics and risks of cancer in patients with IBD, and to evaluate the limited data on patients with IBD and cancer, including management of IBD after a diagnosis of cancer, the effects of cancer treatment on IBD, and the effect of IBD and medications for IBD on cancer outcomes.

Objective: To analyze the relationship between N-nitrosodimethylamine(NDMA)and the risk of digestive tract cancers., Methods: The papers about the relationship between NDMA and the risk of digestive tract cancers published from 1980 to 2012 were retrieved following databases: Chinese BioMedical Literature Database(CBM), the Chinese Journal Full-text Database(CNKI), Wanfang Database, PubMed and EBSCO. The fix and random effect model was used and statistical analyses were conducted by using RevMan 5.1 software., Results: Thirteen papers were found, in which 7 about digestive tract cancers were used in this Meta analysis. The NDMA had significant positive effect on the incidence of digestive tract cancers(RR=1.12, 95% CI: 1.03-1.21). The relationship between NDMA and esophageal cancer was not significant(RR=1.18, 95%CI: 0.98-1.41)but NDMA could increase the risk of gastric cancer(RR=1.08, 95% CI: 1.00-1.18). For the subtypes of esophageal and gastric cancer, NDMA had positive relationship with esophageal squamous cell carcinoma(RR=1.72, 95% CI: 1.01-2.96), but had no significant relationship with esophageal adenocarcinoma, cardiac carcinoma and gastric adenocarcinoma., Conclusion: The population-based cohort studies have showed that the NDMA could significantly increase the risk of digestive tract cancers, but the effects differed with subtypes of esophageal and gastric cancer. However, it is necessary to collect more evidence due to the limited studies and obvious differences in the study design, sampling and exposure measurement of these cohort studies.

Although discussion of the obesity epidemic had become a cocktail party cliché, its impact on public health cannot be dismissed. In the past decade, cancer had joined the list of chronic debilitating diseases whose risk is substantially increased by hypernutrition. Here we discuss recent advances in understanding how obesity increases cancer risk and propose a unifying hypothesis according to which the major tumor-promoting mechanism triggered by hypernutrition is the indolent inflammation that takes place at particular organ sites, including liver, pancreas, and gastrointestinal tract. The mechanisms by which excessive fat deposition feeds this tumor-promoting inflammatory flame are diverse and tissue specific., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Neuroendocrine neoplasms (NENs) are rare cancers mainly of lung and digestive tract. Little is known on risk factors. The aim of this work is to define the risk factors for NEN development by extensive review and meta-analysis of published data., Methods: The search was conducted on Medline, Scopus, and Web of Science following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Newcastle-Ottawa scale was used for study quality. Meta-analyses were conducted by primary site. Odds ratio (OR), hazard ratio, risk ratio, standardized incidence ratio, and associated 95% confidence intervals (CIs) were abstracted. Data were combined and analyses carried out for risk factors considered by at least two studies. Random-effects model was adopted for study variation., Results: Of 1535 extracted articles, 24 were enrolled. Meta-analyses were possible for pancreas, small intestine, and rectum. Risk for NEN associated with: (i) family history of cancer at all investigated sites (lung, stomach, pancreas, small intestine, appendix, and colon; OR 2.12 [95% CI 1.40-3.22, I(2) = 0.0%, P = 0.681] at meta-analysis in pancreas); (ii) body mass index (BMI) or diabetes (stomach, pancreas, and small intestine; OR of 2.76 [95% CI 1.65-4.64, I(2) = 58.5%, P = 0.090] for diabetes at meta-analysis in pancreas); (iii) cigarette smoking (lung, stomach, pancreas, and small intestine; OR of 1.34 [95% CI 1.10-1.63, I(2) = 0.0%, P = 0.780] and of 1.59 [95% CI 1.07-2.37, I(2) = 32.9%, P = 0.225] for smokers versus never-smokers at meta-analysis for pancreas and small intestine); (iv) alcohol consumption (pancreas and rectum; OR of 2.44 [95% CI 1.07-5.59, I(2) = 65.8%, P = 0.054] and of 1.53 [95% CI 0.99-2.35, I(2) = 0.0%, P = 0.630] for heavy drinkers versus never-drinkers at meta-analysis for pancreas and rectum)., Conclusions: Family history of cancer is the most relevant risk factor for NEN development at all investigated sites, followed by BMI and diabetes. Cigarette smoking and alcohol consumption are potential risk factors for selected anatomical sites., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

Objective: The aim of our study was to estimate the incidence of digestive cancers within a cohort of asbestos-exposed workers., Methods: Our study was based on a cohort of 2024 participants occupationally exposed to asbestos. The incidence of digestive cancers was calculated from 1 January 1978 to 31 December 2009 and compared with levels among the local general population using Standardised Incidence Ratios (SIRs). Asbestos exposure was assessed using the company's job-exposure matrix., Results: 119 cases of digestive cancer were observed within our cohort, for an expected number of 77 (SIR=1.54 (1.28 to 1.85)). A significantly elevated incidence was observed for peritoneal mesothelioma, particularly in women. Significantly elevated incidences were also observed among men for: all digestive cancers, even when excluding peritoneal mesothelioma (SIR=1.50 (1.23 to 1.82)), oesophageal cancer (SIR=1.67 (1.08 to 2.47)) and liver cancer (SIR=1.85 (1.09 to 2.92)). Concerning colorectal cancer, a significant excess of risk was observed for men with exposure duration above 25 years (SIR=1.75 (1.05 to 2.73))., Conclusions: Our results are in favour of a link between long-duration asbestos exposure and colorectal cancer in men. They also suggest a relationship between asbestos exposure and cancer of the oesophagus in men. Finally, our results suggest a possible association with small intestine and liver cancers in men., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Obesity and cancer are one of the most important health problems is Spain. Between 23 and 28% of the adult population in Spain are obese, 39% are overweight and 36% have abdominal obesity. The association between obesity and type 2 diabetes mellitus, hypertension, dyslipidemia and sleep obstructive apnea is well known. On the contrary, the association between obesity and cancer is less known, because the recent evidence on it. Several prospective studies have shown during the last years the strong relationship between obesity and cancer of colon, breast in post-menopausal women, endometrial, kidney and pancreas as well as esophageal adenocarcinoma. Furthermore there is recent evidence showing that liver, gallbladder, thyroid and ovarian cancer as well as leukemia, multiple myeloma and Hodgkin lymphomas are probably associated with obesity, yet more studies are needed. A better knowledge of the relation between cancer and obesity will allow improving the prevention strategies against cancer, a more efficient early detection, and a more suitable treatment of obesity and overweight. Although the mechanisms of carcinogenesis of obesity are not well established, avoiding overweight and obesity are considered one of the best approaches to reduce the risk of cancer. Therefore the general population must be aware that cancer is one of the most important hazards associated with the current obesity epidemic in our society., (Copyright © 2014 Elsevier España, S.L.U. All rights reserved.)

Primary sclerosing cholangitis (PSC) is a frequently progressive and fatal disease. Death from cancer occurs in a significant subset of patients with PSC. Patients with PSC have a 10 to 15 % lifetime risk of developing cholangiocarcinoma (CCA). About one third of CCAs are present in the first year after a diagnosis of PSC; the remainder are present with a frequency of about 1.5 % each year. Patients with concomitant PSC and inflammatory bowel disease (IBD) have a 4-fold higher risk of colorectal cancer (CRC) than patients with IBD alone and a 10-fold higher risk of CRC than the general population. The risk does not diminish with liver transplantation. This patient population also has a high frequency of carcinoma in gallbladder mass lesions. The risk for hepatocellular carcinoma (HCC) in the presence of cirrhosis is uncertain-two large cohort studies suggest that HCC is not as common as in other causes of cirrhosis. Although AASLD guidelines do not recommend routine screening for liver tumors in patients with PSC, we recommend MRI/MRCP and serum CA 19-9 levels in patients with PSC every 6 months to screen for CCA, HCC, pancreatic cancer, and gallbladder cancer. Screening colonoscopy at the diagnosis of PSC and surveillance colonoscopies every 1-2 years should be performed in those with PSC and IBD.

Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) modulate exposure levels to ethanol/acetaldehyde. Endoscopic screening of 6,014 Japanese alcoholics yielded high detection rates of esophageal squamous cell carcinoma (SCC; 4.1%) and head and neck SCC (1.0%). The risks of upper aerodigestive tract SCC/dysplasia, especially of multiple SCC/dysplasia, were increased in a multiplicative fashion by the presence of a combination of slow-metabolizing ADH1B*1/*1 and inactive heterozygous ALDH2*1/*2 because of prolonged exposure to higher concentrations of ethanol/acetaldehyde. A questionnaire asking about current and past facial flushing after drinking a glass (≈180 mL) of beer is a reliable tool for detecting the presence of inactive ALDH2. We invented a health-risk appraisal (HRA) model including the flushing questionnaire and drinking, smoking, and dietary habits. Esophageal SCC was detected at a high rate by endoscopic mass-screening in high HRA score persons. A total of 5.0% of 4,879 alcoholics had a history of (4.0%) or newly diagnosed (1.0%) gastric cancer. Their high frequency of a history of gastric cancer is partly explained by gastrectomy being a risk factor for alcoholism because of altered ethanol metabolism, e.g., by blood ethanol level overshooting. The combination of H. pylori-associated atrophic gastritis and ALDH2*1/*2 showed the greatest risk of gastric cancer in alcoholics. High detection rates of advanced colorectal adenoma/carcinoma were found in alcoholics, 15.7% of 744 immunochemical fecal occult blood test (IFOBT)-negative alcoholics and 31.5% of the 393 IFOBT-positive alcoholics. Macrocytosis with an MCV≥106 fl increased the risk of neoplasia in the entire aerodigestive tract of alcoholics, suggesting that poor nutrition as well as ethanol/acetaldehyde exposure plays an important role in neoplasia.

Background: Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice., Methods: Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention., Results and Conclusion: A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Objectives: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009., Methods: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias., Results: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques., Conclusions: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.

Vascular endothelial growth factor (VEGF) polymorphisms, specifically +405G/C (rs2010963), reportedly influence the risk for various digestive cancers. However, the consequences of these polymorphisms remain controversial and ambiguous. Therefore, we performed a meta-analysis of 11 studies with VEGF +405G/C genotyping on 2,862 patients and 3,028 controls using the random effects model. We obtained a pooled odds ratio (OR) of 1.04 (95% confidence interval (CI) = 0.86-1.26) for the recessive genetic model, 1.07 (95% CI = 0.81-1.42) for the dominant genetic model, 1.09 (95% CI = 0.81-1.47) for the homozygote comparison, and 1.03 (95% CI = 0.83-1.27) for the heterozygote comparison. In the subgroup analysis of the recessive model, the OR was 1.20 (95% CI = 1.02-1.40) in colorectal cancer. These results show that VEGF +405G/C polymorphisms are unlikely to be a major determinant of susceptibility to digestive cancer. Furthermore, the subgroup analysis of recessive model indicates that VEGF +405G/C polymorphisms increase the risk for colorectal cancer.