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Japanese Journal of Clinical Oncology Apr 2016The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate...
OBJECTIVE
The upper gastrointestinal characteristics in Japanese familial adenomatous polyposis patients have not yet been clarified. The aim of the present study was to elucidate these characteristics in Japanese familial adenomatous polyposis patients.
METHODS
This study was conducted by the study group for familial adenomatous polyposis in the Japanese Society for Cancer of the Colon and Rectum. Familial adenomatous polyposis patients who underwent surgical resection from 2000 to 2012 were included in the study.
RESULTS
In total, 303 familial adenomatous polyposis patients were enrolled, with 265 cases of classical familial adenomatous polyposis (≥100 adenomas) and 38 cases of attenuated familial adenomatous polyposis (<100 adenomas). Fundic gland polyps were significantly more common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis; however, gastric cancer was significantly less common in classical familial adenomatous polyposis than in attenuated familial adenomatous polyposis. Gastric cancer and duodenal adenoma were significantly more common in familial adenomatous polyposis patients with gastric adenoma than in those without gastric adenoma. Duodenal cancer was detected in 7 of 72 familial adenomatous polyposis patients with duodenal adenoma. The median tumour risk in 50-year-old familial adenomatous polyposis patients was 55.3, 21.8, 3.8, 39.2 and 7.7% for fundic gland polyp, gastric adenoma, gastric cancer, duodenal adenoma and duodenal cancer, respectively.
CONCLUSIONS
Upper gastrointestinal tumours/polyps were frequently found in familial adenomatous polyposis patients, and their incidences were correlated; however, the frequency of gastric cancer in Japanese familial adenomatous polyposis patients was similar to that in the general population.
Topics: Adenoma; Adenomatous Polyposis Coli; Adenomatous Polyps; Adult; Aged; Colectomy; DNA Glycosylases; Duodenal Neoplasms; Female; Genes, APC; Humans; Incidence; Japan; Male; Middle Aged; Mutation; Retrospective Studies; Risk; Stomach Neoplasms
PubMed: 26819281
DOI: 10.1093/jjco/hyv210 -
Alimentary Pharmacology & Therapeutics Nov 2016A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting.
AIM
To clarify the relationship through a meta-analysis of the existing data.
METHODS
A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro.
RESULTS
The initial search using electronic databases and manual searching retrieved 339 peer-reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta-analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42-4.27, P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22-9.99, P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58-10.99, P < 0.001).
CONCLUSIONS
Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta-analysis is limited mainly to cohort studies.
Topics: Adenomatous Polyps; Cohort Studies; Gastric Fundus; Humans; Polyps; Proton Pump Inhibitors; Stomach Neoplasms
PubMed: 27634363
DOI: 10.1111/apt.13800 -
International Journal of Molecular... Oct 2020It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing... (Review)
Review
It is known and accepted that the gut microbiota composition of an organism has an impact on its health. Many studies deal with this topic, the majority discussing gastrointestinal health. Adenomatous colon polyps have a high prevalence as colon cancer precursors, but in many cases, they are hard to diagnose in their early stages. Gut microbiota composition correlated with the presence of adenomatous colon polyps may be a noninvasive and efficient tool for diagnosis with a high impact on human wellbeing and favorable health care costs. This review is meant to analyze the gut microbiota correlated with the presence of adenomatous colon polyps as the first step for early diagnosis, prophylaxis, and treatment.
Topics: Adenomatous Polyps; Colon; Colonic Diseases; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Gastrointestinal Microbiome; Humans
PubMed: 33028024
DOI: 10.3390/ijms21197359 -
Gut and Liver Nov 2017Serrated polyps are important contributors to the burden of colorectal cancers (CRC). These lesions were once considered to have no malignant potential, but currently up... (Review)
Review
Serrated polyps are important contributors to the burden of colorectal cancers (CRC). These lesions were once considered to have no malignant potential, but currently up to 30% of all CRC are recognized to arise from the serrated neoplasia pathway. The primary premalignant lesions are sessile serrated adenomas/polyps (SSA/Ps), although traditional serrated adenomas are relatively uncommon. Compared to conventional adenomas, SSA/Ps are morphologically subtle with indistinct borders, may be difficult to detect endoscopically, are more prevalent than previously thought, are associated with synchronous and metachronous advanced neoplasia, and have a higher risk of incomplete resection. Although many lesions remain "dormant," progressive disease is associated with the development of dysplasia and more rapid progression to CRC. As a result, SSA/Ps are strongly implicated in the development of interval cancers. These factors represent unique challenges that require a meticulous approach to their management. In this review, we summarize the contemporary literature on the characterization, detection and resection of SSA/Ps.
Topics: Adenoma; Adenomatous Polyps; Colonoscopy; Colorectal Neoplasms; Humans; Precancerous Conditions
PubMed: 28494577
DOI: 10.5009/gnl16523 -
EBioMedicine Jun 2019Energy metabolism in carcinogenesis is poorly understood. It is widely accepted the majority of colorectal cancers (CRCs) arise from adenomatous polyps (APs). We aimed...
BACKGROUND
Energy metabolism in carcinogenesis is poorly understood. It is widely accepted the majority of colorectal cancers (CRCs) arise from adenomatous polyps (APs). We aimed to characterize the bioenergetic alterations in APs and CRCs.
METHODS
Fifty-six APs, 93 CRCs and adjacent normal mucosae were tested. Oxygen consumption rate (OCR) was measured representing mitochondrial oxidative phosphorylation (OxPhos), and extracellular acidification rate (ECAR)was measured representing glycolysis. Mitochondrial DNA (mtDNA) variants and mutations were studied. Over-expressed metabolic genes in APs were identified by microarray and validated by qRT-PCR, Western blots and immunohistochemistry. Identified genes were knocked down in WiDr and colo205 CRC cell lines, and their expression was analyzed in APs/CRCs with enhanced glycolysis.
FINDINGS
ECAR, not OCR, was significantly increased in APs. While no difference of ECAR was found between CRCs and normal mucosae, OCR was significantly reduced in CRCs. OCR/ECAR ratio was decreased in APs over 1 cm, APs with a villous component and CRCs, indicating their glycolytic tendencies. The number of mtDNA mutations was increased in APs and CRCs, but not correlated with metabolic profiles. Two metabolic genes ALDOB and SLC16A4 were up-regulated in APs. Both ALDOB-knockdown and SLC16A4-knockdown CRC cell lines showed increased basal motichondrial OxPhos and decreased basal glycolysis. Moreover, the increase of mitochondrial ATP-linked respiration and the decrease of glycolytic capacity were showed in SLC16A4-knockdown cells. Finally, APs/CRCs with enhanced glycolysis had increased SLC16A4 expression.
INTERPRETATION
ATP production shifts from OxPhos to glycolysis in the process of AP enlargement and villous transformation. OxPhos defects are present in CRCs but not in APs. APs and CRCs tend to accumulate mtDNA mutations, but these are not correlated with bioenergetic profiles. Finally, the ALDOB and SLC16A4 may contribute to the glycolytic shift in APs/CRCs.
Topics: Adenocarcinoma; Adenomatous Polyps; Aged; Aged, 80 and over; Biomarkers; Cell Line, Tumor; Colorectal Neoplasms; DNA, Mitochondrial; Energy Metabolism; Female; Fluorodeoxyglucose F18; Humans; Intestinal Mucosa; Male; Middle Aged; Mitochondria; Monocarboxylic Acid Transporters; Muscle Proteins; Mutation; Neoplasm Staging; Oxidative Phosphorylation; Oxygen Consumption; Positron Emission Tomography Computed Tomography; Tumor Burden
PubMed: 31122841
DOI: 10.1016/j.ebiom.2019.05.031 -
Cancer Prevention Research... Sep 2021Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome, which results in the development of hundreds of adenomatous polyps carpeting the...
Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer syndrome, which results in the development of hundreds of adenomatous polyps carpeting the gastrointestinal tract. NSAIDs have reduced polyp burden in patients with FAP and synthetic rexinoids have demonstrated the ability to modulate cytokine-mediated inflammation and WNT signaling. This study examined the use of the combination of an NSAID (sulindac) and a rexinoid (bexarotene) as a durable approach for reducing FAP colonic polyposis to prevent colorectal cancer development. Whole transcriptomic analysis of colorectal polyps and matched normal mucosa in a cohort of patients with FAP to identify potential targets for prevention in FAP was performed. Drug-dose synergism of sulindac and bexarotene in cell lines and patient-derived organoids was assessed, and the drug combination was tested in two different mouse models. This work explored mRNA as a potential predictive serum biomarker for this combination in FAP. Overall, transcriptomic analysis revealed significant activation of inflammatory and cell proliferation pathways. A synergistic effect of sulindac (300 μmol/L) and bexarotene (40 μmol/L) was observed in FAP colonic organoids with primary targeting of polyp tissue compared with normal mucosa. This combination translated into a significant reduction in polyp development in and mice. Finally, the reported data suggest miRNA-21 could serve as a predictive serum biomarker for polyposis burden in patients with FAP. These findings support the clinical development of the combination of sulindac and bexarotene as a treatment modality for patients with FAP. PREVENTION RELEVANCE: This study identified a novel chemopreventive regimen combining sulindac and bexarotene to reduce polyposis in patients with FAP using tools, , and models. This investigation provides the essential groundwork for moving this drug combination forward into a clinical trial.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyps; Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Combined Chemotherapy Protocols; Bexarotene; Carcinogenesis; Case-Control Studies; Cells, Cultured; Female; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; Intestinal Neoplasms; Male; Mice; Mice, Transgenic; Sulindac
PubMed: 34266857
DOI: 10.1158/1940-6207.CAPR-20-0496 -
BioMed Research International 2020The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into carcinoma through the interactions... (Review)
Review
The development of colorectal cancer (CRC) is a multistep process initiated by a benign polyp that has the potential to evolve into carcinoma through the interactions between environmental and genetic factors. CRC incidence rates are constantly increased for young adult patients presenting an advanced tumor stage. The majority of CRCs arise from colonic adenomas originating from aberrant cell proliferation of colon epithelium. Endoscopic polypectomy represents a tool for early detection and removal of polyps, although the occurrence of cancers after negative colonoscopy shows a significant incidence. It has long been recognized that the aberrant regulation of Wingless/It (Wnt)/-Catenin signaling in the pathogenesis of colorectal cancer is supported by its critical role in the differentiation of stem cells in intestinal crypts and in the maintenance of intestinal homeostasis. For this review, we will focus on the development of adenomatous polyps through the interplay between renewal signaling in the colon epithelium and reactive oxygen species (ROS) production. The current knowledge of molecular pathology allows us to deepen the relationships between oxidative stress and other risk factors as lifestyle, microbiota, and predisposition. We underline that the chronic inflammation and ROS production in the colon epithelium can impair the Wnt/-catenin and/or base excision repair (BER) pathways and predispose to polyp development. In fact, the coexistence of oxidative DNA damage and errors in DNA polymerase can foster C>T transitions in various types of cancer and adenomas, leading to a hypermutated phenotype of tumor cells. Moreover, the function of Adenomatous Polyposis Coli () protein in regulating DNA repair is very important as therapeutic implication making DNA damaging chemotherapeutic agents more effective in CRC cells that tend to accumulate mutations. Additional studies will determine whether approaches based on Wnt inhibition would provide long-term therapeutic value in CRC, but it is clear that disruption plays a central role in driving and maintaining tumorigenesis.
Topics: Adenoma; Adenomatous Polyps; Colorectal Neoplasms; DNA Repair; Genetic Predisposition to Disease; Humans; Oxidative Stress; Reactive Oxygen Species; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 32258104
DOI: 10.1155/2020/1726309 -
The Cochrane Database of Systematic... 2004This review was split in 2012 and the review question was to be addressed according to three new protocols: (See:... (Review)
Review
EDITORIAL NOTE
This review was split in 2012 and the review question was to be addressed according to three new protocols: (See: http://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010267.pub2; http://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010291.pub2; http://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010325.pub2). These titles were withdrawn at the protocol stage in 2020 as the authors did not make any progress on the reviews. This original review will no longer be updated and may be superseded by new titles hosted by Cochrane Gut in the future.
BACKGROUND
There is evidence from experimental animals studies, prospective and retrospective observational studies that nonsteroidal anti-inflammatory drugs (NSAIDS) may reduce the development of sporadic colorectal adenomas (CRAs) and cancer (CRC) and may induce the regression of adenomas in familial adenomatous polyposis (FAP).
OBJECTIVES
To conduct a systematic review to determine the effect of NSAIDS for the prevention or regression of CRAs and CRC.
SEARCH STRATEGY
Randomized controlled trials (RCTs) up to September 2003 were identified.
SELECTION CRITERIA
NSAIDS and aspirin (ASA) were the interventions. The primary outcomes were the number of subjects with at least one CRA, the change in polyp burden, and CRC. The secondary outcome was adverse events.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data and assessed trial quality. Dichotomous outcomes were reported as relative risks (RR) with 95% confidence intervals (CI). The data were combined with the random effects model if clinically and statistically reasonable.
MAIN RESULTS
Nine trials with 150 familial adenomatous polyposis (FAP) and 24,143 population subjects met the inclusion criteria. The interventions included sulindac, celecoxib, or aspirin (ASA). From the combined results of three trials, significantly fewer subjects in the low dose ASA group developed recurrent sporadic CRAs [RR 0.77 (95% CI 0.61, 0.96), (NNT 12.5 (95% CI 7.7, 25)] after one to three years. In another three trials, phenotypic FAP subjects that received sulindac or celecoxib had a greater proportional reduction (range: 11.9% to 44%) in the number of CRAs compared to those in the control group (range: 4.5% to 10%). There was no significant difference for the outcomes of CRC or adverse events in any of the trials.
REVIEWERS' CONCLUSIONS
There was evidence from three pooled RCTs that ASA significantly reduces the recurrence of sporadic adenomatous polyps after one to three years. There is evidence from short-term studies to support regression, but not elimination or prevention of CRAs in FAP.
Topics: Adenoma; Adenomatous Polyposis Coli; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carcinoma; Colorectal Neoplasms; Humans; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 15106236
DOI: 10.1002/14651858.CD004079.pub2 -
Best Practice & Research. Clinical... 2021Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare familial gastric cancer syndrome with an autosomal dominant pattern of inheritance. It is... (Review)
Review
Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is a rare familial gastric cancer syndrome with an autosomal dominant pattern of inheritance. It is characterised by fundic gland polyposis of the gastric body and is associated with a significant risk of gastric adenocarcinoma. Unlike sporadic gastric cancer, Helicobacter pylori is usually absent in patients with GAPPS. This opposite-point finding has so far not been fully clarified. Prophylactic total gastrectomy is indicated in all cases of GAPPS with fundic gland polyposis and the presence of any dysplasia. If no dysplasia is found at histology, prophylactic gastrectomy is suggested at between 30 and 35 years of age, or at five years earlier than the age at which the youngest family member developed gastric cancer. Different phenotypes of GAPPS demand an individual approach to particular family members.
Topics: Adenocarcinoma; Adenomatous Polyps; Adult; Female; Helicobacter; Humans; Male; Stomach Neoplasms
PubMed: 33975682
DOI: 10.1016/j.bpg.2021.101728 -
The Cochrane Database of Systematic... Jan 2017This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental... (Review)
Review
BACKGROUND
This is an update of the Cochrane review published in 2002.Colorectal cancer (CRC) is a major cause of morbidity and mortality in industrialised countries. Experimental evidence has supported the hypothesis that dietary fibre may protect against the development of CRC, although epidemiologic data have been inconclusive.
OBJECTIVES
To assess the effect of dietary fibre on the recurrence of colorectal adenomatous polyps in people with a known history of adenomatous polyps and on the incidence of CRC compared to placebo. Further, to identify the reported incidence of adverse effects, such as abdominal pain or diarrhoea, that resulted from the fibre intervention.
SEARCH METHODS
We identified randomised controlled trials (RCTs) from Cochrane Colorectal Cancer's Specialised Register, CENTRAL, MEDLINE and Embase (search date, 4 April 2016). We also searched ClinicalTrials.gov and WHO International Trials Registry Platform on October 2016.
SELECTION CRITERIA
We included RCTs or quasi-RCTs. The population were those having a history of adenomatous polyps, but no previous history of CRC, and repeated visualisation of the colon/rectum after at least two-years' follow-up. Dietary fibre was the intervention. The primary outcomes were the number of participants with: 1. at least one adenoma, 2. more than one adenoma, 3. at least one adenoma greater than or equal to 1 cm, or 4. a new diagnosis of CRC. The secondary outcome was the number of adverse events.
DATA COLLECTION AND ANALYSIS
Two reviewers independently extracted data, assessed trial quality and resolved discrepancies by consensus. We used risk ratios (RR) and risk difference (RD) with 95% confidence intervals (CI) to measure the effect. If statistical significance was reached, we reported the number needed to treat for an additional beneficial outcome (NNTB) or harmful outcome (NNTH). We combined the study data using the fixed-effect model if it was clinically, methodologically, and statistically reasonable.
MAIN RESULTS
We included seven studies, of which five studies with 4798 participants provided data for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions that we would draw. Therefore, the reliability of the findings may have been compromised by these missing data (attrition bias) and should be interpreted with caution.
AUTHORS' CONCLUSIONS
There is a lack of evidence from existing RCTs to suggest that increased dietary fibre intake will reduce the recurrence of adenomatous polyps in those with a history of adenomatous polyps within a two to eight year period. However, these results may be unreliable and should be interpreted cautiously, not only because of the high rate of loss to follow-up, but also because adenomatous polyp is a surrogate outcome for the unobserved true endpoint CRC. Longer-term trials with higher dietary fibre levels are needed to enable confident conclusion.
Topics: Adenoma; Adenomatous Polyps; Aged; Colorectal Neoplasms; Dietary Fiber; Humans; Middle Aged; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic
PubMed: 28064440
DOI: 10.1002/14651858.CD003430.pub2