Dietary Patterns and Risk of Colorectal Cancer Subtypes Classified by Fusobacterium nucleatum in Tumor Tissue

Importance—Fusobacterium nucleatum appears to play a role in colorectal carcinogenesis through suppression of host immune response to tumor. Evidence also suggests that diet influences intestinal F. nucleatum. However, the role of F. nucleatum in mediating the relationship between diet and the risk of colorectal cancer is unknown. Objective—To test the hypothesis that the associations of prudent diets (rich in whole grains and dietary fiber) and Western diets (rich in red and processed meat, refined grains, and desserts) with colorectal cancer risk may differ according to the presence of F. nucleatum in tumor tissue. Design—Prospective cohort study. Setting—The Nurses’ Health Study (1980–2012) and the Health Professionals Follow-up Study (1986–2012). Participants—121,700 US female nurses and 51,529 US male health professionals aged 30 to 55 years and 40 to 75 years, respectively, at enrollment. Exposures—Prudent and Western dietary patterns. Main Outcomes and Measures—Incidence of colorectal carcinoma subclassified by F. nucleatum status in tumor tissue, determined by quantitative polymerase chain reaction. Results—We documented 1,019 incident colon and rectal cancer cases with available F. nucleatum data among predominantly white 137,217 individuals over 26–32 years of follow-up encompassing 3,643,562 person-years. The association of prudent diet with colorectal cancer significantly differed by tissue F. nucleatum status (Pheterogeneity = .01). Prudent diet score was associated with a lower risk of F. nucleatum-positive cancers [Ptrend = .003; multivariable hazard ratio of 0.43 (95% confidence interval 0.25–0.72) for the highest vs. the lowest prudent score quartile], but not with F. nucleatum-negative cancers (Ptrend = .47). Dietary component analyses suggested possible differential associations for the cancer subgroups according to intakes of dietary fiber (Pheterogeneity = .02). There was no significant heterogeneity between the subgroups according to Western dietary pattern scores (Pheterogeneity = .23). Conclusions and Relevance—Prudent diets rich in whole grains and dietary fiber are associated with a lower risk for F. nucleatum-positive colorectal cancer but not F. nucleatum-negative cancer, supporting a potential role for intestinal microbiota in mediating the association between diet and colorectal neoplasms

Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis

Background: Previous approaches to defining subtypes of colorectal carcinoma (CRC) and other cancers based on transcriptomes have assumed the existence of discrete subtypes. We analyze gene expression patterns of colorectal tumors from a large number of patients to test this assumption and propose an approach to identify potentially a continuum of subtypes that are present across independent studies and cohorts. Results: We examine the assumption of discrete CRC subtypes by integrating 18 published gene expression datasets and \u3e3700 patients, and contrary to previous reports, find no evidence to support the existence of discrete transcriptional subtypes. Using a meta-analysis approach to identify co-expression patterns present in multiple datasets, we identify and define robust, continuously varying subtype scores to represent CRC transcriptomes. The subtype scores are consistent with established subtypes (including microsatellite instability and previously proposed discrete transcriptome subtypes), but better represent overall transcriptional activity than do discrete subtypes. The scores are also better predictors of tumor location, stage, grade, and times of disease-free survival than discrete subtypes. Gene set enrichment analysis reveals that the subtype scores characterize T-cell function, inflammation response, and cyclin-dependent kinase regulation of DNA replication. Conclusions: We find no evidence to support discrete subtypes of the CRC transcriptome and instead propose two validated scores to better characterize a continuity of CRC transcriptomes

The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men

INTRODUCTION: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.). METHODS: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012). RESULTS: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% of whom had available tissue data. After accounting for multiple hypothesis testing, the relationship between the sulfur microbial diet and CRC incidence did not differ by subtype. However, there was a suggestion of an association by prostaglandin synthase 2 (PTGS2) status with a multivariable adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.31 (95% confidence interval: 0.99-1.74, Ptrend = 0.07, Pheterogeneity = 0.04) for PTGS2-high CRC. The association of the sulfur microbial diet with distal CRC seemed to differ by the presence of intratumoral Bifidobacterium spp. with an adjusted hazard ratio for highest vs lowest tertile of sulfur microbial diet scores of 1.65 (95% confidence interval: 1.14-2.39, Ptrend = 0.01, Pheterogeneity = 0.03) for Bifidobacterium-negative distal CRC. We observed no apparent heterogeneity by other tested molecular markers. DISCUSSION: Greater long-term adherence to the sulfur microbial diet could be associated with PTGS2-high and Bifidobacterium-negative distal CRC in men. Additional studies are needed to further characterize the role of gut microbial sulfur metabolism and CRC

The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

ABSTRACTAccumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one’s life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations

Epithelial-mesenchymal transition in gastroenterological cancer

Epithelial-mesenchymal transition (EMT) was first reported as an essential process in embryonic cells and later showed that cancer cells, regardless of the context, exhibit a similar phenomenonthat is crucial for tumor progression. Epithelial cells lose their adhesive characteristic capacity which is necessary for their functions but gain a mesenchymal phenotype. This change from epithelial to mesenchymal phenotype of cancer cells makes it difficult tounderstand the mechanism underlying cancer biology and tumor progression. A number of transcription factors involved in tumor cell EMT and miRNA-regulated EMT have been reported. This review discussed recent findings and new players in EMT in gastrointestinal cancers. Since the molecular mechanisms of tumor progression are sometimes context dependent, the recent findings of EMT have been reviewed in the context-dependent manner

Laparoscopic removal of an ingested fish bone that penetrated the stomach and was embedded in the pancreas: a case report

Abstract Background The gastrointestinal tract can occasionally be perforated or penetrated by an ingested foreign body, such as a fish bone. However, there are very few reported cases in which an ingested fish bone penetrated the gastrointestinal tract and was embedded in the pancreas. Case presentation An 80-year-old male presented with epigastric pain. Computed tomography of the abdomen showed a linear, hyperdense, foreign body that penetrated through the posterior wall of the gastric antrum. There was no evidence of free air, abscess formation, migration of the foreign body into the pancreas, or pancreatitis. As the patient had a history of fish bone ingestion, we made a diagnosis of localized peritonitis caused by fish bone penetration of the posterior wall of the gastric antrum. We first attempted to remove the foreign body endoscopically, but failed because it was not detected. Hence, an emergency laparoscopic surgery was performed. A linear, hard, foreign body penetrated through the posterior wall of the gastric antrum and was embedded in the pancreas. The foreign body was safely removed laparoscopically and was identified as a 2.5-cm-long fish bone. Intraperitoneal lavage was performed, and a drain was placed in the lesser sac. The patient recovered without complications and was discharged on the 7th postoperative day. Conclusion Laparoscopic surgery could be performed safely for the removal of an ingested fish bone embedded in the pancreas

Small solid pseudopapillary tumor of the pancreas in a 32-year-old man: Report of a case

A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of a small SPT arising from the head of the pancreas in an asymptomatic 32-year-old man, plus a literature review of this tumor. A 32-year-old man was admitted to our department at Kumamoto University Hospital for the evaluation of a pancreatic mass. The tumor had central necrosis, which was poorly perfused on contrast-enhanced computed tomography (CT) and which had a high intensity on T2-weighted magnetic resonance imaging (MRI). Histology revealed the lesion to be a solid pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla formation and central degeneration. However, no capsule formation was observed. The tumor was positive for CD56, CD10, α1-antitrypsin, α1-antichymotrypsin, β-catenin, and progesterone receptor. However, the tumor was negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these histological findings. Small-sized solid pseudopapillary tumors of the pancreas are being increasingly recognized because of the recent advances in CT and MRI. We should also consider SPT even if it occurs in a male when the tumor contains necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a high intensity on T2-weighted MRI

A Kinetic Pump Integrated Microfluidic Plate (KIM-Plate) with High Usability for Cell Culture-Based Multiorgan Microphysiological Systems

Microphysiological systems (MPSs), including organ-on-a-chip (OoC), have attracted attention as a novel method for estimating the effects and side effects of drugs in drug discovery. To reproduce the dynamic in vivo environment, previous MPSs were connected to pump systems to perfuse culture medium. Therefore, most MPSs are not user-friendly and have poor throughput. We aimed to develop a kinetic pump integrated microfluidic plate (KIM-Plate) by applying the stirrer-based micropump to an open access culture plate to improve the usability of MPSs. The KIM-Plate integrates six multiorgan MPS (MO-MPS) units and meets the ANSI/SBS microplate standards. We evaluated the perfusion function of the kinetic pump and found that the KIM-Plate had sufficient agitation effect. Coculture experiments with PXB cells and hiPS intestinal cells showed that the TEER of hiPS intestinal cells and gene expression levels related to the metabolism of PXB cells were increased. Hence, the KIM-Plate is an innovative tool for the easy coculture of highly conditioned cells that is expected to facilitate cell-based assays in the fields of drug discovery and biology because of its usability and high throughput nature