Multiple Adenomas Research Articles

Abstract 2381: A multiancestral model of colorectal cancer: in vivo evidence that early heterogeneity contributes to cancer progression

Abstract Background: Intratumoral heterogeneity has been linked to tumor progression and chemotherapy resistance in the clinic. Recent models of colorectal tumor evolution indicate that heterogeneity likely arises early during the first few cell divisions and is maintained in a non-Darwinian fashion with discrete clones coevolving. However, how this heterogeneity arises is not fully understood. We propose that some cancers are derived from multiple unique ancestors, and that discrete clones enhance establishment, growth, progression, and resistance to therapy. Methods: Mice carrying the Min allele of Apc and expressing a constitutively active form of PI3K in a subset of colonic epithelial cells develop multiple adenomas and adenocarcinomas in the colon. Cell lineage tracing and fluorescent endoscopy were used to follow the progeny of individual founding cells through establishment, growth, progression, and response to targeted therapy. Cell sorting and 3D tumor spheroid co-culture were used to further examine the growth behavior and treatment response in vitro. Results: Nearly half (44%; 30/68) of the tumors were derived from at least two ancestral clones. The presence of multiple clones was associated with an increased likelihood of a tumor becoming invasive (p = 0.006). Moreover, each clone was more invasive within multi-ancestral tumors than within their homotypic counterparts, indicating that the increased invasion is shared among clones rather than owing to a single dominant clone (p = 0.05). Additionally, the presence of both clones appeared to protect susceptible clones from targeted therapy. In vitro experiments demonstrated that co-evolved clones adopted similar growth patterns, whereas independently evolved clones did not. Conclusions: Taken together, these data strongly indicate that distinct tumor founding cells and their coevolving progeny can contribute to tumor establishment and moreover can enhance growth and survival during tumor progression and response to therapy. Citation Format: Alyssa A. Leystra, Brook Luers, Junbo Son, Chelsie K. Sievers, Amanda M. Wisinger, Alexander R. Schwartz, Christopher D. Zahm, Kristina A. Matkowskyj, Dawn M. Albrecht, Linda Clipson, Dustin A. Deming, Michael A. Newton, Richard B. Halberg. A multiancestral model of colorectal cancer: in vivo evidence that early heterogeneity contributes to cancer progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2381.

A novel pathogenic large germline deletion in adenomatous polyposis coli gene in a Chinese family with familial adenomatous polyposis.

Germline mutations of the APC gene are associated with an autosomal dominant precancerous condition, termed familial adenomatous polyposis (FAP). FAP is clinically manifested by the presence of multiple colorectal adenomas or polyps. Gradually, these colorectal adenomas or polyps inevitably result in colorectal cancer by the third-to fourth decade of life. Surgical interventions or total proctocolectomy is the best possible treatment for FAP. Here, we present a clinical molecular study of a five generation Chinese family with FAP. Diagnosis of FAP was made on the basis of clinical manifestations, family history and medical (colonoscopy and histopathology) records. Blood samples were collected and genomic DNA was extracted. Genetic screening of the APC gene was performed by targeted next-generation sequencing and quantitative real-time PCR. Targeted next generation sequencing identified a novel heterozygous large deletion [exon5-exon16; c.423_8532del] of APC gene, which segregated with the FAP phenotypes in the proband and in all the affected family members. Unaffected family members and normal controls did not carry this deletion. In the Chinese population, most of the previously reported APC gene mutations are missense mutations. This is the first report describing the largest deletion of the APC gene in the Chinese population associated with FAP.

Primary Hyperparathyroidism - Experience at Mayo Hospital, Lahore

The retrospective study was carried out on surgical floor at Mayo Hospital, Lahore, over a span of 15 years. Twenty patients referred from various specialities were included in the study. Seven were male and 13 were female. All patients were diagnosed biochemically and localization was performed with the help of ultrasonography, thallium & technitum subtraction. All patients underwent surgical exploration by adopting four glands exposure technique. Sixteen having single adenoma, two patients having multiple adenoma and two as hyperplasia and no malignancy seen on the basis of histopathological examination. No significant morbidity and no mortality observed in the series.

Identification of familial colorectal cancer and hereditary colorectal cancer syndromes through the Dutch population-screening program: results ofa pilot study

Objectives: In 2014, a population-screening program using immuno-faecal occult blood testing (I-FOBT) has started in the Netherlands. The aims of this study were to evaluate the proportion of individuals in the Dutch screening program with a positive I-FOBT that fulfill the criteria for familial colorectal cancer (FCC) and to evaluate the proportion of participants that needs genetic counseling or colonoscopic surveillance.Material and methods: This retrospective observational study was performed in two large hospitals. Individuals aged between 55 and 75 years with a positive I-FOBT that underwent colonoscopy were included. A detailed family history was obtained in all individuals.Results: A total of 657 individuals with a positive I-FOBT test underwent colonoscopy. A total of 120 (18.3%) participants were found to have a positive family history for CRC, 20 (3.0%) fulfilled the FCC criteria, 4 (0.6%) the Bethesda guidelines and 1 (0.2%) participant the Amsterdam criteria. Multiple adenomas (>10) were found in 21 (3.2%) participants. No cases of serrated polyposis were identified. Based on these criteria and guidelines, a total of 35 (5.3%) required referral to the clinical geneticist and the relatives of 20 (3.0%) participants should be referred for surveillance colonoscopy.Conclusion: Obtaining a detailed family history at the time of intake of participants with a positive I-FOBT in the Dutch surveillance program increased the identification of participants with familial CRC.

Isolated double adrenocorticotropic hormone-secreting pituitary adenomas: A case report and review of the literature.

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas.

Paneth Cells in Colonic Adenomas: Association with Higher Adenoma Burden

Introduction. The association of Paneth cells with colorectal neoplasms has been demonstrated in several studies and case reports. The frequency of Paneth cell-containing adenomas ranges from 0.2 to 39% in the various published studies. Although adenomas with Paneth cells have already been recognized before, there are no studies in the Philippines, that have been done to evaluate their clinicopathologic features. This study was performed to evaluate the clinicopathologic features of Paneth cell-containing adenomas and their association with adenoma burden.Methodology. A total of 326 colorectal adenomas from 133 patients diagnosed consecutively from April 2013 to June 2013 at St. Luke’s Medical Center, Quezon City, Philippines, were reviewed. These were checked for the presence of Paneth cells within the adenomatous crypts. The differences in gender and location were analyzed using one tail z-test, while the association of Paneth-cell containing adenomas with adenoma burden was analyzed using univariate odds ratio at 95% confidence interval.Results. The frequency of Paneth cell-containing adenomas in this study of 326 adenomas is 15% (50 of 326 adenomas). There was no statistical significance in the occurrence of the lesion between male and female patients (32% vs. 15%; p=0.2041). There was also no statistical difference in their occurrence in the proximal and distal colon (18% vs. 14%; p=0.1723). The odds of having multiple adenomas for patients with Paneth cell-containing adenomas are 3.16 times higher than those patients without Paneth cell-containing adenomas (15 patients with one adenoma, 23 patients with more than one adenoma; p=0.0037).Conclusion. This study has demonstrated the increased odds of harboring multiple adenomas in patients with Paneth-cell containing adenomas. This may be attributed in part to the fact that there have been recent studies revolving around Paneth cells that have shown that an established pathway of colorectal tumorigenesis, the APC/Wnt/β-catenin pathway, regulates differentiation towards this cell lineage.

Clinical Characteristics of Multiple Colorectal Adenoma Patients Without Germline APC or MYH Mutations.

Patients with multiple colorectal adenomas (MCRA) without genetic cause are increasingly being diagnosed. The characteristics and natural history of this condition are not well studied. Twenty-seven patients with MCRA, with cumulatively 10 to 99 colorectal adenomas and without deleterious mutations of APC or MYH genes, were investigated. Results of colonoscopies with a mean follow-up of 4.9 years (range, 0 to 27 y) were evaluated. Findings from esophagogastroduodenoscopy and extracolonic manifestations were assessed. The mean age at polyp diagnosis and MCRA diagnosis was 47.8±13.1 years (range, 21 to 72 y) and 50.4±14.6 years (range, 21 to 72 y), respectively. In 22% of patients another family member had MCRA. At first colonoscopy, the mean number of adenomas was 35.0±35.9 (range, 0 to 99). Serrated polyps were rare. Esophagogastroduodenoscopy revealed 47% of patients had upper tract neoplasia. Patients with upper tract findings were diagnosed with MCRA at significantly younger mean age than those without findings, P<0.05. Eighteen patients (67%) underwent colectomy with a mean time from diagnosis of MCRA of 3.1±1.3 years. After surgery, surveyed patients developed recurrent adenomas in retained colorectum. Nine patients (33%) had extracolonic cancers. MCRA patients have a similar clinicopathologic phenotype to known syndromes of attenuated adenomatous polyposis and the majority have need for colectomy. The management of MCRA patients and families should parallel that of attenuated familial adenomatous polyposis and MUTYH-associated polyposis including surveillance of the upper tract.

Association between adenoma location and risk of recurrence

The biological environment varies across the colorectum and may therefore affect neoplastic growth differently in the proximal and distal colon. The aim of the study was to evaluate the risk for recurrent adenomas and their anatomic location based on adenoma location at baseline colonoscopy. Data were extracted from 3 adenoma prevention trials (n= 2430). Participants had at least 1 adenoma at baseline colonoscopy and underwent subsequent surveillance colonoscopy, at which time metachronous adenomas could be detected. We calculated the risk ratio (RR) and the 95% confidence interval (CI) for metachronous adenomas by location of the baseline lesion and considered the impact of advanced neoplasia and multiplicity. At baseline, 522 patients (21.5%) had adenomas only in the proximal colon, 1266 patients (52.1%) had adenomas only in the distal colorectum, and 642 (26.4%) had adenomas in both regions. Overall, 877 patients (36.5%) had metachronous adenomas during the follow-up period. Those with only proximal adenomas at baseline had a higher risk of metachronous adenomas compared with patients with only distal adenomas (RR, 1.17; 95% CI, 1.01-1.35). A greater proximal risk was found after restricting the analysis to patients with multiple proximal adenomas versus multiple distal adenomas (RR, 1.35; 95% CI, 1.10-1.67). The risk of recurrent adenomas on the same side was 48% higher for patients with only proximal adenomas at baseline compared with those with only distal adenomas at baseline (RR, 1.48; 95% CI, 1.22-1.80). Patients with proximal adenomas only have a modestly greater risk of adenoma recurrence than patients with adenomas limited to the distal colon, and have a greater likelihood of adenoma recurrence on the same side compared with patients with distal adenomas. This observation suggests that biological factors may differentially affect neoplasia growth across the colon.

Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial

The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 [38·0%; 95% CI 26·7-49·3] of 71 patients, placebo group 35 [56·5%; 95% CI 44·1-68·8] of 62; p=0·034, risk ratio [RR] 0·67 [95% CI 0·47-0·97]; adenomas: metformin group 22 [30·6%; 95% CI 19·9-41·2] of 71 patients, placebo group 32 [51·6%; 95% CI 39·2-64·1] of 62; p=0·016, RR 0·60 [95% CI 0·39-0·92]). The median number of polyps was zero (IQR 0-1) in the metformin group and one (0-1) in the placebo group (p=0·041). The median number of adenomas was zero (0-1) in the metformin group and zero (0-1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. Ministry of Health, Labour and Welfare, Japan.

Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers.

Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We assessed whether these SNPs are associated with polyp multiplicity in proven APC mutation carriers. Sixteen CRC-associated SNPs were analysed in a cohort of 419 APC germline mutation carriers from 182 families. Clinical data were retrieved from the Dutch Polyposis Registry. Allele frequencies of the SNPs were compared for patients with <100 colorectal adenomas versus patients with ≥100 adenomas, using generalized estimating equations with the APC genotype as a covariate. We found a trend of association of two of the tested SNPs with the ≥100 adenoma phenotype: the C alleles of rs16892766 at 8q23.3 (OR 1.71, 95 % CI 1.05–2.76, p = 0.03, dominant model) and rs3802842 at 11q23.1 (OR 1.51, 95 % CI 1.03–2.22, p = 0.04, dominant model). We identified two risk variants that are associated with a more severe phenotype in APC mutation carriers. These risk variants may partly explain the phenotypic variability in families with the same APC gene defect. Further studies with a larger sample size are recommended to evaluate and confirm the phenotypic effect of these SNPs in FAP.

Multiple Pituitary Adenomas: A Systematic Review.

PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing’s syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA.

Prevalence of colorectal adenoma in patients with multiple gastric adenoma or cancers.

517 Background: It has been reported that patients with single gastric cancer or adenoma are at increased risk of colorectal cancer or adenoma. However, the incidence of colorectal adenoma in patients with multiple gastric neoplasms has not been discussed yet. Methods: We retrospectively analyzed the esophagogastroduodenoscopic and colonoscopic findings as well as the clinicopathologic features between October 2012 and July 2014. The aim of this study was to investigate whether the incidence of colorectal adenoma is higher or not in patients with multiple gastric neoplasms than those with a single gastric neoplasm. Results: A total of 164 patients with gastric neoplasm were divided into two groups whether the number of lesions was single or multiple. Among the 138 patients with single gastric neoplasm, 51 patients performed colonoscopy for surveillance study and 9 patients underwent colonoscopy among the 26 patients with multiple gastric neoplasms. Colorectal adenoma were detected in 58.8% (30/51) of the single gastric neoplasm group, and in 88.8% (8/9) of the multiple gastric neoplasms group (p &lt; 0.001). The mean number of colorectal adenomas was significantly higher in the multiple gastric neoplasm group than in the single group. (4.78 vs. 1.94, p = 0.013). The age, sex, BMI, presence of underlying diseases and the degree of gastric dysplasia were not significantly different between the two groups. Conclusions: The prevalence and the number of colorectal adenoma were significantly higher in patients with multiple gastric neoplasms than in those with single gastric neoplasm. Clinical trial information: KUGH14308-001.

Small bowel adenocarcinoma arising in a patient with hereditary hemorrhagic telangiectasia: A case report.

Patients with hereditary hemorrhagic telangiectasia (HHT) are reportedly at a lower overall risk of malignancies, and small bowel adenocarcinoma (SBA) arising in a HHT patient is extremely rare. In this study, the case of a 37-year-old female with HHT who developed a poorly differentiated jejunal adenocarcinoma five years after ileocecal resection for multiple colonic adenomas is presented. The patient underwent curative resection of the cancer invading the ileum and the mesentery of the transverse colon, but had to overcome critical complications perioperatively, stemming from HHT-associated peripheral capillary dilatation and arteriovenous malformation, including nosebleeds and possible infusion-induced air embolism through pulmonary shunts. The patient subsequently received adjuvant chemotherapy including capecitabine and oxaliplatin for 6 months, and currently remains alive without any evidence of recurrence 12 months after the second surgery. This patient with SBA was an instructive case demonstrating the necessity of careful attention during major surgery in HHT.

Functional Evaluation of Nine Missense-Type Variants of the Human DNA Glycosylase Enzyme MUTYH in the Japanese Population.

Biallelic germline mutations of MUTYH, the gene encoding DNA glycosylase, cause MUTYH-associated polyposis (MAP), characterized by multiple colorectal adenomas and carcinoma(s). However, a considerable number of MUTYH variants are still functionally uncharacterized. Herein, we report the results of functional evaluation of nine missense-type MUTYH variant proteins in the Japanese population. The DNA glycosylase activity and ability to suppress mutations caused by 8-hydroxyguanine, an oxidized form of guanine, were examined for the nine variants of type 2 MUTYH, a nuclear form of the enzyme, by DNA cleavage activity assay and supF forward mutation assay, respectively. Both activities were severely defective in the p.N210S MUTYH type 2 variant corresponding to p.N238S in the reference MUTYH form and partially defective in p.R219G variant corresponding to p.R247G, but nearly fully retained in seven other variants examined. Our results suggest that p.N238S and p.R247G are likely to be pathogenic alleles for MAP.

Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women

Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (≥1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (Ptrend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03-2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer-risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P < 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, ≥1 cm size and location in the proximal colon (all Ptrend < 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma.

Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer.

AIMTo review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)].METHODSWe performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each < 10 mm in size and advanced adenomas as any adenoma ≥ 10 mm size or with > 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC.RESULTSOur search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma.CONCLUSIONData on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.

Fruit and vegetable intakes and risk of colorectal cancer and incident and recurrent adenomas in the PLCO cancer screening trial.

The roles of fruits and vegetables in colorectal cancer development are unclear. Few prospective studies have assessed the association with adenoma, a known precursor to colorectal cancer. Our aim was to evaluate the association between fruit and vegetable intake and colorectal cancer development by evaluating the risk of incident and recurrent colorectal adenoma and colorectal cancer. Study participants were identified from the intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Fruit and vegetable intake was measured using a self-reported dietary questionnaire. Total fruit and vegetable intake was not associated with reduced incident or recurrent adenoma risk overall, but a protective association was observed for multiple adenomas (Odds ratio 3rd tertile vs. 1st tertile = 0.61, 95% confidence interval (CI): 0.38, 1.00). Higher fruit and vegetable intakes were associated with a borderline reduced risk of colorectal cancer (Hazard ratio (HR) 3rd tertile vs. 1st tertile = 0.82, 95% CI: 0.67, 1.01), which reached significance amongst individuals with high processed meat intakes (HR = 0.74, 95% CI: 0.55, 0.99). Our results suggest that increased fruit and vegetable intake may protect against multiple adenoma development and may reduce the detrimental effects of high processed meat intakes on colorectal cancer risk.

Thyroid Adenomas in Children

According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years.

Adenoma development in familial adenomatous polyposis and MUTYH-associated polyposis: somatic landscape and driver genes.

Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss‐of‐function mutations in WTX (9%; p < 9.99e‐06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Opportunity for cardiovascular risk factor reduction in AAA surveillance programs: a systematic review and meta-analysis of cardiovascular mortality in patients with small AAA

Opportunity for cardiovascular risk factor reduction in AAA surveillance programs: a systematic review and meta-analysis of cardiovascular mortality in patients with small AAA