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Sample records for advanced colorectal adenoma

  1. Genetic Variants Associated with Colorectal Adenoma Susceptibility

    PubMed Central

    Abulí, Anna; Castells, Antoni; Bujanda, Luis; Lozano, Juan José; Bessa, Xavier; Hernández, Cristina; Álvarez-Urturi, Cristina; Pellisé, Maria; Esteban-Jurado, Clara; Hijona, Elizabeth; Burón, Andrea; Macià, Francesc; Grau, Jaume; Guayta, Rafael

    2016-01-01

    Background Common low-penetrance genetic variants have been consistently associated with colorectal cancer risk. Aim To determine if these genetic variants are associated also with adenoma susceptibility and may improve selection of patients with increased risk for advanced adenomas and/or multiplicity (≥ 3 adenomas). Methods We selected 1,326 patients with increased risk for advanced adenomas and/or multiplicity and 1,252 controls with normal colonoscopy from population-based colorectal cancer screening programs. We conducted a case-control association study analyzing 30 colorectal cancer susceptibility variants in order to investigate the contribution of these variants to the development of subsequent advanced neoplasia and/or multiplicity. Results We found that 14 of the analyzed genetic variants showed a statistically significant association with advanced adenomas and/or multiplicity: the probability of developing these lesions increased with the number of risk alleles reaching a 2.3-fold risk increment in individuals with ≥ 17 risk alleles. Conclusions Nearly half of the genetic variants associated with colorectal cancer risk are also related to advanced adenoma and/or multiplicity predisposition. Assessing the number of risk alleles in individuals within colorectal cancer screening programs may help to identify better a subgroup with increased risk for advanced neoplasia and/or multiplicity in the general population. PMID:27078840

  2. Serum CD26 is related to histopathological polyp traits and behaves as a marker for colorectal cancer and advanced adenomas

    PubMed Central

    2010-01-01

    Background Serum CD26 (sCD26) levels were previously found diminished in colorectal cancer (CRC) patients compared to healthy donors, suggesting its potential utility for early diagnosis. Therefore we aimed to estimate the utility of the sCD26 as a biomarker for CRC and advanced adenomas in a high-risk group of patients. The relationship of this molecule with polyp characteristics was also addressed. Methods sCD26 levels were measured by ELISA in 299 symptomatic and asymptomatic patients who had undergone a colonoscopy. Patients were diagnosed as having no colorectal pathology, non-inflammatory or inflammatory bowel disease, polyps (hyperplastic, non-advanced and advanced adenomas) or CRC. Results At a 460 ng/mL cut-off, the sCD26 has a sensitivity and specificity of 81.8% (95% CI, 64.5-93.0%) and 72.3% (95% CI, 65.0-77.2%) for CRC regarding no or benign colorectal pathology. Clinicopathological analysis of polyps showed a relationship between the sCD26 and the grade of dysplasia and the presence of advanced adenomas. Hence, a 58.0% (95% CI, 46.5-68.9%) sensitivity detecting CRC and advanced adenomas was obtained, with a specificity of 75.5% (95% CI, 68.5-81.0%). Conclusions Our preliminary results show that measurement of the sCD26 is a non-invasive and reasonably sensitive assay, which could be combined with others such as the faecal occult blood test for the early diagnosis and screening of CRC and advanced adenomas. Additional comparative studies in average-risk populations are necessary. PMID:20584285

  3. Risk Factors of Advanced Adenoma in Small and Diminutive Colorectal Polyp

    PubMed Central

    2016-01-01

    The aims of this study were to review the clinicopathological characteristics of diminutive (≤ 5 mm) and small polyps (> 5 mm but < 10 mm) and to evaluate the risk factors of advanced adenoma for polyps of diameter < 10 mm in the colon. The medical records of 4,711 patients who underwent first colonoscopy at outpatient clinics or health promotion center were reviewed retrospectively. We analyzed the presence and risk factors of advanced adenoma, which was defined as a villous or tubulovillous polyp, high-grade dysplasia or intramucosal carcinoma histologically. Total 5,058 polyps were detected in the 4,711 patients, and 93.0% (4,704/5,058) polyps were < 10 mm in size. Among them, advanced adenoma was noted in 0.6% (28/4,704) with a villous component in 19, high-grade dysplasia in 3, and adenocarcinoma in 6. Advanced and non-advanced adenomas differed significantly in age group, gender, and polyp size. Multivariate analysis showed that an advanced age (> 65 years), a male gender, and a polyp size of > 5 mm were risk factors of advanced adenoma. The incidence of advanced adenoma in polyps of < 10 mm was 0.6%. Polyp size, male gender, and age of > 65 years are independent risk factors of advanced adenoma. PMID:27510386

  4. Associations of cigarette smoking and alcohol consumption with advanced or multiple colorectal adenoma risks: a colonoscopy-based case-control study in Korea.

    PubMed

    Shin, Aesun; Hong, Chang Won; Sohn, Dae Kyung; Chang Kim, Byung; Han, Kyung Su; Chang, Hee Jin; Kim, Jeongseon; Oh, Jae Hwan

    2011-09-01

    The associations between alcohol consumption and cigarette smoking habits and the risk for colorectal adenomatous polyps according to the detailed clinical information about polyps were assessed in a large colonoscopy-based study. The study enrolled participants who visited the National Cancer Center of the Republic of Korea for cancer screening between April 2007 and April 2009. In 1,242 newly diagnosed colorectal adenoma patients and 3,019 polyp-free controls, past smokers (odds ratio (OR) = 1.31, 95% confidence interval (CI): 1.04, 1.65) and current smokers (OR = 1.70, 95% CI: 1.37, 2.11) had increased risks for adenomas compared with nonsmokers. Cigarette smoking conferred an even higher risk for advanced adenomas and 3 or more adenomas than for low-risk adenomas or a single adenoma. Dose-response relations were observed among the daily number of cigarettes smoked, the duration of smoking, the pack-years of smoking, and the risk for adenomas. A longer duration of alcohol consumption was associated with a higher risk for advanced adenomas (for >28 years of consumption: OR = 2.0, 95% CI: 1.10, 3.64) and 3 or more adenomas (OR = 2.19, 95% CI: 1.27, 3.76). In conclusion, cigarette smoking and alcohol consumption play roles in colorectal carcinogenesis, and the association differs by the clinical features of the adenomas.

  5. Development and validation of a risk score for advanced colorectal adenoma recurrence after endoscopic resection

    PubMed Central

    Facciorusso, Antonio; Di Maso, Marianna; Serviddio, Gaetano; Vendemiale, Gianluigi; Muscatiello, Nicola

    2016-01-01

    AIM: To develop and validate a risk score for advanced colorectal adenoma (ACA) recurrence after endoscopic polypectomy. METHODS: Out of 3360 patients who underwent colon polypectomy at University of Foggia between 2004 and 2008, data of 843 patients with 1155 ACAs was retrospectively reviewed. Surveillance intervals were scheduled by guidelines at 3 years and primary endpoint was considered 3-year ACA recurrence. Baseline clinical parameters and the main features of ACAs were entered into a Cox regression analysis and variables with P < 0.05 in the univariate analysis were then tested as candidate variables into a stepwise Cox regression model (conditional backward selection). The regression coefficients of the Cox regression model were multiplied by 2 and rounded in order to obtain easy to use point numbers facilitating the calculation of the score. To avoid overoptimistic results due to model fitting and evaluation in the same dataset, we performed an internal 10-fold cross-validation by means of bootstrap sampling. RESULTS: Median lesion size was 16 mm (12-23) while median number of adenomas was 2.5 (1-3), whereof the number of ACAs was 1.5 (1-2). At 3 years after polypectomy, recurrence was observed in 229 ACAs (19.8%), of which 157 (13.5%) were metachronous neoplasms and 72 (6.2%) local recurrences. Multivariate analysis, after exclusion of the variable “type of resection” due to its collinearity with other predictive factors, confirmed lesion size, number of ACAs and grade of dysplasia as significantly associated to the primary outcome. The score was then built by multiplying the regression coefficients times 2 and the cut-off point 5 was selected by means of a Receiver Operating Characteristic curve analysis. In particular, 248 patients with 365 ACAs fell in the higher-risk group (score ≥ 5) where 3-year recurrence was detected in 174 ACAs (47.6%) whereas the remaining 595 patients with 690 ACAs were included in the low-risk group (score < 5) where 3

  6. Is height a risk factor for colorectal adenoma?

    PubMed Central

    Pyo, Jeung Hui; Hong, Sung Noh; Min, Byung-Hoon; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J.; Kim, Young-Ho

    2016-01-01

    Background/Aims: Although it is generally known that the risk for all types of cancer increases with adult height, combined and for several common site-specific cancers (including colon and rectal), evidence is limited for adenomas, which are precursors to colorectal cancer. We evaluated the association between height and risk of colorectal adenoma at various stages of the adenoma-carcinoma pathway. Methods: We conducted a retrospective study using data from patients who had undergone a complete colonoscopy as part of a health examination at the Health Promotion Center of Samsung Medical Center between October 13, 2009 and December 31, 2011. A total of 1,347 male subjects were included in our study. Multivariate logistic regression analysis was used to evaluate the association between height and colorectal adenoma. Results: Each 5-cm increase in height was associated with 1.6% and 5.3% higher risks of advanced colorectal adenoma and high-risk colorectal adenoma, respectively, but associations were not significant after adjusting for age, body mass index, metabolic syndrome, alcohol intake, smoking, family history of colorectal cancer, and regular aspirin use (p = 0.840 and p = 0.472, respectively). Conclusions: No clear association was found between colorectal adenoma risk and height. Unlike other site-specific tumors reported to have a consistent relationship with height, the association between colorectal tumor and height remains controversial. PMID:26701232

  7. Rate and Risk Factors of the Advanced Adenomas Among Diminutive Colorectal Polyps.

    PubMed

    Aktekin, Ali; Comunoglu, Nil; Odabasi, Mehmet; Muftuoglu, Tolga; Gurleyik, Gunay; Abanonu, Gul Babacan

    2015-12-01

    Only 49 % of diminutive colorectal polyps are neoplastic, but a tiny percentage contains advanced histology. We aimed to determine the rate of advanced diminutive polyps and to evaluate the influence of age, gender, number, and localization. Patients undergoing a videocolonoscopy in October 2010 and April 2012 were collected prospectively. Subjects with polyps ≤5 mm in diameter were recruited into the study. The presence of a villous component of >25 % and a high degree of dysplasia were categorized as polyps with advanced histology. Two hundred eight diminutive polyps were identified in 102 patients. Twenty (9.6 %) diminutive polyps in 13 (12.74 %) patients showed advanced histology. The probability of having an advanced diminutive polyp was higher in patients who have more than one polyp or have polyps localized all along the colon or only to the distal part (p < 0.001 and p = 0.002). Having more than one polyp increases the likelihood of having advanced diminutive polyp according to a multivariate analysis (p = 0.003). Polyps accompanying any dysplastic diminutive polyp, being one of multiple polyps, and distributed all along the colon or localized to only the distal part have an increased probability of being an advanced diminutive polyp (p < 0.001, p = 0.047, p < 0.001, and p = 0.008). Multivariate logistic regression demonstrated that only any accompanying dysplastic diminutive polyp increases the probability of a polyp being advanced diminutive (p = 0.034). Diminutive polyps could have advanced histology. Multiple polyps located in the whole colorectum or to the distal part or accompanying any advanced polyps may harbor an advanced histology and should be removed.

  8. URINARY MUTAGENICITY AND COLORECTAL ADENOMA RISK

    EPA Science Inventory

    Abstract

    We investigated urinary mutagenicity and colorectal adenoma risk in a clinic-based, case-control study of currently nonsmoking cases (n = 143) and controls (n = 156). Urinary organics were extracted by C18/methanol from 12-h overnight urine samples, and mutagenici...

  9. Television watching and risk of colorectal adenoma

    PubMed Central

    Cao, Y; Keum, N N; Chan, A T; Fuchs, C S; Wu, K; Giovannucci, E L

    2015-01-01

    Background: Prolonged TV watching, a major sedentary behaviour, is associated with increased risk of obesity and diabetes and may involve in colorectal carcinogenesis. Methods: We conducted a cross-sectional analysis among 31 065 men with ⩾1 endoscopy in the Health Professionals Follow-up Study (1988–2008) to evaluate sitting while watching TV and its joint influence with leisure-time physical activity on risk of colorectal adenoma. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Prolonged sitting while watching TV was significantly associated with increased risk of colorectal adenoma (n=4280), and adjusting for physical activity or a potential mediator body mass index did not change the estimates. The ORs (95% CIs) across categories of TV watching (0–6, 7–13, 14–20, and 21+ h per week) were 1.00 (referent), 1.09 (1.01–1.17), 1.16 (1.06–1.27), and 1.10 (0.97–1.25) (OR per 14-h per week increment=1.11; 95% CI: 1.04–1.18; Ptrend=0.001). Compared with the least sedentary (0–6 h per week of TV) and most physically active (highest quintile) men, the most sedentary (14+ h per week) and least active (lowest quintile) men had a significant increased risk of adenoma (OR=1.25; 95% CI: 1.05–1.49), particularly for high-risk adenoma. Conclusions: Prolonged TV viewing is associated with modest increased risk of colorectal adenoma independent of leisure-time physical activity and minimally mediated by obesity. PMID:25590667

  10. Fusobacterium is associated with colorectal adenomas.

    PubMed

    McCoy, Amber N; Araújo-Pérez, Félix; Azcárate-Peril, Andrea; Yeh, Jen Jen; Sandler, Robert S; Keku, Temitope O

    2013-01-01

    The human gut microbiota is increasingly recognized as a player in colorectal cancer (CRC). While particular imbalances in the gut microbiota have been linked to colorectal adenomas and cancer, no specific bacterium has been identified as a risk factor. Recent studies have reported a high abundance of Fusobacterium in CRC subjects compared to normal subjects, but this observation has not been reported for adenomas, CRC precursors. We assessed the abundance of Fusobacterium species in the normal rectal mucosa of subjects with (n = 48) and without adenomas (n = 67). We also confirmed previous reports on Fusobacterium and CRC in 10 CRC tumor tissues and 9 matching normal tissues by pyrosequencing. We extracted DNA from rectal mucosal biopsies and measured bacterial levels by quantitative PCR of the 16S ribosomal RNA gene. Local cytokine gene expression was also determined in mucosal biopsies from adenoma cases and controls by quantitative PCR. The mean log abundance of Fusobacterium or cytokine gene expression between cases and controls was compared by t-test. Logistic regression was used to compare tertiles of Fusobacterium abundance. Adenoma subjects had a significantly higher abundance of Fusobacterium species compared to controls (p = 0.01). Compared to the lowest tertile, subjects with high abundance of Fusobacterium were significantly more likely to have adenomas (OR 3.66, 95% CI 1.37-9.74, p-trend 0.005). Cases but not controls had a significant positive correlation between local cytokine gene expression and Fusobacterium abundance. Among cases, the correlation for local TNF-α and Fusobacterium was r = 0.33, p = 0.06 while it was 0.44, p = 0.01 for Fusobacterium and IL-10. These results support a link between the abundance of Fusobacterium in colonic mucosa and adenomas and suggest a possible role for mucosal inflammation in this process.

  11. Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review

    PubMed Central

    Niedermaier, Tobias; Weigl, Korbinian; Hoffmeister, Michael; Brenner, Hermann

    2016-01-01

    OBJECTIVES: Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors. METHODS: We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently. RESULTS: Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting. CONCLUSIONS: Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies. PMID:27253514

  12. Advanced endoscopic imaging to improve adenoma detection

    PubMed Central

    Neumann, Helmut; Nägel, Andreas; Buda, Andrea

    2015-01-01

    Advanced endoscopic imaging is revolutionizing our way on how to diagnose and treat colorectal lesions. Within recent years a variety of modern endoscopic imaging techniques was introduced to improve adenoma detection rates. Those include high-definition imaging, dye-less chromoendoscopy techniques and novel, highly flexible endoscopes, some of them equipped with balloons or multiple lenses in order to improve adenoma detection rates. In this review we will focus on the newest developments in the field of colonoscopic imaging to improve adenoma detection rates. Described techniques include high-definition imaging, optical chromoendoscopy techniques, virtual chromoendoscopy techniques, the Third Eye Retroscope and other retroviewing devices, the G-EYE endoscope and the Full Spectrum Endoscopy-system. PMID:25789092

  13. Assessing individual risk for high-risk colorectal adenoma at first-time screening colonoscopy.

    PubMed

    Cao, Yin; Rosner, Bernard A; Ma, Jing; Tamimi, Rulla M; Chan, Andrew T; Fuchs, Charles S; Wu, Kana; Giovannucci, Edward L

    2015-10-01

    Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening.

  14. Assessing individual risk for high-risk colorectal adenoma at first-time screening colonoscopy.

    PubMed

    Cao, Yin; Rosner, Bernard A; Ma, Jing; Tamimi, Rulla M; Chan, Andrew T; Fuchs, Charles S; Wu, Kana; Giovannucci, Edward L

    2015-10-01

    Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective US studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs. 1.8% for men in the bottom decile (Odds Ratio [OR] = 9.41), and 6.6% vs. 2.1% for women (OR = 3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the US population that may provide guidance for first-time colorectal cancer screening. PMID:25820865

  15. Assessing Individual Risk for High-Risk Colorectal Adenoma at First-Time Screening Colonoscopy

    PubMed Central

    Cao, Yin; Rosner, Bernard A.; Ma, Jing; Tamimi, Rulla M.; Chan, Andrew T.; Fuchs, Charles S.

    2015-01-01

    Assessing risk of colorectal adenoma at first-time colonoscopy that are of higher likelihood of developing advanced neoplasia during surveillance could help tailor first-line colorectal cancer screening. We developed prediction models for high-risk colorectal adenoma (at least one adenoma ≥1 cm, or with advanced histology, or ≥3 adenomas) among 4,881 asymptomatic white men and 17,970 women who underwent colonoscopy as their first-time screening for colorectal cancer in two prospective U.S. studies using logistic regressions. C-statistics and Hosmer-Lemeshow tests were used to evaluate discrimination and calibration. Ten-fold cross-validation was used for internal validation. A total of 330 (6.7%) men and 678 (3.8%) women were diagnosed with high-risk adenoma at first-time screening colonoscopy. The model for men included age, family history of colorectal cancer, BMI, smoking, sitting watching TV/VCR, regular aspirin/NSAID use, physical activity, and a joint term of multivitamin and alcohol. For women, the model included age, family history of colorectal cancer, BMI, smoking, alcohol, beef/pork/lamb as main dish, regular aspirin/NSAID, calcium, and oral contraceptive use. The C-statistic of the model for men was 0.67 and 0.60 for women (0.64 and 0.57 in cross-validation). Both models calibrated well. The predicted risk of high-risk adenoma for men in the top decile was 15.4% vs 1.8% for men in the bottom decile (Odds Ratio[OR]=9.41), and 6.6% vs 2.1% for women (OR=3.48). In summary, we developed and internally validated an absolute risk assessment tool for high-risk colorectal adenoma among the U.S. population that may provide guidance for first-time colorectal cancer screening. PMID:25820865

  16. Paneth Cell in Adenomas of the Distal Colorectum Is Inversely Associated with Synchronous Advanced Adenoma and Carcinoma

    PubMed Central

    Mahon, Megan; Xu, Jie; Yi, Xianghua; Liu, Xiuli; Gao, Nan; Zhang, Lanjing

    2016-01-01

    Recent studies have linked appearance of Paneth cells in colorectal adenomas to adenoma burden and male gender. However, the clinical importance of Paneth cells’ associations with synchronous advanced adenoma (AA) and colorectal carcinoma (CRC) is currently unclear. We performed a comprehensive case-control study using 1,900 colorectal adenomas including 785 from females, and 1,115 from males. We prospectively reviewed and recorded Paneth cell status in the colorectal adenomas consecutively collected between February 2014 and June 2015. Multivariable logistic regression analyses revealed that, in contrast to the adenomas without Paneth cells, the Paneth cell-containing adenomas at distal colorectum were inversely associated with presence of a synchronous AA or CRC (odds ratio [OR] 0.39, P = 0.046), whereas no statistical significance was reached for Paneth cell-containing proximal colorectal adenomas (P = 0.33). Synchronous AA and CRC were significantly associated with older age (60 + versus <60 years, OR 1.60, P = 0.002), male gender (OR 1.42, P = 0.021), and a history of AA or CRC (OR 2.31, P < 0.001). However, synchronous CRC was not associated with Paneth cell status, or a history of AA or CRC. Paneth cell presence in the adenomas of distal colorectum may be a negative indicator for synchronous AA and CRC, and seems to warrant further studies. PMID:27188450

  17. Investigation of human papillomavirus DNA in colorectal carcinomas and adenomas.

    PubMed

    Yavuzer, Dilek; Karadayi, Nimet; Salepci, Taflan; Baloglu, Huseyin; Dabak, Resat; Bayramicli, Oya Uygur

    2011-03-01

    Human papillomavirus (HPV) has been considered to be an etiological agent for anogenital cancers, such as cervical cancer and possibly a subset of cancers of the aerodigestive tract. The aim of the study was to evaluate the presence of human papillomavirus DNA in colorectal carcinomas and adenomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. One hundred and six colorectal carcinomas and 62 adenomas were screened by nested polymerase chain reaction (PCR) for HPV DNA with a control group of 49 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia (CIN). In the study group, we did not find HPV DNA positivity in any of all the colorectal carcinomas and adenomas. In the control group with cervical lesions, 34 out of 49 (69.4%) samples were positive for the HPV DNA. These results indicated that there was no correlation between HPV infection and colorectal carcinomas and adenomas. PMID:20082157

  18. Coffee intake and the risk of colorectal adenoma: The colorectal adenoma study in Tokyo.

    PubMed

    Budhathoki, Sanjeev; Iwasaki, Motoki; Yamaji, Taiki; Sasazuki, Shizuka; Tsugane, Shoichiro

    2015-07-15

    Coffee is a commonly consumed beverage which contains several potential anticarcinogenic and chemopreventive compounds, and has been hypothesized to have protective effects in colorectal neoplasia. However, the limited available data on coffee consumption in relation to colorectal adenoma (CRA), a precursor lesion to most colorectal cancers, remain largely inconsistent. In this study, we evaluated the association of coffee intake with the risk of CRA in a middle-aged Japanese population. Study subjects were selected from examinees who underwent total colonoscopy as part of a cancer screening program and responded to self-administered dietary and lifestyle questionnaires. A total of 738 patients with adenoma and 697 controls were included in the study. Coffee intake was assessed with a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Unconditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) of CRA, with adjustment for potential confounding factors. High coffee consumption was associated with a reduced risk of CRA, with a multivariate-adjusted OR for the highest versus lowest quartile of coffee intake of 0.67 (95% CI = 0.48-0.93; ptrend  = 0.02). The inverse association of coffee intake was limited to proximal (OR = 0.64; 95%CI = 0.44-0.95; ptrend  = 0.04) and distal colon adenoma (OR = 0.62; 95%CI = 0.39-0.99; ptrend  = 0.06), and appeared to be more evident with small (OR = 0.68; 95%CI = 0.49-0.96; ptrend  = 0.04) and single adenomas (OR = 0.65; 95%CI = 0.44-0.95; ptrend  = 0.02). Green tea intake was not found to be associated with CRA risk. This study provides support for the protective effect of coffee drinking on colon adenomas, a precursor of colon cancer.

  19. Dietary Intakes of Red Meat, Poultry, and Fish During High School and Risk of Colorectal Adenomas in Women

    PubMed Central

    Nimptsch, Katharina; Bernstein, Adam M.; Giovannucci, Edward; Fuchs, Charles S.; Willett, Walter C.; Wu, Kana

    2013-01-01

    Adolescent diet may be etiologically relevant for colorectal carcinogenesis. We examined the association between meat and fish intakes during adolescence and the risk of colorectal adenomas later in life among 19,771 women participating in the Nurses' Health Study II. Subjects had completed a validated food frequency questionnaire in 1998 (when aged 34–51 years) about their diets during high school and subsequently underwent at least 1 lower-bowel endoscopy during the study period (1998–2007). During this period, 1,494 subjects were diagnosed with colorectal adenomas. Intake of red meat during adolescence was not associated with colorectal adenoma risk when comparing those in the highest versus lowest category of intake (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.81, 1.35). Similarly, intake of fish during adolescence was not associated with colorectal adenoma risk (OR = 0.96, 95% CI: 0.78, 1.17). Intake of poultry during adolescence was associated with a lower risk of total colorectal (OR = 0.80, 95% CI: 0.64, 0.99), distal (OR = 0.71, 95% CI: 0.51, 0.99), rectal (OR = 0.51, 95% CI: 0.29, 0.90), and advanced (OR = 0.60, 95% CI: 0.38, 0.93) adenomas. Replacement of 1 serving per day of red meat with 1 serving per day of poultry or fish was associated with 41% and 35% decreased risks for rectal adenomas and advanced adenomas, respectively. Our findings do not suggest an association between red meat intake during adolescence and colorectal adenomas later in life, but higher poultry intake during this time was associated with a lower risk of colorectal adenomas. PMID:23785116

  20. Circulating levels of inflammatory cytokines and risk of colorectal adenomas

    PubMed Central

    Kim, Sangmi; Keku, Temitope O.; Martin, Christopher; Galanko, Joseph; Woosley, John T.; Schroeder, Jane C.; Satia, Jessie A.; Halabi, Susan; Sandler, Robert S.

    2009-01-01

    The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-α in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-α were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between levels of inflammatory cytokines, colorectal adenomas, and known risk factors. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines such as older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-α, and to a lesser degree, with CRP. For IL-6, adjusted odds ratios for colorectal adenomas were 1.78 (95% confidence interval [CI]: 1.18–2.68) for the second highest plasma level, and 1.84 (95% CI: 1.24– 2.74) for the highest level compared with the reference level. A similar association was found with TNF-α, with adjusted odds ratios of 1.54 (95% CI: 1.02–2.33) and 1.65 (95% CI: 1.09–2.50), respectively. Our findings indicate that inflammation might be involved in the early development of colorectal neoplasia, and suggest that systemic inflammatory cytokines might be an indicator of obesity and other risk factors for colorectal neoplasia. PMID:18172326

  1. Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas

    PubMed Central

    Lu, Yingying; Chen, Jing; Zheng, Junyuan; Hu, Guoyong; Wang, Jingjing; Huang, Chunlan; Lou, Lihong; Wang, Xingpeng; Zeng, Yue

    2016-01-01

    Recent reports have suggested that the gut microbiota is involved in the progression of colorectal cancer (CRC). The composition of gut microbiota in CRC precursors has not been adequately described. To characterize the structure of adherent microbiota in this disease, we conducted pyrosequencing-based analysis of 16S rRNA genes to determine the bacterial profile of normal colons (healthy controls) and colorectal adenomas (CRC precursors). Adenoma mucosal biopsy samples and adjacent normal colonic mucosa from 31 patients with adenomas and 20 healthy volunteers were profiled using the Illumina MiSeq platform. Principal coordinate analysis (PCoA) showed structural segregation between colorectal adenomatous tissue and control tissue. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with adenomas. Taxonomic analysis illustrated that abundance of eight phyla (Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Chloroflexi, Cyanobacteria, Candidate-division TM7, and Tenericutes) was significantly different. In addition, Lactococcus and Pseudomonas were enriched in preneoplastic tissue, whereas Enterococcus, Bacillus, and Solibacillus were reduced. However, both PCoA and cluster tree analyses showed similar microbiota structure between adenomatous and adjacent non-adenoma tissues. These present findings provide preliminary experimental evidence supporting that colorectal preneoplastic lesion may be the most important factor leading to alterations in bacterial community composition. PMID:27194068

  2. Vasculo-smooth muscle hamartomatous structure is linked to morphogenesis of colorectal polypoid adenoma.

    PubMed

    Nakayama, Hirofumi; Enzan, Hideaki; Yasui, Wataru

    2015-06-01

    To investigate the difference of surrounding stromal structure between the polypoid and flat adenomas in the colorectum, we performed microscopic study including immunohistochemistry in a total of 32 colorectal adenomas (typical 24 polypoid and eight flat adenomas), especially focusing on vessels around muscularis mucosa. All 24 polypoid adenomas accompanied vasculo-smooth muscle hamartomatous structure in association with muscularis mucosa and submucosal vessels, whereas none of eight flat adenomas had vasculo-smooth muscle hamartomatous structure; surrounding muscularis mucosa and submucosa of the flat adenomas are identical to those of normal colorectal tissue. Vasculo-smooth muscle hamartomatous structure is linked to the morphogenesis of colorectal polypoid adenomas.

  3. Characteristics and outcomes of endoscopically resected colorectal cancers that arose from sessile serrated adenomas and traditional serrated adenomas

    PubMed Central

    Seo, Ji Yeon; Choi, Seung Ho; Chun, Jaeyoung; Choi, Ji Min; Jin, Eun Hyo; Hwang, Sung Wook; Im, Jong Pil; Kim, Sang Gyun; Kim, Joo Sung

    2016-01-01

    Background/Aims The efficacy and safety of endoscopic resection of colorectal cancer derived from sessile serrated adenomas or traditional serrated adenomas are still unknown. The aims of this study were to verify the characteristics and outcomes of endoscopically resected early colorectal cancers developed from serrated polyps. Methods Among patients who received endoscopic resection of early colorectal cancers from 2008 to 2011, cancers with documented pre-existing lesions were included. They were classified as adenoma, sessile serrated adenoma, or traditional serrated adenoma according to the baseline lesions. Clinical characteristics, pathologic diagnosis, and outcomes were reviewed. Results Overall, 208 colorectal cancers detected from 198 patients were included: 198 with adenoma, five with sessile serrated adenoma, and five with traditional serrated adenoma. The sessile serrated adenoma group had a higher prevalence of high-grade dysplasia (40.0% vs. 25.8%, P<0.001) than the adenoma group. During follow-up, local recurrence did not occur after endoscopic resection of early colorectal cancers developed from serrated polyps. In contrast, two cases of metachronous recurrence were detected within a short follow-up period. Conclusions Cautious observation and early endoscopic resection are recommended when colorectal cancer from serrated polyp is suspected. Colorectal cancers from serrated polyp can be treated successfully with endoscopy. PMID:27433150

  4. Moderate Alcohol Consumption is Protective Against Colorectal Adenomas in Smokers

    PubMed Central

    Galanko, Joseph A.; Martin, Christopher F.; Sandler, Robert S.

    2009-01-01

    Background Although some studies have shown an association between alcohol consumption and colorectal adenomas, the effect of moderate alcohol consumption is not well-defined, nor is the interaction between alcohol and smoking. Aim To investigate the relationship between different levels of alcohol consumption and colorectal adenomas and to determine whether smoking modifies this relationship. Methods Eligible patients who underwent a complete colonoscopy were included (179 cases and 466 controls). Alcohol consumption was obtained from a lifestyle questionnaire. Patients were divided into three groups: 1) Abstainers: 0 drinks/week; 2) Moderate drinkers: >0-<7 drinks/week; 3) Heavy drinkers: >=7 drinks/week. Odds ratios (OR) were calculated using logistic regression, controlling for gender, age, body mass index, use of non-steroidal anti-inflammatory medications. Results were stratified by the number of years smoked. Results The proportion of patients with adenomas was 29.6% in abstainers, 22.1% in moderate drinkers, and 36.7% in heavy drinkers. There was significant modification of the relationship between alcohol consumption and colorectal adenomas by smoking. For individuals who had never smoked, heavy drinkers were at significantly increased odds of having an adenoma compared to moderate drinkers (OR 3.08; 95% CI: 1.50-6.32), while no difference was seen for abstainers (OR 0.99; 95% CI: 0.52-1.89). Similarly, among individuals who had smoked 1-14 years, heavy drinkers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.61; 95% CI: 1.04-6.51), and no difference was seen for abstainers (OR 1.02; 95% CI: 0.33-3.10). Somewhat unexpectedly, among individuals who had smoked for 15 or more years, abstainers were at increased odds of having an adenoma compared to moderate drinkers (OR 2.04; 95% CI: 0.91-4.59), while heavy drinkers were not at increased odds of having an adenoma (OR 0.73; 95% CI: 0.27-1.97). Conclusions Consumption of less

  5. Meta-Analysis of the Effect of Bowel Preparation on Adenoma Detection: Early Adenomas Affected Stronger than Advanced Adenomas

    PubMed Central

    Prakash, Meher; Manser, Christine N.; Heinrich, Henriette; Misselwitz, Benjamin

    2016-01-01

    Background and Aims Low-quality bowel preparation reduces efficacy of colonoscopy. We aimed to summarize effects of bowel preparation on detection of adenomas, advanced adenomas and colorectal cancer. Methods A systematic literature search was performed regarding detection of colonic lesions after normal and low-quality bowel preparation. Reported bowel preparation quality was transformed to the Aronchick scale with its qualities “excellent”, “good”, “fair”, “poor”, and “insufficient” or “optimal” (good/excellent), “suboptimal” (fair/poor/insufficient), “adequate” (good/excellent/fair) and “inadequate” (poor/insufficient). We identified two types of studies: i) Comparative studies, directly comparing lesion detection according to bowel preparation quality, and ii) repeat colonoscopy studies, reporting results of a second colonoscopy after previous low-quality preparation. Results The detection of early adenomas was reduced with inadequate vs. adequate bowel preparation (Odds Ratio (OR) 0.53, CI: 0.46–0.62, p<0.001). The advanced adenomas were affected less in comparison (0.74, CI: 0.62–0.87, p<0.001). The large number of subjects considered in the present meta-analysis resulted in smaller confidence intervals compared to earlier studies. Classifying the bowel-preparation quality as suboptimal vs. optimal led to the same qualitative conclusion (OR: 0.81, CI: 0.74–0.89, p<0.001 for early adenomas, OR: 0.94, CI: 0.87–1.01, n.s. for advanced adenomas). Bowel preparation was equally important for right-sided/ flat/ serrated vs. other lesions in most observational studies but more relevant in some repeat colonoscopy studies; data regarding carcinoma detection were insufficient. Conclusion Inadequate bowel preparation affects detection of early colonic lesions stronger than advanced lesions. PMID:27257916

  6. A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas

    PubMed Central

    Baron, John A.; Barry, Elizabeth L.; Mott, Leila A.; Rees, Judy R.; Sandler, Robert S.; Snover, Dale C.; Bostick, Roberd M.; Ivanova, Anastasia; Cole, Bernard F.; Ahnen, Dennis J.; Beck, Gerald J.; Bresalier, Robert S.; Burke, Carol A.; Church, Timothy R.; Cruz-Correa, Marcia; Figueiredo, Jane C.; Goodman, Michael; Kim, Adam S.; Robertson, Douglas J.; Rothstein, Richard; Shaukat, Aasma; Seabrook, March E.; Summers, Robert W.

    2015-01-01

    BACKGROUND Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist’s recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT

  7. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

  8. Immunohistochemical Expression of Matrix Metalloproteinase-7 in Human Colorectal Adenomas Using Specified Automated Cellular Image Analysis System: A Clinicopathological Study

    PubMed Central

    Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

    2013-01-01

    Background/Aim: To evaluate the immunohistochemical expression of matrix metalloproteinase-7 (MMP-7) in colorectal adenomas, and to correlate this expression with different clinicopathological parameters. Patients and Methods: The study was retrospectively designed. Thirty three paraffin blocks from patients with colorectal adenoma and 20 samples of non-tumerous colonic tissue taken as control group were included in the study. MMP-7 expression was assessed by immunohistochemistry method. The scoring of immunohistochemical staining was conducted utilizing a specified automated cellular image analysis system (Digimizer). Results: The frequency of positive immunohistochemical expression of MMP-7 was significantly higher in adenoma than control group (45.45% versus 10%) (P value < 0.001). Strong MMP-7 staining was mainly seen in adenoma cases (30.30%) in comparison with control (0%) the difference is significant (P < 0.001). The three digital parameters of MMP-7 immunohistochemical expression (Area (A), Number of objects (N), and intensity (I)) were significantly higher in adenoma than control. Mean (A and I) of MMP-7 showed a significant correlation with large sized adenoma (≥ 1cm) (P < 0.05), also a significant positive correlation of the three digital parameters (A, N, and I) of MMP-7 expression with villous configuration and severe dysplasia in colorectal adenoma had been identified (P < 0.05). Conclusion: MMP-7 plays an important role in the growth and malignant conversion of colorectal adenomas as it is more likely to be expressed in advanced colorectal adenomatous polyps with large size, severe dysplasia and villous histology. The use of automated cellular image analysis system (Digmizer) to quantify immunohistochemical staining yields more consistent assay results, converts semi-quantitative assay to a truly quantitative assay, and improves assay objectivity and reproducibility. PMID:23319034

  9. Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study

    PubMed Central

    van Heijningen, Else-Mariëtte B; Lansdorp-Vogelaar, Iris; Steyerberg, Ewout W; Goede, S Lucas; Dekker, Evelien; Lesterhuis, Wilco; ter Borg, Frank; Vecht, Juda; Spoelstra, Pieter; Engels, Leopold; Bolwerk, Clemens J M; Timmer, Robin; Kleibeuker, Jan H; Koornstra, Jan J; de Koning, Harry J; Kuipers, Ernst J; van Ballegooijen, Marjolein

    2015-01-01

    Objective To determine adherence to recommended surveillance intervals in clinical practice. Design 2997 successive patients with a first adenoma diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical records were reviewed until 1 December 2008. Time to and findings at first surveillance colonoscopy were assessed. A surveillance colonoscopy occurring within ±3 months of a 1-year recommended interval and ±6 months of a recommended interval of 2 years or longer was considered appropriate. The analysis was stratified by period per change in guideline (before 2002: 2–3 years for patients with 1 adenoma, annually otherwise; in 2002: 6 years for 1–2 adenomas, 3 years otherwise). We also assessed differences in adenoma and colorectal cancer recurrence rates by surveillance timing. Results Surveillance was inappropriate in 76% and 89% of patients diagnosed before 2002 and in 2002, respectively. Patients eligible under the pre-2002 guideline mainly received surveillance too late or were absent (57% of cases). For patients eligible under the 2002 guideline surveillance occurred mainly too early (48%). The rate of advanced neoplasia at surveillance was higher in patients with delayed surveillance compared with those with too early or appropriate timed surveillance (8% vs 4–5%, p<0.01). Conclusions There is much room for improving surveillance practice. Less than 25% of patients with adenoma receive appropriate surveillance. Such practice seriously hampers the effectiveness and efficiency of surveillance, as too early surveillance poses a considerable burden on available resources while delayed surveillance is associated with an increased rate of advanced adenoma and especially colorectal cancer. PMID:25586057

  10. Cigarette smoking and the colorectal adenoma-carcinoma sequence: a hypothesis to explain the paradox.

    PubMed

    Terry, M B; Neugut, A I

    1998-05-15

    As recognized precursor lesions to colorectal cancer, colorectal adenomatous polyps have been studied to enhance knowledge of colorectal cancer etiology. Although most of the known risk factors for colorectal cancer are also associated with the occurrence of colorectal adenomas, cigarette smoking has had a strong, consistent relationship with colorectal adenomas but is generally not associated with colorectal cancer. The explanation for this paradox is unknown. With data collected in 1986-1988 during a large case-control study based on colonoscopy results in New York City, New York, the authors investigated the possibility that the paradox may arise because subjects with colorectal adenomas were included in the control group of cancer case-control studies. The authors found a statistically significant increased risk between heavy cigarette smoking (smokers with > or = 40 pack-years of smoking) and risk of adenoma (odds ratio (OR) = 1.61, 95% confidence interval (CI) 1.06-2.44). They saw no increased colorectal cancer risk from heavy cigarette smoking (OR = 1.02, 95% CI 0.52-1.99) using a "manufactured" control group to simulate a typical unscreened, population-based control group. When the authors compared these colorectal cancer cases with an adenoma-free control group examined by colonoscopy in a polytomous model with several case groups (newly diagnosed adenomas, carcinoma in situ, intramucosal carcinoma, and colorectal cancer), they found that the risk for 20-39 pack-years of smoking was elevated, although not statistically significant, and was similar for all four case groups. The risk for the highest smoking category (> or = 40 pack-years) was more strongly elevated in all four case groups, although it was statistically significant for only the newly diagnosed adenoma and the carcinoma in situ cases (adenomas, OR = 1.59, 95% CI 1.05-2.42; carcinoma in situ, OR = 2.05, 95% CI 1.01-4.15; intramucosal carcinoma, OR = 1.30, 95% CI 0.61-2.77; and colorectal cancer

  11. Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas

    PubMed Central

    Kitajima, Takahito; Kawamura, Mikio; Hiro, Junichiro; Kobayashi, Minako; Tanaka, Koji; Inoue, Yasuhiro; Mohri, Yasuhiko; Mori, Takao; Kato, Toshio; Goel, Ajay; Kusunoki, Masato

    2016-01-01

    Background Although there is a growing interest in developing circulating microRNA (miRNA) as noninvasive diagnostic biomarkers for the detection of high-risk colorectal adenomas and early-stage CRCs, but the comparative diagnostic significance of serum vs. exosomal miRNAs remains unexplored. Methods Based upon published literature, we performed an initial discovery step by investigating the expression of a miRNA panel in 20 normal colonic mucosa, 27 adenomas, and 19 CRC tissues. We performed subsequent validation by quantifying expression of candidate miRNAs in total serum and in exosomes from 26 adenoma patients and 47 healthy controls, and evaluated their clinical significance and potential diagnostic value in colorectal adenomas. Results We observed that the expression of four miRNAs, miR-21, miR-29a, miR-92a, and miR-135b, was significantly higher in colorectal adenomas vs. normal colonic mucosa. During validation, expression of miR-21, miR-29a and miR-92a in serum was significantly higher in adenomas vs. healthy controls, significantly correlated with adenoma size and total adenoma number within the colorectum, and significantly discriminated patients with advanced adenomas. In contrast, although exosomal miR-21 and miR-29a levels in adenoma patients were significantly higher than those of healthy volunteers, only exosomal miR-21 significantly correlated with adenoma size and total adenoma number, and could discriminate patients with high-risk adenomas. Conclusion Compared to exosomal miRNAs, serum levels of miR-21, miR-29a and miR-92a are superior diagnostic biomarkers in patients with high-risk adenomatous polyps. PMID:27760147

  12. Differences in Epidemiologic Risk Factors for Colorectal Adenomas and Serrated Polyps by Lesion Severity and Anatomical Site

    PubMed Central

    Burnett-Hartman, Andrea N.; Passarelli, Michael N.; Adams, Scott V.; Upton, Melissa P.; Zhu, Lee-Ching; Potter, John D.; Newcomb, Polly A.

    2013-01-01

    Using a case-control design, we evaluated differences in risk factors for colorectal polyps according to histological type, anatomical site, and severity. Participants were enrollees in the Group Health Cooperative aged 20–79 years who underwent colonoscopy in Seattle, Washington, between 1998 and 2007 and comprised 628 adenoma cases, 594 serrated polyp cases, 247 cases with both types of polyps, and 1,037 polyp-free controls. Participants completed a structured interview, and polyps were evaluated via standardized pathology review. We used multivariable polytomous logistic regression to compare case groups with controls and with the other case groups. Factors for which the strength of the association varied significantly between adenomas and serrated polyps were sex (P < 0.001), use of estrogen-only postmenopausal hormone therapy (P = 0.01), and smoking status (P < 0.001). For lesion severity, prior endoscopy (P < 0.001) and age (P = 0.05) had significantly stronger associations with advanced adenomas than with nonadvanced adenomas; and higher education was positively correlated with sessile serrated polyps but not with other serrated polyps (P = 0.02). Statistically significant, site-specific associations were observed for current cigarette smoking (P = 0.05 among adenomas and P < 0.001 among serrated polyps), postmenopausal estrogen-only therapy (P = 0.01 among adenomas), and obesity (P = 0.01 among serrated polyps). These findings further illustrate the epidemiologic heterogeneity of colorectal neoplasia and may help elucidate carcinogenic mechanisms for distinct pathways. PMID:23459948

  13. Dietary Lignan and Proanthocyanidin Consumption and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

    PubMed Central

    Bobe, Gerd; Murphy, Gwen; Albert, Paul S.; Sansbury, Leah B.; Lanza, Elaine; Schatzkin, Arthur; Cross, Amanda J.

    2011-01-01

    Lignans and proanthocyanidins are plant polyphenols that have shown protective properties against colorectal neoplasms in some human studies. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to prospectively evaluate the association between lignan and proanthocyanidin intake, estimated from databases linked to a food frequency questionnaire, and adenoma recurrence in 1,859 participants of the Polyp Prevention Trial. Overall, individual or total lignans or proanthocyanidins were not associated with colorectal adenoma recurrence. However, in sex-specific analyses, total lignan intake was positively associated with any adenoma recurrence in women (highest versus lowest lignan intake quartile OR = 2.07, 95% CI: 1.22-3.52, P trend = 0.004) but not in men (P interaction = 0.04). To conclude, dietary lignan and proanthocyanidin consumption was not generally related to colorectal adenoma recurrence; however, high lignan intake may increase the risk of adenoma recurrence in women. PMID:21618513

  14. Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma

    PubMed Central

    Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. PMID:26336987

  15. Increased Pulse Wave Velocity Reflecting Arterial Stiffness in Patients with Colorectal Adenomas

    PubMed Central

    Lim, Yun Jeong; Kwack, Won Gun; Lee, Youg-Sup; Hahm, Ki Baik; Kim, Young-Kwon

    2010-01-01

    The obese patients with diabetes or cardiovascular risk factors are associated with increased risk of colorectal cancer as well as adenomas under the shared pathogenesis related to atherosclerosis. Here we determined the association between increased arterial stiffness and colorectal adenomas incorporating parameters including age, gender, waist circumference, body mass index, lipid profiles, fasting glucose, and blood pressure. Subjects who simultaneously underwent colonoscopies and pulse wave velocity (PWV) determinations between July 2005 and September 2006 were analyzed, based on which the subjects were classified into two groups as patients group with colorectal adenomas (n = 49) and control group (n = 200) with normal, non-polypoid benign lesions or hyperplastic polyps. Uni- and multi-variate analyses were performed to calculate the odd ratio for colon adenomas. Based on uni-variate analysis, age, waist circumference, body mass index, heart-femoral PWV (hfPWV), and brachial-ankle PWV were significantly associated with adenomas (p<0.05) and multiple logistic regression analysis showed that the heart-femoral PWV, waist circumference, and the levels of LDL-C were significant risk factor for colorectal adenoma. However, arterial stiffness did not affect the progression of colon adenoma. The finding that hfPWV, reflecting aortic stiffness, was increased in patients with colorectal adenomas lead to conclusion that patients who have prominently increased arterial stiffness can be recommended to undergo colonoscopic examinations and at the same time we also recommend counseling about the risk for atherosclerosis in those who have colorectal adenomas. PMID:21103036

  16. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

    PubMed Central

    Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Newcomb, Polly A; Casey, Graham; Conti, David V; Schumacher, Fred; Gallinger, Steve; Lindor, Noralane M; Hopper, John; Jenkins, Mark; Hunter, David J; Kraft, Peter; Jacobs, Kevin B; Cox, David G; Yeager, Meredith; Hankinson, Susan E; Wacholder, Sholom; Wang, Zhaoming; Welch, Robert; Hutchinson, Amy; Wang, Junwen; Yu, Kai; Chatterjee, Nilanjan; Orr, Nick; Willett, Walter C; Colditz, Graham A; Ziegler, Regina G; Berg, Christine D; Buys, Saundra S; McCarty, Catherine A; Feigelson, Heather Spencer; Calle, Eugenia E; Thun, Michael J; Hayes, Richard B; Tucker, Margaret; Gerhard, Daniela S; Fraumeni, Joseph F; Hoover, Robert N; Thomas, Gilles; Chanock, Stephen J; Yeager, Meredith; Chatterjee, Nilanjan; Ciampa, Julia; Jacobs, Kevin B; Gonzalez-Bosquet, Jesus; Hayes, Richard B; Kraft, Peter; Wacholder, Sholom; Orr, Nick; Berndt, Sonja; Yu, Kai; Hutchinson, Amy; Wang, Zhaoming; Amundadottir, Laufey; Feigelson, Heather Spencer; Thun, Michael J; Diver, W Ryan; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Schumacher, Fredrick R; Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine; Andriole, Gerald L; Crawford, E David; Haiman, Christopher A; Henderson, Brian; Kolonel, Laurence; Marchand, Loic Le; Siddiq, Afshan; Riboli, Elio; Key, Timothy J; Kaaks, Rudolf; Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E; Gronberg, Henrik; Wiklund, Fredrik; Stattin, Pär; Xu, Jianfeng; Zheng, S Lilly; Sun, Jielin; Vatten, Lars J; Hveem, Kristian; Kumle, Merethe; Tucker, Margaret; Gerhard, Daniela S; Hoover, Robert N; Fraumeni, Joseph F; Hunter, David J; Thomas, Gilles; Chanock, Stephen J; Purdue, Mark P; Johansson, Mattias; Zelenika, Diana; Toro, Jorge R; Scelo, Ghislaine; Moore, Lee E; Prokhortchouk, Egor; Wu, Xifeng; Kiemeney, Lambertus A; Gaborieau, Valerie; Jacobs, Kevin B; Chow, Wong-Ho; Zaridze, David; Matveev, Vsevolod; Lubinski, Jan; Trubicka, Joanna; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Péter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Colt, Joanne S; Davis, Faith G; Schwartz, Kendra L; Banks, Rosamonde E; Selby, Peter J; Harnden, Patricia; Berg, Christine D; Hsing, Ann W; Grubb III, Robert L; Boeing, Heiner; Vineis, Paolo; Clavel-Chapelon, Françoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; Duell, Eric J; Quirós, José Ramón; Sanchez, Maria-José; Navarro, Carmen; Ardanaz, Eva; Dorronsoro, Miren; Khaw, Kay-Tee; Allen, Naomi E; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Trichopoulos, Dimitrios; Linseisen, Jakob; Ljungberg, Börje; Overvad, Kim; Tjønneland, Anne; Romieu, Isabelle; Riboli, Elio; Mukeria, Anush; Shangina, Oxana; Stevens, Victoria L; Thun, Michael J; Diver, W Ryan; Gapstur, Susan M; Pharoah, Paul D; Easton, Douglas F; Albanes, Demetrius; Weinstein, Stephanie J; Virtamo, Jarmo; Vatten, Lars; Hveem, Kristian; Njølstad, Inger; Tell, Grethe S; Stoltenberg, Camilla; Kumar, Rajiv; Koppova, Kvetoslava; Cussenot, Olivier; Benhamou, Simone; Oosterwijk, Egbert; Vermeulen, Sita H; Aben, Katja K H; van der Marel, Saskia L; Ye, Yuanqing; Wood, Christopher G; Pu, Xia; Mazur, Alexander M; Boulygina, Eugenia S; Chekanov, Nikolai N; Foglio, Mario; Lechner, Doris; Gut, Ivo; Heath, Simon; Blanche, Hélène; Hutchinson, Amy; Thomas, Gilles; Wang, Zhaoming; Yeager, Meredith; Fraumeni, Joseph F; Skryabin, Konstantin G; McKay, James D; Rothman, Nathaniel; Chanock, Stephen J; Lathrop, Mark; Brennan, Paul; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

    2015-01-01

    The presence of multiple (5–100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10−7). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have ‘polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients. PMID:24801760

  17. Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

  18. Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas

    PubMed Central

    Longman, R; Douthwaite, J; Sylvester, P; O'Leary, D; Warren, B; Corfield, A; Thomas, M

    2000-01-01

    Background—MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection. Aim—To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence. Methods—In a prospective cohort study paired mucosal biopsies of adenomatous and macroscopically "normal" mucosa were obtained from 11 patients with villous and 11 patients with tubulovillous adenomas who underwent primary resection for purpose of cure. The tissues were studied to determine MUC5AC gene expression by immunohistochemistry and in situ hybridisation. Patients were followed up by flexible sigmoidoscopy to detect the presence of early local recurrence. Results—10 villous adenomas showed mature MUC5AC glycoprotein and all 11 expressed MUC5AC mRNA. Five tubulovillous adenomas showed mature MUC5AC glycoprotein and 10 expressed MUC5AC mRNA. Neoexpression of the MUC5AC mucin gene was not detected in any of the mucosal biopsies taken adjacent to either villous or tubulovillous adenomas, even in three patients with early, locally recurrent disease. Conclusions—Aberrant MUC5AC gene expression is not a "field change" in the colorectal mucosa in patients with rectal adenomas and therefore cannot be used to predict local recurrence of villous and tubulovillous adenomas. Key Words: mucin • colorectal adenoma • gene expression • field change PMID:10767823

  19. Establishing the link between hepatitis B virus infection and colorectal adenoma

    PubMed Central

    Lipka, Seth; Shen, Huafeng; Davis-Yadley, Ashley H.; Viswanathan, Prakash

    2015-01-01

    Background Chronic hepatitis B (CHB) infection has been associated with malignancy, most notably hepatocellular carcinoma. Previous research has shown that hepatitis C is associated with increased colorectal adenomas and neoplasia. Currently, there are no studies on the association of CHB and colorectal adenomas. We aimed to identify a possible link between CHB and colorectal adenoma. Methods A retrospective chart review was performed on 588 consecutive patients undergoing screening or diagnostic colonoscopy that were previously screened or diagnosed with hepatitis B. Comparisons between categorical variables were analyzed with Chi Square test and t-test for continuous variables. Unconditional logistic regression was used to generate age-, gender-and race-adjusted odds ratios and their 95% confidence intervals (CI) comparing medication users with non-users. Statistical analyses were performed with SAS 9.3 software. Results A total of 487 patients were analyzed in the control group vs. 71 in the hepatitis B group. The adenoma detection rate was 23.9% in hepatitis B vs. 15.9% in the non-hepatitis B group for all cause colonoscopy; however this did not reach statistical significance. There was a significantly higher number of adenomas present in the distal colon compared to control (OR =2.16; 95% CI, 1.06-4.43; P=0.04). There were no significant findings between hepatitis B infection with size, multiplicity or presence of proximal adenomas. There was a significant difference noted in regards to smoking history, BMI and age between two groups. Conclusions Although the adenoma detection rate was higher in hepatitis B population vs. the non-hepatitis B group this did not reach statistical significance. However, we did find an association between CHB infection and the presence of distal colorectal adenomas. Larger prospective studies are needed to strengthen our findings along with future studies examining hepatitis B virus (HBV) and mechanisms inducing colorectal

  20. The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma

    PubMed Central

    Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

    2016-01-01

    ABSTRACT Objective To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Methods Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student’s t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. Results In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (p<0.001 and p<0.0001, respectively). The immunoreactivity of GSK3β, axin 1 and ubiquitin proteins was significantly higher (p=0.03, p=0.039 and p=0.03, respectively) in colorectal carcinoma than in the colonic adenoma and adjacent non-neoplastic mucosa. The immunohistochemistry staining of these proteins did not show significant differences with the clinical and pathological characteristics of colorectal cancer and colonic adenoma. Conclusions These results suggest that, in adenomas, the lower expression of the beta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. PMID:27462886

  1. ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    EPA Science Inventory

    ASSOCIATION BETWEEN URINARY MUTAGENICITY AND RISK OF COLORECTAL ADENOMAS IN A CLINIC-BASED CASE-CONTROL STUDY

    Humans are exposed to a variety of mutagens from diet, smoking, or occupation. To explore if exposure to mutagens was related to the risk of colorectal adenomas i...

  2. Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

    ClinicalTrials.gov

    2016-05-10

    Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia

  3. Single nucleotide polymorphism array profiling identifies distinct chromosomal aberration patterns across colorectal adenomas and carcinomas.

    PubMed

    Zarzour, Peter; Boelen, Lies; Luciani, Fabio; Beck, Dominik; Sakthianandeswaren, Anuratha; Mouradov, Dmitri; Sieber, Oliver M; Hawkins, Nicholas J; Hesson, Luke B; Ward, Robyn L; Wong, Jason W H

    2015-05-01

    The progression of benign colorectal adenomas into cancer is associated with the accumulation of chromosomal aberrations. Even though patterns and frequencies of chromosomal aberrations have been well established in colorectal carcinomas, corresponding patterns of aberrations in adenomas are less well documented. The aim of this study was to profile chromosomal aberrations across colorectal adenomas and carcinomas to provide a better insight into key changes during tumor initiation and progression. Single nucleotide polymorphism array analysis was performed on 216 colorectal tumor/normal matched pairs, comprising 60 adenomas and 156 carcinomas. While many chromosomal aberrations were specific to carcinomas, those with the highest frequency in carcinomas (amplification of chromosome 7, 13q, and 20q; deletion of 17p and chromosome 18; LOH of 1p, chromosome 4, 5q, 8p, 17p, chromosome 18, and 20p) were also identified in adenomas. Hierarchical clustering using chromosomal aberrations revealed three distinct subtypes. Interestingly, these subtypes were only partially dependent on tumor staging. A cluster of colorectal cancer patients with frequent chromosomal deletions had the least favorable prognosis, and a number of adenomas (n = 9) were also present in the cluster suggesting that, at least in some tumors, the chromosomal aberration pattern is determined at a very early stage of tumor formation. Finally, analysis of LOH events revealed that copy-neutral/gain LOH (CN/G-LOH) is frequent (>10%) in carcinomas at 5q, 11q, 15q, 17p, chromosome 18, 20p, and 22q. Deletion of the corresponding region is sometimes present in adenomas, suggesting that LOH at these loci may play an important role in tumor initiation.

  4. Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas.

    PubMed

    Ieda, S; Watatani, M; Yoshida, T; Kuroda, K; Inui, H; Yasutomi, M

    1996-01-01

    To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.

  5. URINARY MUTAGENICITY AS A BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS AND RISK FOR COLORECTAL ADENOMA

    EPA Science Inventory

    Urinary Mutagenicity as a Biomarker of Cooked-Meat-Associated Mutagens and Risk for Colorectal Adenoma

    In a controlled feeding study involving 60 subjects, we have investigated urinary mutagenicity as a biomarker of exposure to cooked-meat-associated mutagens. In a separa...

  6. Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma.

    PubMed

    Sekine, Shigeki; Yamashita, Satoshi; Tanabe, Taro; Hashimoto, Taiki; Yoshida, Hiroshi; Taniguchi, Hirokazu; Kojima, Motohiro; Shinmura, Kazuya; Saito, Yutaka; Hiraoka, Nobuyoshi; Ushijima, Toshikazu; Ochiai, Atsushi

    2016-06-01

    The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Colorectal cancer risk following adenoma removal: a large prospective population-based cohort study

    PubMed Central

    Coleman, Helen G.; Loughrey, Maurice B.; Murray, Liam J.; Johnston, Brian T.; Gavin, Anna T.; Shrubsole, Martha J.; Bhat, Shivaram K.; Allen, Patrick B.; McConnell, Vivienne; Cantwell, Marie M.

    2015-01-01

    Background Randomised controlled trials have demonstrated significant reductions in colorectal cancer (CRC) incidence and mortality associated with polypectomy. However, little is known about whether polypectomy is effective at reducing CRC risk in routine clinical practice. The aim of this investigation was to quantify CRC risk following polypectomy in a large prospective population-based cohort study. Methods Patients with incident colorectal polyps between 2000 and 2005 in Northern Ireland (NI) were identified via electronic pathology reports received to the NI Cancer Registry (NICR). Patients were matched to the NICR to detect CRC and deaths up to 31st December 2010. CRC standardised incidence ratios (SIRs) were calculated and Cox proportional hazards modelling applied to determine CRC risk. Results During 44,724 person-years of follow-up, 193 CRC cases were diagnosed amongst 6,972 adenoma patients, representing an annual progression rate of 0.43%. CRC risk was significantly elevated in patients who had an adenoma removed (SIR 2.85; 95% CI: 2.61 to 3.25) compared with the general population. Male sex, older age, rectal site and villous architecture were associated with an increased CRC risk in adenoma patients. Further analysis suggested that not having a full colonoscopy performed at, or following, incident polypectomy contributed to the excess CRC risk. Conclusions CRC risk was elevated in individuals following polypectomy for adenoma, outside of screening programmes. Impact This finding emphasises the need for full colonoscopy and adenoma clearance, and appropriate surveillance, after endoscopic diagnosis of adenoma. PMID:26082403

  8. Frequent PTPRK-RSPO3 fusions and RNF43 mutations in colorectal traditional serrated adenoma.

    PubMed

    Sekine, Shigeki; Yamashita, Satoshi; Tanabe, Taro; Hashimoto, Taiki; Yoshida, Hiroshi; Taniguchi, Hirokazu; Kojima, Motohiro; Shinmura, Kazuya; Saito, Yutaka; Hiraoka, Nobuyoshi; Ushijima, Toshikazu; Ochiai, Atsushi

    2016-06-01

    The molecular mechanisms underlying the serrated pathway of colorectal tumourigenesis, particularly those related to traditional serrated adenomas (TSAs), are still poorly understood. In this study, we analysed genetic alterations in 188 colorectal polyps, including hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), TSAs, tubular adenomas, and tubulovillous adenomas by using targeted next-generation sequencing and reverse transcription-PCR. Our analyses showed that most TSAs (71%) contained genetic alterations in WNT pathway components. In particular, PTPRK-RSPO3 fusions (31%) and RNF43 mutations (24%) were frequently and almost exclusively observed in TSAs. Consistent with the WNT pathway activation, immunohistochemical analysis showed diffuse and focal nuclear accumulation of β-catenin in 53% and 30% of TSAs, respectively. APC mutations were observed in tubular and tubulovillous adenomas and in a subset of TSAs. BRAF mutations were exclusively and frequently encountered in serrated lesions. KRAS mutations were observed in all types of polyps, but were most commonly encountered in tubulovillous adenomas and TSAs. This study has demonstrated that TSAs frequently harbour genetic alterations that lead to WNT pathway activation, in addition to BRAF and KRAS mutations. In particular, PTPRK-RSPO3 fusions and RNF43 mutations were found to be characteristic genetic features of TSAs. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26924569

  9. Coffee prevents proximal colorectal adenomas in Japanese men: a prospective cohort study.

    PubMed

    Nakamura, Tomiyo; Ishikawa, Hideki; Mutoh, Michihiro; Wakabayashi, Keiji; Kawano, Atsuko; Sakai, Toshiyuki; Matsuura, Nariaki

    2016-09-01

    This prospective cohort study aimed to show that coffee prevents the recurrence of colorectal tumors (adenomas, precursors of colorectal cancer, and early-stage colorectal cancers) as well as colorectal cancer. The present study included 307 patients who participated in a clinical study that required endoscopy to remove a colorectal tumor. The amount of coffee consumed by the patients at study inclusion and the frequency of colorectal tumors, as detected by colonoscopy over the subsequent 4 years, were assessed. Coffee consumption was determined using a diet survey that included 3-consecutive-day food records. The risk of colorectal tumor recurrence was significantly lower (odds ratio=0.21; 95% confidence interval, 0.06-0.74) in patients who consumed more than three cups of coffee per day compared with those who consumed no coffee. No correlation was observed between the examined factors, including green tea and black tea intake and the amount of caffeine consumed. In subanalysis divided by the tumor location within the colorectum, the odds ratio of colorectal tumor recurrence in the proximal colon showed a tendency toward reduction as coffee consumption increased; however, increased coffee consumption significantly increased colorectal tumor recurrence in the distal colon. We showed that high coffee consumption reduced the overall occurrence of colorectal tumors, affected by the reduction in the proximal colon. PMID:26291025

  10. Prevalence of serrated polyposis syndrome and its association with synchronous advanced adenoma and lifestyle.

    PubMed

    Toyoshima, Naoya; Sakamoto, Taku; Makazu, Makomo; Nakajima, Takeshi; Matsuda, Takahisa; Kushima, Ryoji; Shimoda, Tadakazu; Fujii, Takahiro; Inoue, Haruhiro; Kudo, Shin-Ei; Saito, Yutaka

    2015-01-01

    We assessed the clinicopathological characteristics of patients with serrated polyposis syndrome (SPS) and the incidence of advanced adenoma/colorectal cancer (CRC). We prospectively enrolled 249 consecutive patients who underwent colonoscopy at the National Cancer Center Hospital over a 6-month period. All the polyps were diagnosed using magnification colonoscopy and resection/biopsy. The enrolled patients were divided into two groups, i) those with ≥5 histologically diagnosed hyperplastic polyps (HPs) proximal to the sigmoid colon, with at least 2 polyps >10 mm in diameter and ii) those with ≥20 HPs distributed throughout the colon. The clinical characteristics of the two groups were compared, including lifestyle, family history of CRC and colonoscopic findings. HPs were identified in 228 patients, of whom 21 (8.4%) had SPS. All 21 patients had ≥20 HPs distributed throughout the colon, with none having >2 HPs ≥1 cm in diameter in the right colon. Synchronous advanced adenoma/CRC was diagnosed in 76/249 (30.5%) patients. The prevalence of advanced adenoma/CRC was higher among patients with compared to those without SPS (P=0.075). SPS was also associated with older age and higher body mass index (BMI). Our results suggested that older age and higher BMI are independent risk factors for SPS. Advanced adenoma/CRC tended to occur more frequently among patients with compared to those without SPS, although the difference was not statistically significant.

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

    PubMed

    Kunzmann, Andrew T; Coleman, Helen G; Huang, Wen-Yi; Cantwell, Marie M; Kitahara, Cari M; Berndt, Sonja I

    2016-04-15

    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.

  12. Genetic variability in EGFR, Src and HER2 and risk of colorectal adenoma and cancer

    PubMed Central

    Poole, Elizabeth M; Curtin, Karen; Hsu, Li; Kulmacz, Richard J; Duggan, David J; Makar, Karen W; Xiao, Liren; Carlson, Christopher S; Slattery, Martha L; Caan, Bette J; Potter, John D; Ulrich, Cornelia M

    2011-01-01

    The EGFR signaling pathway is involved in carcinogenesis at multiple sites, particularly colorectal cancer, and is a target of colorectal cancer chemotherapy. EGFR signaling is linked to pro-carcinogenic mechanisms, including cell proliferation, survival, angiogenesis, and more recently prostaglandin synthesis. Genetic variability in this pathway has not yet been studied in relation to colorectal carcinogenesis. In three case-control studies of colorectal adenoma (n=485 cases/578 controls), colon cancer (n=1424 cases/1780 controls) and rectal cancer (n=583 cases/775 controls), we investigated associations between candidate SNPs, tagSNPs and haplotypes in EGFR signaling (EGFR, Src, and HER2) and risk. We also examined associations with tumor subtypes: TP53 and KRAS2 mutations, CpG island methylator phenotype, and microsatellite instability. All three studies were genotyped using an identical Illumina GoldenGate assay, allowing thorough investigation of genetic variability across stages and locations of colorectal neoplasia. The EGFR tagSNP 142572T>C (rs3752651) CC genotype was associated with a suggested increased risk for both colon (OR: 1.40; 95% CI: 1.00-1.96; p-trend=0.04) and rectal cancer (OR: 1.39; 95% CI: 0.81-2.41; p-trend=0.65). In tumor subtype analyses, the association was limited to TP53-mutated colon tumors. Using the Chatterjee 1 df Tukey test to assess gene-gene interactions, we observed a statistically significant (p<0.01) interaction between SNPs in EGFR and Src for colorectal adenoma risk. The association with EGFR 142572 should be investigated in additional studies and the significant gene-gene interaction between EGFR and Src in relation to adenoma risk suggests that these two genes are jointly affecting early stages in colorectal carcinogenesis and requires further follow-up. PMID:22199994

  13. Dysbiosis of Fungal Microbiota in the Intestinal Mucosa of Patients with Colorectal Adenomas

    PubMed Central

    Luan, Chunguang; Xie, Lingling; Yang, Xi; Miao, Huifang; Lv, Na; Zhang, Ruifen; Xiao, Xue; Hu, Yongfei; Liu, Yulan; Wu, Na; Zhu, Yuanmin; Zhu, Baoli

    2015-01-01

    The fungal microbiota is an important component of the human gut microbiome and may be linked to gastrointestinal disease. In this study, the fungal microbiota of biopsy samples from adenomas and adjacent tissues was characterized by deep sequencing. Ascomycota, Glomeromycota and Basidiomycota were identified as the dominant phyla in both adenomas and adjacent tissues from all subjects. Among the 60 genera identified, the opportunist pathogens Phoma and Candida represented an average of 45% of the fungal microbiota. When analyzed at the operational taxonomic unit (OTU) level, however, a decreased diversity in adenomas was observed, and three OTUs differed significantly from the adjacent tissues. Principal Component Analysis (PCA) revealed that the core OTUs formed separate clusters for advanced and non-advanced adenomas for which the abundance of four OTUs differed significantly. Moreover, the size of adenomas and the disease stage were closely related to changes in the fungal microbiota in subjects with adenomas. This study characterized the fungal microbiota profile of subjects with adenomas and identified potential diagnostic biomarkers closely related to different stages of adenomas. PMID:25613490

  14. Exome capture sequencing of adenoma reveals genetic alterations in multiple cellular pathways at the early stage of colorectal tumorigenesis.

    PubMed

    Zhou, Donger; Yang, Liu; Zheng, Liangtao; Ge, Weiting; Li, Dan; Zhang, Yong; Hu, Xueda; Gao, Zhibo; Xu, Jinghong; Huang, Yanqin; Hu, Hanguang; Zhang, Hang; Zhang, Hao; Liu, Mingming; Yang, Huanming; Zheng, Lei; Zheng, Shu

    2013-01-01

    Most of colorectal adenocarcinomas are believed to arise from adenomas, which are premalignant lesions. Sequencing the whole exome of the adenoma will help identifying molecular biomarkers that can predict the occurrence of adenocarcinoma more precisely and help understanding the molecular pathways underlying the initial stage of colorectal tumorigenesis. We performed the exome capture sequencing of the normal mucosa, adenoma and adenocarcinoma tissues from the same patient and sequenced the identified mutations in additional 73 adenomas and 288 adenocarcinomas. Somatic single nucleotide variations (SNVs) were identified in both the adenoma and adenocarcinoma by comparing with the normal control from the same patient. We identified 12 nonsynonymous somatic SNVs in the adenoma and 42 nonsynonymous somatic SNVs in the adenocarcinoma. Most of these mutations including OR6X1, SLC15A3, KRTHB4, RBFOX1, LAMA3, CDH20, BIRC6, NMBR, GLCCI1, EFR3A, and FTHL17 were newly reported in colorectal adenomas. Functional annotation of these mutated genes showed that multiple cellular pathways including Wnt, cell adhesion and ubiquitin mediated proteolysis pathways were altered genetically in the adenoma and that the genetic alterations in the same pathways persist in the adenocarcinoma. CDH20 and LAMA3 were mutated in the adenoma while NRXN3 and COL4A6 were mutated in the adenocarcinoma from the same patient, suggesting for the first time that genetic alterations in the cell adhesion pathway occur as early as in the adenoma. Thus, the comparison of genomic mutations between adenoma and adenocarcinoma provides us a new insight into the molecular events governing the early step of colorectal tumorigenesis. PMID:23301059

  15. Genetic ancestry is associated with colorectal adenomas and adenocarcinomas in Latino populations.

    PubMed

    Hernandez-Suarez, Gustavo; Sanabria, Maria Carolina; Serrano, Marta; Herran, Oscar F; Perez, Jesus; Plata, Jose L; Zabaleta, Jovanny; Tenesa, Albert

    2014-10-01

    Colorectal cancer rates in Latin American countries are less than half of those observed in the United States. Latin Americans are the resultant of generations of an admixture of Native American, European, and African individuals. The potential role of genetic admixture in colorectal carcinogenesis has not been examined. We evaluate the association of genetic ancestry with colorectal neoplasms in 190 adenocarcinomas, 113 sporadic adenomas and 243 age- and sex-matched controls enrolled in a multicentric case-control study in Colombia. Individual ancestral genetic fractions were estimated using the STRUCTURE software, based on allele frequencies and assuming three distinct population origins. We used the Illumina Cancer Panel to genotype 1,421 sparse single-nucleotide polymorphisms (SNPs), and Northern and Western European ancestry, LWJ and Han Chinese in Beijing, China populations from the HapMap project as references. A total of 678 autosomal SNPs overlapped with the HapMap data set SNPs and were used for ancestry estimations. African mean ancestry fraction was higher in adenomas (0.13, 95% confidence interval (95% CI)=0.11-0.15) and cancer cases (0.14, 95% CI=0.12-0.16) compared with controls (0.11, 95% CI=0.10-0.12). Conditional logistic regression analysis, controlling for known risk factors, showed a positive association of African ancestry per 10% increase with both colorectal adenoma (odds ratio (OR)=1.12, 95% CI=0.97-1.30) and adenocarcinoma (OR=1.19, 95% CI=1.05-1.35). In conclusion, increased African ancestry (or variants linked to it) contributes to the increased susceptibility of colorectal cancer in admixed Latin American population. PMID:24518838

  16. Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.

    PubMed

    Bezawada, Navya; Song, Mingyang; Wu, Kana; Mehta, Raaj S; Milne, Ginger L; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Chan, Andrew T

    2014-07-01

    Prostaglandin E2 (PGE2) promotes colorectal carcinogenesis. Overall, systemic PGE2 production can be assessed by measuring its major metabolite, PGE-M, in urine. We examined the potential role of PGE-M as a biomarker for colorectal adenoma risk and chemopreventive response to anti-inflammatory drugs. We conducted a prospective case-control study nested within the Nurses' Health Study. Among women who previously provided a urine sample, we identified 420 cases diagnosed with colorectal adenoma during follow-up and matched them to 420 endoscopy-negative controls. We measured urinary PGE-M using an LC/MS assay. Compared with women in the lowest quartile of urinary PGE-M, women in the highest quartile had a multivariate OR of 1.40 (95% confidence interval (CI), 0.92-2.14) for any adenoma; 0.91 (95% CI, 0.48-1.72) for low-risk adenoma (solitary adenoma <1 cm in greatest diameter with tubular/unspecified histology); and 1.66 (95% CI, 1.04-2.67) for high-risk adenoma (adenoma ≥1 cm in greatest diameter and/or tubulovillous, villous or high-grade dysplasia histology or multiple adenomas of any size or histology). Regular use of anti-inflammatory drugs (≥2 standard tablets of aspirin/NSAIDs per week) was associated with a significant reduction in adenoma risk (multivariate OR, 0.61; 95% CI, 0.43-0.87) in women with high baseline PGE-M (quartiles 2-4), but not low PGE-M (quartile 1).Urinary PGE-M is associated with an increased risk of high-risk adenoma. Anti-inflammatory drugs seem to reduce adenoma risk among women with high, but not low PGE-M. Urinary PGE-M may serve as a biomarker to define subsets of the population who may obtain differential chemopreventive benefit from anti-inflammatory drugs. PMID:24824037

  17. Paleolithic and Mediterranean diet pattern scores and risk of incident, sporadic colorectal adenomas.

    PubMed

    Whalen, Kristine A; McCullough, Marji; Flanders, W Dana; Hartman, Terryl J; Judd, Suzanne; Bostick, Roberd M

    2014-12-01

    The Western dietary pattern is associated with higher risk of colorectal neoplasms. Evolutionary discordance could explain this association. We investigated associations of scores for 2 proposed diet patterns, the "Paleolithic" and the Mediterranean, with incident, sporadic colorectal adenomas in a case-control study of colorectal polyps conducted in Minnesota (1991-1994). Persons with no prior history of colorectal neoplasms completed comprehensive questionnaires prior to elective, outpatient endoscopy; of these individuals, 564 were identified as cases and 1,202 as endoscopy-negative controls. An additional group of community controls frequency-matched on age and sex (n = 535) was also recruited. Both diet scores were calculated for each participant and categorized into quintiles, and associations were estimated using unconditional logistic regression. The multivariable-adjusted odds ratios comparing persons in the highest quintiles of the Paleolithic and Mediterranean diet scores relative to the lowest quintiles were, respectively, 0.71 (95% confidence interval (CI): 0.50, 1.02; Ptrend = 0.02) and 0.74 (95% CI: 0.54, 1.03; Ptrend = 0.05) when comparing cases with endoscopy-negative controls and 0.84 (95% CI: 0.56, 1.26; Ptrend = 0.14) and 0.77 (95% CI: 0.53, 1.11; Ptrend = 0.13) when comparing cases with community controls. These findings suggest that greater adherence to the Paleolithic diet pattern and greater adherence to the Mediterranean diet pattern may be similarly associated with lower risk of incident, sporadic colorectal adenomas. PMID:25326623

  18. Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence.

    PubMed

    Hubner, Richard A; Muir, Kenneth R; Liu, Jo-Fen; Logan, Richard F A; Grainge, Matthew J; Houlston, Richard S

    2008-08-01

    Vitamin D receptor (VDR) activation inhibits proliferation and angiogenesis in the colorectal epithelium, and inhibits metastasis of colorectal tumors. Polymorphisms in the VDR gene alter receptor cellular levels and functioning, and may confer altered susceptibility to colorectal neoplasia. We aimed to investigate the influence of VDR polymorphisms and dietary factors impacting on vitamin D metabolism on colorectal adenoma (CRA) recurrence. Data on dietary intakes of calcium, vitamin D and dairy products were collected from 853 participants in the United Kingdom Colorectal Adenoma Prevention trial, a randomized trial of aspirin and folate for CRA recurrence prevention. The VDR Cdx2, FokI, BsmI, ApaI and TaqI polymorphisms were genotyped in 546 participants with available DNA, and gene-diet interaction analyses performed in 480. Dairy product intake was inversely related to CRA recurrence risk independent of calcium and vitamin D [relative risk (RR) = 0.64; 95% confidence intervals (CIs): 0.47-0.88, for subjects in the highest compared to lowest intake tertile, p(trend) = 0.005]. Milk accounted for 60% of dairy product intake, and on analysis of milk and nonmilk dairy products separately recurrence risk in individuals in the highest tertile of milk intake was half that of lowest tertile individuals (RR = 0.52; 95% CI: 0.38-0.72, p(trend) = 3.2 x 10(-5)), whereas nonmilk dairy products did not influence recurrence. VDR polymorphism genotypes and haplotypes did not directly alter recurrence risk, but the reduction in risk associated with high dairy product intake was confined to individuals with ApaI aA/AA genotype (p(interaction) = 0.02). These findings indicate dairy products, and in particular milk, have chemopreventive activity against CRA recurrence. PMID:18470879

  19. Human Neutrophil Peptides 1-3 – Early Markers in Development of Colorectal Adenomas and Carcinomas

    PubMed Central

    Mothes, Henning; Melle, Christian; Ernst, Günther; Kaufmann, Roland; von Eggeling, Ferdinand; Settmacher, Utz

    2008-01-01

    Expression of Human Neutrophil Peptides (HNP) 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin-expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment. To further specify the role of α-defensins in tumourigenesis and progression, HNP1–3 were analyzed in colorectal adenomas and carcinomas of 87 patients and quantified in relation to cancer stage and grading. Using the ProteinChip arrays, HNP1–3 were found upregulated in both colorectal adenomas and carcinomas. By combining the array with Laser capture microscopy we were able to confirm that HNP1–3 are expressed by tumour cells but not by neutrophils or other tumour invading cells. These findings suggest that α-defensins are more likely to contribute to tumour growth than they are to mount an effective host anti-tumour response. However, the amount of HNP-expression was not found to be related to tumour stage, grading, and serological tumour markers. PMID:18957723

  20. Endoscopic mucosal resection of colorectal adenomas > 20 mm: Risk factors for recurrence

    PubMed Central

    Briedigkeit, Alexander; Sultanie, Omar; Sido, Bernd; Dumoulin, Franz Ludwig

    2016-01-01

    AIM: To evaluate risk factors for local recurrence after endoscopic mucosal resection of colorectal adenomas > 20 mm. METHODS: Retrospective data analysis of 216 endoscopic mucosal resections for colorectal adenomas > 20 mm in 179 patients (40.3% female; median age 68 years; range 35-91 years). All patients had at least 1 follow-up endoscopy with a minimum control interval of 2 mo (mean follow-up 6 mo/2.0-43.4 mo). Possible factors associated with local recurrence were analyzed by univariate and multivariate analysis. RESULTS: Median size of the lesions was 30 mm (20-70 mm), 69.0% were localized in the right-sided (cecum, ascending and transverse) colon. Most of the lesions (85.6%) showed a non-pedunculated morphology and the majority of resections was in piecemeal technique (78.7%). Histology showed carcinoma or high-grade intraepithelial neoplasia in 51/216 (23.6%) lesions including 4 low risk carcinomas (pT1a, L0, V0, R0 - G1/G2). Histologically proven recurrence was observed in 33/216 patients (15.3%). Patient age > 65 years, polyp size > 30 mm, non-pedunculated morphology, localization in the right-sided colon, piecemeal resection and tubular-villous histology were found as associated factors in univariate analysis. On multivariate analysis, only localization in the right-sided colon (HR = 6.842/95%CI: 1.540-30.394; P = 0.011), tubular-villous histology (HR = 3.713/95%CI: 1.617-8.528; P = 0.002) and polyp size > 30 mm (HR = 2.563/95%CI: 1.179-5.570; P = 0.017) were significantly associated risk factors for adenoma recurrence. CONCLUSION: Meticulous endoscopic follow-up is warranted after endoscopic mucosal resection of adenomas localized in the right-sided colon larger than > 30 mm, with tubular-villous histology. PMID:26981180

  1. Increased mRNA expression levels of ERCC1, OGG1 and RAI in colorectal adenomas and carcinomas

    PubMed Central

    Sæbø, Mona; Skjelbred, Camilla Furu; Nexø, Bjørn Andersen; Wallin, Håkan; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H

    2006-01-01

    Background The majority of colorectal cancer (CRC) cases develop through the adenoma-carcinoma pathway. If an increase in DNA repair expression is detected in both early adenomas and carcinomas it may indicate that low repair capacity in the normal mucosa is a risk factor for adenoma formation. Methods We have examined mRNA expression of two DNA repair genes, ERCC1 and OGG1 as well as the putative apoptosis controlling gene RAI, in normal tissues and lesions from 36 cases with adenomas (mild/moderat n = 21 and severe n = 15, dysplasia) and 9 with carcinomas. Results Comparing expression levels of ERCC1, OGG1 and RAI between normal tissue and all lesions combined yielded higher expression levels in lesions, 3.3-fold higher (P = 0.005), 5.6-fold higher(P < 3·10-5) and 7.7-fold higher (P = 0.0005), respectively. The levels of ERCC1, OGG1 and RAI expressions when comparing lesions, did not differ between adenomas and CRC cases, P = 0.836, P = 0.341 and P = 0.909, respectively. When comparing expression levels in normal tissue, the levels for OGG1 and RAI from CRC cases were significantly lower compared to the cases with adenomas, P = 0.012 and P = 0.011, respectively. Conclusion Our results suggest that increased expression of defense genes is an early event in the progression of colorectal adenomas to carcinomas. PMID:16914027

  2. Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma.

    PubMed

    Melle, Christian; Ernst, Günther; Schimmel, Bettina; Bleul, Annett; Mothes, Henning; Kaufmann, Roland; Settmacher, Utz; Von Eggeling, Ferdinand

    2006-01-01

    The aim of the study was to detect proteomic markers usable to distinguish colorectal carcinoma from colon adenoma for a better understanding of the molecular mechanisms in the process of tumourigenesis. Therefore, we microdissected colon carcinoma tissue, epithelial colon adenoma tissue as well as normal adjacent colon epithelium and determined protein profiles by SELDI-TOF MS. A multitude of significantly different signals was detected. For their identification colon biopsis were lysed and subjected to a two-dimensional gel electrophoresis for separation. Subsequently, we identified nearly 100 proteins by tryptic digestion, peptide fingerprint mapping and database search. Calgizzarin (S100A11; S100C) identified by peptide fingerprint mapping correlated very well with a significantly differentially expressed signal found in prior protein profiling. Using an immunodepletion assay we confirmed the identity of this signal as calgizzarin. To localise calgizzarin in tissues we performed immunohistochemistry. For further confirmation of the identity of calgizzarin we re-analysed IHC-positive as well as IHC-negative tissue sections on ProteinChip arrays. This work demonstrates that biomarkers in colorectal cancer can be detected, identified and assessed by a proteomic approach comprising tissue-microdissection, protein profiling and immunological techniques. PMID:16327996

  3. Targeting cyclooxygenase-2 with sodium butyrate and NSAIDs on colorectal adenoma/carcinoma cells

    PubMed Central

    Zhang, Zhi-Hong; Ouyang, Qin; Gan, Hua-Tian

    2004-01-01

    AIM: The protective effects of sodium butyrate and NSAIDs (especially the highly selective COX-2 inhibitors) have attracted considerable interest recently. In this study, primary adenoma cells and HT-29 were used to investigate whether the above drugs would be effective for reducing proliferation and inducing apoptosis. Additionally, it was investigated whether NSAIDs would strengthen the effects of sodium butyrate and its possible mechanisms. METHODS: In vitro primary cell culture of colorectal adenomas and HT-29 were used for this investigation. PGE2 isolated from HT-29 cell culture supernatants was investigated by ELISA. MTT was employed to detect the anti-proliferative effects on both adenoma and HT-29 culture cells. FCM was used for apoptosis rate and cell cycle analysis. The morphology of apoptotic cells was investigated by means of electromicroscopy. RESULTS: Sodium butyrate could stimulate the secretion of PGE2, while NSAIDs inhibited it to below 30 pg/106 cells. Both butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis. The effects were time- and dose-dependent (P < 0.05). Aspirin and NS-398 could enhance the effects of sodium butyrate. The effects were stronger while sodium butyrate was used in combination with NS-398 than it was used in combination with Aspirin. CONCLUSION: Butyrate and NSAIDs could inhibit cell proliferation and induce apoptosis respectively. NSAIDs could enhance the effects of sodium butyrate by down-regulating COX-2 expression. Selective COX-2 inhibitor is better than traditional NSAIDs. PMID:15378772

  4. Colorectal epithelial cell proliferative kinetics and risk factors for colon cancer in sporadic adenoma patients.

    PubMed

    Bostick, R M; Fosdick, L; Grandits, G A; Lillemoe, T J; Wood, J R; Grambsch, P; Louis, T A; Potter, J D

    1997-12-01

    Colorectal epithelial cell proliferative kinetics are altered in patients at increased risk for colon cancer: proliferation rates [labeling index (LI)] are higher and there is a shift of the proliferative zone from one confined to the lower 60% of the colonic crypt to one that includes the entire crypt (higher phi(h)). To assess factors associated with LI and phi(h), we performed a cross-sectional analysis using baseline rectal mucosal biopsies from sporadic adenoma patients participating in a chemoprevention trial. Biopsies (taken without preparatory cleansing) were taken 10 cm above the level of the anus, and proliferation was assessed by detection of endogenous S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. High-quality, scorable biopsies were obtained for 115 patients, and using analysis of covariance and multiple linear regression, the LI and phi(h) were evaluated in relation to diet and other lifestyle factors, demographics, anthropometrics, family history of colon cancer, and polyp history. Statistically significant findings included the following: (a) The LI for those in the upper versus the lowest tertile of vegetable and fruit consumption was, proportionately, 35% lower (3.4% versus 5.3%; P < 0.001); for vitamin supplement users versus nonusers, it was 36% lower (3.3 versus 5.2%; P < 0.001); for recurrent versus incident polyp patients, it was 36% higher (6.2 versus 4.0%; P < 0.001); and for those with rectal polyps only versus those with colon polyps only, it was 28% higher (6.0 versus 4.3%; P = 0.05); and (b) the phi(h) for those in the upper versus the lowest tertile of sucrose consumption was, proportionately, 48% higher (7.1% versus 3.7%; P = 0.01). These results indicate that (a) colorectal epithelial cell proliferation rates are higher in recurrent adenoma patients than in incident adenoma patients and in patients with rectal adenomas only versus those with colon adenomas only, but they are lower in patients

  5. KRAS gene mutations are more common in colorectal villous adenomas and in situ carcinomas than in carcinomas

    PubMed Central

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2013-01-01

    We have evaluated the frequency of KRAS gene mutations during the critical transition from villous adenoma to colorectal carcinoma to assess whether the adenomas contain a KRAS mutation more frequently than carcinomas. We analyzed sporadic villous and tubulovillous adenomas, in situ carcinomas, and primary colorectal carcinomas from multiple patients. The cancers were further evaluated for mucinous status and microsatellite instability. Standard PCR molecular techniques were used for KRAS and microsatellite analyses. A KRAS mutation was found in 61.9% of 134 adenomas, 67.8% of 84 in situ carcinomas, and just 31.6% of 171 carcinomas. Our study clearly demonstrates that tubulovillous and villous adenomas, as well as both the benign and malignant parts of in situ carcinomas, are statistically more likely to contain a somatic KRAS gene mutation than colorectal carcinomas. This difference is confined to the non-mucinous and the microsatellite stable tumors. Our data support the possibility that non-mucinous and microsatellite stable carcinomas with wild-type KRAS gene may have had a mutation in the KRAS gene during their earlier stages, with the mutation lost during further growth. PMID:23565319

  6. Management of Hepatocellular Adenoma: Recent Advances.

    PubMed

    Agrawal, Shefali; Agarwal, Sheela; Arnason, Thomas; Saini, Sanjay; Belghiti, Jacques

    2015-07-01

    Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended.

  7. Management of Hepatocellular Adenoma: Recent Advances.

    PubMed

    Agrawal, Shefali; Agarwal, Sheela; Arnason, Thomas; Saini, Sanjay; Belghiti, Jacques

    2015-07-01

    Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended. PMID:24909909

  8. Immunohistochemical Expression of PCNA and CD34 in Colorectal Adenomas and Carcinomas Using Specified Automated Cellular Image Analysis System: A Clinicopathologic Study

    PubMed Central

    Qasim, Ban J.; Ali, Hussam H.; Hussein, Alaa G.

    2012-01-01

    Background/Aim: To evaluate the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) and CD34 in colorectal adenomas and carcinomas, and to correlate this expression with different clinicopathologic parameters. Materials and Methods: The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas, and a control group of 20 samples of nontumerous colonic tissue, were included in the study. From each block, 3 sections of 5 ΅m thickness were taken, 1 section was stained with hematoxylin and eosin (H and E) and the other 2 sections were stained immunohistochemically for PCNA and CD34. Scoring of the immunohistochemical staining was performed using a specified automated cellular image analysis system (Digimizer). Results: PCNA expression was significantly increased in a sequence of normal mucosa–adenoma–carcinoma. It was significantly higher in adenomas ≥ 1 cm and those with severe dysplasia, and it showed a significant positive correlation with grade and lymph node involvement in colorectal carcinoma. CD34 showed significantly higher expression in carcinoma than adenoma and in adenoma than in the control group. CD34 expression showed a significant correlation with adenomas carrying severe dysplasia and large-sized adenomas (≥1cm). It was significantly correlated with tumor grade, lymphovascular invasion, and lymph node involvement in colorectal carcinoma. Conclusion: PCNA plays an important role in colorectal neoplastic progression and can be utilized as ancillary marker for the risk of malignant transformation in colorectal adenomas as it correlates with high grade dysplasia and size. Intratumoral quantification of the mean (A and N) of CD34 in colorectal carcinoma reflects the grade of tumors and can predict lymph node involvement and lymphovascular invasion, to make a useful additional prognostic

  9. Parathyroid Hormone is Related to Dysplasia and a Higher Rate of Distal Colorectal Adenoma in Women but Not Men.

    PubMed

    Aigner, Elmar; Stadlmayr, Andreas; Huber-Schönauer, Ursula; Zwerina, Jochen; Husar-Memmer, Emma; Niederseer, David; Eder, Sebastian K; Stickel, Felix; Pirich, Christian; Schett, Georg; Patsch, Wolfgang; Datz, Christian

    2015-08-01

    Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5%) of the distal colon compared to women below the cut-off (91/659; 13.8%; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study. PMID:26021763

  10. Parathyroid Hormone is Related to Dysplasia and a Higher Rate of Distal Colorectal Adenoma in Women but Not Men.

    PubMed

    Aigner, Elmar; Stadlmayr, Andreas; Huber-Schönauer, Ursula; Zwerina, Jochen; Husar-Memmer, Emma; Niederseer, David; Eder, Sebastian K; Stickel, Felix; Pirich, Christian; Schett, Georg; Patsch, Wolfgang; Datz, Christian

    2015-08-01

    Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5%) of the distal colon compared to women below the cut-off (91/659; 13.8%; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study.

  11. Many private mutations originate from the first few divisions of a human colorectal adenoma.

    PubMed

    Kang, Haeyoun; Salomon, Matthew P; Sottoriva, Andrea; Zhao, Junsong; Toy, Morgan; Press, Michael F; Curtis, Christina; Marjoram, Paul; Siegmund, Kimberly; Shibata, Darryl

    2015-11-01

    Intratumoural mutational heterogeneity (ITH) or the presence of different private mutations in different parts of the same tumour is commonly observed in human tumours. The mechanisms generating such ITH are uncertain. Here we find that ITH can be remarkably well structured by measuring point mutations, chromosome copy numbers, and DNA passenger methylation from opposite sides and individual glands of a 6 cm human colorectal adenoma. ITH was present between tumour sides and individual glands, but the private mutations were side-specific and subdivided the adenoma into two major subclones. Furthermore, ITH disappeared within individual glands because the glands were clonal populations composed of cells with identical mutant genotypes. Despite mutation clonality, the glands were relatively old, diverse populations when their individual cells were compared for passenger methylation and by FISH. These observations can be organized into an expanding star-like ancestral tree with co-clonal expansion, where many private mutations and multiple related clones arise during the first few divisions. As a consequence, most detectable mutational ITH in the final tumour originates from the first few divisions. Much of the early history of a tumour, especially the first few divisions, may be embedded within the detectable ITH of tumour genomes. PMID:26119426

  12. TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.

    PubMed

    Fessler, Evelyn; Drost, Jarno; van Hooff, Sander R; Linnekamp, Janneke F; Wang, Xin; Jansen, Marnix; De Sousa E Melo, Felipe; Prasetyanti, Pramudita R; IJspeert, Joep Eg; Franitza, Marek; Nürnberg, Peter; van Noesel, Carel Jm; Dekker, Evelien; Vermeulen, Louis; Clevers, Hans; Medema, Jan Paul

    2016-01-01

    The heterogeneous nature of colorectal cancer (CRC) complicates prognosis and is suggested to be a determining factor in the efficacy of adjuvant therapy for individual patients. Based on gene expression profiling, CRC is currently classified into four consensus molecular subtypes (CMSs), characterized by specific biological programs, thus suggesting the existence of unifying developmental drivers for each CMS Using human organoid cultures, we investigated the role of such developmental drivers at the premalignant stage of distinct CRC subtypes and found that TGFβ plays an important role in the development of the mesenchymal CMS4, which is of special interest due to its association with dismal prognosis. We show that in tubular adenomas (TAs), which progress to classical CRCs, the dominating response to TGFβ is death by apoptosis. By contrast, induction of a mesenchymal phenotype upon TGFβ treatment prevails in a genetically engineered organoid culture carrying a BRAF(V) (600E) mutation, constituting a model system for sessile serrated adenomas (SSAs). Our data indicate that TGFβ signaling is already active in SSA precursor lesions and that TGFβ is a critical cue for directing SSAs to the mesenchymal, poor-prognosis CMS4 of CRC.

  13. Advanced endoscopic technologies for colorectal cancer screening

    PubMed Central

    Obstein, Keith L; Valdastri, Pietro

    2013-01-01

    Colorectal cancer is the third most common cancer in men and the second most common cancer in women worldwide. Diagnosing colorectal has been increasingly successful due to advances in technology. Flexible endoscopy is considered to be an effective method for early diagnosis and treatment of gastrointestinal cancer, making it a popular choice for screening programs. However, millions of people who may benefit from endoscopic colorectal cancer screening fail to have the procedure performed. Main reasons include psychological barriers due to the indignity of the procedure, fear of procedure related pain, bowel preparation discomfort, and potential need for sedation. Therefore, an urgent need for new technologies addressing these issues clearly exists. In this review, we discuss a set of advanced endoscopic technologies for colorectal cancer screening that are either already available or close to clinical trial. In particular, we focus on visual-inspection-only advanced flexible colonoscopes, interventional colonoscopes with alternative propulsion mechanisms, wireless capsule colonoscopy, and technologies for intraprocedural bowel cleansing. Many of these devices have the potential to reduce exam related patient discomfort, obviate the need for sedation, increase diagnostic yield, reduce learning curves, improve access to screening, and possibly avert the need for a bowel preparation. PMID:23382621

  14. Differential roles of EPS8 in carcinogenesis: Loss of protein expression in a subset of colorectal carcinoma and adenoma

    PubMed Central

    Abdel-Rahman, Wael M; Ruosaari, Salla; Knuutila, Sakari; Peltomäki, Päivi

    2012-01-01

    AIM: To analyze the epidermal growth factor receptor pathway substrate 8 (EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required for proper maturation in intestinal cells. METHODS: We studied 8 colon cancer cell lines and 58 colorectal tumors (19 adenomas and 39 carcinomas). We performed expression microarray analysis of colon cancer cell lines followed by loss of heterozygosity (LOH) analysis and immunohistochemistry for EPS8 expression in colon tumors. Subsequently, we performed mutation analysis by direct sequencing and methylation analysis by bisulfite sequencing and methylation-specific polymerase chain reaction assays. RESULTS: Expression microarray analysis of colon cancer cell lines showed overexpression of EPS8 transcript in all lines but RKO. Genome wide loss of heterozygosity (LOH) analysis of colon tumors, showed considerable LOH at the EPS8 gene locus. Immunohistochemically, EPS8 was constitutively expressed in normal colonic mucosa with a dot-like supranuclear localization with accentuation at the luminal surface supporting its proposed role in epithelial maturation. Nineteen colon tumors (4 adenoma, 15 carcinoma) out of 51 (37%) showed strikingly tumor specific EPS8 protein loss. Of the remaining tumors, 5/51 (2 adenoma, and 3 carcinoma, 10%) showed marked overexpression, while 27/51 tumors (53%) showed retained expression. Mutation analysis revealed a missense mutation (c.794C>T, p.R265C) in exon 8 in RKO. The EPS8 promoter was also methylated in RKO, but there was no significant methylation in other cell lines or carcinoma specimens. CONCLUSION: The loss of EPS8 expression in colorectal adenomas and carcinomas suggests that down regulation of this gene contributes to the development of a subset of colorectal cancers, a finding which could have applications in diagnosis and treatment. PMID:22876043

  15. A study of prostaglandin pathway genes and interactions with current nonsteroidal anti-inflammatory drug use in colorectal adenoma.

    PubMed

    Edwards, Todd L; Shrubsole, Martha J; Cai, Qiuyin; Li, Guoliang; Dai, Qi; Rex, Douglas K; Ulbright, Thomas M; Fu, Zhenming; Murff, Harvey J; Smalley, Walter; Ness, Reid; Zheng, Wei

    2012-06-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death and usually arises from colorectal polyps. Screening and removal of polyps reduce mortality from CRC. Colorectal polyps are known to aggregate in families; however the genetic determinants for risk of polyps are unknown. In addition, it has been shown that nonsteroidal anti-inflammatory drug (NSAID) use decreases the risk of CRC and the incidence and size of polyps. In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to evaluate selected genes from the prostaglandin (PG) metabolism and signaling pathways for association with risk of polyps and for interactions with NSAIDs. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian polyp cases and 3,285 Caucasian controls. We carried out multivariable logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. We detected association signals in the genes PGE receptor 3 (PTGER3) and 15-hydroxyprostaglandin dehydrogenase (HPGD), both strong biologic candidates for influence on polyp risk. We did not observe the previously reported effects and effect modification in PG-endoperoxide synthase 2 (PTGS2), PGE receptor 2 (PTGER2), or PGE receptor 4 (PTGER4), although we did observe a single nucleotide polymorphism in PTGER2 associated with risk of multiple adenomas. We also observed effect modification of the HPGD signal by NSAID exposure. PMID:22551900

  16. Association Between Consumption of Fruits and Vegetables and Risk of Colorectal Adenoma

    PubMed Central

    Ben, Qiwen; Zhong, Jie; Liu, Jun; Wang, Lifu; Sun, Yunwei; Yv, Lifen; Yuan, Yaozong

    2015-01-01

    Abstract There have been contradictory results about the association of fruits and vegetables intake with colorectal adenoma (CRA) risk, the precursor lesion of colorectal cancer. Herein, we have conducted a meta-analysis of the published observational studies to have a clear understanding about this association. Eligible studies up to November 30, 2014, were identified and retrieved by searching MEDLINE and EMBASE databases along with the manual review of the reference list of the retrieved studies. The quality of the included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale, and random-effects model was used to calculate summary relative risk (SRR) and corresponding 95% confidence interval (CI). A total of 22 studies involving 11,696 CRA subjects were part of this meta-analysis. The SRR for the highest versus the lowest intake of vegetables alone was 0.91 (95% CI: 0.80–1.02, Pheterogeneity = 0.025), whereas for vegetables and fruits combined, it was 0.82 (95% CI: 0.75–0.91, Pheterogeneity = 0.369), and for fruits alone, it was 0.79 (95% CI: 0.71–0.88, Pheterogeneity = 0.111). In addition, linear dose–response analysis also showed similar results, for example, for per 100 g/d increment of fruits, the SRR was 0.94 (95% CI: 0.92–0.97) and for vegetables it was 0.98 (95% CI: 0.96–1.01). Nonlinear association was only observed for vegetables (Pnonlinearity = 0.024), but not for fruits (Pnonlinearity = 0.583). Thus, this meta-analysis suggested that fruits consumption have a significant protective effect on CRA risk, but not vegetables. Moreover, we recommend additional studies with prospective designs that use validated questionnaires and control for important confounders to further validate the overall results. PMID:26496264

  17. Lifestyle and lifestyle-related comorbidities independently associated with colorectal adenoma recurrence in elderly Chinese people

    PubMed Central

    Saiken, Adake; Gu, Fang

    2016-01-01

    Objective The purpose of this study was to determine the lifestyle and lifestyle-related comorbidities independently associated with colorectal adenoma (CRA) recurrence in elderly Chinese people. Methods During the 5-year follow-up after the initial colonoscopy, participants aged >60 years with the diagnosis and removal of CRA underwent a complete surveillance colonoscopy, and 152 participants with CRA recurrence plus 152 participants free of recurrence were included in this analysis. Results Participants with CRA recurrence were more likely to consume less vegetables and fruits, and more red meats compared with the control group (P<0.05 for all). Lifestyle-related comorbidities, including hypertension and nonalcoholic fatty liver disease (NAFLD), were more common in participants with CRA recurrence than in the control group (P<0.05 for all). In the multivariate analysis, pack-years of smoking were independently associated with an increased CRA recurrence (odds ratio [OR]: 1.03; P<0.05). Eating less vegetables (OR: 099; P<0.05) and fruits (OR: 0.98; P<0.05) was identified as a statistically independent factor influencing CRA recurrence, as was eating more red meats (OR: 1.01; P<0.05). Hypertension was also found to be a factor independently associated with an increased CRA recurrence (OR: 2.44; P<0.05). NAFLD had an independent association, with an increased CRA recurrence (OR: 3.43; P<0.05). Conclusion Smoking cigarettes, high consumption of red meats, low intake of fruits and vegetables, and the presence of hypertension and NAFLD were independently associated with an increased CRA recurrence in elderly Chinese people. This conclusion helps elderly Chinese people to make effective behavioral changes, such as smoking cessation, substitution of fruits and vegetables for red meats, and timely treatment of hypertension and NAFLD, to reduce CRA recurrence and colorectal cancer risk. PMID:27382263

  18. Urinary metabolites of prostanoids and risk of recurrent colorectal adenomas in the Aspirin/Folate Polyp Prevention Study (AFPPS).

    PubMed

    Fedirko, Veronika; Bradshaw, Patrick T; Figueiredo, Jane C; Sandler, Robert S; Barry, Elizabeth L; Ahnen, Dennis J; Milne, Ginger L; Bresalier, Robert S; Baron, John A

    2015-11-01

    Aspirin has been shown to protect against colorectal neoplasms; however, the optimal chemopreventive dose and underlying mechanisms are unclear. We aimed to study the relationship between prostanoid metabolites and aspirin's effect on adenoma occurrence. We used data from the Aspirin/Folate Polyp Prevention Study, in which 1,121 participants with a recent adenoma were randomized to placebo or two doses of aspirin (81 or 325 mg/d) to be taken until the next surveillance colonoscopy, anticipated about 3 years later. Urinary metabolites of prostanoids (PGE-M, PGI-M, and dTxB2) were measured using liquid chromatography/mass spectrometry or GC/NICI-MS in 876 participants near the end of treatment follow-up. Poisson regression with a robust error variance was used to calculate relative risks and 95% confidence intervals. PGE-M, PGI-M, and dTxB2 levels were 28%, 37%, and 60% proportionately lower, respectively, in individuals who took 325 mg of aspirin compared with individuals who took placebo (all P < 0.001). Similarly, among individuals who took 81 mg of aspirin, PGE-M, PGI-M, and dTxB2 were, respectively, 18%, 30%, and 57% proportionally lower compared with placebo (all P < 0.005). None of the metabolites or their ratios were statistically significantly associated with the risk of adenoma occurrence. The effect of aspirin in reducing adenoma risk was independent of prostanoid levels. Aspirin use is associated with lower levels of urinary prostanoid metabolites. However, our findings do not support the hypothesis that these metabolites are associated with adenoma occurrence, suggesting that COX-dependent mechanisms may not completely explain the chemopreventive effect of aspirin on colorectal neoplasms. PMID:26304466

  19. Immunohistochemical Expression of Estrogen and Progesterone Receptors in Human Colorectal Adenoma and Carcinoma Using Specified Automated Cellular Image Analysis System: A Clinicopathological Study

    PubMed Central

    Qasim, Ban Jumaa; Ali, Hussam Hasson; Hussein, Alaa Ghani

    2011-01-01

    Objectives To evaluate the immunohistochemical expression of estrogen receptors (ER) and progesterone receptors (PR) in colorectal adenoma and adenocarcinoma and to correlate this immunohistochemical expression with different clinicopathological parameters. Methods The study was retrospectively designed. A total of 86 tissue samples, including 33 paraffin blocks from patients with colorectal adenomas, 33 paraffin blocks from patients with colorectal adenocarcinomas and a control group of 20 samples of non-tumorous colonic tissue, were included in the study. Results The frequency of expression of ER and PR showed a gradual increase from control through adenoma to carcinoma. The frequencies of expression of ER in the control, adenoma and carcinoma were (10%, 15.15% and 42.42% respectively, p<0.001), while the frequency of expression for PR were (10%, 24.24% and 36.36% respectively, p<0.001). Strong ER and PR staining was mainly seen in carcinoma cases (42.42%, 36.36%, respectively) in comparison with adenoma (9.09%, 15.15%, respectively) and control (0%, 0%, respectively). The three digital parameters of ER and PR immunohistochemical expression (Area [A], Number of objects [N], and intensity [I]) were significantly increased in a sequence of normal mucosa-adenoma-carcinoma. There was a significant positive correlation between ER and PR in adenoma (r=0.312, p=0.034) and carcinoma (r=0.321, p=0.0398). Conclusion ER and PR expression increased in a sequence of; normal colonic mucosa-adenoma-carcinoma, and a positive correlation was observed between ER and PR expression in colonic adenoma and carcinoma specimen indicating that ER and PR may play a role in colorectal carcinogenesis. PMID:22125723

  20. Advanced technology for the improvement of adenoma and polyp detection during colonoscopy.

    PubMed

    Moriyama, Tomohiko; Uraoka, Toshio; Esaki, Motohiro; Matsumoto, Takayuki

    2015-04-01

    Early detection and removal of adenomatous polyps reduces colorectal cancer death. However, many studies have reported that up to 20% of adenomas can be missed during colonoscopy. To improve visualization and reduce the blind spot of the colonic mucosa for an increase in the adenoma detection rate, many endoscopic techniques and technologies have been developed. The benefit of the high-definition endoscope for improving adenoma and polyp detection is marginal. Wide-angle colonoscope has failed to improve adenoma detection compared to standard colonoscopy. Although the cap-assisted colonoscope can reduce cecal intubation times, it does not seem to improve adenoma and polyp detection. The diagnostic accuracy of the colon capsule endoscope is low compared to the conventional colonoscope. Third Eye(®) retroscope(®) , which provides additional retrograde viewing, has revealed significant improvement in adenoma and polyp detection compared to standard colonoscopy. However, this device increases procedural times. Recently developed full-spectrum endoscopy colonoscope and extra-wide-angle-view colonoscope have demonstrated a significantly lower miss rate of polyps. However, clinical trials are mandatory to determine the efficacy of these novel technologies for cancer screening. In addition, education and training for these novel techniques and technologies should seriously be considered to improve adenoma and polyp detection. PMID:25556542

  1. MicroRNA-320 family is downregulated in colorectal adenoma and affects tumor proliferation by targeting CDK6

    PubMed Central

    Tadano, Toshihiro; Kakuta, Yoichi; Hamada, Shin; Shimodaira, Yosuke; Kuroha, Masatake; Kawakami, Yoko; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Masamune, Atsushi; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shimosegawa, Tooru

    2016-01-01

    AIM: To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. METHODS: Using microarray, the sequential changes in miRNA expression profiles were compared in colonic lesions from matched samples; histologically, non-neoplastic mucosa, adenoma, and submucosal invasive carcinoma were microdissected from a tissue sample. Cell proliferation assay was performed to observe the effect of miRNA, and its target genes were predicted using bioinformatics approaches and the expression profile of SW480 transfected with the miRNA mimics. mRNA and protein levels of the target gene in colon cancer cell lines with a mimic control or miRNA mimics were measured using qRT-PCR and Western blotting. The expression levels of miRNA and target gene in colorectal tissue samples were also measured. RESULTS: Microarray analysis identified that the miR-320 family, including miR-320a, miR-320b, miR-320c, miR-320d and miR-320e, were differentially expressed in adenoma and submucosal invasive carcinoma. The miR-320 family, which inhibits cell proliferation, is frequently downregulated in colorectal adenoma and submucosal invasive carcinoma tissues. Seven genes including CDK6 were identified to be common in the results of gene expression array and bioinformatics analyses performed to find the target gene of the miR-320 family. We confirmed that mRNA and protein levels of CDK6 were significantly suppressed in colon cancer cell lines with miR-320 family mimics. CDK6 expression was found to increase from non-neoplastic mucosa through adenoma to submucosal invasive carcinoma tissues and showed an inverse correlation with miR-320 family expression. CONCLUSION: MiR-320 family affects colorectal tumor proliferation by targeting CDK6, plays important role in its growth, and is considered to be a biomarker for its early detection. PMID:27559432

  2. Variation in Adenoma Detection Rate and the Lifetime Benefits and Cost of Colorectal Cancer Screening: A Microsimulation Model

    PubMed Central

    Meester, Reinier G.S.; Doubeni, Chyke A.; Lansdorp-Vogelaar, Iris; Jensen, Christopher D.; van der Meulen, Miriam P.; Levin, Theodore R.; Quinn, Virginia P.; Schottinger, Joanne E.; Zauber, Ann G.; Corley, Douglas A.; van Ballegooijen, Marjolein

    2015-01-01

    IMPORTANCE Colonoscopy is the most commonly used colorectal cancer screening test in the United States. Its quality, as measured by adenoma detection rates, varies widely between physicians with unknown consequences for the cost and benefits of screening programs. OBJECTIVE To estimate the lifetime benefits, complications and costs of a colonoscopy screening program at different levels of adenoma detection. DESIGN, SETTING and PARTICIPANTS This study used microsimulation modeling with data from a community-based healthcare system on adenoma detection rate variation and cancer risk among 136 physicians and 57,588 patients for 1998–2010. EXPOSURE Using modeling, no screening was compared to screening initiation with colonoscopy according to adenoma detection rate quintiles (averages 15.3, 21.3, 25.6, 30.9, and 38.7%) at ages 50, 60 and 70 with appropriate surveillance of adenoma patients. MAIN OUTCOMES Estimated lifetime colorectal cancer incidence, mortality, number of colonoscopies, complications and costs per 1,000 patients, all discounted at 3% per year and including 95% confidence intervals from multiway probabilistic sensitivity analysis (95%CI). RESULTS In simulation modeling, among unscreened patients, the lifetime risks of colorectal cancer incidence and mortality were 34.2 (95%CI:25.9–43.6) and 13.4 (95%CI:10.0–17.6) per 1,000, respectively. Among screened patients, simulated lifetime incidence decreased with lower to higher adenoma detection rates (quintile 1 versus 5: 26.6, 95%CI:20.0–34.3 versus 12.5, 95%CI:9.3–16.5) as did mortality (5.7, 95%CI:4.2–7.7 versus 2.3, 95%CI:1.7–3.1). Compared to quintile 1, simulated lifetime incidence and mortality were on average 11.4% (95%CI:10.3–11.9) and 12.8% (95%CI:11.1–13.7) lower, respectively, for every 5 percentage-point higher adenoma detection rate. Total colonoscopies and associated complications were higher from quintile 1 (2,777, 95%CI:2,626–2,943 and 6.0, 95%CI:4.0–8.5) to subsequent

  3. MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

    PubMed

    Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2016-10-01

    Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (P<0.001). Both MLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P<0.001). There was no significant difference in mucinous differentiation, tumor-infiltrating lymphocytes, Crohn-like reaction, and medullary differentiation between the 3 tumor groups. Using Kaplan-Meier survival functions, there was no significant difference in disease-specific survival between the 3 patient groups (P>0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas

  4. Research Advances in Pituitary Adenoma and DNA Methylation.

    PubMed

    Wei, Zhen-Qing; Li, Yang; Li, Wei-Hua; Lou, Jia-Cheng; Zhang, Bo

    2016-08-01

    DNA methylation is closely related to the genesis and development of pituitary adenoma. Studies have shown that high methylation in the promoter region of potassium voltage-gated chanel,shaker related subfamily,beta member 2,O-6-methylguanine-DNA methyltransferase,echinoderm microtubule associated protein like 2 ,ras homolog family member D ,homeobox B1 ,NNAT, and P16 inhibits the expression of these genes and regulates of the proliferation of pituitary adenoma. DNA methylation is also closely related to invasive pituitary adenoma. Therefore,further study on molecular mechanism of DNA methylation of pituitary adenoma will offer a new strategy for the diagnosis and treatment of pituitary adenoma. PMID:27594164

  5. Germline mutations in the proof-reading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas

    PubMed Central

    Palles, Claire; Cazier, Jean-Baptiste; Howarth, Kimberley M; Domingo, Enric; Jones, Angela M.; Broderick, Peter; Kemp, Zoe; Spain, Sarah L; Almeida, Estrella Guarino; Salguero, Israel; Sherborne, Amy; Chubb, Daniel; Carvajal-Carmona, Luis G; Ma, Yusanne; Kaur, Kulvinder; Dobbins, Sara; Barclay, Ella; Gorman, Maggie; Martin, Lynn; Kovac, Michal B; Humphray, Sean; Lucassen, Anneke; Holmes, Christopher; Bentley, David; Donnelly, Peter; Taylor, Jenny; Petridis, Christos; Roylance, Rebecca; Sawyer, Elinor J; Kerr, David J.; Clark, Susan; Grimes, Jonathan; Kearsey, Stephen E; Thomas, Huw JW; McVean, Gilean; Houlston, Richard S; Tomlinson, Ian

    2013-01-01

    Many individuals with multiple or large colorectal adenomas, or early-onset colorectal cancer (CRC), have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline variants in several multiple adenoma and/or CRC cases, but in no controls. The susceptibility variants appear to have high penetrance. POLD1 is also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proof-reading (exonuclease) domain of DNA polymerases ε and δ, and are predicted to impair correction of mispaired bases inserted during DNA replication. In agreement with this prediction, mutation carriers’ tumours were microsatellite-stable, but tended to acquire base substitution mutations, as confirmed by yeast functional assays. Further analysis of published data showed that the recently-described group of hypermutant, microsatellite-stable CRCs is likely to be caused by somatic POLE exonuclease domain mutations. PMID:23263490

  6. Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

    PubMed

    Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

    2010-01-01

    This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

  7. Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses.

    PubMed

    Kasai, Chika; Sugimoto, Kazushi; Moritani, Isao; Tanaka, Junichiro; Oya, Yumi; Inoue, Hidekazu; Tameda, Masahiko; Shiraki, Katsuya; Ito, Masaaki; Takei, Yoshiyuki; Takase, Kojiro

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next-generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species-level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma-in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile, Fusobacterium varium, Haemophilus parainfluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development.

  8. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  9. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  10. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    PubMed Central

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  11. [The colorectal adenoma-carcinoma sequence: the limits between polypectomy and intestinal resection].

    PubMed

    Giacomelli, L; Brescia, A; Pulcini, A; Finizio, R; Fabrizio, G; Granai, A V; Messinetti, S

    1993-01-01

    According to a clinic case, the authors pointed out the role of histological diagnosis in the therapeutic approach of large intestinal adenomas. In order to identify those lesions which can metastasize, having exceeded the muscularis mucosae and having invaded the submucosa, rigorous histological standards must be performed. Intestinal resection versus polypectomy is determined only according to the involvement or not of the muscularis mucosae.

  12. [Recent advance in chemotherapy for advanced colorectal cancer].

    PubMed

    Aiba, K

    1996-04-01

    Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in

  13. Role of dietary polyamines in a phase III clinical trial of difluoromethylornithine (DFMO) and sulindac for prevention of sporadic colorectal adenomas

    PubMed Central

    Raj, K P; Zell, J A; Rock, C L; McLaren, C E; Zoumas-Morse, C; Gerner, E W; Meyskens, F L

    2013-01-01

    Background: The polyamine-inhibitory regimen difluoromethylornithine (DFMO)+sulindac has marked efficacy in preventing metachronous colorectal adenomas. Polyamines are synthesised endogenously and obtained from dietary sources. Here we investigate dietary polyamine intake and outcomes in the DFMO+sulindac colorectal adenoma prevention trial. Methods: Dietary polyamine data were available for 188 of 267 patients completing the study. Total dietary polyamine content was derived by the sum of dietary putrescine, spermine and spermidine values and categorised into two groups: highest (>75–100%) vs the lower three quartiles (0–25, 25–50 and 50–75%). Baseline tissue polyamine concentration and ODC1 genotype were determined. Logistic regression models were used for risk estimation. Results: A significant interaction was detected between dietary polyamine group and treatment with regard to adenoma recurrence (P=0.012). Significant metachronous adenoma risk reduction was observed after DFMO+sulindac treatment in dietary polyamine quartiles 1–3 (risk ratio (RR) 0.19; 95% confidence interval (CI) 0.08–0.42; P<0.0001) but not in quartile 4 (RR 1.51; 95% CI 0.53–4.29; P=0.44). However, a lower number of events in the placebo group within dietary quartile 4 confound the aforementioned risk estimates. Conclusion: These preliminary findings reveal complex relationships between diet and therapeutic prevention, and they support further clinical trial-based investigations where the dietary intervention itself is controlled. PMID:23340449

  14. Derivation and validation of a prediction rule for estimating advanced colorectal neoplasm risk in average-risk Chinese.

    PubMed

    Cai, Quan-Cai; Yu, En-Da; Xiao, Yi; Bai, Wen-Yuan; Chen, Xing; He, Li-Ping; Yang, Yu-Xiu; Zhou, Ping-Hong; Jiang, Xue-Liang; Xu, Hui-Min; Fan, Hong; Ge, Zhi-Zheng; Lv, Nong-Hua; Huang, Zhi-Gang; Li, You-Ming; Ma, Shu-Ren; Chen, Jie; Li, Yan-Qing; Xu, Jian-Ming; Xiang, Ping; Yang, Li; Lin, Fu-Lin; Li, Zhao-Shen

    2012-03-15

    No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (≤3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese. PMID:22328705

  15. Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation.

    PubMed

    Alexander, Melannie; Burch, James B; Steck, Susan E; Chen, Chin-Fu; Hurley, Thomas G; Cavicchia, Philip; Ray, Meredith; Shivappa, Nitin; Guess, Jaclyn; Zhang, Hongmei; Youngstedt, Shawn D; Creek, Kim E; Lloyd, Stephen; Yang, Xiaoming; Hébert, James R

    2015-02-01

    Clock genes are expressed in a self-perpetuating, circadian pattern in virtually every tissue including the human gastrointestinal tract. They coordinate cellular processes critical for tumor development, including cell proliferation, DNA damage response and apoptosis. Circadian rhythm disturbances have been associated with an increased risk for colon cancer and other cancers. This mechanism has not been elucidated, yet may involve dysregulation of the 'period' (PER) clock genes, which have tumor suppressor properties. A variable number tandem repeat (VNTR) in the PERIOD3 (PER3) gene has been associated with sleep disorders, differences in diurnal hormone secretion, and increased premenopausal breast cancer risk. Susceptibility related to PER3 has not been examined in conjunction with adenomatous polyps. This exploratory case-control study was the first to test the hypothesis that the 5-repeat PER3 VNTR sequence is associated with increased odds of adenoma formation. Information on demographics, medical history, occupation and lifestyle was collected prior to colonoscopy. Cases (n=49) were individuals with at least one histopathologically confirmed adenoma. Controls (n=97) included patients with normal findings or hyperplastic polyps not requiring enhanced surveillance. Unconditional multiple logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), after adjusting for potential confounding. Adenomas were detected in 34% of participants. Cases were more likely to possess the 5-repeat PER3 genotype relative to controls (4/5 OR, 2.1; 95% CI, 0.9-4.8; 5/5 OR, 5.1; 95% CI, 1.4-18.1; 4/5+5/5 OR, 2.5; 95% CI, 1.7-5.4). Examination of the Oncomine microarray database indicated lower PERIOD gene expression in adenomas relative to adjacent normal tissue. Results suggest a need for follow-up in a larger sample.

  16. [New advances in hereditary colorectal cancer].

    PubMed

    Moreira, Leticia

    2015-09-01

    Colorectal cancer is the most frequent malignancy in both sexes in Spain. Between 20% and 25% of affected individuals have a family history of the disease, and 5% to 6% have a germ mutation, i.e. the disease develops in the context of a hereditary syndrome. The importance of identifying patients with hereditary syndromes predisposing them to colorectal cancer lies in the possibility of applying preventive measures, screening, and more appropriate management of both patients and their families. The present article outlines the most important studies presented at the congress of the American Gastroenterological Association.

  17. Red and processed meat intake and risk of colorectal adenomas: a meta-analysis of observational studies.

    PubMed

    Xu, Xiaodong; Yu, Enda; Gao, Xianhua; Song, Ning; Liu, Lianjie; Wei, Xubiao; Zhang, Wei; Fu, Chuangang

    2013-01-15

    Inconsistent results regarding the association between red and processed meat intake and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer (CRC), have been reported. To provide a quantitative assessment of this association, we summarized the evidence from observational studies. Relevant studies were identified in MEDLINE and EMBASE until December 31, 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using the Cochran's Q and I(2) statistics. A total of 21 studies (16 case-control studies and five cohort/nested case-control studies) were included in this meta-analysis. The SRRs of CRA were 1.36 (95% CI = 1.17-1.58) for every 100 g/day increase in red meat intake, and 1.24 (95% CI = 1.12-1.36) for the highest versus the lowest level of red meat intake. Nonlinear dose-response meta-analysis indicated that CRA risk increased approximately linearly with increasing intake of red meat up to ~ 90 g/day, where the curve reached its plateau. Subgrouped analyses revealed that the increased risk of CRA with intake of red meat was independent of geographic locations, design and confounders. The SRRs of CRA was 1.28 (95% CI = 1.03-1.60) for per 50 g/day increase in processed meat intake, and 1.17 (95% CI = 1.08-1.26) for the highest versus the lowest level of processed meat intake. Increased intake of red and processed meat is associated with significantly increased risk of CRA.

  18. Comprehensive DNA Methylation Analysis Reveals a Common Ten-Gene Methylation Signature in Colorectal Adenomas and Carcinomas

    PubMed Central

    Patai, Árpád V.; Valcz, Gábor; Hollósi, Péter; Kalmár, Alexandra; Péterfia, Bálint; Patai, Árpád; Wichmann, Barnabás; Spisák, Sándor; Barták, Barbara Kinga; Leiszter, Katalin; Tóth, Kinga; Sipos, Ferenc; Kovalszky, Ilona; Péter, Zoltán; Miheller, Pál; Tulassay, Zsolt; Molnár, Béla

    2015-01-01

    Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dysplasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochemistry. HT29 cells were treated with 5-aza-2’ deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carcinogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory. PMID:26291085

  19. Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

    PubMed Central

    Gelister, J S; Lewin, M R; Driver, H E; Savage, F; Mahmoud, M; Gaffney, P J; Boulos, P B

    1987-01-01

    An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas. PMID:3115868

  20. Advances in endoscopic ultrasound imaging of colorectal diseases.

    PubMed

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS-guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations. PMID:26855535

  1. Prevalence and features of colorectal lesions among Hispanics: A hospital-based study

    PubMed Central

    Ashktorab, Hassan; Laiyemo, Adeyinka O; Lee, Edward; Cruz-Correa, Marcia; Ghuman, Amita; Nouraie, Mehdi; Brim, Hassan

    2015-01-01

    AIM: To evaluate the prevalence and characteristics of colorectal adenoma and carcinoma in an inner city Hispanic population. METHODS: We reviewed the reports of 1628 Hispanic patients who underwent colonoscopy at Howard University from 2000 to 2010. Advanced adenoma was defined as adenoma ≥ 1 cm in size, adenomas with villous histology, high grade dysplasia and/or invasive cancer. Statistical analysis was performed using χ2 statistics and t-test. RESULTS: The median age of the patients was 54 years, 64.2% were females. Polyps were observed in 489 (30.0%) of patients. Adenoma prevalence was 16.8% (n = 273), advanced adenoma 2.4% (n = 39), and colorectal cancer 0.4% (n = 7). Hyperplastic polyps were seen in 6.6% of the cohort (n = 107). Adenomas predominantly exhibited a proximal colonic distribution (53.7%, n = 144); while hyperplastic polyps were mostly located in the distal colon (70%, n = 75). Among 11.7% (n = 191) patients who underwent screening colonoscopy, the prevalence of colorectal lesions was 21.4% adenoma, 2.6% advanced adenoma; and 8.3% hyperplastic polyps. CONCLUSION: Our data showed low colorectal cancer prevalence among Hispanics in the Washington DC area. However, the pre-neoplastic pattern of colonic lesions in Hispanics likely points toward a shift in this population that needs to be monitored closely through large epidemiological studies. PMID:26673447

  2. Advanced colorectal neoplasia risk stratification by penalized logistic regression.

    PubMed

    Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

    2016-08-01

    Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the [Formula: see text]-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance.

  3. Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type.

    PubMed

    Burnett-Hartman, Andrea N; Newcomb, Polly A; Hutter, Carolyn M; Peters, Ulrike; Passarelli, Michael N; Schwartz, Malaika R; Upton, Melissa P; Zhu, Lee-Ching; Potter, John D; Makar, Karen W

    2014-07-15

    We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24-79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type.

  4. Characteristics of and risk factors for colorectal neoplasms in young adults in a screening population

    PubMed Central

    Lee, Seung Eun; Jo, Hee Bum; Kwack, Won Gun; Jeong, Yun Jin; Yoon, Yeo-Jin; Kang, Hyoun Woo

    2016-01-01

    AIM: To investigate prevalence and risk factors for colorectal neoplasms in adults aged < 50 years, for whom screening is not recommended. METHODS: This cross-sectional study compared prevalence and characteristics of colorectal and advanced adenomas in patients aged < 50 years who underwent colonoscopy screening with subjects aged ≥ 50 years. To evaluate risk factors for colorectal and advanced adenoma in young adults, we used multivariable logistic regression models. Colorectal neoplasm characteristics were evaluated and compared with those in older patients. RESULTS: Among 2819 patients included, prevalences of colorectal adenoma and advanced adenoma were 19.7% and 1.5%, respectively. As patient age increased, so did the prevalence of colorectal neoplasm. However, prevalence of advanced adenoma did not differ between age-groups 45-49 years and ≥ 50 years (OR = 0.43, 95%CI: 0.17-1.07, P = 0.070). In younger age-group (< 50 years), colorectal adenoma was significantly associated with older age, waist circumference (OR = 1.72, 95%CI: 1.15-2.55, P = 0.008), and current smoking (OR = 1.60, 95%CI: 1.07-2.41, P = 0.023). Alcohol consumption was an independent risk factor for colorectal advanced adenoma (OR = 3.69, 95%CI: 1.08-12.54, P = 0.037). Multiple neoplasms and large neoplasms (≥ 1 cm) were more prevalent in subjects ≥ 50 years. CONCLUSION: Current screening strategies for colorectal cancer may need to be amended to account for patient age, especially in young subjects with abdominal obesity, current smoking and alcohol consumption. PMID:26973394

  5. Colorectal cancer development and advances in screening

    PubMed Central

    Simon, Karen

    2016-01-01

    Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective. PMID:27486317

  6. Identification and characterization of RET fusions in advanced colorectal cancer

    PubMed Central

    Garrett, Christopher R.; Seery, Tara; Sanford, Eric M.; Balasubramanian, Sohail; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.; Chiu, Vi K.

    2015-01-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  7. Identification and characterization of RET fusions in advanced colorectal cancer.

    PubMed

    Le Rolle, Anne-France; Klempner, Samuel J; Garrett, Christopher R; Seery, Tara; Sanford, Eric M; Balasubramanian, Sohail; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A; Ali, Siraj M; Chiu, Vi K

    2015-10-01

    There is an unmet clinical need for molecularly directed therapies available for metastatic colorectal cancer. Comprehensive genomic profiling has the potential to identify actionable genomic alterations in colorectal cancer. Through comprehensive genomic profiling we prospectively identified 6 RET fusion kinases, including two novel fusions of CCDC6-RET and NCOA4-RET, in metastatic colorectal cancer (CRC) patients. RET fusion kinases represent a novel class of oncogenic driver in CRC and occurred at a 0.2% frequency without concurrent driver mutations, including KRAS, NRAS, BRAF, PIK3CA or other fusion tyrosine kinases. Multiple RET kinase inhibitors were cytotoxic to RET fusion kinase positive cancer cells and not RET fusion kinase negative CRC cells. The presence of a RET fusion kinase may identify a subset of metastatic CRC patients with a high response rate to RET kinase inhibition. This is the first characterization of RET fusions in CRC patients and highlights the therapeutic significance of prospective comprehensive genomic profiling in advanced CRC. PMID:26078337

  8. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis.

  9. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

    PubMed Central

    Ko, Sun-Hye; Baeg, Myong Ki; Bae, Woong Jin; Kim, Pumsoo; Choi, Myung-Gyu

    2016-01-01

    Background/aims Patients being treated for prostate cancer (PCa) have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs) is unknown. We aimed to investigate the risk of CRNs in PCa patients. Materials and methods Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1) histological findings of high-grade dysplasia, 2) inclusion of villous features, 3) tumor ≥1 cm in size, or 4) presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis. Results A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0.001). Other significant risk factors for advanced CRN were age (OR 1.050; 95% CI 1.003–1.009; P=0.036) and body mass index (OR 1.205; 95% CI 1.067–1.361; P=0.003), whereas aspirin use (OR 0.414; 95% CI 0.173–0.990; P=0.047) was a preventive factor. Conclusion The risk of advanced CRN may be significantly increased in patients with PCa. Patients with PCa should have a colonoscopy at the time of PCa diagnosis. PMID:27672332

  10. Derivation and validation of a scoring system to stratify the risk of advanced colorectal neoplasia in asymptomatic adults

    PubMed Central

    Imperiale, Thomas F.; Monahan, Patrick O.; Stump, Timothy E.; Glowinski, Elizabeth A.; Ransohoff, David F.

    2016-01-01

    Background Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. Objective To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps ≥1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. Design Cross-sectional study. Setting Multiple endoscopy units, primarily in the Midwest. Patients Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). Measurements Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. Results Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. Limitations Split-sample validation; results apply to first-time screening. Conclusion This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be

  11. Recent clinical and pathophysiological advances in non-functioning pituitary adenomas.

    PubMed

    Korbonits, Márta; Carlsen, Eivind

    2009-04-01

    Pituitary adenomas are being recognized and diagnosed with increasing frequency. One of the most common forms of pituitary lesion is the clinically non-functioning pituitary adenoma (NFPA), which is often diagnosed incidentally. The vast majority of pituitary adenomas are sporadic, but familial adenomas can occur in the multiple pituitary adenoma type 1 syndrome, in Carney complex or in familial isolated pituitary adenoma. Distinguishing NFPA from prolactinomas can occasionally cause a differential diagnostic problem due to the 'stalk effect'. NFPA often show hormone synthesis on tissue immunostaining without causing clinical symptoms. Most often these are silent gonadotroph adenomas, with silent corticotroph or somatotroph adenomas occurring less frequently. It is unclear why these silent adenomas do not release hormones at a clinically recognizable level, although it is probable that there is a continuum between fully functional and completely silent adenomas. Another intriguing feature of NFPAs is the lack of clinical response to somatostatin analogues, despite the presence of somatostatin receptors and an often good response in the in vitro setting. Temozolomide has been successfully used for the treatment of a few aggressive pituitary adenomas, and the response to this drug could be influenced by the expression of the DNA repair enzyme O-6-methylguanine DNA methyltransferase. The early diagnosis, prediction of long-term outcome and treatment of NFPAs remain a challenge for endocrinologists. PMID:19407508

  12. Incidence of colorectal neoplasms among male pilots

    PubMed Central

    Moshkowitz, Menachem; Toledano, Ohad; Galazan, Lior; Hallak, Aharon; Arber, Nadir; Santo, Erwin

    2014-01-01

    AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots. METHODS: Initial screening colonoscopy was performed on average-risk (no symptoms and no family history) airline pilots at the Integrated Cancer Prevention Center (ICPC) in the Tel-Aviv Medical Center. Visualized polyps were excised and sent for pathological examination. Advanced adenoma was defined as a lesion >10 mm in diameter, with high-grade dysplasia or villous histology. The results were compared with those of an age- and gender-matched random sample of healthy adults undergoing routine screening at the ICPC. RESULTS: There were 270 pilots (mean age 55.2 ± 7.4 years) and 1150 controls (mean age 55.7 ± 7.8 years). The prevalence of colorectal neoplasms was 15.9% among the pilots and 20.6% among the controls (P = 0.097, χ2 test). There were significantly more hyperplastic polyps among pilots (15.5% vs 9.4%, P = 0.004) and a trend towards fewer adenomas (14.8% vs 20.3% P = 0.06). The prevalence of advanced lesions among pilots and control groups was 5.9% and 4.7%, respectively (P = 0.49), and the prevalence of cancer was 0.7% and 0.69%, respectively (P = 0.93). CONCLUSION: There tends to be a lower colorectal adenoma, advanced adenoma and cancer prevalence but a higher hyperplastic polyp prevalence among pilots than the general population. PMID:25083084

  13. Designing an intervention to help people with colorectal adenomas reduce their intake of red and processed meat and increase their levels of physical activity: a qualitative study

    PubMed Central

    2012-01-01

    Background Most cases of colorectal cancer (CRC) arise from adenomatous polyps and malignant potential is greatest in high risk adenomas. There is convincing observational evidence that red and processed meat increase the risk of CRC and that higher levels of physical activity reduce the risk. However, no definitive randomised trial has demonstrated the benefit of behaviour change on reducing polyp recurrence and no consistent advice is currently offered to minimise patient risk. This qualitative study aimed to assess patients’ preferences for dietary and physical activity interventions and ensure their appropriate and acceptable delivery to inform a feasibility trial. Methods Patients aged 60–74 included in the National Health Service Bowel Cancer Screening Programme (NHSBCSP) were selected from a patient tracking database. After a positive faecal occult blood test (FOBt), all had been diagnosed with an intermediate or high risk adenoma (I/HRA) at colonoscopy between April 2008 and April 2010. Interested patients and their partners were invited to attend a focus group or interview in July 2010. A topic guide, informed by the objectives of the study, was used. A thematic analysis was conducted in which transcripts were examined to ensure that all occurrences of each theme had been accounted for and compared. Results Two main themes emerged from the focus groups: a) experiences of having polyps and b) changing behaviour. Participants had not associated polyp removal with colorectal cancer and most did not remember being given any information or advice relating to this at the time. Heterogeneity of existing diet and physical activity levels was noted. There was a lack of readiness to change behaviour in many people in the target population. Conclusions This study has confirmed and amplified recently published factors involved in developing interventions to change dietary and physical activity behaviour in this population. The need to tailor the intervention to

  14. Association Between Consumption of Fruits and Vegetables and Risk of Colorectal Adenoma: A PRISMA-Compliant Meta-Analysis of Observational Studies.

    PubMed

    Ben, Qiwen; Zhong, Jie; Liu, Jun; Wang, Lifu; Sun, Yunwei; Yv, Lifen; Yuan, Yaozong

    2015-10-01

    There have been contradictory results about the association of fruits and vegetables intake with colorectal adenoma (CRA) risk, the precursor lesion of colorectal cancer. Herein, we have conducted a meta-analysis of the published observational studies to have a clear understanding about this association.Eligible studies up to November 30, 2014, were identified and retrieved by searching MEDLINE and EMBASE databases along with the manual review of the reference list of the retrieved studies. The quality of the included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale, and random-effects model was used to calculate summary relative risk (SRR) and corresponding 95% confidence interval (CI).A total of 22 studies involving 11,696 CRA subjects were part of this meta-analysis. The SRR for the highest versus the lowest intake of vegetables alone was 0.91 (95% CI: 0.80-1.02, Pheterogeneity = 0.025), whereas for vegetables and fruits combined, it was 0.82 (95% CI: 0.75-0.91, Pheterogeneity = 0.369), and for fruits alone, it was 0.79 (95% CI: 0.71-0.88, Pheterogeneity = 0.111). In addition, linear dose-response analysis also showed similar results, for example, for per 100 g/d increment of fruits, the SRR was 0.94 (95% CI: 0.92-0.97) and for vegetables it was 0.98 (95% CI: 0.96-1.01). Nonlinear association was only observed for vegetables (Pnonlinearity = 0.024), but not for fruits (Pnonlinearity = 0.583).Thus, this meta-analysis suggested that fruits consumption have a significant protective effect on CRA risk, but not vegetables. Moreover, we recommend additional studies with prospective designs that use validated questionnaires and control for important confounders to further validate the overall results.

  15. Association Between Exposure to Environmental Tobacco Smoke at the Workplace and Risk for Developing a Colorectal Adenoma: A Cross-Sectional Study

    PubMed Central

    Lee, Seung-Hwa; Hong, Ji-Yeon; Lee, Jung-Un

    2016-01-01

    Purpose A colorectal adenoma (CRA) is a well-defined precursor to colorectal cancer (CRC). Additionally, smoking is a potent risk factor for developing a CRA, as well as CRC. However, the association between exposure to environmental tobacco smoke (ETS) and the risk for developing a CRA has not yet been fully evaluated in epidemiologic studies. We performed a cross-sectional analysis on the association between exposure to ETS at the workplace and the risk for developing a CRA. Methods The study was conducted on subjects who had undergone a colonoscopy at a health promotion center from January 2012 to December 2012. After descriptive analyses, overall and subgroup analyses by smoking status were performed by using a multivariate logistic regression. Results Among the 1,129 participants, 300 (26.6%) were diagnosed as having CRAs. Exposure to ETS was found to be associated with CRAs in all subjects (fully adjusted odds ratio [OR], 1.95; 95% confidence interval [CI], 1.08–2.44; P = 0.001). In the subgroup analysis, exposure to ETS in former smokers increased the risk for developing a CRA (fully adjusted OR, 4.44; 95% CI, 2.07–9.51; P < 0.001). Conclusion Exposure to occupational ETS at the workplace, independent of the other factors, was associated with increased risk for developing a CRA in all subjects and in former smokers. Further retrospective studies with large sample sizes may be necessary to clarify the causal effect of this relationship. PMID:27218095

  16. Racial disparities in advanced stage colorectal cancer survival

    PubMed Central

    Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

    2013-01-01

    Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

  17. Intraoperative and external beam irradiation for locally advanced colorectal cancer.

    PubMed Central

    Gunderson, L L; Martin, J K; Bèart, R W; Nagorney, D M; Fieck, J M; Wieand, H S; Martinez, A; O'Connell, M J; Martenson, J A; McIlrath, D C

    1988-01-01

    In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real. PMID:3337561

  18. Diagnostics and Epidemiology of Colorectal Cancer.

    PubMed

    Kolligs, Frank T

    2016-06-01

    Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. Main risk factors include advanced age, family history, male sex, and lifestyle factors. Screening can reduce incidence and death from colorectal cancer. Therefore, prevention and early detection are crucial in order to detect and remove pre-neoplastic adenomas and to detect cancers at early stages. Colonoscopy, flexible sigmoidoscopy, and fecal occult blood tests are established tools for screening. Newer fecal immunochemical tests reveal higher sensitivities for advanced adenoma and cancer than guaiac-based hemoccult tests. Molecular stool and blood tests as well as virtual colonoscopy and colon capsule endoscopy are promising new developments so far not established as routine instruments for the prevention and early detection of colorectal cancer. Colonoscopy is the method of choice for the diagnosis of colorectal cancer and for adenoma removal. Prognosis is essentially dependent on the tumor stage at the time of the initial diagnosis. Proper staging based on imaging prior to therapy is a prerequisite. In rectal cancer, local staging is an essential requirement for the identification of appropriate candidates for neoadjuvant therapy. PMID:27493942

  19. A NONPARAMETRIC MULTIPLE IMPUTATION APPROACH FOR DATA WITH MISSING COVARIATE VALUES WITH APPLICATION TO COLORECTAL ADENOMA DATA

    PubMed Central

    Hsu, Chiu-Hsieh; Long, Qi; Li, Yisheng; Jacobs, Elizabeth

    2015-01-01

    A nearest neighbor-based multiple imputation approach is proposed to recover missing covariate information using the predictive covariates while estimating the association between the outcome and the covariates. To conduct the imputation, two working models are fitted to define an imputing set. This approach is expected to be robust to the underlying distribution of the data. We show in simulation and demonstrate on a colorectal data set that the proposed approach can improve efficiency and reduce bias in a situation with missing at random compared to the complete case analysis and the modified inverse probability weighted method. PMID:24697618

  20. Background Colonic 18F-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission Tomography Is Associated with the Presence of Colorectal Adenoma

    PubMed Central

    Lee, Ko Eun; Yoon, Hai-Jeon; Chang, Ji Young; Son, Hyo Moon; Ryu, Min Sun; Kim, Seong-Eun; Shim, Ki-Nam; Jung, Hye-Kyung; Jung, Sung-Ae

    2016-01-01

    18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is used to evaluate various kinds of tumors. While most studies on PET findings of the colon focus on the colonic uptake pattern, studies regarding background colonic uptake on PET scan are rare. The purpose of this study was to identify the association between the background colonic uptake and the presence of colorectal adenoma (CRA), which is a frequent precancerous lesion. We retrospectively reviewed the medical records of 241 patients with gynecologic malignancy who had received PET or PET/computed tomography (CT) scan and colonoscopy at the same period as a baseline evaluation. Background colonic 18F-FDG uptake was visually graded and the maximal standardized uptake values (SUVmax) of 7 different bowel segments were averaged. In univariate analysis, older age at diagnosis (≥ 50 years, p = 0.034), overweight (BMI ≥ 23 kg/m², p = 0.010), hypercholesterolemia (≥ 200 mg/dL, p = 0.027), and high grade background colonic uptake (p = 0.009) were positively associated with the prevalence of CRA. By multiple logistic regression, high grade background colonic uptake was independently predictive of CRA (odds ratio = 2.25, p = 0.021). The proportion of CRA patients significantly increased as background colonic uptake grade increased from 1 to 4 (trend p = 0.015). Out of the 138 patients who underwent PET/CT, the proportion of CRA patients in the group with high SUVmax (> 2.25) was significantly higher than in the low SUVmax group (27.5% vs. 11.6%, p = 0.031). In conclusion, high grade of background colonic 18F-FDG uptake is significantly associated with the prevalence of CRA. PMID:27509022

  1. Rectal Optical Markers for In-vivo Risk Stratification of Premalignant Colorectal Lesions

    PubMed Central

    Radosevich, Andrew J.; Mutyal, Nikhil N.; Eshein, Adam; Nguyen, The-Quyen; Gould, Bradley; Rogers, Jeremy D.; Goldberg, Michael J; Bianchi, Laura K; Yen, Eugene F.; Konda, Vani; Rex, Douglas K.; Van Dam, Jacques

    2015-01-01

    Purpose Colorectal cancer remains the second leading cause of cancer deaths in the U.S. despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex-vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in-vivo. Experimental Design Measurements from 619 patients were taken using a minimally invasive 3.4 mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring ~1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient μs∗ and mass density distribution factor D. Results The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple non-advanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. Conclusions We demonstrate the viability of in-vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification. PMID:25991816

  2. Genetic Polymorphisms of Flavin Monooxygenase 3 in Sulindac-Induced Regression of Colorectal Adenomas in Familial Adenomatous Polyposis

    PubMed Central

    Hisamuddin, Irfan M.; Wehbi, Mohammad A.; Schmotzer, Brian; Easley, Kirk A.; Hylind, Linda M.; Giardiello, Francis M.; Yang, Vincent W.

    2008-01-01

    Sulindac is a nonsteroidal antiinflammatory drug with a chemopreventive effect in patients with familial adenomatous polyposis (FAP). In vivo, the active form of sulindac is sulindac sulfide, which is inactivated by the hepatic microsomal enzyme, flavin monooxygenase 3 (FMO3). In humans, numerous polymorphisms exist in FMO3, which alter enzymatic activity and subsequent substrate metabolism. We recently showed that certain polymorphic forms of FMO3 with reduced activity were associated with a more favorable response to sulindac in preventing the formation of adenomas in patients with FAP without polyps at baseline. Here, we determined whether these FMO3 polymorphisms correlated with the ability of sulindac to regress polyposis in patients with FAP who had polyps prior to treatment. Nineteen patients were treated with 150 mg sulindac twice a day for 6 months. The size and number of polyps in each patient was assessed at baseline (prior to the administration of sulindac), and at 3 and 6 months. Genotyping was done on seven established FMO3 polymorphisms with functional significance—M66I, E158K, P153L, V257M, E305X, E308G, and R492W. Statistical analyses were done with Wilcoxon rank sum test. Of the loci examined, only E158K and E308G showed polymorphic changes. Six patients exhibited polymorphisms in both E158K and E308G loci and were designated as genotype combination 1. The remaining patients were designated as genotype combination 2. Over the course of treatment, patients with genotype combination 1 had a greater reduction in both the size and number of polyps than those with genotype combination 2. These results suggest that combined polymorphic changes in the E158K and E308G alleles may protect against polyposis in patients with FAP treated with sulindac. PMID:16214918

  3. [News and perspectives in the treatment of advanced gastric and colorectal cancers].

    PubMed

    Diciolla, A; Cristina, V; De Micheli, R; Digklia, A; Wagner, A D

    2015-05-20

    Colorectal and gastric cancers are the fourth and third leading causes of cancer death world-wide. Unfortunately, gastric cancer is usually diagnosed at an advanced stage after becoming metastatic in distant sites, so that palliative therapy is the mainstay of treatment. Major progress in the understanding of the biology, the development of valid biomarkers and molecular targeted drugs have improved the treatment options and prognosis of both cancers significantly in the last years. Here, we review the current standards of care for patients with advanced and metastatic colorectal and gastric cancer and outline the perspectives for the future.

  4. (1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal Neoplasia.

    PubMed

    Amiot, Aurelien; Dona, Anthony C; Wijeyesekera, Anisha; Tournigand, Christophe; Baumgaertner, Isabelle; Lebaleur, Yann; Sobhani, Iradj; Holmes, Elaine

    2015-09-01

    Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we investigated the fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate modeling. The fecal microbiota composition was assessed by quantitative real-time PCR as well as Wif-1 methylation levels in stools, serum, and urine and correlated to the metabolic profile of each patient. The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was 0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased fecal concentrations of four short-chain fatty acids (valerate, acetate, propionate, and butyrate) and decreased signals relating to β-glucose, glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR model was higher than that of the guaiac-fecal occult blood test and the Wif-1 methylation test for predicting advanced colorectal neoplasia. Correlation analysis between fecal metabolites and bacterial profiles revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species with short-chain fatty acids concentration and inverse correlation between Faecalibacterium prausnitzii and glucose. These preliminary results suggest that fecal metabonomics may potentially have a future role in a noninvasive colorectal screening program and may contribute to our understanding of the role of these dysregulated molecules in the cross-talk between the host and its bacterial microbiota.

  5. Parathyroid adenoma

    MedlinePlus

    Hyperparathyroidism - parathryoid adenoma; Overactive parathyroid gland - parathyroid adenoma ... The parathyroid glands in the neck help control calcium use and removal by the body. They do this by producing parathyroid ...

  6. Advanced oxidation protein products and total antioxidant activity in colorectal carcinoma.

    PubMed

    Avinash, S S; Anitha, M; Vinodchandran; Rao, Gayathri M; Sudha, K; Shetty, Beena V

    2009-01-01

    The present study was designed to assess the levels of advanced oxidation protein products (AOPP) and percent hemolysis (that indirectly indicates the degree of membrane damage secondary to lipid peroxidation) in colorectal carcinoma. Glutathione (GSH), total thiols and albumin were measured to determine the antioxidant status. Considering the dynamic interaction between various antioxidants in the body, we measured the total antioxidant activity (AOA). Globulin was measured to assess the inflammatory response secondary to oxidative stress. Investigations were conducted in 45 cases of recently diagnosed primary colorectal adenocarcinoma. As control, 45 age and sex matched healthy persons were chosen. GSH was estimated in whole blood, percent hemolysis in RBC suspension and other parameters in plasma. We observed a very high significant increase (P<0.001) in AOPP, percent hemolysis and a highly significant increase (P<0.01) in globulin in colorectal carcinoma. We observed a very high significant decrease (P<0.001) in whole blood GSH, total thiols, albumin, AOA and a significant decrease (P<0.05) in plasma GSH in colorectal carcinoma. A very high significant negative correlation between percent hemolysis and AOA and an apparent negative correlation between total thiols and AOPP was seen in colorectal carcinoma. This demonstrated oxidative stress, decreased antioxidant status and secondary inflammatory response in colorectal carcinoma.

  7. Fusobacterium nucleatum: an emerging bug in colorectal tumorigenesis.

    PubMed

    Bashir, Arif; Miskeen, Abid Y; Bhat, Ashaqullah; Fazili, Khalid M; Ganai, Bashir A

    2015-09-01

    The human intestinal microbiota is a plethora of diverse microbial species, wherein certain bacteria considered as driver bacteria with procarcinogenic features contribute directly toward colonic epithelium cell damage to initiate colorectal carcinogenesis. However, some bacteria, in particular Fusobacterium nucleatum, which is otherwise a normal resident of the oral microflora and a relatively poor colonizer of the healthy gut, have also been considered to play a role in the development of colorectal cancer. Many studies have reported that F. nucleatum is associated with colorectal adenomas and advanced-stage colorectal cancer, but its precise role in the early stages of colorectal tumorigenesis is poorly understood. Here, we review some of the important features of F. nucleatum, its association with inflammatory bowel disease, modulation of the tumor-immune microenvironment, and E-cadherin/β-catenin signaling.

  8. Colorectal endoscopic submucosal dissection: Recent technical advances for safe and successful procedures

    PubMed Central

    Yamamoto, Katsumi; Michida, Tomoki; Nishida, Tsutomu; Hayashi, Shiro; Naito, Masafumi; Ito, Toshifumi

    2015-01-01

    Endoscopic submucosal dissection (ESD) is very useful in en bloc resection of large superficial colorectal tumors but is a technically difficult procedure because the colonic wall is thin and endoscopic maneuverability is poor because of colonic flexure and extensibility. A high risk of perforation has been reported in colorectal ESD. To prevent complications such as perforation and unexpected bleeding, it is crucial to ensure good visualization of the submucosal layer by creating a mucosal flap, which is an exfoliated mucosa for inserting the tip of the endoscope under it. The creation of a mucosal flap is often technically difficult; however, various types of equipment, appropriate strategy, and novel procedures including our clip-flap method, appear to facilitate mucosal flap creation, improving the safety and success rate of ESD. Favorable treatment outcomes with colorectal ESD have already been reported in many advanced institutions, and appropriate understanding of techniques and development of training systems are required for world-wide standardization of colorectal ESD. Here, we describe recent technical advances for safe and successful colorectal ESD. PMID:26468335

  9. Advances and perspectives of colorectal cancer stem cell vaccine.

    PubMed

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

  10. Prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West

    PubMed Central

    Leshno, Ari; Moshkowitz, Menachem; David, Maayan; Galazan, Lior; Neugut, Alfred I; Arber, Nadir; Santo, Erwin

    2016-01-01

    AIM To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations. METHODS We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma (AA) and colorectal cancer (CRC) were determined in the 40’s and 50’s age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations. RESULTS We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men (P < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups. CONCLUSION The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.

  11. Prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West

    PubMed Central

    Leshno, Ari; Moshkowitz, Menachem; David, Maayan; Galazan, Lior; Neugut, Alfred I; Arber, Nadir; Santo, Erwin

    2016-01-01

    AIM To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations. METHODS We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma (AA) and colorectal cancer (CRC) were determined in the 40’s and 50’s age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations. RESULTS We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men (P < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups. CONCLUSION The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population. PMID:27621582

  12. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options. PMID:27602209

  13. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options.

  14. Diagnostic accuracy of 18F-FDG PET/CT for detecting synchronous advanced colorectal neoplasia in patients with gastric cancer

    PubMed Central

    Choi, Byung Wook; Kim, Hae Won; Won, Kyoung Sook; Song, Bong-Il; Cho, Kwang Bum; Bae, Sung Uk

    2016-01-01

    Abstract Preoperative screening for synchronous colorectal neoplasia (CRN) has been recommended in patients with gastric cancer because patients with gastric cancer are at increased risk for synchronous CRN. The aim of this study was to investigate the diagnostic accuracy of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting synchronous advanced CRN in patients with gastric cancer. A total of 256 patients who underwent colonoscopy and 18F-FDG PET/CT for preoperative staging were enrolled in this study. The diagnosis of focal colonic 18F-FDG uptake on 18F-FDG PET/CT image was made based on histopathologic results from the colonoscopic biopsy. The 18F-FDG PET/CT result was considered as true positive for advanced CRN when focal 18F-FDG uptake matched colorectal carcinoma or adenoma with high-grade dysplasia in the same location on colonoscopy. Synchronous advanced CRN was detected in 21 of the 256 patients (4.7%). Sensitivity, specificity, and accuracy of 18F-FDG PET/CT were 76.2%, 96.2%, and 94.5%. The size of CRN with a true positive result was significantly larger than that with a false negative result. 18F-FDG PET/CT demonstrated high diagnostic accuracy for detecting synchronous advanced CRN in patients with gastric cancer. Colonoscopy is recommended as the next diagnostic step for further evaluation of a positive 18F-FDG PET/CT result in patients with gastric cancer. PMID:27603371

  15. Diagnostic accuracy of 18F-FDG PET/CT for detecting synchronous advanced colorectal neoplasia in patients with gastric cancer.

    PubMed

    Choi, Byung Wook; Kim, Hae Won; Won, Kyoung Sook; Song, Bong-Il; Cho, Kwang Bum; Bae, Sung Uk

    2016-09-01

    Preoperative screening for synchronous colorectal neoplasia (CRN) has been recommended in patients with gastric cancer because patients with gastric cancer are at increased risk for synchronous CRN. The aim of this study was to investigate the diagnostic accuracy of F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting synchronous advanced CRN in patients with gastric cancer.A total of 256 patients who underwent colonoscopy and F-FDG PET/CT for preoperative staging were enrolled in this study. The diagnosis of focal colonic F-FDG uptake on F-FDG PET/CT image was made based on histopathologic results from the colonoscopic biopsy. The F-FDG PET/CT result was considered as true positive for advanced CRN when focal F-FDG uptake matched colorectal carcinoma or adenoma with high-grade dysplasia in the same location on colonoscopy.Synchronous advanced CRN was detected in 21 of the 256 patients (4.7%). Sensitivity, specificity, and accuracy of F-FDG PET/CT were 76.2%, 96.2%, and 94.5%. The size of CRN with a true positive result was significantly larger than that with a false negative result.F-FDG PET/CT demonstrated high diagnostic accuracy for detecting synchronous advanced CRN in patients with gastric cancer. Colonoscopy is recommended as the next diagnostic step for further evaluation of a positive F-FDG PET/CT result in patients with gastric cancer. PMID:27603371

  16. New technologies and techniques to improve adenoma detection in colonoscopy

    PubMed Central

    Bond, Ashley; Sarkar, Sanchoy

    2015-01-01

    Adenoma detection rate (ADR) is a key component of colonoscopy quality assessment, with a direct link between itself and future mortality from colorectal cancer. There are a number of potential factors, both modifiable and non-modifiable that can impact upon ADR. As methods, understanding and technologies advance, so should our ability to improve ADRs, and thus, reduce colorectal cancer mortality. This article will review new technologies and techniques that improve ADR, both in terms of the endoscopes themselves and adjuncts to current systems. In particular it focuses on effective techniques and behaviours, developments in image enhancement, advancement in endoscope design and developments in accessories that may improve ADR. It also highlights the key role that continued medical education plays in improving the quality of colonoscopy and thus ADR. The review aims to present a balanced summary of the evidence currently available and does not propose to serve as a guideline. PMID:26265990

  17. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    PubMed Central

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  18. Morphological Characteristics and Location of Missed, Advanced Colorectal Neoplasms after Colonoscopy.

    PubMed

    Kawamura, Takuji; Uno, Koji; Tanaka, Kiyohito; Ueda, Yuki; Sakiyama, Naokuni; Nishida, Kensei; Rokutan, Kazuhito; Yasuda, Kenjiro

    2016-01-01

    This retrospective study aimed to clarify the clinical characteristics of advanced colorectal neoplasms after colonoscopy, likely to have been missed on the previous colonoscopy. We reviewed a total of 5,768 consecutive colonoscopies performed from April 2010 to September 2013 in 4,841 patients, and analyzed advanced colorectal neoplasms after colonoscopy, particularly focusing on their morphological characteristics and locations, as compared with primary lesions, defined as lesions detected in their first colonoscopy or in a subsequent colonoscopy >5 years after the previous one. Of the 5,768 examinations, 922 advanced neoplasms (including 217 cancers with ≥T2) were detected, and 167 lesions (18.1%) were diagnosed within 5 years after a previous colonoscopy (post-colonoscopy advanced neoplasms). The incidence of right-sided lesions in the post-colonoscopy advanced neoplasms (48.5%, 81/167) was significantly higher than in the primary lesions (34.0%, 257/755; p <0.001). We excluded 217 cancers with ≥T2 from the morphological analysis to characterize early-stage post-colonoscopy advanced neoplasms. The incidence of non-polypoid lesions in the post-colonoscopy advanced neoplasms (25.6%, 41/160) was significantly higher than that in the primary lesions (12.3%, 67/545; p <0.001). These findings suggest that extra attention should be paid to non-polypoid, right-sided advanced colorectal neoplasms during screening and surveillance colonoscopy. J. Med. Invest. 63: 163-170, August, 2016.

  19. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  20. [Advances of minimally invasive technique in colorectal cancer surgery].

    PubMed

    Wang, Xishan

    2016-06-01

    Colorectal surgery is rapidly developing in the direction of minimally invasive surgery and functional surgery. New technology and ideas are constantly emerging recently. Laparoscopic colon surgery has already been recommended by NCCN guideline. However, laparoscopic rectal cancer surgery still needs to wait for survival and recurrence rates of long-term follow-up data for verification. In recent years, with the rapid progression of imaging equipment of laparoscope, the new 3D laparoscopic system will process image more quickly, and surgeons can get space depth feeling like open surgery only with a pair of glasses. The new 3D laparoscopic system has many advantages, and can also shorten the learning curve of the beginners. But it does not mean the traditional 2D laparoscopy has been out of date. It is admitted that dialectical view on the development of the technology and equipment is still required. New things also need the accumulation of time and validation, and the deficiency of imaging system remains to be improved. At present, the robotic colorectal cancer surgery is still in its infancy, and its application is relatively common in colon surgery. In respect of robotic rectal cancer surgery, it still lacks of long-term follow-up survival results for verification. To reduce physical and psychological trauma for patients is the goal of the surgeon. Surgeons are experiencing the change from minimally invasion to non-invasion. Natural orifice translumenal endoscopic surgery (NOTES) and natural orifice specimen extraction surgery (NOSES) arise at the historic moment. Among them, transanal total mesorectal excision (taTME) incorporates the concepts of NOTES, anal minimally invasive surgery and total mesorectum excision, guaranteeing the radical cure and no scar of abdomen, but it still needs multicenter, large sample and long-term follow-up clinical data to prove its safety, efficacy and indication. Therefore, surgical procedure is transforming from conventional

  1. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer

    PubMed Central

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-01-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m2) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1–14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  2. Evaluation of serum nucleoside diphosphate kinase A for the detection of colorectal cancer

    PubMed Central

    Otero-Estévez, Olalla; De Chiara, Loretta; Barcia-Castro, Leticia; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco Javier; Cubiella, Joaquín; Hernández, Vicent; Martínez-Zorzano, Vicenta Soledad

    2016-01-01

    We previously described the over-expression of nucleoside diphosphate kinase A (NDKA) in tumours and serum from colorectal cancer (CRC) patients, suggesting its use as biomarker. In this study we evaluated the diagnostic accuracy of serum NDKA to detect advanced neoplasia (CRC or advanced adenomas). Furthermore, the performance of NDKA was compared with the faecal immunochemical test (FIT). The study population included a case-control cohort and a screening cohort (511 asymptomatic first-degree relatives of CRC patients that underwent a colonoscopy and a FIT). Serum NDKA was elevated in CRC patients in the case-control cohort (p = 0.002). In the screening cohort, NDKA levels were higher for advanced adenomas (p = 0.010) and advanced neoplasia (p = 0.006) compared to no neoplasia. Moreover, elevated NDKA was associated with severe characteristics of adenomas (≥3 lesions, size ≥ 1 cm or villous component). Setting specificity to 85%, NDKA showed a sensitivity of 30.19% and 29.82% for advanced adenomas and advanced neoplasia, respectively. NDKA combined with FIT (100 ng/mL cut-off) detected advanced adenomas and advanced neoplasia with 45.28% and 49.12% sensitivity, with specificity close to 90%. The combination of serum NDKA and FIT can improve the detection of advanced neoplasia, mainly for lesions located on the proximal colon, in asymptomatic individuals with CRC family-risk. PMID:27222072

  3. Targeting BRAF aberrations in advanced colorectal carcinoma: from bench to bedside.

    PubMed

    Abdel-Rahman, Omar

    2016-01-01

    Colorectal cancer (CRC) is a global health problem with profound mortality and morbidity effects particularly in the advanced/metastatic setting. Because of the recent understanding of the biology of this disease, many candidate targets have come into light for therapeutic evaluation. The current review is about evaluating the preclinical and clinical aspects of BRAF as a therapeutic target in this disease. The available clinical results suggest that while the use of unselective RAF inhibitors (e.g., sorafenib) has been ineffective in the management of advanced CRC patients with KRAS mutation, combination of selective BRAF inhibitors plus EGFR inhibitors may represent a good therapeutic strategy in BRAF-mutant CRC. PMID:26616508

  4. GNAS gene mutation may be present only transiently during colorectal tumorigenesis

    PubMed Central

    Zauber, Peter; Marotta, Stephen P; Sabbath-Solitare, Marlene

    2016-01-01

    Mutations of the gene GNAS have been shown to activate the adenylate cyclase gene and lead to constitutive cAMP signaling. Several preliminary reports have suggested a role for GNAS gene mutations during colorectal carcinogenesis, particularly mucinous carcinomas. The aim of this study was to clarify the incidence of GNAS mutations in adenomas (tubular, tubulovillous, and villous), carcinomas with residual adenoma, and carcinomas, and to relate these findings to mutations of the KRAS gene and to the mucinous status of the tumors. We used standard PCR techniques and direct gene sequencing to evaluate tumors for gene mutations. No GNAS mutations were identified in 25 tubular adenomas, but were present in 6.4% of tubulovillous adenomas and 11.2% of villous adenomas. A GNAS mutation was found in 9.7% of the benign portion of carcinoma with residual adenoma, but in none of 86 carcinomas. A similar trend was seen for KRAS mutation across the five groups of tumors. GNAS mutations may function as an important driver mutation during certain phases of colorectal carcinogenesis, but may then be lost once the biological advantage gained by the mutated gene is no longer necessary to sustain or advance tumor development. PMID:27186325

  5. Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer

    PubMed Central

    Ryan, Bríd M.; Zanetti, Krista A.; Robles, Ana I.; Schetter, Aaron J.; Goodman, Julie; Hayes, Richard B.; Huang, Wen-Yi; Gunter, Marc J.; Yeager, Meredith; Burdette, Laurie; Berndt, Sonja I.; Harris, Curtis C.

    2013-01-01

    Chronic inflammation has been implicated in the etiology of colorectal adenoma and cancer; however, few key inflammatory genes mediating this relationship have been identified. In this study, we investigated the association of germline variation in innate immunity genes in relation to the risk of colorectal neoplasia. Our study was based on the analysis of samples collected from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We investigated the association between 196 tag single nucleotide polymorphisms (SNPs) in 20 key innate immunity genes with risk of advanced colorectal adenoma and cancer in 719 adenoma cases, 481 cancer cases and 719 controls. Logistic regression was used to estimate odds ratios and 95% confidence intervals. After Bonferroni correction, the AG/GG genotype of rs5995355, which is upstream of NCF4, was associated with an increased risk of colorectal cancer (odds ratio [OR] 2.43, 95% confidence interval [95% CI] 1.73 – 3.39; P<0.0001). NCF4 is part of the NAPDH complex, a key factor in biochemical pathways and the innate immune response. While not definitive, our analyses suggest that the variant allele does not affect expression of NCF4, but rather modulates activity of the NADPH complex. Additional studies on the functional consequences of rs5995355 in NCF4 may help to clarify the mechanistic link between inflammation and colorectal cancer. PMID:23982929

  6. Two Phenotypes of Traditional Serrated Adenomas Nationwide Survey in Iceland.

    PubMed

    Rubio, Carlos A; Jónasson, Jón G

    2015-09-01

    Iceland has a total population of 300,000 inhabitants. All patients consulting for symptoms of the lower digestive tract during a four-year period (2003-2006) were subjected to a colonoscopic examination; all polyps were endoscopically removed. Out of the total 3,037 colorectal adenomas (CRAs), 308 (10.2%) were traditional serrated adenomas (TSAs). TSAs were divided according the predominant histological phenotype (>50%) into those with ectopic crypt formations (ECF), and those with unlocked serrations (US). ECF-TSA accounted for 5.9% (178/3037) and US-TSA for 4.3% (130/3037). The majority of patients with ECF-TSA and US-TSA were ≥ 60 years of age (74.1% and 76.2%, respectively). Notwithstanding, when patients having advanced adenomas (with high-grade dysplasia, with or without intramucosal carcinoma) were listed by age, those with ECF-TSA were significantly younger than those with US-TSA (p<0.05). ECF-TSA were more frequently left-sided (71.8%), whereas US-TSA were more frequently right-sided (60.0%). Invasive carcinoma evolved more frequently in ECF-TSA (7.8%) and in US-TSA (7.7%) than in tubular adenomas and in villous/tubulovillous adenomas (0.1% and 4.4%, respectively). Comparative studies indicated that the incidence rates/year of ECF-TSA and US-TSA were significantly higher in Iceland than in Sweden or in Italy (p<0.05). Genetic and putative epigenetic (environmental) factor(s) might account for the high incidence rate/year of ECF-TSA and US-TSA in this country.

  7. The analysis of a large Danish family supports the presence of a susceptibility locus for adenoma and colorectal cancer on chromosome 11q24.

    PubMed

    Rudkjøbing, Laura Aviaja; Eiberg, Hans; Mikkelsen, Hanne Birte; Binderup, Marie Louise Mølgaard; Bisgaard, Marie Luise

    2015-09-01

    Hereditary colorectal cancer accounts for approximately 30% of all colorectal cancers, but currently only 5% of these families can be explained by highly penetrant, inherited mutations. In the remaining 25% it is not possible to perform a gene test to identify the family members who would benefit from prophylactic screening. Consequently, all family members are asked to follow a screening program. The purpose of this study was to localize a new gene which causes colorectal cancer. We performed a linkage analysis using data from a SNP6.0 chip in one large family with 12 affected family members. We extended the linkage analysis with microsatellites (STS) and single nucleotide polymorphisms (SNP's) and looked for the loss of heterozygosity in tumour tissue. Furthermore, we performed the exome sequencing of one family member and we sequenced candidate genes by use of direct sequencing. Major rearrangements were excluded after karyotyping. The linkage analysis with SNP6 data revealed three candidate areas, on chromosome 2, 6 and 11 respectively, with a LOD score close to two and no negative LOD scores. After extended linkage analysis, the area on chromosome 6 was excluded, leaving areas on chromosome 2 and chromosome 11 with the highest possible LOD scores of 2.6. Two other studies have identified 11q24 as a candidate area for colorectal cancer susceptibility and this area is supported by our results. PMID:25724759

  8. Treatment-related gastrointestinal toxicities and advanced colorectal or pancreatic cancer: A critical update

    PubMed Central

    Aprile, Giuseppe; Rihawi, Karim; De Carlo, Elisa; Sonis, Stephen T

    2015-01-01

    Gastrointestinal toxicities (GIT), including oral mucositis, nausea and vomiting, and diarrhea, are common side effects of chemotherapy and targeted agents in patients with advanced colorectal cancer and pancreatic cancer. Being often underreported, it is still difficult to precisely establish their burden in terms of both patient’s quality of life and cancer care costs. Moreover, with the use of more intensive upfront combination regimens, the frequency of these toxicities is rapidly growing with a potential negative effect also on patient’s outcome, as a result of dose reductions, delays or even discontinuation of active treatments. Thus, identifying patients at higher risk of developing GIT as well as an optimal management are paramount in order to improve patient’s compliance and outcome. After the description of the main treatment-induced GIT, we discuss the current knowledge on the pathophysiology of these side effects and comment the scales commonly used to assess and grade them. We then provide a critical update on GIT incidence based on the results of key randomized trials conducted in patients with metastatic colorectal cancer and advanced pancreatic cancer. PMID:26557003

  9. Familial pituitary adenomas.

    PubMed

    Vandeva, S; Vasilev, V; Vroonen, L; Naves, L; Jaffrain-Rea, M-L; Daly, A F; Zacharieva, S; Beckers, A

    2010-12-01

    Pituitary adenomas are benign intracranial neoplasms that present a major clinical concern because of hormonal overproduction or compression symptoms of adjacent structures. Most arise in a sporadic setting with a small percentage developing as a part of familial syndromes such as multiple endocrine neoplasia type 1 (MEN1), Carney complex (CNC), and the recently described familial isolated pituitary adenomas (FIPA) and MEN-4. While the genetic alterations responsible for the formation of sporadic adenomas remain largely unknown, considerable advances have been made in defining culprit genes in these familial syndromes. Mutations in MEN1 and PRKAR1A genes are found in the majority of MEN1 and CNC patients, respectively. About 15% of FIPA kindreds present with mutations of the aryl hydrocarbon receptor-interacting protein (AIP) gene. Mutations in the CDKN1B gene, encoding p27(Kip)¹ were identified in MEN4 cases. Familial tumours appear to differ from their sporadic counterparts not only in genetic basis but also in clinical characteristics. Evidence suggests that, especially in MEN1 and FIPA, they are more aggressive and affect patients at younger age, therefore justifying the importance of early diagnosis. In this review, we summarize the genetic and clinical characteristics of these familial pituitary adenomas. PMID:20961530

  10. KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer

    PubMed Central

    2010-01-01

    Executive Summary In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of the literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario. Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenomics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports. The following reports can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Gene Expression Profiling for Guiding Adjuvant Chemotherapy Decisions in Women with Early Breast Cancer: An Evidence-Based and Economic Analysis Epidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: an Evidence-Based and Economic Analysis K-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based and Economic Analysis. Objective The objective of this systematic review is to determine the predictive value of KRAS testing in the treatment of metastatic colorectal cancer (mCRC) with two anti-EGFR agents, cetuximab and panitumumab. Economic analyses are also being conducted to evaluate the cost-effectiveness of KRAS testing. Clinical Need: Condition and Target Population Metastatic colorectal cancer (mCRC) is usually defined as stage IV disease according to the American Joint Committee on Cancer

  11. Tests to Detect Colorectal Cancer and Polyps

    MedlinePlus

    ... be acceptable screening tests for colorectal cancer: High-sensitivity fecal occult blood tests (FOBT). Both polyps and ... higher than that of gFOBT or FIT. Test sensitivity for adenomas is low. False-positive test results ...

  12. Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients.

    PubMed

    Kehlet, S N; Sanz-Pamplona, R; Brix, S; Leeming, D J; Karsdal, M A; Moreno, V

    2016-01-01

    During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer. PMID:27465284

  13. Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients

    PubMed Central

    Kehlet, S. N.; Sanz-Pamplona, R.; Brix, S.; Leeming, D. J.; Karsdal, M. A.; Moreno, V.

    2016-01-01

    During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of protein fragments of collagen type I, III and IV as novel biomarkers for colorectal cancer. Specific fragments of degraded type I, III and IV collagen (C1M, C3M, C4M) and type III collagen formation (Pro-C3) were assessed in serum from colorectal cancer patients, subjects with adenomas and matched healthy controls using well-characterized and validated ELISAs. Serum levels of the biomarkers were significantly elevated in colorectal cancer patients compared to subjects with adenomas (C1M, Pro-C3, C3M) and controls (C1M, Pro-C3). When patients were stratified according to their tumour stage, all four biomarkers were able to differentiate stage IV metastatic patients from all other stages. Combination of all markers with age and gender in a logistic regression model discriminated between metastatic and non-metastatic patients with an AUROC of 0.80. The data suggest that the levels of these collagen remodeling biomarkers may be a measure of tumour activity and invasiveness and may provide new clinical tools for monitoring of patients with advanced stage colorectal cancer. PMID:27465284

  14. Malakoplakia and colonic adenoma: a rare association.

    PubMed

    Rizzo, Elena; Sandmeier, Dominique; Hack, Isabelle; Matter, Maurice; Bouzourene, Hanifa

    2004-12-01

    We report the case of a 73-year-old woman who presented respectively a caecal adenocarcinoma, two high-grade dysplastic tubulo-villous adenomas of the right colon, and a well differentiated adenocarcinoma developed on a high-grade dysplastic tubulo-villous adenoma of the left colon. One of the right colonic adenomas was ulcerated and showed typical foci of malakoplakia in the lamina propria. Malakoplakia is a histiocytic inflammatory response that may be associated with inflammatory and infectious diseases, immunosuppressive therapy, or colorectal carcinoma. Association of malakoplakia with colonic adenoma is rare; only three cases have been described in the literature thus far. To verify if this association is more common than usually suspected, we reviewed 100 colonic adenomas measuring at least 2 cm. No other case of malakoplakia associated with adenoma was found. The patient did not suffer from any other inflammatory or infectious disease and she was not under any medication or immunosuppressive therapy. Our observation confirms the isolated association of malakoplakia and colonic adenomas and the rarity of this association.

  15. Molecular testing to optimize therapeutic decision making in advanced colorectal cancer

    PubMed Central

    Kim, Edward J.

    2016-01-01

    Colorectal cancer (CRC) is a leading cause of cancer death in the United States. In recent years, therapeutic advances have prolonged the survival of patients with advanced disease. Along with the addition of new treatments, an increasing body of literature explores the potential benefit of using molecular testing to define tumor, circulating, or host biomarkers of benefit to specific treatment strategies. At present, testing for specific mutations in exons 2, 3, and 4 of KRAS and NRAS has become accepted practice to select patients for treatment with epidermal growth factor receptor (EGFR)-targeted agents. Additionally, testing for the BRAF V600E mutation is used to refine decisions based on patient prognosis. The presence of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *28 polymorphism is associated with toxicity from irinotecan, although it has not been universally applied. Nonetheless, molecular markers to predict response and toxicity of cytotoxic therapy are evolving. While the development of selection biomarkers for anti-angiogenic treatments has not proved fruitful to date, improved development strategies and novel targeted agents are anticipated to revolutionize the approach to treatment of advanced CRC in the near future. This review summarizes currently available data to select treatment strategies in patients with advanced CRC. PMID:27034809

  16. Molecular testing to optimize therapeutic decision making in advanced colorectal cancer.

    PubMed

    Semrad, Thomas J; Kim, Edward J

    2016-04-01

    Colorectal cancer (CRC) is a leading cause of cancer death in the United States. In recent years, therapeutic advances have prolonged the survival of patients with advanced disease. Along with the addition of new treatments, an increasing body of literature explores the potential benefit of using molecular testing to define tumor, circulating, or host biomarkers of benefit to specific treatment strategies. At present, testing for specific mutations in exons 2, 3, and 4 of KRAS and NRAS has become accepted practice to select patients for treatment with epidermal growth factor receptor (EGFR)-targeted agents. Additionally, testing for the BRAF V600E mutation is used to refine decisions based on patient prognosis. The presence of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) *28 polymorphism is associated with toxicity from irinotecan, although it has not been universally applied. Nonetheless, molecular markers to predict response and toxicity of cytotoxic therapy are evolving. While the development of selection biomarkers for anti-angiogenic treatments has not proved fruitful to date, improved development strategies and novel targeted agents are anticipated to revolutionize the approach to treatment of advanced CRC in the near future. This review summarizes currently available data to select treatment strategies in patients with advanced CRC. PMID:27034809

  17. Pituitary adenomas in childhood and adolescence.

    PubMed

    Jackman, Suzanne; Diamond, Frank

    2013-07-01

    Scientific advances are revealing the complexity of pituitary development, which is controlled by multiple transcription factors and signaling molecules. Unregulated pituitary cell growth, resulting in pituitary adenoma, is usually sporadic and results from monoclonal expansion of a single mutated cell. However, some adenomas develop as part of a genetic syndrome. Prolactinoma is the most common hormonally active pituitary adenoma in children. The non-functioning (non-secreting) pituitary adenoma is the second most common and often stains positive for GH, PRL, and/or TSH. While Cushing disease, resulting from an ACTH-secreting adenoma, commonly manifests as weight gain with growth deceleration in children, GH excess causes gigantism with rapid, accelerated growth inappropriate for the height of the family. TSH secreting pituitary adenomas are rare, and biochemical analysis will show an elevated thyroxine level with a non-suppressed or high TSH. Though the natural history of pituitary incidentalomas in children is unknown, adult practice guidelines are established. PMID:23957196

  18. Hepatocellular adenoma: An update.

    PubMed

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-11-01

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions.

  19. Calcium Intake and Ion Transporter Genetic Polymorphisms Interact in Human Colorectal Neoplasia Risk in a 2-Phase Study123

    PubMed Central

    Zhu, Xiangzhu; Liang, Ji; Shrubsole, Martha J.; Ness, Reid M.; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Wiese, Dawn; Zhang, Bing; Smalley, Walter E.; Edwards, Todd L.; Giovannucci, Edward; Zheng, Wei; Dai, Qi

    2014-01-01

    Background: The kidney-specific sodium-potassium-chloride cotransporter (NKCC2) protein encoded by solute carrier family 12 member 1 (SLC12A1) is the direct downstream effector of the inward-rectifier potassium channel (ROMK) encoded by potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), both of which are critical for calcium reabsorption in the kidney. Objective: We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. Methods: We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. Results: In phase I, we identified 5 single-nucleotide polymorphisms (SNPs) that significantly interacted with calcium intake in adenoma risk. In phase II, rs2855798 in KCNJ1 was replicated. In combined analysis of phases I and II, the P values for interactions between calcium intake and rs2855798 were 1 × 10−4 for all adenoma and 5 × 10−3 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with no variant allele but was significantly associated with a 41% reduced adenoma risk among those who carried at least 1 variant allele in KCNJ1. The corresponding reduction in risk of multiple or advanced adenomas was 52% among those with at least 1 variant allele. The P values for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 × 10−5 for adenoma and 9.9 × 10−5 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with nonvariant alleles in 2 genes but was significantly associated with a 34% reduced adenoma risk among those who carried a variant allele in 1 of the genes. The corresponding reduction in risk of multiple or advanced adenomas was 64% among those with variant alleles in both genes. Conclusion: These findings, if confirmed, will be critical for the development of personalized

  20. Colonoscopy detects significantly more flat adenomas than 3-tesla magnetic resonance colonography: a pilot trial

    PubMed Central

    Hüneburg, Robert; Kukuk, Guido; Nattermann, Jacob; Endler, Christoph; Penner, Arndt-Hendrik; Wolter, Karsten; Schild, Hans; Strassburg, Christian; Sauerbruch, Tilman; Schmitz, Volker; Willinek, Winfried

    2016-01-01

    Background and study aims: Colorectal cancer (CRC) is one of the most common cancers worldwide, and several efforts have been made to reduce its occurrence or severity. Although colonoscopy is considered the gold standard in CRC prevention, it has its disadvantages: missed lesions, bleeding, and perforation. Furthermore, a high number of patients undergo this procedure even though no polyps are detected. Therefore, an initial screening examination may be warranted. Our aim was to compare the adenoma detection rate of magnetic resonance colonography (MRC) with that of optical colonoscopy. Patients and methods: A total of 25 patients with an intermediate risk for CRC (17 men, 8 women; mean age 57.6, standard deviation 11) underwent MRC with a 3.0-tesla magnet, followed by colonoscopy. The endoscopist was initially blinded to the results of MRC and unblinded immediately after examining the distal rectum. Following endoscopic excision, the size, anatomical localization, and appearance of all polyps were described according to the Paris classification. Results: A total of 93 lesions were detected during colonoscopy. These included a malignant infiltration of the transverse colon due to gastric cancer in 1 patient, 28 adenomas in 10 patients, 19 hyperplastic polyps in 9 patients, and 45 non-neoplastic lesions. In 5 patients, no lesion was detected. MRC detected significantly fewer lesions: 1 adenoma (P = 0.001) and 1 hyperplastic polyp (P = 0.004). The malignant infiltration was seen with both modalities. Of the 28 adenomas, 23 (82 %) were 5 mm or smaller; only 4 adenomas 10 mm or larger (14 %) were detected. Conclusion: MRC does not detect adenomas sufficiently independently of the location of the lesion. Even advanced lesions were missed. Therefore, colonoscopy should still be considered the current gold standard, even for diagnostic purposes. PMID:26878043

  1. Recent advances in active specific cancer vaccine treatment for colorectal cancer.

    PubMed

    Okuno, Kiyotaka; Sugiura, Fumiaki; Itoh, Kyogo; Yoshida, Koji; Tsunoda, Takuya; Nakamura, Yusuke

    2012-06-01

    Cloning techniques to identify genes and peptides of tumor-associated antigens have created new possibilities for the immunotherapy of patients with advanced cancer. Here, we review recent clinical trials of specific cancer vaccines, mainly HLA-restricted peptides, and epitope-encoding vectors for advanced colorectal cancer (CRC). Many researchers initially focused on carcinoembryonic antigen (CEA) as an immunologic target antigen that is overexpressed on virtually all CRCs. A recombinant vaccine containing the CEA gene and dendritic cells (DCs) loaded with CEA peptide was administered to patients with CEA-elevated CRC. Although CEA-specific responses were detected, the clinical responses were limited. Recently, new types of clinical trials--namely, a personalized protocol to take into account the immunological diversity of cytotoxic T cell responses among patients and a novel cancer-testis antigen protocol that uses multiple peptides derived from genes identified by the cDNA array method--have been introduced. The personalized protocol seemed to be better than the classical (non-personalized) protocol in terms of clinical response and survival. Novel cancer-testis antigen protocols that use multiple CRC-derived peptides were recently conducted in patients with advanced CRC. The preliminary study yielded promising results regarding specific T cell responses to peptides and survival benefits. In this review, we summarize these results and discuss future perspectives. PMID:22339221

  2. Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

    PubMed

    Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

    2015-03-01

    Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

  3. The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy

    PubMed Central

    Wong, Martin CS; Ching, Jessica YL; Chan, Victor CW; Sung, Joseph JY

    2015-01-01

    Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions, and costs including screening compliance, polypectomy, colonoscopy complications, and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC. PMID:26338314

  4. The comparative cost-effectiveness of colorectal cancer screening using faecal immunochemical test vs. colonoscopy.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Sung, Joseph J Y

    2015-01-01

    Faecal immunochemical tests (FITs) and colonoscopy are two common screening tools for colorectal cancer(CRC). Most cost-effectiveness studies focused on survival as the outcome, and were based on modeling techniques instead of real world observational data. This study evaluated the cost-effectiveness of these two tests to detect colorectal neoplastic lesions based on data from a 5-year community screening service. The incremental cost-effectiveness ratio (ICER) was assessed based on the detection rates of neoplastic lesions, and costs including screening compliance, polypectomy, colonoscopy complications, and staging of CRC detected. A total of 5,863 patients received yearly FIT and 4,869 received colonoscopy. Compared with FIT, colonoscopy detected notably more adenomas (23.6% vs. 1.6%) and advanced lesions or cancer (4.2% vs. 1.2%). Using FIT as control, the ICER of screening colonoscopy in detecting adenoma, advanced adenoma, CRC and a composite endpoint of either advanced adenoma or stage I CRC was US$3,489, US$27,962, US$922,762 and US$23,981 respectively. The respective ICER was US$3,597, US$439,513, -US$2,765,876 and US$32,297 among lower-risk subjects; whilst the corresponding figure was US$3,153, US$14,852, US$184,162 and US$13,919 among higher-risk subjects. When compared to FIT, colonoscopy is considered cost-effective for screening adenoma, advanced neoplasia, and a composite endpoint of advanced neoplasia or stage I CRC. PMID:26338314

  5. Favorable lifestyle before diagnosis associated with lower risk of screen-detected advanced colorectal neoplasia

    PubMed Central

    Knudsen, Markus D; de Lange, Thomas; Botteri, Edoardo; Nguyen, Dung-Hong; Evensen, Helge; Steen, Chloé B; Hoff, Geir; Bernklev, Tomm; Hjartåker, Anette; Berstad, Paula

    2016-01-01

    AIM: To investigate the association between adherence to health recommendations and detection of advanced colorectal neoplasia (ACN) in colorectal cancer (CRC) screening. METHODS: A total of 14832 women and men were invited to CRC screening, 6959 in the fecal immunochemical test arm and 7873 in the flexible sigmoidoscopy arm. These were also sent a self-reported lifestyle questionnaire to be completed prior to their first CRC screening. A lifestyle score was created to reflect current adherence to healthy behaviors in regard to smoking, body mass index, physical activity, alcohol consumption and food consumption, and ranged from zero (poorest) to six (best). Odds ratios (ORs) and 95%CIs were calculated using multivariable logistic regression to evaluate the association between the single lifestyle variables and the lifestyle score and the probability of detecting ACN. RESULTS: In all 6315 women and men completed the lifestyle questionnaire, 3323 (53%) in the FIT arm and 2992 (47%) in the FS arm. This was 89% of those who participated in screening. ACN was diagnosed in 311 (5%) participants of which 25 (8%) were diagnosed with CRC. For individuals with a lifestyle score of two, three, four, and five-six, the ORs (95%CI) for the probability of ACN detection were 0.82 (0.45-1.16), 0.43 (0.28-0.73), 0.41 (0.23-0.64), and 0.41 (0.22-0.73), respectively compared to individuals with a lifestyle score of zero-one. Of the single lifestyle factors, adherence to non-smoking and moderate alcohol intake were associated with a decreased probability of ACN detection compared to being a smoker or having a high alcohol intake 0.53 (0.42-0.68) and 0.63 (0.43-0.93) respectively. CONCLUSION: Adopted healthy behaviors were inversely associated with the probability of ACN detection. Lifestyle assessment might be useful for risk stratification in CRC screening. PMID:27468217

  6. Innate immunity gene polymorphisms and the risk of colorectal neoplasia

    PubMed Central

    Berndt, Sonja I.

    2013-01-01

    Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case–control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57–0.83, P = 7.7 × 10–5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30–0.55, P = 2.4 × 10− 9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69–1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37–0.69 and ORper T allele = 0.72, 95% CI: 0.54–0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia. PMID:23803696

  7. Meta-analysis of chemotherapy with irinotecan or oxaliplatin-involved regimen for untreated metastatic advanced colorectal cancer.

    PubMed

    Zhuang, Luhong; Bai, Jianling; Huang, Huaying; Tang, Cuiju; Yang, Jinsong; Zhou, Baoning; Gong, Yongling; Duanmu, Zhong; Chen, Jinfei

    2010-01-01

    A large number of randomized controlled trials involving chemotherapy in the management of advanced colorectal cancer were conducted. 5-FU/LV in combination with irinotecan (IRI) or oxaliplatin (OXA) was used. The aim of the meta-analysis was to compare and evaluate the effectiveness and safety of the two therapeutic approaches for patients with advanced colorectal cancer. A literature search, study selection and assessment, data collection, and analysis were undertaken by two reviewers according to the Cochrane Handbook for Systematic Reviews of Interventions. Randomized controlled trials (RCTs) or quasi-RCTs comparing IRI versus OXA, in combination with 5-FU/LV in the treatment of advanced colorectal cancer were performed. Seven studies involving 2,107 patients met the inclusion criteria. The OXA + 5-FU/LV regimen showed a significant increase in survival by lower hazard ratios (HR) [HR 1.28; 95% CI (1.13-1.45)] and was associated with lower toxicities. The OXA + 5-FU/LV regimen was superior or equal to the IRI + 5-FU/LV regimen in prolonging time to progression and median survival. The IRI + 5-FU/LV regimen resulted in higher hazard ratios in nausea vomiting/emesis and diarrhea [HR 1.99, 95% CI (1.19-3.31); HR 1.83, 95% CI (1.38-2.44)] and lower hazard ratios in paresthesia, sensory neuropathy, and thrombocytopenia [HR 0.09, 95% CI (0.03-0.23); HR 0.04 95% CI (0.01-0.13); HR 0.19 95% CI (0.05-0.64)] than the OXA + 5-FU/LV regimen. Compared with IRI, OXA is more appropriate for the treatment of advanced colorectal cancer when combined with 5-FU/LV. OXA + 5-FU/LV should be considered as the first-line standard of care for advanced CRC patients.

  8. Current concepts in colorectal cancer prevention

    PubMed Central

    Thompson, Patricia A; Gerner, Eugene W

    2009-01-01

    Colorectal cancer chemoprevention, or chemoprophylaxis, is a drug-based approach to prevent colorectal cancer. Preventing colorectal adenomas with currently available agents demonstrates the promise of pharmacologic strategies directed at critical regulatory pathways. However, agent toxicity, lesion breakthrough and competing efficacy from endoscopy procedures challenge population-based implementation. This article reviews the role of colorectal cancer chemoprevention in the context of existing screening and surveillance guidelines and practice. Emphasis is placed on the role of the colorectal adenoma as a cancer precursor and its surrogacy in assessing individual risk and for evaluating chemoprevention efficacy. We discuss the importance of risk stratification for identifying subjects at moderate-to-high risk for colorectal cancer who are most likely to benefit from chemoprevention at an acceptable level of risk. PMID:19673624

  9. [Study of the Efficacy of Aprepitant in FOLFOX/FOLFIRI for Elderly Patients with Advanced Colorectal Cancer].

    PubMed

    Hanaka, Junichi; Takahashi, Misaki; Nakayama, Hiromichi; Terashima, Teruaki

    2016-05-01

    For patients undergoing cancer chemotherapy, sufficient supportive antiemetic therapy is important for maintaining the quality of life. Although there are many studies on antiemetic support therapy for high emetic risk regimens, studies on moderately emetic risk regimens are scarce. FOLFOX and FOLFIRI are generic regimens for the treatment of advanced colorectal cancer; evidence for antiemetic supportive therapy at the time of this treatment is scarce. In addition, research on patients over 65 years of age is limited. Among the advanced colorectal cancer patients who received treatment with FOLFOX or FOLFIRI at Koyama Memorial Hospital, patients older than 65 years of age were selected in order to assess the effectiveness of aprepitant as an antiemetic supportive therapy. Aprepitant was used in combination with granisetron and dexamethasone in 14 patients. After 5 days of treatment, complete control rate of emesis was 100%, and complete control rate of nausea was 64.3%. Our results suggest that aprepitant can be used as a safe antiemetic supportive therapy in elderly advanced colorectal cancer patients undergoing FOLFOX and FOLFIRI, as well as granisetron and dexamethasone. PMID:27210087

  10. Detection Rate, Distribution, Clinical and Pathological Features of Colorectal Serrated Polyps

    PubMed Central

    Cao, Hai-Long; Chen, Xue; Du, Shao-Chun; Song, Wen-Jing; Wang, Wei-Qiang; Xu, Meng-Que; Wang, Si-Nan; Piao, Mei-Yu; Cao, Xiao-Cang; Wang, Bang-Mao

    2016-01-01

    Background: Colorectal serrated polyp is considered as histologically heterogeneous lesions with malignant potential in western countries. However, few Asian studies have investigated the comprehensive clinical features of serrated polyps in symptomatic populations. The aim of the study was to evaluate the features of colorectal serrated polyps in a Chinese symptomatic population. Methods: Data from all consecutive symptomatic patients were documented from a large colonoscopy database and were analyzed. Chi-square test or Fisher's exact test and logistic regression analysis were used for the data processing. Results: A total of 9191 (31.7%) patients were detected with at least one colorectal polyp. The prevalence of serrated polyps was 0.53% (153/28,981). The proportions of hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma (TSA) of all serrated polyps were 41.2%, 7.2%, and 51.6%, respectively, which showed a lower proportion of HP and SSA/P and a higher proportion of TSA. Serrated polyps appeared more in males and elder patients while there was no significant difference in the subtype distribution in gender and age. The proportions of large and proximal serrated polyps were 13.7% (21/153) and 46.4% (71/153), respectively. In total, 98.9% (89/90) serrated adenomas were found with dysplasia. Moreover, 14 patients with serrated polyps were found with synchronous advanced colorectal neoplasia, and large serrated polyps (LSPs) (odds ratio: 3.446, 95% confidence interval: 1.010–11.750, P < 0.05), especially large HPs, might have an association with synchronous advanced neoplasia (AN). Conclusions: The overall detection rate of colorectal serrated polyps in Chinese symptomatic patient population was low, and distribution pattern of three subtypes is different from previous reports. Moreover, LSPs, especially large HPs, might be associated with an increased risk of synchronous AN. PMID:27748334

  11. Distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer.

    PubMed

    Marchoudi, N; Amrani Hassani Joutei, H; Jouali, F; Fekkak, J; Rhaissi, H

    2013-12-01

    Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer (CRC) in order to introduce targeted therapy in the arsenal of therapeutic modalities for management of this cancer in Morocco. In this study, 92 samples obtained from patients with CRC were tested for the presence of the nine most common mutations in the KRAS gene and BRAF gene. Among the tested patients, 76.09% of patients had wt-KRAS genotype and 23.91% were KRAS mutants and the majority of mutations would result in an amino acid substitution of glycine by aspartic acid (68.2%) The predominant mutations are G>A transitions and G>T transversions. Around 5% (5.43%) of the tested patients bore the V600E mutation in BRAF gene. Only one patient showing to have the V600E mutation in BRAF was also mutated-KRAS. Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non responsive patients for the anti-EGFR treatment is 28.26%.

  12. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer

    PubMed Central

    Huisman, Marc C.; Vugts, Danielle J.; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R.; Schuit, Robert C.; Boellaard, Ronald; Hoekstra, Otto S.; van Dongen, Guus AMS; Verheul, Henk M.W.

    2015-01-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of 89Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq 89Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients 89Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with 89Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without 89Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC. PMID:26309164

  13. 89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.

    PubMed

    Menke-van der Houven van Oordt, Catharina Willemien; Gootjes, Elske C; Huisman, Marc C; Vugts, Danielle J; Roth, Chantal; Luik, Anne Marije; Mulder, Emma R; Schuit, Robert C; Boellaard, Ronald; Hoekstra, Otto S; van Dongen, Guus Ams; Verheul, Henk M W

    2015-10-01

    Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of (89)Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq (89)Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients (89)Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with (89)Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without (89)Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.

  14. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

    PubMed Central

    Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

  15. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX.

    PubMed

    Bano, Nusrat; Najam, Rahila; Mateen, Ahmed

    2013-01-01

    The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m(2)), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m(2)) after few treatment cycles.

  16. Lymph node staging in colorectal cancer: Old controversies and recent advances

    PubMed Central

    Resch, Annika; Langner, Cord

    2013-01-01

    Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor node metastasis (TNM) system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer. For affected patients, the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen, several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging. These include changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected. Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression. Outcome prediction based on the lymph node ratio, defined as the number of positive lymph nodes divided by the total number of retrieved nodes, may be superior to the absolute numbers of involved nodes. Extracapsular invasion has been identified as additional prognostic factor. Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis. The clinical value of more recent technical advances, such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined. PMID:24379568

  17. Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

    PubMed

    Duffour, J; Gourgou, S; Seitz, J F; Senesse, P; Boutet, O; Castera, D; Kramar, A; Ychou, M

    2002-01-01

    This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols. PMID:12552984

  18. Apoptotic pathways as a therapeutic target for colorectal cancer treatment.

    PubMed

    Abraha, Aman M; Ketema, Ezra B

    2016-08-15

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment. PMID:27574550

  19. Apoptotic pathways as a therapeutic target for colorectal cancer treatment

    PubMed Central

    Abraha, Aman M; Ketema, Ezra B

    2016-01-01

    Colorectal cancer is the second leading cause of death from cancer among adults. The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer. Appropriate apoptotic signaling is fundamentally important to preserve a healthy balance between cell death and cell survival and in maintaining genome integrity. Evasion of apoptotic pathway has been established as a prominent hallmark of several cancers. During colorectal cancer development, the balance between the rates of cell growth and apoptosis that maintains intestinal epithelial cell homeostasis gets progressively disturbed. Evidences are increasingly available to support the hypothesis that failure of apoptosis may be an important factor in the evolution of colorectal cancer and its poor response to chemotherapy and radiation. The other reason for targeting apoptotic pathway in the treatment of cancer is based on the observation that this process is deregulated in cancer cells but not in normal cells. As a result, colorectal cancer therapies designed to stimulate apoptosis in target cells would play a critical role in controlling its development and progression. A better understanding of the apoptotic signaling pathways, and the mechanisms by which cancer cells evade apoptotic death might lead to effective therapeutic strategies to inhibit cancer cell proliferation with minimal toxicity and high responses to chemotherapy. In this review, we analyzed the current understanding and future promises of apoptotic pathways as a therapeutic target in colorectal cancer treatment. PMID:27574550

  20. Evaluation of Colon Cancer – Specific Antigen 2 as a Potential Serum Marker for Colorectal Cancer

    PubMed Central

    Leman, Eddy S.; Schoen, Robert E.; Magheli, Ahmed; Sokoll, Lori J.; Chan, Daniel W.; Getzenberg, Robert H.

    2015-01-01

    Purpose A blood test to detect colon cancer at a preventable stage would represent a major advancement. We have previously identified colon cancer – specific markers using focused proteomics analysis of nuclear structural proteins. Two of these markers, colon cancer – specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is a distinct novel colon cancer marker identified using focused proteomics. Experimental Design Using an indirect ELISA on serum samples obtained from two institutions, we evaluated CCSA-2 as a serum-based colon cancer marker. A total of111serumsamples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study. Results Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 µg/mL has overall specificity of 78.4% [95% confidence interval (95% CI), 67.3–87.1%] and sensitivity of 97.3% (95% CI, 85.8–99.5%) in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90 (95% CI, 0.83–0.95). Conclusion Our initial study shows that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity. PMID:18316554

  1. [Broncho-pulmonary adenomas].

    PubMed

    Sousa, Vítor; Pinto, Eugénia; Franca, Teresa; Carvalho, Lina

    2004-01-01

    Adenomas of solitary gland type together with papillomas are the true benign tumours in or around the bronchial tree. Alveolar adenoma and papillary adenoma are more frequently observed in peripheral parenchime although this group of tumours is very rare and often incidentally diagnosed. Presenting usually as solitary nodules in adults after 45 years, are easily recognized because of distinct morphology but alveolar adenomas may be difficult to evaluate in frozen sections. Two cases of pleomorphic adenoma and alveolar adenoma are presented and a review of literature is made.

  2. Metastatic salivary pleomorphic adenoma.

    PubMed

    Sim, D W; Maran, A G; Harris, D

    1990-01-01

    Pleomorphic adenomas of the salivary gland are usually regarded as benign tumours. We report a case in which a solitary pulmonary metastasis arose from a pleomorphic adenoma of the right parotid gland. The mechanism of metastasis is discussed.

  3. Hepatocellular adenoma: An update

    PubMed Central

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-01-01

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions. PMID:26557953

  4. The ADENOMA Study. Accuracy of Detection using Endocuff Vision™ Optimization of Mucosal Abnormalities: study protocol for randomized controlled trial

    PubMed Central

    Bevan, Roisin; Ngu, Wee Sing; Saunders, Brian P.; Tsiamoulos, Zacharias; Bassett, Paul; Hoare, Zoe; Rees, Colin J.

    2016-01-01

    Background: Colonoscopy is the gold standard investigation for the diagnosis of bowel pathology and colorectal cancer screening. Adenoma detection rate is a marker of high quality colonoscopy and a high adenoma detection rate is associated with a lower incidence of interval cancers. Several technological advancements have been explored to improve adenoma detection rate. A new device called Endocuff Vision™ has been shown to improve adenoma detection rate in pilot studies. Methods/Design: This is a prospective, multicenter, randomized controlled trial comparing the adenoma detection rate in patients undergoing Endocuff Vision™-assisted colonoscopy with standard colonoscopy. All patients above 18 years of age referred for screening, surveillance, or diagnostic colonoscopy who are able to consent are invited to the study. Patients with absolute contraindications to colonoscopy, large bowel obstruction or pseudo-obstruction, colon cancer or polyposis syndromes, colonic strictures, severe diverticular segments, active colitis, anticoagulant therapy, or pregnancy are excluded. Patients are randomized according to site, age, sex, and bowel cancer screening status to receive Endocuff Vision™-assisted colonoscopy or standard colonoscopy on the day of procedure. Baseline data, colonoscopy, and polyp data including histology are collected. Nurse assessment of patient comfort and patient comfort questionnaires are completed post procedure. Patients are followed up at 21 days and complete a patient experience questionnaire. This study will take place across seven NHS Hospital Trusts: one in London and six within the Northern Region Endoscopy Group. A maximum of 10 colonoscopists per site will recruit a total of 1772 patients, with a maximum of four bowel screening colonoscopists permitted per site. Discussion: This is the first trial to evaluate the adenoma detection rate of Endocuff Vision™ in all screening, surveillance, and diagnostic patient groups. This timely

  5. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    PubMed

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis.

  6. Advances in targeted and immunobased therapies for colorectal cancer in the genomic era

    PubMed Central

    Seow, Heng Fong; Yip, Wai Kien; Fifis, Theodora

    2016-01-01

    Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC) can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for cancer therapy. PMID:27099521

  7. The prevalence and characteristics of colorectal neoplasia in acromegaly.

    PubMed

    Renehan, A G; Bhaskar, P; Painter, J E; O'Dwyer, S T; Haboubi, N; Varma, J; Ball, S G; Shalet, S M

    2000-09-01

    An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.

  8. Treatment of advanced colorectal cancer with high-dose intensity folinic acid and 5-fluorouracil plus supportive care.

    PubMed

    Petrioli, R; Lorenzi, M; Aquino, A; Marsili, S; Frediani, B; Palazzuoli, V; Marzocca, G; Botta, G; Tani, F; De Martino, A

    1995-11-01

    This randomised clinical trial, involving patients with advanced colorectal cancer, was carried out to compare the effectiveness of accelerated folinic acid (FA) plus 5-fluorouracil (5-FU) with that of the conventional regimen of 5-FU alone. Both regimens were administered with simulataneous supportive care. 185 patients were eligible: 94 were randomly allocated to receive FA 200 mg/m2 i.v. plus 5-FU 400 mg/m2 i.v. on days 1-5 every 3 weeks; and 91 to receive 5-FU 400 mg/m2 i.v. on days 1-5 every 4 weeks. The response rate was 33.3% in the accelerated FA/5-FU and 18.6% in the 5-FU arm (P = 0.045). Median survival was 13.5 months in the FA/5-FU arm and 7.5 months in the 5-FU arm (P = 0.039). Toxicity was mild and slightly more pronounced in the FA/5-FU arm (P = 0.078). This study indicates that, in patients with advanced colorectal cancer, accelerated chemotherapy with FA and 5-FU and simultaneous supportive care is capable of achieving a higher response rate and longer survival than conventional 5-FU alone, without severe toxicity. PMID:8562173

  9. A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology Network study

    PubMed Central

    Frank, Daniel; Jumonville, Alcee; Schelman, William R; Mulkerin, Daniel; Lubner, Sam; Richter, Katie; Winterle, Natalie; Wims, Mary Beth; Dietrich, Leah; Winkler, J. Mitchell; Volk, Michael; Kim, KyungMann; Holen, Kyle D.

    2012-01-01

    Background Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects. Methods This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m2 by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol. Results Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients. Conclusions Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma. PMID:22811876

  10. Current targeted therapies in the treatment of advanced colorectal cancer: a review

    PubMed Central

    Moriarity, Andrew; O’Sullivan, Jacintha; Kennedy, John; Mehigan, Brian; McCormick, Paul

    2016-01-01

    Treatment strategies for metastatic colorectal cancer (mCRC) patients have undergone dramatic changes in the past decade and despite improved patient outcomes, there still exist areas for continued development. The introduction of targeted agents has provided clinicians with additional treatment options in mCRC, however, results have been mixed at best. These novel therapies were designed to interfere with specific molecules involved in the cellular carcinogenesis pathway and ultimately deliver a more focused treatment. Currently, their use in mCRC has been limited primarily as an adjunct to conventional chemotherapy regimens. This review explores the relevant cell-signaling networks in colorectal cancer, provides focus on the current targeted agent armamentarium approved for use in mCRC and explores the usefulness of predictive mCRC biomarkers. PMID:27482287

  11. Traditional serrated adenomas of the upper digestive tract.

    PubMed

    Rubio, C A

    2016-01-01

    For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma-carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract. PMID:26468393

  12. Colorectal cancer manifesting with metastasis to prolactinoma: report of a case involving symptoms mimicking pituitary apoplexy.

    PubMed

    Thewjitcharoen, Yotsapon; Shuangshoti, Shanop; Lerdlum, Sukalaya; Siwanuwatn, Rungsak; Sunthornyothin, Sarat

    2014-01-01

    Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

  13. Radioimmunodetection of colorectal cancer

    SciTech Connect

    Kim, E.E.; Deland, F.H.; Casper, S.; Corgan, R.L.; Primus, F.J.; Goldenberg, D.M.

    1980-03-15

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with /sup 131/I at a total dose of at least 1.0 ..mu..Ci. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the /sup 131/I-labeled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with /sup 131/I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the apparent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.

  14. Radioimmunodetection of colorectal cancer.

    PubMed

    Kim, E E; Deland, F H; Casper, S; Corgan, R L; Primus, F J; Goldenberg, D M

    1980-03-15

    This study examines the accuracy of colorectal cancer radioimmunodetection. Twenty-seven patients with a history of histologically-confirmed colonic or rectal carcinoma received a high-titer, purified goat anti-CEA IgG labelled with 131-I at a total dose of at least 1.0 muCi. Various body views were scanned at 24 and 48 hours after administration of the radioantibody. Three additional cases were evaluated; one had a villous adenoma in the rectum and received the 131-I-labelled anti-CEA IgG, while two colonic carcinoma patients received normal goat IgG labelled with 131-I. All of the 7 cases with primary colorectal cancer showed true-positive tumor localization, while 20 of 25 sites of metastatic colorectal cancer detected by immune scintigraphy were corroborated by other detection measures. The sensitivity of the radioimmunodetection of colorectal cancers (primary and metastatic) was found to be 90% (true-positive rate), the putative specificity (true-negative rate) was 94%, and the appraent overall accuracy of the technique was 93%. Neither the case of a villous adenoma receiving the anti-CEA IgG nor the two cases of colonic cancer receiving normal goat IgG showed tumor radiolocalization. Very high circulating CEA titers did not appear to hinder successful tumor radiolocalization. These findings suggest that in colorectal cancers the method of CEA radioimmunodetection may be of value in preoperatively determining the location and extent of disease, in assessing possible recurrence or spread postoperatively, and in localizing the source of CEA production in patients with rising or elevated CEA titers. An ancilliary benefit could be a more tumor-specific detection test for confirming the findings of other, more conventional diagnostic measures.

  15. Cronkhite-Canada syndrome containing colon cancer and serrated adenoma lesions.

    PubMed

    Yashiro, Masakazu; Kobayashi, Hikaru; Kubo, Naoshi; Nishiguchi, Yukio; Wakasa, Kenichi; Hirakawa, Kosei

    2004-01-01

    We describe a case of Cronkhite-Canada syndrome associated with sigmoid colon cancer, and provide a literature review. A 77-year-old man was diagnosed with sigmoid colon cancer after presenting with hypoproteinemia, nail atrophy, loss of scalp hair, hyperpigmentation, and gastrointestinal polyposis. The findings were consistent with Cronkhite-Canada syndrome. The colon polyps were histologically serrated adenomas, whose crypts showed a saw-toothed growth pattern with dysplasia, or tubular adenoma. Cronkhite-Canada syndrome associated with colon cancer has been reported in 31 cases. The availability of histologic material permitted reexamination of 25 of these cases. Serrated adenoma of the polypoid lesions was retrospectively found in 10 (40%) of the 25 cases. By comparison, the incidence of serrated adenomas has been estimated to occur in about 1% of all general polyps. Taken together, it is suggested that Cronkhite-Canada syndrome associated with colorectal cancer frequently has polyps containing serrated adenoma lesions. In the case described here, microsatellite instability and overexpression of the p53 protein were found in the cancer lesion and serrated adenoma lesions, and none of the lesions showed a loss of heterozygosity of various genes or K-RAS mutations. Thus, genetic alterations between the serrated adenoma and the colorectal cancer was correlated in this case. These findings suggested the possibility of a serrated adenoma-carcinoma sequence in this case of Cronkhite-Canada syndrome.

  16. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas

    PubMed Central

    Jogunoori, Wilma; Menon, Vipin; Majumdar, Avijit; Chen, Jiun-Sheng; Gi, Young Jin; Jeong, Yun Seong; Phan, Liem; Belkin, Mitchell; Gu, Shoujun; Kundra, Suchin; Mistry, Nipun A.; Zhang, Jianping; Su, Xiaoping; Li, Shulin; Lin, Sue-Hwa; Javle, Milind; McMurray, John S.; Rahlfs, Thomas F.; Mishra, Bibhuti; White, Jon; Rashid, Asif; Beauchemin, Nicole; Weston, Brian R.; Shafi, Mehnaz A.; Stroehlein, John R.; Davila, Marta; Akbani, Rehan; Weinstein, John N.; Wu, Xifeng; Mishra, Lopa

    2016-01-01

    Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression. PMID:27100181

  17. Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas.

    PubMed

    Chen, Jian; Raju, Gottumukkala S; Jogunoori, Wilma; Menon, Vipin; Majumdar, Avijit; Chen, Jiun-Sheng; Gi, Young Jin; Jeong, Yun Seong; Phan, Liem; Belkin, Mitchell; Gu, Shoujun; Kundra, Suchin; Mistry, Nipun A; Zhang, Jianping; Su, Xiaoping; Li, Shulin; Lin, Sue-Hwa; Javle, Milind; McMurray, John S; Rahlfs, Thomas F; Mishra, Bibhuti; White, Jon; Rashid, Asif; Beauchemin, Nicole; Weston, Brian R; Shafi, Mehnaz A; Stroehlein, John R; Davila, Marta; Akbani, Rehan; Weinstein, John N; Wu, Xifeng; Mishra, Lopa

    2016-01-01

    Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression. PMID:27100181

  18. A Phase I Study of EKB-569 in Combination with Capecitabine in Patients with Advanced Colorectal Cancer

    PubMed Central

    Laheru, Dan; Croghan, Gary; Bukowski, Ronald; Rudek, Michelle; Messersmith, Wells; Erlichman, Charles; Pelley, Robert; Jimeno, Antonio; Donehower, Ross; Boni, Joseph; Abbas, Richat; Martins, Patricia; Zacharchuk, Charles; Hidalgo, Manuel

    2011-01-01

    Purpose To determine the maximum tolerated dose (MTD), characterize the principal toxicities, and assess the pharmacokinetics of EKB-569, an oral selective irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with capecitabine in patients with advanced colorectal cancer. Experimental Design Patients were treated with EKB-569 daily for 21days and capecitabine twice daily for14 days of a 21-day cycle. The dose levels of EKB-569 (mg/day) and capecitabine (mg/m2 twice daily) assessed were 25/750, 50/750, 50/1,000 and 75/1,000. An expanded cohort was enrolled at the MTD to better study toxicity and efficacy. Samples of plasma were collected to characterize the pharmacokinetics of the agents. Treatment efficacy was assessed every other cycle. Results A total of 37 patients, the majority of whom had prior chemotherapy, received a total of 163 cycles of treatment. Twenty patients were treated at the MTD, 50 mg EKB-569, daily and 1,000 mg/m2 capecitabine twice daily. Dose-limiting toxicities were diarrhea and rash. No patients had complete or partial responses but 48% had stable disease. The conversion of capecitabine to 5-fluorouracil was higher for the combination of EKB-569 and capecitabine (321 ± 151 ng*h/mL) than for capecitabine alone (176 ± 62 ng*hours/mL; P = 0.0037). Conclusion In advanced colorectal cancer, 50 mg EKB-569 daily can be safely combined with 1,000 mg/m2 capecitabine twice a day. A statistically significant increase in plasma levels of 5-fluorouracil for the combination of EKB-569 and capecitabine may be due to the single-dose versus multiple-dose exposure difference, variability in exposure or a potential drug interaction. PMID:18765554

  19. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.

    PubMed

    Winawer, Sidney J; Zauber, Ann G; Fletcher, Robert H; Stillman, Jonathon S; O'brien, Michael J; Levin, Bernard; Smith, Robert A; Lieberman, David A; Burt, Randall W; Levin, Theodore R; Bond, John H; Brooks, Durado; Byers, Tim; Hyman, Neil; Kirk, Lynne; Thorson, Alan; Simmang, Clifford; Johnson, David; Rex, Douglas K

    2006-01-01

    Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma > or =1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (< 1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up in 5 to 10 years

  20. Colorectal polyps

    MedlinePlus

    ... Villous adenomas; Serrated polyp; Serrated adenoma; Precancerous polyps; Colon cancer - polyps ... 50. Those with a family history of colon cancer or colon polyps may need to be screened at an ...

  1. Advances in dynamic modeling of colorectal cancer signaling-network regions, a path toward targeted therapies

    PubMed Central

    Kolch, Walter; Kholodenko, Boris N.; Ambrosi, Cristina De; Barla, Annalisa; Biganzoli, Elia M.; Nencioni, Alessio; Patrone, Franco; Ballestrero, Alberto; Zoppoli, Gabriele; Verri, Alessandro; Parodi, Silvio

    2015-01-01

    The interconnected network of pathways downstream of the TGFβ, WNT and EGF-families of receptor ligands play an important role in colorectal cancer pathogenesis. We studied and implemented dynamic simulations of multiple downstream pathways and described the section of the signaling network considered as a Molecular Interaction Map (MIM). Our simulations used Ordinary Differential Equations (ODEs), which involved 447 reactants and their interactions. Starting from an initial “physiologic condition”, the model can be adapted to simulate individual pathologic cancer conditions implementing alterations/mutations in relevant onco-proteins. We verified some salient model predictions using the mutated colorectal cancer lines HCT116 and HT29. We measured the amount of MYC and CCND1 mRNAs and AKT and ERK phosphorylated proteins, in response to individual or combination onco-protein inhibitor treatments. Experimental and simulation results were well correlated. Recent independently published results were also predicted by our model. Even in the presence of an approximate and incomplete signaling network information, a predictive dynamic modeling seems already possible. An important long term road seems to be open and can be pursued further, by incremental steps, toward even larger and better parameterized MIMs. Personalized treatment strategies with rational associations of signaling-proteins inhibitors, could become a realistic goal. PMID:25671297

  2. Hyperplastic polyposis: association with colorectal cancer.

    PubMed

    Leggett, B A; Devereaux, B; Biden, K; Searle, J; Young, J; Jass, J

    2001-02-01

    Hyperplastic polyposis is a loosely defined syndrome initially thought not to confer a clinically important predisposition to colorectal cancer. The aim of the current study was to examine the clinical, histologic, and molecular features of a prospective series of cases meeting a strict definition of the condition. Twelve patients were identified, seven of whom had developed colorectal cancer. Most polyps were hyperplastic, but 11 patients also had polyps containing dysplasia as either serrated adenomas. mixed polyps, or traditional adenomas. The mean percentage of dysplastic polyps in patients with cancer was 35%, and in patients without cancer, 11% (p < 0.05). Microsatellite instability (MSI) was present in 3 of 47 hyperplastic polyps and two of eight serrated adenomas. Kras was mutated in 8 of 47 hyperplastic polyps and two of eight serrated adenomas. No polyps showed loss of heterozygosity of chromosomes 5q, 1p, or 18q. Two of seven cancers showed a high level of MSI. It is concluded that hyperplastic polyposis is associated with a high risk of colorectal cancer. Hyperplastic polyps are the dominant type of polyp, but most cases have some dysplastic epithelium. A higher proportion of dysplastic polyps is associated with increased cancer risk. Clonal genetic changes are observed in some hyperplastic polyps and serrated adenomas.

  3. Serum matrix metalloproteinase-9 in colorectal cancer family-risk population screening

    PubMed Central

    Otero-Estévez, Olalla; Chiara, Loretta De; Rodríguez-Girondo, Mar; Rodríguez-Berrocal, Francisco Javier; Cubiella, Joaquín; Castro, Inés; Hernández, Vicent; Martínez-Zorzano, Vicenta Soledad

    2015-01-01

    Matrix metalloproteinase-9 (MMP-9) is related to tumour development and progression in colorectal cancer (CRC) and its utility as biomarker has been suggested. The aim of our study was to measure serum MMP-9 in asymptomatic first-degree relatives of CRC patients, and to analyse its diagnostic accuracy for the detection of advanced neoplasia (AN: advanced adenomas and CRC). Additionally, we compared its diagnostic capability with the most used non-invasive faecal immunochemical test (FIT). Serum MMP-9 was quantified by ELISA in 516 asymptomatic individuals that underwent a colonoscopy and a FIT. MMP-9 levels were significantly related to age and gender and therefore the concentration was corrected by these confounders. Corrected MMP-9 (cMMP-9) levels were higher in individuals with advanced adenomas (AA; p-value = 0.029) and AN (p-value = 0.056) compared to individuals with no neoplasia. Moreover, elevated cMMP-9 concentration was associated with more severe characteristics of adenomas (number of lesions, size and histology). Nevertheless, the diagnostic accuracy of cMMP-9 was considerably lower than that of FIT for identifying AA (22.64% vs. 47.17% sensitivity, 90% specificity) or AN (19.30% vs. 52.63% sensitivity, 90% specificity). According to our results, serum MMP-9 cannot be considered of utility for the diagnosis of AN in CRC family-risk population screening. PMID:26264519

  4. Determinants of Bowel Preparation Quality and Its Association With Adenoma Detection: A Prospective Colonoscopy Study.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Luk, Arthur K C; Tang, Raymond S Y; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2016-01-01

    The predictors of poor bowel preparation in colorectal cancer screening participants have not been adequately studied, and the association between the quality of bowel preparation and adenoma detection has not been firmly established. This study examined the determinants of poor bowel preparation, and evaluated its relationship with adenoma detection.We included subjects aged between 50 and 70 years who received colonoscopy between 2008 and 2014 in a colorectal cancer screening program in Hong Kong. The quality of the bowel preparation was assessed by colonoscopists, and the factors associated with poor bowel cleansing were evaluated by a binary logistic regression analysis. A multivariate regression model was constructed to evaluate if poor bowel preparation was associated with detection of colorectal neoplasia.From 5470 screening participants (average age 57.7 years, SD 4.9), 1891 (34.6%) had poor or fair bowel preparation. The average cecal intubation time was 7.0 minutes (SD 5.4; range 1.22-36.9 minutes) and the average colonoscopy withdrawal time was 10.8 minutes (SD 6.9; range 6.0-107.0 minutes). Among all, 26.5% had colorectal neoplasia and 5.5% had advanced neoplasia. Older age (≥60 years; adjusted odds ratio [AOR] = 1.19-1.38, P = 0.02-0.04), male sex (AOR = 1.38, 95% confidence interval [CI] 1.19-1.60, P < 0.001), and current smoking (AOR = 1.41, 95% CI 1.14-1.75, P = 0.002) were significantly associated with poor/fair bowel preparation. Poorer cleansing resulted in significantly lower detection rate of neoplasia (AOR = 0.35-0.62) and advanced neoplasia (AOR = 0.36-0.50) irrespective of polyp size.Steps to improve proper procedures of bowel preparation are warranted, especially among subjects at risk of poor bowel preparation. Strategies should be implemented to improve bowel cleansing, which is now demonstrated as a definite quality indicator. PMID:26765402

  5. Prognostic impact and the relevance of PTEN copy number alterations in patients with advanced colorectal cancer (CRC) receiving bevacizumab.

    PubMed

    Price, Timothy J; Hardingham, Jennifer E; Lee, Chee K; Townsend, Amanda R; Wrin, Joseph W; Wilson, Kate; Weickhardt, Andrew; Simes, Robert J; Murone, Carmel; Tebbutt, Niall C

    2013-06-01

    Loss of phosphatase and tensin homologue (PTEN) expression may be prognostic in colorectal cancer (CRC) and may have a correlation with vascular endothelial growth factor (VEGF) expression via hypoxia-inducible factor 1 (HIF-1) alpha, and the PI3K/mTOR pathways. We therefore have explored the prognostic association of PTEN loss and the potential that PTEN loss may be predictive of outcome with bevacizumab. Patients enrolled in the AGITG MAX trial, a randomized Phase III trial of capecitabine (C) +/- bevacizumab (B) (+/- mitomycin C [M]) with available tissues were analyzed for PTEN expression (loss vs. no loss) as assessed using a Taqman® copy number assay (CNA). Of the original 471 patients enrolled, tissues from 302 (64.1%) patients were analyzed. PTEN loss was observed in 38.7% of patients. There was no relationship between PTEN loss and KRAS or BRAF mutation. PTEN status was not prognostic for progression-free survival (PFS) or overall survival (OS) in multivariate analyses adjusting for other baseline factors; loss versus no loss PFS hazard ratio (HR) 0.9 (0.7-1.16), OS HR 1.04 (0.79-1.38). PTEN was not prognostic when assessed by KRAS and BRAF status. By using the comparison of C versus CB+CBM, PTEN status was not significantly predictive of the effectiveness of B for PFS or OS. PTEN status was not prognostic for survival in advanced colorectal cancer, irrespective of KRAS or BRAF status. PTEN status did not significantly predict different benefit with bevacizumb therapy.

  6. Validity of APCS score as a risk prediction score for advanced colorectal neoplasia in Chinese asymptomatic subjects

    PubMed Central

    Li, Wenbin; Zhang, Lili; Hao, Jianyu; Wu, Yongdong; Lu, Di; Zhao, Haiying; Wang, Zhenjie; Xu, Tianming; Yang, Hong; Qian, Jiaming; Li, Jingnan

    2016-01-01

    Abstract The Asia-Pacific Colorectal Screening (APCS) score is a risk-stratification tool that helps predict the risk for advanced colorectal neoplasia (ACN) in asymptomatic Asian populations, but has not yet been assessed for its validity of use in Mainland China. The aim of the study was to assess the validity of APCS score in asymptomatic Chinese population, and to identify other risk factors associated with ACN. Asymptomatic subjects (N = 1010) who underwent colonoscopy screening between 2012 and 2014 in Beijing were enrolled. APCS scores based on questionnaires were used to stratify subjects into high, moderate, and average-risk tiers. Cochran–Armitage test for trend was used to assess the association between ACN and risk tiers. Univariate and multivariate logistic regression was performed with ACN as the outcome, adjusting for APCS score, body mass index, alcohol consumption, self-reported diabetes, and use of nonsteroidal anti-inflammatory drugs as independent variables. The average age was 53.5 (standard deviation 8.4) years. The prevalence of ACN was 4.1% overall, and in the high, moderate, and average-risk tiers, the prevalence was 8.8%, 2.83%, and 1.55%, respectively (P < 0.001). High-risk tier had 3.3 and 6.1-fold increased risk of ACN as compared with those in the moderate and average-risk tiers, respectively. In univariate analysis, high-risk tier, obesity, diabetes, and alcohol consumption were associated with ACN. In multivariate analysis, only high-risk tier was an independent predictor of ACN. The APCS score can effectively identify a subset of asymptomatic Chinese population at high risk for ACN. Further studies are required to identify other risk factors, and the acceptability of the score to the general population will need to be further examined. PMID:27741134

  7. Colonoscopy Reduces Risk of Death from Colorectal Cancer in High-Risk Patients

    Cancer.gov

    Long-term results from the National Polyp Study confirm that removing precancerous adenomas not only reduces the risk of colorectal cancer but also reduces the number of deaths from the disease by more than half.

  8. Prognostic evaluation of metallothionein expression in human colorectal neoplasms.

    PubMed Central

    Ioachim, E E; Goussia, A C; Agnantis, N J; Machera, M; Tsianos, E V; Kappas, A M

    1999-01-01

    AIM: To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression: expression of cathepsin D (CD), CD44, p53, Rb, bcl-2, c-erbB-2, epidermal growth factor receptor (EGFR), proliferation indices (Ki-67, proliferating cell nuclear antigen (PCNA)), and conventional clinicopathological variables. METHODS: The immunohistochemical expression of metallothionein was investigated in 23 cases of colorectal adenoma and 94 adenocarcinomas. Metallothionein expression was examined by the avidinbiotin peroxidase immunoperoxidase (ABC) using the monoclonal mouse antibody E9, on formalin fixed, paraffin embedded tissue. RESULTS: Positive metallothionein expression (> 5% of neoplastic cells) was observed in 30.4% of adenomas and 25.5% of adenocarcinomas, while 8.7% of adenomas and 14.9% carcinomas showed focal metallothionein positivity. In contrast, 60.9% of adenomas and 59.6% of carcinomas almost completely lacked metallothionein expression. In the series of adenocarcinomas, metallothionein expression was inversely correlated with CD44 in neoplastic cells (p = 0.01). There was no statistically significant difference of metallothionein expression, or the other variables examined, between adenocarcinomas and adenomas. CONCLUSIONS: Metallothionein expression does not seem to indicate aggressive biological behaviour in colorectal adenocarcinomas, in comparison with the other types of carcinoma. The inverse correlation with CD44 could suggest that the decreased metallothionein expression may contribute to the metastatic spread of the lymph node involvement in colorectal cancer. Metallothionein expression does not seem to represent an independent prognostic marker in colorectal cancer. Images PMID:10711249

  9. Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway: novel targeted therapies and advances in the treatment of colorectal cancer

    PubMed Central

    Yu, Ming

    2012-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the USA, and more effective treatment of CRC is therefore needed. Advances in our understanding of the molecular pathogenesis of this malignancy have led to the development of novel molecule-targeted therapies. Among the most recent classes of targeted therapies being developed are inhibitors targeting the phosphatidylinositol 3-kinase (PI3K) signaling pathway. As one of the most frequently deregulated pathways in several human cancers, including CRC, aberrant PI3K signaling plays an important role in the growth, survival, motility and metabolism of cancer cells. Targeting this pathway therefore has considerable potential to lead to novel and more effective treatments for CRC. Preclinical and early clinical studies have revealed the potential efficacy of drugs that target PI3K signaling for the treatment of CRC. However, a major challenge that remains is to study these agents in phase III clinical trials to see whether these early successes translate into better patient outcomes. In this review we focus on providing an up-to-date assessment of our current understanding of PI3K signaling biology and its deregulation in the molecular pathogenesis of CRC. Advances in available agents and challenges in targeting the PI3K signaling pathway in CRC treatment will be discussed and placed in the context of the currently available therapies for CRC. PMID:22973417

  10. Contemporary issues in the evaluation and management of pituitary adenomas.

    PubMed

    Pekic, S; Stojanovic, M; Popovic, V

    2015-12-01

    treatment modalities fail to completely control the disease and prevent the associated morbidity and mortality. This article reviews the advances in our understanding of pituitary adenoma, the guidance in evaluation and management of different subtypes of pituitary adenomas and the possibility of new therapeutic approaches.

  11. Computer Aided Diagnosis for Confocal Laser Endomicroscopy in Advanced Colorectal Adenocarcinoma

    PubMed Central

    Ştefănescu, Daniela; Streba, Costin; Cârţână, Elena Tatiana; Săftoiu, Adrian; Gruionu, Gabriel; Gruionu, Lucian Gheorghe

    2016-01-01

    Introduction Confocal laser endomicroscopy (CLE) is becoming a popular method for optical biopsy of digestive mucosa for both diagnostic and therapeutic procedures. Computer aided diagnosis of CLE images, using image processing and fractal analysis can be used to quantify the histological structures in the CLE generated images. The aim of this study is to develop an automatic diagnosis algorithm of colorectal cancer (CRC), based on fractal analysis and neural network modeling of the CLE-generated colon mucosa images. Materials and Methods We retrospectively analyzed a series of 1035 artifact-free endomicroscopy images, obtained during CLE examinations from normal mucosa (356 images) and tumor regions (679 images). The images were processed using a computer aided diagnosis (CAD) medical imaging system in order to obtain an automatic diagnosis. The CAD application includes image reading and processing functions, a module for fractal analysis, grey-level co-occurrence matrix (GLCM) computation module, and a feature identification module based on the Marching Squares and linear interpolation methods. A two-layer neural network was trained to automatically interpret the imaging data and diagnose the pathological samples based on the fractal dimension and the characteristic features of the biological tissues. Results Normal colon mucosa is characterized by regular polyhedral crypt structures whereas malignant colon mucosa is characterized by irregular and interrupted crypts, which can be diagnosed by CAD. For this purpose, seven geometric parameters were defined for each image: fractal dimension, lacunarity, contrast correlation, energy, homogeneity, and feature number. Of the seven parameters only contrast, homogeneity and feature number were significantly different between normal and cancer samples. Next, a two-layer feed forward neural network was used to train and automatically diagnose the malignant samples, based on the seven parameters tested. The neural network

  12. Pituitary adenoma: a radiotherapeutic perspective.

    PubMed

    Platta, Christopher S; Mackay, Christopher; Welsh, James S

    2010-08-01

    Pituitary adenomas comprise approximately 10% to 20% of all central nervous system neoplasms whereas autopsy series have suggested that the incidence of pituitary adenoma in the general population may approach 25%. Several treatment modalities are used in the treatment of pituitary adenomas, including observation, surgery, medical intervention, and radiotherapy. The treatment modality employed depends greatly on the type of pituitary adenoma and presenting symptoms. This review will discuss the biology of pituitary adenomas and the current management principles for the treatment of prolactinomas, Cushing disease, acromegaly, and nonsecretory adenomas, with an emphasis on the published radiotherapeutic literature.

  13. The Mendelian colorectal cancer syndromes

    PubMed Central

    2015-01-01

    A small minority of colorectal cancers (CRCs) (≤5%) are caused by a single, inherited faulty gene. These diseases, the Mendelian colorectal cancer (CRC) syndromes, have been central to our understanding of colorectal carcinogenesis in general. Most of the approximately 13 high-penetrance genes that predispose to CRC primarily predispose to colorectal polyps, and each gene is associated with a specific type of polyp, whether conventional adenomas (APC, MUTYH, POLE, POLD1, NTHL1), juvenile polyps (SMAD4, BMPR1A), Peutz-Jeghers hamartomas (LKB1/STK11) and mixed polyps of serrated and juvenile types (GREM1). Lynch syndrome (MSH2, MLH1, MSH6, PMS2), by contrast, is associated primarily with cancer risk. Major functional pathways are consistently inactivated in the Mendelian CRC syndromes: certain types of DNA repair (proofreading of DNA replication errors, mismatch repair and base excision repair) and signalling (bone morphogenetic protein (BMP), Wnt signalling and mTOR). The inheritance of the CRC syndromes also varies: most are dominant but some of the DNA repair deficiencies are recessive. Some of the Mendelian CRC genes are especially important because they play a role through somatic inactivation in sporadic CRC (APC, MLH1, SMAD4, POLE). Additional Mendelian CRC genes may remain to be discovered and searches for these genes are ongoing, especially in patients with multiple adenomas and hyperplastic polyps. PMID:26169059

  14. A phase II randomised trial of 5-fluorouracil with or without interferon alpha-2a in advanced colorectal cancer.

    PubMed Central

    Piga, A.; Cascinu, S.; Latini, L.; Marcellini, M.; Bavosi, M.; Acito, L.; Bascioni, R.; Giustini, L.; Francini, G.; Pancotti, A.; Rossi, G.; Del Papa, M.; Carle, F.; Cellerino, R.

    1996-01-01

    With the association of 5-fluorouracil (5-FU) and alpha-interferon (IFN), objective responses as high as 26 63% have been reported in untreated patients with advanced colorectal cancer. However, grade 3-4 toxicity has also been reported. We have conducted a prospective phase II randomised study comparing 5-FU to 5-FU + IFN, to investigate whether the addition of IFN to a weekly 5-FU regimen devoid of significant toxicity used at our institutions could improve the effectiveness of 5-FU while maintaining acceptable toxicity. Patients with histologically proven advanced colorectal carcinoma were randomised to receive 5-FU 500 mg m-2 intravenous (i.v.) bolus on days 1-5 followed by 5-FU 500 mg m-2 i.v. bolus weekly from day 15, with or without IFN alpha-2a intramuscularly (i.m.) 1.5 mU daily on days 6-12 and 3 mU i.m. daily thereafter. The treatment was administered on an outpatient basis. Response was evaluated every 3 months, and treatment continued until progression or after two consecutive judgements of stable disease. Response rate was the main end point of the study. Of 141 patients eligible, 72 were randomised to 5-FU alone (arm A) and 69 to 5-FU + IFN (arm B). Responses were 9/72 (12.5%) in arm A and 6/69 (8.7%) in arm B; complete responses were three in arm A and two in arm B. Progression-free survival (median 4 months) and survival (median 12 months) were identical in the two arms. Toxicity was almost absent in arm A and moderate in arm B, represented mainly by haematological toxicity (usually leucopenia). In conclusion, overall survival was good in both arms of treatment and toxicity was moderate. While the response rate with 5-FU alone was in accord with the literature data, response to 5-FU + IFN was lower than expected. At least at this dosage and schedule, the association of 5-FU and IFN is no better than 5-FU alone and is of no clinical interest. PMID:8826868

  15. Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization

    PubMed Central

    Passarelli, Michael N.; Newcomb, Polly A.; Makar, Karen W.; Burnett-Hartman, Andrea N.; Potter, John D.; Upton, Melissa P.; Zhu, Lee-Ching; Rosenfeld, Michael E.; Schwartz, Stephen M.; Rutter, Carolyn M.

    2015-01-01

    Purpose Studies linking cholesterol levels to the development of colorectal neoplasia are inconsistent, and Mendelian randomization has been suggested as a way to help avoid problems with confounding and reverse causation. Methods We genotyped individuals who received a colonoscopy at Group Health (1998–2007) for 96 of 102 single-nucleotide polymorphisms (SNPs) identified by the Global Lipids Genetics Consortium. Participants included 139 advanced adenoma cases, 518 non-advanced adenoma cases, 380 non-adenomatous polyp cases, and 754 polyp-free controls. All had at least one available pre-colonoscopy lipid measurement from electronic records maintained by Group Health. Results Advanced adenoma cases were more likely than controls to have higher pre-colonoscopy zenith low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) (odds ratio, OR, per 20 mg/dL LDL increase: 1.16, 95% confidence interval, CI, 1.03–1.30; per 40 mg/dL TG increase: 1.09, 1.03–1.16; and per 20 mg/dL TC increase: 1.09, 1.02–1.18). For these traits, genotype-polyp ORs using weighted allele scores were not statistically significant (OR per increase in score scaled to a 20 mg/dL LDL increase: 1.17, 0.78–1.75; a 40 mg/dL TG increase: 1.12, 0.91–1.38; a 20 mg/dL TC increase: 0.99, 0.71–1.38). Conclusions Cholesterol levels may be associated with advanced adenomas, but larger studies are warranted to determine whether this association can be attributed to genetics. PMID:25618792

  16. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. PMID:27127793

  17. Continuous infusion of 5-fluorouracil with alpha 2b interferon for advanced colorectal carcinoma.

    PubMed Central

    Ferguson, J. E.; Hulse, P.; Lorigan, P.; Jayson, G.; Scarffe, J. H.

    1995-01-01

    Thirty patients with symptomatic colorectal carcinoma were commenced on treatment with 5-fluorouracil (2.5 g week-1) administered by continuous intravenous infusion and alpha 2b interferon (3 x 10(6) U s.c. three times a week). Six out of 30 patients (20%) achieved a partial response. Three patients (10%) had stable disease and 21 patients (70%) progressed on treatment. Twenty patients (67%) completed ten or more weeks of treatment. In nine patients, treatment was withdrawn after 2-9 weeks because of disease progression or death. One patient's treatment was interrupted by emergency surgery. The median survival for all patients was 210 days (7 months). The principal side-effects were oral mucositis (12/30 patients), nausea (8/30 patients) and transient diarrhoea (4/30 patients), and initial constitutional symptoms due to alpha 2b interferon. The combination of low-dose continuous infusional 5-fluorouracil and low-dose alpha 2b interferon is well tolerated but has no obvious advantage over alternative infusional regimens using 5-fluorouracil as a single agent. PMID:7599051

  18. Colorectal tumors: the histology report.

    PubMed

    Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

    2011-03-01

    Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed.

  19. PIK3CA Amplification Is Common in Left Side-Tubular Adenomas but Uncommon Sessile Serrated Adenomas Exclusively with KRAS Mutation

    PubMed Central

    Lee, Hyunsu; Lee, Jae-Ho; Kim, Dae-Kwang; Choi, In-Jang; Hwang, Ilseon; Kang, Yu-Na; Kim, Shin

    2015-01-01

    Colorectal cancer is a heterogeneous disorder than arises via multiple distinct pathways, from tubular adenomas (TAs) and sessile serrated adenomas (SSAs), which are clinically, morphologically, and molecularly different. We examined PIK3CA amplification in colorectal precancerous legions, including TAs and SSAs. DNA was isolated from paired normal and tumoral tissues in 64 TAs and 32 SSAs. PIK3CA amplification, KRAS mutation, and BRAF mutation were analyzed by real-time PCR and pyrosequencing. PIK3CA amplification was found in 25% of TAs and 9.4% of SSAs, respectively. KRAS and BRAF mutations were mutually exclusive in both TAs and SSAs. In TAs, PIK3CA amplification was associated with left side and it was mutually exclusive with KRAS mutation. These results suggest that PIK3CA amplification may be early and important event in colorectal carcinogenesis and may drive the development of left-side TAs independently with KRAS mutation. PMID:26019684

  20. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

    PubMed Central

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  1. Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.

    PubMed

    Beckers, Albert; Aaltonen, Lauri A; Daly, Adrian F; Karhu, Auli

    2013-04-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  2. A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer.

    PubMed Central

    Gulliford, T.; English, J.; Colston, K. W.; Menday, P.; Moller, S.; Coombes, R. C.

    1998-01-01

    Preclinical studies have shown that the vitamin D analogue EB 1089 has significantly less calcaemic activity than its parent compound 1,25-dihydroxyvitamin D (1,25(OH)2D3) and significant anti-tumour activity. This phase I trial was designed to evaluate the calcaemic effect of the drug in patients with advanced cancer. EB 1089 was given to 36 patients with advanced breast and colorectal cancer in doses of between 0.15 and 17.0 microg m(-2) day(-1). Serial serum and urine calcium, urine creatinine and serum parathyroid hormone (PTH) were monitored. Hypercalcaemia was seen in all patients receiving 17.0 microg m(-2) day(-1). Hypercalcaemia attributable to EB 1089 was reversible by discontinuing or reducing EB 1089 therapy. During the first 5 days of treatment, urine calcium (P = 0.0001) and serum-corrected calcium (P = 0.027) were related to EB 1089 dose, whereas serum parathyroid hormone (P = 0.0001) showed an inverse relationship. Twenty-one patients received compassionate treatment for between 10 and 234 days. No complete or partial responses were seen. Six patients on treatment for more than 90 days showed stabilization of disease. EB 1089 was well tolerated and adverse events considered to be caused by EB 1089 were limited to dose-dependent effects on calcium metabolism. The dose estimated to be tolerable for most patients from this study is around 7 microg m(-2) day(1). These data support previous work that has demonstrated EB 1089 to be significantly less calcaemic than 1,25-dihydroxyvitamin D3. PMID:9662243

  3. Pregnancy and pituitary adenomas.

    PubMed

    Glezer, Andrea; Jallad, Raquel S; Machado, Marcio C; Fragoso, Maria C; Bronstein, Marcello D

    2016-09-01

    Infertility is frequent in patients harboring pituitary adenomas. The mechanisms involved include hypogonadism secondary to hormonal hypersecretion (prolactin, growth hormone and cortisol), stalk disconnection and pituitary damage. With the improvement of clinical and surgical treatment, pregnancy in women harboring pituitary adenomas turned into a reality. Pituitary hormonal hyper- and hyposecretion influences pregnancy outcomes, as well as pregnancy can interfere on pituitary tumors, especially in prolactinomas. We review literature about specific follow-up and management in pregnant women harboring prolactinomas, acromegaly, or Cushings disease and the impact of clinical and surgical treatment on each condition. PMID:26977888

  4. Biology of colorectal cancer

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2015-01-01

    Colorectal cancer is a serious health problem, a challenge for research, and a model for studying the molecular mechanisms involved in its development. According to its incidence, this pathology manifests itself in three forms: family, hereditary, and most commonly sporadic, apparently not associated with any hereditary or familial factor. For the types having inheritance patterns and a family predisposition, the tumours develop through defined stages ranging from adenomatous lesions to the manifestation of a malignant tumour. It has been established that environmental and hereditary factors contribute to the development of colorectal cancer, as indicated by the accumulation of mutations in oncogenes, genes which suppress and repair DNA, signaling the existence of various pathways through which the appearance of tumours may occur. In the case of the suppressive and mutating tracks, these are characterised by genetic disorders related to the phenotypical changes of the morphological progression sequence in the adenoma/carcinoma. Moreover, alternate pathways through mutation in BRAF and KRAS genes are associated with the progression of polyps to cancer. This review surveys the research done at the cellular and molecular level aimed at finding specific alternative therapeutic targets for fighting colorectal cancer. PMID:25932044

  5. Computational Identification of Novel Stage-Specific Biomarkers in Colorectal Cancer Progression

    PubMed Central

    Palaniappan, Ashok; Ramar, Karthick; Ramalingam, Satish

    2016-01-01

    It is well-known that the conversion of normal colon epithelium to adenoma and then to carcinoma stems from acquired molecular changes in the genome. The genetic basis of colorectal cancer has been elucidated to a certain extent, and much remains to be known about the identity of specific cancer genes that are associated with the advancement of colorectal cancer from one stage to the next. Here in this study we attempted to identify novel cancer genes that could underlie the stage-specific progression and metastasis of colorectal cancer. We conducted a stage-based meta-analysis of the voluminous tumor genome-sequencing data and mined using multiple approaches for novel genes driving the progression to stage-II, stage-III and stage-IV colorectal cancer. The consensus of these driver genes seeded the construction of stage-specific networks, which were then analyzed for the centrality of genes, clustering of subnetworks, and enrichment of gene-ontology processes. Our study identified three novel driver genes as hubs for stage-II progression: DYNC1H1, GRIN2A, GRM1. Four novel driver genes were identified as hubs for stage-III progression: IGF1R, CPS1, SPTA1, DSP. Three novel driver genes were identified as hubs for stage-IV progression: GSK3B, GGT1, EIF2B5. We also identified several non-driver genes that appeared to underscore the progression of colorectal cancer. Our study yielded potential diagnostic biomarkers for colorectal cancer as well as novel stage-specific drug targets for rational intervention. Our methodology is extendable to the analysis of other types of cancer to fill the gaps in our knowledge. PMID:27243824

  6. Plasma miR-601 and miR-760 Are Novel Biomarkers for the Early Detection of Colorectal Cancer

    PubMed Central

    Wang, Qifeng; Huang, Zhaohui; Ni, Shujuan; Xiao, Xiuying; Xu, Qinghua; Wang, Lisha; Huang, Dan; Tan, Cong; Sheng, Weiqi; Du, Xiang

    2012-01-01

    Background Colorectal cancer (CRC) is a major cause of death worldwide. Sensitive, non-invasive diagnostic screen methods are urgently needed to improve its survival rates. Stable circulating microRNA offers unique opportunities for the early diagnosis of several diseases, including cancers. Our aim has been to find new plasma miRNAs that can be used as biomarkers for the detection of CRC. Methodology/Principal Findings According to the results of miRNA profiling performed on pooling plasma samples form 10 CRC patients or 10 healthy controls, a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188-3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa-let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large scale validation by qRT-PCR performed on another 191 independent individuals (90 CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels of plasma miR-601 and miR-760 were significantly decreased in colorectal neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC curve analysis showed that plasma miR-601 and miR-760 were of significant diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1% specificity in discriminating advanced adenomas from normal controls. Conclusions/Significance Plasma miR-601 and miR-760 can potentially serve as promising non-invasive biomarkers for the early detection of CRC. PMID:22970209

  7. Colon tumors with the simultaneous induction of driver mutations in APC, KRAS, and PIK3CA still progress through the adenoma-to-carcinoma sequence

    PubMed Central

    Hadac, Jamie N.; Leystra, Alyssa A.; Olson, Terrah J. Paul; Maher, Molly E.; Payne, Susan N; Yueh, Alexander E.; Schwartz, Alexander R.; Albrecht, Dawn M.; Clipson, Linda; Pasch, Cheri A.; Matkowskyj, Kristina A.; Halberg, Richard B.; Deming, Dustin A.

    2015-01-01

    Human colorectal cancers often possess multiple mutations, including 3–6 driver mutations per tumor. The timing of when these mutations occur during tumor development and progression continues to be debated. More advanced lesions carry a greater number of driver mutations, indicating that colon tumors might progress from adenomas to carcinomas through the stepwise accumulation of mutations following tumor initiation. However, mutations that have been implicated in tumor progression have been identified in normal-appearing epithelial cells of the colon, leaving the possibility that these mutations might be present prior to the initiation of tumorigenesis. We utilized mouse models of colon cancer to investigate whether tumorigenesis still occurs through the adenoma-to-carcinoma sequence when multiple mutations are present at the time of tumor initiation. To create a model in which tumors could concomitantly possess mutations in Apc, Kras, and Pik3ca, we developed a novel minimally invasive technique to administer an adenovirus expressing Cre recombinase to a focal region of the colon. Here we demonstrate that the presence of these additional driver mutations at the time of tumor initiation results in increased tumor multiplicity and an increased rate of progression to invasive adenocarcinomas. These cancers can even metastasize to retroperitoneal lymph nodes or the liver. However, despite having as many as three concomitant driver mutations at the time of initiation, these tumors still proceed through the adenoma-to-carcinoma sequence. PMID:26276752

  8. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma.

    PubMed

    Twelves, C; Boyer, M; Findlay, M; Cassidy, J; Weitzel, C; Barker, C; Osterwalder, B; Jamieson, C; Hieke, K

    2001-03-01

    Standard therapy for advanced or metastatic colorectal cancer consists of 5-fluorouracil plus leucovorin (5-FU/LV) administered intravenously (i.v.). Capecitabine (Xeloda), an oral fluoropyrimidine carbamate which is preferentially activated by thymidine phosphorylase in tumour cells, mimics continuous 5-FU and is a recently developed alternative to i.v. 5-FU/LV. The choice of oral rather than intravenous treatment may affect medical resource use because the two regimens do not require the same intensity of medical intervention for drug administration, and have different toxicity profiles. Here we examine medical resource use in the first-line treatment of colorectal cancer patients with capecitabine compared with those receiving the Mayo Clinic regimen of 5-FU/LV. In a prospective, randomised phase III clinical trial, 602 patients with advanced or metastatic colorectal cancer recruited from 59 centres worldwide were randomised to treatment with either capecitabine or the Mayo regimen of 5-FU/LV. In addition to clinical efficacy and safety endpoints, data were collected on hospital visits required for drug administration, hospital admissions, and drugs and unscheduled consultations with physicians required for the treatment of adverse events. Capecitabine treatment in comparison to 5-FU/LV in advanced colorectal carcinoma resulted in superior response rates (26.6% versus 17.9%, P=0.013) and improved safety including less stomatitis and myelosuppression. Capecitabine patients required substantially fewer hospital visits for drug administration than 5-FU/LV patients. Medical resource use analysis showed that patients treated with capecitabine spent fewer days in hospital for the management of treatment related adverse events than did patients treated with 5-FU/LV. In addition, capecitabine reduced the requirement for expensive drugs, in particular antimicrobials fluconazole and 5-HT3-antagonists to manage adverse events. As anticipated with an oral home-based therapy

  9. Chemoprevention of colorectal cancer.

    PubMed

    Lang, Michaela; Gasche, Christoph

    2015-01-01

    Colorectal cancer has become one of the most prevalent malignant diseases for both men and women. Patients with inflammatory bowel diseases or certain inherited cancer syndromes are at high risk of developing colorectal cancer and have naturally the highest need for cancer prevention. In familial adenomatous polyposis (FAP) and Lynch syndrome, most of the underlying germline mutations can be detected by DNA sequencing, and medical counselling of affected individuals involves both surveillance tests and chemopreventive measures. However, as the mechanisms leading to colorectal cancer differ in these high-risk groups, the molecular action of chemopreventive drugs needs to be adjusted to the certain pathway of carcinogenesis. In the last decades, a number of drugs have been tested, including sulindac, aspirin, celecoxib, and mesalazine, but some of them are still controversially discussed. This review summarizes the advances and current standards of colorectal cancer prevention in patients with inflammatory bowel disease, FAP and Lynch syndrome. PMID:25531498

  10. Colorectal Cancer

    MedlinePlus

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  11. First-line cetuximab-based chemotherapies for patients with advanced or metastatic KRAS wild-type colorectal cancer

    PubMed Central

    Uemura, Mamoru; Kim, Ho Min; Hata, Tsuyoshi; Sakata, Kazuya; Okuyama, Masaki; Takemoto, Hiroyoshi; Fujii, Hitoshi; Fukuzaki, Takayuki; Morita, Tetsushi; Hata, Taishi; Takemasa, Ichiro; Satoh, Taroh; Mizushima, Tsunekazu; Doki, Yuichiro; Mori, Maski

    2016-01-01

    Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. A burgeoning number of studies have demonstrated that the addition of cetuximab to another standard first-line regimen markedly improves the outcome of CRC treatment. However, at present, the efficacy and safety of cetuximab-based combination chemotherapy has not been well described in Japan. The aim of the present study was to evaluate the efficacy and safety of first-line chemotherapies that included cetuximab for patients with advanced or metastatic Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type CRC in Japan. This prospective multicenter observational study was conducted at 13 affiliated medical institutions. A total of 64 patients were enrolled between 2010 and 2013. The patients met the following criteria for eligibility: i) histologically confirmed, advanced or metastatic KRAS wild-type CRC; and ii) cetuximab-based chemotherapies administered as a first-line treatment. First-line cetuximab-based treatments were administered as follows: 29 patients (45.3%) received a combination of infusional fluorouracil, leucovorin and oxaliplatin; 14 patients (21.9%) received a combination of capecitabine and oxaliplatin; and 10 patients (15.6%) received a combination of infusional fluorouracil, leucovorin and irinotecan. The overall response rate (including complete plus partial responses) was 50% (32/64 patients). Initially, 48 lesions were diagnosed as unresectable. Among those, 13 lesions (27.1%) were converted to a resectable status following cetuximab-based combination chemotherapy treatments. The median overall survival time and the progression-free survival time were 1,189 and 359 days, respectively. The most frequent grade 3/4 adverse event was neutropenia, which occurred in 20.3% of the patients. The incidence of grade 3/4 skin toxicity was 17.2% (11/64 patients). Cetuximab-based therapies may represent a promising first-line regimen for patients with advanced or

  12. Paediatric pituitary adenomas: a decade of change.

    PubMed

    Guaraldi, Federica; Storr, Helen L; Ghizzoni, Lucia; Ghigo, Ezio; Savage, Martin O

    2014-01-01

    Pituitary adenomas, although rare in the paediatric age range and mostly benign, represent very challenging disorders for diagnosis and management. The recent identification of genetic alterations in young individuals with pituitary adenomas has broadened the scope of molecular investigations and contributed to the understanding of mechanisms of tumorigenesis. Recent identification of causative mutations of genes such as GNAS, PRKAR1A, MEN1 and AIP has introduced the concept of molecular screening of young apparently healthy family members. Population-based studies have reported a significantly higher number of affected subjects and genetic variations than expected. Radiological techniques have advanced, yet many microadenomas remain undetectable on scanning. However, experience with transsphenoidal and endoscopic pituitary surgery has led to higher rates of cure. Prolactinomas, corticotroph and somatotroph adenomas remain the most prevalent, with each diagnosis presenting its own challenges. As paediatric pituitary adenomas occur very infrequently within the paediatric age range, paediatric endocrine units cannot provide expert management in isolation. Consequently, close co-operation with adult endocrinology colleagues with experience of pituitary disease is strongly recommended. PMID:24525527

  13. Seeing better - Evidence based recommendations on optimizing colonoscopy adenoma detection rate

    PubMed Central

    Aranda-Hernández, Javier; Hwang, Jason; Kandel, Gabor

    2016-01-01

    Colorectal cancer is one of the three most frequent causes of cancer deaths in men and women in Europe and North America. Diagnosis and resection of adenomas has convincingly demonstrated its utility in diminishing colorectal cancer incidence. Therefore, colonoscopy is now the gold standard for colorectal cancer screening. But it is also known that colonoscopy effectiveness varies among endoscopists. Among different quality indicators, the most used is the adenoma detection rate (ADR) which is the percentage of average-risk patients for colorectal cancer who are found to have at least one adenoma or adenocarcinoma during a screening colonoscopy. There is compelling evidence supporting an inverse correlation between ADR and interval colorectal cancer (cancer found after a screening colonoscopy). Many factors such as quality of precolonoscopy preparation, additional observers, manoeuvres with the endoscope (second view, retroflexion, water inflation rather than air), time spent during withdrawal, changes in patient position, fold-flattener devices, new imaging or endoscopic modalities and use of intravenous or through the scope sprayed drugs, have been studied and developed with the aim of increasing the ADR. This reviews discusses these factors, and the current evidence, to “see better” in the colon and optimize ADR. PMID:26855536

  14. The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants

    PubMed Central

    Wong, Martin C. S.; Ching, Jessica Y. L.; Ng, Simpson; Lam, Thomas Y. T.; Luk, Arthur K. C.; Wong, Sunny H.; Ng, Siew C.; Ng, Simon S. M.; Wu, Justin C. Y.; Chan, Francis K. L.; Sung, Joseph J. Y.

    2016-01-01

    We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50–70 years in a colonoscopy screening programme(2008–2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56–0.65, with sensitivities ranging from 0.04–0.44 and specificities from 0.74–0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58–0.72). The NNS (12–19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed. PMID:26838178

  15. Composite Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorder and Tubular Adenoma in a Rectal Polyp.

    PubMed

    Lo, Amy A; Gao, Juehua; Rao, M Sambasivia; Yang, Guang-Yu

    2016-02-01

    Composite tumors are formed when there is intermingling between two components of separate tumors seen histologically. Cases demonstrating composite tubular adenoma with other types of tumors in the colon are rare. Composite tubular adenomas with nonlymphoid tumors including carcinoids, microcarcinoids, and small cell undifferentiated carcinoma have been reported in the literature. The occurrence of composite lymphoma and tubular adenoma within the colorectal tract is extremely rare. Only three cases have been reported and include one case of mantle cell lymphoma and two cases of diffuse large B-cell lymphoma arising in composite tubular adenomas. We present the first case of composite Epstein-Barr virus-associated B-cell lymphoproliferative disorder and tubular adenoma in a rectal polyp with a benign endoscopic appearance.

  16. Giant intrathyroidal parathyroid adenoma

    PubMed Central

    Vilallonga, Ramon; Zafón, Carlos; Migone, Raul; Baena, Juan Antonio

    2012-01-01

    Primary hyperparathyroidism (PHPT) is not an uncommon endocrine disorder. However, acute primary hyperparathyroidism, or parathyroid crisis (PC), is a rare clinical entity characterized by life-threatening hypercalcemia of a sudden onset in patients with PHPT. We describe a patient with PC who presented with acute worsening of depressive symptoms, nausea and vomiting, and required emergency surgery. Serum calcium, alkaline phosphatase, and parathyroid hormone were elevated and serum phosphorus was low. An emergency hemithyroidectomy was performed because of none medical control of hypercalcemia. A giant intrathyroidal parathyroid adenoma was diagnosed. PHTP can be a life-threatening situation for patients, requiring immediate surgical treatment. A giant intrathyroidal parathyroid adenoma is an uncommon cause of PC. PMID:22787355

  17. Tubuloalveolar adenoma of salivary gland.

    PubMed

    Pulitzer, D R; Reed, R J; Megehee, J A

    1985-06-01

    An unusual monomorphic salivary gland adenoma, occurring in a 57-year-old woman, is described. The lesion was histologically similar to the so-called tubular adenoma; however, occasional microscopic foci of serous (acinar cell) differentiation were present. The term tubuloalveolar adenoma is proposed to describe salivary gland tumors that are histologically benign and composed of cells resembling those of normal intercalated ducts and secretory units (acini).

  18. Defined morphological criteria allow reliable diagnosis of colorectal serrated polyps and predict polyp genetics.

    PubMed

    Rau, Tilman T; Agaimy, Abbas; Gehoff, Anastasia; Geppert, Carol; Jung, Klaus; Knobloch, Katharina; Langner, Cord; Lugli, Alessandro; Groenbus-Lurkin, Irene; Nagtegaal, Iris D; Rüschoff, Josef; Saegert, Xavier; Sarbia, Mario; Schneider-Stock, Regine; Vieth, Michael; Zwarthoff, Ellen C; Hartmann, Arndt

    2014-06-01

    Criteria for the diagnosis of serrated colorectal lesions (hyperplastic polyp, sessile serrated adenoma without or with dysplasia--which we called mixed polyp--and traditional serrated adenoma) for which consensus has been reached should be validated for applicability in daily practice in terms of inter-observer reproducibility and their association with clinical features and (epi)genetic events. A study set was created from a consecutive series of colorectal polyps (n = 1,926) by selecting all sessile serrated adenomas, traditional serrated adenomas and mixed polyps. We added consecutive series of hyperplastic polyps, classical adenomas and normal mucosa samples for a total of 200 specimens. With this series, we conducted an inter-observer study, encompassing ten pathologists with gastrointestinal pathology experience from five European countries, in three rounds in which all cases were microscopically evaluated. An assessment of single morphological criteria was included, and these were correlated with clinical parameters and the mutation status of KRAS, BRAF and PIK3CA and the methylation status of MLH1. Gender, age and localisation were significantly associated with certain types of lesions. Kappa statistics revealed moderate to good inter-observer agreement for polyp classification (κ = 0.56 to 0.63), but for single criteria, this varied considerably (κ = 0.06 to 0.82). BRAF mutations were frequently found in hyperplastic polyps (86 %, 62/72) and sessile serrated adenomas (80 %, 41/51). KRAS mutations occurred more frequently in traditional serrated adenomas (78 %, 7/9) and less so in classical adenomas (20 %, 10/51). Single morphological criteria for sessile serrated adenomas showed significant correlation with BRAF mutation (all p ≤ 0.001), and those for classical adenomas or traditional serrated adenoma correlated significantly with KRAS mutation (all p < 0.001). Therefore, single well-defined morphological criteria are predictive for

  19. A Phase I Trial to Evaluate Antibody-Dependent Cellular Cytotoxicity of Cetuximab and Lenalidomide in Advanced Colorectal and Head and Neck Cancer.

    PubMed

    Bertino, Erin M; McMichael, Elizabeth L; Mo, Xiaokui; Trikha, Prashant; Davis, Melanie; Paul, Bonnie; Grever, Michael; Carson, William E; Otterson, Gregory A

    2016-09-01

    mAbs can induce antibody-dependent cellular cytotoxicity (ADCC) via the innate immune system's ability to recognize mAb-coated cancer cells and activate immune effector cells. Lenalidomide is an immunomodulatory agent with the capacity to stimulate immune cell cytokine production and ADCC activity. This phase I trial evaluated the combination of cetuximab with lenalidomide for the treatment of advanced colorectal and head and neck squamous cell cancers (HNSCC). This trial included patients with advanced colorectal cancer or HNSCC. Treatment consisted of cetuximab 500 mg/m(2) i.v. every two weeks with lenalidomide given orally days 1-21 on a 28-day cycle. Three dose levels of lenalidomide were evaluated (15, 20, 25 mg). Correlative studies included measurement of ADCC, FcγRIIIA polymorphism genotyping, measurement of serum cytokine levels, and flow cytometric analysis of immune cell subtypes. Twenty-two patients were enrolled (19 colorectal cancer, 3 HNSCC). Fatigue was the only dose-limiting toxicity. One partial response was observed and 8 patients had stable disease at least 12 weeks. The recommended phase II dose is cetuximab 500 mg/m(2) with lenalidomide 25 mg daily, days 1-21. Correlative studies demonstrated a dose-dependent increase in natural killer cytotoxic activity with increasing doses of lenalidomide. Cetuximab and lenalidomide were well tolerated. There was a lenalidomide dose-dependent increase in ADCC with higher activity in patients enrolled in cohort 3 than those enrolled in cohorts 1/2. Although response was not a primary endpoint, there was evidence of antitumor activity for the combination therapy. Further investigation of lenalidomide as an immunomodulator in solid tumors is warranted. Mol Cancer Ther; 15(9); 2244-50. ©2016 AACR. PMID:27458141

  20. Pleomorphic adenoma of the palate.

    PubMed

    Erdem, Mehmet Ali; Cankaya, Abdulkadir Burak; Güven, Gülşah; Olgaç, Vakur; Kasapoğlu, Cetin

    2011-05-01

    Pleomorphic adenoma is the most common mixed benign tumor of major salivary glands. Approximately 80% of these tumors arise in the parotid gland, whereas 7% arise in the minor salivary glands. The most common sites for minor salivary gland where pleomorphic adenoma arises are the palates followed by lips and cheek. We report a palate mass in a 46-year-old male patient. The initial cytologic diagnosis by fine-needle aspiration biopsy was pleomorphic adenoma. This report describes a case of pleomorphic adenoma regarding all distinctive diagnoses with the review of the literature.

  1. Canalicular adenoma of the palate.

    PubMed

    Yüce, Salim; Uysal, Ismail Önder; Doğan, Mansur; Ersin, Tuncer; Müderris, Suphi

    2012-09-01

    Canalicular adenomas are uncommon, benign epithelial neoplasm of the salivary glands that usually involve the upper lip and the buccal mucosa of elderly people. Differential diagnosis of the canalicular adenoma versus adenocarcinoma is important because it may result in unjustified radiotherapy or extensive and aggressive surgery. Despite the benign nature of canalicular adenomas, complete surgical removal and a regular clinical follow-up are recommended. The current study describes the diagnostic procedures, surgical management, and follow-up of a canalicular adenoma involving the palate of a 79-year-old man.

  2. Disparities of conjugating protective enzyme activities in the colon of patients with adenomas and carcinomas

    PubMed Central

    Hoensch, Harald P; Roelofs, Hennie MJ; Edler, Lutz; Kirch, Wilhelm; Peters, Wilbert HM

    2013-01-01

    AIM: To investigate the metabolic enzymatic capacity of the colon mucosa to detoxify noxious carcinogenic compounds. METHODS: We investigated the activity of 2 conjugating enzymes-the microsomal uridine glucuronosyltransferase (UGT) and the cytosomal glutathione S-transferase (GST) in the uninvolved mucosa of the colon transversum and sigmoideum in patients with adenomatous polyps and colorectal cancer. Biopsies were taken from the mucosa during colonoscopies which were done for clinical (diagnostic) reasons. After storage, the biopsy material was homogenized and after differential centrifugation the enzyme assays were performed with 4-nitrophenol (UGT) and 1-chloro 2,4-dinitrobenzene (GST) as substrates. RESULTS: About 48 patients were included of which 28 had adenomas and 20 had colorectal carcinomas confirmed by histopathology. Enzyme activities were expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute protein for the UGT. Analysis of variance (F-test) indicated that both enzymes were more widely distributed in adenoma than in cancer patients. The means ± SD were smaller for cancer patients: GST for adenomas 268 ± 152 vs 241 ± 69 for carcinomas and UGT for adenomas 197 ± 200 vs 150 ± 86 for carcinomas. CONCLUSION: Compared to patients with adenomatous colon polyps those with colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism and their activities clustered over a smaller range. PMID:24106402

  3. Gut mucosal microbiome across stages of colorectal carcinogenesis

    PubMed Central

    Nakatsu, Geicho; Li, Xiangchun; Zhou, Haokui; Sheng, Jianqiu; Wong, Sunny Hei; Wu, William Ka Kai; Ng, Siew Chien; Tsoi, Ho; Dong, Yujuan; Zhang, Ning; He, Yuqi; Kang, Qian; Cao, Lei; Wang, Kunning; Zhang, Jingwan; Liang, Qiaoyi; Yu, Jun; Sung, Joseph J. Y.

    2015-01-01

    Gut microbial dysbiosis contributes to the development of colorectal cancer (CRC). Here we catalogue the microbial communities in human gut mucosae at different stages of colorectal tumorigenesis. We analyse the gut mucosal microbiome of 47 paired samples of adenoma and adenoma-adjacent mucosae, 52 paired samples of carcinoma and carcinoma-adjacent mucosae and 61 healthy controls. Probabilistic partitioning of relative abundance profiles reveals that a metacommunity predominated by members of the oral microbiome is primarily associated with CRC. Analysis of paired samples shows differences in community configurations between lesions and the adjacent mucosae. Correlations of bacterial taxa indicate early signs of dysbiosis in adenoma, and co-exclusive relationships are subsequently more common in cancer. We validate these alterations in CRC-associated microbiome by comparison with two previously published data sets. Our results suggest that a taxonomically defined microbial consortium is implicated in the development of CRC. PMID:26515465

  4. Differential expression of a new tumor-associated antigen, TLP, during human colorectal cancer tumorigenesis.

    PubMed

    Guadagni, F; Graziano, P; Roselli, M; Mariotti, S; Bernard, P; Sinibaldi-Vallebona, P; Rasi, G; Garaci, E

    1999-04-01

    Tumour liberated particles (TLP) have been proposed as a potential new serum tumor marker. In particular, a high percentage of patients with early stages of lung cancer scored positive for serum TLP, suggesting its possible role as a marker for early diagnosis of disease. The aim of the present study was to analyze the expression of TLP in the colorectal adenoma-carcinoma sequence in order to determine whether its expression correlates with the various stages of cancer transformation. TLP distribution was assessed by immunohistochemistry in normal, premalignant, and malignant colorectal lesions. Normal colonic mucosa and hyperplastic polyps showed no positive staining, whereas adenomas and adenocarcinomas reacted to anti-TLP serum. The percentage of positive tumor cells increased from adenomas with mild dysplasia to adenomas with severe dysplasia. Moreover, a supranuclear staining pattern was observed mainly in adenomas with mild dysplasia, whereas adenomas with severe dysplasia as well as adenocarcinomas showed a characteristic diffuse staining pattern and a strong staining intensity. Only a few cases of adenocarcinoma were found to be TLP-negative and all were poorly differentiated. Our results suggest that TLP antigen expression may be considered as a marker of epithelial atypia in the colorectal tract and as a potential target for new diagnostic and/or therapeutic approaches to human colorectal cancer.

  5. Habitual intake of flavonoid subclasses and risk of colorectal cancer in 2 large prospective cohorts12

    PubMed Central

    Nimptsch, Katharina; Zhang, Xuehong; Cassidy, Aedín; Song, Mingyang; O’Reilly, Éilis J; Lin, Jennifer H; Pischon, Tobias; Rimm, Eric B; Willett, Walter C; Fuchs, Charles S; Ogino, Shuji; Chan, Andrew T; Giovannucci, Edward L; Wu, Kana

    2016-01-01

    Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a secondary analysis of a randomized controlled trial, the Polyp Prevention Trial, a higher intake of one subclass, flavonols, was statistically significantly associated with a reduced risk of recurrent advanced adenoma. Most previous prospective studies on colorectal cancer evaluated only a limited number of flavonoid subclasses and intake ranges, yielding inconsistent results. Objective: In this study, we examined whether higher habitual dietary intakes of flavonoid subclasses (flavonols, flavones, flavanones, flavan-3-ols, and anthocyanins) were associated with a lower risk of colorectal cancer. Design: Using data from validated food-frequency questionnaires administered every 4 y and an updated flavonoid food composition database, we calculated flavonoid intakes for 42,478 male participants from the Health Professionals Follow-Up Study and for 76,364 female participants from the Nurses’ Health Study. Results: During up to 26 y of follow-up, 2519 colorectal cancer cases (1061 in men, 1458 in women) were documented. Intakes of flavonoid subclasses were not associated with risk of colorectal cancer in either cohort. Pooled multivariable adjusted RRs (95% CIs) comparing the highest with the lowest quintiles were 1.04 (0.91, 1.18) for flavonols, 1.01 (0.89, 1.15) for flavones, 0.96 (0.84, 1.10) for flavanones, 1.07 (0.95, 1.21) for flavan-3-ols, and 0.98 (0.81, 1.19) for anthocyanins (all P values for heterogeneity by sex >0.19). In subsite analyses, flavonoid intake was also not associated with colon or rectal cancer risk. Conclusion: Our findings do not support the hypothesis that a higher habitual intake of any flavonoid subclass decreases the risk of colorectal cancer. PMID:26537935

  6. Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum.

    PubMed

    Cui, Guanglin; Goll, Rasmus; Olsen, Trine; Steigen, Sonja Eriksson; Husebekk, Anne; Vonen, Barthold; Florholmen, Jon

    2007-07-01

    Cytokines have been suggested to be key factors in modulating immune response against tumorigenesis in the microenvironment. Therefore, characterization of cytokine expression along the colorectal adenoma-carcinoma sequence may add important information for understanding the immune-related mechanisms of the development of colorectal carcinoma (CRC). In this study, biopsies from 32 patients with colorectal adenoma (CRA), 20 patients with CRC and 18 healthy controls were examined. Cytokine gene expressions of interleukin-4 (IL-4), IL-10, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and its upstream inducers (IL-12A and IL-18) were measured at messenger RNA (mRNA) level with quantitative real-time PCR (Q-PCR). Cytokine expressing cells were characterized using immunohistochemistry (IHC). A distinct different cytokine profile between adenoma and CRC was observed: the Th1 cytokines (IFN-gamma, TNF-alpha, IL-12A and IL-18) were increased in local tissues of CRA and decreased in CRC. Consistent with the quantitative cytokine data, IHC examinations revealed slightly increased densities of Th1 cytokine-expressing cells in CRA and a remarkably decreased density of the Th1 cells in CRC. In CRA, the cytokine-expressing cells were highly polarized to the subepithelial stroma while the cells were evenly distributed through the stroma in CRC. In conclusion, distinct changes in the Th1 cytokine profile appear along the colorectal adenoma-carcinoma sequence. This may reflect a change in the host immune regulatory function in the adenoma-carcinoma sequence. PMID:17160410

  7. Subclinical hyperfunctioning pituitary adenomas: The silent tumors

    PubMed Central

    Cooper, Odelia; Melmed, Shlomo

    2012-01-01

    Pituitary adenomas are classified by function as defined by clinical symptoms and signs of hormone hypersecretion with subsequent confirmation on immunohistochemical staining. However, positive immunostaining for pituitary cell types has been shown for clinically nonfunctioning adenomas, and this entity is classified as silent functioning adenoma. Most common in these subtypes include silent gonadotroph adenomas, silent corticotroph adenomas and silent somatotroph adenomas. Less commonly, silent prolactinomas and thyrotrophinomas are encountered. Appropriate classification of these adenomas may affect follow-up care after surgical resection. Some silent adenomas such as silent corticotroph adenomas follow a more aggressive course, necessitating closer surveillance. Furthermore, knowledge of the immunostaining characteristics of silent adenomas may determine postoperative medical therapy. This article reviews the incidence, clinical behavior, and pathologic features of clinically silent pituitary adenomas. PMID:22863387

  8. Pleomorphic adenoma of the epiglottis.

    PubMed

    Baptista, P M; Garcia-Tapia, R; Vazquez, J J

    1992-10-01

    Pleomorphic adenoma is the most common benign tumor of the major salivary glands. A pleomorphic adenoma in the larynx constitutes a rarity. A small number of cases have been reported in the literature. We report on a case seen in our hospital, and have reviewed those cases published in the medical literature during the last 25 years.

  9. Prostatic adenoma of ductal origin.

    PubMed

    Min, K W; Gyorkey, F

    1980-07-01

    A case of prostatic adenoma believed to originate from the prostatic duct is described. There were morphologic similarities to basal cell adenomas of salivary glands, and it was concluded that the tumor is a benign counterpart of "salivary gland" carcinomas, rarely observed in the prostate.

  10. Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago.

    PubMed

    Chino, A; Nagayama, S; Ishikawa, H; Morishige, K; Kishihara, T; Arai, M; Sugiura, Y; Motoi, N; Yamamoto, N; Tamegai, Y; Igarashi, M

    2016-01-01

    Since the serrated neoplastic pathway has been regarded as an important pathway of colorectal carcinogenesis, few reports have been published on clinical cases of cancer derived from sessile serrated adenoma/polyp, especially on recurrence after resected sessile serrated adenoma/polyp. An elderly woman underwent endoscopic mucosal resection of a flat elevated lesion, 30 mm in diameter, in the ascending colon; the histopathological diagnosis at that time was a hyperplastic polyp, now known as sessile serrated adenoma/polyp. Five years later, cancer due to the malignant transformation of the sessile serrated adenoma/polyp was detected at the same site. The endoscopic diagnosis was a deep invasive carcinoma with a remnant sessile serrated adenoma/polyp component. The carcinoma was surgically removed, and the pathological diagnosis was an adenocarcinoma with sessile serrated adenoma/polyp, which invaded the muscularis propria. The surgically removed lesion did not have a B-RAF mutation in either the sessile serrated adenoma/polyp or the carcinoma; moreover, the initial endoscopically resected lesion also did not have a B-RAF mutation. Immunohistochemistry confirmed negative MLH1 protein expression in only the cancer cells. Lynch syndrome was not detected on genomic examination. The lesion was considered to be a cancer derived from sessile serrated adenoma/polyp recurrence after endoscopic resection, because both the surgically and endoscopically resected lesions were detected at the same location and had similar pathological characteristics, with a serrated structure and low-grade atypia. Furthermore, both lesions had a rare diagnosis of a sessile serrated adenoma/polyp without B-RAF mutation. This report highlights the need for the follow-up colonoscopy after endoscopic resection and rethinking our resection procedures to improve treatment. PMID:26538462

  11. Pleomorphic adenoma of the palate.

    PubMed

    Clauser, Luigi; Mandrioli, Stefano; Dallera, Vittorio; Sarti, Elisabetta; Galiè, Manilio; Cavazzini, Luigi

    2004-11-01

    Pleomorphic adenoma, is the most common tumor (50%) of the major and minor salivary glands. Seventy percent of the tumors of the minor salivary glands are pleomorphic adenomas, and the most common intraoral site is the palate, followed by the upper lip and buccal mucosa. Pleomorphic adenoma appears as a painless firm mass and, in most cases, does not cause ulceration of the overlying mucosa. Generally it is mobile, except when it occurs in the hard palate. Intraoral mixed tumors, especially those noted within the palate, lack a well-defined capsule. Lesions of the palate frequently involve periosteum or bone. Approximately 25% of benign mixed tumors undergo malignant transformation. Treatment for the pleomorphic adenoma is radical surgery. Inadequate resection leads to local recurrence. The authors report a palate pleomorphic adenoma in a 67-year-old female patient.

  12. Practical opportunities to improve early detection and prevention of colorectal cancer (CRC) in members of high-risk families.

    PubMed

    Patel, S G; Lowery, J T; Gatof, D; Ahnen, D J

    2015-03-01

    Colorectal cancer (CRC) incidence and mortality are steadily declining and CRC screening rates are increasing in the United States. Although this a very good news, several definable groups still have very low screening rates including younger (under age 50) members of high-risk CRC families. This opinion piece describes five strategies that could be incorporated into routine practice to improve identification and guideline-based screening in members of high-risk families. Routine incorporation of a simple family history screening tool and outreach to high-risk family members could substantially improve guideline-based screening in this population. Identification of CRCs and advanced adenomas in the endoscopy suite defines another group of high-risk families for similar outreach. Lynch syndrome families can be identified by testing CRCs and selected adenomas for microsatellite instability or loss of DNA repair protein expression. Finally, selective addition of aspirin to surveillance endoscopy can decrease the risk of new adenomas and CRCs. The rationale for these strategies as well as mechanisms for their implementation and evaluation in clinical practice is described. PMID:25698379

  13. Is Retroflexion Helpful in Detecting Adenomas in the Right Colon?: A Single Center Interim Analysis

    PubMed Central

    Lee, Hyun Seok

    2015-01-01

    Background/Aims Colonoscopy is less effective at screening for colorectal cancer in the right side of the colon. Retroflexion during colonoscopy is expected to improve the detection rate of colorectal adenomas. The aim of the present study was to evaluate the usefulness of retroflexion in the right-sided colon. Methods From April to November 2013, a total of 398 patients were enrolled in this study. For each patient, a cap-assisted colonoscopic examination was performed. After cecal intubation, a forward view examination from the cecum up to the hepatic flexure was performed and all identified polyps were removed. The colonoscope was reinserted to the cecum, and a careful second forward view examination of the cecum to the hepatic flexure was performed, with removal of additionally identified polyps. The colonoscope was then reinserted to the cecum and retroflexed; a third colonoscopic examination was then performed to the hepatic flexure in retroflexion with removal of additional polyps. Total polyp numbers and characteristics were compared between the two forward view examinations and the retroflexion examination. Results A successful retroflexion was performed in 90.2% of patients. A total of 213 polyps and 143 adenomas were detected in the right-sided colon using the routine method of examining the right colon twice in forward view. An additional 35 polyps and 24 adenomas were detected on retroflexion. Of these 35 polyps, 27 (77.1%) were small-sized polyps (≤5 mm) and 24 (71.4%) were adenomas. Finding additional adenomas using the retroflexion technique was associated with older age. Conclusions Colonoscopic retroflexion is helpful in the detection of cecum and ascending colon adenomas, especially small-sized adenomas (≤5 mm). It is particularly useful in older patients. PMID:26576138

  14. The use of the terms monomorphic adenoma, basal cell adenoma, and canalicular adenoma as applied to salivary gland tumors.

    PubMed

    Gardner, D G; Daley, T D

    1983-12-01

    There is considerable confusion in the literature concerning the terms monomorphic adenoma, basal cell adenoma, and canalicular adenoma. This article traces the history of these terms as applied to the pathology of salivary gland tumors and attempts to clarify their usage. It is recommended (1) that monomorphic adenoma be used, as it was originally intended, as a nosologic grouping for all benign epithelial salivary gland tumors that are not pleomorphic adenomas, (2) that basal cell adenoma be used to identify a specific entity that is one component of the monomorphic adenoma group and exhibits a number of histologic subtypes, and (3) that canalicular adenoma be used to describe another entity, distinct from basal cell adenomas but also belonging to the monomorphic adenoma group.

  15. [Non-serrated precursor lesions of colorectal tumours].

    PubMed

    Langner, C

    2011-11-01

    Non-serrated precursor lesions of colorectal tumours include conventional adenomas (tubular, tubulovillous and villous), inflammatory bowel disease-associated dysplasia (intraepithelial neoplasia), and hamartoma-associated dysplasia. This short review summarizes the current literature on the adenoma-carcinoma sequence, focusing on colonic stem cells and functional crypt organization, patterns of stem cell division, niche succession and clonal conversion in the formation of a monocryptal adenoma. The process of clonal interaction between neighboring crypts as well as the development of large monoclonal adenomas from small polyclonal precursor lesions is discussed in detail. Finally, the molecular pathogenesis as well as the clinical significance of inflammatory bowel disease- and hamartoma-associated carcinogenesis is addressed.

  16. [Hereditary and familial colorectal cancer].

    PubMed

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes.

  17. Population screening for colorectal cancer.

    PubMed

    2006-09-01

    Each year in the UK, around 16,000 people die from colorectal cancer. At disease presentation, around 55% of people have advanced cancer that has spread to lymph nodes, metastasised to other organs or is so locally advanced that surgery is unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but only 7% at most in those presenting with metastatic disease. These facts underlie the current introduction of national bowel screening programmes in the UK. Here we assess the role of screening of the general population in reducing mortality from colorectal cancer. We do not consider the screening arrangements needed for high-risk populations, including those with inflammatory bowel disease or a strong family history of colorectal cancer. PMID:17009566

  18. Canalicular adenoma of buccal mucosa.

    PubMed

    Maamouri, F; Bellil, K; Bellil, S; Chelly, I; Mekni, A; Kchir, N; Haouet, S; Zitouna, M

    2007-06-01

    Canalicular adenoma is a benign tumor which comprises 1% of salivary gland neoplasms and 4% of minor salivary gland tumors. It occurs in the upper lip mucosa in about 90% of cases. The next most common location is the buccal mucosa (9.5% of tumors). We present herein a new case of canalicular adenoma of buccal mucosa involving a 74-year-old man. He was suffering of a slowly growing and painless nodule of the right buccal mucosa. The treatment was surgery and histological findings were consistent with the diagnosis of canalicular adenoma. No recurrence was noted one year later.

  19. Phase II trial of fluorouracil and recombinant interferon alfa-2a in patients with advanced colorectal carcinoma: an Eastern Cooperative Oncology Group study.

    PubMed

    Wadler, S; Lembersky, B; Atkins, M; Kirkwood, J; Petrelli, N

    1991-10-01

    In a pilot clinical trial, treatment of patients with advanced colorectal carcinoma with the combination of fluorouracil (5FU) and recombinant interferon alfa-2a (IFN) resulted in objective tumor regression in 62% of patients. To confirm these findings in a multiinstitutional setting, a phase II clinical trial was initiated by the Eastern Cooperative Oncology Group (ECOG) in 1989. The treatment regimen was identical to that used in the earlier study: 5FU 750 mg/m2/d for 5 days as a continuous infusion followed by weekly outpatient bolus therapy and IFN 9MU subcutaneously beginning day 1 and administered three times per week. Doses were modified for gastrointestinal, hematologic, and neurologic toxicity and for fatigue, similarly to those used in the previous pilot trial. Thirty-eight patients were registered; 36 are evaluable for response (one lost to follow-up and one with nonmeasurable disease). All patients had metastatic or locally recurrent disease beyond the scope of resection; 31 of 38 had liver metastases, and 20 of 38 had two or more sites of involvement. Eight patients had grade 4 toxicities, including sepsis (nonneutropenic) (one), watery diarrhea (two), and granulocytopenia (six). Grade 3 neurologic toxicities were observed in two (5%) patients and included slurred speech and gait disturbance. Objective response was 42% (95% confidence interval [Cl], 27% to 58%), including one clinical complete responder and 14 partial responders. Among the responding patients, the median time to treatment failure was 8 months. Two patients remain on treatment at 10+ and 16+ months: median survival has not been reached. The results of this multiinstitutional trial suggest that the addition of IFN to 5FU enhances the objective response rates achieved in patients with advanced colorectal carcinoma and that the toxicities of this regimen are acceptable. PMID:1919631

  20. Serrated and non-serrated precursor lesions of colorectal cancer.

    PubMed

    Langner, Cord

    2015-01-01

    Although often viewed as a single disease, colorectal cancer more accurately represents a family of diseases with different precursor lesions. Conventional (tubular, tubulovillous and villous) adenomas are the most common neoplastic lesions occurring in the large intestine. They have adenomatous polyposis coli (APC) mutations and arise from dysplastic aberrant crypt foci, initially as polyclonal lesions. In sporadic tumours, neoplastic progression follows the traditional pathway (chromosomal instability pathway), resulting in CpG island methylator phenotype (CIMP)-negative, microsatellite-stable (MSS), BRAF and KRAS wild-type cancers. Germline mutations in the APC gene lead to familial adenomatous polyposis. Conventional adenomas are also the precursors of Lynch syndrome-associated microsatellite-instable (MSI-high) cancers. Sessile serrated adenoma/polyp (SSA/P) is the principal precursor lesion of the serrated pathway, in which BRAF mutation can lead to colorectal cancer with MSI-high CIMP-high or MSS CIMP-high phenotype. SSA/Ps have been associated with synchronous and metachronous invasive adenocarcinomas as well as so-called interval carcinomas. Serrated polyposis is rare but most likely underdiagnosed. Affected individuals bear an increased but unspecified risk for the development of colorectal cancer; close endoscopic surveillance is warranted. Traditional serrated adenomas (TSAs) are much less common than the other serrated lesions. Cancers originating from TSAs may show KRAS mutation with a CIMP-high MSS phenotype.

  1. The intraoral basal cell adenoma.

    PubMed

    Pogrel, M A

    1987-12-01

    The histological and clinical behaviour of nine intraoral salivary basal cell adenomas is described. Despite problems in classification, this study confirms the impression that these are all benign salivary gland tumours which respond well to localized excision only.

  2. The human gut microbiome as a screening tool for colorectal cancer.

    PubMed

    Zackular, Joseph P; Rogers, Mary A M; Ruffin, Mack T; Schloss, Patrick D

    2014-11-01

    Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information.

  3. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer.

    PubMed

    Aung, Kyaw L; Stockley, Tracy L; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L; Siu, Lillian L

    2016-09-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients' clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics. PMID:27626067

  4. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer

    PubMed Central

    Aung, Kyaw L.; Stockley, Tracy L.; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L.; Siu, Lillian L.

    2016-01-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients’ clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics.

  5. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer

    PubMed Central

    Aung, Kyaw L.; Stockley, Tracy L.; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L.; Siu, Lillian L.

    2016-01-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients’ clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics. PMID:27626067

  6. Correlation between Helicobacter pylori-associated gastric diseases and colorectal neoplasia

    PubMed Central

    Qing, Ying; Wang, Min; Lin, Ying-Min; Wu, Dong; Zhu, Jing-Yu; Gao, Lang; Liu, Yan-Yan; Yin, Teng-Fei

    2016-01-01

    AIM: To explore the correlation between Helicobacter pylori (H. pylori)-associated gastric diseases and colorectal neoplasia. METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy (EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status (including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations. RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia (HGIEN) (OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN (5.333, 1.025-27.758) and adenocarcinoma (1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN (3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN (0.874, 0.414-1.845) and adenocarcinoma (0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN (3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN (1.481, 0.138-15.941) and adenocarcinoma (2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN (1.067, 0.264-4.314), adenoma with HGIEN (2.667, 0

  7. A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer

    PubMed Central

    Kumegawa, Kohei; Maruyama, Reo; Yamamoto, Eiichiro; Ashida, Masami; Kitajima, Hiroshi; Tsuyada, Akihiro; Niinuma, Takeshi; Kai, Masahiro; Yamano, Hiro-o; Sugai, Tamotsu; Tokino, Takashi; Shinomura, Yasuhisa; Imai, Kohzoh; Suzuki, Hiromu

    2016-01-01

    Long noncoding RNAs (lncRNAs) have emerged as key components in multiple cellular processes, although their physiological and pathological functions are not fully understood. To identify cancer-related lncRNAs, we screened for those that are epigenetically silenced in colorectal cancer (CRC). Through a genome-wide analysis of histone modifications in CRC cells, we found that the transcription start sites (TSSs) of 1,027 lncRNA genes acquired trimethylation of histone H3 lysine 4 (H3K4me3) after DNA demethylation. Integrative analysis of chromatin signatures and the DNA methylome revealed that the promoter CpG islands (CGIs) of 66 lncRNA genes contained cancer-specific methylation. By validating the expression and methylation of lncRNA genes in CRC cells, we ultimately identified 20 lncRNAs, including ZNF582-AS1, as targets of epigenetic silencing in CRC. ZNF582-AS1 is frequently methylated in CRC cell lines (87.5%), primary CRCs (77.2%), colorectal adenomas (44.7%) and advanced adenomas (87.8%), suggesting that this methylation is an early event during colorectal tumorigenesis. Methylation of ZNF582-AS1 is associated with poor survival of CRC patients, and ectopic expression of ZNF582-AS1 suppressed colony formation by CRC cells. Our findings offer insight into the association between epigenetic alterations and lncRNA dysregulation in cancer and suggest that ZNF582-AS1 may be a novel tumor-suppressive lncRNA. PMID:27215978

  8. Feasibility of Unbiased RNA Profiling of Colorectal Tumors: A Proof of Principle.

    PubMed

    Moshayoff, Vardit; Faktor, Ouriel; Laghi, Luigi; Celesti, Giuseppe; Peretz, Tamar; Keret, Dan; Cohen, Dana; Israeli, Eran

    2016-01-01

    Despite recent advances in molecular profiling of colorectal cancer (CRC), as of yet this has not translated into an unbiased molecular liquid biopsy profile which can accurately screen for early CRC. In this study we depict the profile of early stage CRC as well as for advanced adenomas (AA) by combination of current molecular knowledge with microarray technology, using efficient circulating free plasma RNA purification from blood and RNA amplification technologies. We joined literature search with Affymetrix gene chip experimental procedure to draw the circulating free plasma RNA profile of colorectal cancer disease reflected in blood. The RNA panel was tested by two datasets comparing patients with CRC with healthy subjects and patients with AA to healthy subjects. For the CRC patient cohort (28 CRC cases vs. 41 healthy controls), the ROC analysis of the selected biomarker panel generated a sensitivity of 75% and a specificity of 93% for the detection of CRC using 8-gene classification model. For the AA patient cohort (28 subjects vs. 46 healthy controls), a sensitivity of 60% and a specificity of 87% were calculated using a 2-gene classification model. We have identified a panel of 8 plasma RNA markers as a preliminary panel for CRC detection and subset markers suitable for AA detection. Subjected to extensive clinical validation we suggest that this panel represents a feasible approach and a potential strategy for noninvasive early diagnosis, as a first-line screening test for asymptomatic, average-risk population before colonoscopy. PMID:27441409

  9. Colorectal polyp type and the association with charred meat consumption, smoking, and microsomal epoxide hydrolase polymorphisms.

    PubMed

    Burnett-Hartman, Andrea N; Newcomb, Polly A; Mandelson, Margaret T; Adams, Scott V; Wernli, Karen J; Shadman, Mazyar; Wurscher, Michelle A; Makar, Karen W

    2011-01-01

    We determined the association between charred meat consumption, cigarette smoking, microsomal epoxide hydrolase (mEH) polymorphisms (rs1051740 and rs2234922), and colorectal adenomas and hyperplastic polyps (HPs) and explored gene-environment interactions. Men and women with colorectal adenomas (n = 519), HPs (n = 691), or concurrently with both types of polyps (n = 227) and polyp-free controls (n = 772) receiving a colonoscopy from December 2004 to September 2007 were recruited. Participants completed telephone interviews and provided buccal cell samples; genotyping of mEH was completed using Taqman assays. We conducted polytomous regression and calculated odd ratios (OR) and 95% confidence intervals. Interactions were evaluated using Wald chi-square tests. Consumption of >3 servings of charred meat per week was associated with distal HPs (OR = 2.0, 1.2-3.4) but not adenomas nor either type of proximal polyp. Heavy cigarette smoking (≥ 22 pack-years) was associated with an increased risk for colorectal adenomas (OR = 1.7, 95% CI: 1.2-2.4), HPs (OR = 2.4, 95% CI: 1.7-3.3), and both types (OR = 2.8, 95% CI: 1.8-4.3) with the strongest association for distal polyps. There was no association between mEH genotype and colorectal polyps, nor were any statistically significant gene-environment interactions identified. Future investigation of BaP exposure and colorectal neoplasia should analyze whether associations are dependent upon anatomic location.

  10. Management of Colorectal Trauma

    PubMed Central

    2011-01-01

    Although the treatment strategy for colorectal trauma has advanced during the last part of the twentieth century and the result has improved, compared to other injuries, problems, such as high septic complication rates and mortality rates, still exist, so standard management for colorectal trauma is still a controversial issue. For that reason, we designed this article to address current recommendations for management of colorectal injuries based on a review of literature. According to the reviewed data, although sufficient evidence exists for primary repair being the treatment of choice in most cases of nondestructive colon injuries, many surgeons are still concerned about anastomotic leakage or failure, and prefer to perform a diverting colostomy. Recently, some reports have shown that primary repair or resection and anastomosis, is better than a diverting colostomy even in cases of destructive colon injuries, but it has not fully established as the standard treatment. The same guideline as that for colonic injury is applied in cases of intraperitoneal rectal injuries, and, diversion, primary repair, and presacral drainage are regarded as the standards for the management of extraperitoneal rectal injuries. However, some reports state that primary repair without a diverting colostomy has benefit in the treatment of extraperitoneal rectal injury, and presacral drainage is still controversial. In conclusion, ideally an individual management strategy would be developed for each patient suffering from colorectal injury. To do this, an evidence-based treatment plan should be carefully developed. PMID:21980586

  11. [Prevention of colorectal cancer: acetylsalicyclic acid and cyclo-oxygenase-2 inhibitors are only partially effective].

    PubMed

    Kleibeuker, J H; de Vries, E G

    2003-11-01

    Acetylsalicylic acid was recently shown to inhibit the development of colorectal adenomas in subjects with a moderately increased risk for colorectal cancer. The mechanisms by which acetylsalicylic acid and other NSAIDs, including COX-2 inhibitors, exert this effect include: inhibition of COX-2, induction of apoptosis and induction of the P21 protein that controls the development of crypt cells. For the majority of the population, a healthy lifestyle and healthy eating habits are the best means of preventing colorectal cancer. In addition, population-wide screening should be encouraged. For people with an increased risk of colorectal cancer, acetylsalicylic acid only has a partial effect and therefore endoscopic surveillance is still indicated. Sulindac or celecoxib may be useful for patients with familial adenomatous polyposis and in particular for inhibiting the development of rectal adenomas after subtotal colectomy with ileorectal anastomosis. However, in these cases endoscopic surveillance is also still necessary.

  12. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.

    PubMed

    Winawer, Sidney J; Zauber, Ann G; Fletcher, Robert H; Stillman, Jonathon S; O'Brien, Michael J; Levin, Bernard; Smith, Robert A; Lieberman, David A; Burt, Randall W; Levin, Theodore R; Bond, John H; Brooks, Durado; Byers, Tim; Hyman, Neil; Kirk, Lynne; Thorson, Alan; Simmang, Clifford; Johnson, David; Rex, Douglas K

    2006-05-01

    Adenomatous polyps are the most common neoplastic findings discovered in people who undergo colorectal screening or who have a diagnostic work-up for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas and missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which showed clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance take place 3 years after polypectomy for most patients. In 2003 these guidelines were updated and colonoscopy was recommended as the only follow-up examination, stratification at baseline into low risk and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have shown that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present report, a careful analytic approach was designed to address all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be stratified more definitely at their baseline colonoscopy into those at lower risk or increased risk for a subsequent advanced neoplasia. People at increased risk have either 3 or more adenomas, high-grade dysplasia, villous features, or an adenoma 1 cm or larger in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have 1 or 2 small (<1 cm) tubular adenomas with no high-grade dysplasia can have a follow-up evaluation in 5-10 years, whereas

  13. Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome.

    PubMed

    Flanagan, L; Schmid, J; Ebert, M; Soucek, P; Kunicka, T; Liska, V; Bruha, J; Neary, P; Dezeeuw, N; Tommasino, M; Jenab, M; Prehn, J H M; Hughes, D J

    2014-08-01

    Commensal bacteria in the colon may play a role in colorectal cancer (CRC) development. Recent studies from North America showed that Fusobacterium nucleatum (Fn) infection is over-represented in disease tissue versus matched normal tissue in CRC patients. Using quantitative real-time polymerase chain reaction (qPCR) of DNA extracted from colorectal tissue biopsies and surgical resections of three European cohorts totalling 122 CRC patients, we found an over-abundance of Fn in cancerous compared to matched normal tissue (p < 0.0001). To determine whether Fn infection is an early event in CRC development, we assayed Fn in colorectal adenoma (CRA) tissue from 52 Irish patients. While for all CRAs the Fn level was not statistically significantly higher in disease versus normal tissue (p = 0.06), it was significantly higher for high-grade dysplasia (p = 0.015). As a secondary objective, we determined that CRC patients with low Fn levels had a significantly longer overall survival time than patients with moderate and high levels of the bacterium (p = 0.008). The investigation of Fn as a potential non-invasive biomarker for CRC screening showed that, while Fn was more abundant in stool samples from CRC patients compared to adenomas or controls, the levels in stool did not correlate with cancer or adenoma tissue levels from the same individuals. This is the first study examining Fn in the colonic tissue and stool of European CRC and CRA patients, and suggests Fn as a novel risk factor for disease progression from adenoma to cancer, possibly affecting patient survival outcomes. Our results highlight the potential of Fn detection as a diagnostic and prognostic determinant in CRC patients.

  14. Modeling and Control of Colorectal Cancer.

    PubMed

    Song, Li-Peng; Wang, Hao-Yu

    2016-01-01

    Colorectal Cancer (CRC) is becoming a major threat to people's life in China. Screening methods adopted by many other countries as effective counter-cancer methods have not been explicitly explored for people there. Thus, we present a Markov model with detailed precancerous adenoma states and then evaluate various screening strategies in this paper. Different from current researches, our model considers the population's heterogeneous risk of developing adenomas and observation-based screening strategies. Furthermore, we also give a new cost-effectiveness metric. After calibrating, the model is simulated using the Monte Carlo method. Numerical results show that there are threshold values of compliance rates below which strategy with every ten-year colonoscopy becomes the most cost-effective method; otherwise, an observation-based screening strategy is the most cost-effective. We also find that strategy with single colonoscopy for adenoma-free individuals and every three-year colonoscopy for those with adenoma is recommended when the observation-based strategy is not considered. Our findings give an explicit and complete instruction in CRC screening protocol in average-risk Chinese. PMID:27536786

  15. Modeling and Control of Colorectal Cancer

    PubMed Central

    Song, Li-Peng; Wang, Hao-Yu

    2016-01-01

    Colorectal Cancer (CRC) is becoming a major threat to people’s life in China. Screening methods adopted by many other countries as effective counter-cancer methods have not been explicitly explored for people there. Thus, we present a Markov model with detailed precancerous adenoma states and then evaluate various screening strategies in this paper. Different from current researches, our model considers the population’s heterogeneous risk of developing adenomas and observation-based screening strategies. Furthermore, we also give a new cost-effectiveness metric. After calibrating, the model is simulated using the Monte Carlo method. Numerical results show that there are threshold values of compliance rates below which strategy with every ten-year colonoscopy becomes the most cost-effective method; otherwise, an observation-based screening strategy is the most cost-effective. We also find that strategy with single colonoscopy for adenoma-free individuals and every three-year colonoscopy for those with adenoma is recommended when the observation-based strategy is not considered. Our findings give an explicit and complete instruction in CRC screening protocol in average-risk Chinese. PMID:27536786

  16. First-Line Cetuximab Plus Capecitabine in Elderly Patients with Advanced Colorectal Cancer: Clinical Outcome and Subgroup Analysis According to KRAS Status from a Spanish TTD Group Study

    PubMed Central

    Grávalos, Cristina; Rivera, Fernando; Massuti, Bartomeu; Valladares-Ayerbes, Manuel; Marcuello, Eugenio; Manzano, José L.; Benavides, Manuel; Hidalgo, Manuel; Díaz-Rubio, Eduardo; Aranda, Enrique

    2012-01-01

    Single-agent cetuximab is safe and active in elderly patients with advanced colorectal cancer (CRC). A cetuximab–capecitabine combination has not previously been tested in elderly patients with advanced CRC. Material and Methods. Sixty-six patients with advanced CRC were treated with cetuximab as a 400 mg/m2 i.v. infusion followed by 250 mg/m2 i.v. weekly plus capecitabine at a dose of 1,250 mg/m2 every 12 hours. After the inclusion of 27 patients, the protocol was amended for safety reasons, reducing the dose of capecitabine to 1,000 mg/m2 every 12 hours. Thirty-nine additional patients were treated with the reduced dose of capecitabine. Results. The overall response rate was 31.8%. KRAS status was determined in 58 patients (88%). Fourteen of 29 patients with wild-type KRAS tumors responded (48.3%; 95% confidence interval [CI], 29.4%–67.5%), compared with six of 29 patients with mutant KRAS tumors (20.7%; 95% CI, 8.0%–39.7%). The median progression-free survival (PFS) interval was 7.1 months. The median PFS interval for patients whose tumors were wild-type KRAS was significantly longer than for those with mutant KRAS tumors (8.4 months versus 6.0 months; p = .024). The high incidence of severe paronychia (29.6%) declined (7.7%) after capecitabine dose adjustment. Conclusions. Cetuximab plus capecitabine at a dose of 1,000 mg/m2 every 12 hours may be an alternative to more aggressive regimens in elderly patients with advanced wild-type KRAS CRC. PMID:22363067

  17. [Diagnostics and treatment of hepatocellular adenomas].

    PubMed

    Klompenhouwer, A J; de Man, R A; Thomeer, M G J; Doukas, M; IJzermans, J N M

    2016-01-01

    - Hepatocellular adenomas are essentially benign tumours of the liver that occur mostly in women of reproductive age. - The four different subtypes described, which can be distinguished both radiologically and histopathologically, are: steatotic, inflammatory, β-catenin mutated and unclassified adenomas. These subtypes differ in the risk of complications.- Contrast-enhanced liver MRI is the best method for diagnostics and characterization of hepatocellular adenomas. - Possible complications include bleeding, rupture, and malignant degeneration of the hepatocellular adenoma. These complications are rare in adenomas < 5 cm. - Men with hepatocellular adenomas are at higher risk for malignant degeneration. - In women, lifestyle changes (cessation of oral contraceptive and weight reduction) can cause regression of the adenoma, which can prevent the necessity for liver surgery. - In pregnant women there is a risk of growth of hepatocellular adenoma. It is, therefore, it is recommended to check the tumour in pregnant women every 6-12 weeks using ultrasound. PMID:27650020

  18. Villous adenoma of the distal appendix.

    PubMed

    Taylor, J V; Thomas, M G; Kelly, S; Sutton, R

    1997-04-01

    Villous adenoma confined to the distal appendix has not been previously reported in conjunction with acute apendicitis. The presence of an adenoma indicates a need for further investigation due to an association with neoplasia elsewhere.

  19. Multiple pulmonary metastases from benign pleomorphic adenoma.

    PubMed

    Sit, Ko Yung; Chui, Wing Hung; Wang, Elaine; Chiu, Shui Wah

    2008-01-01

    Metastasizing pleomorphic adenoma is a rare condition of metastasis from a histologically benign salivary gland tumor. We report a case of metastasizing pleomorphic adenoma presenting with multiple bilateral lung metastases, and discuss the clinical aspects of this disease.

  20. A case of metastasizing pleomorphic adenoma.

    PubMed

    Goodisson, D W; Burr, R G; Creedon, A J; Stirling, R W; Morgan, P R; Odell, E W; Buff, R G

    1999-03-01

    The pleomorphic adenoma is the most common benign salivary neoplasm. A case is presented in which a palatal pleomorphic adenoma seeded a metastasis in the medullary cavity of the anterior maxilla, apparently by hematogenous spread after surgical manipulation.

  1. [Familial isolated pituitary adenoma syndrome].

    PubMed

    Dénes, Judit; Korbonits, Márta; Hubina, Erika; Kovács, Gábor László; Kovács, László; Görömbey, Zoltán; Czirják, Sándor; Góth, Miklós

    2011-05-01

    Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor. PMID:21498161

  2. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation.

  3. Double pituitary adenomas: six surgical cases.

    PubMed

    Sano, T; Horiguchi, H; Xu, B; Li, C; Hino, A; Sakaki, M; Kannuki, S; Yamada, S

    1999-05-01

    While double pituitary adenomas have been found in approximately 1% of autopsy pituitaries, those in surgically resected material have been only rarely reported. We report herein 6 cases of double pituitary adenomas, which consisted of two histologically and/or immunohistochemically different areas among approximately 450 surgical specimens. Five out of 6 patients were men and the age was ranged between 18 and 61 years old. All these 6 patients presented acromegaly or acrogigantism and hyperprolactinemia was noted in 3 patients. In 2 patients (cases 1 and 2) the two adenomas belonged to different adenoma groups (GH-PRL-TSH group and FSH/LH group), while in the remaining 4 patients (cases 3-6) the two adenomas belonged to the same group (GH-PRL-TSH group). Thus, in all patients at least one of the two adenomas was GH-producing adenoma. Reasons for a high incidence of GH-producing adenomas in surgically resected double pituitary adenomas may include the presence of a variety of histologic subtypes among GH-producing adenomas and the advantage of cytokeratin immunostaining to distinguish these subtypes. In regard to pathogenesis of double pituitary adenomas, adenomas in cases 1 and 2 may be of multicentric occurrence, while those in cases 3-6 may occur through different clonal proliferation within originally one adenoma, resulting in diverse phenotypic expressions. Since there were patients with familial MEN 1 (case 2) and familial pituitary adenoma unrelated MEN 1 (case 3), genetic background should be also considered. Double pituitary adenomas in surgically resected material may not be so infrequent. Further molecular analysis will provide new insights into understanding the pathogenesis of pituitary adenomas and their mechanisms of multidirectional phenotypic diffrentiation. PMID:11081204

  4. [Nutrition and colorectal cancer].

    PubMed

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

    Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

  5. Loss of expression and promoter methylation of SLIT2 are associated with sessile serrated adenoma formation.

    PubMed

    Beggs, Andrew D; Jones, Angela; Shepherd, Neil; Arnaout, Abed; Finlayson, Caroline; Abulafi, A Muti; Morton, Dion G; Matthews, Glenn M; Hodgson, Shirley V; Tomlinson, Ian P M

    2013-05-01

    Serrated adenomas form a distinct subtype of colorectal pre-malignant lesions that may progress to malignancy along a different molecular pathway than the conventional adenoma-carcinoma pathway. Previous studies have hypothesised that BRAF mutation and promoter hypermethylation plays a role, but the evidence for this is not robust. We aimed to carry out a whole-genome loss of heterozygosity analysis, followed by targeted promoter methylation and expression analysis to identify potential pathways in serrated adenomas. An initial panel of 9 sessile serrated adenomas (SSA) and one TSA were analysed using Illumina Goldengate HumanLinkage panel arrays to ascertain regions of loss of heterozygosity. This was verified via molecular inversion probe analysis and microsatellite analysis of a further 32 samples. Methylation analysis of genes of interest was carried out using methylation specific PCR (verified by pyrosequencing) and immunohistochemistry used to correlate loss of expression of genes of interest. All experiments used adenoma samples and normal tissue samples as control. SSA samples were found on whole-genome analysis to have consistent loss of heterozygosity at 4p15.1-4p15.31, which was not found in the sole TSA, adenomas, or normal tissues. Genes of interest in this region were PDCH7 and SLIT2, and combined MSP/IHC analysis of these genes revealed significant loss of SLIT2 expression associated with promoter methylation of SLIT2. Loss of expression of SLIT2 by promoter hypermethylation and loss of heterozygosity events is significantly associated with serrated adenoma development, and SLIT2 may represent a epimutated tumour suppressor gene according to the Knudson "two hit" hypothesis.

  6. Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting

    PubMed Central

    Chen, Hongda; Werner, Simone; Butt, Julia; Zörnig, Inka; Knebel, Phillip; Michel, Angelika; Eichmüller, Stefan B.; Jäger, Dirk; Waterboer, Tim; Pawlita, Michael; Brenner, Hermann

    2016-01-01

    Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005–2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13–45%) for early stage CRC at a specificity of 90% (95% CI, 83–94%) in the validation set. Notably, it also detected 20% (95% CI, 13–29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection. PMID:26909861

  7. Canalicular adenoma arising in the esophagus.

    PubMed

    Grimm, Erin E; Rulyak, Stephen J; Sekijima, John H; Yeh, Matthew M

    2007-10-01

    Canalicular adenomas are benign neoplasms that arise from salivary glands and often present as painless enlarging nodules. They have a predilection for upper lip but can be found throughout the oropharynx. To our knowledge, canalicular adenoma arising in the esophagus has never been described in the English literature. Here we report a canalicular adenoma occurring in the esophagus.

  8. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer

    PubMed Central

    2013-01-01

    Background The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. Methods Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. Results DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. Conclusions DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers. PMID:23902796

  9. Measurement of serum antibodies against NY-ESO-1 by ELISA: A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer.

    PubMed

    Long, Yan-Yan; Wang, Yu; Huang, Qian-Rong; Zheng, Guang-Shun; Jiao, Shun-Chang

    2014-10-01

    NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; P<0.001). Therefore, monitoring serum Abs against NY-ESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC.

  10. BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis

    PubMed Central

    Koh, Jiwon; Kwak, Yoonjin; Seo, An Na; Park, Kyoung Un; Kim, Duck-Woo; Kang, Sung-Bum; Kim, Woo Ho; Lee, Hye Seung

    2016-01-01

    Background Anti-EGFR antibody–based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC); despite this, several mutations—including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification—are associated with the mechanisms underlying the development of resistance to anti-EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC. Methods KRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR) in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI) status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases. Results Mutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%), 6 (3.1%), and 25 (13.1%) cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6%) and 16 (8.4%) cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3%) than KRAS wild type (6.9%) (P = 0.020). In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively). In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004). When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7%) CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%). Conclusions KRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients. PMID

  11. [Prostatilen treatment of prostatic adenoma].

    PubMed

    Al'-Shukri, S Kh; Gorbachev, A G; Borovets, S Iu; Belousov, V Ia; Kuz'min, I V; Chushkin, K A

    2006-01-01

    We studied efficacy of repeated courses of prostatilen in suppositories with dimexide in prostatic adenoma patients with normal micturition. Rectal suppositories contain 30 mg prostatilen and 90 mg dimexide. The course consisted of 15 suppositories. The treatment reduced clinical symptoms of infravesical obstruction, residual urine volume in administration of prostatilen in 15-day courses each 3 months. This suggests possibility of suppository prostatilen use not only as an alternative for expensive drugs but also in combination with them in treatment of initial prostatic adenoma.

  12. Colorectal Cancer: Chemopreventive Role of Curcumin and Resveratrol

    PubMed Central

    Patel, Vaishali B.; Misra, Sabeena; Patel, Bhaumik B.; Majumdar, Adhip P. N.

    2013-01-01

    Colorectal cancer (CRC) is a second leading cause of cancer deaths in the Western world. Currently there is no effective treatment except resection at a very early stage with or with-out chemotherapy. Of various epithelial cancers, CRC in particular has a potential for prevention, since most cancers follow the adenoma-carcinoma sequence, and the interval between detection of an adenoma and its progression to carcinoma is usually about a decade. However no effective chemopreventive agent except COX-2 inhibitors, limited in their scope due to cardiovascular side effects, have shown promise in reducing adenoma recurrence. To this end, natural agents that can target important carcinogenic pathways without demonstrating discernible adverse effects would serve as ideal chemoprevention agents. In this review, we discuss merits of two such naturally occurring dietary agents—curcumin and resveratrol—for chemoprevention of CRC. PMID:20924971

  13. A Systematic Review and Network Meta-Analysis of Biologic Agents in the First Line Setting for Advanced Colorectal Cancer

    PubMed Central

    Kumachev, Alexander; Yan, Marie; Berry, Scott; Ko, Yoo-Joung; Martinez, Maria C. R.; Shah, Keya; Chan, Kelvin K. W.

    2015-01-01

    Background Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab (BEV) are used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have directly compared their relative efficacy on progression-free survival (PFS) and overall survival (OS). Methods We conducted a systematic review of first-line RCTs comparing (1) EGFRis vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs. chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using Cochrane methodology. Data on and PFS and OS were extracted using the Parmar method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were conducted to estimate the direct, indirect and combined PFS and OS hazard ratios (HRs) comparing EGFRis to BEV. Results Seventeen RCTs contained extractable data for quantitative analysis. Combining direct and indirect data using an NMA did not show a statistical difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92–1.36) and OS HR = 0.91 (95% CR: 0.75–1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs) and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a difference between EGFRis and BEV. Meta-analysis of OS using direct evidence, largely influenced by one trial, showed an improvement with EGFRis therapy (HR = 0.79 (95% CR: 0.65–0.98)), while indirect and combined NMA of OS did not show a difference between EGFRis and BEV Successive inclusions of trials over time in the combined NMA did not show superiority of EGFRis over BEV. Conclusions Our findings did not support OS or PFS benefits of EGFRis over BEV in first-line mCRC. PMID:26474403

  14. Population pharmacokinetics of oxaliplatin (85 mg/m2) in combination with 5-fluorouracil in patients with advanced colorectal cancer.

    PubMed

    Kho, Yuhan; Jansman, Frank G A; Prins, Nicolaas H; Neef, Cees; Brouwers, Jacobus R B J

    2006-04-01

    Pharmacokinetic (PK) studies of oxaliplatin, using a dose regimen of 85 mg/m, are lacking. A PK model may be used in future studies to investigate the relationship between pharmacokinetics and dose limiting toxicity. The purpose of this study was to construct a population PK model to describe platinum (Pt) concentrations in plasma in 33 patients with colorectal cancer. The secondary objective was to determine the relationship between the amount of Pt in 24-hour urine and the amount of Pt in fractionated urine collection periods. Plasma and urine samples were collected from patients during their first oxaliplatin treatment course. Population PK analysis was performed with WinNonMix. The model that best described the Pt concentrations in plasma was a two-compartment PK model. The elimination clearance (CL) and the elimination clearance of the peripheral compartment (CL2) (median +/- SE) were 25.2 +/- 6.3 L/hr and 68 +/- 24.8 L/hr, respectively. The median volume of distribution (V1) was determined to be 41.6 +/- 9.4 L and the median volume of distribution of the peripheral compartment (V2) was 452.5 +/- 96.4 L. The relationship between the cumulative amount of Pt in urine in the first 12 hours compared with the amount of Pt in 24 hours urine was reflected by a correlation coefficient (r2) of 0.95. The cumulative Pt concentration in urine in the first 10 hours and the first 8 hours compared with 24 hours was reflected by correlation coefficients r2 = 0.93 and r2 = 0.897, respectively. This PK model could be useful in identifying predictors for PK and pharmacodynamic variability to individualize dosing. The results of this study suggest that fractionated urine samples can replace 24-hour urine collection. PMID:16628132

  15. Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results

    PubMed Central

    Schoffelen, R; Boerman, O C; Goldenberg, D M; Sharkey, R M; van Herpen, C M L; Franssen, G M; McBride, W J; Chang, C-H; Rossi, E A; van der Graaf, W T A; Oyen, W J G

    2013-01-01

    Background: Radiolabelled antibody targeting of cancer is limited by slow blood clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves tumour localisation. The primary goals of this first pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC). Methods: Different dose schedules were studied in four cohorts of five patients: (1) shortening the interval between the bsMAb and peptide administration (5 days vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 μg). After confirmation of tumour targeting by 111In-IMP288, patients were treated with a bsMAb/177Lu-IMP288 cycle. Results: Rapid and selective tumour targeting of the radiolabelled peptide was visualised within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour targeting was achieved with a 1-day interval between the administration of the bsMAb and the peptide and with the 25-μg peptide dose. High 177Lu-IMP288 doses (2.5–7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions, and transient grades 3–4 thrombocytopaenia in 10% of the patients who received 177Lu-IMP288. Conclusion: This phase I study demonstrates for the first time that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted. PMID:23860529

  16. [Image diagnosis and pleomorphic adenoma].

    PubMed

    Ruiz Jaureguizuría, J C; Crovetto de la Torre, M A; Bárcena Robredo, M V; Grande Icarán, D

    1989-01-01

    We examined the imaging technical findings of 11 benign pleomorphic adenomas of major salivary glands. The imaging technical included sialography, echography, computed tomography and gammagraphy. We compared the diagnostic usefulness of each of these imaging technical. The purpose of this paper is to identify the actual advantages, disadvantages and uses of these diagnostic methods.

  17. Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma

    PubMed Central

    Lee, Min Ho; Lee, Ju Hee; Seol, Ho Jun; Lee, Jung-Il; Kim, Jong Hyun; Kong, Doo-Sik

    2016-01-01

    Background Non-functioning pituitary adenomas (NFPA) are clinically challenging because they present at a late stage with local mass effects or hypopituitarism. Surgery for non-functioning pituitary adenoma requires a special strategic approach for both minimal morbidity and radical resection. However, the clinical predictive factors associated with recurrence are limited. Here, we investigated optimal treatment of non-functioning pituitary adenoma. Methods We enrolled 289 patients who presented with non-functioning pituitary adenoma between January 2000 and January 2012 and who had received follow-up for at least one year for this retrospective study. Of these patients, 152 were male and 137 were female, with a median age of 51 years (range 15.79 years) and a median follow-up of four years (range 1.12.6 years). Characteristics of patients and tumors were reviewed with electronic medical records and radiologic images, retrospectively. Results Of the tumors, 193 were gross-totally resected, 53 were near-totally resected, and 43 were sub-totally resected. The extent of resection and adjuvant radiotherapy were both statistically significant prognostic factors of recurrence. Immunohistochemistry of tumor specimens did not yield consistent results. Conclusion With a high rate of recurrence, NFPA should be closely followed-up over a long-term period. Improvement of surgical techniques with advanced surgical equipment and adjuvant radiosurgery would lead to reduce the recurrence rate and improve patients' outcome. PMID:27195254

  18. Pituitary adenomas: historical perspective, surgical management and future directions

    PubMed Central

    Theodros, Debebe; Patel, Mira; Ruzevick, Jacob; Lim, Michael; Bettegowda, Chetan

    2016-01-01

    Pituitary adenomas are among the most common central nervous system tumors. They represent a diverse group of neoplasms that may or may not secrete hormones based on their cell of origin. Epidemiologic studies have documented the incidence of pituitary adenomas within the general population to be as high as 16.7%. A growing body of work has helped to elucidate the pathogenesis of these tumors. Each subtype has been shown to demonstrate unique cellular changes potentially leading to tumorigenesis. Surgical advancements over several decades have included microsurgery and the employment of the endoscope for surgical resection. These advancements increase the likelihood of gross-total resection and have resulted in decreased patient morbidity. PMID:26497533

  19. The genetics of pituitary adenomas.

    PubMed

    Vandeva, Silvia; Jaffrain-Rea, Marie-Lise; Daly, Adrian F; Tichomirowa, Maria; Zacharieva, Sabina; Beckers, Albert

    2010-06-01

    Pituitary adenomas are one of the most frequent intracranial tumors with a prevalence of clinically-apparent tumors close to 1:1000 of the general population. They are clinically significant because of hormone overproduction and/or tumor mass effects in addition to the need for neurosurgery, medical therapies and radiotherapy. The majority of pituitary adenomas have a sporadic origin with recognized genetic mutations seldom being found; somatotropinomas are an exception, presenting frequent somatic GNAS mutations. In this and other phenotypes, tumorigenesis could possibly be explained by altered function of genes implicated in cell cycle regulation, growth factors or their receptors, cell-signaling pathways, specific hormonal factors or other molecules with still unclear mechanisms of action. Genetic changes, such as allelic loss or gene amplification, and epigenetic changes, usually by promoter methylation, have been implicated in abnormal gene expression, but alternative mechanisms may be present. Familial cases of pituitary adenomas represent 5% of all pituitary tumors. MEN1 mutations cause multiple endocrine neoplasia type 1 (MEN1), while the Carney complex (CNC) is characterized by mutations in the protein kinase A regulatory subunit-1alpha (PRKAR1A) gene or changes in a locus at 2p16. Recently, a MEN1-like condition, MEN4, was found to be related to mutations in the CDKN1B gene. The clinical entity of familial isolated pituitary adenomas (FIPA) is characterized by genetic defects in the aryl hydrocarbon receptor interacting protein (AIP) gene in about 15% of all kindreds and 50% of homogenous somatotropinoma families. Identification of familial cases of pituitary adenomas is important as these tumors may be more aggressive than their sporadic counterparts. PMID:20833337

  20. [Genetics of Colorectal Tumorigenesis (Possibilities of Testing and Screening Prediction of Hereditary Form of Colorectal Cancer--Lynch Syndrome)].

    PubMed

    Mľkva, I

    2016-01-01

    Colorectal cancer is currently one of the most frequent cancers in developed countries. Understanding the molecular principles of its pathogenesis has recently come into focus of many oncogenetic studies. Colorectal cancer also represents an ideal model for the study of molecular basis of cancerogenesis owing to the wide availability of its precursor lesions and the existence of several notorious genetic predispositions such as familial adenomatous polyposis and Lynch syndrome. The classical model of colorectal tumorigenesis, described by Fearon and Vogelstein, suggested the idea of a conventional progression from adenoma to carcinoma. It was based on a careful analysis of mutations occurring within particular stages of carcinogenesis with regards to their stepwise accumulations leading to neoplastic transformation of the colonic epithelium. Recently, new evidence has pointed to an alternative model of colorectal tumorigenesis introducing the concept of serrated precursors. This alternative pathway, known as the serrated pathway, has provided a new perspective on colorectal cancer development. Nowadays, three molecular pathways leading to colorectal tumorigenesis are recognized: 1. the chromosomal instability pathway typified by familial adenomatous polyposis; 2. the mutator pathway characterized by inactivation of DNA mismatch repair genes such as in Lynch syndrome or a number of sporadic colorectal cancers; 3. the hypermethylation serrated neoplasia pathway characterized by excessive methylation of some CpG islands in the promoter region of certain genes (positive CpG islands methylator phenotype) (CIMP+).

  1. Use of integrin alpha 6 transcripts in a stool mRNA assay for the detection of colorectal cancers at curable stages

    PubMed Central

    Beaulieu, Jean-François; Herring, Elizabeth; Kanaoka, Shigeru; Tremblay, Éric

    2016-01-01

    Objective An important criterion for colorectal cancer (CRC) screening is the ability to detect lesions at a curable stage. In the present study, we have assessed the integrin α6 subunit transcript (ITGA6) as part of a stool assay for the detection of colorectal lesions. Results In comparison with control samples, ITGA6 levels were found to be significantly increased at all stages (P < 0.01). Receiver operating characteristic analysis revealed areas under the curve of 0.89 for the prediction of CRC with 81% sensitivity and 88% specificity and of 0.90 for the prediction of advanced adenomas (Ad) with 75% sensitivity and 88% specificity. The ITGA6A variant was also found to be increased relative to ITGA6 in stage II and III CRCs. Combining ITGA6 with other selected transcripts and/or immunochemical fecal occult blood test (iFOBT) results further increased sensitivity and specificity for the detection of colorectal lesions. Patients and Methods ITGA6 detection used alone and under various combinations including detection of other mRNA markers and iFOBT was assessed on stool samples obtained from 175 patients (91 CRCs, 24 Ad and 60 healthy controls). Conclusions These data confirm the usefulness and reliability of an mRNA stool assay for the detection of colorectal lesions. The validation of additional candidate genes and their analysis in multiplex qPCR represents a powerful and robust approach that can be combined with iFOBT results to improve the detection of colorectal lesions. PMID:26895101

  2. Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study)

    PubMed Central

    NISHI, TOMOHIRO; HAMAMOTO, YASUO; NAGASE, MICHITAKA; DENDA, TADAMICHI; YAMAGUCHI, KENSEI; AMAGAI, KENJI; MIYATA, YOSHINORI; YAMANAKA, YASUHIRO; YANAI, KAI; ISHIKAWA, TSUTOMU; KUROKI, YOSHIFUMI; FUJII, HIROFUMI

    2016-01-01

    Little is known about the clinical impact of salvage panitumumab with irinotecan for metastatic colorectal cancer (mCRC) patients. The present study conducted a single-arm, multicenter phase II trial for mCRC with skin toxicity prevention program. The subjects were mCRC patients with wild-type KRAS, who showed resistance to fluoropyrimidine, oxaliplatin and irinotecan. Panitumumab was administered at a dose of 6 mg/kg every 2 weeks by intravenous infusion over 60 min, and irinotecan was administered at a dose of 100–180 mg/m2 every 2 weeks by intravenous infusion over 90 min, depending on the preceding treatment dose. To prevent skin toxicities, a moisturizer was applied and oral antibiotics (100 mg minocycline twice daily) were initiated for 6 weeks. The primary endpoint was the response rate (RR) determined by independent reviewers. Secondary endpoints were the disease control rate (DCR), progression-free survival (PFS) time, overall survival (OS) time and adverse events. A total of 35 patients were enrolled between October 2010 and March 2012. The median age was 61 years (range, 41–76 years), with 25 male and 10 female patients. The initial irinotecan dose was 150 mg/m2 in 19 patients and 180 mg/m2 in 1 patient. The remaining patients were treated with ≤120 mg/m2. A central review indicated a partial response in 8 patients (22.9%) and stable disease in 6 patients (17.1%), with an RR of 22.9% (95% confidence interval, 12.1–39.0) and a DCR of 40%. The RR of the patients with standard-dose irinotecan (150 or 180 mg/m2) was 30%, although that of low-dose irinotecan (100–120 mg/m2) was 13%. The median PFS time was 2.7 months, and the median OS time was 6.3 months. A grade 3 or above acne-like rash developed in 25.7% of patients. In conclusion, panitumumab and irinotecan as salvage therapy for mCRC KRAS wild-type patients with skin toxicity prevention exhibits limited efficacy. In particular, the effect of low-dose irinotecan with panitumumab appears to be

  3. Biological Mechanisms Underlying Structural Changes Induced by Colorectal Field Carcinogenesis Measured with Low-Coherence Enhanced Backscattering (LEBS) Spectroscopy

    PubMed Central

    Mutyal, Nikhil N.; Radosevich, Andrew; Tiwari, Ashish K.; Stypula, Yolanda; Wali, Ramesh; Kunte, Dhananjay; Roy, Hemant K.; Backman, Vadim

    2013-01-01

    We previously reported the utility of Low-Coherence Enhanced Backscattering (LEBS) Spectroscopy in detecting optical changes in uninvolved rectal mucosa, changes that are indicative of the presence of advanced colorectal adenomas elsewhere in the colon (field carcinogenesis). We hypothesized that the alterations in optical signatures are due to structural changes in colonocytes. To elucidate those colonocyte changes, we used LEBS and an early time point in an animal model of colorectal field carcinogenesis – rats treated with azoxymethane (AOM). Changes in LEBS markers in intact mucosa from AOM-treated rats could be at least partially attributed to changes in colonocytes. To investigate the molecular mechanisms underlying the colonocyte abnormalities in premalignant colon, we took a candidate approach. We compared expression profiles of genes implicated directly or indirectly in cytoskeletal dysregulation in colorectal tissues from saline-treated versus AOM-treated rats. Our data suggest that a number of genes known to affect colon tumorigenesis are up-regulated in colonocytes, and genes previously reported to be tumor suppressors in metastatic cancer are down-regulated in colonocytes, despite the colonocytes being histologically normal. To further understand the role of the cytoskeleton in generating changes in optical markers of cells, we used pharmacological disruption (using colchicine) of the cytoskeleton. We found that differences in optical markers (between AOM- and control-treated rats) were negated by the disruption, suggesting cytoskeletal involvement in the optical changes. These studies provide significant insights into the micro-architectural alterations in early colon carcinogenesis, and may enable optimization of both bio-photonic and molecular risk stratification techniques to personalize colorectal cancer screening. PMID:23431406

  4. Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases

    PubMed Central

    2013-01-01

    Background More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer. Methods From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome. Results In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion. Conclusions Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread. PMID:23497091

  5. Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.

    PubMed

    Kissiedu, Juliana O; Prayson, Richard A

    2016-02-01

    We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas.

  6. Sellar gangliocytoma with adrenocorticotropic and prolactin adenoma.

    PubMed

    Kissiedu, Juliana O; Prayson, Richard A

    2016-02-01

    We report a case of a 60-year-old man who presented with weight gain, headaches, dizziness, erectile dysfunction and decreased libido. He was found to have elevated adrenocorticotropic hormone (ACTH) and prolactin serum levels. The imaging studies revealed a 1.4 cm sella/suprasellar mass which was compressing the optic chiasm. Histologic slides of the lesion showed a pituitary adenoma, marked by a proliferation of biphenotypic appearing cells, associated with a gangliocytoma, and marked by a proliferation of atypical appearing neuronal cells arranged against a glial-appearing background. Pituitary adenoma-gangliocytomas are benign combination tumors that rarely occur in the sellar region. Adenomas in this setting are sometimes functional, and rare patients with mixed adenomas (adenomas secreting more than one hormone) have been reported. To our knowledge, there has been only one other report of a combined ACTH and prolactin-producing adenoma with gangliocytoma, reported in a patient who also had acromegaly. In our patient, the immunohistochemical stains demonstrated that the bulk of the adenoma cells stained with prolactin antibody, and scattered clusters of cells within the adenoma stained positively for ACTH. The adenoma did not stain with antibodies to any of the other anterior pituitary hormones. Postoperatively, the elevated prolactin and ACTH levels returned to normal levels and there was no evidence of residual tumor. Adequate sampling and immunohistochemistry are important in rendering a correct diagnosis and in identifying the hormone status of mixed adenoma-gangliocytomas. PMID:26314658

  7. Laparoscopic Colorectal Training Gap in Colorectal and Surgical Residents

    PubMed Central

    Soliman, Mark; Williamson, Paul; Ferrara, Andrea

    2016-01-01

    Background and Objectives: Laparoscopic colorectal surgery is an established safe procedure with demonstrated benefits. Proficiency in this specialty correlates with the volume of cases. We examined training in this surgical field for both general surgery and colon and rectal surgery residents to determine whether the number of cases needed for proficiency is being realized. Methods: We examined the Accreditation Council for Graduate Medical Education (ACGME) and American Board of Colorectal Surgeons (ABCRS) operative statistics for graduating general surgery and colon and rectal surgery residents. Results: Although the number of advanced laparoscopy cases had increased for general surgery residents, there was still a significant gap in case volume between the average number of laparoscopic colorectal operations performed by graduating general surgery residents (21.6) and those performed by graduating colon and rectal surgery residents (81.9) in 2014. Conclusion: There is a gap between general surgery and colon and rectal surgery residency training for laparoscopic colorectal surgery. General surgery residents are not meeting the volume of cases necessary for proficiency in colorectal surgery. This deficit represents a structural difference in training. PMID:27493468

  8. Colorectal hepatic metastasis: Evolving therapies

    PubMed Central

    Macedo, Francisco Igor B; Makarawo, Tafadzwa

    2014-01-01

    The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection. PMID:25067997

  9. Berberine may rescue Fusobacterium nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment

    PubMed Central

    Zhao, Hui-Jun; Sun, Tian-Tian; Chen, Hui-Min; Chen, Hao-Yan; An, Hui-Fang; Weng, Yu-Rong; Yu, Jun; Li, Min; Qin, Wen-Xin; Ma, Xiong; Shen, Nan; Hong, Jie; Fang, Jing-Yuan

    2015-01-01

    Background Accumulating evidence links colorectal cancer (CRC) with the intestinal microbiota. However, the disturbance of intestinal microbiota and the role of Fusobacterium nucleatum during the colorectal adenoma-carcinoma sequence have not yet been evaluated. Methods 454 FLX pyrosequencing was used to evaluate the disturbance of intestinal microbiota during the adenoma-carcinoma sequence pathway of CRC. Intestinal microbiota and mucosa tumor-immune cytokines were detected in mice after introducing 1,2-dimethylhydrazine (DMH), F. nucleatum or Berberine (BBR), using pyrosequencing and Bio-Plex Pro™ cytokine assays, respectively. Protein expressions were detected by western blotting. Results The levels of opportunistic pathogens, such as Fusobacterium, Streptococcus and Enterococcus spp. gradually increased during the colorectal adenoma-carcinoma sequence in human fecal and mucosal samples. F. nucleatum treatment significantly altered lumen microbial structures, with increased Tenericutes and Verrucomicrobia (opportunistic pathogens) (P < 0.05 = in wild-type C57BL/6 and mice with DMH treatment). BBR intervention reversed the F. nucleatum-mediated increase in opportunistic pathogens, and the secretion of IL-21/22/31, CD40L and the expression of p-STAT3, p-STAT5 and p-ERK1/2 in mice, compared with mice fed with F. nucleatum alone. Conclusions F. nucleatum colonization in the intestine may prompt colorectal tumorigenesis. BBR could rescue F. nucleatum-induced colorectal tumorigenesis by modulating the tumor microenvironment and blocking the activation of tumorigenesis-related pathways. PMID:26397137

  10. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2012-09-01

    Colorectal cancer (CRC) is one of the most frequent neoplasms in developed countries and up to 5% of all cases occur in the context of a hereditary syndrome. These hereditary forms often require a high index of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has major consequences not only for the patient--for whom there are highly effective preventive measures--but also for the patient's relatives, who may carry the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of Lynch's syndrome and serrated polyposis syndrome.

  11. [Genetics of colorectal cancer].

    PubMed

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes.

  12. Longitudinal molecular characterization of endoscopic specimens from colorectal lesions

    PubMed Central

    Minarikova, Petra; Benesova, Lucie; Halkova, Tereza; Belsanova, Barbora; Suchanek, Stepan; Cyrany, Jiri; Tuckova, Inna; Bures, Jan; Zavoral, Miroslav; Minarik, Marek

    2016-01-01

    AIM: To compare molecular profiles of proximal colon, distal colon and rectum in large adenomas, early and late carcinomas. To assess feasibility of testing directed at molecular markers from this study in routine clinical practice. METHODS: A prospective 3-year study has resulted in the acquisition of samples from 159 large adenomas and 138 carcinomas along with associated clinical parameters including localization, grade and histological type for adenomas and localization and stage for carcinomas. A complex molecular phenotyping has been performed using multiplex ligation-dependent probe amplification technique for the evaluation of CpG-island methylator phenotype (CIMP), PCR fragment analysis for detection of microsatellite instability and denaturing capillary electrophoresis for sensitive detection of somatic mutations in KRAS, BRAF, TP53 and APC genes. RESULTS: Molecular types according to previously introduced Jass classification have been evaluated for large adenomas and early and late carcinomas. An increase in CIMP+ type, eventually accompanied with KRAS mutations, was notable between large adenomas and early carcinomas. As expected, the longitudinal observations revealed a correlation of the CIMP+/BRAF+ type with proximal location. CONCLUSION: Prospective molecular classification of tissue specimens is feasible in routine endoscopy practice. Increased frequency of some molecular types corresponds to the developmental stages of colorectal tumors. As expected, a clear distinction is notable for tumors located in proximal colon supposedly arising from the serrated (methylation) pathway. PMID:27239120

  13. Can We Select Patients for Colorectal Cancer Prevention with Aspirin?

    PubMed

    Kraus, Sarah; Sion, Daniel; Arber, Nadir

    2015-01-01

    Aspirin has been extensively investigated in the context of the prevention of cardiovascular disease. It has one of the strongest cumulative evidence supporting its use in colorectal cancer (CRC) chemoprevention. Epidemiological, clinical, and observational studies have demonstrated that aspirin and non-steroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, can protect against CRC and significantly reduce its incidence. Moreover, prospective randomized controlled trials of colorectal polyp recurrence and in patients with hereditary CRC syndromes have shown that aspirin can produce regression of existing colorectal adenomas and prevent the formation of new polyps. However, the lowest effective doses, treatment duration, target populations, and the effects on survival are not entirely clear. Although not common serious side effects and in particular gastrointestinal and intracerebral hemorrhage do occur, better selection of individuals who might benefit the most from aspirin use must be carefully performed in order to maximize their risk/benefit ratio. In the era of precision medicine, genetic information, blood and/or urinary biomarkers, could potentially help in tailoring chemopreventive therapeutic strategies, based on aspirin use, while limiting adverse toxic effects. The current review will cover the use of aspirin for the prevention of colorectal adenomas and CRC, potential markers for chemoprevention, and patient stratification. PMID:26369678

  14. A Phase II Clinical Study of mFOLFOX6 Plus Bevacizumab as First-line Therapy for Japanese Advanced/Recurrent Colorectal Cancer Patients

    PubMed Central

    Nishina, Tomohiro; Takano, Yoshinao; Denda, Tadamichi; Yasui, Hisateru; Takeda, Koji; Ura, Takashi; Esaki, Taito; Okuyama, Yusuke; Kondo, Ken; Takahashi, Yasuo; Sugiyama, Yasuyuki; Muro, Kei

    2013-01-01

    Objective In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer. Methods Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m2) and levofolinate calcium (200 mg/m2) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m2) was injected, followed by infusion of 5-fluorouracil (2400 mg/m2) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate. Results Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0–63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4–14.5 months) and 28.5 months [95% confidence interval: 23.1 months–(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy. Conclusions Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate. PMID:23999770

  15. An internally and externally validated nomogram for predicting the risk of irinotecan-induced severe neutropenia in advanced colorectal cancer patients

    PubMed Central

    Ichikawa, W; Uehara, K; Minamimura, K; Tanaka, C; Takii, Y; Miyauchi, H; Sadahiro, S; Fujita, K; Moriwaki, T; Nakamura, M; Takahashi, T; Tsuji, A; Shinozaki, K; Morita, S; Ando, Y; Okutani, Y; Sugihara, M; Sugiyama, T; Ohashi, Y; Sakata, Y

    2015-01-01

    Background: In Asians, the risk of irinotecan-induced severe toxicities is related in part to UGT1A1*6 (UGT, UDP glucuronosyltransferase) and UGT1A1*28, variant alleles that reduce the elimination of SN-38, the active metabolite of irinotecan. We prospectively studied the relation between the UGT1A1 genotype and the safety of irinotecan-based regimens in Japanese patients with advanced colorectal cancer, and then constructed a nomogram for predicting the risk of severe neutropenia in the first treatment cycle. Methods: Safety data were obtained from 1312 patients monitored during the first 3 cycles of irinotecan-based regimen in a prospective observational study. In development of the nomogram, multivariable logistic regression analysis was used to test the associations of candidate factors to severe neutropenia in the first cycle. The final nomogram based on the results of multivariable analysis was constructed and validated internally using a bootstrapping technique and externally in an independent data set (n=350). Results: The UGT1A1 genotype was confirmed to be associated with increased risks of irinotecan-induced grade 3 or 4 neutropenia and diarrhoea. The final nomogram included type of regimen, administered dose of irinotecan, gender, age, UGT1A1 genotype, Eastern Cooperative Oncology Group performance status, pre-treatment absolute neutrophil count, and total bilirubin level. The model was validated both internally (bootstrap-adjusted concordance index, 0.69) and externally (concordance index, 0.70). Conclusions: Our nomogram can be used before treatment to accurately predict the probability of irinotecan-induced severe neutropenia in the first cycle of therapy. Additional studies should evaluate the effect of nomogram-guided dosing on efficacy in patients receiving irinotecan. PMID:25880011

  16. Prolactin-Secreting Pituitary Adenomas

    PubMed Central

    Martin, Mary C.; Schriock, Eldon D.; Jaffe, Robert B.

    1983-01-01

    Prolactin-secreting pituitary adenoma is a common cause of gynecologic problems that include oligomenorrhea, infertility, amenorrhea and galactorrhea. Diagnosis requires a combination of endocrine testing and radiologic evaluation. The diagnosis of macroadenomas is usually straightforward and these large tumors may be associated with mass effects such as severe headache, nerve palsies or visual changes. Microadenomas may be more subtle in presentation, and the diagnosis of hyperprolactinemia without radiologic evidence of a tumor frequently is problematic. The management of prolactin-secreting adenoma remains controversial, with no clear consensus or indication for surgical versus medical treatment. Surgical intervention is a realistic option for those patients who have access to an experienced neurosurgeon and who have tumor characteristics that offer a reasonable hope for cure. Many questions remain to be answered, including the cause, natural history of development and the optimum treatment for individual cases. Images PMID:6659490

  17. Benign pleomorphic adenomas in children.

    PubMed

    Malone, B; Baker, S R

    1984-01-01

    Benign pleomorphic adenomas of the salivary glands in children are rare. Reported are 30 patients under the age of 21 years presenting with this neoplasm. Twelve patients were first seen with recurrent or persistent tumor following previous attempts at removal. Retreatment resulted in control of the neoplasm in eight patients with follow-up from 5 to 24 years. Two additional patients have developed malignant degeneration of their neoplasms. All 18 previously untreated patients have remained free of recurrence. As with adults, the treatment of choice for benign pleomorphic adenomas of the parotid gland developing in children is parotidectomy with preservation of the facial nerve. Tumors arising in the submandibular gland are best treated by complete excision of the gland as well as the tumor.

  18. Cytomorphology of tubular adenoma breast--a case report.

    PubMed

    Ravindra, Savithri; Suguna, B V

    2006-04-01

    Tubular adenoma a 'pure adenoma' is a benign neoplasm of breast presenting clinically like fibroadenoma. We report cytological and histological features of tubular adenoma in a 24 year old female with brief review of literature.

  19. Fibrosarcoma complicating irradiated pituitary adenoma

    SciTech Connect

    Shi, T.; Farrell, M.A.; Kaufmann, J.C.

    1984-09-01

    Eight years after radiation therapy (5000 rads of 60Co) for a pituitary adenoma, a patient developed a sellar fibrosarcoma. The tumor had an aggressive growth pattern: it infiltrated the optic nerve, sphenoidal air sinus, hypothalamus, and both cavernous sinuses, where compression of the left internal carotid artery resulted in a massive hemispheric infarction. Surgery was ineffective in arresting rapid growth of the lesion; death occurring 5 months after onset of symptoms.

  20. Pleomorphic adenoma of the larynx.

    PubMed

    Argat, M; Born, I A; Maier, H; Mohadjer, C

    1994-01-01

    Tumors arising from minor salivary glands are extremely rare neoplasms in the larynx. Of the few reports of pleomorphic adenomas in this site, most have subglottic locations while only one case has involved the true vocal cord and seven cases have had supraglottic locations. We present a case of benign mixed tumor located in the posterior commissure which, to our knowledge, is the first reported in the world literature.

  1. [Cystic degeneration of autonomous adenomas (author's transl)].

    PubMed

    Galvan, G; Pohl, G B

    1976-01-01

    Follow-up examinations in four patients with autonomous adenomas showed cystic degeneration in the autonomous adenomas 20 to 45 months after the first examination, confirmed by fine needle biopsy. Clinical improvement occurred three times with scintigraphic compensation, decompensation occurred once without clinical deterioration. In particular cases a therapeutic policy of wait and see is justified in patients with autonomous adenomas because they may remain clinically inconspicuous for a long time; on the other hand there is a possibility of a cystic degeneration.

  2. Clinically silent somatotroph adenomas are common

    PubMed Central

    Wade, Alisha N; Baccon, Jennifer; Grady, M Sean; Judy, Kevin D; O’Rourke, Donald M; Snyder, Peter J

    2011-01-01

    Objective Somatotroph adenomas are typically recognized when they secrete GH excessively and cause acromegaly. Both ‘silent’ somatotroph adenomas (immunohistochemical evidence of GH excess without biochemical or clinical evidence) and ‘clinically silent’ somatotroph adenomas (immunohistochemical and biochemical evidence but no clinical evidence) have occasionally been reported. The relative frequency of each presentation is unknown. The goal of this study was, therefore, to determine the frequency of clinically silent somatotroph adenomas, a group that is potentially recognizable in vivo. Design We retrospectively identified 100 consecutive patients who had surgically excised and histologically confirmed pituitary adenomas. Methods Each pituitary adenoma was classified immunohistochemically by pituitary cell type. Somatotroph adenomas were further classified as ‘classic’ (obvious clinical features of acromegaly and elevated serum IGF1), ‘subtle’ (subtle clinical features of acromegaly and elevated IGF1), ‘clinically silent’ (no clinical features of acromegaly but elevated IGF1), and ‘silent’ (no clinical features of acromegaly and normal IGF1). Results Of the 100 consecutive pituitary adenomas, 29% were gonadotroph/glycoprotein, 24% somatotroph, 18% null cell, 15% corticotroph, 6% lactotroph, 2% thyrotroph, and 6% not classifiable. Of the 24 patients with somatotroph adenomas, classic accounted for 45.8%, subtle 16.7%, clinically silent 33.3%, and silent 4.2%. Conclusions Clinically silent somatotroph adenomas are more common than previously appreciated, representing one-third of all somatotroph adenomas. IGF1 should be measured in all patients with a sellar mass, because identification of a mass as a somatotroph adenoma expands the therapeutic options and provides a tumor marker to monitor treatment. PMID:21493729

  3. Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway.

    PubMed

    Ito, Miki; Kanno, Shinichi; Nosho, Katsuhiko; Sukawa, Yasutaka; Mitsuhashi, Kei; Kurihara, Hiroyoshi; Igarashi, Hisayoshi; Takahashi, Taiga; Tachibana, Mami; Takahashi, Hiroaki; Yoshii, Shinji; Takenouchi, Toshinao; Hasegawa, Tadashi; Okita, Kenji; Hirata, Koichi; Maruyama, Reo; Suzuki, Hiromu; Imai, Kohzoh; Yamamoto, Hiroyuki; Shinomura, Yasuhisa

    2015-09-15

    Human gut microbiota is being increasingly recognized as a player in colorectal cancers (CRCs). Evidence suggests that Fusobacterium nucleatum (F. nucleatum) may contribute to disease progression and is associated with CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) in CRCs; however, to date, there are no reports about the relationship between F. nucleatum and molecular features in the early stage of colorectal tumorigenesis. Therefore, we investigated the presence of F. nucleatum in premalignant colorectal lesions. In total, 465 premalignant lesions (343 serrated lesions and 122 non-serrated adenomas) and 511 CRCs were studied. We determined the presence of F. nucleatum and analyzed its association with molecular features including CIMP, MSI and microRNA-31 status. F. nucleatum was detected in 24% of hyperplastic polyps, 35% of sessile serrated adenomas (SSAs), 30% of traditional serrated adenomas (TSAs) and 33% of non-serrated adenomas. F. nucleatum was more frequently detected in CIMP-high premalignant lesions than in CIMP-low/zero lesions (p = 0.0023). In SSAs, F. nucleatum positivity increased gradually from sigmoid colon to cecum (p = 0.042). F. nucleatum positivity was significantly higher in CRCs (56%) than in premalignant lesions of any histological type (p < 0.0001). In conclusion, F. nucleatum was identified in premalignant colorectal lesions regardless of histopathology but was more frequently associated with CIMP-high lesions. Moreover, F. nucleatum positivity increased according to histological grade, suggesting that it may contribute to the progression of colorectal neoplasia. Our data also indicate that F. nucleatum positivity in SSAs may support the "colorectal continuum" concept.

  4. Faecal immunochemical test-based colorectal cancer screening programme SVIT in Slovenia: pilot phase.

    PubMed

    Tepeš, Bojan; Stabuc, Borut; Stefanovič, Milan; Bračko, Matej; Frkovič Grazio, Snežana; Novak Mlakar, Dominika; Maučec Zakotnik, Jožica

    2014-07-01

    Colorectal cancer (CRC) is the second most common cancer in Slovenia. The 5-year survival of patients depends on the clinical stage at presentation. More than 70% of patients with CRC are diagnosed as being in stage III or IV, with a 5-year survival rate of 52.7%. To improve the detection rate of CRC and to detect CRC in its early and more curable stage, a national screening programme is needed. In the year 2008, we started a pilot phase of the National CRC screening programme. We invited 9091 Slovene residents aged 64-68 years from Ljubljana, Kranj, and Celje regions, of whom 3807 responded to our invitation (41.9%). Two kits of the faecal immune test were sent to 3117 participants who met the inclusion criteria, and 2829 (90.7%) tests were returned. The compliance rate in our pilot programme was 32.9%. Among the patients who responded positively, 7.5% were positive. Until February 2009, 193 colonoscopies had been performed at DC Bled, DC Lipa and AM DC Rogaška. Intubation to the caecum was carried out in 99.4% of colonoscopies. Histology specimens were taken from 135 patients (70%). The adenoma detection rate was 53.8% (59.8% for men and 47.9% for women; P<0.05). We detected 1-17 adenomas per patient (2.4 on average). Advanced adenomas were detected in 60 patients (31%; 35.1% of men and 27.1% of women; P<0.05). Invasive carcinoma was detected in 15 patients (7.7%; 12.4% of men and 3.1% of women; P<0.05). Ten of them (73.3%) were in clinical stage I or II. In the pilot phase of the CRC screening programme the majority of CRCs were detected at early clinical stages. Invasive cancers were detected in 7.7% of patients. In almost all patients adenomas were resected at screening colonoscopy, thus reducing the possibility of later development of CRC in those patients.

  5. A case-cohort study for the disease natural history of adenoma-carcinoma and de novo carcinoma and surveillance of colon and rectum after polypectomy: implication for efficacy of colonoscopy.

    PubMed

    Chen, C-D; Yen, M-F; Wang, W-M; Wong, J-M; Chen, T H-H

    2003-06-16

    The disease natural history of colorectal neoplasm regarding two opposing theories, adenoma-carcinoma sequence and de novo carcinoma theory, is controversial and rarely quantified. The aims of this study are therefore to estimate the dwelling times of adenoma-carcinoma sequence by adenoma size and histological type, taking de novo carcinoma into account. The efficacy of polypectomy was therefore estimated making allowance for two pathways. A case-cohort design, underpinning a cohort with 13 908 subjects (including 10 496 normal subjects, 2652 polyps, 760 colorectal cancers) who underwent the first examination of colonoscopy between 1979 and 1998, was devised to estimate parameters associated with two opposing theories by randomly selecting 305 normal subjects, 300 patients with polyps, and 116 colorectal cancers from the cohort. All the 2652 polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy. For the five-state model associated with adenoma size, dwelling times of small (0.6-1 cm) and large adenoma (>1 cm) are 7.75 and 5.27 years for the model without considering de novo, and 17.48 and 15.90 years for the model taking de novo carcinoma into account. Similar findings are observed for the model associated with histological type. The estimated proportions of de novo carcinoma are 31.87% from the model by adenoma size and 27.81% from the model by histological type. Compared to size less than 5 mm, patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold (0.67-10.74) and 4.25-fold (1.23-14.70), respectively, for the risk of malignant transformation. There are similar findings for the model by histological type. The estimates of overall efficacy of colonoscopy in reducing CRC is 73% for the model allowing for de novo carcinoma and 88% for the model without considering de novo carcinoma theory. The efficacy of diminutive adenoma and small adenoma increases with follow

  6. Primary prevention of colorectal cancer: lifestyle, nutrition, exercise.

    PubMed

    Martínez, María Elena

    2005-01-01

    The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in

  7. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively. PMID:26738269

  8. [Old phenotype and new genotypes. Pituitary adenomas].

    PubMed

    Gérard, C; Jedidi, H; Petrossians, P; Krzesinski, F; Daly, A; Beckers, A

    2015-11-01

    Gigantism and acromegaly, usually caused by a pituitary adenoma linked inappropriate secretion of growth hormone (GH), are generally considered as very rare diseases, even if, according to some authors, their cumulative prevalence is about 1/5000. Starting from the historical case of a giant from Liège we shall describe the different types of GH pituitary adenomas and their pathophysiology. We shall particularly discuss rare forms of inherited GH secreting pituitary adenomas like the FIPA (familial inherited isolated pituitary adenomas) and the X-LAG (X linked acrogigantism), both described for the first time in Liège, in 2000 and 2014, respectively.

  9. Carcinomas ex monomorphic adenoma of salivary glands.

    PubMed

    Luna, M A; Batsakis, J G; Tortoledo, M E; del Junco, G W

    1989-08-01

    A clinicopathological analysis of eight examples of carcinomas arising from salivary gland monomorphic adenomas, carcinomas ex monomorphic adenoma, is presented. These uncommon to rare neoplasms have a predilection for the parotid glands, are diagnosed about a decade later than their benign precursors, and most often arise from the dermal analogue type of monomorphic adenoma. As judged by follow-up periods of two to 16 years, carcinomas ex monomorphic adenoma are locally aggressive neoplasms with the clinical course marred by recurrences but without regional or distant metastases.

  10. B-RAF mutations are a rare event in pituitary adenomas.

    PubMed

    De Martino, I; Fedele, M; Palmieri, D; Visone, R; Cappabianca, P; Wierinckx, A; Trouillas, J; Fusco, A

    2007-01-01

    Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis. PMID:17318013

  11. Emerging stool-based and blood-based non-invasive DNA tests for colorectal cancer screening: the importance of cancer prevention in addition to cancer detection.

    PubMed

    Pickhardt, Perry J

    2016-08-01

    Colorectal cancer (CRC) screening can be undertaken utilizing a variety of distinct approaches, which provides both opportunities and confusion. Traditionally, there has often been a trade-off between the degree of invasiveness of a screening test and its ability to prevent cancer, with fecal occult blood testing (FOBT) and optical colonoscopy (OC) at each end of the spectrum. CT colonography (CTC), although currently underutilized for CRC screening, represents an exception since it is only minimally invasive, yet provides accurate evaluation for advanced adenomas. More recently, the FDA approved a multi-target stool DNA test (Cologuard) and a blood-based test (Epi proColon) for average-risk CRC screening. This commentary will provide an overview of these two new non-invasive tests, including the clinical indications, mechanism of action, and diagnostic performance. Relevance to radiology practice, including a comparison with CTC, will also be discussed. PMID:27259335

  12. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer

    PubMed Central

    Church, Timothy Robert; Wandell, Michael; Lofton-Day, Catherine; Mongin, Steven J; Burger, Matthias; Payne, Shannon R; Castaños-Vélez, Esmeralda; Blumenstein, Brent A; Rösch, Thomas; Osborn, Neal; Snover, Dale; Day, Robert W; Ransohoff, David F

    2014-01-01

    Background As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting. Objective We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population. Design Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates. Results 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I–IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%). Conclusions Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas. Clinical Trial Registration Number: NCT00855348 PMID:23408352

  13. Five Myths about Colorectal Cancer

    MedlinePlus

    ... ACS » Your Local Offices Close + - Text Size Five Myths About Colorectal Cancer In many cases, colorectal cancer ... screening tests you need, when you need them. Myth: Colorectal cancer is a man’s disease. Truth: Colorectal ...

  14. Interendoscopist variability in proximal colon polyp detection is twice higher for serrated polyps than adenomas

    PubMed Central

    Bretagne, Jean-François; Hamonic, Stéphanie; Piette, Christine; Viel, Jean-François; Bouguen, Guillaume

    2016-01-01

    AIM To assess the interendoscopist variability in the detection of colorectal polyps according to their location and histological type. METHODS This study was a retrospective analysis of prospectively collected data from a regional colorectal cancer (CRC) screening program; 2979 complete colonoscopies from 18 endoscopists were included. Variability in performance between endoscopists for detection of at least one adenoma (A), one proximal adenoma (PA), one distal adenoma (DA), and one proximal serrated polyp (PSP) was assessed by using multilevel logistic regression models. RESULTS The observed detection rates among the 18 endoscopists ranged from 24.6% to 47.6% (mean = 35.7%) for A, from 19.1% to 39.0% (mean = 29.4%) for DA, from 6.0% to 22.9% (mean = 12.4%) for PA, and from 1.3% to 19.3% (mean = 6.9%) for PSP. After adjusting for patient-level variables (sex, age), the interendoscopist detection rates variability achieved a significant level for A, PA, and PSP but not for DA (P = 0.03, P = 0.02, P = 0.02 and P = 0.08, respectively). This heterogeneity, as measured by the variance partition coefficient, was approximately threefold higher for PA (6.6%) compared with A (2.1%), and twofold higher for PSP (12.3%) compared with PA. CONCLUSION These results demonstrate significant interendoscopist variability for proximal polyp particularly for serrated polyps, but not for distal adenoma detection. These findings contribute to explain the decreased effectiveness of complete colonoscopies at preventing proximal CRCs and the need to carefully assess the proximal colon during scope procedure. PMID:27784967

  15. Escape from negative regulation of growth by transforming growth factor beta and from the induction of apoptosis by the dietary agent sodium butyrate may be important in colorectal carcinogenesis.

    PubMed

    Hague, A; Manning, A M; van der Stappen, J W; Paraskeva, C

    1993-09-01

    There are a number of lines of evidence suggesting that transforming growth factor beta (TGF beta) has an important role in the control of intestinal growth and differentiation. In vivo localization studies show that TGF beta expression occurs predominantly in the differentiated non proliferating cells of the intestinal epithelium. The use of an antisense expression vector for TGF beta resulted in an increased tumorigenicity in an antisense-transfected cancer cell line. In vitro proliferation studies showed colorectal premalignant adenoma cells to be more sensitive to the growth inhibitory effects of TGF beta than colorectal cancer cells. Furthermore the conversion of an adenoma to a carcinoma was accompanied by a reduced response to the inhibitory effects of TGF beta. The acquisition of partial or complete resistance to the inhibitory effects of TGF beta may be an important late event in colorectal carcinogenesis. Of further interest is the possibility that clonal selection could occur even more rapidly in colorectal tumour cells which not only had lost response to TGF beta inhibition but produced TGF beta and were growth stimulated by it. This could have the advantage of not only inhibiting the growth of surrounding less malignantly advanced cells but of also escaping from their potential growth suppressive influence. Carcinogenesis is not, however, simply losing response to negative regulators of growth; the fully malignant cell has to acquire new characteristics of invasiveness and metastatic potential. Growth factors including TGF beta may have a role in the complex cascade of events leading to the activation of proteolytic enzymes which are involved in progression to an invasive phenotype. Cell proliferation in the large bowel, as well as being under the control of endogenous growth factors, is also under the influence of dietary components in the lumen such as the naturally occurring fatty acid sodium butyrate. Sodium butyrate at physiological concentrations

  16. Epigenetic silencing of monoallelically methylated miRNA loci in precancerous colorectal lesions

    PubMed Central

    Menigatti, M; Staiano, T; Manser, C N; Bauerfeind, P; Komljenovic, A; Robinson, M; Jiricny, J; Buffoli, F; Marra, G

    2013-01-01

    Epigenetic silencing of protein-encoding genes is common in early-stage colorectal tumorigenesis. Less is known about the methylation-mediated silencing of genes encoding microRNAs (miRNAs), which are also important epigenetic modulators of gene expression. Using quantitative PCR, we identified 56 miRNAs that were expressed in normal colorectal mucosa and in HT29 colorectal cancer cells treated with demethylating agents but not in untreated HT29 cells, suggesting that they probably undergo methylation-induced silencing during colorectal tumorigenesis. One of these, miR-195, had recently been reported to be underexpressed in colorectal cancers and to exert tumor-suppressor effects in colorectal cancer cells. We identified the transcription start site (TSS) for primary miRNA (pri-miR)-497/195, the primary precursor that yields miR-195 and another candidate on our list, miR-497, and a single CpG island upstream to the TSS, which controls expression of both miRNAs. Combined bisulfite restriction analysis and bisulfite genomic sequencing studies revealed monoallelic methylation of this island in normal colorectal mucosa (50/50 samples) and full methylation in most colorectal adenomas (38/50; 76%). The hypermethylated precancerous lesions displayed significantly downregulated expression of both miRNAs. Similar methylation patterns were observed at two known imprinted genes, MEG3 and GNAS-AS1, which encode several of the 56 miRNAs on our list. Imprinting at these loci was lost in over half the adenomas (62% at MEG3 and 52% at GNAS-AS1). Copy-number alterations at MEG3, GNAS-AS1 and pri-miR-497/195, which are frequent in colorectal cancers, were less common in adenomas and confined to tumors displaying differential methylation at the involved locus. Our data show that somatically acquired, epigenetic changes at monoallelically methylated regions encoding miRNAs are relatively frequent in sporadic colorectal adenomas and might contribute to the onset and progression of

  17. Epigenetic silencing of monoallelically methylated miRNA loci in precancerous colorectal lesions.

    PubMed

    Menigatti, M; Staiano, T; Manser, C N; Bauerfeind, P; Komljenovic, A; Robinson, M; Jiricny, J; Buffoli, F; Marra, G

    2013-01-01

    Epigenetic silencing of protein-encoding genes is common in early-stage colorectal tumorigenesis. Less is known about the methylation-mediated silencing of genes encoding microRNAs (miRNAs), which are also important epigenetic modulators of gene expression. Using quantitative PCR, we identified 56 miRNAs that were expressed in normal colorectal mucosa and in HT29 colorectal cancer cells treated with demethylating agents but not in untreated HT29 cells, suggesting that they probably undergo methylation-induced silencing during colorectal tumorigenesis. One of these, miR-195, had recently been reported to be underexpressed in colorectal cancers and to exert tumor-suppressor effects in colorectal cancer cells. We identified the transcription start site (TSS) for primary miRNA (pri-miR)-497/195, the primary precursor that yields miR-195 and another candidate on our list, miR-497, and a single CpG island upstream to the TSS, which controls expression of both miRNAs. Combined bisulfite restriction analysis and bisulfite genomic sequencing studies revealed monoallelic methylation of this island in normal colorectal mucosa (50/50 samples) and full methylation in most colorectal adenomas (38/50; 76%). The hypermethylated precancerous lesions displayed significantly downregulated expression of both miRNAs. Similar methylation patterns were observed at two known imprinted genes, MEG3 and GNAS-AS1, which encode several of the 56 miRNAs on our list. Imprinting at these loci was lost in over half the adenomas (62% at MEG3 and 52% at GNAS-AS1). Copy-number alterations at MEG3, GNAS-AS1 and pri-miR-497/195, which are frequent in colorectal cancers, were less common in adenomas and confined to tumors displaying differential methylation at the involved locus. Our data show that somatically acquired, epigenetic changes at monoallelically methylated regions encoding miRNAs are relatively frequent in sporadic colorectal adenomas and might contribute to the onset and progression of

  18. FIT for the future: a case for risk-based colorectal cancer screening using the faecal immunochemical test.

    PubMed

    Cooper, J A; Moss, S M; Smith, S; Seaman, H E; Taylor-Phillips, S; Parsons, N; Halloran, S P

    2016-07-01

    Worldwide, the guaiac faecal occult blood test (gFOBT) is being replaced with the more accurate faecal immunochemical test (FIT) for colorectal cancer (CRC) screening. From January 2016, the National Screening Committee in the UK has recommended a change from the gFOBT to the FIT following a successful Bowel Cancer Screening Programme pilot study with over 40 000 participants. Although the test has shown improved uptake and the ability to detect significantly more colorectal cancers and advanced adenomas, the higher uptake and test positivity will challenge the capacity of colonoscopy services. One of the main advantages of the FIT is that it provides a quantitative haemoglobin concentration which has been shown to relate to the risk of CRC. Risk scoring systems which combine the FIT concentration with risk factor assessment have been shown to improve the sensitivity of the test. This individualized approach to screening could enable those at greatest risk to be referred for colonoscopy, optimizing resource use and ultimately patient outcomes. PMID:27135192

  19. Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study.

    PubMed

    Zhu, Xiangzhu; Shrubsole, Martha J; Ness, Reid M; Hibler, Elizabeth A; Cai, Qiuyin; Long, Jirong; Chen, Zhi; Li, Guoliang; Jiang, Ming; Hou, Lifang; Kabagambe, Edmond K; Zhang, Bing; Smalley, Walter E; Edwards, Todd L; Giovannucci, Edward L; Zheng, Wei; Dai, Qi

    2016-10-01

    Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18-0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54-0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer. © 2015 Wiley Periodicals, Inc.

  20. Relationship between expression of onco-related miRNAs and the endoscopic appearance of colorectal tumors.

    PubMed

    Nakagawa, Yoshihito; Akao, Yukihiro; Taniguchi, Kohei; Kamatani, Akemi; Tahara, Tomomitsu; Kamano, Toshiaki; Nakano, Naoko; Komura, Naruomi; Ikuno, Hirokazu; Ohmori, Takafumi; Jodai, Yasutaka; Miyata, Masahiro; Nagasaka, Mistuo; Shibata, Tomoyuki; Ohmiya, Naoki; Hirata, Ichiro

    2015-01-01

    Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We examined the expression of onco-related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52 sporadic flat elevated adenomas or early cancers to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. The expression levels of miR-143, -145, and -34a were significantly reduced in most of the exophytic tumors compared with those in the flat elevated ones. In type 2 cancers, the miRNA expression profile was very similar to that of the exophytic tumors. The expression levels of miR-7 and -21 were significantly up-regulated in some flat elevated adenomas compared with those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down-regulated cases of the adenoma-carcinoma sequence and in some of the de novo types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed to the triggering mechanism leading to the carcinogenetic process. These findings indicated that the expression of onco-related miRNA was associated with the morphological appearance of colorectal tumors. PMID:25584614

  1. Bilateral canalicular adenoma of the parotid gland.

    PubMed

    Liess, Benjamin D; Lane, Robert V; Frazier, Shellaine; Zitsch, Robert P

    2006-03-01

    Canalicular adenoma is a rare benign salivary gland tumor that occurs almost exclusively in the upper lip. Rarely, this benign tumor may occur multifocally in the oral cavity. We report a case of canalicular adenoma in bilateral parotid glands, discuss histological characteristics, and review this tumor.

  2. Prevalence of Adenomas Found on Colonoscopy in Patients With HIV

    PubMed Central

    Gutkin, Ellen; Hussain, Syed A.; Mehta, Preeti; Kim, Sang H.; Pollack, Simcha; Rubin, Moshe

    2012-01-01

    Background The life expectancy of patients with HIV has increased significantly since the introduction of highly active antiretroviral therapy in 1995. Although this population of patients now carries less risk for the development of AIDS defining illnesses and malignancies, they are still at risk for non-AIDS defining cancers, such as colon, prostate, and breast. Several studies have shown that HIV infected patients have a higher prevalence of advanced colonic neoplasia which occur at a younger age. Our aim is to examine the prevalence of adenomas and adenocarcinoma in HIV patients undergoing colonoscopy. Methods HIV patients seen in our gastroenterology clinic and inpatient service undergoing colonoscopy were identified from 2010 - 2011. Indication was screening in 27 patients and diagnostic in 23 patients. Significant lesions were defined as adenomas, serrated polyps, and adenocarcinoma. Results Total 50 patients were included in the study, 32 male and 18 female (mean age: 53.6; range 37 - 72 years), 25 patients were African American, 21 were Hispanic, 3 were Caucasian, and one was Indian, 39 patients had undetectable HIV RNA, 30 patients had CD4 lymphocyte counts greater than 500, 20 had CD4 lymphocyte counts less than 500, and 4 patients had CD4 lymphocyte counts less than 200, 52% (26/50) of patients had polyps. Significant lesions (adenomas and serrated polyps) were seen in 34% (17/50) of patients, 39% in diagnostic and 30% in screening procedures (P = 0.56). Males were found to have significant lesions 28% of the time as compared to 44% of females (P = 0.35), 43% of Hispanics had significant lesions versus 24% of African Americans (P = 0.22), 25% of the patients under age 50 were found to have significant lesions, 45% of the patients with detectable HIV RNA levels were found to have significant lesions vs 31% (P = 0.48). Surprisingly, patients with CD4 counts > 500 had significantly more adenomas than those with CD4 counts < 500, 47% vs 15% (P = 0.03). No

  3. [The recurrent multifocal pleomorphic adenoma].

    PubMed

    Vigili, M G; Sciarretta, F; Marzetti, A; Marzetti, F

    1993-01-01

    Pleomorphic adenoma (P.A.), the most common tumor of the salivary gland, demonstrates a peculiar clinicopathological behaviour for numerous reasons: the high recurrence rate following primary surgery (up to 50%), the appearance of malignancy (2-9%), the reported number of distant metastases histologically identical to the primary P.A. From among 71 cases of benign parotid tumors treated from Nov. 89 to Nov. 92 in the ENT Department of "Regina Elena", the National Cancer Institute in Rome, six particular cases showed multiple force of P.A. recurring after primary surgery performed from 3 to 32 years previously and are object of discussion in this study. All of these six cases had multiple recurrences, usually manifest as nodular clusters in the parotid area, while in three cases appeared as well a recurrence in the soft tissue of the neck, far removed from the parotid space, with no involvement of neck nodes as was revealed through histological examination following neck dissection. A hypothetical mechanism of diffusion is discussed. The Authors agree with the opinion which holds the surgeon's inability to successfully eradicate primary tumors responsible for the high frequency of recurrences. The surgical technique of "enucleation" is, in fact, inadequate in P.A. excision owing the high risk of mishandling or rupturing the tumor capsule with a consequent seeding of the tumor onto the surgical bed. Lateral lobectomy, with identification of the facial nerve, or total conservative parotidectomy (for deep lobe adenoma) are correct techniques in treating primary P.A.. The Authors also discuss management of recurrent P.A. in relation to facial nerve involvement. Preservation of the seventh nerve with eventual post-operative radiation should be considered an alternative to nerve sacrifice in selected cases of recurrent pleomorphic adenoma.

  4. Metastasizing pleomorphic adenoma with myoepithelial cell predominance.

    PubMed

    Cresson, D H; Goldsmith, M; Askin, F B; Reddick, R L; Postma, D S; Siegal, G P

    1990-12-01

    The biological behavior of pleomorphic adenomas (mixed tumors) of salivary gland origin is complex. Tumors with benign histologic features may exhibit recurrence and locally aggressive behavior especially after incomplete excision. A small percentage of pleomorphic adenomas have obvious malignant components in epithelial or in both epithelial and mesenchymal components and can metastasize. There are also rare case reports which appear to document typical pleomorphic adenomas of salivary gland with histologically identical visceral and lymph node metastases. Recently myoepithelial cell proliferation has been identified as a possible predictor of aggressive clinical behavior in otherwise histologically benign pleomorphic adenomas. We report such a parotid gland lesion with local recurrence and retroperitoneal spread. DNA-flow cytometry of cells from the paraffin-embedded primary and metastasis showed similar aneuploid populations. Aneuploidy appeared to reflect the malignant potential of this particular pleomorphic adenoma and suggests that DNA-flow cytometry of salivary gland tumors may yield important prognostic information.

  5. Non-functioning pituitary adenomas.

    PubMed

    Chanson, P; Brochier, S

    2005-01-01

    The vast majority (>80%) of clinically non-functioning pituitary adenomas (NFPAs) are gonadotroph-cell adenomas, as demonstrated by immunocytochemistry. However, they are rarely associated with increased levels of dimeric LH or FSH. Increased levels of uncombined subunits (free alpha-subunit mainly, LH-beta subunit more rarely) are more frequently encountered, but are generally modest. The main problems raised by NFPA are mass effects problems, responsible for optic chiasm compression or deficient hormone secretion resulting from compression of normal anterior pituitary cells. The therapeutic management of NFPA may require combination of different options. The strategy of observation only for patients with incidentally discovered pituitary adenomas may be appropriate, provided that the tumor is well-delimited, small, has no extension with risk of neurological or visual chiasm compression, and that a meticulous hormonal work-up has ruled out the possibility of a minimal hormonal hypersecretion. Transsphenoidal surgery allows improvement in visual disturbances due to chiasmal syndrome in most patients, and sometimes, in pituitary function. After surgery alone, nearly 30% (between 10 and 69%, according to the series) of patients relapse within 5 to 10 yr. Radiotherapy is proposed either as a systematic adjunct or only if a significant remnant persists. Systematic radiation therapy is supported by the low relapse rate (mean, 11%; range, 6-21%) observed when radiation therapy is systematically associated with surgery. However, irradiation is almost always followed by hypopituitarism which might be associated with a reduction in life expectancy, despite appropriate replacement therapy. Results of medical treatment are disappointing. Dopamine agonist bromocriptine decreases gonadotropin and alpha-subunit in vitro and in vivo, but, in clinical studies, was poorly effective in reducing supranormal gonadotropins and free subunits levels, and rarely produced a minimal tumoral

  6. Pleomorphic adenoma of the breast.

    PubMed

    Chen, K T

    1990-06-01

    The clinicopathologic features of 2 new and 24 previously reported cases of pleomorphic adenoma of the breast are reviewed. This benign breast tumor resembles its salivary gland counterpart histologically. The circumscription and preferential juxta-areolar location suggest large breast duct origin of the tumors. Inappropriate surgery, i.e., mastectomy, was performed in 42% of the cases. Misdiagnosis and the resulting inappropriate treatment can easily be avoided if the pathologist includes this entity in the differential diagnosis when confronted with unusual differentiated epithelial breast lesions.

  7. Diet, microbiota, and colorectal cancer.

    PubMed

    Akin, Hakan; Tözün, Nurdan

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications. PMID:25291132

  8. Synchronous occurrence of appendiceal mucinous cystadenoma, with colon adenocarcinoma and tubulovillous rectal adenoma: Management and review of the literature

    PubMed Central

    Salemis, Nikolaos S.; Nakos, Georgios; Katikaridis, Ilias; Zografidis, Andreas

    2016-01-01

    Appendiceal mucocele (AM) is a rare clinical entity comprising 8% of all appendiceal tumors, and it is seen in 0.2-0.3% of all appendectomy specimens. Apart from sporadic cases, there are no enough published data about the incidence of synchronous appendiceal tumors in patients with colorectal cancer. We describe a very rare case of synchronous occurrence of AM, colon adenocarcinoma, and tubulovillous adenoma of the rectum and review the relevant literature. We conclude that thorough preoperative and perioperative evaluations are mandatory in patients undergoing surgery for colorectal cancer to exclude a synchronous colon or an appendiceal primary tumor. Larger prospective studies are necessary to accurately determine the incidence of synchronous appendiceal tumors and colorectal cancer. PMID:27433069

  9. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth

    PubMed Central

    Grivennikov, Sergei I.; Wang, Kepeng; Mucida, Daniel; Stewart, C. Andrew; Schnabl, Bernd; Jauch, Dominik; Taniguchi, Koji; Yu, Guann-Yi; Osterreicher, Christoph H.; Hung, Kenneth E.; Datz, Christian; Feng, Ying; Fearon, Eric R.; Oukka, Mohamed; Tessarollo, Lino; Coppola, Vincenzo; Yarovinsky, Felix; Cheroutre, Hilde; Eckmann, Lars; Trinchieri, Giorgio; Karin, Michael

    2013-01-01

    colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth. PMID:23034650

  10. Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

    PubMed Central

    Fitzlaff, Rüdiger; Röming, Hermann; Ameis, Detlev; Heinecke, Achim; Kunsch, Steffen; Ellenrieder, Volker; Ströbel, Philipp; Schepke, Michael; Meister, Tobias

    2014-01-01

    Objectives The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC). Methods This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR). Results The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates. Conclusions EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas. Trial Registration ClinicalTrials.gov NCT02034929. PMID:25470133

  11. Colorectal Cancer Prevention

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  12. Sessile serrated adenomas in the proximal colon are likely to be flat, large and occur in smokers

    PubMed Central

    Rustagi, Tarun; Rangasamy, Priya; Myers, Matthew; Sanders, Melinda; Vaziri, Haleh; Wu, George Y; Birk, John W; Protiva, Petr; Anderson, Joseph C

    2013-01-01

    AIM: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs). METHODS: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period. RESULTS: One hundred and twenty patients with SSAs were identified: 61% were distal and 39% were proximal SSAs. Proximal SSAs were more likely to be flat than distal (100% vs 78% respectively; P = 0.0001). Proximal SSAs were more likely to occur in smokers (OR = 2.63; 95%CI: 1.17-5.90; P = 0.02) and in patients with family history of colorectal cancer (OR = 4.72; 95%CI: 1.43-15.55; P = 0.01) compared to distal. Proximal SSAs were statistically more likely to be ≥ 6 mm in size (OR = 2.94; P = 0.008), and also more likely to be large (≥ 1 cm) (OR = 4.55; P = 0.0005) compared to the distal lesions. Smokers were more likely to have proximal (P = 0.02), flat (P = 0.01) and large (P = 0.007) SSAs compared to non-smokers. Compared to proximal tubular adenomas, proximal SSAs were more likely to be large and occur in smokers. CONCLUSION: Proximal SSAs which accounted for two-fifths of all SSAs were more likely to present as flat lesions, larger SSAs, and were more likely to occur in smokers and in patients with family history of colorectal cancer. Our data has implications for colorectal cancer screening. PMID:23983429

  13. Colorectal Cancer Epidemiology in the Nurses’ Health Study

    PubMed Central

    Lee, Dong Hoon; Giovannucci, Edward L.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to identifying risk and protective factors for colorectal adenomas and colorectal cancer (CRC). Methods. We performed a narrative review of the publications using the NHS between 1976 and 2016. Results. Existing epidemiological studies using the NHS have reported that red and processed meat, alcohol, smoking, and obesity were associated with an increased risk of CRC, whereas folate, calcium, vitamin D, aspirin, and physical activity were associated with decreased risk of CRC. Moreover, modifiable factors, such as physical activity, vitamin D, folate, insulin and insulin-like growth factor binding protein-1, and diet quality, were identified to be associated with survival among CRC patients. In recent years, molecular pathological epidemiological studies have been actively conducted and have shown refined results by molecular subtypes of CRC. Conclusions. The NHS has provided new insights into colorectal adenomas, CRC etiology, and pathogenic mechanisms. With its unique strengths, the NHS should continue to contribute to the field of CRC epidemiology and play a major role in public health. PMID:27459444

  14. Mineralocorticoid production of adrenal cortical adenomas.

    PubMed

    Gláz, E; Rácz, K; Varga, I; Kiss, R; Tóth, M; Fütö, L

    1993-04-01

    We studied in vitro and in vivo corticosteroid production as well as the presence of symptoms of an increased mineralocorticoid effect in patients with 'silent' adrenal cortical adenomas, and compared these results to those found in patients with classical mineralocorticoid excess syndromes. We found that under in vitro conditions, cells from 'silent' adrenal cortical adenomas (n = 19) produced substantial amounts of both zona glomerulosa and fasciculata steroids, although the production of steroids in these cells was lower compared to that in mineralocorticoid-producing adenoma cells (n = 26). Patients with aldosterone-producing and 'silent' adenomas had significantly increased plasma atrial natriuretic peptide levels, which remained non-suppressible after upright posture and furosemide administration. Of the 25 patients with 'silent' adenomas, 11 had low and non-stimulable plasma renin activity (PRA) before but, in most cases, not after adrenal surgery. When compared to those with normal PRA (n = 14), patients with low PRA 'silent' adenomas (n = 11) had higher blood pressure which was significantly reduced after surgery, and a mild hypokalemia before but not after surgery. Although basal plasma concentrations of aldosterone, 18-hydroxy-corticosterone, corticosterone, deoxycorticosterone, 18-hydroxy-DOC, cortisol,11-deoxycortisol and 17-hydroxy-progesterone (17-OH-P) were not increased in either groups of 'silent' adenomas, ACTH stimulation produced a hyperreactive response for all measured steroids, of which an extremely high 17-OH-P seemed to be one of the most intriguing findings. We consider that these observations in 'silent' adrenal cortical adenomas may justify surgical intervention, irrespective of the size and potential malignancy of these adenomas. PMID:8481352

  15. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed Central

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  16. Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer

    PubMed Central

    Wang, Qian; Li, Zexin; Yang, Yiqiong; Chen, Zhiguo; Wang, Jianguo; Zhao, Weixing; Zhang, Huijuan; Chen, Jiwang; Dong, Huali; Shen, Kui; Diamond, Alan M.; Yang, Wancai

    2016-01-01

    PRSS8 is a membrane-anchored serine protease prostasin and has been shown an association with carcinogenesis. Herein we found that PRSS8 expression was significantly reduced in colorectal adenomas and adenocarcinomas. The decreased PRSS8 was well correlated with clinical stages, poor differentiation and shorter survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the inhibition of colorectal cancer cell proliferation, knockdown of PRSS8 accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer cell growth in nude mice. Mechanistic studies revealed that PRSS8 inhibited Sphk1/S1P/Stat3/Akt signaling pathway, in terms of inverse association between PRSS8 and Sphk1 in human colorectal cancers and in Sphk1-/− mice. In conclusion, PRSS8 acts as a tumor suppressor by inhibiting Sphk1/S1P/Stat3/Akt signaling pathway, and could be used as a biomarker to monitor colorectal carcinogenesis and predict outcomes. PMID:27050145

  17. Tumor suppressor PRSS8 targets Sphk1/S1P/Stat3/Akt signaling in colorectal cancer.

    PubMed

    Bao, Yonghua; Li, Kai; Guo, Yongchen; Wang, Qian; Li, Zexin; Yang, Yiqiong; Chen, Zhiguo; Wang, Jianguo; Zhao, Weixing; Zhang, Huijuan; Chen, Jiwang; Dong, Huali; Shen, Kui; Diamond, Alan M; Yang, Wancai

    2016-05-01

    PRSS8 is a membrane-anchored serine protease prostasin and has been shown an association with carcinogenesis. Herein we found that PRSS8 expression was significantly reduced in colorectal adenomas and adenocarcinomas. The decreased PRSS8 was well correlated with clinical stages, poor differentiation and shorter survival time of colorectal cancer. Furthermore, increase of PRSS8 led to the inhibition of colorectal cancer cell proliferation, knockdown of PRSS8 accelerated cell proliferation in vitro, and overexpressing PRSS8 retarded cancer cell growth in nude mice. Mechanistic studies revealed that PRSS8 inhibited Sphk1/S1P/Stat3/Akt signaling pathway, in terms of inverse association between PRSS8 and Sphk1 in human colorectal cancers and in Sphk1-/- mice. In conclusion, PRSS8 acts as a tumor suppressor by inhibiting Sphk1/S1P/Stat3/Akt signaling pathway, and could be used as a biomarker to monitor colorectal carcinogenesis and predict outcomes. PMID:27050145

  18. Giant Pleomorphic Adenoma of the Parotid Gland.

    PubMed

    Sajid, Muhammad; Rehman, Sajid; Misbah, Junaid

    2015-10-01

    Salivary gland tumours are a relatively rare entity. Pleomorphic adenoma is the most common amongst these, comprising 60 - 70% of all parotid tumours. Pleomorphic adenomas are benign and tend to increase in size slowly. Here we are presenting a case of giant pleomorphic adenoma of the parotid, being the largest in size to be excised in Pakistan in recorded literature measuring 24 x 22 x 12 cm and weighing 1.8 kgs. Superficial parotidectomy was done with an excellent cosmetic outcome. PMID:26522191

  19. Vitamin E deficiency ataxia associated with adenoma.

    PubMed

    Benomar, A; Yahyaoui, M; Marzouki, N; Birouk, N; Bouslam, N; Belaidi, H; Amarti, A; Ouazzani, R; Chkili, T

    1999-01-01

    Vitamin E is one of the most important lipid-soluble antioxidant nutrient. Severe vitamin E deficiency (VED) can have a profound effect on the central nervous system. VED causes ataxia and peripheral neuropathy that resembles Friedreich's ataxia. We report here a patient presenting this syndrome, but also a prolactin and FSH adenoma. Both the neurological syndromes and the adenoma regressed after treatment with alpha-tocopherol. Although, the presence of the prolactinoma in this patient may not be related to his vitamin E deficiency, alpha-tocopherol treatment seems to be beneficial and might usefully be tested in patients with hypophyseal secreting other forms of adenoma. PMID:10064178

  20. [Pleomorphic adenoma of minor salivary glands].

    PubMed

    Cwalina, Piotr; Skorek, Andrzej; Narozny, Waldemar; Stankiewicz, Czesław

    2002-01-01

    Pleomorphic adenoma, a benign tumor often seen in ENT practice, arises either from minor as well from major salivary glands. 5-14% of tumors occur in minor glands. Sixteen cases of minor salivary gland pleomorphic adenomas are studied. Eight of them originate from the oral cavity: 6 from the palate, one from the lower lip and one from the cheek. Two oral adenomas were malignant. In 4 patients tumors occur in the nasal cavity and in two other patients--in the neck. The clinical and pathological features of these patients are presented. Special attention is given to malignant transformation and the rate of recurrence of the tumors.

  1. Giant pleomorphic adenoma of the parotid gland.

    PubMed

    Çetin, Mehmet Ali; Ikincioğulları, Aykut; Saygı, Gökçe; Hatipoğlu, Hatice Gül; Köseoğlu, Sabri; Dere, Hüseyin

    2012-01-01

    Pleomorphic adenomas are the most common benign tumors of the salivary glands. These adenomas generally present without pain and are slowly enlarged. However, they can reach enormous sizes, because they are often neglected by the patient and due to late diagnosis and intervention because of fear of surgery or sociocultural factors. This may lead to functional, aesthetic and social problems. In this article, we present a 55-year-old female patient with a giant pleomorphic adenoma in size of 15x15x20 cm, who presented with the complaint of a mass enlarged and swollen for 20 years in her left neck and face and underwent a successful surgery.

  2. [Pleomorphic adenoma of the maxillary sinus].

    PubMed

    Leunig, A; Grevers, G

    1994-11-01

    Pleomorphic adenoma is the most common benign tumour of the salivary glands, especially the parotid gland. In the present paper we introduce the rare case of a pleomorphic adenoma of the maxillary sinus in a 82-year-old man who was referred to our outpatient clinic with nasal obstruction and occasional events of nose bleeding. Thorough investigation, using endoscopy and computed tomography, revealed a mass extending from the left maxillary sinus to the nasal cavity; the tumour was removed surgically; pathological examination showed a pleomorphic adenoma with no signs of malignancy.

  3. Metastasizing pleomorphic adenoma of the nasal septum.

    PubMed

    Freeman, S B; Kennedy, K S; Parker, G S; Tatum, S A

    1990-11-01

    Pleomorphic adenoma is the most common benign tumor of glandular tissue occurring in the head and neck region. There have been several reports of metastasis of this benign-appearing tumor from the salivary glands to distant sites, suggesting hematogenous spread and implantation. Although occurrence of pleomorphic adenoma on the nasal septum has been described, to our knowledge this is the first reported case of recurrent septal pleomorphic adenoma with histologically benign tissue in an enlarged metastatic ipsilateral submandibular lymph node, suggesting lymphatic spread. The literature concerning the subject is reviewed. Wide septal excision and modified neck dissection is the recommended treatment.

  4. Immunotherapy for colorectal cancer.

    PubMed

    Koido, Shigeo; Ohkusa, Toshifumi; Homma, Sadamu; Namiki, Yoshihisa; Takakura, Kazuki; Saito, Keisuke; Ito, Zensho; Kobayashi, Hiroko; Kajihara, Mikio; Uchiyama, Kan; Arihiro, Seiji; Arakawa, Hiroshi; Okamoto, Masato; Gong, Jianlin; Tajiri, Hisao

    2013-12-14

    The incidence of colorectal cancer (CRC) is on the rise, and the prognosis for patients with recurrent or metastatic disease is extremely poor. Although chemotherapy and radiation therapy can improve survival rates, it is imperative to integrate alternative strategies such as immunotherapy to improve outcomes for patients with advanced CRC. In this review, we will discuss the effect of immunotherapy for inducing cytotoxic T lymphocytes and the major immunotherapeutic approaches for CRC that are currently in clinical trials, including peptide vaccines, dendritic cell-based cancer vaccines, whole tumor cell vaccines, viral vector-based cancer vaccines, adoptive cell transfer therapy, antibody-based cancer immunotherapy, and cytokine therapy. The possibility of combination therapies will also be discussed along with the challenges presented by tumor escape mechanisms. PMID:24379570

  5. Robotics in Colorectal Surgery

    PubMed Central

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  6. Pituitary adenoma-neuronal choristoma is a pituitary adenoma with ganglionic differentiation.

    PubMed

    Nguyen, Michaela T; Lavi, Ehud

    2015-12-01

    The presence of ganglion cells within an endocrine pituitary tumor has been named hamartoma, choristoma, gangliocytoma, or most recently pituitary adenoma-neuronal choristoma (PANCH). The presence of neuronal differentiation in regular pituitary adenomas has been previously suggested, however, its origin, the extent of its presence, and the relationship between the neuronal elements and the pituitary adenoma remain uncertain. Thus, to further explore the neuronal potential of pituitary tumors, we used immunohistochemistry on pituitary tumors of different grades, with a neuronal antigen protein (NeuN) antibody as a specific marker for mature neuronal differentiation. We found NeuN expression in 26.47% (9/34) cases of pituitary tumors without ganglionic differentiation (7 adenomas, 1 atypical adenoma and 1 pituitary carcinoma), in addition to NeuN expression in pituitary adenomas with ganglionic cells (2/2). Thus, neuronal expression is an innate property of pituitary adenomas. We propose that the rare presence of ganglionic cells in pituitary adenomas is not the result of a separate lesion or "collision sellar tumors", as previously suggested, but a ganglionic neuronal differentiation in an endocrine neoplasm. The ganglionic cells may be arising from uncommitted stem/progenitor cells that contain both neuronal and endocrine properties. A label of "pituitary adenoma with ganglionic differentiation" would better reflect the dual differentiation in a neuroendocrine tumor than the current label "PANCH".

  7. Postoperative radiosurgery of pituitary adenomas.

    PubMed

    Valentino, V

    1991-01-01

    From 1984-1990, 52 patients with pituitary adenomas had postoperative radiosurgery for incomplete surgical removal or regrowth of the tumor. The atraumatic Greitz-Bergström fixation head device was adopted for the stereotactic procedure and irradiation was performed with a linear accelerator. Because of the variability of the tumor response, a 10-20 Gy single dose was directed at 1-2 targets and radiosurgery repeated if the result was unsatisfactory. The median radiation dose was 30 Gy. No adverse effects occurred. Regression of pretreatment symptoms caused by tumor mass was observed in 67% of patients. GH and PRL activity decreased in 20 patients, was stable in 11 and increased in 2 prolactinomas. CT studies showed disappearance of the tumor in 4 patients and shrinkage in 36. Postoperative radiosurgery is a valuable method of treatment whenever pituitary surgery has been incomplete.

  8. Sessile serrated adenoma/polyps: Where are we at in 2016?

    PubMed Central

    Singh, Rajvinder; Zorrón Cheng Tao Pu, Leonardo; Koay, Doreen; Burt, Alastair

    2016-01-01

    It is currently known that colorectal cancers (CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway (50%-70%); the mutator “Lynch syndrome” route (3%-5%); and the serrated pathway (30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA), the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders, submucosal injection of a dye solution (for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.

  9. Sessile serrated adenoma/polyps: Where are we at in 2016?

    PubMed Central

    Singh, Rajvinder; Zorrón Cheng Tao Pu, Leonardo; Koay, Doreen; Burt, Alastair

    2016-01-01

    It is currently known that colorectal cancers (CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway (50%-70%); the mutator “Lynch syndrome” route (3%-5%); and the serrated pathway (30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA), the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders, submucosal injection of a dye solution (for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions. PMID:27678358

  10. Improved Detection of Microsatellite Instability in Early Colorectal Lesions

    PubMed Central

    Albrecht, Dawn M.; Grimes, Ian C.; Weiss, Jennifer M.; Matkowskyj, Kristina A.; Agni, Rashmi M.; Vyazunova, Irina; Clipson, Linda; Storts, Douglas R.; Thliveris, Andrew T.; Halberg, Richard B.

    2015-01-01

    Microsatellite instability (MSI) occurs in over 90% of Lynch syndrome cancers and is considered a hallmark of the disease. MSI is an early event in colon tumor development, but screening polyps for MSI remains controversial because of reduced sensitivity compared to more advanced neoplasms. To increase sensitivity, we investigated the use of a novel type of marker consisting of long mononucleotide repeat (LMR) tracts. Adenomas from 160 patients, ranging in age from 29–55 years old, were screened for MSI using the new markers and compared with current marker panels and immunohistochemistry standards. Overall, 15 tumors were scored as MSI-High using the LMRs compared to 9 for the NCI panel and 8 for the MSI Analysis System (Promega). This difference represents at least a 1.7-fold increase in detection of MSI-High lesions over currently available markers. Moreover, the number of MSI-positive markers per sample and the size of allelic changes were significantly greater with the LMRs (p = 0.001), which increased confidence in MSI classification. The overall sensitivity and specificity of the LMR panel for detection of mismatch repair deficient lesions were 100% and 96%, respectively. In comparison, the sensitivity and specificity of the MSI Analysis System were 67% and 100%; and for the NCI panel, 75% and 97%. The difference in sensitivity between the LMR panel and the other panels was statistically significant (p<0.001). The increased sensitivity for detection of MSI-High phenotype in early colorectal lesions with the new LMR markers indicates that MSI screening for the early detection of Lynch syndrome might be feasible. PMID:26252492

  11. MicroRNAs in Human Pituitary Adenomas

    PubMed Central

    Wang, Elaine Lu; Qian, Zhi Rong

    2014-01-01

    MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. PMID:25548562

  12. Genetics Home Reference: familial isolated pituitary adenoma

    MedlinePlus

    ... 1,000 people. FIPA, though, is quite rare, accounting for approximately 2 percent of pituitary adenomas. More ... be inherited? More about Inheriting Genetic Conditions Diagnosis & Management These resources address the diagnosis or management of ...

  13. Palatal pleomorphic adenoma in a child.

    PubMed

    Noghreyan, A; Gatot, A; Maor, E; Fliss, D M

    1995-04-01

    Benign salivary gland tumours in childhood are rare. We present a case of a pleomorphic adenoma arising in a minor salivary gland within the hard palate, review the literature and discuss the diagnostic and therapeutic features of the condition.

  14. [Malignant pleomorphic adenoma of the palate].

    PubMed

    Martín Vázquez, C; Muñoz Colado, M; Lorente Tortosa, J M; Abad Róyo, J M; Alvarez Montero, O L

    1998-03-01

    Pleomorphic adenoma or mixed tumor is the most common benign neoplasm of the minor salivary glands. These tumors rarely have malignant features. Three varieties are differentiated by histological features and tumor behavior. Whether malignant tumors develop on benign adenomas or are malignant from onset is still not known. A malignant mixed tumor of the minor salivary glands of the palate is reported. The difficulty of histological diagnosis, in spite of immunohistochemical techniques, is emphasized and the surgical treatment is described.

  15. Canalicular adenoma of the parotid gland.

    PubMed

    Philpott, Carl M; Kendall, Charles; Murty, George E

    2005-01-01

    Canalicular adenomas are a rare form of benign tumour that occur in salivary glands, occurring mainly in the upper lip and minor salivary glands of the buccal mucosa. The authors report the fifth case and the first in the otorhinolaryngological literature of a canalicular adenoma of the parotid gland. Its specific histological features are difficult to detect on fine needle aspiration and its multifocal nature can lead to recurrence and this must be considered in the clinical management.

  16. Pleomorphic adenoma of the nasal septum.

    PubMed

    Jassar, P; Stafford, N D; MacDonald, A W

    1999-05-01

    Pleomorphic adenoma is the commonest benign tumour of the major salivary glands. It can also occur in minor salivary glands, mainly in the oral cavity, but also in other sites in the head and neck both within and outwith the upper aerodigestive tract. We present a rare case of pleomorphic adenoma of the nasal septum with consideration of the clinical management and a review of the literature.

  17. [Pleomorphic adenoma with bilateral pulmonary metastasis].

    PubMed

    De Kerangal, X; Poirrier, P; Soulard, R; Dot, J M; Ségneuric, J B; L'Her, P; Jancovici, R; Saint-Blancart, P

    2001-11-01

    We report a new case of pleomorphous adenoma of the submaxillary glands with multiple lung metastases. Histological proof was obtained on the thoracoscopic surgical specimen. Clinically, this benign tumor presents as a malignant tumor. Diagnosis has been a subject of debate; surgical resection is indicated. Diagnosis is achieved by elimination in a patient with one or several nodules occurring in a context of recurrent pleomorphous adenoma.

  18. [Some problems of clinical characteristics, diagnostics and treatment of pleomorphic adenoma of salivary glands].

    PubMed

    Stojnev, I

    1989-01-01

    The author evaluates the clinical characteristics in the light of the concepts proceeding from the International histological classification of tumours of the salivary glands on the base of his own experience in the treatment of 208 patients with pleomorphic adenoma of the salivary glands. The existing hospital documentation of the treated patients was analyzed as well as a repeated evaluation of the histological diagnosis made during the treatment and control of the therapeutic results via periodical inquiry of the treated patients. The author confirms the ratified unified nomenclature of the International classification and the benign nature of the pleomorphic adenoma. In that aspect he defends the surgical treatment of the pleomorphic adenoma as the method of choice and the high diagnostic value of the urgent intraoperative histological study. He advances the thesis for the application of more radical methods in the surgical treatment of recurrent pleomorphic adenoma of the parotid gland. According to the author, the morphological characteristics of the pleomorphic adenoma have no effect on the choice of the surgical methods for the treatment of that tumour.

  19. Intra-mandibular canalicular adenoma: report of a rare case.

    PubMed

    Dayisoylu, Ezher Hamza; Pampu, Ali Alper; Mungan, Sevdegul; Taskesen, Fatih

    2012-11-01

    Canalicular adenomas are uncommon benign salivary gland neoplasms of the oral cavity. They are typically located on the upper lip, buccal mucosa and infrequently found on the palate and derived from minor salivary glands. Intra-mandibular localization of canalicular adenoma is extremely rare. Due to benign character of the tumour, canalicular adenomas rarely present with bone erosion. Histologically, trabecular type of basal cell adenoma, pleomorphic adenoma and polymorphous low-grade adenocarcinoma should be discriminated from canalicular adenomas. A-56- year old female patient with asymptomatic intra-mandibular canalicular adenoma was presented. The lesion was managed surgically under local anesthesia and 2 year's follow up was uneventful. Only two other intra-mandibular canalicular adenoma cases have been reported up till now. This case report describes the third intra-mandibular canalicular adenoma, and reviews the literature.

  20. Polyploidy in pleomorphic adenomas with cytological atypia.

    PubMed

    Thunnissen, F B; Peterse, J L; Buchholtz, R; Van der Beek, J M; Bosman, F T

    1992-01-01

    Occasionally, in fine-needle aspirates of pleomorphic salivary gland adenomas, considerable cytonuclear atypia is present, which may give rise to a false-positive diagnosis. In this study DNA cytophotometry was performed on Feulgen restained smears prepared from material obtained by needle aspirates of normal salivary glands (n = 4), pleomorphic adenomas with (n = 5) and without (n = 4) atypia and a carcinoma in a pleomorphic adenoma. The results showed a clear diploid DNA histogram in the specimens of normal salivary gland and pleomorphic adenomas without atypia. In contrast, in the pleomorphic adenomas with atypia a distinct polyploid pattern was present in three out of the five DNA histograms with DNA values in 2c, 4c and 8c ranges. In two of these cases a 16c peak was also present and in the two remaining cases tetraploidy was demonstrated. In the carcinoma a main stemline at 4c was found. This report once more emphasizes the possible atypia which may be present in FNA of pleomorphic adenomas of the salivary gland. The atypia is due to polyploidy in a histologically benign tumour.

  1. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

    PubMed Central

    Lorentzen, Jon A.; Grzyb, Krzysztof; De Angelis, Paula M.; Hoff, Geir; Eide, Tor J.; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID:27656095

  2. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study.

    PubMed

    Lorentzen, Jon A; Grzyb, Krzysztof; De Angelis, Paula M; Hoff, Geir; Eide, Tor J; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID:27656095

  3. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

    PubMed Central

    Lorentzen, Jon A.; Grzyb, Krzysztof; De Angelis, Paula M.; Hoff, Geir; Eide, Tor J.; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers.

  4. Colorectal Chemoprevention with Calcium and Vitamin D | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION: In this application we propose to complete CA098286, a double-blind, randomized, controlled trial of supplementation with vitamin D and/or calcium for the prevention of colorectal adenomas. The study builds on extensive epidemiological and experimental data indicating that both vitamin D and calcium have anti-neoplastic effects in the large bowel and that these agents interact, each requiring the other for full effect. Despite the strong supporting |

  5. Immunohistochemical aspects of basal cell adenoma and canalicular adenoma of salivary glands.

    PubMed

    Machado de Sousa, S O; Soares de Araújo, N; Corrêa, L; Pires Soubhia, A M; Cavalcanti de Araújo, V

    2001-06-01

    Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Those cells may be distributed in various arrangements as solid, trabecular, tubular and membranous. Canalicular adenoma is also a benign neoplasm composed by columnar cells arranged in branching and interconnecting cords of single or double cell thick rows. There is some disagreement among investigators about whether canalicular adenoma should be included within the basal cell adenoma histologic spectrum. In the present study we compared the expression of cytokeratins (CK), vimentin and muscle-specific actin, utilizing immunohistochemical technique, in three cases diagnosed as basal cell adenomas predominantly of the solid type, and three cases of canalicular adenomas. The results obtained showed a distinct immunoprofile for both neoplasms. Solid areas of basal cell adenomas did not stain for any of the tested antibodies; only when there was tubular differentiation, those structures expressed CKs 7, 8, 14, and 19 in luminal cells and vimentin in non-luminal cells. On the other hand, canalicular adenomas strongly expressed CKs 7 and 13. The panel of antibodies utilized supports the separation of the two entities.

  6. Optical coherence tomography imaging of colonic crypts in a mouse model of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Welge, Weston A.; Barton, Jennifer K.

    2016-03-01

    Aberrant crypt foci (ACF) are abnormal epithelial lesions that precede development of colonic polyps. As the earliest morphological change in the development of colorectal cancer, ACF is a highly studied phenomenon. The most common method of imaging ACF is chromoendoscopy using methylene blue as a contrast agent. Narrow- band imaging is a contrast-agent-free modality for imaging the colonic crypts. Optical coherence tomography (OCT) is an attractive alternative to chromoendoscopy and narrow-band imaging because it can resolve the crypt structure at sufficiently high sampling while simultaneously providing depth-resolved data. We imaged in vivo the distal 15 mm of colon in the azoxymethane (AOM) mouse model of colorectal cancer using a commercial swept-source OCT system and a miniature endoscope designed and built in-house. We present en face images of the colonic crypts and demonstrate that different patterns in healthy and adenoma tissue can be seen. These patterns correspond to those reported in the literature. We have previously demonstrated early detection of colon adenoma using OCT by detecting minute thickening of the mucosa. By combining mucosal thickness measurement with imaging of the crypt structure, OCT can be used to correlate ACF and adenoma development in space and time. These results suggest that OCT may be a superior imaging modality for studying the connection between ACF and colorectal cancer.

  7. Synchronous trifocal colorectal cancer

    PubMed Central

    Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory

    2016-01-01

    Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery. PMID:27695171

  8. Colorectal neoplasm and acromegaly.

    PubMed

    Bhansali, Anil; Dutta, Pinaki; Bhat, Mohammad Hayat; Sinha, S K; Kochar, R; Vaiphi, K

    2006-01-01

    The risk for colorectal carcinoma in acromegaly remains controversial. In our earlier study, we have demonstrated that the risk of colorectal carcinoma in Asian Indians with acromegaly is not increased and after this report, routine colonoscopy in our patients with acromegaly was abandoned. Subsequently, two consecutive young men aged 30 and 35, one 6 years after and other at the time of diagnosis of acromegaly had colorectal carcinoma respectively. None of them had family history of colonic neoplasm. These two younger patients with no other predisposition for colorectal neoplasm suggests that colonoscopy should be done in all patients with acromegaly at diagnosis and they should remain under surveillance.

  9. Synchronous trifocal colorectal cancer

    PubMed Central

    Charalampoudis, Petros; Kykalos, Stylianos; Stamopoulos, Paraskevas; Kouraklis, Gregory

    2016-01-01

    Synchronous colorectal cancers (SCRCs) have been increasingly diagnosed due to emerging diagnostic modalities. The presence of three or more synchronous colorectal cancers has, however, only rarely been reported. A 76-year-old white man presented for management of two concurrent colorectal adenocarcinomas in the left colon evidenced on total colonoscopy. Preoperative abdominal ultrasonography and thoracoabdominal computed tomography were negative for metastatic disease. The patient underwent an elective left hemicolectomy. The pathology report ultimately showed the presence of three moderately differentiated, distinct colorectal cancers. The patient experienced an uneventful recovery.

  10. Aflibercept in the Treatment of Metastatic Colorectal Cancer

    PubMed Central

    Wang, Tzu-Fei; Lockhart, Albert Craig

    2012-01-01

    Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept. PMID:22253552

  11. Lack of association between human papillomavirus infection and colorectal cancer

    PubMed Central

    Taherian, Hanieh; Fard, Zahra Tahmasebi; Abdirad, Afshin

    2014-01-01

    Introduction Colorectal cancer is the third leading cause of cancer-related deaths worldwide, with nearly one million new cases identified annually. Different factors might cause colorectal cancer, one of the most prevalent cancers among both men and women. Viral aetiology in cancerous malignancies is a very important issue and so far a number of viral strains have been identified as tumour oncogene viruses. Viral infections, such as human papillomavirus (HPV), have recently been suggested as a risk factor for colorectal cancer. However, the aetiology of the disease is still unknown. Aim To assessed the association between HPV infection and colorectal cancer. Material and methods In this study, 50 cancer tissue samples and 50 samples without colon cancer were studied in order to identify HPV through polymerase chain reaction (PCR). Of 42 adenocarcinomas, 10 were well differentiated, 30 moderated differentiated, and 2 were poorly differentiated. DNA extraction was verified by beta globin gene amplification; specific PCR was carried out based on HPV L1 consensus primers MY09/MY11. Results HPV DNA was not identified in any of the normal, adenocarcinoma, or adenoma samples. Conclusions In contrast with previous studies, the current research failed to establish a relationship between HPV infection and the incidence of colon cancer. Considering the existing inconsistencies, it is recommended that further studies be conducted with larger sample size. PMID:25396002

  12. Mammary analogue secretory carcinoma mimicking salivary adenoma.

    PubMed

    Williams, Lindsay; Chiosea, Simion I

    2013-12-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas.

  13. Fascin expression in colorectal carcinomas

    PubMed Central

    Ozerhan, Ismail Hakki; Ersoz, Nail; Onguru, Onder; Ozturk, Mustafa; Kurt, Bulent; Cetiner, Sadettin

    2010-01-01

    PURPOSE The purpose of this study was to investigate the significance of fascin expression in colorectal carcinoma. METHODS This is a retrospective study of 167 consecutive, well-documented cases of primary colorectal adenocarcinoma for which archival material of surgical specimens from primary tumor resections were available. We chose a representative tissue sample block and examined fascin expression by immunohistochemistry using a primary antibody against “fascin”. We calculated the “immunohistochemical score (IHS)” of fascin for each case, which was calculated from the multiplication of scores for the percentage of stained cells and the staining intensity. RESULTS Fascin immunoreactivity was observed in 59 (35.3%) of all cases with strong reactivity in 24 (14.4%), moderate reactivity in 25 (14.9%) and weak reactivity in 10 (6.0%) cases. Strong/moderate immunoreactivities were mostly observed in invasive fronts of the tumors or in both invasive and other areas. Fascin immunoreactivity scores were significantly higher in tumors with lymph node metastasis (p:0.002) and advanced stage presentation (p:0.007). There was no relation between fascin expression and age, gender, depth of invasion, distant metastasis or histological grade (p>0.05). There was a higher and statistically significant correlation between fascin immunoreactivity in the invasive borders of tumors and lymph node metastasis (r:0.747, p:0.005). In stage III/IV tumors, two-year survival was 92.2% in tumors without fascin immunoreactivity, and only 60.0% in tumors with a fascin IHS>10 (p:0.003). CONCLUSION These findings suggest that fascin is heterogeneously expressed in approximately one third of colorectal carcinomas with a significant association with lymph node metastasis, tumor stage and location. Moreover, these results indicate that fascin may have a role in the lymph node metastasis of colorectal carcinomas. PMID:20186299

  14. The Role of Aspirin, Vitamin D, Exercise, Diet, Statins, and Metformin in the Prevention and Treatment of Colorectal Cancer.

    PubMed

    Sehdev, Amikar; O'Neil, Bert H

    2015-09-01

    Colorectal cancer (CRC) is a worldwide health problem leading to significant morbidity and mortality. Several strategies based on either lifestyle modifications or pharmacological interventions have been developed in an attempt to reduce the risk of CRC. In this review article, we discuss these interventions including aspirin (and other non-steroidal anti-inflammatory drugs), vitamin D, exercise, diet, statins, and metformin. Depending upon the risk of developing CRC, the current evidence supports the beneficial role of aspirin, vitamin D, diet, and exercise especially in high-risk individuals (advanced adenoma or CRC). However, even with these established interventions, there are significant knowledge gaps such as doses of aspirin and 25-hydroxy vitamin D are not well established. Similarly, there is no convincing data from randomized controlled trials that a high fiber diet or a low animal fat diet reduces the risk of CRC. Some potential interventions, such as statins and metformin, do not have convincing data for clinical use even in high-risk individuals. However, these may have emerging roles in the prevention and treatment of CRC. Greater understanding of molecular mechanisms and the application of genomic tools to risk stratify an individual and tailor the interventions based on that individual's risk will help further advance the field. Some of this work is already underway and is a focus of this article. PMID:26187794

  15. Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test

    PubMed Central

    Otero-Estévez, O; De Chiara, L; Rodríguez-Berrocal, F J; de la Cadena, M Páez; Cubiella, J; Castro, I; Gonzalez-Mao, C; Hernandez, V; Martínez-Zorzano, V S

    2015-01-01

    Background: The development of specific screening programs for individuals with a family history of colorectal cancer (CRC) is a priority. This study evaluates the diagnostic performance of serum soluble CD26 (sCD26) in family-risk individuals and compares this marker with the faecal immunochemical test for the detection of advanced neoplasia (AN) (CRC or advanced adenomas; AA). Methods: Five hundred and sixteen asymptomatic individuals with at least one first-degree relative with CRC were included. Serum sCD26 was measured in all the individuals who also underwent a colonoscopy (53 AA and four cancer cases were found) and a faecal immunochemical test. Results: Setting specificity to 90% and 95%, respectively, sCD26 showed a sensitivity of 39.6% and 28.3% for AA, and of 42.1% and 28.1% for AN. The combination of sCD26 and the faecal test detected AA and AN with a 52.8% and 56.1% sensitivity, corresponding to 93.5% specificity. Conclusions: The combination of serum sCD26 and the faecal blood test could result a valuable strategy for detecting AN in familial-risk CRC screening. PMID:25461801

  16. Sporadic and syndromic hyperplastic polyps and serrated adenomas of the colon: classification, molecular genetics, natural history, and clinical management.

    PubMed

    East, James E; Saunders, Brian P; Jass, Jeremy R

    2008-03-01

    There is now strong evidence for an alternative pathway of colorectal carcinogenesis implicating hyperplastic polyps and serrated adenomas. This article briefly reviews the evidence for this serrated pathway, provides diagnostic criteria for clinically significant hyperplastic polyps and allied serrated polyps, and suggests how this information may be translated into safe, effective guidelines for colonoscopy-based colon cancer prevention. Consideration also is given to the definition and management of hyperplastic polyposis syndrome. The currently proposed management plan for serrated polyps is tentative because of incomplete knowledge of the nature and behavior of these polyps. This article highlights key areas warranting further research.

  17. A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

    PubMed

    Evans, W K; Nixon, D W; Daly, J M; Ellenberg, S S; Gardner, L; Wolfe, E; Shepherd, F A; Feld, R; Gralla, R; Fine, S

    1987-01-01

    One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less

  18. MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms

    PubMed Central

    Amankwatia, E B; Chakravarty, P; Carey, F A; Weidlich, S; Steele, R J C; Munro, A J; Wolf, C R; Smith, G

    2015-01-01

    Background: Colorectal cancers arise from benign adenomas, although not all adenomas progress to cancer and there are marked interpatient differences in disease progression. We have previously associated KRAS mutations with disease progression and reduced survival in colorectal cancer patients. Methods: We used TaqMan low-density array (TLDA) qRT–PCR analysis to identify miRNAs differentially expressed in normal colorectal mucosa, adenomas and cancers and in isogeneic KRAS WT and mutant HCT116 cells, and used a variety of phenotypic assays to assess the influence of miRNA expression on KRAS activity, chemosensitivity, proliferation and invasion. Results: MicroRNA-224 was differentially expressed in dysplastic colorectal disease and in isogeneic KRAS WT and mutant HCT116 cells. Antagomir-mediated miR-224 silencing in HCT116 KRAS WT cells phenocopied KRAS mutation, increased KRAS activity and ERK and AKT phosphorylation. 5-FU chemosensitivity was significantly increased in miR-224 knockdown cells, and in NIH3T3 cells expressing KRAS and BRAF mutant proteins. Bioinformatics analysis of predicted miR-224 target genes predicted altered cell proliferation, invasion and epithelial–mesenchymal transition (EMT) phenotypes that were experimentally confirmed in miR-224 knockdown cells. Conclusions: We describe a novel mechanism of KRAS regulation, and highlight the clinical utility of colorectal cancer-specific miRNAs as disease progression or clinical response biomarkers. PMID:25919696

  19. [Clinicopathological characteristics of colorectal carcinoma in the elderly].

    PubMed

    Tao, Kaixiong; Gao, Jinbo; Wang, Guobin

    2016-05-01

    Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized

  20. [Clinicopathological characteristics of colorectal carcinoma in the elderly].

    PubMed

    Tao, Kaixiong; Gao, Jinbo; Wang, Guobin

    2016-05-01

    Elderly patients with colorectal cancer have different clincopathological characteristics from younger patients. Colorectal cancers tend to localize in the proximal colon, from cecum to the splenic flexure in the elderly patients. Changes in the stools, rectal bleeding or black stool, abdominal pain, fatigue, weight loss and anemia are the common symptoms. Analysis showed that age is one of independent risk factors for lower completion rates of colonoscopy. Therefore, the choice of diagnosis methods in elderly patients should be careful. Achieving a clear diagnosis and avoiding complications should be considered at the same time. Most colorectal cancers in elderly are highly and moderately differentiated adenocarcinomas and locally advanced, and have less lymphatic and blood metastasis. The proportion of poorly differentiated adenocarcinoma increases with the increase of age, which should be concerned. Multiple colorectal cancers and colorectal cancer with extra-colorectal malignancy are not rare in the elderly patients. The common extra-colorectal tumors consist of gastric cancer, lung cancer, biliary carcinoma, pancreas cancer and malignancy from blood system. Molecular events, such as mutations of KARS, BRAF, TP53 and deficiency of DNA mismatch repair, are more frequent in elderly colorectal cancer patients. Many factors have impact on treatment decision in elderly patients with colorectal cancer, including age, comorbidities, physiological functions of organs and willingness of patients and their relatives. Although surgery is still the main treatment, the proportion of radical surgery is lower and emergency surgery is higher as compared to younger patients. With the development of minimally invasive surgical techniques and advances in anesthesia and perioperative management, laparoscopic surgery has become widespread in elderly patients with colorectal cancer. In addition, more attention should be paid to adjuvant therapy. Comprehensive individualized

  1. Endoluminal Therapy in Colorectal Cancer.

    PubMed

    Kelley, Katherine A; Tsikitis, V Liana

    2016-09-01

    Appropriate endoscopic resection for colorectal polyps can present a challenge to endoscopists, as these lesions may harbor malignancy. With recent advances in endoscopy, however, we are now entering an exciting frontier of endoscopic therapy for gastrointestinal lesions. These techniques include endoluminal mucosal resection and endoscopic submucosal dissection, which may be utilized on several colonic lesions. This article will discuss these principle endoscopic techniques, their outcomes, and briefly highlight their influence on endoscopic interventions, including transanal endoscopic microsurgery and natural orifice transluminal endoscopic surgery. PMID:27582646

  2. GIANT PITUITARY ADENOMA WITH NORMAL VISION AND MISLEADING RADIOLOGICAL FINDINGS.

    PubMed

    Khalid, Muhammad; Raina, Umer Farooq; uz Zaman, Khaleeq; Tahir, Muhammad

    2015-01-01

    Giant pituitary adenomas are rare and present with visual loss. Giant pituitary adenoma has rarely been reported presenting with normal vision. We report Giant pituitary adenoma with Normal vision in a 35 years old patient presenting with adult onset epilepsy and headache. PMID:26721053

  3. Dysplastic pleomorphic adenoma of the sublingual salivary gland.

    PubMed

    Clark, J; Bailey, B M; Eveson, J W

    1993-12-01

    All tumours of the sublingual gland are rare and paradoxically the large majority are malignant. A case of pleomorphic adenoma in the sublingual gland is described. The tumour showed areas of dysplasia and the difficulties in distinguishing this from benign pleomorphic adenoma or carcinoma in pleomorphic adenoma are considered, and the literature is reviewed.

  4. [A case of very late malignant degeneration of pleomorphic adenoma].

    PubMed

    Darche, V; Hustin, J; Lejuste, P; Robillard, T; Piette, E

    1998-12-01

    Incomplete excision of a pleomorphic adenoma exposes to a high risk of recurrence and tumor spread, making secondary surgery more difficult or a malignant transformation with a poor vital prognosis likely. Three histological types of pleomorphic adenomas can be observed when the tumor undergoes a transformation, namely the carcinoma ex-pleomorphic adenoma, the true malignant mixed tumor and the benign metastasizing mixed tumour.

  5. Tissue Specific Promoters in Colorectal Cancer

    PubMed Central

    Rama, A. R.; Aguilera, A.; Melguizo, C.; Caba, O.; Prados, J.

    2015-01-01

    Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. PMID:26648599

  6. Gallium-68 PSMA uptake in adrenal adenoma.

    PubMed

    Law, W Phillip; Fiumara, Frank; Fong, William; Miles, Kenneth A

    2016-08-01

    Gallium-68 (Ga-68) labelled prostate-specific membrane antigen (PSMA) imaging by positron emission tomography (PET) has emerged as a promising tool for staging of prostate cancer and restaging of disease in recurrence or biochemical failure after definitive treatment of prostate cancer. Ga-68 PSMA PET produces high target-to-background images of prostate cancer and its metastases which are reflective of the significant overexpression of PSMA in these cells and greatly facilitates tumour detection. However, relatively little is known about the PSMA expression of benign neoplasms and non-prostate epithelial malignancies. This is a case report of PSMA uptake in an adrenal adenoma incidentally discovered on PET performed for restaging of biochemically suspected prostate cancer recurrence. With the increasing use of PSMA PET in the management of prostate cancer - and the not infrequent occurrence of adrenal adenomas - the appearance of low- to moderate-grade PSMA uptake in adrenal adenomas should be one with which reporting clinicians are familiar.

  7. Preoperative volume determination for pituitary adenoma

    NASA Astrophysics Data System (ADS)

    Zukic, Dženan; Egger, Jan; Bauer, Miriam H. A.; Kuhnt, Daniela; Carl, Barbara; Freisleben, Bernd; Kolb, Andreas; Nimsky, Christopher

    2011-03-01

    The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92%+/-7.24%. A manual segmentation took about four minutes and our algorithm required about one second.

  8. Pleomorphic multicentric adenoma in the submandibular gland.

    PubMed

    Alves, Carlos Augusto Ferreira; Ribeiro Júnior, Ophir; Borba, Alexandre Meireles; Gouveia, Marcia Maria; Guimarães Júnior, Jayro; Aburad, Arlindo; de Souza, Suzana Cantanhede Orsini Machado

    2007-12-01

    Neoplasms of salivary glands represent a small group among the diseases involving the head and neck complex. In this group, the pleomorphic adenoma is the most frequent neoplasm, yet involves the submandibular gland in only 12.3% of cases. A patient presenting a swelling in the region of the submandibular gland was submitted to an incisional biopsy, where a fragment of the gland and one juxtaposed node were removed. Histologically they were defined as pleomorphic adenoma. Later, the patient was submitted to submandibulectomy and two other nodes were found close to the gland and removed. All specimens were histologically defined as pleomorphic adenoma. This multicentric finding is of great interest, perhaps explaining the recurrence rate of this neoplasm. The patient is in continuous follow-up and has not presented signs of recurrence.

  9. CEA and CA19.9 as early predictors of progression in advanced/metastatic colorectal cancer patients receiving oxaliplatin-based chemotherapy and bevacizumab.

    PubMed

    Petrioli, Roberto; Licchetta, Antonella; Roviello, Giandomenico; Pascucci, Alessandra; Francini, Edoardo; Bargagli, Gianluca; Conca, Raffaele; Miano, Salvatora Tindara; Marzocca, Giuseppe; Francini, Guido

    2012-01-01

    We evaluated the changes of the tumor markers CEA and CA19.9 as early predictors of progression in metastatic colorectal cancer (mCRC) patients participating in a clinical study and receiving chemotherapy and bevacizumab (Bev). Seventy-two patients had high baseline CEA or CA19.9 serum levels. By ROC analyses, the areas under the curves were 0.83 for variable CEA cutoff values for distinguishing progressive disease (PD) versus stable disease (SD)/partial remission (PR)/complete remission (CR), and 0.80 for variable CA19.9 cutoff values for distinguishing PD versus SD/PR/CR. Rises in CEA and CA19.9 may early signal the occurrence of progression in mCRC patients receiving chemotherapy and Bev. PMID:22236191

  10. Intraprocedural bowel cleansing with the JetPrep cleansing system improves adenoma detection

    PubMed Central

    Hoffman, Arthur; Murthy, Sanjay; Pompetzki, Lena; Rey, Johannes Wilhelm; Goetz, Martin; Tresch, Achim; Galle, Peter Robert; Kiesslich, Ralf

    2015-01-01

    AIM: To investigate the impact of JetPrep cleansing on adenoma detection rates. METHODS: In this prospective, randomized, crossover trial, patients were blindly randomized to an intervention arm or a control arm. In accordance with the risk profile for the development of colorectal carcinoma, the study participants were divided into high-risk and low-risk groups. Individuals with just one criterion (age > 70 years, adenoma in medical history, and first-degree relative with colorectal cancer) were regarded as high-risk patients. Bowel preparation was performed in a standardized manner one day before the procedure. Participants in the intervention arm underwent an initial colonoscopy with standard bowel cleansing using a 250-mL syringe followed by a second colonoscopy that included irrigation by the use of the JetPrep cleansing system. The reverse sequence was used in the control arm. The study participants were divided into a high-risk group and a low-risk group according to their respective risk profiles for the development of colorectal carcinoma. RESULTS: A total of 64 patients (34 men and 30 women) were included in the study; 22 were included in the high-risk group. After randomization, 30 patients were assigned to the control group (group A) and 34 to the intervention group (group B). The average Boston Bowel Preparation Scale score was 5.15 ± 2.04. The withdrawal time needed for the first step was significantly longer in group A using the JetPrep system (9.41 ± 3.34 min) compared to group B (7.5 ± 1.92 min). A total of 163 polyps were discovered in 64 study participants who underwent both investigation steps. In group A, 49.4% of the polyps were detected during the step of standard bowel cleansing while the miss rate constituted 50.7%. Group B underwent cleansing with the JetPrep system during the first examination step, and as many as 73.9% of polyps were identified during this step. Thus, the miss rate in group B was a mere 26.1% (P < 0.001). When

  11. Pleomorphic adenoma of the nasal columella.

    PubMed

    Ceylan, Alper; Celenk, Fatih; Poyraz, Aylar; Uslu, Sabri

    2008-01-01

    Pleomorphic adenoma (mixed tumor) is the most common benign neoplasm of the salivary glands. It is considered to occur primarily in the major salivary glands, such as the parotid and submandibular glands. It is much less common in the minor salivary glands, and rarely occurs at other sites, such as larynx, pharynx, trachea, lacrimal gland, and sinonasal tract. An external nose localization of this lesion is very rare. Irrespective of the site where the lesion originates, its preferred treatment should be surgery. We describe a very rare case of recurrent pleomorphic adenoma originating from the columella.

  12. [Basal cell adenomas of the salivary glands].

    PubMed

    Kozlovskiĭ, O M

    1975-01-01

    The author presents data on morphology and clinical features of basal-cell adenomas of the salivary gland (10 cases). Singling out this neoplasm into independent onconosological group seems reasonable since basal-cell adenoma not infrequently is erroneously diagnosed as cylindroma or mixed tumour of the salivary gland, which may lead to a wrong clinical prognosis and inadequate therapeutic measures. The clinical course of this tumour is benign. The main morphological feature of the tumour is a monomorphic character of cell elements, their palisade-like distribution over the periphery of individual tumour structures and a clear-cut delimination of the parenchyma from the stroma.

  13. Sebaceous adenoma of the submandibular gland: a case report.

    PubMed

    Zare-Mahmoodabadi, Reza; Salehinejad, Jahanshah; Saghafi, Shadi; Ghazi, Narges; Mahmoudi, Parviz; Harraji, Afshin

    2009-12-01

    Sebaceous adenoma of the salivary gland is a rare tumor comprising 0.1% of all salivary gland neoplasms and less than 0.5% of salivary adenomas. Histologically, sebaceous adenomas are benign neoplasms consisting of sebaceous cells arranged in nests forming acinar and duct-like structures. Oncocytic metaplasia may also occur in some areas. We describe a case of sebaceous adenoma in the submandibular gland. Under a presumptive diagnosis of sialadenitis/sialolithiasis, the patient was administered multiple courses of antibiotics; however, these were not effective. Excisional biopsy resulted in a diagnosis of sebaceous adenoma. A 1-year follow-up showed no recurrence.

  14. Missense Polymorphisms in the Adenomatous Polyposis Coli Gene and Colorectal Cancer Risk

    PubMed Central

    Cleary, Sean P.; Kim, Hyeja; Croitoru, Marina E.; Redston, Mark; Knight, Julia A.; Gallinger, Steven; Gryfe, Robert

    2009-01-01

    PURPOSE Whereas truncating germline mutations of the adenomatous polyposis coli (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of APC may confer a weaker risk for colorectal cancer. METHODS We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas. Missense adenomatous polyposis coli alterations identified in this colorectal cancer multiple-polyp population were analyzed in a population-based series of patients with colorectal cancer and healthy control subjects. RESULTS Germline APC or mutY human homologue (MYH) alterations were identified in 16 of 39 colorectal cancer-multiple polyp patients. Four missense APC gene alterations (S130G, E1317Q, Dl822V, G2502S) were observed in 13 individuals and 3 additional patients carried presumed pathogenic (APC Y94X, biallelic MYH Y165C and heterozygous MYH G382D) mutations. When independently assessed in 971 patients with colorectal cancer and 954 healthy control subjects, none of the identified missense APC alterations conferred a significantly increased risk for colorectal cancer, odds ratio (95 percent confidence intervals): S130G=3.1 (0.29–32.25), E1317Q= 1.08 (0.59–2.74), G2502S= 1 (0.65–1.63), D1822V (heterozygous)=0.79 (0.64–0.98), D1822V (homozygous) =0.82 (0.63–1.27). CONCLUSIONS Germline missense APC alterations observed in 33 percent of patients with multiple colorectal neoplasms seemed to play a limited role in colorectal cancer risk when independently assessed by a population-based, case-control analysis. PMID:18612690

  15. [Clinical and genetic characterization of FIPA (familial isolated pituitary adenomas)].

    PubMed

    Beckers, A; Apetrii, P; Daly, A; Tichomirova, M; Vanbellingen, J F; Georges, M; Bours, V

    2009-01-01

    Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary adenomas have been available. Recently, a cross-sectional study conducted in Liège, Belgium, noted that clinically-apparent pituitary adenomas occurred with a prevalence of 1:1064 inhabitants, which is 3.5-5 times the previously reported prevalence. Pituitary adenomas occur predominantly as sporadic tumors, but also in a familial setting or associated to some familial/isolated tumoral syndromes. The recent characterization of the novel clinical entity FIPA (Familial Isolated Pituitary Adenomas) increased the prevalence of familial pituitary adenomas which account now for about 5% of pituitary tumors. Distinct genetic mechanisms are continuously identified and increase our understanding of the complex clinical presentation and sometimes unpredictable evolution of pituitary adenomas.

  16. Etiology and management of recurrent parotid pleomorphic adenoma.

    PubMed

    Witt, Robert L; Eisele, David W; Morton, Randall P; Nicolai, Piero; Poorten, Vincent Vander; Zbären, Peter

    2015-04-01

    The objective of this review study was to encompass the relevant literature and current best practice options for this challenging, sometimes incurable problem. The source of the data was Ovid MEDLINE from 1946 to 2014. Review methods consisted of articles with clinical correlates. The most important cause of recurrence is enucleation with rupture and incomplete tumor excision at operation. Incomplete pseudocapsule, extracapsular extension, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule are also likely linked to recurrent pleomorphic adenoma. Most recurrent pleomorphic adenoma are multinodular. Magnetic resonance imaging is the imaging study of choice for recurrent pleomorphic adenoma. Nerve integrity monitoring may reduce morbidity for recurrent pleomorphic adenoma. Treatment of recurrent pleomorphic adenoma must be individualized. Total parotidectomy, given the multicentricity of recurrent pleomorphic adenoma, is appropriate in many patients, but may be inadequate to control recurrent pleomorphic. There is accumulating evidence from retrospective series that postoperative radiation therapy results in significantly better local control.

  17. PTK7 overexpression in colorectal tumors: Clinicopathological correlation and prognosis relevance

    PubMed Central

    Tian, Xiuyun; Yan, Liang; Zhang, Donghai; Guan, Xiaoya; Dong, Bin; Zhao, Min; Hao, Chunyi

    2016-01-01

    Colorectal cancer (CRC) has one of the highest mortality rates in the worldwide and its incidence has been increasing in recent years. Protein tyrosine kinase-7 (PTK7) is an inactive member of receptor protein tyrosine kinase (RPTK)-like molecules, which is involved in tumorigenesis of a variety of cancers. Our study aimed to investigate expression of PTK7 in colorectal tumors (including benign adenomas and malignant carcinomas), and its potential function in tumorigenesis and prognosis. A total of 209 CRC patients and 28 colonic adenoma patients were included in this study. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR were performed in 14 pairs of fresh frozen tissues to evaluate mRNA expression of PTK7. Expression of PTK7 protein in 209 CRC tissues with paired non-cancerous mucosa and 28 adenoma specimens were tested using immunohistochemistry. The expression difference and its correlation with clinicopathological features and overall survival were assessed by SPSS statistics (version 22). P<0.05 was considered significant. RT-PCR and quantitative real-time PCR showed a higher expression of PTK7 mRNA in CRC compared with non-tumorous mucosa (4.87±3.71 vs. 1.33±1.05; P<0.001). PTK7 expression was significantly higher in adenoma (75%) and CRC (68.3%) than in non-tumorous mucosa (P<0.001). PTK7 expression was correlated with tumor differentiation (P=0.027), lymph node metastasis (P=0.005), distant metastasis (P=0.001) and TNM stage (P=0.028) of CRC patients. Significant correlation between PTK7 overexpression and favorable overall survival of CRC patients was observed (P=0.005). Therefore, it may act as a candidate biomarker to predict the occurrence and prognosis of colorectal tumor. PMID:27499181

  18. Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study

    PubMed Central

    Suenaga, Mitsukuni; Mizunuma, Nobuyuki; Matsusaka, Satoshi; Shinozaki, Eiji; Ozaka, Masato; Ogura, Mariko; Yamaguchi, Toshiharu

    2015-01-01

    Background The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. Methods Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR) after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease. Results Thirty-three patients were enrolled. The median age was 62 (range: 35–77) years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8–57.0) and the response rate (complete response and partial response) was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m2. Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment-related deaths. Conclusion Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior

  19. Fractionated proton beam irradiation of pituitary adenomas

    SciTech Connect

    Ronson, Brian B.; Schulte, Reinhard W.; Han, Khanh P.; Loredo, Lilia N.; Slater, James M.; Slater, Jerry D. . E-mail: jdslater@dominion.llumc.edu

    2006-02-01

    Purpose: Various radiation techniques and modalities have been used to treat pituitary adenomas. This report details our experience with proton treatment of these tumors. Methods and Materials: Forty-seven patients with pituitary adenomas treated with protons, who had at least 6 months of follow-up, were included in this analysis. Forty-two patients underwent a prior surgical resection; 5 were treated with primary radiation. Approximately half the tumors were functional. The median dose was 54 cobalt-gray equivalent. Results: Tumor stabilization occurred in all 41 patients available for follow-up imaging; 10 patients had no residual tumor, and 3 had greater than 50% reduction in tumor size. Seventeen patients with functional adenomas had normalized or decreased hormone levels; progression occurred in 3 patients. Six patients have died; 2 deaths were attributed to functional progression. Complications included temporal lobe necrosis in 1 patient, new significant visual deficits in 3 patients, and incident hypopituitarism in 11 patients. Conclusion: Fractionated conformal proton-beam irradiation achieved effective radiologic, endocrinological, and symptomatic control of pituitary adenomas. Significant morbidity was uncommon, with the exception of postradiation hypopituitarism, which we attribute in part to concomitant risk factors for hypopituitarism present in our patient population.

  20. Monomorphic adenoma, canalicular variant: report of case.

    PubMed

    Wiener, A P; Meadows, F

    1977-05-01

    A case of monomorphic adenoma, canalicular variant, has been presented. This lesion is a rare benign neoplasm most often found in the minor salivary glands of the upper lip. This appears to be the first reported case of the lesion in a non-Caucasian.

  1. Suprasellar salivary gland-like pleomorphic adenoma.

    PubMed

    Yao, Kun; Duan, Zejun; Bian, Yu; Wang, Mengyang; Qi, Xueling

    2014-01-01

    Suprasellar salivary gland-Like pleomorphic adenoma is not a common disease and seldom reported so far. We are reporting a case of a 23-year-old man with recurrent suprasellar salivary gland-like pleomorphic adenoma, who underwent an operation of subtotal, subfrontal resection under the wrong pathology diagnosis of benign teratoma in another hospital 4-year-ago. Four years later, he was admitted to our hospital for additional visual loss of the right eye (left, 1.0; right, 0.4) resulting from tumor regrowth. Magnetic resonance imaging revealed that suprasellar extension and compressed optic chiasm resulted in visual disturbance of the patient. The tumor was totally excised and histological examination evidenced the pathological features of intrasellar salivary gland-like pleomorphic adenoma. The patient did not receive any further treatment and he is free from tumor recurrence for 30 months after the operation. From this point of view, clinical prognosis of intrasellar salivary gland-like pleomorphic adenoma was good after total surgical resection.

  2. Endoscopic endonasal transsphenoidal surgery for treating pituitary adenoma via a sub-septum mucosa approach

    PubMed Central

    Nie, Sheng; Li, Keqin; Huang, Yi; Zhao, Jikuang; Gao, Xiang; Sun, Jie

    2015-01-01

    A novel sub-suptum mucusa approach was used to investigate the surgical method via an endonasal sub-septum-mucosa approach to pituitary adenoma under endoscopy. In this work, we aim to ensure the quality of operation and to reduce the operation trauma and complications. By endoscopy, the nasal mucosa was incised in the nasal septum, and all mucosal flaps were retained, a sub-septum-mucosa surgical corridor was made where the endoscope was used in the mucosa cavity for operation and to remove the pituitary adenoma. 52 patients (28 women, mean age 46.76 years) underwent endoscopic endonasal transsphenoidal sub-septum-mucosa approach for treating pituitary adenoma. 46 patients (88.5%) underwent gross total removal (GTR) for the tumor; 6 patients (11.5%) went through partial tumor removal (PTR). After operation, all nasal mucosa was retained, no complications such as nasal bleeding, loss of sense of smell or cerebrospinal fluid rhinorrhea. Our results showed that treating pituitary adenoma using endonasal transsphenoidal surgeries by keeping nasal mucosa under neuroendoscopy tend to have smaller trauma. This novel method more advanced since it provides a clear operation field, a flexible transformation of operation modes and leads to less postoperative complications. PMID:26131087

  3. Evolving management of colorectal cancer

    PubMed Central

    van Zijp, Jochem van der Voort; Hoekstra, Harald J; Basson, Marc D

    2008-01-01

    This article reviews recent advances in surgical techniques and adjuvant therapies for colorectal cancer, including total mesorectal excision, the resection of liver and lung metastasis and advances in chemoradiation and foreshadows some interventions that may lie just beyond the frontier. In particular, little is known about the intracellular and extracellular cascades that may influence colorectal cancer cell adhesion and metastasis. Although the phosphorylation of focal adhesion kinases and focal adhesion associated proteins in response to integrin-mediated cell matrix binding (”outside in integrin signaling”) is well described, the stimulation of cell adhesion by intracellular signals activated by pressure prior to adhesion represents a different signal paradigm. However, several studies have suggested that increased pressure and shear stress activate cancer cell adhesion. Further studies of the pathways that regulate integrin-driven cancer cell adhesion may identify ways to disrupt these signals or block integrin-mediated adhesion so that adhesion and eventual metastasis can be prevented in the future. PMID:18609678

  4. Colorectal Tumors from APC*I1307K Carriers Principally Harbor Somatic APC Mutations outside the A8 Tract

    PubMed Central

    Zauber, Peter; Bishop, Timothy; Taylor, Claire; Sabbath-Solitare, Marlene; Marotta, Stephen; Tomlinson, Ian

    2014-01-01

    Purpose APC*I1307K (c.3920T>A) is an inherited variant associated with colorectal tumour risk found almost exclusively in those of Ashkenazi Jewish ancestry. A single nucleotide substitution creates an oligo-adenine tract (A8) that appears to be inherently prone to further mis-pairing and slippage. The reported multiple tumor phenotype of carriers is not easily reconciled with molecular and population genetics data. We postulated that some c.3920T>A carriers with multiple adenomas have other unidentified APC germ line or somatic mutations. Methods DNA from 82 colonic tumours and accompanying normal tissue collected from 29 carriers with multiple colorectal tumors was directly sequenced between codons 716 and 1604. We also assessed APC gene loss of heterozygosity. Results One patient (3.4%) was found to have an additional APC germ line mutation. Twenty-five of the tumours showed no significant somatic molecular change, 36 showed one change, 20 showed two, and one tumour showed more than 2 changes. Our data suggest a correlation between advancing histology and fewer beta-catenin binding sites remaining in the mutant proteins. Conclusions There were no other common germ line variants identified within the region of the APC gene examined, suggesting that any effect from this region on tumour production is attributable to the c.3920T>A allele. Our findings further suggest the only somatic genetic change clearly attributable to the c.3920T>A mutation is the c.3924_3925insA. PMID:24416237

  5. Thyroid Adenomas After Solid Cancer in Childhood

    SciTech Connect

    Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Adjadj, Elisabeth; Thomas-Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Jackson, Angela; Munzer, Martine; N'Guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Bridier, Andre; Lefkopoulos, Dimitri; Schlumberger, Martin; Rubino, Carole; Diallo, Ibrahima; Vathaire, Florent de

    2012-10-01

    Purpose: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. Methods and Materials: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. Results: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. Conclusions: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

  6. Colorectal cancer risk variants on 11q23 and 15q13 are associated with unexplained adenomatous polyposis

    PubMed Central

    Hes, Frederik J; Ruano, Dina; Nieuwenhuis, Marry; Tops, Carli M; Schrumpf, Melanie; Nielsen, Maartje; Huijts, Petra E A; Wijnen, Juul T; Wagner, Anja; Gómez García, Encarna B; Sijmons, Rolf H; Menko, Fred H; Letteboer, Tom G W; Hoogerbrugge, Nicoline; Harryvan, Jan; Kampman, Ellen; Morreau, Hans; Vasen, Hans F A; van Wezel, Tom

    2013-01-01

    Background Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH. However, in about 20–30% of patients no underlying gene defect can be identified. In this study, we tested if recently identified CRC risk variants play a role in patients with >10 adenomas. Methods We analysed a total of 16 SNPs with a reported association with CRC in a cohort of 252 genetically unexplained index patients with >10 colorectal adenomas and 745 controls. In addition, we collected detailed clinical information from index patients and their first-degree relatives (FDRs). Results We found a statistically significant association with two of the variants tested: rs3802842 (at chromosome 11q23, OR=1.60, 95% CI 1.3 to 2.0) and rs4779584 (at chromosome 15q13, OR=1.50, 95% CI 1.2 to 1.9). The majority of index patients (84%) had between 10 and 100 adenomas and 15% had >100 adenomas. Only two index patients (1%), both with >100 adenomas, had FDRs with polyposis. Forty-one per cent of the index patients had one or more FDRs with CRC. Conclusions These SNPs are the first common, low-penetrant variants reported to be associated with adenomatous polyposis not caused by a defect in the APC, MUTYH, POLD1 and POLE genes. Even though familial occurrence of polyposis was very rare, CRC was over-represented in FDRs of polyposis patients and, if confirmed, these relatives will therefore benefit from surveillance. PMID:24253443

  7. The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions

    PubMed Central

    Staiano, Teresa; Bertoni, Ramona; Ancona, Nicola; Marra, Giancarlo; Resta, Leonardo

    2016-01-01

    Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous

  8. The Immune Landscapes of Polypoid and Nonpolypoid Precancerous Colorectal Lesions.

    PubMed

    Maglietta, Antonella; Maglietta, Rosalia; Staiano, Teresa; Bertoni, Ramona; Ancona, Nicola; Marra, Giancarlo; Resta, Leonardo

    2016-01-01

    Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous

  9. Developing Screening Services for Colorectal Cancer on Android Smartphones

    PubMed Central

    Wu, Hui-Ching; Chang, Chiao-Jung; Lin, Chun-Che; Tsai, Ming-Chang; Chang, Che-Chia

    2014-01-01

    Abstract Introduction: Colorectal cancer (CRC) is an important health problem in Western countries and also in Asia. It is the third leading cause of cancer deaths in both men and women in Taiwan. According to the well-known adenoma-to-carcinoma sequence, the majority of CRC develops from colorectal adenomatous polyps. This concept provides the rationale for screening and prevention of CRC. Removal of colorectal adenoma could reduce the mortality and incidence of CRC. Mobile phones are now playing an ever more crucial role in people's daily lives. The latest generation of smartphones is increasingly viewed as hand-held computers rather than as phones, because of their powerful on-board computing capability, capacious memories, large screens, and open operating systems that encourage development of applications (apps). Subjects and Methods: If we can detect the potential CRC patients early and offer them appropriate treatments and services, this would not only promote the quality of life, but also reduce the possible serious complications and medical costs. In this study, an intelligent CRC screening app on Android™ (Google™, Mountain View, CA) smartphones has been developed based on a data mining approach using decision tree algorithms. For comparison, the stepwise backward multivariate logistic regression model and the fecal occult blood test were also used. Results: Compared with the stepwise backward multivariate logistic regression model and the fecal occult blood test, the proposed app system not only provides an easy and efficient way to quickly detect high-risk groups of potential CRC patients, but also brings more information about CRC to customer-oriented services. Conclusions: We developed and implemented an app system on Android platforms for ubiquitous healthcare services for CRC screening. It can assist people in achieving early screening, diagnosis, and treatment purposes, prevent the occurrence of complications, and thus reach the goal of

  10. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis.

    PubMed

    Spier, Isabel; Kerick, Martin; Drichel, Dmitriy; Horpaopan, Sukanya; Altmüller, Janine; Laner, Andreas; Holzapfel, Stefanie; Peters, Sophia; Adam, Ronja; Zhao, Bixiao; Becker, Tim; Lifton, Richard P; Holinski-Feder, Elke; Perner, Sven; Thiele, Holger; Nöthen, Markus M; Hoffmann, Per; Timmermann, Bernd; Schweiger, Michal R; Aretz, Stefan

    2016-04-01

    In up to 30% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, and POLE or POLD1, causing Polymerase-Proofreading-associated polyposis can be identified, although a hereditary etiology is likely. To uncover new causative genes, exome sequencing was performed using DNA from leukocytes and a total of 12 colorectal adenomas from seven unrelated patients with unexplained sporadic adenomatous polyposis. For data analysis and variant filtering, an established bioinformatics pipeline including in-house tools was applied. Variants were filtered for rare truncating point mutations and copy-number variants assuming a dominant, recessive, or tumor suppressor model of inheritance. Subsequently, targeted sequence analysis of the most promising candidate genes was performed in a validation cohort of 191 unrelated patients. All relevant variants were validated by Sanger sequencing. The analysis of exome sequencing data resulted in the identification of rare loss-of-function germline mutations in three promising candidate genes (DSC2, PIEZO1, ZSWIM7). In the validation cohort, further variants predicted to be pathogenic were identified in DSC2 and PIEZO1. According to the somatic mutation spectra, the adenomas in this patient cohort follow the classical pathways of colorectal tumorigenesis. The present study identified three candidate genes which might represent rare causes for a predisposition to colorectal adenoma formation. Especially PIEZO1 (FAM38A) and ZSWIM7 (SWS1) warrant further exploration. To evaluate the clinical relevance of these genes, investigation of larger patient cohorts and functional studies are required. PMID:26780541

  11. Cell-surface markers for colon adenoma and adenocarcinoma

    PubMed Central

    Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S.; Wojtkowiak, Jonathan W.; Stark, Valerie E.; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L.

    2016-01-01

    Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC. PMID:26894861

  12. VEGF and CD31 association in pituitary adenomas.

    PubMed

    Cristina, Carolina; Perez-Millan, María Inés; Luque, Guillermina; Dulce, Raúl Ariel; Sevlever, Gustavo; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2010-09-01

    Pituitary tumors are usually less vascularized than the normal pituitary, and the role of angiogenesis in these adenomas is contentious. Appraisal of microvascular density and expression of the potent angiogenic vascular endothelial growth factor (VEGF) by immunohistochemistry has yielded controversial results, as a broad spectrum of immunostaining can be found. We determined the protein expression of VEGF and CD31, an endothelial marker, in a series of 56 surgically removed pituitary adenomas using Western blot assay. Prolactinomas had higher VEGF protein expression compared to nonfunctioning or ACTH- and GH-secreting adenomas, while CD31 was similar in the different adenoma histotypes. VEGF and CD31 were not affected by sex, age, years of adenoma evolution, or proliferation rate (Ki67 and PCNA) for all adenoma types. Only in nonfunctioning adenomas CD31 concentration increased significantly with age. There was a positive correlation between CD31 and VEGF expression when all adenoma histotypes were considered, or when prolactinomas and nonfunctioning adenomas were evaluated separately. The positive association of VEGF and CD31 expression suggests the participation of angiogenesis in adenoma development, while epithelial cell proliferation in pituitary tumors is not directly related to VEGF or CD31 expression, and other factors, such as primary genetic alterations may be involved. PMID:20473646

  13. TP53 mutation at early stage of colorectal cancer progression from two types of laterally spreading tumors.

    PubMed

    Sakai, Eiji; Fukuyo, Masaki; Matsusaka, Keisuke; Ohata, Ken; Doi, Noriteru; Takane, Kiyoko; Matsuhashi, Nobuyuki; Fukushima, Junichi; Nakajima, Atsushi; Kaneda, Atsushi

    2016-06-01

    Although most sporadic colorectal cancers (CRC) are thought to develop from protruded adenomas through the adenoma-carcinoma sequence, some CRC develop through flat lesions, so-called laterally spreading tumors (LST). We previously analyzed epigenetic aberrations in LST and found that LST are clearly classified into two molecular subtypes: intermediate-methylation with KRAS mutation and low-methylation with absence of oncogene mutation. Intermediate-methylation LST were mostly granular type LST (LST-G) and low-methylation LST were mostly non-granular LST (LST-NG). In the present study, we conducted a targeted exon sequencing study including 38 candidate CRC driver genes to gain insight into how these genes modulate the development of LST. We identified a mean of 11.5 suspected nonpolymorphic variants per sample, including indels and non-synonymous mutations, although there was no significant difference in the frequency of total mutations between LST-G and LST-NG. Genes associated with RTK/RAS signaling pathway were mutated more frequently in LST-G than LST-NG (P = 0.004), especially KRAS mutation occurring at 70% (30/43) of LST-G but 26% (13/50) of LST-NG (P < 0.0001). Both LST showed high frequency of APC mutation, even at adenoma stage, suggesting its involvement in the initiation stage of LST, as it is involved at early stage of colorectal carcinogenesis via adenoma-carcinoma sequence. TP53 mutation was never observed in adenomas, but was specifically detected in cancer samples. TP53 mutation occurred during development of intramucosal cancer in LST-NG, but during development of cancer with submucosal invasion in LST-G. It is suggested that TP53 mutation occurs in the early stages of cancer development from adenoma in both LST-G and LST-NG, but is involved at an earlier stage in LST-NG. PMID:26991699

  14. Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature.

    PubMed

    Galamb, Orsolya; Györffy, Balázs; Sipos, Ferenc; Spisák, Sándor; Németh, Anna Mária; Miheller, Pál; Tulassay, Zsolt; Dinya, Elek; Molnár, Béla

    2008-01-01

    Gene expression analysis of colon biopsies using high-density oligonucleotide microarrays can contribute to the understanding of local pathophysiological alterations and to functional classification of adenoma (15 samples), colorectal carcinomas (CRC) (15) and inflammatory bowel diseases (IBD) (14). Total RNA was extracted, amplified and biotinylated from frozen colonic biopsies. Genome-wide gene expression profile was evaluated by HGU133plus2 microarrays and verified by RT-PCR. We applied two independent methods for data normalization and used PAM for feature selection. Leave one-out stepwise discriminant analysis was performed. Top validated genes included collagenIValpha1, lipocalin-2, calumenin, aquaporin-8 genes in CRC; CD44, met proto-oncogene, chemokine ligand-12, ADAM-like decysin-1 and ATP-binding casette-A8 genes in adenoma; and lipocalin-2, ubiquitin D and IFITM2 genes in IBD. Best differentiating markers between Ulcerative colitis and Crohn's disease were cyclin-G2; tripartite motif-containing-31; TNFR shedding aminopeptidase regulator-1 and AMICA. The discriminant analysis was able to classify the samples in overall 96.2% using 7 discriminatory genes (indoleamine-pyrrole-2,3-dioxygenase, ectodermal-neural cortex, TIMP3, fucosyltransferase-8, collectin sub-family member 12, carboxypeptidase D, and transglutaminase-2). Using routine biopsy samples we successfully performed whole genomic microarray analysis to identify discriminative signatures. Our results provide further insight into the pathophysiological background of colonic diseases. The results set up data warehouse which can be mined further.

  15. Methylation pattern of ALX4 gene promoter as a potential biomarker for blood-based early detection of colorectal cancer

    PubMed Central

    Salehi, Rasoul; Atapour, Norollah; Vatandoust, Nasimeh; Farahani, Najmeh; Ahangari, Fatemeh; Salehi, Ahmad Reza

    2015-01-01

    Background: To develop a non-invasive screening method for colorectal cancer, we evaluated the methylation of ALX4 gene promoter in serum samples from patients with colorectal cancer (CRC) and equal number of healthy individuals. Materials and Methods: In serum samples from 25 patients with colorectal cancer and 25 healthy control subjects, isolated serum free-floating DNA was treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction (MSP) with primers specific for methylated or unmethylated promoter CpG island sequences of the ALX4 gene. Results: Methylation of the ALX4 gene promoter was present in the serum DNA of patients with adenoma and colorectal cancer. A sensitivity of 68% and specificity of 88% were achieved in the detection of promoter methylation in colorectal neoplasia samples. The difference in methylation status of the ALX4 promoter between the patients with colorectal neoplasia and the control group was statistically highly significant (P < 0.001). Conclusions: The results indicate that this serum free DNA test of methylation of the ALX4 gene promoter is a sensitive and specific method. Therefore in combination with other useful markers it seems ALX4 has the potential of a clinically useful test for the early detection of colorectal cancer. PMID:26918234

  16. Inherited Colorectal Cancer Syndromes

    PubMed Central

    Kastrinos, Fay; Syngal, Sapna

    2011-01-01

    Colorectal cancer is the most common gastrointestinal malignancy and the second leading cause of cancer death in both men and women in the United States. Most colorectal cancer cases diagnosed annually are due to sporadic events but up to 5% are attributed to known monogenic disorders including Lynch syndrome, Familial Adenomatous Polyposis, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. These inherited colorectal cancer syndromes confer a markedly increased risk for the development of multiple cancers and predictive genetic testing is available to identify mutation carriers and at-risk family members. Through personalized strategies for diagnosis and management, a substantial reduction in morbidity and mortality has been appreciated among patients at highest risk for the development of colorectal cancer. PMID:22157284

  17. Colorectal Cancer Coalition

    MedlinePlus

    ... Reports Press Room Contact Us Sign Up We fight for Moms Dads Uncles Aunts Friends Brothers Sisters ... on Congress. Take Action Your Guide in the Fight Free resource for stage III & stage IV colorectal ...

  18. Tests for Colorectal Cancer

    MedlinePlus

    ... to look for colorectal cancer Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to ... has spread to the liver. Ultrasound Ultrasound uses sound waves and their echoes to create images of the ...

  19. Epidemiology of colorectal cancer

    PubMed Central

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

    Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies. PMID:27766137

  20. Colorectal carcinoma: Pathologic aspects

    PubMed Central

    Fleming, Matthew; Ravula, Sreelakshmi; Tatishchev, Sergei F.

    2012-01-01

    Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance. PMID:22943008

  1. Pharmacological and dietary prevention for colorectal cancer

    PubMed Central

    2013-01-01

    Background Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics. Discussion The studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results. Conclusion The results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be

  2. Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles

    PubMed Central

    Khondee, Supang; Rabinsky, Emily F.; Owens, Scott R.; Joshi, Bishnu P.; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D.

    2015-01-01

    Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35 days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, P<0.01. On immunohistochemistry, we observed a significant reduction in phospho-S6 but not β-catenin expression and reduced tumor cell proliferation, suggesting greater inhibition of downstream mTOR signaling. We observed significantly reduced renal toxicity for peptide-labeled rapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity. PMID:25483425

  3. Future of Minimally Invasive Colorectal Surgery.

    PubMed

    Whealon, Matthew; Vinci, Alessio; Pigazzi, Alessio

    2016-09-01

    Minimally invasive surgery is slowly taking over as the preferred operative approach for colorectal diseases. However, many of the procedures remain technically difficult. This article will give an overview of the state of minimally invasive surgery and the many advances that have been made over the last two decades. Specifically, we discuss the introduction of the robotic platform and some of its benefits and limitations. We also describe some newer techniques related to robotics. PMID:27582647

  4. [One case of laryngeal pleomorphic adenoma].

    PubMed

    An, Huiqin; Bu, Guiqing; Guo, Mingli

    2013-05-01

    A male patient, 55 years old, suffered from intermittent sound,voice depression and shortness of breath for one year,and from dysphagia for 3-4 months. Through fiber laryngoscopy,we could see tumor in the left posterior aryepiglottic fold. The tumor's surface was smooth. A portion of the tumor protruded to the laryngeal cavity and the aryepiglottic fold external,it also covered most of the glottis. Bilateral vocal cord were smooth and had good mobility. Throat CT demonstrated an irregular soft tissue mass on the left side of the aryepiglottic fold in supraglottic area with obscure normal boundary from adjacent structure. The left side of pyriform sinus became shallow without obvious bone destruction. The pathological report showed pleomorphic adenoma. The diagnosis was laryngeal pleomorphic adenoma. PMID:23898619

  5. Metastasizing pleomorphic adenoma of the salivary gland.

    PubMed

    Manucha, Varsha; Ioffe, Olga B

    2008-09-01

    Metastasizing pleomorphic adenoma of salivary glands is a group of rare tumors that are histologically identical to benign mixed tumors and that inexplicably metastasize. A review of the literature revealed that it usually occurs after multiple local recurrences, and the interval between diagnosis of primary pleomorphic adenoma and metastases ranges between 3 and 52 years. The most common site for metastasis is bone, followed by the head and neck and lung. No histologic or molecular parameters exist at the present time that could predict the development of metastasis in these neoplasms. Metastasectomy confers significant survival advantage over nonoperative treatment for localized and accessible metastases, but there is no definite treatment protocol available in cases of widespread metastases.

  6. Basal cell adenoma of the sublingual gland.

    PubMed

    Lin, Hsin-Ching; Chien, Chih-Yen; Huang, Shun-Chen; Su, Chih-Ying

    2003-12-01

    Salivary gland tumors constitute about 3% to 4% of all head and neck neoplasms. Approximately 80% originate in the parotid gland, and they rarely present in the sublingual gland; however, a disproportionately large majority of sublingual gland tumors are malignant. Basal cell adenoma is a benign epithelial salivary gland tumor that appears to have unique histologic characteristics, different from those of mixed tumors, and has a predilection for development in the parotid and minor salivary glands. No case has ever been reported as arising from the sublingual gland in the otolaryngology literature. We report here a case of a middle-aged woman with basal cell adenoma of the sublingual gland. The clinical presentation, pathological features, differential diagnosis, and treatment options for this relatively rare tumor are discussed.

  7. Giant pleomorphic adenoma of the parotid gland.

    PubMed

    Takahama, Ademar; da Cruz Perez, Danyel Elias; Magrin, José; de Almeida, Oslei Paes; Kowalski, Luiz Paulo

    2008-01-01

    Pleomorphic adenoma is the most common type of all benign and malignant salivary gland tumors, involving more frequently the parotid gland. It is a benign tumor with a slow and continuous growth that without treatment can reach an enormous size. We present a case of a giant pleomorphic adenoma in a 78-year-old man with a history of more than 30 years of a growing lesion in the parotid gland. Clinical examination revealed a giant mass on the right side of the face, however without any sign of facial nerve damage. The tumor was completely resected by total parotidectomy and preservation of the facial nerve. Macroscopically, the tumor measured 28 cm and weighed 4.0 Kg. On the histological examination there was a predominance of epithelial and myoepithelial cells in a hyaline and myxoid stroma. It was not found any area of malignant transformation. In the post-operatory the aesthetic and functional results were excellent.

  8. Pleomorphic adenoma causing acute airway obstruction.

    PubMed

    Moraitis, D; Papakostas, K; Karkanevatos, A; Coast, G J; Jackson, S R

    2000-08-01

    A case is reported of a pleomorphic adenoma of the minor salivary glands of the oral cavity presenting with acute airway obstruction. This is the first reported case to our knowledge of a mixed salivary tumour of the upper respiratory tract causing upper airway obstruction and acute respiratory failure. The patient had to be intubated and transferred to the intensive care unit. After an elective tracheostomy was performed, the adenoma was excised from its fibrous capsule. It was found to originate from the soft palate and occupied the parapharyngeal space. A high index of suspicion should be kept in order to diagnose tumours of the parapharyngeal space with unusual presentation. These tumours which are usually benign should be considered in the differential diagnosis from more common infectious or traumatic conditions and surgical morbidity should be minimal.

  9. Local inflammatory response in colorectal cancer.

    PubMed

    Łaskowski, P; Klim, B; Ostrowski, K; Szkudlarek, M; Litwiejko-Pietryńczak, E; Kitlas, K; Nienartowicz, S; Dzięcioł, J

    2016-06-01

    Type and intensity of tumor-infiltrating lymphocytes (TILs) in close proximity to the primary tumor are prognostically significant in postoperative patients. High intensity of TILs is considered to be a prognostically beneficial factor. The research included 66 postoperative colorectal cancer patients. The control group comprised 20 colon segments. Monoclonal antibodies LCA, CD3, CD4, CD5, CD8, CD20, CD23 and CD138 were used to differentiate between T and B lymphocytes. Types of cells in the infiltrate were defined. We found greater numbers of T and B lymphocytes located in close proximity to the cancerous tissue when compared to the control group. T lymphocyte intensity in the inflammatory infiltrations was directly correlated with the size of resected tumors, presence of regional lymphatic node metastases and histological grade of malignancy. Lymphocytic infiltrations of greater intensity located in close proximity to the primary tumor were found in subjects with less advanced colorectal cancer. The research presented here proves direct dependence between the immune system and colorectal cancer. The presence of lymphocytes in the inflammatory infiltrations located in close proximity to the cancerous tissue has been proved to be prognostically beneficial. The obtained results support the application of immunotherapy in colorectal cancer treatment. PMID:27543872

  10. Risks of Colorectal Cancer Screening

    MedlinePlus

    ... Genetics of Colorectal Cancer Colorectal cancer is the second leading cause of death from cancer in the ... professional versions have detailed information written in technical language. The patient versions are written in easy-to- ...

  11. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  12. Update on Hereditary Colorectal Cancer.

    PubMed

    DA Silva, Felipe Carneiro; Wernhoff, Patrik; Dominguez-Barrera, Constantino; Dominguez-Valentin, Mev

    2016-09-01

    In the past two decades, significant advances have been made in our understanding of colorectal (CRC) tumors with DNA mismatch (MMR) repair deficiency. The knowledge from molecular and genetic alterations in a variety of clinical conditions has refined the disease terminology and classification. Hereditary non-polyposis colorectal cancer (HNPCC) encompasses a spectrum of conditions that have significant phenotypic overlapping that makes clinical diagnosis a challenging task. Distinguishing among the HNPCC disorders is clinically important, as the approach to surveillance for patients and their at-risk family members differs according to risks for colonic and extracolonic cancer associated with each syndrome. Prospective and next-generation studies will provide valuable clinical information regarding the natural history of disease that will help differentiate the Lynch syndrome mimics and guide diagnosis and management for heterogeneous conditions currently grouped under the category of familial CRC. The review is intended to present and discuss the molecular nature of various conditions related to MMR deficiency and discusses the tools and strategies that have been used in detecting these conditions. PMID:27630275

  13. Cutaneous leiomyomatosis and parotid pleomorphic adenoma.

    PubMed

    Ocampo-Candiani, Jorge; Vázquez-Martínez, Osvaldo; Regalado-Briz, Arturo; Barboza-Quintana, Oralia; Méndez-Olvera, Nora

    2005-01-01

    We present a case of cutaneous leiomyomas (CL) arising in a pleomorphic adenoma (PA) of the parotid gland. PA and CL are benign tumors arising from the parotid gland and the erector pilli muscle, respectively. They both have a benign clinical course and in most cases leiomyomas are multiple in nature. PAs of the parotid are the most frequent benign tumors of the major salivary glands. To our knowledge this is the first case of PA with CL.

  14. Incidental Superior Hypophygeal Artery Aneurysm Embedded within Pituitary Adenoma

    PubMed Central

    Choi, Hong-Seok; Kim, Min-Su; Jung, Young-Jin

    2013-01-01

    Intra-cranial aneurysm can be incidental findings in patients with pituitary adenomas, and are usually located outside the pituitary region. However, the coexistence of intrasellar (not intracranial) aneurysms with pituitary adenomas is extremely rare. We report a patient with an incidental superior hypophygeal aneurysm embedded within a non-functional pituitary adenoma which was treated by transsphenoidal surgery after endovascular coil embolization. PMID:24278658

  15. Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

    PubMed

    Doster, A R; Armstrong, D L; Bargar, T W

    1989-05-01

    A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline.

  16. Seminoma and parathyroid adenoma in a snow leopard (Panthera unica).

    PubMed

    Doster, A R; Armstrong, D L; Bargar, T W

    1989-05-01

    A seminoma and parathyroid adenoma were diagnosed in an aged snow leopard. The ultrastructural appearance of the seminoma was similar to that described in the dog and in man. The lack of significant amounts of rough endoplasmic reticulum, Golgi complexes and free ribosomes in the parathyroid adenoma suggested that it was non-functional. Parathyroid adenoma has not been previously described in a large wild feline. PMID:2760281

  17. Subcutaneous pleomorphic adenomas in two different areas of the face.

    PubMed

    Tsukuno, Mari; Nakamura, Akiko; Takai, Shigeharu; Kurihara, Kunihiro

    2002-01-01

    A 41-year-old woman developed two subcutaneous pleomorphic adenomas on her face. Pleomorphic adenoma usually arises as a benign tumour of a major salivary gland and often develops multifocally within the gland. These two pleomorphic adenomas originated in the subcutaneous layer of the face, also multifocally. They were excised, she made a good recovery, and she had no signs of recurrence a year later.

  18. Pleomorphic adenoma of the minor salivary gland of the cheek.

    PubMed

    Sharma, Arpit; Deshmukh, Shraddha; Shaikh, Ahmed; Dabholkar, Jyoti

    2013-09-01

    Pleomorphic adenoma is the most common tumour of the salivary gland. While the majority arises from the parotid gland, only a small percentage arises from the minor salivary glands. The cheek, however, is a rarely affected site with respect to pleomorphic adenomas of the minor salivary glands. Herein, we report a case of pleomorphic adenoma of the cheek, which presented with intraoral swelling, and conclude that complete surgical excision can be a curative treatment for this benign tumour.

  19. Schwannoma-like pleomorphic adenoma of the parotid.

    PubMed

    Tille, Jean-Christophe; Reychler, Hervé; Hamoir, Marc; Schmitz, Sandra; Weynand, Birgit

    2011-10-21

    Pleomorphic adenoma is the most common benign salivary gland tumour. It can occur in any salivary gland, but is most frequently found in the parotid gland. Chondroid metaplasia is a frequent finding in pleomorphic adenoma. Other forms of metaplasia have been described, but are encountered less frequently. We report a rare case of unusual pleomorphic adenoma of the parotid gland with schwannoma-like feature.

  20. Life-threatening intrathyroidal parathyroid adenoma

    PubMed Central

    Dogan, Ugur; Koc, Umit; Mayir, Burhan; Habibi, Mani; Dogan, Berna; Gomceli, Ismail; Bulbuller, Nurullah

    2015-01-01

    Acute primary hyperparathyroidism and parathyroid crisis are characterized by life-threatening hypercalcemia, a rare disorder. A 69-year-old female patient presented at our hospital’s neurology clinic with weakness, nausea, vomiting, depression, and hypercalcemia. Treatment of hypercalcemia resulted in no improvement in neurological symptoms, indicating resistance to treatment. Thyroid ultrasonography and parathyroid scintigraphy revealed hypoechoic nodules in the right lobe, pieces of nodules in the left lobe, and high serum calcium and parathyroid hormone levels. After provision of intensive medical treatment including hydration, diuresis, and bisphosphonate infusion resulted in only minimal decrease in the calcium level, urgent surgical treatment was performed. Frozen biopsy of the right intrathyroidal giant parathyroid adenoma in the right lobe confirmed initial diagnosis of primary hyperparathyroidism. Based on the biopsy findings, right parathyroidectomy and right total and left subtotal thyroidectomy were performed. Histopathologic examination revealed a parathyroid adenoma localized inside large thyroid nodules. Review of the findings resulted in diagnosis of intrathyroidal parathyroid adenoma. Symptoms of hypercalcemia improved rapidly during the postoperative period. PMID:25785164

  1. Pituitary Adenoma Volumetry with 3D Slicer

    PubMed Central

    Nimsky, Christopher; Kikinis, Ron

    2012-01-01

    In this study, we present pituitary adenoma volumetry using the free and open source medical image computing platform for biomedical research: (3D) Slicer. Volumetric changes in cerebral pathologies like pituitary adenomas are a critical factor in treatment decisions by physicians and in general the volume is acquired manually. Therefore, manual slice-by-slice segmentations in magnetic resonance imaging (MRI) data, which have been obtained at regular intervals, are performed. In contrast to this manual time consuming slice-by-slice segmentation process Slicer is an alternative which can be significantly faster and less user intensive. In this contribution, we compare pure manual segmentations of ten pituitary adenomas with semi-automatic segmentations under Slicer. Thus, physicians drew the boundaries completely manually on a slice-by-slice basis and performed a Slicer-enhanced segmentation using the competitive region-growing based module of Slicer named GrowCut. Results showed that the time and user effort required for GrowCut-based segmentations were on average about thirty percent less than the pure manual segmentations. Furthermore, we calculated the Dice Similarity Coefficient (DSC) between the manual and the Slicer-based segmentations to proof that the two are comparable yielding an average DSC of 81.97±3.39%. PMID:23240062

  2. Sebaceous adenoma of the parotid gland.

    PubMed

    de Vicente Rodríguez, Juan Carlos; Fresno Forcelledo, Manuel Florentino; González García, Manuel; Aguilar Andrea, Carolina

    2006-08-01

    Tumors of the salivary glands constitute an important field of oral and maxillofacial pathology. The majority of salivary gland neoplasms are benign, with malignant salivary tumors accounting for 15 to 32 percent. The most common site for salivary gland tumors is the parotid gland, accounting up to 80 percent of all cases. This article reports the pathologic picture in a case of sebaceous adenoma of the parotid gland. The tumor was composed of epithelial cells lining ducts and closely associated with broad areas of sebaceous differentiation. The growth pattern was predominantly cystic, with cavities filled with sebaceous material. Areas of oncocytic metaplasia were also seen. The presence of sebaceous glands in salivary neoplasms is frequent, however, and in spite of this, salivary neoplasms constituted partially or entirely of these cells are rarely observed. To the surgeon and pathologist, the major problem in dealing with sebaceous adenoma is the recognition of this rare entity, avoiding confusing with other more aggressive neoplasms. The treatment involves surgical excision. The addition of the current case to the previously published data brings the total number of parotid sebaceous adenoma to seven.

  3. [The transphincteric approach excision of rectal villous adenomas].

    PubMed

    Qiu, H; Tang, W; Zhu, Y

    1995-03-01

    Twenty-four patients with rectal villous adenomas were operated on which posterior transphincteric approach. They had benign villous adenona in (13 patients), villous adenomas showing atypia (2), and villous adenomas developed malignancy (9). All the patients gained excellent results, except one with wounded infection after operation. No patient died at operation. No patient developed rectal fistula and incontinence of feces. The different methods of operation with excised villous adenoma of the rectum were discussed and compared. We conclude that the posterior transsphincteric approach is better than others. PMID:7555388

  4. Oncocytic changes in pleomorphic adenoma: Report of a rare case

    PubMed Central

    Kaur, Milanjeet; Bhogal, Jasmine

    2015-01-01

    Pleomorphic adenoma is the most common benign salivary gland tumor, accounting for almost three-fourths of all such tumors. Cells with oncocytic change are a common finding in salivary glands and in salivary gland tumors. When found within pleomorphic adenomas, cells with oncocytic changes may be perceived as evidence of malignancy, and lead to a misdiagnosis of carcinoma ex-pleomorphic adenoma. A case of pleomorphic adenoma arising de novo in the minor salivary glands with oncocytic changes is discussed here. PMID:26392734

  5. [Metastasizing pleomorphic adenoma of the submandibular gland: a case report].

    PubMed

    Zheng, Ya-Ge; Zhao, Ye; Wu, Lan-Yan

    2007-06-01

    Metastasizing pleomorphic adenomas without histological evidence of malignancy have rarely been reported. A case of 30-year-old woman with a mass which showed a benign pleomorphic adenoma appearanced histologically in the left submandibular gland and right supercollarbone respectively was described. Eight years ago, the patient suffered from pleomorphic adenoma of the left submandibular gland. It revealed histopathologic features consistent with the recurrent and metastasizing tumor. The clinic pathological features, possible mechanism and prevention approach of metastasizing pleomorphic adenoma were discussed based on previously reports in the literature.

  6. Colonoscopy in Colorectal Cancer Screening: Current Aspects.

    PubMed

    Triantafillidis, John K; Vagianos, Constantine; Malgarinos, George

    2015-09-01

    Colonoscopy represents a very important diagnostic modality for screening for colorectal cancer, because it has the ability to both detect and effectively remove pro-malignant and malignant lesions. It is recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality or, following a positive fecal occult blood test, to be performed every 10 years in individuals of average risk starting from the age of 50. However, a significant problem is the so-called post-screening (interval) polyps and cancers found some years after the index colonoscopy. In order to reduce the rate of interval cancers it is extremely necessary to optimize the quality and effectiveness of colonoscopy. Bowel preparation is of paramount importance for both accurate diagnosis and subsequent treatment of lesions found on colonoscopy. The quality of bowel preparation could be significantly improved by splitting the dose regimens, a strategy that has been shown to be superior to single-dose regimen. A good endoscopic technique and optimal withdrawal time offering adequate time for inspection, would further optimize the rate of cecal intubation and the number of lesions detected. During the last years, sophisticated devices have been introduced that would further facilitate cecal intubation. The percentage of total colonoscopies is now super-passing the level of 95 % allowing the adenoma detection rate to be greater than the suggestive level of 25 % in men and 15 % in women. This review aims to provide the reader with the current knowledge concerning indications, usefulness, limitations and future perspectives of this probably most important screening technique for colorectal cancer available today. PMID:27217671

  7. Accuracy of early detection of colorectal tumours by stool methylation markers: A meta-analysis

    PubMed Central

    Zhang, Hu; Qi, Jian; Wu, Ya-Qiong; Zhang, Ping; Jiang, Jun; Wang, Qi-Xian; Zhu, You-Qing

    2014-01-01

    AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours. METHODS: Electronic databases including PubMed, Web of Science, Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool (QADAS) was used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis. RESULTS: Thirty-seven articles met the inclusion criteria, and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer (CRC) were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. For adenoma, the sensitivity and specificity were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic OR was 47.57 (95%CI: 20.08-112.72), the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: sensitivity was 43% (95%CI: 38%-49%), specificity was 94% (95%CI: 91%-97%), the diagnostic OR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563. CONCLUSION: Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis. PMID:25320544

  8. HPP1: A transmembrane protein-encoding gene commonly methylated in colorectal polyps and cancers

    PubMed Central

    Young, Joanne; Biden, Kelli G.; Simms, Lisa A.; Huggard, Phillip; Karamatic, Rozemary; Eyre, Helen J.; Sutherland, Grant R.; Herath, Nirmitha; Barker, Melissa; Anderson, Gregory J.; Fitzpatrick, David R.; Ramm, Grant A.; Jass, Jeremy R.; Leggett, Barbara A.

    2001-01-01

    Adenomas are the precursors of most colorectal cancers. Hyperplastic polyps have been linked to the subset of colorectal cancers showing DNA microsatellite instability, but little is known of their underlying genetic etiology. Using a strategy that isolates differentially methylated sequences from hyperplastic polyps and normal mucosa, we identified a 370-bp sequence containing the 5′ untranslated region and the first exon of a gene that we have called HPP1. Rapid amplification of cDNA ends was used to isolate HPP1 from normal mucosa. Using reverse transcription–PCR, HPP1 was expressed in 28 of 30 (93%) normal colonic samples but in only seven of 30 (23%) colorectal cancers (P < 0.001). The 5′ region of HPP1 included a CpG island containing 49 CpG sites, of which 96% were found to be methylated by bisulfite sequencing of DNA from colonic tumor samples. By COBRA analysis, methylation was detected in six of nine (66%) adenomas, 17 of 27 (63%) hyperplastic polyps, and 46 of 55 (84%) colorectal cancers. There was an inverse relationship between methylation level and mRNA expression in cancers (r = −0.67; P < 0.001), and 5-aza-2-deoxycytidine treatment restored HPP1 expression in two colorectal cancer cell lines. In situ hybridization of HPP1 indicated that expression occurs in epithelial and stromal elements in normal mucosa but is silenced in both cell types in early colonic neoplasia. HPP1 is predicted to encode a transmembrane protein containing follistatin and epidermal growth factor-like domains. Silencing of HPP1 by methylation may increase the probability of neoplastic transformation. PMID:11120884

  9. Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: implications for colon carcinogenesis.

    PubMed

    McMillan, L; Butcher, S; Wallis, Y; Neoptolemos, J P; Lord, J M

    2000-06-24

    Butyrate is produced in the colon by fermentation of dietary fibre and induces apoptosis in colon adenoma and cancer cell lines, which may contribute to the protective effect of a high fibre diet against colorectal cancer (CRC). However, butyrate is present in the colon together with unconjugated bile acids, which are tumour promoters in the colon. We show here that bile acids deoxycholate (DCA) and chenodeoxycholate (CDCA), at levels present in the colon, gave a modest increase in cell proliferation and decreased spontaneous apoptosis in AA/C1 adenoma cells. Bile acids significantly inhibited the induction of apoptosis by butyrate in AA/C1 cells. However, the survival-inducing effects of bile acids on AA/C1 cells could be overcome by increasing the concentration of sodium butyrate. These results suggest that dysregulation of apoptosis in colonic epithelial cells by dietary factors is a key factor in the pathophysiology of CRC.

  10. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.

  11. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-09-28

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  12. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  13. Narrow-band imaging observation of colorectal lesions using NICE classification to avoid discarding significant lesions

    PubMed Central

    Hattori, Santa; Iwatate, Mineo; Sano, Wataru; Hasuike, Noriaki; Kosaka, Hidekazu; Ikumoto, Taro; Kotaka, Masahito; Ichiyanagi, Akihiro; Ebisutani, Chikara; Hisano, Yasuko; Fujimori, Takahiro; Sano, Yasushi

    2014-01-01

    AIM: To assess the risk of failing to detect diminutive and small colorectal cancers with the “resect and discard” policy. METHODS: Patients who received colonoscopy and polypectomy were recruited in the retrospective study. Probable histology of the polyps was predicted by six colonoscopists by the use of NICE classification. The incidence of diminutive and small colorectal cancers and their endoscopic features were assessed. RESULTS: In total, we found 681 cases of diminutive (1-5 mm) lesions in 402 patients and 197 cases of small (6-9 mm) lesions in 151 patients. Based on pathology of the diminutive and small polyps, 105 and 18 were non-neoplastic polyps, 557 and 154 were low-grade adenomas, 18 and 24 were high-grade adenomas or intramucosal/submucosal (SM) scanty invasive carcinomas, 1 and 1 were SM-d carcinoma, respectively. The endoscopic features of invasive cancer were classified as NICE type 3 endoscopically. CONCLUSION: The risk of failing to detect diminutive and small colorectal invasive cancer with the “resect and discard” strategy might be avoided through the use of narrow-band imaging observation with the NICE classification scheme and magnifying endoscopy. PMID:25512769

  14. History, evolution, and current status of radiologic imaging tests for colorectal cancer screening.