-
International Journal of Molecular... Jun 2021Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The... (Review)
Review
Gastric cancer is still an important disease causing many deaths worldwide, although there has been a marked reduction in prevalence during the last few decades. The decline in gastric cancer prevalence is due to a reduction in infection which has occurred for at least 50 years. The most probable mechanism for the carcinogenic effect of is hypergastrinemia since infected individuals do not have increased risk of gastric cancer before the development of oxyntic atrophy. When atrophy has developed, the carcinogenic process continues independent of . Autoimmune gastritis also induces oxyntic atrophy leading to marked hypergastrinemia and development of ECL cell neoplasia as well as adenocarcinoma. Similarly, long-term treatment with efficient inhibitors of acid secretion like the proton pump inhibitors (PPIs) predisposes to ECL cell neoplasia of a different degree of malignancy. Contrasting the colon where most cancers develop from polyps, most polyps in the stomach have a low malignant potential. Nevertheless, gastric polyps may also give rise to cancer and have some risk factors and mechanisms in common with gastric cancer. In this overview the most common gastric polyps, i.e., hyperplastic polyps, adenomatous polyps and fundic gland polyps will be discussed with respect to etiology and particularly use of PPIs and relation to gastric carcinogenesis.
Topics: Adenomatous Polyps; Animals; Gastritis; Helicobacter pylori; Humans; Stomach Neoplasms
PubMed: 34207192
DOI: 10.3390/ijms22126548 -
Archives of Pathology & Laboratory... Nov 2019Familial adenomatous polyposis (FAP) is a rare genetic disorder with autosomal dominant inheritance, defined by numerous adenomatous polyps, which inevitably progress to... (Review)
Review
CONTEXT.—
Familial adenomatous polyposis (FAP) is a rare genetic disorder with autosomal dominant inheritance, defined by numerous adenomatous polyps, which inevitably progress to colorectal carcinoma unless detected and managed early. Greater than 70% of patients with this syndrome also develop extraintestinal manifestations, such as multiple osteomas, dental abnormalities, and a variety of other lesions located throughout the body. These manifestations have historically been subcategorized as Gardner syndrome, Turcot syndrome, or gastric adenocarcinoma and proximal polyposis of the stomach. Recent studies, however, correlate the severity of gastrointestinal disease and the prominence of extraintestinal findings to specific mutations within the adenomatous polyposis coli gene (), supporting a spectrum of disease as opposed to subcategorization. Advances in immunohistochemical and molecular techniques shed new light on the origin, classification, and progression risk of different entities associated with FAP.
OBJECTIVE.—
To provide a comprehensive clinicopathologic review of neoplastic and nonneoplastic entities associated with FAP syndrome, with emphasis on recent developments in immunohistochemical and molecular profiles of extraintestinal manifestations in the thyroid, skin, soft tissue, bone, central nervous system, liver, and pancreas, and the subsequent changes in classification schemes and risk stratification.
DATA SOURCES.—
This review will be based on peer-reviewed literature and the authors' experiences.
CONCLUSIONS.—
In this review we will provide an update on the clinicopathologic manifestations, immunohistochemical profiles, molecular features, and prognosis of entities seen in FAP, with a focus on routine recognition and appropriate workup of extraintestinal manifestations.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyposis Coli Protein; Brain Neoplasms; Colorectal Neoplasms; Gardner Syndrome; Humans; Immunohistochemistry; Mutation; Neoplastic Syndromes, Hereditary; Prognosis; Skin
PubMed: 31070935
DOI: 10.5858/arpa.2018-0570-RA -
Best Practice & Research. Clinical... 2022Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are rare inherited polyposis syndromes with a high colorectal cancer (CRC) risk. Therefore,... (Review)
Review
Familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) are rare inherited polyposis syndromes with a high colorectal cancer (CRC) risk. Therefore, frequent endoscopic surveillance including polypectomy of relevant premalignant lesions from a young age is warranted in patients. In FAP and less often in MAP, prophylactic colectomy is indicated followed by lifelong endoscopic surveillance of the retained rectum after (sub)total colectomy and ileal pouch after proctocolectomy to prevent CRC. No consensus is reached on the right type and timing of colectomy. As patients with FAP and MAP nowadays have an almost normal life-expectancy due to adequate treatment of colorectal polyposis, challenges in the management of FAP and MAP have shifted towards the treatment of duodenal and gastric adenomas as well as desmoid treatment in FAP. Whereas up until recently upper gastrointestinal surveillance was mostly diagnostic and patients were referred for surgery once duodenal or gastric polyposis was advanced, nowadays endoscopic treatment of premalignant lesions is widely performed. Aiming to reduce polyp burden in the colorectum as well as in the upper gastrointestinal tract, several chemopreventive agents are currently being studied.
Topics: Adenomatous Polyposis Coli; Adenomatous Polyps; Colorectal Neoplasms; Humans; Stomach Neoplasms
PubMed: 35988966
DOI: 10.1016/j.bpg.2022.101793 -
Gut and Liver Sep 2021Proton pump inhibitors (PPIs) are used worldwide to treat of acid-related disorders such as peptic ulcer and gastroesophageal reflux disease and to prevent... (Review)
Review
Proton pump inhibitors (PPIs) are used worldwide to treat of acid-related disorders such as peptic ulcer and gastroesophageal reflux disease and to prevent gastroduodenal injuries due to nonsteroidal anti-inflammatory drugs. PPIs are the most potent inhibitors of gastric acid secretion currently available, and they are one of the most commonly prescribed classes of drugs because of their high efficacy and low toxicity. However, long-term PPI use causes histopathological changes such as parietal cell protrusion into the gland lumen, cystic dilation of gastric fundic glands, and foveolar epithelial hyperplasia. These changes can manifest on endoscopic examination as fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, or black spots. Clinicians must be aware of PPI-induced endoscopic features in patients with chronic long-term PPI use. Conversely, identifying patients with long-term PPI use based on their endoscopic findings is important. Recently, potassium-competitive acid blockers (P-CABs), a new class of acid suppressants that inhibit gastric acid secretion more strongly than PPIs, have recently been introduced clinically. Further long-term prospective studies on these gastric mucosal lesions in patients with either PPI or P-CAB use are required to investigate their association with histopathological changes and to establish the clinical significance of these findings.
Topics: Adenomatous Polyps; Gastric Mucosa; Humans; Prospective Studies; Proton Pump Inhibitors; Stomach Neoplasms
PubMed: 32327613
DOI: 10.5009/gnl20036 -
Circulation Aug 2018Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal...
BACKGROUND
Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer.
METHODS
HF was induced by inflicting large anterior myocardial infarction in APC mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort.
RESULTS
The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APC mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index).
CONCLUSIONS
We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.
Topics: Adenomatous Polyps; Adult; Aged; Animals; Anterior Wall Myocardial Infarction; Case-Control Studies; Cell Proliferation; Disease Models, Animal; Female; Genes, APC; HT29 Cells; Heart Failure; Humans; Inflammation Mediators; Intercellular Signaling Peptides and Proteins; Intestinal Neoplasms; Intestinal Polyps; Male; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Signal Transduction; Time Factors; Tumor Burden; Ventricular Remodeling
PubMed: 29459363
DOI: 10.1161/CIRCULATIONAHA.117.030816 -
Nature Communications Mar 2015Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly...
Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.
Topics: Actinobacteria; Adenomatous Polyps; Aged; Aged, 80 and over; Bacteroidetes; Case-Control Studies; Colorectal Neoplasms; Diet; Disease Progression; Feces; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Male; Metagenome; Middle Aged; Proteobacteria; Red Meat; Risk Factors; Vegetables
PubMed: 25758642
DOI: 10.1038/ncomms7528 -
Endoscopy Mar 2017ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of...
ESGE recommends cold snare polypectomy (CSP) as the preferred technique for removal of diminutive polyps (size ≤ 5 mm). This technique has high rates of complete resection, adequate tissue sampling for histology, and low complication rates. (High quality evidence, strong recommendation.) ESGE suggests CSP for sessile polyps 6 - 9 mm in size because of its superior safety profile, although evidence comparing efficacy with hot snare polypectomy (HSP) is lacking. (Moderate quality evidence, weak recommendation.) ESGE suggests HSP (with or without submucosal injection) for removal of sessile polyps 10 - 19 mm in size. In most cases deep thermal injury is a potential risk and thus submucosal injection prior to HSP should be considered. (Low quality evidence, strong recommendation.) ESGE recommends HSP for pedunculated polyps. To prevent bleeding in pedunculated colorectal polyps with head ≥ 20 mm or a stalk ≥ 10 mm in diameter, ESGE recommends pretreatment of the stalk with injection of dilute adrenaline and/or mechanical hemostasis. (Moderate quality evidence, strong recommendation.) ESGE recommends that the goals of endoscopic mucosal resection (EMR) are to achieve a completely snare-resected lesion in the safest minimum number of pieces, with adequate margins and without need for adjunctive ablative techniques. (Low quality evidence; strong recommendation.) ESGE recommends careful lesion assessment prior to EMR to identify features suggestive of poor outcome. Features associated with incomplete resection or recurrence include lesion size > 40 mm, ileocecal valve location, prior failed attempts at resection, and size, morphology, site, and access (SMSA) level 4. (Moderate quality evidence; strong recommendation.) For intraprocedural bleeding, ESGE recommends endoscopic coagulation (snare-tip soft coagulation or coagulating forceps) or mechanical therapy, with or without the combined use of dilute adrenaline injection. (Low quality evidence, strong recommendation.)An algorithm of polypectomy recommendations according to shape and size of polyps is given (Fig. 1).
Topics: Adenomatous Polyps; Algorithms; Colon; Colonoscopy; Colorectal Neoplasms; Endoscopic Mucosal Resection; Humans; Intestinal Polyps; Postoperative Complications; Rectum
PubMed: 28212588
DOI: 10.1055/s-0043-102569 -
Endoscopy Sep 2019ESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and...
ESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90 %.ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100 %.
Topics: Adenomatous Polyposis Coli; Colectomy; Early Detection of Cancer; Endoscopy, Gastrointestinal; Humans; Population Surveillance
PubMed: 31342472
DOI: 10.1055/a-0965-0605 -
Clinics in Colon and Rectal Surgery Dec 2016Colonic polyps are considered to be precursors of colon cancer based on several different molecular pathway models and should be resected with a principle of complete... (Review)
Review
Colonic polyps are considered to be precursors of colon cancer based on several different molecular pathway models and should be resected with a principle of complete excisional biopsy. Several techniques are available for excisional biopsy, ranging from endoscopic techniques such as snare polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) to surgical colonic resection and colonic endolaparoscopic surgery (CELS). This article focuses on these modalities with contemporary recommendations for choice of modality based on the size and features of the polyp encountered upon endoscopy. In addition, the morphologically apparent risk factors for polyps harboring invasive malignancy are discussed along with implications for management. Current literature on the comparative risks and benefits of EMR, ESD, CELS, and surgical resection is reviewed, as well as recommendations regarding cancer risk and subsequent surveillance.
PubMed: 31777461
DOI: 10.1055/s-0036-1584090