Trimodal endoscopic imaging for the detection and differentiation of colorectal adenomas: a prospective single-centre clinical evaluation.

PubMed

Rotondano, Gianluca; Bianco, Maria Antonia; Sansone, Stefano; Prisco, Antonio; Meucci, Costantino; Garofano, Maria Lucia; Cipolletta, Livio

2012-03-01

The purpose of this study is to evaluate an endoscopic trimodal imaging (ETMI) system (high resolution, autofluorescence, and NBI) in the detection and differentiation of colorectal adenomas. A prospective randomised trial of tandem colonoscopies was carried out using the Olympus XCF-FH260AZI system. Each colonic segment was examined twice for lesions, once with HRE and once with AFI, in random order per patient. All detected lesions were assessed with NBI for pit pattern and with AFI for colour. All lesions were removed and sent for histology. Any lesion identified on the second examination was considered as missed by the first examination. Outcome measures are adenoma miss rates of AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating neoplastic from non-neoplastic lesions. Ninety-four patients underwent colonoscopy with ETMI (47 in each group). Among 47 patients examined with AFI first, 31 adenomas in 15 patients were detected initially [detection rate 0.66 (0.52-0.75)]. Subsequent HRE inspection identified six additional adenomas. Among 47 patients examined with HRE first, 29 adenomas in 14 patients were detected initially [detection rate 0.62 (0.53-0.79)]. Successive AFI yielded seven additional adenomas. Adenoma miss rates of AFI and HRE were 14% and 16.2%, respectively (p = 0.29). Accuracy of AFI alone for differentiation was lower than NBI (63% vs. 80%, p < 0.001). Combined use of AFI and NBI achieved improved accuracy for differentiation (84%), showing a trend for superiority compared with NBI alone (p = 0.064). AFI did not significantly reduce the adenoma miss rate compared with HRE. AFI alone had a disappointing accuracy for adenoma differentiation, which could be improved by combination of AFI and NBI.

Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials.

PubMed

Williet, Nicolas; Tournier, Quentin; Vernet, Chloé; Dumas, Olivier; Rinaldi, Leslie; Roblin, Xavier; Phelip, Jean-Marc; Pioche, Mathieu

2018-04-26

Yield of Endocuff-assisted colonoscopy (EAC) compared with standard colonoscopy is conflicting in terms of adenoma detection rate (ADR). A meta-analysis of randomized controlled trials (RCTs) appears necessary. PubMed and Google Scholar were searched in December 2017. Abstracts from Digestive Disease Week and United European Gastroenterology Week meetings were also searched to 2017. All RCTs comparing EAC with standard colonoscopy were included. Analysis was conducted by using the Mantel-Haenszel models. Heterogeneity was quantified using the I 2 test. Of the 265 articles reviewed, 12 RCTs were included, with a total of 8376 patients (EAC group 4225; standard colonoscopy group 4151). In the meta-analysis, ADR was significantly increased in the EAC group vs. the standard colonoscopy group (41.3 % vs. 34.2 %; risk ratio [RR] = 1.20, 95 % confidence interval [CI] 1.06 to 1.36; P  = 0.003; I 2  = 79 %), especially for operators with low-to-moderate ADRs (< 35 %): RR = 1.51, 95 %CI 1.35 to 1.69; P  < 0.001; I 2  = 43 %). In contrast, this benefit was not reached for operators with high ADRs (> 45 %): RR = 1.01, 95 %CI 0.93 to 1.09; P  = 0.87; I 2  = 0.0 %). The mean number of adenomas per patient tended to be higher with EAC (mean difference = 0.11 adenomas/patient, 95 %CI - 0.17 to 0.38). Similar results were shown for polyp detection rates (61.6 % vs. 51.4 %; RR = 1.20, 95 %CI 1.06 to 1.36; P  = 0.004). Use of the Endocuff did not impact the cecal intubation rate (95.1 % vs. 95.7 %; P  = 0.08), or the procedure time compared with standard colonoscopy. Adverse events related to Endocuff were rare and exclusively mild mucosal erosion (4.0 %; 95 %CI 2.0 % to 8.0 %). With moderate-quality evidence, this study showed an improvement in ADR with EAC without major adverse events, especially for operators with low-to-moderate ADRs. © Georg Thieme Verlag KG Stuttgart · New

Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial.

PubMed

Bai, Yu; Fang, Jun; Zhao, Sheng-Bing; Wang, Dong; Li, Yan-Qing; Shi, Rui-Hua; Sun, Zi-Qin; Sun, Ming-Jun; Ji, Feng; Si, Jian-Min; Li, Zhao-Shen

2018-02-01

 Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR.  This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores.  583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P  = 0.04; advanced ADR 9.0 % vs. 7.0 %, P  = 0.38). The mean number of adenomas detected was 2.20 ± 1.36 vs. 1.63 ± 0.89 ( P  = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS ≥ 6 in 88.3 % vs. 75.2 % ( P  < 0.001) and bubble scores of 1.00 ± 1.26 vs. 3.98 ± 2.50 ( P  < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs . 19.7 %, P  < 0.001) than in the PEG alone group.  Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population. © Georg Thieme Verlag KG Stuttgart · New York.

New endoscopy advances to refine adenoma detection rate for colorectal cancer screening: None is the winner.

PubMed

Maida, Marcello; Camilleri, Salvatore; Manganaro, Michele; Garufi, Serena; Scarpulla, Giuseppe

2017-10-15

Colorectal cancer (CRC) is the third most common cancer in males and second in females, and globally the fourth cause for cancer death worldwide. Oncological screening of CRC has a major role in the management of the disease and it is mostly performed by colonoscopy. Anyway, effectiveness of endoscopic screening for CRC strictly depends on adequate detection and removal of potentially precancerous lesions, and accuracy of colonoscopy in detection of adenomas is still suboptimal. For this reason, several technological advances have been implemented in order to improve the diagnostic sensitivity of colonoscopy in adenoma detection. Among these: (1) Visual technologies such as chromoendoscopy and narrow band imaging; (2) optical innovation as high definition endoscopy, full-spectrum endoscopy or Third Eye Retroscope; and (3) mechanical advances as Cap assisted colonoscopy, Endocuff, Endoring and G-Eye endoscope. All these technologies advances have been tested over time by clinical studies with mixed results. Which of them is more likely to be successful in the next future?

Adenoma detection rate is not influenced by full-day blocks, time, or modified queue position.

PubMed

Lurix, Einar; Hernandez, Adrian V; Thoma, Matthew; Castro, Fernando

2012-04-01

Recent studies have shown the adenoma detection rate (ADR) to decrease from endoscopist fatigue. Our primary objective was to evaluate the afternoon ADR in half-day versus full-day blocks. Secondary objectives were to determine whether time or complexity of prior procedures (modified queue position) influence ADR. Retrospective chart review on consecutive colonoscopies. Tertiary-care teaching hospital. This study involved all patients in our database who were over age 45 and who underwent screening and surveillance colonoscopies. ADR. A total of 3085 patients were included in the study, with an overall 31% ADR. Of these procedures, 2148 (70%) were done in the morning, and 937 (30%) were done in the afternoon (512 full-day block, 425 half-day block). By multivariate analysis, there was no difference in ADR between full-day blocks compared with afternoon-only blocks (35% vs 32%; odds ratio [OR] 1.1; 95% confidence interval [CI], 0.8-1.5; P = .2). For all afternoon colonoscopies, no decrease in ADR was noted with increasing queue position (P = .9) or time (P = .3). In addition, no difference was found comparing ADR between all afternoon colonoscopies versus morning colonoscopies (33% vs 30%; OR 1.1; CI, 1.0-1.3; P = .1). No difference was found for advanced adenomas and number of adenomas between either afternoon-only blocks versus afternoon colonoscopy in full-day blocks or morning versus all afternoon cases. Retrospective study; not all withdrawal times were recorded; trainees performed some of the procedures. Our data show that colonoscopy can be performed in full-day blocks and 30-minute slots without compromising ADR. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Development of new non-invasive tests for colorectal cancer screening: the relevance of information on adenoma detection.

PubMed

Haug, Ulrike; Knudsen, Amy B; Lansdorp-Vogelaar, Iris; Kuntz, Karen M

2015-06-15

Researchers are actively pursuing the development of a new non-invasive test (NIT) for colorectal cancer (CRC) screening as an alternative to fecal occult blood tests (FOBTs). The majority of pilot studies focus on the detection of invasive CRC rather than precursor lesions (i.e., adenomas). We aimed to explore the relevance of adenoma detection for the viability of an NIT for CRC screening by considering a hypothetical test that does not detect adenomas beyond chance. We used the Simulation Model of Colorectal Cancer (SimCRC) to estimate the effectiveness of CRC screening and the lifetime costs (payers' perspective) for a cohort of US 50-years-old persons to whom CRC screening is offered from age 50-75. We compared annual screening with guaiac and immunochemical FOBTs (with sensitivities up to 70 and 24% for CRC and adenomas, respectively) to annual screening with a hypothetical NIT (sensitivity of 90% for CRC, no detection of adenomas beyond chance, specificity and cost similar to FOBTs). Screening with the NIT was not more effective, but was 29-44% more costly than screening with FOBTs. The findings were robust to varying the screening interval, the NIT's sensitivity for CRC, adherence rates favoring the NIT, and the NIT's unit cost. A comparative modelling approach using a model that assumes a shorter adenoma dwell time (MISCAN-COLON) confirmed the superiority of the immunochemical FOBT over an NIT with no ability to detect adenomas. Information on adenoma detection is crucial to determine whether a new NIT is a viable alternative to FOBTs for CRC screening. Current evidence thus lacks an important piece of information to identify marker candidates that hold real promise and deserve further (large-scale) evaluation. © 2014 UICC.

Carbon Dioxide Insufflation Increases Colonoscopic Adenoma Detection Rate Compared With Air Insufflation.

PubMed

Mills, Christopher D; McCamley, Chere; Swan, Michael P

2018-03-07

To determine the effect of carbon dioxide insufflation on the most important outcome measure of colonoscopic quality: adenoma detection rate (ADR). Bowel cancer is the second most common cause of cancer deaths in males and females in Australia. Carbon dioxide has in recent times become the insufflation methodology of choice for screening colonoscopy for bowel cancer, as this has been shown to have significant advantages when compared with traditional air insufflation. Endoscopies performed over a period of 9 months immediately before and after the implementation of carbon dioxide insufflation at endoscopy centers were eligible for inclusion. The difference in ADR between the carbon dioxide and air insufflation methods was statistically significant, with an increased ADR in the carbon dioxide group. The superiority of carbon dioxide insufflation was sustained with a logistic regression model, which showed ADR was significantly impacted by insufflation method. Carbon dioxide insufflation is known to reduce abdominal pain, postprocedural duration of abdominal pain, abdominal distension, and analgesic requirements. This study represents for the first time the beneficial effect of carbon dioxide insufflation upon the key quality colonoscopy indicator of ADR.

Quality in Colonoscopy: Beyond the Adenoma Detection Rate Fever

PubMed Central

Taveira, Filipe; Areia, Miguel; Elvas, Luís; Alves, Susana; Brito, Daniel; Saraiva, Sandra; Cadime, Ana Teresa

2017-01-01

Background Colonoscopy quality is a hot topic in gastroenterological communities, with several actual guidelines focusing on this aspect. Although the adenoma detection rate (ADR) is the single most important indicator, several other metrics are described and need reporting. Electronic medical reports are essential for the audit of quality indicators; nevertheless, they have proved not to be faultless. Aim The aim of this study was to analyse and audit quality indicators (apart from ADR) using only our internal electronic endoscopy records as a starting point for improvement. Methods An analysis of electronically recorded information of 8,851 total colonoscopies from a single tertiary centre from 2010 to 2015 was performed. Results The mean patient age was 63.4 ± 8.5 years; 45.5% of them were female, and in 14.6% sedation was used. Photographic documentation was done in 98.4% with 10.7 photographs on average, and 37.4% reports had <8 pictures per exam. Bowel preparation was rated as adequate in 67%, fair in 27% and inadequate in 4.9% of cases. The adjusted caecal intubation rate (CIR) was 92%, while negative predictors were inadequate preparation (OR 119, 95% CI 84–170), no sedation (OR 2.39, 95% CI 1.81–3.15), female gender (OR 1.61, 95% CI 1.38–1.88) and age ≥65 years (OR 1.56, 95% CI 1.34–1.82). In 28% of patients, a snare polypectomy was performed, correlating with adequate preparation (OR 5.75, 95% CI 3.90–8.48), male gender (OR 1.82, 95% CI 1.64–2.01) and age ≥65 years (OR 1.25, 95% CI 1.13–1.37; p < 0.01) as positive predictors. An annual evolution was observed with improvements in photographic documentation (10.7 vs. 12.9; p < 0.001), CIR (91 vs. 94%; p = 0.002) and “adequate” bowel preparation (p = 0.004). Conclusions: There is much more to report than the ADR to ensure quality in colonoscopy practice. Better registry systematization and integrated software should be goals to achieve in the short term. PMID:29255755

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

PubMed

Lee, T J W; Blanks, R G; Rees, C J; Wright, K C; Nickerson, C; Moss, S M; Chilton, A; Goddard, A F; Patnick, J; McNally, R J Q; Rutter, M D

2013-01-01

Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy. © Georg Thieme Verlag KG Stuttgart · New York.

Sessile Serrated Adenomas: How to Detect, Characterize and Resect

PubMed Central

Ma, Michael X.; Bourke, Michael J.

2017-01-01

Serrated polyps are important contributors to the burden of colorectal cancers (CRC). These lesions were once considered to have no malignant potential, but currently up to 30% of all CRC are recognized to arise from the serrated neoplasia pathway. The primary premalignant lesions are sessile serrated adenomas/polyps (SSA/Ps), although traditional serrated adenomas are relatively uncommon. Compared to conventional adenomas, SSA/Ps are morphologically subtle with indistinct borders, may be difficult to detect endoscopically, are more prevalent than previously thought, are associated with synchronous and metachronous advanced neoplasia, and have a higher risk of incomplete resection. Although many lesions remain “dormant,” progressive disease is associated with the development of dysplasia and more rapid progression to CRC. As a result, SSA/Ps are strongly implicated in the development of interval cancers. These factors represent unique challenges that require a meticulous approach to their management. In this review, we summarize the contemporary literature on the characterization, detection and resection of SSA/Ps. PMID:28494577

Simple colonoscopy reporting system checking the detection rate of colon polyps.

PubMed

Kim, Jae Hyun; Choi, Youn Jung; Kwon, Hye Jung; Park, Seun Ja; Park, Moo In; Moon, Won; Kim, Sung Eun

2015-08-21

To present a simple colonoscopy reporting system that can be checked easily the detection rate of colon polyps. A simple colonoscopy reporting system Kosin Gastroenterology (KG quality reporting system) was developed. The polyp detection rate (PDR), adenoma detection rate (ADR), serrated polyp detection rate (SDR), and advanced adenoma detection rate (AADR) are easily calculated to use this system. In our gastroenterology center, the PDR, ADR, SDR, and AADR test results from each gastroenterologist were updated, every month. Between June 2014, when the program was started, and December 2014, the overall PDR and ADR in our center were 62.5% and 41.4%, respectively. And the overall SDR and AADR were 7.5% and 12.1%, respectively. We envision that KG quality reporting system can be applied to develop a comprehensive system to check colon polyp detection rates in other gastroenterology centers.

Differences in Detection Rates of Adenomas and Serrated Polyps in Screening Versus Surveillance Colonoscopies, Based on the New Hampshire Colonoscopy Registry

PubMed Central

ANDERSON, JOSEPH C.; BUTTERLY, LYNN; GOODRICH, MARTHA; ROBINSON, CHRISTINA M.; WEISS, JULIA E.

2013-01-01

BACKGROUND & AIMS The adenoma detection rate (ADR) is an important quality indicator originally developed for screening colonoscopies. However, it is unclear whether the ADR should be calculated using data from screening and surveillance examinations. The recommended benchmark ADR for screening examinations is 20% (15% for women and 25% for men ≥ 50 y). There are few data available to compare ADRs from surveillance vs screening colonoscopies. We used a population-based registry to compare ADRs from screening vs surveillance colonoscopies. The serrated polyp detection rate (SDR), a potential new quality indicator, also was examined. METHODS By using data from the statewide New Hampshire Colonoscopy Registry, we excluded incomplete and diagnostic colonoscopies, and those performed in patients with inflammatory bowel disease, familial syndromes, or poor bowel preparation. We calculated the ADR and SDR (number of colonoscopies with at least 1 adenoma or serrated polyp detected, respectively, divided by the number of colonoscopies) from 9100 colonoscopies. The ADR and SDR were compared by colonoscopy indication (screening, surveillance), age at colonoscopy (50–64 y, ≥65 y), and sex. RESULTS The ADR was significantly higher in surveillance colonoscopies (37%) than screening colonoscopies (25%; P < .001). This difference was observed for both sexes and age groups. There was a smaller difference in the SDR of screening (8%) vs surveillance colonoscopies (10%; P < .001). CONCLUSIONS In a population-based study, we found that addition of data from surveillance colonoscopies increased the ADR, but had a smaller effect on the SDR. These findings indicate that when calculating ADR as a quality measure, endoscopists should use screening, rather than surveillance colonoscopy, data. PMID:23660415

Differences in detection rates of adenomas and serrated polyps in screening versus surveillance colonoscopies, based on the new hampshire colonoscopy registry.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Goodrich, Martha; Robinson, Christina M; Weiss, Julia E

2013-10-01

The adenoma detection rate (ADR) is an important quality indicator originally developed for screening colonoscopies. However, it is unclear whether the ADR should be calculated using data from screening and surveillance examinations. The recommended benchmark ADR for screening examinations is 20% (15% for women and 25% for men ≥50 y). There are few data available to compare ADRs from surveillance vs screening colonoscopies. We used a population-based registry to compare ADRs from screening vs surveillance colonoscopies. The serrated polyp detection rate (SDR), a potential new quality indicator, also was examined. By using data from the statewide New Hampshire Colonoscopy Registry, we excluded incomplete and diagnostic colonoscopies, and those performed in patients with inflammatory bowel disease, familial syndromes, or poor bowel preparation. We calculated the ADR and SDR (number of colonoscopies with at least 1 adenoma or serrated polyp detected, respectively, divided by the number of colonoscopies) from 9100 colonoscopies. The ADR and SDR were compared by colonoscopy indication (screening, surveillance), age at colonoscopy (50-64 y, ≥65 y), and sex. The ADR was significantly higher in surveillance colonoscopies (37%) than screening colonoscopies (25%; P < .001). This difference was observed for both sexes and age groups. There was a smaller difference in the SDR of screening (8%) vs surveillance colonoscopies (10%; P < .001). In a population-based study, we found that addition of data from surveillance colonoscopies increased the ADR but had a smaller effect on the SDR. These findings indicate that when calculating ADR as a quality measure, endoscopists should use screening, rather than surveillance colonoscopy, data. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Impact of fair bowel preparation quality on adenoma and serrated polyp detection: data from the New Hampshire colonoscopy registry by using a standardized preparation-quality rating.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Robinson, Christina M; Goodrich, Martha; Weiss, Julia E

2014-09-01

The effect of colon preparation quality on adenoma detection rates (ADRs) is unclear, partly because of lack of uniform colon preparation ratings in prior studies. The New Hampshire Colonoscopy Registry collects detailed data from colonoscopies statewide, by using a uniform preparation quality scale after the endoscopist has cleaned the mucosa. To compare the overall and proximal ADR and serrated polyp detection rates (SDR) in colonoscopies with differing levels of colon preparation quality. Cross-sectional. New Hampshire statewide registry. Patients undergoing colonoscopy. We examined colon preparation quality for 13,022 colonoscopies, graded by using specific descriptions provided to endoscopists. ADR and SDR are the number of colonoscopies with at least 1 adenoma or serrated polyp (excluding those in the rectum and/or sigmoid colon) detected divided by the total number of colonoscopies, for the preparation categories: optimal (excellent and/or good), fair, and poor. Overall/proximal ADR/SDR. The overall detection rates in examinations with fair colon preparation quality (SDR 8.9%; 95% confidence interval [CI], 7.4-10.7, ADR 27.1%; 95% CI, 24.6-30.0) were similar to rates observed in colonoscopies with optimal preparation quality (SDR 8.8%; 95% CI, 8.3-9.4, ADR 26.3%; 95% CI, 25.6-27.2). This finding also was observed for rates in the proximal colon. A logistic regression model (including withdrawal time) found that proximal ADR was statistically lower in the poor preparation category (odds ratio 0.45; 95% CI, 0.24-0.84; P < .01) than in adequately prepared colons. Homogeneous population. In our sample, there was no significant difference in overall or proximal ADR or SDR between colonoscopies with fair versus optimal colon preparation quality. Poor colon preparation quality may reduce the proximal ADR. Published by Mosby, Inc.

Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial.

PubMed

Cadoni, Sergio; Falt, Přemysl; Rondonotti, Emanuele; Radaelli, Franco; Fojtik, Petr; Gallittu, Paolo; Liggi, Mauro; Amato, Arnaldo; Paggi, Silvia; Smajstrla, Vit; Urban, Ondřej; Erriu, Matteo; Koo, Malcolm; Leung, Felix W

2017-05-01

Background and study aims  Single-center studies, which were retrospective and/or involved unblinded colonoscopists, have suggested that water exchange, but not water immersion, compared with air insufflation significantly increases the adenoma detection rate (ADR), particularly in the proximal and right colon. Head-to-head comparison of the three techniques with ADR as primary outcome and blinded colonoscopists has not been reported to date. In a randomized controlled trial with blinded colonoscopists, we aimed to evaluate the impact of the three insertion techniques on ADR. Patients and methods  A total of 1224 patients aged 50 - 70 years (672 males) and undergoing screening colonoscopy were randomized 1:1:1 to water exchange, water immersion, or air insufflation. Split-dose bowel preparation was adopted to optimize colon cleansing. After the cecum had been reached, a second colonoscopist who was blinded to the insertion technique performed the withdrawal. The primary outcome was overall ADR according to the three insertion techniques (water exchange, water immersion, and air insufflation). Secondary outcomes were other pertinent overall and right colon procedure-related measures. Results  Baseline characteristics of the three groups were comparable. Compared with air insufflation, water exchange achieved a significantly higher overall ADR (49.3 %, 95 % confidence interval [CI] 44.3 % - 54.2 % vs. 40.4 % 95 %CI 35.6 % - 45.3 %; P  = 0.03); water exchange showed comparable overall ADR vs. water immersion (43.4 %, 95 %CI 38.5 % - 48.3 %; P  = 0.28). In the right colon, water exchange achieved a higher ADR than air insufflation (24.0 %, 95 %CI 20.0 % - 28.5 % vs. 16.9 %, 95 %CI 13.4 % - 20.9 %; P  = 0.04) and a higher advanced ADR (6.1 %, 95 %CI 4.0 % - 9.0 % vs. 2.5 %, 95 %CI 1.2 % - 4.6 %; P  = 0.03). Compared with air insufflation, the mean number of

High-resolution(18)F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for pituitary adenoma detection in Cushing disease.

PubMed

Chittiboina, Prashant; Montgomery, Blake K; Millo, Corina; Herscovitch, Peter; Lonser, Russell R

2015-04-01

OBJECT High-resolution PET (hrPET) performed using a high-resolution research tomograph is reported as having a resolution of 2 mm and could be used to detect corticotroph adenomas through uptake of(18)F-fluorodeoxyglucose ((18)F-FDG). To determine the sensitivity of this imaging modality, the authors compared(18)F-FDG hrPET and MRI detection of pituitary adenomas in Cushing disease (CD). METHODS Consecutive patients with CD who underwent preoperative(18)F-FDG hrPET and MRI (spin echo [SE] and spoiled gradient recalled [SPGR] sequences) were prospectively analyzed. Standardized uptake values (SUVs) were calculated from hrPET and were compared with MRI findings. Imaging findings were correlated to operative and histological findings. RESULTS Ten patients (7 females and 3 males) were included (mean age 30.8 ± 19.3 years; range 11-59 years). MRI revealed a pituitary adenoma in 4 patients (40% of patients) on SE and 7 patients (70%) on SPGR sequences.(18)F-FDG hrPET demonstrated increased(18)F-FDG uptake consistent with an adenoma in 4 patients (40%; adenoma size range 3-14 mm). Maximum SUV was significantly higher for(18)F-FDG hrPET-positive tumors (difference = 5.1, 95% CI 2.1-8.1; p = 0.004) than for(18)F-FDG hrPET-negative tumors.(18)F-FDG hrPET positivity was not associated with tumor volume (p = 0.2) or dural invasion (p = 0.5). Midnight and morning ACTH levels were associated with(18)F-FDG hrPET positivity (p = 0.01 and 0.04, respectively) and correlated with the maximum SUV (R = 0.9; p = 0.001) and average SUV (R = 0.8; p = 0.01). All(18)F-FDG hrPET-positive adenomas had a less than a 180% ACTH increase and(18)F-FDG hrPET-negative adenomas had a greater than 180% ACTH increase after CRH stimulation (p = 0.03). Three adenomas were detected on SPGR MRI sequences that were not detected by(18)F-FDG hrPET imaging. Two adenomas not detected on SE (but no adenomas not detected on SPGR) were detected on(18)F-FDG hrPET. CONCLUSIONS While(18)F-FDG hrPET imaging can

Polyp detection rates using magnification with narrow band imaging and white light.

PubMed

Gilani, Nooman; Stipho, Sally; Panetta, James D; Petre, Sorin; Young, Michele A; Ramirez, Francisco C

2015-05-16

To compare the yield of adenomas between narrow band imaging and white light when using high definition/magnification. This prospective, non-randomized comparative study was performed at the endoscopy unit of veteran affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first average risk colorectal cancer screening colonoscopy were selected. Two experienced gastroenterologists performed all the procedures that were blinded to each other's findings. Demographic details were recorded. Data are presented as mean ± SEM. Proportional data were compared using the χ(2) test and means were compared using the Student's t test. Tandem colonoscopy was performed in a sequential and segmental fashion using one of 3 strategies: white light followed by narrow band imaging [Group A: white light (WL) → narrow band imaging (NBI)]; narrow band imaging followed by white light (Group B: NBI → WL) and, white light followed by white light (Group C: WL → WL). Detection rate of missed polyps and adenomas were evaluated in all three groups. Three hundred patients were studied (100 in each Group). Although the total time for the colonoscopy was similar in the 3 groups (23.8 ± 0.7, 22.2 ± 0.5 and 24.1 ± 0.7 min for Groups A, B and C, respectively), it reached statistical significance between Groups B and C (P < 0.05). The cecal intubation time in Groups B and C was longer than for Group A (6.5 ± 0.4 min and 6.5 ± 0.4 min vs 4.9 ± 0.3 min; P < 0.05). The withdrawal time for Groups A and C was longer than Group B (18.9 ± 0.7 min and 17.6 ± 0.6 min vs 15.7 ± 0.4 min; P < 0.05). Overall miss rate for polyps and adenomas detected in three groups during the second look was 18% and 17%, respectively (P = NS). Detection rate for polyps and adenomas after first look with white light was similar irrespective of the light used during the second look (WL → WL: 13.7% for polyps, 12.6% for adenomas; WL → NBI: 14.2% for polyps, 11.3% for adenomas). Miss rate of

Prospective multicenter randomized controlled trial comparing adenoma detection rate in colonoscopy using water exchange, water immersion, and air insufflation.

PubMed

Hsieh, Yu-Hsi; Tseng, Chih-Wei; Hu, Chi-Tan; Koo, Malcolm; Leung, Felix W

2017-07-01

Adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma of any size, is a quality indicator. We tested the hypothesis that water exchange (WE) improves ADR but water immersion (WI) has no adverse effect on ADR compared with air insufflation (AI). A prospective study was conducted at the Dalin Tzu Chi Hospital in southern Taiwan and the Hualien Tzu Chi Hospital in eastern Taiwan on patients randomly assigned to WE, WI, or AI with stratification by the 3 study colonoscopists. The primary outcome was ADR. From July 2013 to December 2015, 651 patients were recruited and randomized into 3 groups with a 1:1:1 ratio (217 patients per group). Overall, ADR met quality standards: WE 49.8% (95% CI, 43.2%-56.4%), AI 37.8% (95% CI, 31.6%-44.4%), and WI 40.6% (95% CI, 34.2%-47.2%). Compared with AI, WE significantly increased ADR (P = .016). There was no difference between WI and WE. ADRs of WI and AI were comparable. Compared with AI, WE confirmed a longer insertion time, higher cleanliness score, but similar adenoma per positive colonoscopy (APPC) and withdrawal time with polypectomy. Subgroup analysis found WE significantly increased ADR in propofol-sedated patients. Multivariate generalized linear mixed model analysis revealed that age ≥50 years, WE (vs AI), colonoscopy indication, no previous history of colonoscopy, and withdrawal time >8 minutes were significant predictors of increased ADR. Confirmation of prior reports showing WE, but not WI, increased ADR further strengthened the validity of our observations. WE significantly increased ADR in propofol-sedated patients. The outcome differences justify assessment of the role of WE in colorectal cancer prevention. Similar APPC and withdrawal times suggest that adequate inspection was performed on colonoscope withdrawal in each of the study arms. (Clinical trial registration number: NCT01894191.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. All rights reserved.

Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies

PubMed Central

Kim, Nam Hee; Suh, Jung Yul; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Choi, Kyuyong

2017-01-01

Purpose Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy. Materials and Methods This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling. Results The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26–1.77; ptrend<0.001], 1.22 (95% CI, 1.04–1.43; ptrend=0.024), 1.22 (95% CI, 1.02–1.46; ptrend=0.046), 1.36 (95% CI, 1.14–1.63; ptrend=0.004), and 1.19 (95% CI, 0.99–1.42; ptrend=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas. Conclusion The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas. PMID:28120565

Polyp detection rates using magnification with narrow band imaging and white light

PubMed Central

Gilani, Nooman; Stipho, Sally; Panetta, James D; Petre, Sorin; Young, Michele A; Ramirez, Francisco C

2015-01-01

AIM: To compare the yield of adenomas between narrow band imaging and white light when using high definition/magnification. METHODS: This prospective, non-randomized comparative study was performed at the endoscopy unit of veteran affairs medical center in Phoenix, Arizona. Consecutive patients undergoing first average risk colorectal cancer screening colonoscopy were selected. Two experienced gastroenterologists performed all the procedures that were blinded to each other’s findings. Demographic details were recorded. Data are presented as mean ± SEM. Proportional data were compared using the χ2 test and means were compared using the Student’s t test. Tandem colonoscopy was performed in a sequential and segmental fashion using one of 3 strategies: white light followed by narrow band imaging [Group A: white light (WL) → narrow band imaging (NBI)]; narrow band imaging followed by white light (Group B: NBI → WL) and, white light followed by white light (Group C: WL → WL). Detection rate of missed polyps and adenomas were evaluated in all three groups. RESULTS: Three hundred patients were studied (100 in each Group). Although the total time for the colonoscopy was similar in the 3 groups (23.8 ± 0.7, 22.2 ± 0.5 and 24.1 ± 0.7 min for Groups A, B and C, respectively), it reached statistical significance between Groups B and C (P < 0.05). The cecal intubation time in Groups B and C was longer than for Group A (6.5 ± 0.4 min and 6.5 ± 0.4 min vs 4.9 ± 0.3 min; P < 0.05). The withdrawal time for Groups A and C was longer than Group B (18.9 ± 0.7 min and 17.6 ± 0.6 min vs 15.7 ± 0.4 min; P < 0.05). Overall miss rate for polyps and adenomas detected in three groups during the second look was 18% and 17%, respectively (P = NS). Detection rate for polyps and adenomas after first look with white light was similar irrespective of the light used during the second look (WL → WL: 13.7% for polyps, 12.6% for adenomas; WL → NBI: 14.2% for polyps, 11.3% for

Long-term recurrence rate of pleomorphic adenoma and postoperative facial nerve paresis (in parotid surgery).

PubMed

Zernial, Oliver; Springer, Ingo N; Warnke, Patrick; Härle, Franz; Risick, Christian; Wiltfang, Jörg

2007-04-01

The purpose of this study was to evaluate recurrence rates and comorbidity in patients with pleomorphic adenomas of patients after superficial and total conservative parotidectomy. Localization of pleomorphic adenomas, age, sex distribution and facial nerve function of 73 patients were examined in this retrospective study. The recurrence rate could be determined in 43 of these patients. The interval between surgery and last recall varied between 2 and 20 years (median: 8.1 years). Most of the patients were female (67%) with a parotid pleomorphic adenoma. No recurrence was found regard less of whether a superficial or total conservative parotidectomy had been performed. Our data did show that the total conservative parotidectomy is associated with a higher incidence of temporary impaired facial nerve function, which was seen in 42% of this group. Temporary decreased nerve function after superficial parotidectomy was rare being apparent in only 16% of this group. A more radical procedure does not significantly lower the recurrence rate. We suggest that the indication for a total conservative parotidectomy in cases of superficial adenomas should be considered carefully.

Adenoma Detection Rates for Screening Colonoscopies in Smokers and Obese Adults: Data From the New Hampshire Colonoscopy Registry.

PubMed

Anderson, Joseph C; Weiss, Julia E; Robinson, Christina M; Butterly, Lynn F

To examine screening adenoma detection rates (ADR) and serrated detection rates (SDR) among smokers and obese adults in the New Hampshire Colonoscopy Registry. ADR, a quality measure for screening colonoscopies, is associated with protection from interval colorectal cancer. Currently, only sex-specific ADR benchmarks are reported. However, obesity and smoking ≥20 pack-years are strong predictors for colorectal neoplasia, as highlighted by the 2009 American College of Gastroenterology CRC Screening Guidelines. Data comparing ADR in smokers and obese adults to those without these risks are limited. We calculated ADR, SDR, and 95% confidence intervals for screening colonoscopies in participants ≥50 years. Sex-specific and sex-age-specific rates were compared by smoking exposure (never vs. <20 vs. ≥20 pack-years) and body mass index (<30 vs. ≥30). A total of 21,539 screening colonoscopies were performed by 77 endoscopists at 20 facilities (April 2009 to September 2013). The difference in ADR between nonsmokers and smokers with ≥20 pack-years was 8.8% (P<0.0001) and between obesity groups 5.0% (P<0.0001). Significant sex-specific and sex-age-specific increases in ADR and SDR were found among smokers and obese participants. ADR and SDR for smokers and obese adults were significantly higher than their counterparts without those risks. Endoscopists should consider the prevalence of these risks within their screening population when comparing their rates to established benchmarks. Calculating sex-specific or sex-age-specific ADR and SDR based on smoking and obesity may provide optimal protection for populations with a particularly high prevalence of smokers and obese adults.

Colorectal adenoma recurrence rates among post-polypectomy patients in the placebo-controlled groups of randomized clinical trials: a meta-analysis

PubMed Central

Shi, Xin; Yang, Zhiping; Wu, Qiong; Fan, Daiming

2017-01-01

Background Evidence regarding the benefit of therapy to prevent the post-polypectomy recurrence of colorectal adenoma is limited. Endoscopic recurrence is the main outcome according to an evaluation of trials involving recurrence prevention. Aim To estimate the recurrence rates of post-polypectomy colorectal adenoma in placebo-controlled arms of randomized clinical trials and to identify the prognostic factors influencing these rates. Methods We combined data from all randomized controlled trials evaluating therapies for colorectal adenoma using placebo from 1988 to 2016. The data were combined in a random-effects model. Primary outcomes were endoscopic adenoma and advanced adenoma recurrence of colorectal adenoma. Results The pooled estimates of the adenoma recurrence rates were 37% (95% confidence interval [CI], 33%-41%; range, 33%-52%) at 1 year, 47% (95% CI, 41%-54%; range, 46%-51%) at 2 years, 41% (95% CI, 33%-48%; range, 20%-61%) at 3 years, 48% (95% CI, 38%-57%; range, 37%-53%) at 4 years, and 60% (95% CI, 52%-68%; range, 48%-68%) at 5 years. The pooled estimates of the advanced adenoma recurrence rates were 10% (95% CI, 6%-15%; range, 7%-13%) at 1 year, 12% (95% CI, 8%-16%; range, 3%-19%) at 3 years, 14% (95% CI, 10%-18%; range, 13%-16%) at 4 years, and 14% (95% CI, 10%-19%; range, 9%-21%) at 5 years. Significant heterogeneity among the randomized clinical trials (P < 0.001) was observed for each recurrence rate. Conclusions This meta-analysis confirms the heterogeneity of recurrence rates among post-polypectomy colorectal adenoma patients who received placebo. No single design variable was identified that might explain the heterogeneity. PMID:28977952

Anatomical distribution and detection rate of colorectal neoplasms according to age in the colonoscopic screening of a Korean population.

PubMed

Lee, Suk-Young; Song, Wan Hee; Oh, Sang Cheul; Min, Byung-Wook; Lee, Sun Il

2018-01-01

Because data as a basis for the determination of proper age and modality for screening of colorectal neoplasms is lacking, we evaluated detection rates and anatomical distribution of colorectal neoplasms according to age in healthy individuals who underwent total colonoscopy for health checkup. A total of 16,100 cases that had received the colonoscopic examination from January to December in 2014 were analyzed. The total number of individuals who received total colonoscopy were divided by the number of individuals harboring colorectal adenoma to calculate the detection rate of colorectal adenoma. Individuals ≤50 years old were classified as young-age group and aged >50 were old-age group. Differences in anatomical locations of colorectal neoplasms were analyzed in the 2 age groups by chi-square test. Risk factors for colorectal adenoma in each age group were analyzed using univariate and multivariate logistic regression analyses. Detection rates of colorectal adenoma were 13.7% in all cases and 12.8% for those in their 40's. The main anatomical location of colorectal adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was mainly distributed to the distal colon in both age groups (P < 0.001). Distal colon was the major site for colorectal cancer in the old-age group (P = 0.001). Proximal location of neoplasms was a risk factor for colorectal adenoma in both age groups with multivariate analysis. These data could be the bases for earlier initiation of screening for colorectal neoplasms with total colonoscopy to detect clinically significant colorectal polyps.

Endoscopic management of colorectal adenomas.

PubMed

Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

2017-01-01

Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy.

Endoscopic management of colorectal adenomas

PubMed Central

Meier, Benjamin; Caca, Karel; Fischer, Andreas; Schmidt, Arthur

2017-01-01

Colorectal adenomas are well known precursors of invasive adenocarcinoma. Colonoscopy is the gold standard for adenoma detection. Colonoscopy is far more than a diagnostic tool, as it allows effective treatment of colorectal adenomas. Endoscopic resection of colorectal adenomas has been shown to reduce the incidence and mortality of colorectal cancer. Difficult resection techniques are available, such as endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic full-thickness resection. This review aims to provide an overview of the different endoscopic resection techniques and their indications, and summarizes the current recommendations in the recently published guideline of the European Society of Gastrointestinal Endoscopy. PMID:29118553

New-Generation High-Definition Colonoscopes Increase Adenoma Detection when Screening a Moderate-Risk Population for Colorectal Cancer.

PubMed

Bond, Ashley; O'Toole, Paul; Fisher, Gareth; Subramanian, Sreedhar; Haslam, Neil; Probert, Chris; Cox, Trevor; Sarkar, Sanchoy

2017-03-01

Adenoma detection rate (ADR) is the most important quality indicator for screening colonoscopy, due to its association with colorectal cancer outcomes. As a result, a number of techniques and technologies have been proposed that have the potential to improve ADR. The aim of this study was to assess the potential impact of new-generation high-definition (HD) colonoscopy on ADR within the Bowel Cancer Screening Programme (BCSP). This was a retrospective single-center observational study in patients undergoing an index screening colonoscopy. The examination was performed with either standard-definition colonoscopes (Olympus Q240/Q260 series) or HD colonoscopes (Olympus HQ290 EVIS LUCERA ELITE system) with the primary outcome measures of ADR and mean adenoma per procedure (MAP) between the 2 groups. A total of 395 patients (60.5% male, mean age 66.8 years) underwent screening colonoscopy with 45% performed with HD colonoscopes. The cecal intubation rate was 97.5% on an intention-to-treat basis and ADR was 68.6%. ADR with standard-definition was 63.13%, compared with 75.71% with HD (P = .007). The MAP in the HD group was 2.1 (± 2.0), whereas in the standard-definition group it was 1.6 (± 1.8) (P = .01). There was no significant difference in withdrawal time between the 2 groups. In the multivariate regression model, only HD scopes (P = .03) and male sex (P = .04) independently influenced ADR. Olympus H290 LUCERA ELITE HD colonoscopes improved adenoma detection within the moderate-risk population. A 12% improvement in ADR might be expected to increase significantly the protection afforded by colonoscopy against subsequent colorectal cancer mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs.

PubMed

Cubiella, Joaquín; Castells, Antoni; Andreu, Montserrat; Bujanda, Luis; Carballo, Fernando; Jover, Rodrigo; Lanas, Ángel; Morillas, Juan Diego; Salas, Dolores; Quintero, Enrique

2017-03-01

The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. The median ADR was 31% (range, 14%-51%) in the colonoscopy group and 55% (range, 21%-83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson's coefficient 0.716; p  < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 ( p  = 0.009); sex, 0.09 ( p  = 0.09); age, 0.3 ( p  = 0.5); and region 0.00 ( p  = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%-56%). ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated.

Correlation between adenoma detection rate in colonoscopy- and fecal immunochemical testing-based colorectal cancer screening programs

PubMed Central

Castells, Antoni; Andreu, Montserrat; Bujanda, Luis; Carballo, Fernando; Jover, Rodrigo; Lanas, Ángel; Morillas, Juan Diego; Salas, Dolores; Quintero, Enrique

2016-01-01

Background The adenoma detection rate (ADR) is the main quality indicator of colonoscopy. The ADR recommended in fecal immunochemical testing (FIT)-based colorectal cancer screening programs is unknown. Methods Using the COLONPREV (NCT00906997) study dataset, we performed a post-hoc analysis to determine if there was a correlation between the ADR in primary and work-up colonoscopy, and the equivalent figure to the minimal 20% ADR recommended. Colonoscopy was performed in 5722 individuals: 5059 as primary strategy and 663 after a positive FIT result (OC-Sensor™; cut-off level 15 µg/g of feces). We developed a predictive model based on a multivariable lineal regression analysis including confounding variables. Results The median ADR was 31% (range, 14%–51%) in the colonoscopy group and 55% (range, 21%–83%) in the FIT group. There was a positive correlation in the ADR between primary and work-up colonoscopy (Pearson’s coefficient 0.716; p < 0.001). ADR in the FIT group was independently related to ADR in the colonoscopy group: regression coefficient for colonoscopy ADR, 0.71 (p = 0.009); sex, 0.09 (p = 0.09); age, 0.3 (p = 0.5); and region 0.00 (p = 0.9). The equivalent figure to the 20% ADR was 45% (95% confidence interval, 35%–56%). Conclusions ADR in primary and work-up colonoscopy of a FIT-positive result are positively and significantly correlated. PMID:28344793

Removal of infused water predominantly during insertion (water exchange) is consistently associated with an increase in adenoma detection rate - review of data in randomized controlled trials (RCTs) of water-related methods

PubMed Central

Harker, JO; Leung, JW; Siao-Salera, RM; Mann, SK; Ramirez, FC; Friedland, S; Amato, A; Radaelli, F; Paggi, S; Terruzzi, V; Hsieh, YH

2011-01-01

Introduction Variation in outcomes in RcTs comparing water-related methods and air insufflation raises challenging questions regarding the new approach. This report reviews impact of water exchange - simultaneous infusion and removal of infused water during insertion on adenoma detection rate (ADR) defined as proportion of patients with a least one adenoma of any size. Methods Medline (2008–2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of colonoscope. Results Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts, n=1728) described ADR in patients randomized to be examined by air and water-related methods. The water-related methods differed in timing of removal of the infused water -predominantly during insertion (water exchange) (n=825) or predominantly during withdrawal (water immersion) (n=903). Water immersion was associated with both increases and decreases in ADR compared to respective air method patients and the net overall change (-7%) was significant. On the other hand water exchange was associated with increases in ADR consistently and the net changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all significant. Conclusion Comparative data generated the hypothesis that significantly larger increases in overall and proximal colon ADRs were associated with water exchange than water immersion or air insufflation during insertion. The hypothesis should be evaluated by RCTs to elucidate the mechanism of water exchange on adenoma detection. PMID:22163082

The Expression and Significance of Feces Cyclooxygensae-2 mRNA in Colorectal Cancer and Colorectal Adenomas

PubMed Central

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

Background/Aim: This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. Materials and Methods: The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. Results: The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842, P = 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525, P = 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. Conclusions: High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer. PMID:28139497

The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas.

PubMed

Li, Xiaofeng; Kong, Lixia; Liao, Suhuan; Lu, Jing; Ma, Lin; Long, Xiaohua

2017-01-01

This study aims to explore the expression and significance of feces cyclooxygensae-2 (COX-2) mRNA in colorectal cancer and colorectal adenomas. The expression of feces COX-2 mRNA in colorectal cancer (n = 28), colorectal adenomas (n = 54), and normal control group (n = 11) were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The positive rate of fecal occult blood test (FOBT) were detected in colorectal cancer (n = 30), colorectal adenomas (n = 56), and normal control group (n = 11); the sensitivity of the two methods was also compared. The positive rate of feces COX-2 mRNA in colorectal cancer was 82.1% (25/28), which was significantly higher than colorectal adenomas 59.3% (32/54), and normal tissues 18.2% (2/11), the difference being significant between the three groups (χ2= 13.842,P= 0.001). The positive rate of FOBT in colorectal cancer was 73.3% (10/30), which was significantly higher than colorectal adenomas 10.7% (6/56) and normal tissues 9.1% (1/11), the difference being significant between these three groups (χ2= 7.525,P= 0.023). There was no significant association between feces COX-2 expression and various clinical pathological features of colorectal cancer and colorectal adenomas (P > 0.05). The sensitivity of the RT-PCR method is higher than FOBT, however, the specificity of FOBT is slightly higher than RT-PCR. High expression of feces COX-2 mRNA in colorectal adenomas and colorectal cancer is a common event; it is an early event in the development of colorectal adenomas to colorectal cancer. Feces COX-2 mRNA has a high sensitivity for detect colorectal cancer; combination with FOBT will be the best alternative. Feces COX-2 can be potentially used in the early diagnosis and screening of colorectal cancer.

A Novel Technology for Localization of Parathyroid Adenoma: Ultrasound-Guided Fine Needle Aspiration Combined With Rapid Parathyroid Hormone Detection and Nano-Carbon Technology.

PubMed

Yan, Shouyi; Zhao, Wenxin; Wang, Bo; Zhang, Liyong

2018-06-01

The study aims to evaluate the clinic feasibility of rapid parathyroid hormone (PTH) detection and nano-carbon technology in preoperative diagnosis and localization of parathyroid adenoma. With the guidance of ultrasound, the operator performed the parathyroid puncture and tested the PTH value by using a PTH test kit, and then injected nano-carbon into parathyroid adenoma as a marker to observe whether the parathyroid adenoma was stained black during the final operation. Meanwhile, a part of excised specimen was made into homogenate and detected rapidly again by using the PTH test kit. The remaining was confirmed by intraoperative frozen pathological examination. The sensitivity (12/12) of preoperative diagnosis was significantly higher than that of ultrasound (6/12), magnetic resonance imaging (7/12), and MIBI (9/12). During the operation, we found that the inner part of the parathyroid adenoma was stained black, and the PTH value of the specimen homogenate confirmed as parathyroid adenoma was more than 3000 pg/mL. This novel technology, as a very positive method for localization of parathyroid adenoma, plays an important role in guaranteeing the surgical reliability of parathyroid adenoma with help of nano-carbon technology.

Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey.

PubMed

Barret, Maximilien; Boustiere, Christian; Canard, Jean-Marc; Arpurt, Jean-Pierre; Bernardini, David; Bulois, Philippe; Chaussade, Stanislas; Heresbach, Denis; Joly, Isabelle; Lapuelle, Jean; Laugier, René; Lesur, Gilles; Pienkowski, Patrice; Ponchon, Thierry; Pujol, Bertrand; Richard-Molard, Bruno; Robaszkiewicz, Michel; Systchenko, Rémi; Abbas, Fatima; Schott-Pethelaz, Anne-Marie; Cellier, Christophe

2013-01-01

Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.

Public reporting of colonoscopy quality is associated with an increase in endoscopist adenoma detection rate.

PubMed

Abdul-Baki, Heitham; Schoen, Robert E; Dean, Katie; Rose, Sherri; Leffler, Daniel A; Kuganeswaran, Eliathamby; Morris, Michele; Carrell, David; Mehrotra, Ateev

2015-10-01

Colonoscopy is the predominant method for colorectal cancer screening in the United States. Previous studies have documented variation across physicians in colonoscopy quality as measured by the adenoma detection rate (ADR). ADR is the primary quality measure of colonoscopy examinations and an indicator of the likelihood of subsequent colorectal cancer. There is interest in mechanisms to improve the ADR. In Central Illinois, a local employer and a quality improvement organization partnered to publically report physician colonoscopy quality. We assessed whether this initiative was associated with an improvement in the ADR. We compared ADRs before and after public reporting at a private practice endoscopy center with 11 gastroenterologists in Peoria, Illinois, who participated in the initiative. To generate the ADR, colonoscopy and pathology reports from examinations performed over 4 years at the endoscopy center were analyzed by using previously validated natural language processing software. A central Illinois endoscopy center. The ADR in the pre-public reporting period was 34.3% and 39.2% in the post-public reporting period (an increase of 4.9%, P < .001). The increase in the right-sided ADR was 5.1% (P < .01), whereas the increase in the left-sided ADR was 2.1% (P < .05). The increase in the ADR was 7.8% for screening colonoscopies (P < 0.05) and 3.5% for nonscreening colonoscopies (P < .05). All but 1 physician's ADR increased (range -2.7% to 10.5%). There was no statistically significant change in the advanced ADR (increase of 0.8%, P = .22). There was no concurrent control group to assess whether the increased ADR was due to a secular trend. A public reporting initiative on colonoscopy quality was associated with an increase in ADR. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Infrequent detectable somatic mutations of the RET and glial cell line-derived neurotrophic factor (GDNF) genes in human pituitary adenomas.

PubMed

Yoshimoto, K; Tanaka, C; Moritani, M; Shimizu, E; Yamaoka, T; Yamada, S; Sano, T; Itakura, M

1999-02-01

RET is a receptor tyrosine kinase expressed in neuroendocrine cells and tumors. RET is activated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor-alpha (GDNFR-alpha). Activating mutations of the RET proto-oncogene were found in multiple endocrine neoplasia (MEN) 2 and in sporadic medullary thyroid carcinoma and pheochromocytoma of neuroendocrine origin. Mutations of the RET proto-oncogene and the glial cell line-derived neurotrophic factor (GDNF) gene were examined in human pituitary tumors. No mutations of the RET proto-oncogene including the cysteine-rich region or codon 768 and 918 in the tyrosine kinase domain were detected in 172 human pituitary adenomas either by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) or by PCR-restriction fragment length polymorphism (RFLP). Further, somatic mutations of the GDNF gene in 33 human pituitary adenomas were not detected by PCR-SSCP. One polymorphism of the GDNF gene at codon 145 of TGC or TGT was observed in a prolactinoma. The RET proto-oncogene message was detected in a normal human pituitary gland or 4 of 4 human pituitary adenomas with reverse transcription (RT)-PCR, and in rodent pituitary tumor cell lines with Western blotting. The expression of GDNF gene was detected in 1 of 4 human somatotroph adenomas, 1 of 2 corticotroph adenomas, and 2 of 6 rodent pituitary tumor cell lines with RT-PCR. Based on these, it is concluded that somatic mutations of the RET proto-oncogene or the GDNF gene do not appear to play a major role in the pituitary tumorigenesis in examined tumors.

Factors Associated with Adenoma Detection Rate and Diagnosis of Polyps and Colorectal Cancer during Colonoscopy in France: Results of a Prospective, Nationwide Survey

PubMed Central

Barret, Maximilien; Boustiere, Christian; Canard, Jean-Marc; Arpurt, Jean-Pierre; Bernardini, David; Bulois, Philippe; Chaussade, Stanislas; Heresbach, Denis; Joly, Isabelle; Lapuelle, Jean; Laugier, René; Lesur, Gilles; Pienkowski, Patrice; Ponchon, Thierry; Pujol, Bertrand; Richard-Molard, Bruno; Robaszkiewicz, Michel; Systchenko, Rémi; Abbas, Fatima; Schott-Pethelaz, Anne-Marie; Cellier, Christophe

2013-01-01

Introduction Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. Methods An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. Results A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). Conclusions For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy. PMID:23874822

Protein and glycomic plasma markers for early detection of adenoma and colon cancer.

PubMed

Rho, Jung-Hyun; Ladd, Jon J; Li, Christopher I; Potter, John D; Zhang, Yuzheng; Shelley, David; Shibata, David; Coppola, Domenico; Yamada, Hiroyuki; Toyoda, Hidenori; Tada, Toshifumi; Kumada, Takashi; Brenner, Dean E; Hanash, Samir M; Lampe, Paul D

2018-03-01

To discover and confirm blood-based colon cancer early-detection markers. We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Expression of CD10 in tumor-associated fibroblast of cancerized or recurrent colorectal adenomas].

PubMed

Zheng, Jiangjiang; Zhu, Yin; Li, Changshui; Li, Yinya; Nie, Qianqian; Zhu, Ziling; Deng, Hong

2016-05-25

Objective: To investigate the expression of CD10 in tumor-associated fibroblasts (TAF) in colorectal adenomas and its relation to cancerization and recurrence of adenoma. Methods: Tissue samples of low-grade adenoma ( n =50), high-grade adenoma ( n =50) and colorectal adenocarcinoma ( n =50) were collected, and tissue samples at the distal margin of corresponding colorectal lesions were taken as controls. The expression of CD10 in the stromal TAFs, and the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry (Envision). The correlation of CD10 expression in stromal TAFs with the expressions of β-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed by Spearmen. One hundred samples of low-grade colorectal adenoma were collected, including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF CD10 were determined and compared among groups. Results: There was no TAF in normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma, high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%, respectively (all P <0.05). The expression of Ki-67 and β-catenin in low-grade adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all P <0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in colorectal adenocarcinoma and low-grade adenoma (all P >0.05). The expression of p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in low grade adenoma (all P <0.01). The expression of TAF CD10 was correlated with the expression of p53, Ki-67 and β-catenin-nucleus( r =0.264、0.307、0.320, all P <0.01),but not correlated with CyclinD1 and β-catenin-membrane ( r =0.012、-0.073, all P >0.05). The TAF CD10 level was significantly higher in low-grade adenoma with recurrence than that in those without recurrence ( P <0.05).The

Clinical evaluation of endoscopic trimodal imaging for the detection and differentiation of colonic polyps.

PubMed

van den Broek, Frank J C; Fockens, Paul; Van Eeden, Susanne; Kara, Mohammed A; Hardwick, James C H; Reitsma, Johannes B; Dekker, Evelien

2009-03-01

Endoscopic trimodal imaging (ETMI) incorporates high-resolution endoscopy (HRE) and autofluorescence imaging (AFI) for adenoma detection, and narrow-band imaging (NBI) for differentiation of adenomas from nonneoplastic polyps. The aim of this study was to compare AFI with HRE for adenoma detection and to assess the diagnostic accuracy of NBI for differentiation of polyps. This was a randomized trial of tandem colonoscopies. The study was performed at the Academic Medical Center in Amsterdam. One hundred patients underwent colonoscopy with ETMI. Each colonic segment was examined twice for polyps, once with HRE and once with AFI, in random order per patient. All detected polyps were assessed with NBI for pit pattern and with AFI for color, and subsequently removed. Histopathology served as the gold standard for diagnosis. The main outcome measures of this study were adenoma miss-rates of AFI and HRE, and diagnostic accuracy of NBI and AFI for differentiating adenomas from nonneoplastic polyps. Among 50 patients examined with AFI first, 32 adenomas were detected initially. Subsequent inspection with HRE identified 8 additional adenomas. Among 50 patients examined with HRE first, 35 adenomas were detected initially. Successive AFI yielded 14 additional adenomas. The adenoma miss-rates of AFI and HRE therefore were 20% and 29%, respectively (P = .351). The sensitivity, specificity, and overall accuracy of NBI for differentiation were 90%, 70%, and 79%, respectively; corresponding figures for AFI were 99%, 35%, and 63%, respectively. The overall adenoma miss-rate was 25%; AFI did not significantly reduce the adenoma miss-rate compared with HRE. Both NBI and AFI had a disappointing diagnostic accuracy for polyp differentiation, although AFI had a high sensitivity.

Hypopituitarism after stereotactic radiosurgery for pituitary adenomas.

PubMed

Xu, Zhiyuan; Lee Vance, Mary; Schlesinger, David; Sheehan, Jason P

2013-04-01

Studies of new-onset Gamma Knife stereotactic radiosurgery (SRS)-induced hypopituitarism in large cohort of pituitary adenoma patients with long-term follow-up are lacking. We investigated the outcomes of SRS for pituitary adenoma patients with regard to newly developed hypopituitarism. This was a retrospective review of patients treated with SRS at the University of Virginia between 1994 and 2006. A total of 262 patients with a pituitary adenoma treated with SRS were reviewed. Thorough endocrine assessment was performed immediately before SRS and in regular follow-ups. Assessment consisted of 24-hour urine free cortisol (patients with Cushing disease), serum adrenocorticotropic hormone, cortisol, follicle-stimulating hormone, luteinizing hormone, insulin-like growth factor-1, growth hormone, testosterone (men), prolactin, thyroid-stimulating hormone, and free T(4). Endocrine remission occurred in 144 of 199 patients with a functioning adenoma. Tumor control rate was 89%. Eighty patients experienced at least 1 axis of new-onset SRS-induced hypopituitarism. The new hypopituitarism rate was 30% based on endocrine follow-up ranging from 6 to 150 months; the actuarial rate of new pituitary hormone deficiency was 31.5% at 5 years after SRS. On univariate and multivariate analyses, variables regarding the increased risk of hypopituitarism included suprasellar extension and higher radiation dose to the tumor margin; there were no correlations among tumor volume, prior transsphenoidal adenomectomy, prior radiation therapy, and age at SRS. SRS provides an effective and safe treatment option for patients with a pituitary adenoma. Higher margin radiation dose to the adenoma and suprasellar extension were 2 independent predictors of SRS-induced hypopituitarism.

The association between cecal insertion time and colorectal neoplasm detection

PubMed Central

2013-01-01

Background Information on the impact of cecal insertion time on colorectal neoplasm detection is limited. Our objective was to determine the association between cecal insertion time and colorectal neoplasm detection rate in colonoscopy screening. Methods We performed a cross-sectional study of 12,679 consecutive subjects aged 40–79 years undergoing screening colonoscopy in routine health check-ups at the Center for Health Promotion of the Samsung Medical Center from December 2007 to June 2009. Fixed effects logistic regression conditioning on colonoscopist was used to eliminate confounding due to differences in technical ability and other characteristics across colonoscopists. Results The mean cecal insertion time was 5.9 (SD, 4.4 minutes). We identified 4,249 (33.5%) participants with colorectal neoplasms, of whom 1,956 had small single adenomas (<5 mm), 595 had medium single adenomas (5–9 mm), and 1,699 had multiple adenomas or advanced colorectal neoplasms. The overall rates of colorectal neoplasm detection by quartiles of cecal insertion time were 36.8%, 33.4%, 32.7%, and 31.0%, respectively (p trend <0.001).The odds for small single colorectal adenoma detection was 16% lower (adjusted OR 0.84; 95% CI 0.71 to 0.99) in the fourth compared to the first quartile of insertion time (p trend 0.005). Insertion time was not associated with the detection rate of single adenomas ≥5 mm, multiple adenomas or advanced colorectal neoplasms. Conclusion Shorter insertion times were associated with increased rates of detection of small colorectal adenomas <5 mm. Cecal insertion time may be clinically relevant as missed small colorectal adenomas may progress to more advanced lesions. PMID:23915303

International collaboration between Japan and Chile to improve detection rates in colorectal cancer screening.

PubMed

Okada, Takuya; Tanaka, Koji; Kawachi, Hiroshi; Ito, Takashi; Nishikage, Tetsuro; Odagaki, Tomoyuki; Zárate, Alejandro J; Kronberg, Udo; López-Köstner, Francisco; Karelovic, Stanko; Flores, Sergio; Estela, Ricardo; Tsubaki, Masahiro; Uetake, Hiroyuki; Eishi, Yoshinobu; Kawano, Tatsuyuki

2016-01-01

In Chile, mortality from colorectal cancer (CRC) has increased rapidly. To help address this issue, the Prevention Project for Neoplasia of the Colon and Rectum (PRENEC) program was initiated in 2012 with intensive support from Tokyo Medical and Dental University (TMDU) in Tokyo, Japan, as part of an international collaboration. From June 2012 to July 2014, a total of 10,575 asymptomatic participants were enrolled in PRENEC. Participants with positive immunochemical fecal occult blood test (iFOBT) results or a family history of CRC underwent colonoscopy. The colonoscopy results from a similar, previous project in Chile (PREVICOLON) were compared with those from PRENEC. Furthermore, the initial colonoscopies of 1562 participants in PRENEC were analyzed according to whether the colonoscopists were from TMDU or Chile. The complete colonoscopy, adenoma detection, and cancer detection rates were 88.0%, 26.7%, and 1.1%, respectively, in PREVICOLON, while the corresponding values were 94.4%, 41.8%, and 6.0%, respectively, in PRENEC. In PRENEC, 107 cases of CRC were detected, amounting for 1.0% of all participants. Considering initial colonoscopies in PRENEC, the complete colonoscopy, adenoma detection, and cancer detection rates were 97.4%, 45.3%, and 9.3%, respectively, for physicians at TMDU and 93.3%, 41.5%, and 5.1%, respectively for Chilean physicians. The detection rates of intramucosal cancer were 7.3% and 3.7%, respectively, for TMDU and Chilean physicians. Quality indicators of colonoscopy substantially improved from PREVICOLON to PRENEC. The assessments made by Chilean physicians alone were improved in PRENEC, but remained better in the TMDU group. Moreover, physicians from TMDU detected more CRCs than Chilean physicians, especially at earlier stages. © 2015 American Cancer Society.

Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia.

PubMed

Bartley, Angela N; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J; Buckmeier, Julie A; Corley, Lynda; Phipps, Ron A; Gallick, Gary; Lance, Peter; Thompson, Patricia A; Hamilton, Stanley R

2013-11-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma ("recurrence"), has not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1-labeling indices (ALI) were similar across patient characteristics and in advanced and nonadvanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (P = 0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (P = 0.03). A best-fit algorithm-based cutoff point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem cell target for chemoprevention. ©2013 AACR

Colorectal adenoma stem-like cell populations: Associations with adenoma characteristics and metachronous colorectal neoplasia

PubMed Central

Bartley, Angela N.; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J.; Buckmeier, Julie A.; Corley, Lynda; Phipps, Ron A.; Gallick, Gary; Lance, Peter; Thompson, Patricia A.; Hamilton, Stanley R.

2014-01-01

Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma (“recurrence”), have not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1 labeling indices (ALIs) were similar across patient characteristics and in advanced and non-advanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (p=0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma-free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (p=0.03). A best-fit algorithm-based cut-point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem-cell target for chemoprevention. PMID:24008128

Usefulness of composite methionine-positron emission tomography/3.0-tesla magnetic resonance imaging to detect the localization and extent of early-stage Cushing adenoma.

PubMed

Ikeda, Hidetoshi; Abe, Takehiko; Watanabe, Kazuo

2010-04-01

Fifty to eighty percent of Cushing disease is diagnosed by typical endocrine responses. Recently, the number of diagnoses of Cushing disease without typical Cushing syndrome has been increasing; therefore, improving ways to determine the localization of the adenoma and making an early diagnosis is important. This study was undertaken to determine the present diagnostic accuracy for Cushing microadenoma and to compare the differences in diagnostic accuracy between MR imaging and PET/MR imaging. During the past 3 years the authors analyzed the diagnostic accuracy in a series of 35 patients with Cushing adenoma that was verified by surgical pituitary exploration. All 35 cases of Cushing disease, including 20 cases of "overt" and 15 cases of "preclinical" Cushing disease, were studied. Superconductive MR images (1.5 or 3.0 T) and composite images from FDG-PET or methionine (MET)-PET and 3.0-T MR imaging were compared with the localization of adenomas verified by surgery. The diagnostic accuracy of superconductive MR imaging for detecting the localization of Cushing microadenoma was only 40%. The causes of unsatisfactory results for superconductive MR imaging were false-negative results (10 cases), false-positive results (6 cases), and instances of double pituitary adenomas (3 cases). In contrast, the accuracy of microadenoma localization using MET-PET/3.0-T MR imaging was 100% and that of FDG-PET/3.0-T MR imaging was 73%. Moreover, the adenoma location was better delineated on MET-PET/MR images than on FDG-PET/MR images. There was no significant difference in maximum standard uptake value of adenomas evaluated by MET-PET between preclinical Cushing disease and overt Cushing disease. Composite MET-PET/3.0-T MR imaging is useful for the improvement of the delineation of Cushing microadenoma and offers high-quality detectability for early-stage Cushing adenoma.

Genomic Landscape of Colorectal Mucosa and Adenomas in Familial Adenomatous Polyposis

PubMed Central

Borras, Ester; San Lucas, F. Anthony; Chang, Kyle; Zhou, Ruoji; Masand, Gita; Fowler, Jerry; Mork, Maureen E.; You, Y. Nancy; Taggart, Melissa W.; McAllister, Florencia; Jones, David A.; Davies, Gareth E.; Edelmann, Winfried; Ehli, Erik A.; Lynch, Patrick M.; Hawk, Ernest T.; Capella, Gabriel; Scheet, Paul; Vilar, Eduardo

2016-01-01

Purpose The molecular basis of the adenoma to carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. Experimental Design We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Results Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer-driver genes (APC, KRAS, FBXW7, TCF7L2) and allelic imbalances in chromosomes 5, 7 and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. Conclusions The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis. PMID:27221540

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

Vegetarianism as a protective factor for colorectal adenoma and advanced adenoma in Asians.

PubMed

Lee, Chang Geun; Hahn, Suk Jae; Song, Min Keun; Lee, Jun Kyu; Kim, Jae Hak; Lim, Yun Jeong; Koh, Moon-Soo; Lee, Jin Ho; Kang, Hyoun Woo

2014-05-01

Although epidemiologic and animal studies suggest a vegetarian diet protects against the development of colorectal cancer, the relationship between vegetarian diet and incidence of colorectal adenoma is not yet conclusive, especially for Asians. The purpose of this study was to examine the protective effect of a vegetarian diet against colorectal adenoma and advanced adenoma. This cross-sectional study compared the prevalence of colorectal adenoma among Buddhist priests, who are obligatory vegetarians, with that among age and sex-matched controls. All the subjects underwent health checkups in a health-promotion center in Korea. Colorectal adenoma and advanced adenoma were both more prevalent in the general population group than in the Buddhist priest group (25.2 vs. 17.9 %, 6.7 vs. 2.0 %). However, the prevalence of metabolic syndrome, high body mass index, and waist circumference were higher in the Buddhist priest group. According to univariate analysis, non-vegetarian diet (general population) significantly increased the prevalence of colorectal adenoma and advanced adenoma compared with a vegetarian diet (Buddhist priests) (OR 1.54, 95 % CI 1.08-2.21, P = 0.018; OR 3.60, 95 % CI 1.53-8.48, P = 0.003). In a conditional regression analysis model, non-vegetarian diet was also a significant risk factor for colorectal adenoma and advanced adenoma (OR 1.52, 95 % CI 0.75-2.07, P = 0.043; OR 2.94, CI 0.97-7.18, P = 0.036). Vegetarianism may be effective in preventing both colorectal adenoma and advanced adenoma in Asians.

Nonbleeding adenomas: Evidence of systematic false-negative fecal immunochemical test results and their implications for screening effectiveness-A modeling study.

PubMed

van der Meulen, Miriam P; Lansdorp-Vogelaar, Iris; van Heijningen, Else-Mariëtte B; Kuipers, Ernst J; van Ballegooijen, Marjolein

2016-06-01

If some adenomas do not bleed over several years, they will cause systematic false-negative fecal immunochemical test (FIT) results. The long-term effectiveness of FIT screening has been estimated without accounting for such systematic false-negativity. There are now data with which to evaluate this issue. The authors developed one microsimulation model (MISCAN [MIcrosimulation SCreening ANalysis]-Colon) without systematic false-negative FIT results and one model that allowed a percentage of adenomas to be systematically missed in successive FIT screening rounds. Both variants were adjusted to reproduce the first-round findings of the Dutch CORERO FIT screening trial. The authors then compared simulated detection rates in the second screening round with those observed, and adjusted the simulated percentage of systematically missed adenomas to those data. Finally, the authors calculated the impact of systematic false-negative FIT results on the effectiveness of repeated FIT screening. The model without systematic false-negativity simulated higher detection rates in the second screening round than observed. These observed rates could be reproduced when assuming that FIT systematically missed 26% of advanced and 73% of nonadvanced adenomas. To reduce the false-positive rate in the second round to the observed level, the authors also had to assume that 30% of false-positive findings were systematically false-positive. Systematic false-negative FIT testing limits the long-term reduction of biennial FIT screening in the incidence of colorectal cancer (35.6% vs 40.9%) and its mortality (55.2% vs 59.0%) in participants. The results of the current study provide convincing evidence based on the combination of real-life and modeling data that a percentage of adenomas are systematically missed by repeat FIT screening. This impairs the efficacy of FIT screening. Cancer 2016;122:1680-8. © 2016 American Cancer Society. © 2016 American Cancer Society.

Adenoma Prevalence and Distribution Among US Latino Subgroups Undergoing Screening Colonoscopy.

PubMed

Chablani, Sumedha V; Jandorf, Lina; DuHamel, Katherine; Lee, Kristen K; Sriphanlop, Pathu; Villagra, Cristina; Itzkowitz, Steven H

2017-06-01

Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.

Bowel cancer screening is safe, detects earlier stage cancer and adenomas in 50% of cases: experience of the prevalent round of screening from two first wave centres in the North East of England.

PubMed

Rajasekhar, P T; Clifford, G M; Lee, T J W; Rutter, M D; Waddup, G; Ritchie, M; Nylander, D; Painter, J; Singh, J; Ward, I; Dempsey, N; Bowes, J; Handley, G; Henry, J; Rees, C J

2012-01-01

The NHS Bowel Cancer Screening Programme (BCSP) began roll-out in 2006 aiming to reduce cancer mortality through detection at an earlier stage. We report results from the prevalent round of screening at two first wave centres and compare with the UK pilot study. This is a service evaluation study. Data were collected prospectively for all individuals undergoing faecal occult blood testing (FOBt) and colonoscopy including: uptake and outcomes of FOBt, colonoscopic performance, findings, histological data and complications. Continuous data were compared using a two-tailed test of two proportions. The South of Tyne and Tees Bowel Cancer Screening centres. Participants of the BCSP. 1) Colonoscopy Quality Assurance and 2) Cancer stage shift. 195,772 individuals were invited to participate. Uptake was 54% and FOBt positivity 1.7%. 1524 underwent colonoscopy with caecal intubation in 1485 (97%). 180 (12%) cancers were detected. Dukes stages were: 76 (42%) A; 47 (26%) B; 47 (26%) C; 8 (4%) D and 2 (1%) unknown. This demonstrates a significantly earlier stage at diagnosis compared with data from 2867 non-screening detected cancers (p<0.001). Adenomas were detected in 758 (50%). One perforation occurred (0.07%) and two intermediate bleeds requiring transfusion only (0.12%). Both caecal intubation and adenoma detection were significantly higher than in the UK pilot study (p<0.001). The prevalent round of screening demonstrates a high adenoma and cancer detection rate and significantly earlier stage at diagnosis. Complications were few providing reassurance regarding safety. Efforts are required to improve uptake.

Bowel cancer screening is safe, detects earlier stage cancer and adenomas in 50% of cases: experience of the prevalent round of screening from two first wave centres in the North East of England

PubMed Central

Rajasekhar, P T; Clifford, G M; Lee, T J W; Rutter, M D; Waddup, G; Ritchie, M; Nylander, D; Painter, J; Singh, J; Ward, I; Dempsey, N; Bowes, J; Handley, G; Henry, J; Rees, C J

2012-01-01

Objective The NHS Bowel Cancer Screening Programme (BCSP) began roll-out in 2006 aiming to reduce cancer mortality through detection at an earlier stage. We report results from the prevalent round of screening at two first wave centres and compare with the UK pilot study. Design This is a service evaluation study. Data were collected prospectively for all individuals undergoing faecal occult blood testing (FOBt) and colonoscopy including: uptake and outcomes of FOBt, colonoscopic performance, findings, histological data and complications. Continuous data were compared using a two-tailed test of two proportions. Setting The South of Tyne and Tees Bowel Cancer Screening centres. Patients Participants of the BCSP. Main Outcome Measures 1) Colonoscopy Quality Assurance and 2) Cancer stage shift. Results 195,772 individuals were invited to participate. Uptake was 54% and FOBt positivity 1.7%. 1524 underwent colonoscopy with caecal intubation in 1485 (97%). 180 (12%) cancers were detected. Dukes stages were: 76 (42%) A; 47 (26%) B; 47 (26%) C; 8 (4%) D and 2 (1%) unknown. This demonstrates a significantly earlier stage at diagnosis compared with data from 2867 non-screening detected cancers (p<0.001). Adenomas were detected in 758 (50%). One perforation occurred (0.07%) and two intermediate bleeds requiring transfusion only (0.12%). Both caecal intubation and adenoma detection were significantly higher than in the UK pilot study (p<0.001). Conclusions The prevalent round of screening demonstrates a high adenoma and cancer detection rate and significantly earlier stage at diagnosis. Complications were few providing reassurance regarding safety. Efforts are required to improve uptake. PMID:28839624

Serrated and adenomatous polyp detection increases with longer withdrawal time: results from the New Hampshire Colonoscopy Registry.

PubMed

Butterly, Lynn; Robinson, Christina M; Anderson, Joseph C; Weiss, Julia E; Goodrich, Martha; Onega, Tracy L; Amos, Christopher I; Beach, Michael L

2014-03-01

Detection and removal of adenomas and clinically significant serrated polyps (CSSPs) is critical to the effectiveness of colonoscopy in preventing colorectal cancer. Although longer withdrawal time has been found to increase polyp detection, this association and the use of withdrawal time as a quality indicator remains controversial. Few studies have reported on withdrawal time and serrated polyp detection. Using data from the New Hampshire Colonoscopy Registry, we examined how an endoscopist's withdrawal time in normal colonoscopies affects adenoma and serrated polyp detection. We analyzed 7,996 colonoscopies performed in 7,972 patients between 2009 and 2011 by 42 endoscopists at 14 hospitals, ambulatory surgery centers, and community practices. CSSPs were defined as sessile serrated polyps and hyperplastic polyps proximal to the sigmoid. Adenoma and CSSP detection rates were calculated based on median endoscopist withdrawal time in normal exams. Regression models were used to estimate the association of increased normal withdrawal time and polyp, adenoma, and CSSP detection. Polyp and adenoma detection rates were highest among endoscopists with 9 min median normal withdrawal time, and detection of CSSPs reached its highest levels at 8-9 min. Incident rate ratios for adenoma and CSSP detection increased with each minute of normal withdrawal time above 6 min, with maximum benefit at 9 min for adenomas (1.50, 95% confidence interval (CI) (1.21, 1.85)) and CSSPs (1.77, 95% CI (1.15, 2.72)). When modeling was used to set the minimum withdrawal time at 9 min, we predicted that adenomas and CSSPs would be detected in 302 (3.8%) and 191 (2.4%) more patients. The increase in detection was most striking for the CSSPs, with nearly a 30% relative increase. A withdrawal time of 9 min resulted in a statistically significant increase in adenoma and serrated polyp detection. Colonoscopy quality may improve with a median normal withdrawal time benchmark of 9 min.

OCCURRENCE OF COLORECTAL ADENOMAS IN YOUNGER ADULTS: AN EPIDEMIOLOGIC NECROPSY STUDY

PubMed Central

Pendergrass, Cheryl J.; Edelstein, Daniel L.; Hylind, Linda M.; Phillips, Blaine T.; Iacobuzio-Donahue, Christine; Romans, Katharine; Griffin, Constance A.; Cruz-Correa, Marcia; Tersmette, Anne C.; Offerhaus, G. Johan A.; Giardiello, Francis M.

2009-01-01

Background and Aims The colorectal adenoma is the precursor lesion in virtually all colorectal cancers. Occurrence of colorectal adenomas has been studied in older adults but analysis in younger adults is lacking. Methods The prevalence by age, sex, race, and location, and the number of colorectal adenomas detected was investigated using epidemiologic necropsy in 3558 persons aged 20–89 autopsied from 1985 to 2004 at the Johns Hopkins Hospital. Results were standardized to the general population. Younger adults 20–49 years old were compared to older adults 50 to 89 years old. Results The prevalence of colorectal adenomas in younger adults increased from 1.72% to 3.59% from the 3rd to 5th decade of life and then sharply increased after age 50. In younger adults, adenomas were more prevalent in men than women (RR= 1.09, CI 1.07–1.11) and whites than blacks (RR=1.28, CI 1.26–1.31). Overall, both younger and older adults had predominately left-sided adenomas, but blacks in both age groups had more right-sided adenomas. Occurrence of two or more adenomas in younger adults and five or more in older adults was greater than 2 standard deviations from the mean. Conclusions Colorectal adenomas infrequently occur in younger adults and are more prevalent in the left colon. Irrespective of age, blacks have more right-sided adenomas suggesting need for screening the entire colorectum. Two or more adenomas in younger adults and five or more in older adults represents polyp burden outside the normal expectation. PMID:18558514

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.

High resolution colonoscopy in a bowel cancer screening program improves polyp detection

PubMed Central

Banks, Matthew R; Haidry, Rehan; Butt, M Adil; Whitley, Lisa; Stein, Judith; Langmead, Louise; Bloom, Stuart L; O’Bichere, Austin; McCartney, Sara; Basherdas, Kalpesh; Rodriguez-Justo, Manuel; Lovat, Laurence B

2011-01-01

AIM: To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS: Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS:There were no differences in procedure duration (χ2 P = 0.98), caecal intubation rates (χ2 P = 0.67), or depth of sedation (χ2 P = 0.64). Mild discomfort was more common in the Pentax group (χ2 P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (χ2 test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION: Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs. PMID:22090787

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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma.

PubMed

Moy, Andrea P; Arora, Kshitij; Deshpande, Vikram

2016-09-01

Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH. © 2016 John Wiley & Sons Ltd.

The effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma.

PubMed

Han, Min Seok; Lee, Hyun Jung; Park, Soo Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-08-01

Existing studies suggest that metformin lowers the risk and mortality of colorectal cancer. However, the effect of metformin on the suppression and prevention of colorectal adenomas is not clear. The aim of this study was to evaluate the effect of metformin on the recurrence of colorectal adenoma in diabetic patients with previous colorectal adenoma. Among 423 diabetic patients who underwent surveillance colonoscopy after resection of colorectal adenoma between 2005 and 2011, 257 patients were retrospectively reviewed. The patients were divided into two groups: one group comprising 106 patients who took metformin and another group comprising 151 patients who did not take metformin. The clinical characteristics, colorectal adenoma recurrence, and valuable factors for adenoma recurrence were analyzed. At surveillance colonoscopy after colonoscopic polypectomy for adenoma, 38 patients (35.8%) exhibited colorectal adenoma among 106 patients who took metformin, compared with 85 patients (56.3%) with colorectal adenoma among 151 patients who did not take metformin (odds ratio 0.434, 95% confidence interval 0.260-0.723, P = 0.001). Multivariate Cox analysis showed that metformin was associated with decreased recurrence of colorectal adenoma (hazard ratio 0.572, 95% confidence interval 0.385-0.852, P = 0.006) in diabetic patients with previous colorectal adenoma. The cumulative probability of colorectal adenoma recurrence was significantly lower in the metformin group than in the non-metformin group (P = 0.001). Metformin use in diabetic patients with previous colorectal adenoma is associated with a lower risk of colorectal adenoma recurrence.

Associations Between Markers of Colorectal Cancer Stem Cells and Adenomas Among Ethnic Groups

PubMed Central

Leavell, Bonita J.; Van Buren, Eric; Antaki, Fadi; Axelrod, Bradley N.; Rambus, Mary Ann; Majumdar, Adhip P. N.

2013-01-01

Background and Purposes Most colorectal tumors develop from adenomatous polyps, which are detected by colonoscopy. African Americans (AAs) have higher incidence of colorectal cancer (CRC) and greater mortality from this disease than Caucasian Americans (CAs). We investigated whether differences in predisposition to CRC and its surrogate (colonic adenomas) between these ethnic groups were related to numbers of cancer stem or stem-like cells (CSCs) in colonocytes. Methods We analyzed colonic effluent from 11 AA and 14 CA patients who underwent scheduled colonoscopy examinations at the John D. Dingell Veterans Affairs Medical Center. We determined proportions of cells that expressed the CSC markers CD44 and CD166 by flow cytometry. Results The proportion of colonocytes that were CD44+CD166– in effluent from patients with adenomas was significantly greater than from patients without adenomas (P = 0.01); the proportion of CD44+CD166+ colonocytes was also greater (P = 0.07). Effluent from AAs with adenomas had 60 % more CD44+166– colonocytes than from CAs with adenomas. Using cutoff values of 8 % for AAs and 3 % for CAs, the proportion of CD44+166– colonocytes that had positive predictive value for detection of adenomas was 100 % for AAs and CAs, determined by receiver operator characteristic curve analysis. Conclusion The proportion of CD44+166– colonocytes in colonic effluent can be used to identify patients with adenoma. AAs with adenomas have a higher proportion of CD44+166– colonocytes than CA. The increased proportion of CSCs in colonic tissue from AA might be associated with the increased incidence of CRC in this population. PMID:22562538

Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.

PubMed

Kikuchi, Ryogo; Toda, Masahiro; Tomita, Toshiki; Ogawa, Kaoru; Yoshida, Kazunari

2017-01-01

This study aimed to assess the efficacy of endoscopic endonasal surgery, conducted by a team of neurosurgeons and otolaryngologists. We studied 40 patients who were undergoing surgery for primary non-functional pituitary adenomas with Knosp grades 1 to 3, at Keio University Hospital between 2005 and 2012. We compared the endoscopic endonasal transsphenoidal approach (team-eTSS; T-eTSS), with a microscopic transsphenoidal approach (mTSS). Analyses were conducted for differences between the two groups in tumor resection rates, operating durations, and complications from the non-functional pituitary adenomas. We also compared the heminostril and binostril approaches for T-eTSS. Tumor resection rates were higher when the surgeries were conducted by T-eTSS than mTSS. In particular, when the maximum tumor diameter was more than 25 mm, resection rates were significantly higher for T-eTSS than for mTSS. There were no unexpected complications in either group. There was no significant difference in resection rates between the heminostril and binostril approaches when T-eTSS was performed. T-eTSS is an efficacious surgical option for non-functional pituitary adenomas, particularly when the adenoma is of large size. Benefits of the heminostril approach are evident.

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis

PubMed Central

Niccum, David E.; Billings, Joanne L.; Dunitz, Jordan M.; Khoruts, Alexander

2018-01-01

Background Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. Methods We analyzed prospectively collected results of colonoscopies initiated at age 40 years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30–39 years performed during the same time period at the Center. Results The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. Conclusions Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population. PMID:26851188

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial.

PubMed

Dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-07-01

The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

Functioning and nonfunctioning thyroid adenomas involve different molecular pathogenetic mechanisms.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Ceccarini, G; Perri, A; Cavaliere, R; Mazzi, B; Naccarato, A G; Viacava, P; Miccoli, P; Pinchera, A; Chiovato, L

1999-11-01

The molecular biology of follicular cell growth in thyroid nodules is still poorly understood. Because gain-of-function (activating) mutations of the thyroid-stimulating hormone receptor (TShR) and/or Gs alpha genes may confer TSh-independent growth advantage to neoplastic thyroid cells, we searched for somatic mutations of these genes in a series of hyperfunctioning and nonfunctioning follicular thyroid adenomas specifically selected for their homogeneous gross anatomy (single nodule in an otherwise normal thyroid gland). TShR gene mutations were identified by direct sequencing of exons 9 and 10 of the TShR gene in genomic DNA obtained from surgical specimens. Codons 201 and 227 of the Gs alpha gene were also analyzed. At histology, all hyperfunctioning nodules and 13 of 15 nonfunctioning nodules were diagnosed as follicular adenomas. Two nonfunctioning thyroid nodules, although showing a prevalent microfollicular pattern of growth, had histological features indicating malignant transformation (a minimally invasive follicular carcinoma and a focal papillary carcinoma). Activating mutations of the TShR gene were found in 12 of 15 hyperfunctioning follicular thyroid adenomas. In one hyperfunctioning adenoma, which was negative for TShR mutations, a mutation in codon 227 of the Gs alpha gene was identified. At variance with hyperfunctioning thyroid adenomas, no mutation of the TShR or Gs alpha genes was detected in nonfunctioning thyroid nodules. In conclusion, our findings clearly define a different molecular pathogenetic mechanism in hyperfunctioning and nonfunctioning follicular thyroid adenomas. Activation of the cAMP cascade, which leads to proliferation but maintains differentiation of follicular thyroid cells, typically occurs in hyperfunctioning thyroid adenomas. Oncogenes other than the TShR and Gs alpha genes are probably involved in nonfunctioning follicular adenomas.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis.

PubMed

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-03-01

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

PubMed

Sáez, C; Japón, M A; Ramos-Morales, F; Romero, F; Segura, D I; Tortolero, M; Pintor-Toro, J A

1999-09-23

The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Weiss, Julia E; Robinson, Christina M

2017-06-01

Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n = 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks. By using colonoscopies in adults aged ≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%, ≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5 mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively. A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P = .69) and ADR/PSDR (P = .79) and a strong positive correlation (P = .82) for CSSDR/PSDR (P < .0001 for all) was observed. For ADR ≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%). Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR = 7% and PSDR = 11%) that may guide

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial

PubMed Central

dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-01-01

OBJECTIVES: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR. PMID:28792997

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas.

PubMed

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-05-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance.

Immunohistochemical detection of Ym1/Ym2 chitinase-like lectins associated with hyalinosis and polypoid adenomas of the transitional epithelium in a mouse with acute myeloid leukemia.

PubMed

Marchesi, F; Minucci, S; Pelicci, P G; Gobbi, A; Scanziani, E

2006-09-01

An 8-month-old PML/RARalpha knock-in female mouse developed a promyelocytic-like myeloid leukemia with an expected latency. At necropsy, besides the typical findings associated with myeloid leukemia, a severe unilateral hydronephrosis was observed. By histopathologic examination, 2 polypoid adenomas arising from the transitional epithelium of the renal pelvis and ureter were detected. The epithelial cells of the polypoid adenomas showed accumulation of hyaline eosinophilic material within the cytoplasm. Large amounts of extracellular eosinophilic crystals were also associated with the transitional cell adenomas. Immunohistochemical analysis revealed that the eosinophilic intracytoplasmic material and the extracellular eosinophilic crystals were composed of Ym proteins. A unilateral hyaline droplet tubular nephropathy was associated with the myeloid leukemia. Expression of Ym proteins characterized both the neoplastic myeloid infiltrates and the tubular hyaline droplets. In the present PML/RARalpha knock-in female mouse, the accumulation of Ym proteins associated with the myeloid leukemia and with the polypoid adenomas of the transitional epithelium underlies 2 distinct pathogenetic mechanisms.

The prevalence of colorectal adenomas in asymptomatic Korean men and women.

PubMed

Yang, Moon Hee; Rampal, Sanjay; Sung, Jidong; Choi, Yoon-Ho; Son, Hee Jung; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee

2014-03-01

Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women. In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed. ©2014 AACR.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis

PubMed Central

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-01-01

Background Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population. PMID:29511562

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

PubMed

Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

2018-04-01

 Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

CpG island methylator phenotype and its association with malignancy in sporadic duodenal adenomas

PubMed Central

Sun, Lifeng; Guzzetta, Angela A; Fu, Tao; Chen, Jinming; Jeschke, Jana; Kwak, Ruby; Vatapalli, Rajita; Baylin, Stephen B; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Ahuja, Nita

2014-01-01

CpG island methylator phenotype (CIMP) has been found in multiple precancerous and cancerous lesions, including colorectal adenomas, colorectal cancers, and duodenal adenocarcinomas. There are no reports in the literature of a relationship between CIMP status and clinicopathologic features of sporadic duodenal adenomas. This study sought to elucidate the role of methylation in duodenal adenomas and correlate it with KRAS and BRAF mutations. CIMP+ (with more than 2 markers methylated) was seen in 33.3% of duodenal adenomas; 61% of these CIMP+ adenomas were CIMP-high (with more than 3 markers methylated). Furthermore, CIMP+ status significantly correlated with older age of patients, larger size and villous type of tumor, coexistent dysplasia and periampullary location. MLH1 methylation was seen in 11.1% of duodenal adenomas and was significantly associated with CIMP+ tumors, while p16 methylation was an infrequent event. KRAS mutations were frequent and seen in 26.3% of adenomas; however, no BRAF mutations were detected. Furthermore, CIMP-high status was associated with larger size and villous type of tumor and race (non-white). These results suggest that CIMP+ duodenal adenomas may have a higher risk for developing malignancy and may require more aggressive management and surveillance. PMID:24518818

Transplantable, STH-producing and diabetogenic pituitary adenoma of the BD IX-strain of rats.

PubMed

Stekar, J

1976-03-19

A chromophobic pituitary adenoma induced on BD IX-rats has been grafted on animals of the same strain. The transplanted tumour takes in 90-100%; it grows at a slow rate (in 7 months after grafting a weight of 7-20 g is attained). Tumour-bearing animals display gigantism and hypertrophy of adrenals; moreover, in 33% of cases, diabetes is observed. With non-diabetic animals, splenomegaly and marked leukocytosis are observed; immature white and red cells are present in the peripheral blood. Spontaneous regression of the tumour never occurs. After surgical removal, tumour regrowth and the formation of metastases are observed. Diabetes is characterised by pronounced hyperglycaemia, glucosuria, polyphagia and polydipsia. Histochemically, insulin cannot be detected in pancreas. Splenomegaly is never observed in diabetic animals. Transplanted adenoma frequently tends to stop growing. No recurrence is observable after extirpation. Spontaneous regression of the tumour sometimes occurs. Gigantism, hypertrophy of adrenals and diabetes are considered as consequences of growth hormone- and ACTH-secretion of the transplanted adenoma. At present the tumour is running in the 8th passage. It did not change its characteristics over a period of 5 years.

Systematic review with meta-analysis: the incidence of advanced neoplasia after polypectomy in patients with and without low-risk adenomas.

PubMed

Hassan, C; Gimeno-García, A; Kalager, M; Spada, C; Zullo, A; Costamagna, G; Senore, C; Rex, D K; Quintero, E

2014-05-01

Patients with one to two tubular adenomas <1 cm in size without high-grade dysplasia (low-risk group) are considered at low risk for colorectal cancer. However, it is uncertain whether they have the same risk of subsequent advanced neoplasia as those with no neoplasia at baseline colonoscopy. To compare incidence of metachronous advanced neoplasia between patients in the low-risk adenoma group and those without neoplasia at index colonoscopy. Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1992-2013. Studies comparing the incidence of post-polypectomy advanced neoplasia (adenomas ≥10 mm/high-grade dysplasia/villous or cancer) between the low-risk group and patients without colorectal neoplasia at the first colonoscopy were included. Detection rates for advanced neoplasia at endoscopic surveillance were extracted. Study quality was ascertained according to Newcastle-Ottawa Scale. Forest plot was produced based on random-effect models. Inter-study heterogeneity was assessed using the I(2) statistic. Seven studies provided data on 11 387 patients. Mean surveillance periods ranged between 2 and 5 years. Altogether, 267 patients with post-polypectomy advanced neoplasia were detected in the two groups. The incidence of advanced neoplasia was 1.6% (119/7308) in those without neoplasia and 3.6% (148/4079) in those with low-risk adenoma, respectively, corresponding to a relative risk of 1.8 (95% CI: 1.3-2.6). Inter-study heterogeneity was only moderate (I(2) : 37%). No publication bias was present. Patients with low-risk adenomas at baseline had a higher risk of metachronous advanced neoplasia than the group with no adenomas at baseline, though the absolute risk was low in both groups. © 2014 John Wiley & Sons Ltd.

Secondary hypertension due to concomitant aldosterone-producing adenoma and parathyroid adenoma.

PubMed

Chau, Katrina; Holmes, Daniel; Melck, Adrienne; Chan-Yan, Clifford

2015-02-01

There is a growing body of evidence supporting a bidirectional relationship between parathyroid hormone (PTH) and aldosterone (Aldo). We report a case of secondary hypertension due to concomitant Aldo-producing adenoma (APA) and parathyroid adenoma (PA) requiring both unilateral adrenalectomy and parathyroidectomy. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endoscopic laser treatment for rectosigmoid villous adenoma: factors effecting the results

NASA Astrophysics Data System (ADS)

Brunetaud, Jean Marc; Maunoury, Vincent; Cochelard, Dominique; Boniface, Brigitte

1994-12-01

This present work reports the long term results after endoscopic laser treatment in 474 patients with benign rectosigmoid villous adenomas revealed by biopsy. Two types of wavelength were used: The 1.06 micrometers infrared light from the Nd:YAG laser and the green light from the argon laser or the Nd:YAG frequency doubled laser. In some patients, both wavelengths were used. Treatment was completed in 415 patients. Total tumor destruction was obtained in 92.8% of them, a carcinoma was detected in 6.5% on biopsy specimens obtained during laser treatment, and benign villous tissue persisted in 0.7%. During the average 30 mo. follow up period of the patients with total tumor destruction, 18% had a tumor recurrence. Treatment was well tolerated with a 1.8% complication rate (one perforation, one hemorrhage, and 7 stenosis requiring dilatation). Because treatment is long and difficult and cancer rate is high, endoscopic laser should be limited in patients with a circumferential villous adenoma to nonsurgical candidates. The risk of complication after surgery (some being fatal) has to be balanced against the risk of undetected carcinoma in the other patients and the indication for endoscopic laser treatment should be discussed case by case.

Transsphenoidal Surgery for Mixed Pituitary Gangliocytoma-Adenomas.

PubMed

Shepard, Matthew J; Elzoghby, Mohamed A; Ghanim, Daffer; Lopes, M Beatriz S; Jane, John A

2017-12-01

Most sellar gangliocytomas are discovered with a concurrent pituitary adenoma, also known as a mixed gangliocytoma-adenoma (MGA). MGAs are rare, with fewer than 100 cases reported in the literature to date and only 1 previously documented surgical series. Because MGAs are radiologically indistinguishable from pituitary adenomas, they are often diagnosed after surgery. Combined with the paucity of clinical outcome data for these tumors, this makes their diagnosis and management challenging. Here we describe the clinical presentation and outcomes of 10 individuals who were diagnosed with a MGA at a single institution. This retrospective case series study included patients diagnosed with a combined sellar MGA between 1993 and 2016. This series comprised 10 patients, mean age of 44 years (range, 28-63 years) diagnosed with an MGA. The mean tumor size was 1.6 cm (range, 0.4-2.4 cm). Five patients presented with acromegaly, and 1 patient had recurrent Cushing disease. Transsphenoidal surgery was performed in all cases, and gross total resection was achieved in 7 patients (70%). Histologically, 9 of the 10 MGAs were identified as mixed somatotroph adenoma-gangliocytomas. The median duration of follow-up was 74 months (range, 2-180 months). Following adjuvant treatment (n = 3), all patients with acromegaly (n = 4) achieved biochemical remission, and no patient experienced recurrence of the pituitary tumor with a median radiographic follow-up of 48 months. MGAs are often associated with a hypersecretory adenoma. Transsphenoidal surgery is well tolerated by most patients, and when performed in combination with adjuvant therapy, a low rate of recurrence and reversal of preoperative endocrinopathy can be expected. Copyright © 2017 Elsevier Inc. All rights reserved.

Meat, meat cooking methods and preservation, and risk for colorectal adenoma.

PubMed

Sinha, Rashmi; Peters, Ulrike; Cross, Amanda J; Kulldorff, Martin; Weissfeld, Joel L; Pinsky, Paul F; Rothman, Nathaniel; Hayes, Richard B

2005-09-01

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.

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

PubMed Central

PU, JIUJUN; WANG, ZHIMING; ZHOU, HUI; ZHONG, AILING; JIN, KAI; RUAN, LUNLIANG; YANG, GANG

2016-01-01

Only a few cases of double or multiple pituitary adenomas have previously been reported in the literature; however, isolated double adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas are even more rare. The present study reports a rare case of a 50-year-old female patient who presented with typical clinical features of Cushing's disease and was diagnosed with isolated double ACTH-secreting pituitary adenomas. Endocrinological examination revealed an ACTH-producing pituitary adenoma, and preoperative magnetic resonance imaging (MRI) demonstrated a microadenoma with a lower intensity on the right side of the pituitary gland. The patient underwent endoscopic endonasal transsphenoidal surgery, which revealed another pituitary tumor in the left side of the pituitary gland. The two, clearly separated, pituitary adenomas identified in the same gland were completely resected. Immunohistochemistry and pathology revealed that the clearly separated double pituitary adenomas were positive for ACTH, thyroid-stimulating, growth and prolactin hormones. Postoperatively, the levels of ACTH and cortisol hormone decreased rapidly. The case reported in the present study is considerably rare, due to the presence of a second pituitary adenoma in the same gland, which was not detected by preoperative MRI scan, but was noticed during surgery. Intraoperative evaluation may be important in the identification of double or multiple pituitary adenomas. PMID:27347184

Non-functioning pituitary adenoma: immunohistochemical analysis of 85 cases.

PubMed

Mahta, Ali; Haghpanah, Vahid; Lashkari, Anahita; Heshmat, Ramin; Larijani, Bagher; Tavangar, Seyed Mohammad

2007-01-01

Pituitary adenomas without clinically active hypersecretion are summarized under the term non-functioning pituitary adenoma (NFPA). Since there are no specific serum markers, the differential diagnosis and treatment imply special difficulties. By using immunohistochemical methods we will have new insight into the nature and pathogenesis of these tumours. Ki-67 is a nuclear antigen detected by the monoclonal antibody MIB-1 and its labelling index (LI) is considered a marker of normal and abnormal cell proliferation. The aim of this study was to investigate the possible role of immunohistochemistry and MIB1-LI determination in NFPAs to predict tumoural behaviour and better management. In this clinicopathological study, 85 cases of NFPAs were analysed immunohistochemically. MIB1-LI was also determined in studied cases. Clinical presentation, treatment and follow-up data were also reviewed and the correlation between clinical and pathologic findings was established. Eighteen adenomas (21.2%) were immunoreactive to one or two adenohypophysial hormones of which 4 GH positive adenomas had aggressive behaviour (2 significant juxtasellar extensions and 2 recurrences). MIB-1 LI was more than 5% in only 5 cases including 2 invasive adenomas but with no evidence of recurrence. No significant statistical difference between clinical presentations in immunoreactive and non-immunoreactive NFPAs was observed except for unilateral temporal hemianopia which was more common in immunoreactive adenomas (P=0.022). NFPAs comprise several pathologically different types of tumours, some of which are potentially hormone producing, but some defects in hormone secretion or production of biologically inactive or insufficient amount of hormone may be the culprit in the lack of evidence of rising serum hormone levels. MIB-1 LI may be indicative of invasiveness but not a predictor of recurrence. Silent somatotropinomas may have more aggressive behaviour in comparison with other NFPAs.

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Incidence of colorectal adenomas: birth cohort analysis among 4.3 million participants of screening colonoscopy.

PubMed

Brenner, Hermann; Altenhofen, Lutz; Stock, Christian; Hoffmeister, Michael

2014-09-01

Most colorectal cancers develop from adenomas. We aimed to estimate sex- and age-specific incidence rates of colorectal adenomas and to assess their potential implications for colorectal cancer screening strategies. Sex- and age-specific incidence rates of colorectal adenomas were derived by a birth cohort analysis using data from 4,322,085 screening colonoscopies conducted in Germany and recorded in a national database in 2003-2012. In addition, cumulative risks of colorectal cancer among colonoscopically neoplasm-free men and women were estimated by combining adenoma incidence rates with previously derived adenoma-colorectal cancer transition rates. Estimated annual incidence in percentage (95% confidence interval) in age groups 55-59, 60-64, 65-69, 70-74, and 75-79 was 2.4 (2.2-2.6), 2.3 (2.1-2.6), 2.4 (2.1-2.6), 2.2 (1.8-2.5), and 1.8 (1.2-2.3) among men, and 1.4 (1.3-1.5), 1.5 (1.4-1.7), 1.6 (1.4-1.8), 1.6 (1.3-1.8), and 1.2 (0.8-1.6) among women. Estimated 10- and 15-year risks of clinically manifest colorectal cancer were 0.1% and 0.5% or lower, respectively, in all groups assessed. Annual incidence rates of colorectal adenomas are below 2.5% and 2% among men and women, respectively, and show little variation by age. Risk of clinically manifest colorectal cancer is expected to be very small within 10 years and beyond after negative colonoscopy for men and women at all ages. The use of rescreening after a negative screening colonoscopy above 60 years of age may be very limited. ©2014 American Association for Cancer Research.

Clinically non-functioning pituitary adenomas: Pathogenic, diagnostic and therapeutic aspects.

PubMed

Mercado, Moises; Melgar, Virgilio; Salame, Latife; Cuenca, Dalia

Clinically non-functioning pituitary adenomas (NFPAs) are among the most common tumors in the sellar region. These lesions do not cause a hormonal hypersecretion syndrome, and are therefore found incidentally (particularly microadenomas) or diagnosed based on compressive symptoms such as headache and visual field defects, as well as clinical signs of pituitary hormone deficiencies. Immunohistochemically, more than 45% of these adenomas stain for gonadotropins or their subunits and are therefore called gonadotropinomas, while 30% of them show no immunostaining for any hormone and are known as null cell adenomas. The diagnostic approach to NFPAs should include visual field examination, an assessment of the integrity of all anterior pituitary hormone systems, and magnetic resonance imaging of the sellar region to define tumor size and extension. The treatment of choice is transsphenoidal resection of the adenoma, which in many instances cannot be completely accomplished. The recurrence rate after surgery may be up to 30%. Persistent or recurrent adenomas are usually treated with radiation therapy. In a small proportion of these cases, drug treatment with dopamine agonists and, to a lesser extent, somatostatin analogs may achieve reduction or at least stabilization of the tumor. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Mice with Inactivation of Aryl Hydrocarbon Receptor-Interacting Protein (Aip) Display Complete Penetrance of Pituitary Adenomas with Aberrant ARNT Expression

PubMed Central

Raitila, Anniina; Lehtonen, Heli J.; Arola, Johanna; Heliövaara, Elina; Ahlsten, Manuel; Georgitsi, Marianthi; Jalanko, Anu; Paetau, Anders; Aaltonen, Lauri A.; Karhu, Auli

2010-01-01

Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been shown to predispose to pituitary adenoma predisposition, a condition characterized by growth hormone (GH)-secreting pituitary tumors. To study AIP-mediated tumorigenesis, we generated an Aip mouse model. Heterozygous mice developed normally but were prone to pituitary adenomas, in particular to those secreting GH. A complete loss of AIP was detected in these lesions, and full penetrance was reached at the age of 15 months. No excess of any other tumor type was found. Ki-67 analysis indicated that Aip-deficient tumors have higher proliferation rates compared with Aip-proficient tumors, suggesting a more aggressive disease. Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function. The Aip+/− mouse appears to be an excellent model for the respective human disease phenotype. This model constitutes a tool to further study AIP-associated pituitary tumorigenesis and may be potentially valuable in efforts to develop therapeutic strategies to treat pituitary adenomas. PMID:20709796

Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor

PubMed Central

Paradis, Valerie; Pote, Nicolas; Jakate, Shriram; Ferrell, Linda D

2016-01-01

Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33–75 years) and four women (29–65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma

Obesity-related parameters and colorectal adenoma development.

PubMed

Kim, Tae Jun; Kim, Jee Eun; Choi, Yoon-Ho; Hong, Sung Noh; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Min-Ji; Jung, Sin-Ho; Son, Hee Jung

2017-12-01

Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development. In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy. In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences [odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09-1.57)]. Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02-1.04), male sex (OR 1.49; 95% CI 1.17-1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10-1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10-1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24-2.06). Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.

Predictive value of diminutive colonic adenoma trial: the PREDICT trial.

PubMed

Schoenfeld, Philip; Shad, Javaid; Ormseth, Eric; Coyle, Walter; Cash, Brooks; Butler, James; Schindler, William; Kikendall, Walter J; Furlong, Christopher; Sobin, Leslie H; Hobbs, Christine M; Cruess, David; Rex, Douglas

2003-05-01

Diminutive adenomas (1-9 mm in diameter) are frequently found during colon cancer screening with flexible sigmoidoscopy (FS). This trial assessed the predictive value of these diminutive adenomas for advanced adenomas in the proximal colon. In a multicenter, prospective cohort trial, we matched 200 patients with normal FS and 200 patients with diminutive adenomas on FS for age and gender. All patients underwent colonoscopy. The presence of advanced adenomas (adenoma >or= 10 mm in diameter, villous adenoma, adenoma with high grade dysplasia, and colon cancer) and adenomas (any size) was recorded. Before colonoscopy, patients completed questionnaires about risk factors for adenomas. The prevalence of advanced adenomas in the proximal colon was similar in patients with diminutive adenomas and patients with normal FS (6% vs. 5.5%, respectively) (relative risk, 1.1; 95% confidence interval [CI], 0.5-2.6). Diminutive adenomas on FS did not accurately predict advanced adenomas in the proximal colon: sensitivity, 52% (95% CI, 32%-72%); specificity, 50% (95% CI, 49%-51%); positive predictive value, 6% (95% CI, 4%-8%); and negative predictive value, 95% (95% CI, 92%-97%). Male gender (odds ratio, 1.63; 95% CI, 1.01-2.61) was associated with an increased risk of proximal colon adenomas. Diminutive adenomas on sigmoidoscopy may not accurately predict advanced adenomas in the proximal colon.

Ovarian hyperstimulation, hyperprolactinaemia and LH gonadotroph adenoma.

PubMed

Castelo-Branco, Camil; del Pino, Marta; Valladares, Esther

2009-08-01

This report considers a highly exceptional case of ovarian hyperstimulation syndrome due to a gonadotroph adenoma secreting LH in a 31-year-old patient who presented with amenorrhoea and galactorrhoea syndrome and a complex bilateral ovarian mass. Magnetic resonance imaging revealed a pituitary adenoma, and laboratory tests corroborated the hyperprolactinaemia without other hormonal pituitary abnormalities. Ovarian hyperstimulation syndrome due to a gonadotroph adenoma with normal gonadotrophins is extremely rare. Most of the described cases are caused by FSH adenomas. Due to the originality of the case, it was considered useful for understanding the management of this entity, and it is proposed that LH adenomas should also be considered in the differential diagnosis of patients with spontaneous ovarian hyperstimulation syndrome.

Modification of hormonal secretion in clinically silent pituitary adenomas.

PubMed

Daems, Tania; Verhelst, Johan; Michotte, Alex; Abrams, Pascale; De Ridder, Dirk; Abs, Roger

2009-01-01

Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

Clinical characteristics of pain in patients with pituitary adenomas.

PubMed

Dimopoulou, C; Athanasoulia, A P; Hanisch, E; Held, S; Sprenger, T; Toelle, T R; Roemmler-Zehrer, J; Schopohl, J; Stalla, G K; Sievers, C

2014-11-01

Clinical presentation of pituitary adenomas frequently involves pain, particularly headache, due to structural and functional properties of the tumour. Our aim was to investigate the clinical characteristics of pain in a large cohort of patients with pituitary disease. In a cross-sectional study, we assessed 278 patients with pituitary disease (n=81 acromegaly; n=45 Cushing's disease; n=92 prolactinoma; n=60 non-functioning pituitary adenoma). Pain was studied using validated questionnaires to screen for nociceptive vs neuropathic pain components (painDETECT), determine pain severity, quality, duration and location (German pain questionnaire) and to assess the impact of pain on disability (migraine disability assessment, MIDAS) and quality of life (QoL). We recorded a high prevalence of bodily pain (n=180, 65%) and headache (n=178, 64%); adrenocorticotropic adenomas were most frequently associated with pain (n=34, 76%). Headache was equally frequent in patients with macro- and microadenomas (68 vs 60%; P=0.266). According to painDETECT, the majority of the patients had a nociceptive pain component (n=193, 80%). Despite high prevalence of headache, 72% reported little or no headache-related disability (MIDAS). Modifiable factors including tumour size, genetic predisposition, previous surgery, irradiation or medical therapy did not have significant impact neither on neuropathic pain components (painDETECT) nor on headache-related disability (MIDAS). Neuropathic pain and pain-related disability correlated significantly with depression and impaired QoL. Pain appears to be a frequent problem in pituitary disease. The data suggest that pain should be integrated in the diagnostic and therapeutic work-up of patients with pituitary disease in order to treat them appropriately and improve their QoL. © 2014 European Society of Endocrinology.

Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

PubMed

Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

2014-06-01

Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

Variation of adenoma prevalence by age, sex, race, and colon location in a large population: implications for screening and quality programs.

PubMed

Corley, Douglas A; Jensen, Christopher D; Marks, Amy R; Zhao, Wei K; de Boer, Jolanda; Levin, Theodore R; Doubeni, Chyke; Fireman, Bruce H; Quesenberry, Charles P

2013-02-01

Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members ≥50 years of age who received a screening colonoscopy examination (102 gastroenterologists, 2006-2008). Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval [CI], 2.05-2.80; 70-74 vs 50-54 years) than in the distal colon (OR, 1.89; 95% CI, 1.63-2.19). Prevalence was higher among men vs women at all ages (OR, 1.77; 95% CI, 1.66-1.89), increasing in men from 25% to 39% at ≥70 years and in women from 15% at 50-54 years to 26% (P < .001). Proximal adenoma prevalence was higher among blacks than whites (OR, 1.26; 95% CI, 1.04-1.54), although total prevalence was similar, including persons <60 years old (OR, 1.17; 95% CI, 0.91-1.50). Prevalence of detected adenomas increases substantially with age and is much higher in men; proximal adenomas are more common among blacks than whites, although the total prevalence and the prevalence for ages <60 years were similar by race. These demographic differences are such that current adenoma detection guidelines may not be valid, without adjustment, for comparing providers serving different populations. The variation in prevalence and location may also have implications for the effectiveness of screening methods in different demographic groups. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Promoter CpG methylation of multiple genes in pituitary adenomas: frequent involvement of caspase-8.

PubMed

Bello, M Josefa; De Campos, Jose M; Isla, Alberto; Casartelli, Cacilda; Rey, Juan A

2006-02-01

The epigenetic changes in pituitary adenomas were identified by evaluating the methylation status of nine genes (RB1, p14(ARF), p16(INK4a), p73, TIMP-3, MGMT, DAPK, THBS1 and caspase-8) in a series of 35 tumours using methylation-specific PCR analysis plus sequencing. The series included non-functional adenomas (n=23), prolactinomas (n=6), prolactinoma plus thyroid-stimulating hormone adenoma (n=1), growth hormone adenomas (n=4), and adrenocorticotropic adenoma (n=1). All of the tumours had methylation of at least one of these genes and 40% of samples (14 of 35) displayed concurrent methylation of at least three genes. The frequencies of aberrant methylation were: 20% for RB1, 17% for p14(ARF), 34% for p16(INK4a), 29% for p73, 11% for TIMP-3, 23% for MGMT, 6% for DAPK, 43% for THBS1 and 54% for caspase-8. No aberrant methylation was observed in two non-malignant pituitary samples from healthy controls. Although some differences in the frequency of gene methylation between functional and non-functional adenomas were detected, these differences did not reach statistical significance. Our results suggest that promoter methylation is a frequent event in pituitary adenoma tumourigenesis, a process in which inactivation of apoptosis-related genes (DAPK, caspase-8) might play a key role.

Dexmedetomidine could enhance surgical satisfaction in Trans-sphenoidal resection of pituitary adenoma.

PubMed

Salimi, Alireza; Sharifi, Guive; Bahrani, Houshang; Mohajerani, Seyed A; Jafari, Alireza; Safari, Farhad; Jalessi, Maryam; Mirkheshti, Alireza; Mottaghi, Kamran

2017-02-01

Excessive bleeding is an unwanted complication of trans-sphenoidal resection of pituitary adenoma due to increases in intracranial pressure (ICP) and hemodynamic instability. Dexmedetomidine (Dex) anα2-agonists is the drug of choice in intensive care units (ICU) and cardiac surgeries to control abrupt changes in hemodynamic. Severe cardiovascular responses occur during trans-sphenoidal resection (TSR) of the pituitary adenoma despite adequate depth of anesthesia. The aim of this paper was to determine the effect of Dexmedetomidine on bleeding as primary outcome, and surgeon's satisfaction and hemodynamic stability as secondary outcomes in patients undergoing trans-sphenoidal resection of pituitary adenoma. Total numbers of 60 patients between 18-65 years old and candidate for elective trans-sphenoidal resection of pituitary adenoma were randomLy allocated to two groups; Dexmedetomidine infusion (0.6µg/kg/hour) or normal saline infusion. Mean arterial pressure (MAP), heart rate (HR), dose of hypnotics and narcotics during surgery, bleeding, and surgeon's satisfaction were recorded. Propofol maintenance dose (µg/kg/min) and total Fentanyl use (µg) were significantly lower in Dex group compare to control group (P=0.01 and 0.003, respectively). Total bleeding amount during operation in Dex group was significantly lower than control group (P=0.012). Surgeon's satisfaction was significantly higher in Dex group at the end of surgery. MAP and heart rate throughout surgery were significantly lower in Dex group compare to control group (P=0.001). Dexmedetomidine infusion (0.6µg/kg/hour) could reduce bleeding and provide surgeon's satisfaction during trans-sphenoidal resection of pituitary adenoma.

Treatment of Pituitary Carcinomas and Atypical Pituitary Adenomas: A Review

PubMed Central

HIROHATA, Toshio; ISHII, Yudo; MATSUNO, Akira

2014-01-01

Atypical pituitary adenomas (APAs) are aggressive tumors, harboring a Ki-67 (MIB-1) staining index of 3% or more, and positive immunohistochemical staining for p53 protein, according to the World Health Organization (WHO) classification in 2004. Pituitary carcinomas (PC) usually develop from progressive APAs and predominantly consist of hormone-generating tumors, defined by the presence of disseminations in the cerebrospinal system or systemic metastases. Most of the cases with these malignant pituitary adenomas underwent surgeries, irradiations and adjuvant medical treatments, nevertheless, the therapies are mainly palliative. Recently, the efficacy of temozolomide (TMZ), an orally administered alkylating agent, has been reported as an alternative medical treatment. However, some recent studies have demonstrated a significant recurrence rate after effective response to TMZ. Further clinical and pathological researches of malignant pituitary adenomas will be required to improve the outcome of patients with these tumors. PMID:25446382

Effects of calcium on the incidence of recurrent colorectal adenomas

PubMed Central

Veettil, Sajesh K.; Ching, Siew Mooi; Lim, Kean Ghee; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-01-01

Abstract Background: Protective effects of calcium supplementation against colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Our objective was to update and systematically evaluate the evidence for calcium supplementation taking into consideration the risks of systematic and random error and to GRADE the evidence. Methods: The study comprised a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCTs). We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. Primary outcome measures were the incidences of any recurrent adenomas and of advanced adenomas. Meta-analytic estimates were calculated with the random-effects model and random errors were evaluated with trial sequential analyses (TSAs). Results: Five randomized trials (2234 patients with a history of adenomas) were included. Two of the 5 trials showed either unclear or high risks of bias in most criteria. Meta-analysis of good quality RCTs suggest a moderate protective effect of calcium supplementation on recurrence of adenomas (relative risk [RR], 0.88 [95% CI 0.79–0.99]); however, its effects on advanced adenomas did not show statistical significance (RR, 1.02 [95% CI 0.67–1.55]). Subgroup analyses demonstrated a greater protective effect on recurrence of adenomas with elemental calcium dose ≥1600 mg/day (RR, 0.74 [95% CI 0.56–0.97]) compared to ≤1200 mg/day (RR, 0.84 [95% CI 0.73–0.97]). No major serious adverse events were associated with the use of calcium, but there was an increase in the incidence of hypercalcemia (P = .0095). TSA indicated a lack of firm evidence for a beneficial effect. Concerns with directness and imprecision rated down the quality of the evidence to “low.” Conclusion: The available good quality RCTs suggests a possible beneficial effect of calcium supplementation on the recurrence of adenomas

[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.

Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma.

PubMed

Yuan, Hai-Xia; Cao, Jia-Ying; Kong, Wen-Tao; Xia, Han-Sheng; Wang, Xi; Wang, Wen-Ping

2015-04-01

Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical resection. It is difficult to differentiate adenoma from other gallbladder polyps using imaging examinations. The study aimed to illustrate characteristics of contrast-enhanced ultrasound (CEUS) and its diagnostic value in gallbladder adenoma. Thirty-seven patients with 39 gallbladder adenomatoid lesions (maximal diameter ≥10 mm and without metastasis) were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individually among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. Adenoma lesions showed iso-echogenicity in ultrasound, and an eccentric enhancement pattern, "fast-in and synchronous-out" contrast enhancement pattern and homogeneous at peak-time enhancement in CEUS. The homogenicity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion (100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively). The characteristic of the eccentric enhancement pattern had the highest diagnostic ability in differentiating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, respectively. CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps (≥10 mm in diameter). Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

A challenging case of an ectopic parathyroid adenoma.

PubMed

Panchani, Roopal; Varma, Tarun; Goyal, Ashutosh; Gupta, Nitinranjan; Saini, Ashish; Tripathi, Sudhir

2012-12-01

The occurrence of ectopic parathyroid adenomas is not uncommon (3-4% of all parathyroid adenomas). A 42-year-old female diagnosed as having GH secreting pituitary adenoma presented with an ectopic mediastinal parathyroid adenoma located between left (Lt) pulmonary artery and Lt main bronchus. The aim of presenting this case is not to appreciate the rarity of the condition but to rather discuss some of the vital practical problems faced during its management. Patient presenting in endocrine OPD with nausea, vomiting, drowsiness and chronic constipation was investigated biochemically and with various imaging modalities and accordingly managed. Patient was also investigated from the perspective of MEN 1 syndrome. Baseline routine investigations revealed hypercalcemia (corrected S. Ca- 16.9 mg/dl) due to primary hyperparathyroidism (PHP, PTH-1190 ng/L) with adenoma located between Lt main bronchus and Lt pulmonary artery. Patient was medically managed and after proper preoperative preparation, surgical excision by open thoracotomy was planned but two days before surgery she developed pulmonary embolism and was shifted to ICU where she died after 20 days. An accurate preoperative localization by various imaging procedures plays a decisive role in case of ectopic adenomas in the chest. Ectopic parathyroid adenomas are frequent cause of failed initial surgery. The best surgical approach to these ectopic adenomas is still controversial. Equally effective newer medical treatment modalities are also required in patients who are awaiting or are unfit for surgery. Lastly combination of MEN 1 with ectopic parathyroid adenoma is rare.

Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization.

PubMed Central

Lloyd, R. V.; Cano, M.; Chandler, W. F.; Barkan, A. L.; Horvath, E.; Kovacs, K.

1989-01-01

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:2466405

Endoscopic endonasal pituitary adenomas surgery: the surgical experience of 178 consecutive patients and learning curve of two neurosurgeons.

PubMed

Shou, Xuefei; Shen, Ming; Zhang, Qilin; Zhang, Yichao; He, Wenqiang; Ma, Zengyi; Zhao, Yao; Li, Shiqi; Wang, Yongfei

2016-11-30

We aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery. We retrospectively analyzed 178 endoscopic endonasal pituitary adenomas surgery from March 2011 to May 2014. Endonasal approach included the routine transnasal-sphenoidal approach, transnasal- maxillary sinus approach in four cases and transnasal-clivus approach in one case. According to postoperative imaging data and endocrine examination results, total removal was achieved in 129 patients (72.5%), and endocrinological remission was achieved in 38 patients with functional adenomas (44.1%). Statistical analysis of the clinical data showed that total removal rate was much closely related to tumor volume (P = 0.006), and tumor invasiveness (P < 0.001). In this study, we found tumor sizes and invasion of cavernous sinus were related to total removal rate and endocrinological remission rate; the direction and degree of tumor invasion, and the surgeon's experience were the key influence factors of the endocrinological remission rate for invasive functional pituitary adenomas.

Colonic diverticulosis is not a risk factor for colonic adenoma.

PubMed

Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

2018-01-01

Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

Dynamic CT for Parathyroid Adenoma Detection: How Does Radiation Dose Compare With Nuclear Medicine?

PubMed

Czarnecki, Caroline A; Einsiedel, Paul F; Phal, Pramit M; Miller, Julie A; Lichtenstein, Meir; Stella, Damien L

2018-05-01

Dynamic CT is increasingly used for preoperative localization of parathyroid adenomas, but concerns remain about the radiation effective dose of CT compared with that of 99m Tc-sestamibi scintigraphy. The purpose of this study was to compare the radiation dose delivered by three-phase dynamic CT with that delivered by 99m Tc-sestamibi SPECT/CT performed in accordance with our current protocols and to assess the possible reduction in effective dose achieved by decreasing the scan length (i.e., z-axis) of two phases of the dynamic CT protocol. The effective dose of a 99m Tc-sestamibi nuclear medicine parathyroid study performed with and without coregistration CT was calculated and compared with the effective dose of our current three-phase dynamic CT protocol as well as a proposed protocol involving CT with reduced scan length. The median effective dose for a 99m Tc-sestamibi nuclear medicine study was 5.6 mSv. This increased to 12.4 mSv with the addition of coregistration CT, which is higher than the median effective dose of 9.3 mSv associated with the dynamic CT protocol. Reducing the scan length of two phases in the dynamic CT protocol could reduce the median effective dose to 6.1 mSv, which would be similar to that of the dose from the 99m Tc-sestamibi study alone. Dynamic CT used for the detection of parathyroid adenoma can deliver a lower radiation dose than 99m Tc-sestamibi SPECT/CT. It may be possible to reduce the dose further by decreasing the scan length of two of the phases, although whether this has an impact on accuracy of the localization needs further investigation.

Hepatocellular carcinoma arising in a telangiectatic hepatocellular adenoma.

PubMed

González-Lara, María Fernanda; Córdova-Ramón, Juan Carlos; Gamboa-Domínguez, Armando; Cosme-Labarthe, Juan; Carrillo-Pérez, Diego Luis

2013-01-01

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of benign liver tumor that may very rarely undergo transformation into hepatocellular carcinoma. We report an unusual case of a 75-year-old woman with no history of oral contraceptive use that underwent malignant transformation of a telangiectactic hepatocellular adenoma. No risk factors for adenoma development were identified in this otherwise healthy woman. Radiological characteristics, gross features and histopathology are herein described. In conclusion, telangiectatic hepatocellular adenoma can undergo malignant transformation. Further studies are needed to better clarify the factors associated with malignant progression.

Diagnosis and treatment of pituitary adenomas.

PubMed

Chanson, P; Salenave, S

2004-12-01

Pituitary tumors cause symptoms by secreting hormones (prolactin, PRL, responsible for amenorrhea-galactorrhea in women and decreased libido in men; growth hormone, GH, responsible for acromegaly; adrenocorticotropic hormone, ACTH, responsible for Cushing's syndrome; thyroid-stimulating hormone, TSH, responsible for hyperthyroidism), depressing the secretion of hormones (hypopituitarism), or by mass-related effects (headaches, visual field abnormalities...). All patients with pituitary tumors should be evaluated for gonadal, thyroid and adrenal function as well as PRL and GH secretion. Specific stimulation and suppression tests for pituitary hormones are performed in selected situations for detecting the type of hypersecretion or the response to treatment. Imaging procedures (mainly magnetic resonance imaging, MRI, nowadays) determine the presence, size and extent of the lesion. The classification of pituitary tumors is based on the staining properties of the cell cytoplasm viewed by light microscopy and immunocytochemistry revealing the secretory pattern of the adenoma. Treatment of pituitary adenomas consists of surgery (performed in more than 99% of cases via a transphenoidal route) and radiotherapy, generally fractionated or, in selected cases, using stereotactic techniques such as gamma-knife. The availability of medical treatment (dopamine, DA, agonists, somatostatin analogs, GH-receptor antagonists...) has profoundly modified the indications of radiotherapy, drugs being now generally used as a second-line treatment, after surgery (or even as first-line treatment). Based on the results of the different treatment modalities for each type of pituitary adenoma, recommendations will be proposed. They may be summarized as follows. For treatment of GH-secreting adenomas, trans-sphenoidal surgery is the first-line therapy except when the macroadenoma is giant or if surgery is contra-indicated; postoperative radiation therapy (fractionated, or by gamma-knife) is

Understanding the potential and challenges of adenoma treatment as a prevention opportunity: insights from the BeWEL formative study.

PubMed

Stead, Martine; Caswell, Stephen; Craigie, Angela M; Eadie, Douglas; Anderson, Annie S

2012-01-01

To explore prevention opportunities presented by colorectal adenoma diagnosis and inform engagement strategies for the BeWEL study (body weight and physical activity lifestyle intervention for colorectal cancer screening participants who have undergone adenoma removal). Qualitative study comprising 4 purposively sampled focus groups conducted in urban and rural areas in Tayside, Scotland, with different deprivation levels. Participants were men and women (n=17) aged 50-74 with BMI>25 kg/m(2) with removal of adenoma detected by colorectal cancer screening. Adenoma diagnosis presents both opportunities and challenges for prevention. Some patients perceived adenoma as minor and not sufficiently motivating to act as a 'teachable moment'. Patients had low awareness of the relationship between adenoma and lifestyle factors, and received little information on prevention during screening and treatment. Consequently they interpreted post-treatment 'all clear' messages as validation of existing lifestyles, and did not see the relevance of prevention advice. Receptiveness increased when the association between lifestyle, adenoma recurrence and other illness was explained. The study illustrates the value of exploratory research into patient understanding to improve communications and health services. Without unduly worrying patients, professionals should explain how to reduce risk of adenoma, cancer and other diseases, particularly through diet, physical activity and weight reduction. Copyright © 2011 Elsevier Inc. All rights reserved.

Selenium supplementation and colorectal adenomas: an analysis of the nutritional prevention of cancer trial.

PubMed

Reid, Mary E; Duffield-Lillico, Anna J; Sunga, Annette; Fakih, Marwan; Alberts, David S; Marshall, James R

2006-04-01

Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow-up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow-up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination post-randomization during the follow-up period) or incident (identified at the second or subsequent examination). Ninety-nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43-1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09-0.77) and current smokers (OR = 0.27, 95% CI = 0.11-0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57-1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers.

Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.

PubMed

Rastogi, Amit; Early, Dayna S; Gupta, Neil; Bansal, Ajay; Singh, Vikas; Ansstas, Michael; Jonnalagadda, Sreenivasa S; Hovis, Christine E; Gaddam, Srinivas; Wani, Sachin B; Edmundowicz, Steven A; Sharma, Prateek

2011-09-01

Missing adenomas and the inability to accurately differentiate between polyp histology remain the main limitations of standard-definition white-light (SD-WL) colonoscopy. To compare the adenoma detection rates of SD-WL with those of high-definition white-light (HD-WL) and narrow-band imaging (NBI) as well as the accuracy of predicting polyp histology. Multicenter, prospective, randomized, controlled trial. Two academic medical centers in the United States. Subjects undergoing screening or surveillance colonoscopy. Subjects were randomized to undergo colonoscopy with one of the following: SD-WL, HD-WL, or NBI. The proportion of subjects detected with adenomas, adenomas detected per subject, and the accuracy of predicting polyp histology real time. A total of 630 subjects were included. The proportion of subjects with adenomas was 38.6% with SD-WL compared with 45.7% with HD-WL and 46.2% with NBI (P = .17 and P = .14, respectively). Adenomas detected per subject were 0.69 with SD-WL compared with 1.12 with HD-WL and 1.13 with NBI (P = .016 and P = .014, respectively). HD-WL and NBI detected more subjects with flat and right-sided adenomas compared with SD-WL (all P values <.005). NBI had a superior sensitivity (90%) and accuracy (82%) to predict adenomas compared with SD-WL and HD-WL (all P values <.005). Academic medical centers with experienced endoscopists. There was no difference in the proportion of subjects with adenomas detected with SD-WL, HD-WL, and NBI. However, HD-WL and NBI detected significantly more adenomas per subject (>60%) compared with SD-WL. NBI had the highest accuracy in predicting adenomas in real time during colonoscopy. ( NCT 00614770.). Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Primary Endoscopic Transnasal Transsphenoidal Surgery for Giant Pituitary Adenoma.

PubMed

Kuo, Chao-Hung; Yen, Yu-Shu; Wu, Jau-Ching; Chang, Peng-Yuan; Chang, Hsuan-Kan; Tu, Tsung-Hsi; Huang, Wen-Cheng; Cheng, Henrich

2016-07-01

Giant pituitary adenoma (>4 cm) remains challenging because the optimal surgical approach is uncertain. Consecutive patients with giant pituitary adenoma who underwent endoscopic transnasal transsphenoidal surgery (ETTS) as the first and primary treatment were retrospectively reviewed. Inclusion criteria were tumor diameter ≥4 cm in at least 1 direction, and tumor volume ≥10 cm(3). Exclusion criteria were follow-ups <2 years and diseases other than pituitary adenoma. All the clinical and radiologic outcomes were evaluated. A total of 38 patients, average age 50.8 years, were analyzed with a mean follow-up of 72.9 months. All patients underwent ETTS as the first and primary treatment, and 8 (21.1%) had complete resection without any evidence of recurrence at the latest follow-up. Overall, mean tumor volume decreased from 29.7 to 3.2 cm(3) after surgery. Residual and recurrent tumors (n = 30) were managed with 1 of the following: Gamma Knife radiosurgery (GKRS), reoperation (redo ETTS), both GKRS and ETTS, medication, conventional radiotherapy, or none. At last follow-up, most of the patients had favorable outcomes, including 8 (21.1%) who were cured and 29 (76.3%) who had a stable residual condition without progression. Only 1 (2.6%) had late recurrence at 66 months after GKRS. The overall progression-free rate was 97.4%, with few complications. In this series of giant pituitary adenoma, primary (ie, the first) ETTS yielded complete resection and cure in 21.1%. Along with adjuvant therapies, including GKRS, most patients (97.4%) were stable and free of disease progression. Therefore, primary ETTS appeared to be an effective surgical approach for giant pituitary adenoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review

PubMed Central

Yamanaka, Ryuya; Sato, Toshiteru; Hayano, Azusa; Takashima, Yasuo

2017-01-01

Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959–2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3–14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5–9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall

Adenomas - Genetic factors in colorectal cancer prevention.

PubMed

Witold, Kycler; Anna, Kubiak; Maciej, Trojanowski; Jakub, Janowski

2018-01-01

Colorectal cancer is the second most common type of cancer both in Europe and Poland. During the last 30 years more than a 3-fold increase has been observed in Poland due to environmental and genetic factors. Almost all colorectal malignancies are related to the formation and malignant transformation of colorectal dysplasia and adenoma. Efforts aiming to decrease the number of colorectal cancer deaths are focused on the disease early detection. Genetic diagnosis for hereditary syndromes predisposing to colorectal cancer has been developed and is a part of the routine treatment. Most cancers are sporadic. They often develop from polyps in the colon. In addition to the genetic events described in the 1990s, showing the adenoma transformation into carcinoma that has been a prime example of malignant transformation for a long time, there are also other possibilities of neoplastic transformation. The recognition of colorectal cancer risk factors make sense as their nature is lifestyle- and diet-related. In this review paper those risk factors are presented and the prevention of colorectal cancer is discussed taking into account genetic factors.

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

PubMed

Lilja, Ylva; Gustafsson, Oscar; Ljungberg, Maria; Starck, Göran; Lindblom, Bertil; Skoglund, Thomas; Bergquist, Henrik; Jakobsson, Karl-Erik; Nilsson, Daniel

2017-09-01

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation

Recent Evolution of Endoscopic Endonasal Surgery for Treatment of Pituitary Adenomas

PubMed Central

NISHIOKA, Hiroshi

2017-01-01

For the treatment of pituitary tumors, microscopic transsphenoidal surgery has been considered the “gold standard” since the late 1960s. Over the last two decades, however, a worldwide shift towards endoscopic endonasal surgery is in progress for many reasons. These include a wide panoramic view, improved illumination, an ability to look around anatomical corners using angled tip and, in addition, application to the extended approaches for parasellar tumors. Both endoscopic and microscopic approaches appear equally effective for nonfunctioning adenomas without significant suprasellar or lateral extensions, whereas the endoscopic approach may improve outcomes associated with the extent of resection and postoperative complications for larger tumors. Despite many theoretical benefits in the endoscopic surgery, remission rates of functioning adenomas do not substantially differ between the approaches in experienced hands. The endoscopic approach is a valid alternative to the microscopic approach for adenomas. The benefits will be more appreciated in the extended surgery for parasellar tumors. PMID:28239067

Synthesis of 19-nor-aldosterone, 18-hydroxy-19-nor-corticosterone and 18,19-dihydroxycorticosterone in the human aldosterone-producing adenoma.

PubMed

Takeda, Y; Lewicka, S; Koch, S; Bige, K; Vecsei, P; Abdelhamid, S; Cojocaru, M; Harnik, M

1990-11-30

The recently synthesized 18-C-steroid derivative, 19-nor-aldosterone(19-nor- aldo) and 18-hydroxy-19-nor-corticosterone(18-OH-19-nor-corticosterone) possess mineralocoroticoid and hypertensinogenic activity. They and an additional newly synthesized steriod, 18,19-dihydroxycorticosterone[18,19(OH)2-corticosterone], may play a role in the etiology and pathogenesis of disorders thought to be caused by steroids with mineralocorticoid and hypertensionogenic properties. In this study we provide evidence that 19-nor-aldo, 18-OH-19-nor-corticosterone and 18,19(OH)2-corticosterone are produced in vitro by aldosterone-producing adrenal adenomas and adenomas and adenoma of Cushing's syndrome. "silent" adrenal adenomas and the adjacent adrenal tissue. Measurable amounts of these steroids were found in the incubation fluids of adrenal tissues using specific RIAs performed after a sequence of HPLC systems. The rates of production of the three steroids were high in the aldosterone-producing adrenal adenomas and in adrenal hyperplasia compared with in either Cushing's adenoma or "silent" adenoma.

Monomorphous Plurihormonal Pituitary Adenoma of Pit-1 Lineage in a Giant Adolescent with Central Hyperthyroidism.

PubMed

Pereira, Bernardo Dias; Raimundo, Luísa; Mete, Ozgur; Oliveira, Ana; Portugal, Jorge; Asa, Sylvia L

2016-03-01

Thyrotropin (TSH)-secreting pituitary adenomas are exceedingly rare at the pediatric age and no cases of co-secretion with other pituitary hormones in these tumors have been described in this age range. We present a case of a monomorphous plurihormonal pituitary adenoma that co-secreted TSH and GH in a pediatric patient. A 13-year-old male presented with increasing height velocity (17.75 cm/year, 9.55SD), weight loss, and visual impairment. Initial biochemical evaluations revealed secondary hyperthyroidism. A giant pituitary tumor compressing the surrounding structures was detected by magnetic resonance, and a transsphenoidal surgery was initially performed. Pathological examinations revealed an atypical, monomorphous plurihormonal Pit-1 lineage tumor with mixed features of silent subtype 3 adenoma and acidophil stem cell adenoma. In the postoperative period, secondary hyperthyroidism recurred with high levels of both GH and IGF1. In addition, due to tumor re-growth, a multimodality treatment plan was undertaken including surgery, somatostatin analogs, and radiotherapy. We report the first pediatric case of a plurihormonal TSH- and GH-secreting pituitary adenoma, further expanding the clinical manifestations of pediatric pituitary tumors. Comprehensive pathological evaluation and close follow-up surveillance are crucial to the prompt delivery of the best therapeutic options in the context of this particularly aggressive pituitary tumor.

Application of intraoperative magnetic resonance imaging in large invasive pituitary adenoma surgery.

PubMed

Li, Jie; Cong, Zixiang; Ji, Xueman; Wang, Xiaoliang; Hu, Zhigang; Jia, Yue; Wang, Handong

2015-07-01

To investigate the clinical application value of intraoperative magnetic resonance imaging (iMRI) in large invasive pituitary adenoma surgery. A total of 30 patients with large pituitary adenoma underwent microscopic tumor resection under the assistance of an iMRI system; 26 cases received surgery through the nasal-transsphenoidal approach, and the remaining four cases received surgery through the pterion approach. iMRI was performed one or two times depending on the need of the surgeon. If a residual tumor was found, further resection was conducted under iMRI guidance. iMRI revealed residual tumors in 12 cases, among which nine cases received further resection. Of these nine cases, iMRI rescanning confirmed complete resection in six cases, and subtotal resection in the remaining three. Overall, 24 cases of tumor were totally resected, and six cases were subtotally resected. The total resection rate of tumors increased from 60% to 80%. iMRI can effectively determine the resection extent of pituitary adenomas. In addition, it provides an objective basis for real-time judgment of surgical outcome, subsequently improving surgical accuracy and safety, and increasing the total tumor resection rate. Copyright © 2015. Published by Elsevier Taiwan.

Endoscopic endonasal transsphenoidal surgery: surgical results of 228 pituitary adenomas treated in a pituitary center.

PubMed

Gondim, Jackson A; Schops, Michele; de Almeida, João Paulo C; de Albuquerque, Lucas Alverne F; Gomes, Erika; Ferraz, Tânia; Barroso, Francisca Andréa C

2010-01-01

Pituitary tumors are challenging tumors in the sellar region. Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The introduction of the endoscope have revolutionized pituitary surgery. The aim of this study is to report the results of a consecutive series of patients undergoing pituitary surgery using a pure endoscopic endonasal approach and to evaluate the efficacy and safety of this procedure. We reviewed the data of 228 consecutive patients who underwent endonasal transsphenoidal adenoma removal over an 10-year period. Pre- and post-operative hormonal status (at least 3 months after surgery) were analyzed and compared with clinical parameters presented by the patients. Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 228 patients with pituitary adenomas who underwent 251 procedures between December 1998 and December 2007. There were 93 nonfunctioning adenomas, 58 growth hormone-secreting, 41 prolactin-secreting, 28 adrenocorticotropin hormone secreting, 7 FSH-LH secreting and 1 thyroid-stimulating hormone-secreting adenomas. Gross total removal was achieved in 79.3% of the cases after a median follow-up of 61.5 months. The remission results for patients with nonfunctioning adenomas was 83% and for functioning adenomas were 76.3% (70.6% for GH hormone-secreting, 85.3% for prolactin hormone-secreting, 71.4% for ACTH hormone-secreting, 85.7% for FSH-LH hormone-secreting and 100% for TSH hormone-secreting), with no recurrence at the time of the last follow-up. Post-operative complications were present in 35 (13.9%) cases. The most frequent complications were temporary and permanent diabetes insipidus (six and two cases, respectively), syndrome of inappropriate antidiuretic hormone secretion (two cases) and CSF leaks (eight cases). There was no death related to the procedure in this series. The endoscopic endonasal approach for resection of pituitary adenomas, provides

[Multicentre study on hepatic adenomas].

PubMed

Ramia, José Manuel; Bernardo, Carmen; Valdivieso, Andrés; Dopazo, Cristina; Jover, José María; Albiol, M Teresa; Pardo, Fernando; Fernandez Aguilar, José Luis; Gutierrez Calvo, Alberto; Serrablo, Alejandro; Diez Valladares, Luis; Pereira, Fernando; Sabater, Luis; Muffak, Karim; Figueras, Joan

2014-02-01

Hepatic adenomas (HA) are benign tumours which can present serious complications, and as such, in the past all were resected. It has now been shown that those smaller than 3 cm not expressing β-catenin only result in complications in exceptional cases and therefore the therapeutic strategy has been changed. Retrospective study in 14 HPB units. patients with resected and histologically confirmed HA. 1995-2011. 81 patients underwent surgery. Age: 39.5 years (range: 14-75). Sex: female (75%). Consumption of oestrogen in women: 33%. Size: 8.8 cm (range, 1-20 cm). Only 6 HA (7.4%) were smaller than 3 cm. The HA median was 1 (range: 1-12). Nine patients had adenomatosis (>10HA). A total of 51% of patients displayed symptoms, the most frequent (77%) being abdominal pain. Eight patients (10%) began with acute abdomen due to rupture and/or haemorrhage. A total of 67% of the preoperative diagnoses were correct. Surgery was scheduled for 90% of patients. The techniques employed were: major hepatectomy (22%), minor hepatectomy (77%) and one liver transplantation. A total of 20% were performed laparoscopically. The morbidity rate was 28%. There were no cases of mortality. Three patients had malignisation (3.7%). The follow-up period was 43 months (range 1-192). Two recurrences were detected and resected. Patients with resected HA are normally women with large lesions and oestrogen consumption was lower than expected. Its correct preoperative diagnosis is acceptable (70%). The major hepatectomy rate is 25% and the laparoscopy rate is 20%. There was a low morbidity rate and no mortality. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Detection of Sessile Serrated Adenomas in Proximal Colon Using Wide-field Fluorescence Endoscopy

PubMed Central

Joshi, Bishnu P.; Dai, Zhenzhen; Gao, Zhenghong; Lee, Jeong Hoon; Ghimire, Navin; Chen, Jing; Prabhu, Anoop; Wamsteker, Erik J.; Kwon, Richard S.; Elta, Grace H.; Stoffel, Elena M.; Pant, Asha; Kaltenbach, Tonya; Soetikno, Roy M.; Appelman, Henry D.; Kuick, Rork; Turgeon, D. Kim; Wang, Thomas D.

2018-01-01

Background & Aims Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients. Methods We used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 µmol/L and 22 patients were given 76.4 µmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hrs after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy, to identify suspicious regions. The fluorescently labeled peptide (76.4 µmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide

Nipple adenoma in a 2-year-old boy.

PubMed

Fujisawa, Kou; Kato, Motoi; Kono, Tatsuki; Utsunomiya, Hiroki; Watanabe, Azusa; Watanabe, Shoji

2018-05-01

Nipple adenoma is an uncommon proliferative process of the breast and predominantly occurs in women aged 40-50. Its incidence is extremely low in men, and it has not been reported in a boy. Although nipple adenoma is rare and benign, being familiar with it is important because it clinically resembles Paget disease and histologically adenocarcinoma. We report a case of nipple adenoma in a boy. © 2018 Wiley Periodicals, Inc.

Primary aldosteronism: results of adrenalectomy for nonsingle adenoma.

PubMed

Quillo, Amy R; Grant, Clive S; Thompson, Geoffrey B; Farley, David R; Richards, Melanie L; Young, William F

2011-07-01

Historically, treatment of confirmed primary aldosteronism has been adrenalectomy for unilateral adenoma; bilateral hypersecretion is treated medically. Increasingly, we use adrenal venous sampling (AVS) to define unilateral hypersecretion. Histology of glands resected based on AVS often reveals multiple nodules or hyperplasia. The aim of this study was to compare patients with multiple nodules or hyperplasia with those with single adenoma with regard to cure, preoperative imaging, AVS ratio, and biochemical evaluation to determine if a nonsingle adenoma (NSA) process could be predicted to impact extent of adrenalectomy. This was a retrospective study reviewing a single-institutional surgical experience at a tertiary academic center from 1993 to 2008, during which 215 patients with primary aldosteronism underwent unilateral adrenalectomy based on imaging of a single adenoma (normal contralateral gland) or AVS ratios. Histology included single adenoma versus NSA; cure was defined as normal immediate postoperative plasma or urine aldosterone level, normal aldosterone:renin ratio, or normotension without antihypertensive medications. Follow-up (mean 13 months, range 0 to 185 months) was available for 167 patients: 132 (79%) single adenoma and 35 (21%) NSA. All 35 patients with NSA and 128 patients (97%) with single adenoma were cured. Imaging studies correctly predicted NSA in 29% and 57% when combined with AVS. Identifying patients with NSA preoperatively was impossible biochemically: mean serum and urinary aldosterone levels and AVS ratios were not different than those of the single adenoma group. Twenty-one percent of patients had NSA, all cured by unilateral adrenalectomy. No preoperative evaluation reliably predicted NSA. Therefore, total unilateral adrenalectomy was safest given the potential for incomplete resection with partial adrenalectomy. Accurate AVS is highly predictive of cure irrespective of the unilateral adrenal histology. Copyright © 2011 American

Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

PubMed Central

Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

2011-01-01

Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly.

PubMed

Metyolkina, L; Peresedov, V

1995-01-01

Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma.

Risk of Metachronous High-Risk Adenomas and Large Serrated Polyps in Individuals With Serrated Polyps on Index Colonoscopy: Data From the New Hampshire Colonoscopy Registry.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Robinson, Christina M; Weiss, Julia E; Amos, Christopher; Srivastava, Amitabh

2018-01-01

Surveillance guidelines for serrated polyps (SPs) are based on limited data on longitudinal outcomes of patients. We used the New Hampshire Colonoscopy Registry to evaluate risk of clinically important metachronous lesions associated with SPs detected during index colonoscopies. We collected data from a population-based colonoscopy registry that has been collecting and analyzing data on colonoscopies across the state of New Hampshire since 2004, including rates of adenoma and SP detection. Patients completed a questionnaire to determine demographic characteristics, health history, and risk factors for colorectal cancer, and were followed from index colonoscopy through all subsequent surveillance colonoscopies. Our analyses included 5433 participants (median age, 61 years; 49.7% male) with 2 colonoscopies (median time to surveillance, 4.9 years). We used multivariable logistic regression models to assess effects of index SPs (n = 1016), high-risk adenomas (HRA, n = 817), low-risk adenomas (n = 1418), and no adenomas (n = 3198) on subsequent HRA or large SPs (>1 cm) on surveillance colonoscopy (metachronous lesions). Synchronous SPs, within each index risk group, were assessed for size and by histology. SPs comprise hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas. In this study, SSA/Ps and traditional serrated adenomas are referred to collectively as STSAs. HRA and synchronous large SP (odds ratio [OR], 5.61; 95% confidence interval [CI], 1.72-18.28), HRA with synchronous STSA (OR, 16.04; 95% CI, 6.95-37.00), and HRA alone (OR, 3.86; 95% CI, 2.77-5.39) at index colonoscopy significantly increased the risk of metachronous HRA compared to the reference group (no index adenomas or SPs). Large index SPs alone (OR, 14.34; 95% CI, 5.03-40.86) or index STSA alone (OR, 9.70; 95% CI, 3.63-25.92) significantly increased the risk of a large metachronous SP. In an analysis of data from a population-based colonoscopy

Gross total resection of pituitary adenomas after endoscopic vs. microscopic transsphenoidal surgery: a meta-analysis.

PubMed

Almutairi, Reem D; Muskens, Ivo S; Cote, David J; Dijkman, Mark D; Kavouridis, Vasileios K; Crocker, Erin; Ghazawi, Kholoud; Broekman, Marike L D; Smith, Timothy R; Mekary, Rania A; Zaidi, Hasan A

2018-05-01

Microscopic transsphenoidal surgery (mTSS) is a well-established method to address adenomas of the pituitary gland. Endoscopic transsphenoidal surgery (eTSS) has become a viable alternative, however. Advocates suggest that the greater illumination, panoramic visualization, and angled endoscopic views afforded by eTSS may allow for higher rates of gross total tumor resection (GTR). The aim of this meta-analysis was to determine the rate of GTR using mTSS and eTSS. A meta-analysis of the literature was conducted using PubMed, EMBASE, and Cochrane databases through July 2017 in accordance with PRISMA guidelines. Seventy case series that reported GTR rate in 8257 pituitary adenoma patients were identified. For all pituitary adenomas, eTSS (GTR=74.0%; I 2  = 92.1%) was associated with higher GTR as compared to mTSS (GTR=66.4%; I 2  = 84.0%) in a fixed-effect model (P-interaction < 0.01). For functioning pituitary adenomas (FPAs) (n = 1170 patients), there was no significant difference in GTR rate between eTSS (GTR=75.8%; I 2  = 63.9%) and mTSS (GTR=75.5%; I 2  = 79.0%); (P-interaction = 0.92). For nonfunctioning pituitary adenomas (NFPAs) (n = 2655 patients), eTSS (GTR=71.0%; I 2  = 86.4%) was associated with higher GTR as compared to mTSS (GTR=60.7%; I 2  = 87.5%) in a fixed-effect model (P-interaction < 0.01). None of the associations were significant in a random-effect model (all P-interaction > 0.05). No significant publication bias was identified for any of the outcomes. Among patients who were not randomly allocated to either approach, eTSS resulted in a higher rate of GTR as compared to mTSS for all patients and for NFPA patients alone, but only in a fixed-effect model. For FPA, however, eTSS did not seem to offer a significantly higher rate of GTR. These conclusions should be interpreted with caution because of the nature of the included non-comparative studies.

Endoscopic Endonasal Versus Microscopic Transsphenoidal Surgery for Recurrent and/or Residual Pituitary Adenomas.

PubMed

Esquenazi, Yoshua; Essayed, Walid I; Singh, Harminder; Mauer, Elizabeth; Ahmed, Mudassir; Christos, Paul J; Schwartz, Theodore H

2017-05-01

Surgery for recurrent/residual pituitary adenomas is increasingly being performed through endoscopic surgery. Whether this new technology has altered the indications and outcomes of surgery is unknown. We conducted a systematic review and meta-analysis of published studies to compare the indications and outcomes between microscopic and endoscopic approaches. A PubMed search was conducted (1985-2015) to identify surgical series of endoscopic endonasal and microscopic transsphenoidal resection of residual or recurrent pituitary adenomas. Data were extracted regarding tumor characteristics, surgical treatment, extent of resection, endocrine remission, visual outcome, and complications. Twenty-one studies met inclusion criteria. A total of 292 patients were in the endoscopic group, and 648 patients were in the microscopic group. Endoscopic cases were more likely nonfunctional (P < 0.001) macroadenomas (P < 0.001) with higher rates of cavernous sinus invasion (P = 0.012). The pooled rate of gross total tumor resection was 53.5% for the endoscopic group and 46.6% for the microscopic group. Endocrine remission was achieved in 53.0% and 46.7% of patients, and visual improvement occurred in 73.2% and 49.6% for the endoscopic and microscopic groups. Cerebrospinal fluid leak and pituitary insufficiency were higher in the endoscopic group. This meta-analysis indicates that the use of the endoscope to reoperate on residual or recurrent adenomas has only led to modest increases in resection rates. However, larger more complex cases are being tackled, so direct comparisons are misleading. The most dramatic change has been in visual improvement along with modest increases in risk. Reoperation for recurrent or residual adenomas is a safe and effective treatment option. Copyright © 2017 Elsevier Inc. All rights reserved.

Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach.

PubMed

Sandow, N; Klene, W; Elbelt, U; Strasburger, C J; Vajkoczy, P

2015-10-01

Initial successful surgical treatment of pituitary adenomas is crucial to reach long-term remission. Indocyanine green (ICG) videoangiography (VA) is well established in vascular neurosurgery nowadays and several reports described ICG application in brain tumor surgery. We designed this study to evaluate the feasibility of intravenous application of ICG and visualisation of a pituitary lesion via the fluorescence mode of the operation microscope. 22 patients with pituitary adenomas were treated with transsphenoidal microsurgery and were included in this study. Intraoperatively 25 mg ICG was administered intravenously and visualized via the fluorescence mode of the operation microscope (Pentero/Zeiss). 22 patients qualified for transsphenoidal surgery presenting with different clinical symptoms (13 patients with acromegaly, 6 with M. Cushing and 3 with other symptoms like vision disorder or dizziness) and identification of a pituitary lesion (21 of 22 patients) in preoperative MR-imaging (mean diameter: 9 mm; SD 3.6; 6 macroadenomas, 15 microadenomas, 1 MR-negative). In all 22 patients ICG VA was performed during surgery. No technical failures or adverse events after drug administration occurred. Visualization was optimal approximately 2.4 min after intravenous application. In all patients the adenoma could be detected via two different types of visualization: direct visualization by fluorophore emission versus indirect detection of the adenoma by a lower ICG fluorescence compared to the surrounding tissue. Our data show that intraoperative ICG VA can be a useful and easily applicable additional diagnostic tool for visualization of pituitary lesions using the microscopic approach.

[Prevalence of altered mismatch repair protein nuclear expression detected by immunohistochemistry on adenomas with high-grade dysplasia and features associated with this risk in a population-based study].

PubMed

Basterra, Marta; Gomez, Marta; Mercado, María Del Rosario; Irisarri, Rebeca; Amorena, Edurne; Arrospide, Arantzazu; Montes, Marta; Aisa, Gregorio; Cambra, Koldo Iñaki; Urman, Jesús

2016-10-01

Alteration of mismatch repair system protein expression detected by immunohistochemistry (IHQ) in tumoural tissue is a useful technique for Lynch Syndrome (LS) screening. A recent review proposes LS screening through immunohistochemical study not only in all diagnosed cases of colorectal cancer (CRC) but also in advanced adenomas, especially in young patients. To assess the prevalence of altered IHQ carried out in all adenomas with high-grade dysplasia (HGD) diagnosed in our community in 2011, as well as the variables associated with this alteration. We included all the cases of adenomatous polyps with HGD diagnosed in the three public pathology laboratories of Navarre during 2011 and performed a statistical study to assess the association between different patient and lesion characteristics and altered IHQ results. A total of 213 colonic adenomas with HGD were diagnosed, and 26 (12.2%) cases were excluded from the final analysis (2 known LS, 22 without IHQ study and 2 with inconclusive IHQ studies). The final number of adenomas included was 187. Pathologic results were found in 10 cases (5.35%)-6 cases in MLH1 and PMS2, 2 cases in PMS2, 1 case in MSH6 and 1 case in MSH2 and MSH6. The factors showing a statistically significant association with the presence of abnormal proteins were the synchronous presence of CRC, the presence of only one advanced adenoma, proximal location of HGD and age <50 years. The percentage of pathologic nuclear expression found in IHQ is high. Consequently, screening of all diagnosed HGD could be indicated, especially in young patients, with a single AA and proximal HGD. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Factors Associated With Shorter Colonoscopy Surveillance Intervals for Patients With Low-Risk Colorectal Adenomas and Effects on Outcome.

PubMed

Anderson, Joseph C; Baron, John A; Ahnen, Dennis J; Barry, Elizabeth L; Bostick, Roberd M; Burke, Carol A; Bresalier, Robert S; Church, Timothy R; Cole, Bernard F; Cruz-Correa, Marcia; Kim, Adam S; Mott, Leila A; Sandler, Robert S; Robertson, Douglas J

2017-06-01

Endoscopists do not routinely follow guidelines to survey individuals with low-risk adenomas (LRAs; 1-2 small tubular adenomas, < 1 cm) every 5-10 years for colorectal cancer; many recommend shorter surveillance intervals for these individuals. We aimed to identify the reasons that endoscopists recommend shorter surveillance intervals for some individuals with LRAs and determine whether timing affects outcomes at follow-up examinations. We collected data from 1560 individuals (45-75 years old) who participated in a prospective chemoprevention trial (of vitamin D and calcium) from 2004 through 2008. Participants in the trial had at least 1 adenoma, detected at their index colonoscopy, and were recommended to receive follow-up colonoscopy examinations at 3 or 5 years after adenoma identification, as recommended by the endoscopist. For this analysis we collected data from only participants with LRAs. These data included characteristics of participants and endoscopists and findings from index and follow-up colonoscopies. Primary endpoints were frequency of recommending shorter (3-year) vs longer (5-year) surveillance intervals, factors associated with these recommendations, and effect on outcome, determined at the follow-up colonoscopy. A 3-year surveillance interval was recommended for 594 of the subjects (38.1%). Factors most significantly associated with recommendation of 3-year vs a 5-year surveillance interval included African American race (relative risk [RR] to white, 1.41; 95% confidence interval [CI], 1.14-1.75), Asian/Pacific Islander ethnicity (RR to white, 1.7; 95% CI, 1.22-2.43), detection of 2 adenomas at the index examination (RR vs 1 adenoma, 1.47; 95% CI, 1.27-1.71), more than 3 serrated polyps at the index examination (RR=2.16, 95% CI, 1.59-2.93), or index examination with fair or poor quality bowel preparation (RR vs excellent quality, 2.16; 95% CI, 1.66-2.83). Other factors that had a significant association with recommendation for a 3-year

Outcomes of Aggressive Surgical Resection in Growth Hormone-Secreting Pituitary Adenomas with Cavernous Sinus Invasion.

PubMed

Park, Hun Ho; Kim, Eui Hyun; Ku, Cheol Ryong; Lee, Eun Jig; Kim, Sun Ho

2018-06-12

Cavernous sinus (CS) invasion is an unfavorable factor hindering remission of growth hormone (GH)-secreting pituitary adenomas. However, few data exist on aggressive surgical resection. The authors investigate the role of CS exploration for GH-secreting pituitary adenomas with CS invasion. We classified 132 patients with GH-secreting pituitary adenomas invading CS into 4 groups. The patients underwent surgery using a microsurgical transsphenoidal approach (TSA) with assistance of an endoscope. For adenomas with CS invasion confined to the medial compartment of ICA (internal carotid artery), they were divided into type A (without radiological evidence) and B (with radiological evidence). For adenomas with ICA encasement, tumors were divided according to the surgical approach: type C (standard TSA) and D (far-lateral TSA). Surgical and endocrinologic outcomes were compared between each group. Gross total resection rates were 100%, 73.6%, 14.7%, 0% and endocrinologic remission rates by surgery alone were 100% , 62.3%, 26.5%, 0% for type A, B, C, and D tumors, respectively. There was no endocrinologic remission by surgery alone for type D tumors. Nevertheless, it showed marked reduction of postoperative nadir GH at 1 week, 6 months, 1 year, and IGF-I at 1 year compared to type C tumors. For tumors with CS invasion confined to the medial compartment of ICA, total resection should be attempted by direct visualization of the entire medial wall of CS. Even for tumors with ICA encasement, aggressive tumor resection by far-lateral TSA can increase the chance of remission with the help of adjuvant treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of craniopharyngioma and pituitary adenoma.

PubMed

Guaraldi, Federica; Prencipe, Nunzia; di Giacomo, Valentina; Scanarini, Massimo; Gasco, Valentina; Gardiman, Marina Paola; Berton, Alessandro M; Ghigo, Ezio; Grottoli, Silvia

2013-08-01

Intracranial tumors of different histologic types infrequently affect patients with pituitary adenomas and no history of head irradiation. The association with craniopharyngioma is extremely rare. Aims of this paper are: (1) to provide a critical literature review of typical features of pituitary adenoma presenting in association with craniopharyngioma; (2) to describe the first documented (clinically, biochemically, histologically, and radiologically) case of aggressive, suprasellar papillary craniopharyngioma presenting with amenorrhea, progressive reduction of visual field, and severe headache in a 38-year-old woman, a decade after surgical cure for microprolactinoma associated with empty sella, during which she had carried two pregnancies; and (3) to discuss common etiopathogenetic mechanisms, in relation to the management of these lesions. Systematic literature search for English literature focusing on the association of craniopharyngioma and pituitary adenoma was performed using PubMed database. Additional relevant articles from references lists were also included. Clinical, laboratory, and radiological examinations performed in our patient for the two brain lesions at diagnosis and follow up were collected. Literature search retrieved nine articles. Typically, craniopharyngioma were of adamantinomatous type, occurred simultaneously to pituitary adenoma, presented with headache and visual loss, and affected men. No case of clearly documented metachronous lesion affecting a woman after pregnancy had been described before. Although very rare and with uncertain etiopathogenesis, second tumors (i.e., craniopharyngioma) should be considered in patients with a history of pituitary adenoma, presenting with suggestive signs and symptoms, even after a long disease-free period, in order to provide proper and prompt treatment.

Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention.

PubMed

Benamouzig, Robert; Uzzan, Bernard; Martin, Antoine; Deyra, Jacques; Little, Julian; Girard, Bernard; Chaussade, Stanislas

2010-05-01

Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas. To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo. Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied. COX-2 expression could be assessed in 219 adenomas from 136 128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with 16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial. Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.

Silent subtype 3 pituitary adenomas are not always silent and represent poorly differentiated monomorphous plurihormonal Pit-1 lineage adenomas.

PubMed

Mete, Ozgur; Gomez-Hernandez, Karen; Kucharczyk, Walter; Ridout, Rowena; Zadeh, Gelareh; Gentili, Fred; Ezzat, Shereen; Asa, Sylvia L

2016-02-01

Originally classified as a variant of silent corticotroph adenoma, silent subtype 3 adenomas are a distinct histologic variant of pituitary adenoma of unknown cytogenesis. We reviewed the clinical, biochemical, radiological, immunohistochemical and ultrastructural features of 31 silent subtype 3 adenomas to clarify their cellular origin. Among 25 with clinical and/or radiological data, all were macroadenomas; there was cavernous sinus invasion in 30% of cases and involvement of the clivus in 17% of cases. Almost 90% of patients were symptomatic; 67% had mass effect symptoms, 37% were hypogonadal and 8% had secondary adrenal insufficiency. Significant hormonal excess in 29% of cases included hyperthyroidism in 17%, acromegaly in 8% and hyperprolactinemia above 150 μg/l in 4%. Two individuals with hyperprolactinemia who were younger than 30 years had multiple endocrine neoplasia type 1. Immunohistochemically, all 31 tumors were diffusely positive for the pituitary lineage-specific transcription factor Pit-1. Although three only expressed Pit-1, others revealed variable positivity for one or more hormones of Pit-1 cell lineage (growth hormone, prolactin, thyroid-stimulating hormone), as well as alpha-subunit and estrogen receptor. Most tumors exhibited perinuclear reactivity for keratins with the CAM5.2 antibody; scattered fibrous bodies were noted in five (16%) tumors. The mean MIB-1 labeling index was 4% (range, 1-9%). Fourteen cases examined by electron microscopy were composed of a monomorphous population of large polygonal or elongated cells with nuclear spheridia. Sixty-five percent of patients had residual disease after surgery; after a mean follow-up of 48.4 months (median 41.5; range=2-171) disease progression was documented in 53% of those cases. These data identify silent subtype 3 adenomas as aggressive monomorphous plurihormonal adenomas of Pit-1 lineage that may be associated with hyperthyroidism, acromegaly or galactorrhea and amenorrhea. Our

Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

PubMed

Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

2017-08-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

ClinicalTrials.gov

2018-06-04

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

Individual polyp detection rate in routine daily endoscopy practice depends on case-mix.

PubMed

Loffeld, R J L F; Liberov, B; Dekkers, P E P

2015-07-01

The adenoma detection rate (ADR), a marker of endoscopic quality, is confounded by selection bias. It is not known what the ADR is in normal daily practice. To study the polyp detection rate (PDR) in different endoscopists in the course of years. All consecutive endoscopies of the colon done in 11 years were included. Endoscopies in the regular surveillance programme after polyp removal and after surgery because of colorectal cancer or diverticular disease were scored separately. The number of yearly procedures per endoscopist and presence of polyps, anastomoses, surveillance and cancer were noted. In the period of 11 years, 14,908 consecutive endoscopies of colon and rectum were done by four endoscopists. Two endoscopists had a significantly lower PDR than the other two (p < 0.001), these two had the longest careers in endoscopy. The two younger endoscopists did significantly less often procedures in patients with anastomoses and because of surveillance (p < 0.001, respectively). One endoscopist detected significantly less colorectal cancers than the other three endoscopists (p < 0.001). This study presents the PDR in normal routine daily endoscopy practice. It can be concluded that the PDR, implicating the ADR, in unselected patients can be lower in individual endoscopists than recommended in the literature. This highly depends on the case-mix of patients presented for endoscopy. This result debates the use of the ADR as quality indicator for individual endoscopists.

Noncirrhotic hepatocellular carcinoma: derivation from hepatocellular adenoma? Clinicopathologic analysis

PubMed Central

Liu, Ta-Chiang; Vachharajani, Neeta; Chapman, William C.; Brunt, Elizabeth M.

2018-01-01

The majority of hepatocellular carcinomas arise in background chronic liver disease, particularly cirrhosis. The pathogenesis of non-cirrhotic hepatocellular carcinomas remains unclear. While malignant transformation reportedly occurs in <15% of hepatocellular adenoma, the prevalence of noncirrhotic hepatocellular carcinomas arising from a pre-existing adenoma is a challenge to study. Cirrhotic hepatocellular carcinoma and hepatocellular adenoma may be subclassified by molecular pathways, but little is known in noncirrhotic hepatocellular carcinoma. We aim to delineate clinical, morphologic and immunohistochemical features of noncirrhotic hepatocellular carcinoma to evaluate for possible derivation from hepatocellular adenoma. We evaluated the clinicopathologic features of 74 noncirrhotic hepatocellular carcinomas from 72 patients for underlying clinical conditions and immunohistochemical markers known to be associated with hepatocellular adenoma. Men were more commonly affected (59%); however, in the < 50 year old group, women predominated (8:1). The age range was wide: 18year – 83year; median 64year. Underlying liver diseases were identified in only 7%; however 25% had diabetes mellitus, 69% were overweight or obese, and 58% had metabolic syndrome. Only 50% of the noncirrhotic hepatocellular carcinoma were encapsulated. As published in hepatocellular adenoma, multifocality and larger tumor size were more common in liver fatty acid binding protein-negative noncirrhotic hepatocellular carcinoma. Beta-catenin nuclear positivity was uncommon (5%), and was restricted to hepatocellular carcinomas in older men. Serum amyloid A positivity was not restricted to any subtype. In summary, we present the largest series to date examining noncirrhotic hepatocellular carcinoma. We evaluated these with current hepatocellular adenoma subclassification markers for possible associations. Thirty percent of the 74 noncirrhotic hepatocellular carcinoma had some clinical

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.

PubMed

Al-Ahwal, Mahmoud; Gomaa, Wafaey; Emam, Eman; Qari, Yousif; Buhmeida, Abdelbaset; Radwi, Salman; Al-Maghrabi, Basim; Al-Qahtani, Mohammad; Al-Maghrabi, Jaudah

2016-11-01

p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC). Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed. Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325). Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

[Clinical and endoscopic features of a selected population with serrated colorectal adenomas in a private clinic in Lima - Peru].

PubMed

Castillo, Ofelia; Barreda, Carlos; Recavarren, Sixto; Barriga, José A; Salazar M, Fernando; Yriberry, Simón; Barriga, Eduardo; Salazar C, Fernando

2013-01-01

To describe the clinical and endoscopic caracteristics of a population that has only serrated polyps of colon (mainly sessile serrated adenomas) in a private clinic in Lima, Perú, from 2009-2011. Retrospective study conducted at the endoscopy center of Clinic Ricardo Palma, Lima, Peru. Olympus colonoscope was used with high definition, including NBI (narrow band imaging) and electronic magnification. Patients had pathologic diagnosis of “polyps and / or colorectal serrated adenomas” and excluded those with synchronous tubular or villous adenomas. Images were evaluated by two endoscopists and then by a third gastroenterologist. We found 201 serrated polyps in 108 patients. Women were 60.2% and overweight predominated. Eighty (74.1%) had only one serrated adenoma and 23 (21.3%) with at least one synchronous hyperplastic polyp. The average size of sessile serrated adenomas was 5.12 mm (± 3.87 DS) and the flat type was 91 (58.7%). There were significant differences in the diameter of sessile serrated adenomas between the distal and proximal colon (4.47 mm ± 2.23 vs. 6.90 mm ± 6.25; p<0.000). The common features of sessile serrated adenomas were: White (31/36, 86.1%), smooth (28/36, 77.8%) and regular margins (26/36, 72.2%). There was a relationship between vascular pattern according NBI and serrated polyp histology (p=0.024). The endoscopic features of sessile serrated adenomas can evade detection to white light. NBI is a useful tool to define some features of these lesions.

Nonampullary duodenal adenoma: Current understanding of its diagnosis, pathogenesis, and clinical management

PubMed Central

Lim, Chul-Hyun; Cho, Young-Seok

2016-01-01

Nonampullary duodenal adenomas are relatively common in familial adenomatous polyposis (FAP), but nonampullary sporadic duodenal adenomas (SDAs) are rare. Emerging evidence shows that duodenal adenomas, regardless of their anatomic location and whether they are sporadic or FAP-related, share morphologic and molecular features with colorectal adenomas. The available data suggest that duodenal adenomas develop to duodenal adenocarcinomas via similar mechanisms. The optimal approach for management of duodenal adenomas remains to be determined. The techniques for endoscopic resection of duodenal adenoma include snare polypectomy, endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and argon plasma coagulation ablation. EMR may facilitate removal of large duodenal polyps. Although several studies have reported cases of successful ESD for duodenal adenomas, the procedure is technically difficult to perform safely because of the anatomical properties of the duodenum. Although current clinical practice recommends endoscopic resection of all large duodenal adenomas in patients with FAP, endoscopic treatment is usually insufficient to guarantee a polyp-free duodenum. Surgery is indicated for FAP patients with severe polyposis or nonampullary SDAs or FAP-related polyps not amenable to endoscopic resection. Further studies are needed to develop newer endoscopic techniques to guide diagnostic and therapeutic decisions for future management of nonampullary duodenal adenomas. PMID:26811631

A novel balloon colonoscope detects significantly more simulated polyps than a standard colonoscope in a colon model.

PubMed

Hasan, Nazia; Gross, Seth A; Gralnek, Ian M; Pochapin, Mark; Kiesslich, Ralf; Halpern, Zamir

2014-12-01

Although standard colonoscopy is considered the optimal test to detect adenomas, it can have a significant adenoma miss rate. A major contributing factor to high miss rates is the inability to visualize adenomas behind haustral folds and at anatomic flexures. To compare the diagnostic yield of balloon-assisted colonoscopy versus standard colonoscopy in the detection of simulated polyps in a colon model. Prospective, cohort study. International gastroenterology meeting. A colon model composed of elastic material, which mimics the flexible structure of haustral folds, allowing for dynamic responses to balloon inflation, with embedded simulated colon polyps (n = 12 silicone "polyps"). Fifty gastroenterologists were recruited to identify simulated colon polyps in a colon model, first using standard colonoscopy immediately followed by balloon-assisted colonoscopy. Detection of simulated polyps. The median polyp detection rate for all simulated polyps was significantly higher with balloon-assisted as compared with standard colonoscopy (91.7% vs 45.8%, respectively; P < .0001). The significantly higher simulated polyp detection rate with balloon-assisted versus standard colonoscopy was notable both for non-obscured polyps (100.0% vs 75.0%; P < .0001) and obscured polyps (88.0% vs 25.0%; P < .0001). Non-randomized design, use of a colon model, and simulated colon polyps. As compared with standard colonoscopy, balloon-assisted colonoscopy detected significantly more obscured and non-obscured simulated polyps in a colon model. Clinical studies in human participants are being pursued to further evaluate this new colonoscopic technology. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

PubMed

Khalid-de Bakker, Carolina A J; Jonkers, Daisy M A E; Sanduleanu, Silvia; de Bruïne, Adriaan P; Meijer, Gerrit A; Janssen, Jan B M J; van Engeland, Manon; Stockbrügger, Reinhold W; Masclee, Ad A M

2011-10-01

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

PubMed

Salman, Rida; Sebaaly, Mikhael G; Wehbe, Mohammad Rachad; Sfeir, Pierre; Khalife, Mohamad; Al-Kutoubi, Aghiad

2017-06-01

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salman, Rida; Sebaaly, Mikhael G.; Wehbe, Mohammad Rachad

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

TERT, HRAS, and EIF1AX Mutations in a Patient with Follicular Adenoma.

PubMed

Topf, Michael C; Wang, Zi-Xuan; Tuluc, Madalina; Pribitkin, Edmund A

2018-06-01

Molecular markers are increasingly used as diagnostic tools in the management of thyroid nodules. There is a paucity of studies evaluating the prevalence of molecular markers in benign lesions. A 68-year-old woman with hypothyroidism presented with a right thyroid nodule, which was atypia of undetermined significance on cytology. The fine-needle aspirate of the nodule was examined with next-generation sequencing and found to harbor a C228T mutation in the TERT gene, a Q61R mutation in the HRAS gene, and an A113_splice mutation in the EIF1AX gene. Right thyroid lobectomy was performed, with final pathology showing follicular adenoma. All three mutations detected in the original fine-needle aspirate specimen were detected in the final surgical specimen as well. A rare case of TERT, HRAS, and EIF1AX mutations is reported in a patient with follicular adenoma. TERT promoter mutations may be an early genetic event in the molecular pathogenesis of follicular thyroid carcinoma.

Fresh vs Frozen Samples and Ambient Temperature Have Little Effect on Detection of Colorectal Cancer or Adenomas by a Fecal Immunochemical Test in a Colorectal Cancer Screening Cohort in Germany.

PubMed

Chen, Hongda; Werner, Simone; Brenner, Hermann

2017-10-01

frozen samples were used (95% CI, 21.4%-35.1%) and 25.6% sensitivity when fresh samples were used (95% CI, 19.8%-32.1%). Specificity values were 97.7% when frozen samples were used (95% CI, 96.8%-98.4%) and 97.6% when fresh samples were used (95% CI, 96.7%-98.3%). We did not observe any differences in detection of neoplasms during different seasons that were based on outdoor temperature. In a prospective study of 3466 individuals who underwent screening colonoscopies and received FITs, we found that use of fresh vs frozen samples slightly affected positivity rates and the proportions of CRCs or adenomas detected at the recommended Hgb cutoff value. However, after we adjusted Hgb cutoff values to produce equal proportions of positive results for fresh vs frozen samples, the performance of the FIT was similar with each sample type. Season of sample collection (based on outdoor temperature) did not affect detection of CRC using either sample type in this study from Middle Europe. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

A randomised tandem colonoscopy trial of narrow band imaging versus white light examination to compare neoplasia miss rates.

PubMed

Kaltenbach, T; Friedland, S; Soetikno, R

2008-10-01

Colonoscopy, the "gold standard" screening test for colorectal cancer (CRC), has known diagnostic limitations. Advances in endoscope technology have focused on improving mucosal visualisation. In addition to increased angle of view and resolution features, recent colonoscopes have non-white-light optics, such as narrow band imaging (NBI), to enhance image contrast. We aimed to study the neoplasia diagnostic characteristics of NBI, by comparing the neoplasm miss rate when the colonoscopy was performed under NBI versus white light (WL). Randomised controlled trial. US Veterans hospital. Elective colonoscopy adults. We randomly assigned patients to undergo a colonoscopic examination using NBI or WL. All patients underwent a second examination using WL, as the reference standard. The primary end point was the difference in the neoplasm miss rate, and secondary outcome was the neoplasm detection rate. In 276 tandem colonoscopy patients, there was no significant difference of miss or detection rates between NBI or WL colonoscopy techniques. Of the 135 patients in the NBI group, 17 patients (12.6%; 95% confidence interval (CI) 7.5 to 19.4%) had a missed neoplasm, as compared with 17 of the 141 patients (12.1%; 95% CI 7.2 to 18.6%) in the WL group, with a miss rate risk difference of 0.5% (95% CI -7.2 to 8.3). 130 patients (47%) had at least one neoplasm. Missed lesions with NBI showed similar characteristics to those missed with WL. All missed neoplasms were tubular adenomas, the majority (78%) was < or = 5 mm and none were larger than 1 cm (one-sided 95% CI up to 1%). Nonpolypoid lesions represented 35% (13/37) of missed neoplasms. NBI did not improve the colorectal neoplasm miss rate compared to WL; the miss rate for advanced adenomas was less than 1% and for all adenomas was 12%. The neoplasm detection rates were similar high using NBI or WL; almost a half the study patients had at least one adenoma. Clinicaltrials.gov identifier: NCT00628147.

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

Clinical and histopathological features of adenomas of the ciliary pigment epithelium.

PubMed

Chang, Ying; Wei, Wen Bin; Shi, Ji Tong; Xian, Jun Fang; Yang, Wen Li; Xu, Xiao Lin; Bai, Hai Xia; Li, Bin; Jonas, Jost B

2016-11-01

Adenomas of the ciliary pigment epithelium (CPE) are rare benign tumours which have mainly to be differentiated from malignant ciliary body melanomas. Here we report on a consecutive series of patients with CPE adenomas and describe their characteristics. The retrospective hospital-based case series study included all patients who were consecutively operated for CPE adenomas. Of the 110 patients treated for ciliary body tumours, five patients (4.5%) had a CPE adenoma. Mean age was 59.0 ± 9.9 years (range: 46-72 years). Mean tumour apical thickness was 6.6 ± 1.7 mm. Tumour colour was mostly homogenously brown to black, and the tumour surface was smooth. The tumour masses pushed the iris tissue forward without infiltrating iris or anterior chamber angle. Sonography revealed an irregular echogram with sharp lesion borders and signs of blood flow in Color Doppler flow imaging. Ultrasonographic biomicroscopy demonstrated medium-low internal reflectivity and acoustic attenuation. In magnetic resonance imaging (MRI), the tumours as compared to brain were hyperintense on T1-weighted images and hypointense on T2-weighted images. Tumour tissue consisted of cords and nests of pigment epithelium cells separated by septa of vascularized fibrous connective tissue, leading to a pseudo-glandular appearance. The melanin granules in the cytoplasm were large and mostly spherical in shape. In four patients, the tumours were hyperpigmented. Tumour cells were large with round or oval nuclei and clearly detectable nucleoli. These clinical characteristics of CPE adenomas, such as homogenous dark brown colour, smooth surface, iris dislocation and anterior chamber angle narrowing but no iris infiltration, segmental cataract, pigment dispersion, and, as compared to brain tissue, hypointensity and, as compared to extraocular muscles or lacrimal gland, hyperintensity on T2-weighted MRI images, may be helpful for the differentiation from ciliary body malignant melanomas. © 2016 Acta

Pleomorphic adenoma of the palate in a child.

PubMed

Bovino, Brian F; Sohn, Andy; Winston, Daniel

2013-01-01

Presented is a pleomorphic adenoma of the palate in a 12-year-old boy. Pleomorphic adenoma is usually found in adults and is rarely found in patients under 20 years of age. We present initial exam, diagnosis, treatment and a review of literature.

The risks of overlooking the diagnosis of secreting pituitary adenomas.

PubMed

Brue, Thierry; Castinetti, Frederic

2016-10-06

Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow-growing tumours. The rarity of these conditions means that their diagnosis is not familiar to most non-specialist physicians. Consequently, pituitary adenomas may be overlooked and remain untreated, and affected individuals may develop serious comorbidities that reduce their quality of life and life expectancy. Because many signs and symptoms of pituitary adenomas overlap with those of other, more common disorders, general practitioners and non-endocrinology specialists need to be aware of the "red flags" suggestive of these conditions. A long duration of active disease in patients with secreting pituitary adenomas is associated with an increased risk of comorbidities and reduced quality of life. Appropriate treatment can lead to disease remission, and, although some symptoms may persist in some patients, treatment usually reduces the incidence and severity of comorbidities and improves quality of life. Therefore, correct, early diagnosis and characterization of a pituitary adenoma is crucial for patients, to trigger timely, appropriate treatment and to optimize outcome. This article provides an overview of the epidemiology of hormonal syndromes associated with pituitary adenomas, discusses the difficulties of and considerations for their diagnosis, and reviews the comorbidities that may develop, but can be prevented, by accurate diagnosis and appropriate treatment. We hope this review will help general practitioners and non-endocrinology specialists to suspect secreting pituitary adenomas and refer patients to an endocrinologist for confirmation of the diagnosis and treatment.

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland

PubMed Central

Matsuda, Eriko; Fukuhara, Takahiro; Donishi, Ryohei; Kawamoto, Katsuyuki; Hirooka, Yasuaki; Takeuchi, Hiromi

2018-01-01

Background Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. Methods We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. Results While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. Conclusion Our novel classification system based on anechoic area patterns demonstrated by the tumors had high

Usefulness of a Novel Ultrasonographic Classification Based on Anechoic Area Patterns for Differentiating Warthin Tumors from Pleomorphic Adenomas of the Parotid Gland.

PubMed

Matsuda, Eriko; Fukuhara, Takahiro; Donishi, Ryohei; Kawamoto, Katsuyuki; Hirooka, Yasuaki; Takeuchi, Hiromi

2017-12-01

Ultrasonographic homogeneity is an important differential finding between Warthin tumor and pleomorphic adenoma, two types of benign parotid gland tumors, with the former likely to be heterogeneous and the latter homogeneous. However, differences in the performance of ultrasound machines or the homogeneity cut-off level affect the judgment of ultrasonographic homogeneity. Therefore, in this study, we adopted a novel system for classifying the composition of tumors via ultrasonography, using anechoic area as a substitute for differences in homogeneity to differentiate between Warthin tumors and pleomorphic adenomas. We evaluated 68 tumors that were histopathologically diagnosed as Warthin tumor or pleomorphic adenoma between July 2009 and November 2015. Ultrasonographic images of the tumors were evaluated on the basis of key differentiating features, including features on B-mode imaging and color Doppler imaging. Additionally, the tumors were classified into four groups based on anechoic area, and findings were compared between Warthin tumors and pleomorphic adenomas. While 38 of the tumors were pleomorphic adenomas, 30 were Warthin tumors. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for detection of Warthin tumors using our novel classification system were 73.3%, 76.3%, 71.0%, 78.4% and 75.0%, respectively. Compared to pleomorphic adenomas, Warthin tumors showed large or sponge-like anechoic areas, rich vascularization and an oval shape even at large tumor sizes, and the difference was significant. On defining Warthin tumor as a tumor demonstrating two or more of the findings noted above, the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for its detection were 73.3%, 84.2%, 78.6%, 80.0% and 79.4%, respectively. Our novel classification system based on anechoic area patterns demonstrated by the tumors had high sensitivity, specificity and

Serrated adenoma of the gallbladder: a case report.

PubMed

Rubio, Carlos A

2015-06-01

A case of serrated adenomatous polyp found in a cholecystectomy specimen is reported. The adenoma was built with mucosal crypts exhibiting unlocked serrations lined with up to high-grade dysplastic cells. A desmoplastic sclerotic tissue having multiple stromal hubs with branched thin spokes replaced the subjacent lamina propia, muscularis mucosae, and submucosa. The generous serrated configurations covering a multi-branched sclerotic stroma, gave the adenoma a papillary appearance. Review of the literature indicates that this appears to be the first reported case of serrated adenoma of the gallbladder. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Epidemiology, clinical presentation and diagnosis of non-functioning pituitary adenomas.

PubMed

Ntali, Georgia; Wass, John A

2018-04-01

Non-functioning pituitary adenomas (NFPAs) are benign pituitary neoplasms that do not cause a hormonal hypersecretory syndrome. An improved understanding of their epidemiology, clinical presentation and diagnosis is needed. A literature review was performed using Pubmed to identify research reports and clinical case series on NFPAs. They account for 14-54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population. Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from being completely asymptomatic to causing significant hypothalamic/pituitary dysfunction and visual field compromise due to their large size. Most patients present with symptoms of mass effect, such as headaches, visual field defects, ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning pituitary incidentalomas are found on brain imaging performed for an unrelated reason. Diagnostic approach includes magnetic resonance imaging of the sellar region, laboratory evaluations, screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. This article reviews the epidemiology, clinical behaviour and diagnostic approach of non-functioning pituitary adenomas.

Sedentary behavior is associated with colorectal adenoma recurrence in men

PubMed Central

Molmenti, Christine L. Sardo; Hibler, Elizabeth A.; Ashbeck, Erin L.; Thomson, Cynthia A.; Garcia, David O.; Roe, Denise; Harris, Robin B.; Lance, Peter; Cisneroz, Martin; Martinez, Maria Elena; Thompson, Patricia A.; Jacobs, Elizabeth T.

2014-01-01

Purpose The association between physical activity and colorectal adenoma is equivocal. This study was designed to assess the relationship between physical activity and colorectal adenoma recurrence. Methods Pooled analyses from two randomized, controlled trials included 1,730 participants who completed the Arizona Activity Frequency Questionnaire at baseline, had a colorectal adenoma removed within 6 months of study registration, and had a follow-up colonoscopy during the trial. Logistic regression modeling was employed to estimate the effect of sedentary behavior, light-intensity physical activity, and moderate-vigorous physical activity on colorectal adenoma recurrence. Results No statistically significant trends were found for any activity type and odds of colorectal adenoma recurrence in the pooled population. However, males with the highest levels of sedentary time experienced 47% higher odds of adenoma recurrence. Compared to the lowest quartile of sedentary time, the ORs (95% CIs) for the second, third, and fourth quartiles among men were 1.23 (0.88, 1.74), 1.41 (0.99, 2.01), and 1.47 (1.03, 2.11) respectively (P trend=0.03). No similar association was observed for women. Conclusions This study suggests that sedentary behavior is associated with a higher risk of colorectal adenoma recurrence among men, providing evidence of detrimental effects of a sedentary lifestyle early in the carcinogenesis pathway. PMID:25060482

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease.

PubMed

Hayashi, Kyohei; Inoshita, Naoko; Kawaguchi, Kohei; Ibrahim Ardisasmita, Arif; Suzuki, Hisanori; Fukuhara, Noriaki; Okada, Mitsuo; Nishioka, Hiroshi; Takeuchi, Yasuhiro; Komada, Masayuki; Takeshita, Akira; Yamada, Shozo

2016-02-01

Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one- to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion. Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD. USP8 mutations as well as clinicopathological characteristics were examined in 60 corticotroph adenomas including 15 Crooke's cell adenomas (CCAs), a rare histological variant presenting with generally aggressive behavior, using qRT-PCR and/or immunohistochemistry. USP8 mutations were exclusively detected in women, except for one case, with a prevalence of 42.2% in non-CCA and 13.3% in CCA (overall 35%). Clinically well-behaved presentations including microadenoma and curative resection were more common in mutated cases. The expression of EGFR was not associated with the mutation status. In contrast, mutated tumors expressed significantly higher levels of POMC, SSTR5, and MGMT. Microadenomas that strongly express POMC were common among mutated tumors, which may lead to the mechanisms by which very small adenomas secrete excess ACTH to present overt CD. While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR-mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5. In contrast, non-mutated aggressive tumors such as CCA may respond better to the alkylating agent temozolomide because of their significantly weak expression of MGMT. © 2016 European Society of Endocrinology.

Immunophenotype of nipple adenoma in a male patient.

PubMed

Fernandez-Flores, Angel; Suarez-Peñaranda, Jose-Manuel

2011-03-01

Adenoma of the nipple is rare in men. It must be distinguished from a breast carcinoma and from Paget disease. In this sense, immunohistochemistry can be of some help. In women, for instance, immunoexpression of c-erbB-2 favors a diagnosis of Paget disease, according to some studies. Nevertheless, we have not found any studies on HER2/neu status, estrogen receptors, or progesterone receptors in nipple adenoma of male patients. We present a case of an adenoma of the nipple in a 21-year-old man in which we carried out a wide immunohistochemical study. The lesion did not express estrogen receptors, progesterone receptors, or androgen receptors. The HercepTest was negative. Smooth muscle Actin and p63 were remarked in the basal layer of the tumoral tubules, supporting the benignancy of the lesion. This case of adenoma of the nipple in a male shows an immunophenotype that is similar to the ones reported in female patients.

Spontaneous remission of acromegaly or gigantism due to subclinical apoplexy of pituitary growth hormone adenoma.

PubMed

Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming

2011-11-01

Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.

Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.

PubMed

Paradis, Valerie; Benzekri, Asmae; Dargère, Delphine; Bièche, Ivan; Laurendeau, Ingrid; Vilgrain, Valerie; Belghiti, Jacques; Vidaud, Michel; Degott, Claude; Bedossa, Pierre

2004-05-01

"Telangiectatic focal nodular hyperplasia" designate atypical lesions considered as variants of focal nodular hyperplasia (FNH). However, because "telangiectatic FNH" share several morphologic patterns with hepatocellular adenomas, classification of such lesions deserve further clarification. Therefore, the aim of the present study was to reconsider the classification of telangiectatic FNH with the help of a molecular approach. Ten telangiectatic FNH, 6 typical FNH, and 6 hepatocellular adenomas were studied. DNA, RNA, and protein from each lesion were extracted. Clonality was assessed by the study of the X chromosome inactivation pattern (HUMARA assay). Angiopoietin (ANGPT-1 and ANGPT-2) mRNA, genes the expression of which is typically modified in FNH, were quantified by a real-time RT-PCR procedure. Protein profiles were analyzed by SELDI-TOF PROTEINCHIP (Cyphergen Biosystem, Inc., Fremont, CA) technology. Although all informative cases of FNH (5 of 6) and hepatocellular adenomas (6 of 6) were polyclonal and monoclonal, respectively, clonal analysis showed a nonrandom pattern of X chromosome inactivation consistent with a monoclonal lesion in 6 of 8 cases of telangiectatic FNH. The mean value of the ANGPT-1/ANGPT-2 mRNA ratio was 21.4 in FNH, 2.6 in adenomas, and 2.1 in telangiectatic FNH (P adenomas. These results show that telangiectatic FNH display a molecular pattern closer to that of hepatocellular adenomas than to FNH and suggest that these lesions should instead be referred to as "telangiectatic hepatocellular adenomas."

Pathology of the human pituitary adenomas

PubMed Central

Kajiya, Hanako; Takei, Mao; Egashira, Noboru; Tobita, Maya; Takekoshi, Susumu; Teramoto, Akira

2008-01-01

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology. PMID:18688636

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

Nipple adenoma arising from axillary accessory breast: a case report

PubMed Central

2012-01-01

Nipple adenoma is a relatively rare benign breast neoplasm, and cases of the disease arising from the axillary accessory breast have very seldom been reported in the English literature. We report a case of nipple adenoma arising from axillary accessory breast including clinical and pathological findings. An 82-year-old woman presented with the complaint of a small painful mass in the right axilla. Physical examination confirmed a well-defined eczematous crusted mass that was 8 mm in size. The diagnosis of nipple adenoma was made from an excisional specimen on the basis of characteristic histological findings. Microscopic structural features included a compact proliferation of small tubules lined by epithelial and myoepithelial cells, and the merging of glandular epithelial cells of the adenoma into squamous epithelial cells in the superficial epidermal layer. Because clinically nipple adenoma may resemble Paget’s disease and pathologically can be misinterpreted as tubular carcinoma, the correct identification of nipple adenoma is an important factor in the differential diagnosis for axillary tumor neoplasms. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1186821489769063 PMID:23186145

Estimation of Recurrence of Colorectal Adenomas with Dependent Censoring Using Weighted Logistic Regression

PubMed Central

Hsu, Chiu-Hsieh; Li, Yisheng; Long, Qi; Zhao, Qiuhong; Lance, Peter

2011-01-01

In colorectal polyp prevention trials, estimation of the rate of recurrence of adenomas at the end of the trial may be complicated by dependent censoring, that is, time to follow-up colonoscopy and dropout may be dependent on time to recurrence. Assuming that the auxiliary variables capture the dependence between recurrence and censoring times, we propose to fit two working models with the auxiliary variables as covariates to define risk groups and then extend an existing weighted logistic regression method for independent censoring to each risk group to accommodate potential dependent censoring. In a simulation study, we show that the proposed method results in both a gain in efficiency and reduction in bias for estimating the recurrence rate. We illustrate the methodology by analyzing a recurrent adenoma dataset from a colorectal polyp prevention trial. PMID:22065985

A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas.

PubMed

Casar-Borota, Olivera; Øystese, Kristin Astrid Berland; Sundström, Magnus; Melchior, Linea; Popovic, Vera

2016-08-01

Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas. We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses. In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses. IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.

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.

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study).

PubMed

van den Broek, Frank J C; de Graaf, Eelco J R; Dijkgraaf, Marcel G W; Reitsma, Johannes B; Haringsma, Jelle; Timmer, Robin; Weusten, Bas L A M; Gerhards, Michael F; Consten, Esther C J; Schwartz, Matthijs P; Boom, Maarten J; Derksen, Erik J; Bijnen, A Bart; Davids, Paul H P; Hoff, Christiaan; van Dullemen, Hendrik M; Heine, G Dimitri N; van der Linde, Klaas; Jansen, Jeroen M; Mallant-Hent, Rosalie C H; Breumelhof, Ronald; Geldof, Han; Hardwick, James C H; Doornebosch, Pascal G; Depla, Annekatrien C T M; Ernst, Miranda F; van Munster, Ivo P; de Hingh, Ignace H J T; Schoon, Erik J; Bemelman, Willem A; Fockens, Paul; Dekker, Evelien

2009-03-13

Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma > or = 3 cm, located between 1-15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10

K-ras mutations and HLA-DR expression in large bowel adenomas.

PubMed Central

Norheim Andersen, S.; Breivik, J.; Løvig, T.; Meling, G. I.; Gaudernack, G.; Clausen, O. P.; Schjölberg, A.; Fausa, O.; Langmark, F.; Lund, E.; Rognum, T. O.

1996-01-01

A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although two-way analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P = 0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:8679466

Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma.

PubMed

Müssig, K; Gallwitz, B; Honegger, J; Strasburger, C J; Bidlingmaier, M; Machicao, F; Bornemann, A; Ranke, M B; Häring, H-U; Petersenn, S

2007-03-01

Gigantism is rare with the majority of cases caused by a growth hormone (GH)-secreting pituitary adenoma. Treatment options for GH-secreting pituitary adenomas have been widened with the availability of long-acting dopamine agonists, depot preparations of somatostatin analogues, and recently the GH receptor antagonist pegvisomant. A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance. Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment.

G protein abnormalities in pituitary adenomas.

PubMed

Spada, A; Lania, A; Ballarè, E

1998-07-25

It has been demonstrated that the majority of secreting and nonsecreting adenomas is monoclonal in origin suggesting that these neoplasia arise from the replication of a single mutated cell, in which growth advantage results from either activation of protooncogenes or inactivation of antioncogenes. Although a large number of genes has been screened for mutations, only few genetic abnormalities have been found in pituitary tumors such as allelic deletion of chromosome 11q13 where the MEN-1 gene has been localised, and mutations in the gene encoding the alpha subunit of the stimulatory Gs and Gi2 protein. These mutations constitutively activate the alpha subunit of the Gs and Gi2 protein by inhibiting their intrinsic GTPase activity. Both Gs alpha and Gi2alpha can be considered products of protooncogenes (gsp and gip2, respectively) since gain of function mutations that activate mitogenic signals have been recognized in human tumors. Gsp oncogene is found in 30-40% of GH-secreting adenomas, in a low percentage of nonfunctioning and ACTH-secreting pituitary adenomas, in toxic thyroid adenomas and differentiated thyroid carcinomas. The same mutations, occurred early in embriogenesis, have been also identified in tissues from patients affected with the McCune Albright syndrome. These mutations result in an increased cAMP production and in the subsequent overactivation of specific pathways involved in both cell growth and specific programmes of cell differentiation. By consequence, the endocrine tumors expressing gsp oncogene retain differentiated functions. The gip2 oncogene has been identified in about 10% of nonfunctioning pituitary adenomas, in tumors of the ovary and the adrenal cortex. However, it remains to be established whether Gi proteins activate mitogenic signals in pituitary cells. Since Gi proteins are involved in mediating the effect of inhibitory neurohormones on intracellular effectors, it has been proposed that in pituitary tumors the low expression of

Glucose Intolerance, Plasma Insulin Levels, and Colon Adenomas in Japanese Men

PubMed Central

Kono, Suminori; Abe, Hiroshi; Eguchi, Hiroyuki; Shimazaki, Kae; Hatano, Ben; Hamada, Hiroaki

2001-01-01

Hyperinsulinemia may be related to colon carcinogenesis. Several studies have suggested that diabetes mellitus is related to increased risk of colon cancer. We examined cross‐sectionally the relation of fasting plasma insulin levels and glucose tolerance status to colon adenomas. In a consecutive series of 951 men undergoing total colonoscopy for a health examination at the Japan Self Defense Forces Fukuoka Hospital from April 1998 to August 1999, we identified 233 cases of colon adenomas and 497 controls with normal colonoscopy. Glucose tolerance status was determined by a 75‐g oral glucose tolerance test, and subjects were classified as normal, unpaired glucose tolerance (IGT) or non‐insulin dependent diabetes mellitus (NIDDM). Plasma insulin levels were measured after subjects had fasted overnight. Logistic regression analysis and analysis of covariance was used to control for age and obesity. While plasma insulin levels were unrelated to colon adenomas, NIDDM was associated with a significantly increased risk of colon adenomas. There was no association between IGT and colon adenomas. NIDDM was more strongly associated with proximal colon adenomas. The findings suggest that long‐term hyperinsulinemic status associated with NIDDM may increase the risk of colon adenomas, and subsequently of colon cancer. PMID:11509114

Gut microbiome development along the colorectal adenoma-carcinoma sequence.

PubMed

Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

2015-03-11

Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy.

PubMed

Joshi, Bishnu P; Dai, Zhenzhen; Gao, Zhenghong; Lee, Jeong Hoon; Ghimire, Navin; Chen, Jing; Prabhu, Anoop; Wamsteker, Erik J; Kwon, Richard S; Elta, Grace H; Stoffel, Elena M; Pant, Asha; Kaltenbach, Tonya; Soetikno, Roy M; Appelman, Henry D; Kuick, Rork; Turgeon, D Kim; Wang, Thomas D

2017-04-01

Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients. We used phage display to identify a peptide that binds specifically to SSAs, using subtractive hybridization with HT29 colorectal cancer cells containing the V600E mutation in BRAF and Hs738.St/Int cells as a control. Binding of fluorescently labeled peptide to colorectal cancer cells was evaluated with confocal fluorescence microscopy. Rats received intra-colonic 0.0086 mg/kg, 0.026 mg/kg, or 0.86 mg/kg peptide or vehicle and morbidity, mortality, and injury were monitored twice daily to assess toxicity. In the clinical safety study, fluorescently labeled peptide was topically administered, using a spray catheter, to the proximal colon of 25 subjects undergoing routine outpatient colonoscopies (3 subjects were given 2.25 μmol/L and 22 patients were given 76.4 μmol/L). We performed blood cell count, chemistry, liver function, and urine analyses approximately 24 hours after peptide administration. In the clinical imaging study, 38 subjects undergoing routine outpatient colonoscopies, at high risk for colorectal cancer, or with a suspected unresected proximal colonic polyp, were first evaluated by white-light endoscopy to identify suspicious regions. The fluorescently labeled peptide (76.4 μmol/L) was administered topically to proximal colon, unbound peptide was washed away, and white-light, reflectance, and fluorescence videos were recorded digitally. Fluorescence intensities of SSAs were compared with those of normal colonic mucosa. Endoscopists resected identified lesions, which were analyzed histologically by gastrointestinal pathologists (reference standard). We also analyzed the ability of the peptide to identify SSAs vs

Relationship of Diet to Small and Large Adenomas of the Sigmoid Colon

PubMed Central

Imanishi, Koji; Shinchi, Koichi; Yanai, Fumio

1993-01-01

The relation of dietary factors to the risk of adenomas of the sigmoid colon was examined in men receiving a retirement health examination at the Self‐Defense Forces Fukuoka Hospital between October 1986 and 1990. A total of 187 adenoma cases and 1557 controls with normal colonoscopy were identified in the series. Cases were further classified into small‐adenoma (<5 mm, n=78) and large‐adenoma (≥5 mm, n=67) groups. The consumptions of selected foods and beverages were ascertained before colonoscopy by means of a self‐administered questionnaire. After adjustment for smoking, alcohol use, rank and body mass index, low rice consumption and high meat intake were independently associated with an increased risk of large adenomas. The risk of small adenomas was not related to either rice consumption or meat intake. Adjusted odds ratios of large adenomas for the low, intermediate and high consumption levels of rice were estimated to be 1.0 (referent), 0.83 and 0.43, respectively (trend P= 0.08), and the corresponding figures for meat consumption were 1.0 (referent), 1.58 and 2.38, respectively (trend P=0.02). The findings suggest that low rice consumption and high meat intake may promote the growth of colon adenomas, thereby increasing the risk of colon cancer. PMID:8449821

Unmetabolized Folic Acid, Tetrahydrofolate, and Colorectal Adenoma Risk.

PubMed

Rees, Judy R; Morris, Carolyn B; Peacock, Janet L; Ueland, Per M; Barry, Elizabeth L; McKeown-Eyssen, Gail E; Figueiredo, Jane C; Snover, Dale C; Baron, John A

2017-08-01

In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF ( P linear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend ( P linear trend =0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants ( P linear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451-8. ©2017 AACR . ©2017 American Association for Cancer Research.

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

Rotating night shift work, sleep, and colorectal adenoma in women.

PubMed

Devore, Elizabeth E; Massa, Jennifer; Papantoniou, Kyriaki; Schernhammer, Eva S; Wu, Kana; Zhang, Xuehong; Willett, Walter C; Fuchs, Charles S; Chan, Andrew T; Ogino, Shuji; Giovannucci, Edward; Wei, Esther K

2017-07-01

This study aims to investigate the associations of rotating night shift work history and sleep duration with risk of colorectal adenoma. We evaluated 56,275 cancer-free participants of the Nurses' Health Study II, who had their first colonoscopy or sigmoidoscopy between 1991 and 2011; rotating night shift work and sleep duration were reported by mailed questionnaire. Multivariable-adjusted logistic regression was used to estimate relative risks (RR) of colorectal adenoma, with 95% confidence intervals (CI), across categories of rotating night shift work history (none, 1-4, 5-9, and ≥10 years) and sleep duration (≤5, 6, 7, 8, and ≥9 h/day). We found no association between duration of rotating night shift work and occurrence of colorectal adenoma (p-trend across shift work categories = 0.5). Women with the longest durations of rotating night shift work (≥10 years) had a similar risk of adenoma compared to women without a history of rotating night shift work (multivariable-adjusted RR = 0.96, 95% CI = 0.83-1.11). Similarly, there were no associations of shorter or longer sleep durations with adenoma risk (p-trend = 0.2 across sleep durations of ≤5 through 7 h/day and p-trend = 0.5 across sleep durations of 7 through ≥9 h/day). Results were similar when we examined associations according to adenoma location and subtype. Our results do not support an association between rotating night shift work or sleep duration and risk of colorectal adenoma in women.

High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial

PubMed Central

Lanza, Elaine; Hartman, Terryl J.; Albert, Paul S.; Shields, Rusty; Slattery, Martha; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Schatzkin, Arthur

2006-01-01

Adequate fruit and vegetable intake was suggested to protect against colorectal cancer and colorectal adenomas; however, several recent prospective studies reported no association. We examined the association between fruits and vegetables and adenomatous polyp recurrence in the Polyp Prevention Trial (PPT). The PPT was a low-fat, high-fiber, high-fruit, and vegetable dietary intervention trial of adenoma recurrence, in which there were no differences in the rate of adenoma recurrence in participants in the intervention and control arms of the trial. In this analysis of the entire PPT trial–based cohort, multiple logistic regression analysis was used to estimate the odds ratio (OR) of advanced and nonadvanced adenoma recurrence within quartiles of baseline and change (baseline minus the mean over 3 y) in fruit and vegetable intake, after adjustment for age, total energyy intake, use of nonsteroidal anti-inflammatory drugs, BMI, and gender. There were no significant associations between nonadvanced adenoma recurrence and overall change in fruit and vegetable consumption; however, those in the highest quartile of change in dry bean intake (greatest increase) compared with those in the lowest had a significantly reduced OR for advanced adenoma recurrence (OR = 0.35; 95% CI, 0.18–0.69; P for trend = 0.001). The median in the highest quartile of change in dry bean intake was 370% higher than the baseline intake. The PPT trial–based cohort provides evidence that dry beans may be inversely associated with advanced adenoma recurrence. PMID:16772456

Giant pituitary adenoma: histological types, clinical features and therapeutic approaches.

PubMed

Iglesias, Pedro; Rodríguez Berrocal, Víctor; Díez, Juan José

2018-06-16

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors. They are mostly clinically non-functioning adenomas and occur predominantly in males. The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarism. Functioning adenomas give rise to specific symptoms of hormonal hypersecretion. The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients. Neurosurgical treatment, either through transsphenoidal or transcranial surgery, continues to be the treatment of choice in the majority of patients with giant pituitary adenomas. The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients.

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

PubMed

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-05-14

To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). Our results suggest a modest chemopreventive

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials

PubMed Central

Bonovas, Stefanos; Fiorino, Gionata; Lytras, Theodore; Malesci, Alberto; Danese, Silvio

2016-01-01

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or “high-risk” adenomas), and rated each trial’s risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our

Nephrogenic adenoma of the urinary bladder: a report of three cases and a review of the literature.

PubMed

Kuzaka, Bolesław; Pudełko, Paweł; Powała, Agnieszka; Górnicka, Barbara; Radziszewski, Piotr

2014-04-01

Nephrogenic adenoma (NA) is a rare, benign disease of the urinary tract, usually as a response to chronic irritation or trauma. Its diagnosis, staging, and treatment are not well established. We report on 3 cases of nephrogenic adenoma of the urinary bladder treated in our hospital between February 2011 and December 2012 to assess our experience and clinical outcome updating and reviewing the literature concerning this issue. All patients had undergone previous open urosurgery. Two patients had kidney transplantation. Gross hematuria and microhematuria were found in 2 patients. One patient had recurrent urinary tract infection. One patient had NA associated with transitional cell carcinoma (TCC). Recurrent nephrogenic adenomas were diagnosed in 2 patients (time to disease relapse was 5 and 9 months). All nephrogenic adenomas and recurrent tumors were treated with transurethral resection. Although NA is a benign metaplastic lesion of the urothelium, its recurrence rate is relatively high, thus careful and regular follow-up is necessary. Endoscopic characteristics of NA are not specific and a definite diagnosis must be made after histological analysis of resected specimens.

Thyroid Adenomas After Solid Cancer in Childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine

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 receivedmore » 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.« less

Gaze patterns hold key to unlocking successful search strategies and increasing polyp detection rate in colonoscopy.

PubMed

Lami, Mariam; Singh, Harsimrat; Dilley, James H; Ashraf, Hajra; Edmondon, Matthew; Orihuela-Espina, Felipe; Hoare, Jonathan; Darzi, Ara; Sodergren, Mikael H

2018-02-07

The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR. 18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses - screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis. Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P  = 0.02; anatomy: r = 0.62, P  < 0.01). Fixation distribution to the "bottom U" of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P  = 0.01). HMM demarcated the VGPs into three PDR groups. This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment. © Georg Thieme Verlag KG Stuttgart · New York.

The frequency of early colorectal cancer derived from sessile serrated adenoma/polyps among 1858 serrated polyps from a single institution.

PubMed

Chino, A; Yamamoto, N; Kato, Y; Morishige, K; Ishikawa, H; Kishihara, T; Fujisaki, J; Ishikawa, Y; Tamegai, Y; Igarashi, M

2016-02-01

Sessile serrated adenoma/polyps (SSAPs) are suspected to have a high malignant potential, although few reports have evaluated the incidence of carcinomas derived from SSAPs using the new classification for serrated polyps (SPs). The aim of study was to compare the frequency of cancer coexisting with the various SP subtypes including mixed polyps (MIXs) and conventional adenomas (CADs). A total of 18,667 CADs were identified between April 2005 and December 2011, and 1858 SPs (re-classified as SSAP, hyperplastic polyp (HP), traditional serrated adenoma (TSA), or MIX) were removed via snare polypectomy, endoscopic mucosal resection, or endoscopic sub-mucosal dissection. Among 1160 HP lesions, 1 (0.1%) coexisting sub-mucosal invasive carcinoma (T1) was detected. Among 430 SSAP lesions, 3 (0.7%) high-grade dysplasia (HGD/Tis) and 1 (0.2%) T1 were detected. All of the lesions were detected in the proximal colon, with a mean tumor diameter of 18 mm (SD 9 mm). Among 212 TSA lesions, 3 (1%) HGD/Tis were detected but no T1 cancer. Among 56 MIX lesions, 9 (16%) HGD/Tis and 1 (2%) T1 cancers were detected, and among 18,677 CAD lesions, 964 (5%) HGD/Tis and 166 (1%) T1 cancers were identified. Among the resected lesions that were detected during endoscopic examination, a smaller proportion (1%) of SSAPs harbored HGD or coexisting cancer, compared to CAD or MIX lesions. Therefore, more attention should be paid to accurately identifying lesions endoscopically for intentional resection and the surveillance of each SP subtype.

Prevalence of any size adenomas and advanced adenomas in 40- to 49-year-old individuals undergoing screening colonoscopy because of a family history of colorectal carcinoma in a first-degree relative.

PubMed

Gupta, Akshay K; Samadder, Jewel; Elliott, Eric; Sethi, Saurabh; Schoenfeld, Philip

2011-07-01

Per current guidelines, patients with a first-degree relative (FDR) with colorectal cancer (CRC) should get screened at least at age 40. Data about the prevalence of adenomas and advanced adenomas (AAs) in these patients are lacking. To examine the prevalence of adenomas and AAs in 40- to 49-year-old individuals undergoing screening colonoscopy for family history of CRC. Retrospective chart review. Asymptomatic patients 40 to 49 years of age undergoing their first screening colonoscopy at the University of Michigan during the period 1999 to 2009 because of an FDR with CRC. Prevalence of adenomas (any size), AAs, and risk factors associated with adenomas. Among 640 study patients, the prevalence of adenomas (any size) was 15.4% and 3.3% for AAs. Adenoma prevalence was lower if the FDR with CRC was younger than 60 years of age versus an FDR with CRC older than 60 years of age (12.4% vs 19%, P = .034). Male sex (odds ratio 2.6; 95% CI, 1.06-4.4) and advancing age (odds ratio 1.16; 95% CI, 1.03-1.31) were associated with adenomas. Limited data on risk factor exposure and insufficient sample size to assess risk factors for AAs. Among 40- to 49-year-old patients undergoing screening colonoscopy because of an FDR with CRC, the prevalence of adenomas and AAs is low. Further research should determine whether these individuals have a higher prevalence of adenomas compared with average-risk individuals. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas

PubMed Central

2013-01-01

Background Recent studies suggest that bacterial endotoxins may be associated with various chronic diseases, including colorectal adenomas and cancer. Given the evidence linking inflammation and colorectal cancer, we sought to determine if plasma endotoxin concentrations are associated with indicators of systemic or local inflammation and colorectal adenomas. Methods This cross-sectional study consisted of participants who underwent screening colonoscopies and included adenoma cases (n=138) and non-adenoma controls (n=324). Plasma concentrations of endotoxin were measured with Limulus Amebocyte Lysate (LAL) assay. We quantified concentrations of inflammatory cytokines, interleukin-4 (IL-4), IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) in plasma by ELISA and mRNA expression levels in rectal mucosal biopsies by quantitative RT-PCR. Interleukin-17 was evaluated only in the rectal mucosa. Results Compared to subjects with low plasma endotoxin concentrations, those with higher concentrations were more likely to have adenomas (OR 1.4, 95% CI 1.0-2.1). Among subjects with adenomas, those with villous histology were more likely to have higher endotoxin concentrations (5.4 vs. 4.1EU/mL, p=0.05) and lower plasma IFN-γ (0 vs. 1.64 pg/mL, p=0.02) compared to those with only tubular adenomas. Cases showed a trend of having higher plasma TNF-α levels than controls (p=0.06), but none of the other plasma or rectal mucosal cytokine levels differed between cases and controls. Elevated mucosal IL-12 levels were associated with having multiple adenomas (p=0.04). Higher concentrations of plasma endotoxin predicted increased plasma IL-12 levels (OR 1.5, 95% CI 1.0-2.2) and rectal mucosal IL-12 (OR 1.9, 95% CI 1.0-3.7) and IL-17 gene expression (OR 2.2, 95% CI 1.0-4.6). Conclusions These findings suggest that interactions between elevated plasma endotoxin concentrations and inflammatory cytokines may be relevant to the development of

MEN1 and pituitary adenomas.

PubMed

Delemer, Brigitte

2012-04-01

MEN1 gene mutations predispose carriers to pituitary tumors. Molecular pathways involved in the development of these tumors seem different to what is known in sporadic tumors. Clinical studies showed that all types of adenomas can be found with a predominance of prolactinoma and macroadenoma compared to a control population. These MEN1 tumors seem more aggressive, invasive and resistant to treatment requiring a very careful long-life follow-up. Occurrence of these tumors can be described in the pediatric population and it can be the first and only manifestation of MEN1 for some years asking the question of the systematic screening for MEN1 gene mutation in pediatric population with pituitary adenoma. Copyright © 2012. Published by Elsevier Masson SAS.

Association between markers of glucose metabolism and risk of colorectal adenoma.

PubMed

Rampal, Sanjay; Yang, Moon Hee; Sung, Jidong; Son, Hee Jung; Choi, Yoon-Ho; Lee, Jun Haeng; Kim, Young-Ho; Chang, Dong Kyung; Rhee, Poong-Lyul; Rhee, Jong Chul; Guallar, Eliseo; Cho, Juhee

2014-07-01

Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location. In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma. Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (a

Screening, management and surveillance for the sessile serrated adenomas/polyps.

PubMed

Fu, Xiangsheng; Qiu, Ye; Zhang, Yali

2014-01-01

The incidence and mortality rates from right-sided colorectal cancers (CRCs) have not decreased, compared with the significant reduction of CRCs in the left colon in recent years. It is likely that a significant proportion of right-sided CRCs evolve from undetected sessile serrated adenomas/polyps (SSA/Ps) in the primary colonoscopy. Increasing evidences suggest that SSA/Ps are high-risk lesions, with 15% of the SSA/P patients developing subsequent CRCs or adenomas with high-grade dysplasia. However, there are many issues in the screening, management and surveillance of SSA/Ps. Based on new evidences, this review addresses major issues in the diagnostic criteria for the serrated polyps of the colorectum, new endoscopic techniques (high-resolution magnifying endoscopy, narrow-band imaging, autofluorescence imaging, confocal laser endoscopy, and endocytoscopy) for the realtime identification of SSA/Ps, and the management of SSA/Ps by endoscopic mucosal resection, endoscopic sub-mucosal dissection or surgical resection in practice.

Pituitary adenoma and unexpected sudden infant death: a case report.

PubMed

Matsuura, H; Kitazawa, Y; Tanaka, M; Morooka, K

1994-01-01

Pituitary adenomas can cause sudden death in adults, but they are quite rare during infancy. Herein we present an unusual case of sudden infant death associated with a pituitary adenoma. The clinical presentations were "quietness" complained of by the parents and probable gigantism with accelerated growth rate during the first 2 months of life. The female infants had been in good health until one day when, at the age of 3 months, she was found immobile in bed. Microscopic examination showed that the cells of the entire pituitary gland were replaced by bizarre undifferentiated tumor cells. There were no invasive lesions in the surrounding brain tissue. It was also found that the cortex of the adrenal glands was atrophic. No metastatic lesions were observed in any organ. While the mechanism leading our infant to death is both controversial and unknown, we speculated that insufficient secretion of steroid hormones might have caused cardiovascular collapse.

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

PubMed Central

van den Broek, Frank JC; de Graaf, Eelco JR; Dijkgraaf, Marcel GW; Reitsma, Johannes B; Haringsma, Jelle; Timmer, Robin; Weusten, Bas LAM; Gerhards, Michael F; Consten, Esther CJ; Schwartz, Matthijs P; Boom, Maarten J; Derksen, Erik J; Bijnen, A Bart; Davids, Paul HP; Hoff, Christiaan; van Dullemen, Hendrik M; Heine, G Dimitri N; van der Linde, Klaas; Jansen, Jeroen M; Mallant-Hent, Rosalie CH; Breumelhof, Ronald; Geldof, Han; Hardwick, James CH; Doornebosch, Pascal G; Depla, Annekatrien CTM; Ernst, Miranda F; van Munster, Ivo P; de Hingh, Ignace HJT; Schoon, Erik J; Bemelman, Willem A; Fockens, Paul; Dekker, Evelien

2009-01-01

Background Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment. Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures. Based on comparable recurrence rates for TEM and EMR of 3.3% and

Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma.

PubMed

Glebauskiene, Brigita; Liutkeviciene, Rasa; Vilkeviciute, Alvita; Gudinaviciene, Inga; Rocyte, Aurelija; Simonaviciute, Dovile; Mazetyte, Ruta; Kriauciuniene, Loresa; Zaliuniene, Dalia

2018-01-01

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL-17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion . IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

Tubular Adenoma of the Breast: A Rare Presentation and Review of the Literature

PubMed Central

Salemis, Nikolaos S.; Gemenetzis, Georgios; Karagkiouzis, Gregorios; Seretis, Charalambos; Sapounas, Konstantinos; Tsantilas, Vlasios; Sambaziotis, Dimitrios; Lagoudianakis, Emmanuel

2012-01-01

Tubular adenomas, also known as pure adenomas, are rare epithelial tumors of the breast. Only a few cases have been reported in the literature, especially in young women of reproductive age. Postmenopausal women are very rarely affected. We describe here a very rare case of tubular breast adenoma in a postmenopausal woman who presented with a gradually enlarging breast lump. Clinical examination and imaging studies revealed a non-tender well circumscribed left breast tumor suggestive of a fibroadenoma. Due to the history of progressive enlargement of the breast lump, a surgical excision was performed. Histological findings were suggestive of a tubular breast adenoma. We conclude that although tubular breast adenoma is rare, it should always be considered in the differential diagnosis in postmenopausal patients presenting with a gradually enlarging breast mass. Preoperative diagnosis is difficult because tubular adenoma is indistinguishable from a fibroadenoma on physical examination and breast imaging. Surgical excision is necessary to establish a definitive diagnosis. Clinical presentation and management of our patient are discussed along with a review of the literature. Keywords Tubular adenoma; Breast; Breast mass. PMID:22383931

Tubular adenoma of the breast: a rare presentation and review of the literature.

PubMed

Salemis, Nikolaos S; Gemenetzis, Georgios; Karagkiouzis, Gregorios; Seretis, Charalambos; Sapounas, Konstantinos; Tsantilas, Vlasios; Sambaziotis, Dimitrios; Lagoudianakis, Emmanuel

2012-02-01

Tubular adenomas, also known as pure adenomas, are rare epithelial tumors of the breast. Only a few cases have been reported in the literature, especially in young women of reproductive age. Postmenopausal women are very rarely affected. We describe here a very rare case of tubular breast adenoma in a postmenopausal woman who presented with a gradually enlarging breast lump. Clinical examination and imaging studies revealed a non-tender well circumscribed left breast tumor suggestive of a fibroadenoma. Due to the history of progressive enlargement of the breast lump, a surgical excision was performed. Histological findings were suggestive of a tubular breast adenoma. We conclude that although tubular breast adenoma is rare, it should always be considered in the differential diagnosis in postmenopausal patients presenting with a gradually enlarging breast mass. Preoperative diagnosis is difficult because tubular adenoma is indistinguishable from a fibroadenoma on physical examination and breast imaging. Surgical excision is necessary to establish a definitive diagnosis. Clinical presentation and management of our patient are discussed along with a review of the literature. Tubular adenoma; Breast; Breast mass.

Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

PubMed Central

Lee, Bo-In; Hong, Sung Pil; Kim, Seong-Eun; Kim, Se Hyung; Hong, Sung Noh; Yang, Dong-Hoon; Shin, Sung Jae; Lee, Suck-Ho; Park, Dong Il; Kim, Young-Ho; Kim, Hyun Jung; Yang, Suk-Kyun; Kim, Hyo Jong; Jeon, Hae Jeong

2012-01-01

Now colorectal cancer is the second most common cancer in males and the fourth most common cancer in females in Korea. Since most of colorectal cancers occur after the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are one of the most effective methods to prevent colorectal cancer. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish Korean guideline for colorectal cancer screening and polyp detection. The guideline was developed by the Korean Multi-Society Take Force and we tried to establish the guideline by evidence-based methods. Parts of the statements were draw by systematic reviews and meta-analyses. Herein we discussed epidemiology of colorectal cancers and adenomas in Korea and optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations. PMID:22741131

Correlation of Ki-67, p53, and Adnab-9 immunohistochemical staining and ploidy with clinical and histopathologic features of severely dysplastic colorectal adenomas.

PubMed

Sheikh, Rafiq A; Min, Byung Hee; Yasmeen, Shagufta; Teplitz, Raymond; Tesluk, Henry; Ruebner, Boris Henry; Tobi, Martin; Hatfield, James; Fligiel, Suzanne; Lawson, Michael J

2003-01-01

Variations of Ki-67, p53, and Adnab-9 monoclonal antibody reactions in colonic adenomas may be associated with colonic cancer risk. We studied the predictive value of these markers for adverse behavior in severely dysplastic colorectal adenomas, such as an associated carcinoma, multiplicity of adenomas, and subsequent development of adenomas. For this purpose we compared theclinical, gross, and histologic characteristics of highly dysplastic index polyps in 42 patients with Ki 67, p53, and Adnab-9 immunostaining and other molecular markers. Polyps were removed endoscopically, and severely dysplastic polyps were stained immunohistochemically with Ki-67, Adnab-9, and p53 protein by the avidin biotin conjugate (ABC) technique. Quantitative DNA (QDNA) was analyzed by computer-assisted image analysis. Ki-67 immunohistochemistry showed reversal of normal distribution of nuclear staining from the normal basal position to the upper third of the colonic crypts. This abnormality of immunostaining in dysplastic adenomas was the earliest detected by the panel we used. A statistically significant correlation was seen between invasiveness of carcinoma in the index polyp and polyp size (P = 0.003), sessile morphology (P = 0.037), and villous or tubulovillous histology (P = 0.019). In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025). Although p53 positivity and aneuploidy were correlated with invasiveness of carcinoma in the index polyp (P = 0.025), Adnab-9 positivity was not. However, Adnab-9 positivity in the index polyp was associated with multiplicity of adenomas (P = 0.04) as well as recurrence of adenomas (P < 0.024). In conclusion, in addition to the morphologic and histologic markers already known, Ki-67, Adnab-9 antibody, and p53 protein may be prognostic indicators useful in follow-up of patients

Increased tumor necrosis factor receptor 1 expression in human colorectal adenomas

PubMed Central

Hosono, Kunihiro; Yamada, Eiji; Endo, Hiroki; Takahashi, Hirokazu; Inamori, Masahiko; Hippo, Yoshitaka; Nakagama, Hitoshi; Nakajima, Atsushi

2012-01-01

AIM: To determine the expression statuses of tumor necrosis factor (TNF)-α, its receptors (TNF-R) and downstream effector molecules in human colorectal adenomas. METHODS: We measured the serum concentrations of TNF-α and its receptors in 62 colorectal adenoma patients and 34 healthy controls. The protein expression of TNF-α, TNF-R1, TNF-R2 and downstream signals of the TNF receptors, such as c-Jun N-terminal kinase (JNK), nuclear factor-κ B and caspase-3, were also investigated in human colorectal adenomas and in normal colorectal mucosal tissues by immunohistochemistry. Immunofluorescence confocal microscopy was used to investigate the consistency of expression of TNF-R1 and phospho-JNK (p-JNK). RESULTS: The serum levels of soluble TNF-R1 (sTNF-R1) in adenoma patients were significantly higher than in the control group (3.67 ± 0.86 ng/mL vs 1.57 ± 0.72 ng/mL, P < 0.001). Receiver operating characteristic analysis revealed the high diagnostic sensitivity of TNF-R1 measurements (AUC was 0.928) for the diagnosis of adenoma, and the best cut-off level of TNF-R1 was 2.08 ng/mL, with a sensitivity of 93.4% and a specificity of 82.4%. There were no significant differences in the serum levels of TNF-α or sTNF-R2 between the two groups. Immunohistochemistry showed high levels of TNF-R1 and p-JNK expression in the epithelial cells of adenomas. Furthermore, a high incidence of co-localization of TNF-R1 and p-JNK was identified in adenoma tissue. CONCLUSION: TNF-R1 may be a promising biomarker of colorectal adenoma, and it may also play an important role in the very early stages of colorectal carcinogenesis. PMID:23082052

Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations.

PubMed

Koutourousiou, Maria; Gardner, Paul A; Fernandez-Miranda, Juan C; Paluzzi, Alessandro; Wang, Eric W; Snyderman, Carl H

2013-03-01

Giant pituitary adenomas (> 4 cm in maximum diameter) represent a significant surgical challenge. Endoscopic endonasal surgery (EES) has recently been introduced as a treatment option for these tumors. The authors present the results of EES for giant adenomas and analyze the advantages and limitations of this technique. The authors retrospectively reviewed the medical files and imaging studies of 54 patients with giant pituitary adenomas who underwent EES and studied the factors affecting surgical outcome. Preoperative visual impairment was present in 45 patients (83%) and partial or complete pituitary deficiency in 28 cases (52%), and 7 patients (13%) presented with apoplexy. Near-total resection (> 90%) was achieved in 36 patients (66.7%). Vision was improved or normalized in 36 cases (80%) and worsened in 2 cases due to apoplexy of residual tumor. Significant factors that limited the degree of resection were a multilobular configuration of the adenoma (p = 0.002) and extension to the middle fossa (p = 0.045). Cavernous sinus invasion, tumor size, and intraventricular or posterior fossa extension did not influence the surgical outcome. Complications included apoplexy of residual adenoma (3.7%), permanent diabetes insipidus (9.6%), new pituitary insufficiency (16.7%), and CSF leak (16.7%, which was reduced to 7.4% in recent years). Fourteen patients underwent radiation therapy after EES for residual mass or, in a later stage, for recurrence, and 10 with functional pituitary adenomas received medical treatment. During a mean follow-up of 37.9 months (range 1-114 months), 7 patients were reoperated on for tumor recurrence. Three patients were lost to follow-up. Endoscopic endonasal surgery provides effective initial management of giant pituitary adenomas with favorable results compared with traditional microscopic transsphenoidal and transcranial approaches.

Dietary fibre for the prevention of recurrent colorectal adenomas and carcinomas.

PubMed

Yao, Yibo; Suo, Tao; Andersson, Roland; Cao, Yongqing; Wang, Chen; Lu, Jingen; Chui, Evelyne

2017-01-08

for analyses in this review. The mean ages of the participants ranged from 56 to 66 years. All participants had a history of adenomas, which had been removed to achieve a polyp-free colon at baseline. The interventions were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources alone or in combination. The comparators were low-fibre (2 to 3 g per day), placebo, or a regular diet. The combined data showed no statistically significant difference between the intervention and control groups for the number of participants with at least one adenoma (5 RCTs, n = 3641, RR 1.04, 95% CI 0.95 to 1.13, low-quality evidence), more than one adenoma (2 RCTs, n = 2542, RR 1.06, 95% CI 0.94 to 1.20, low-quality evidence), or at least one adenoma 1 cm or greater (4 RCTs, n = 3224, RR 0.99, 95% CI 0.82 to 1.20, low-quality evidence) at three to four years. The results on the number of participants diagnosed with colorectal cancer favoured the control group over the dietary fibre group (2 RCTS, n = 2794, RR 2.70, 95% CI 1.07 to 6.85, low-quality evidence). After 8 years of comprehensive dietary intervention, no statistically significant difference was found in the number of participants with at least one recurrent adenoma (1 RCT, n = 1905, RR 0.97, 95% CI 0.78 to 1.20), or with more than one adenoma (1 RCT, n = 1905, RR 0.89, 95% CI 0.64 to 1.24). More participants given ispaghula husk group had at least one recurrent adenoma than the control group (1 RCT, n = 376, RR 1.45, 95% CI 1.01 to 2.08). Other analyses by types of fibre intervention were not statistically significant. The overall dropout rate was over 16% in these trials with no reasons given for these losses. Sensitivity analysis incorporating these missing data shows that none of the results can be considered as robust; when the large numbers of participants lost to follow-up were assumed to have had an event or not, the results changed sufficiently to alter the conclusions

Adenomas of the common bile duct in familial adenomatous polyposis

PubMed Central

Yan, Mao-Lin; Pan, Jun-Yong; Bai, Yan-Nan; Lai, Zhi-De; Chen, Zhong; Wang, Yao-Dong

2015-01-01

Familial adenomatous polyposis (FAP) or Gardner’s syndrome is often accompanied by adenomas of the stomach and duodenum. We experienced a case of adenomas of the common bile duct in a 40-year-old woman with FAP presenting with acute cholangitis. Only 8 cases of adenomas or adenocarcinoma of the common bile duct have been reported in the literature in patients with FAP or Gardner’s syndrome. Those patients presented with acute cholangitis or pancreatitis. Local excision or Whipple procedure may be the reasonable surgical option. PMID:25780319

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

PubMed

Asa, S L; Casar-Borota, O; Chanson, P; Delgrange, E; Earls, P; Ezzat, S; Grossman, A; Ikeda, H; Inoshita, N; Karavitaki, N; Korbonits, M; Laws, E R; Lopes, M B; Maartens, N; McCutcheon, I E; Mete, O; Nishioka, H; Raverot, G; Roncaroli, F; Saeger, W; Syro, L V; Vasiljevic, A; Villa, C; Wierinckx, A; Trouillas, J

2017-04-01

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients. © 2017 Society for Endocrinology.

Toxic adenoma of the thyroid gland and Wolff-Parkinson-White syndrome

PubMed Central

Naço, M; Çeliku, E; Llukaçaj, A; Shehaj, J; Kameniku, R

2009-01-01

We report the case of a 17-year-old girl with toxic adenoma scheduled for surgery right lobectomy and isthmectomy of thyroid gland. During the examination before surgery, patient was diagnosed for the first time as having with Wolff – Parkinson – White (WPW) syndrome. In the operating room, after the induction of anesthesia, the electrocardiogram showed wide QRS complex tachycardia with a rate of 180 beats/min, which was diagnosed as paroxysmal supraventricular tachycardia. The patient was treated immediately with antiarrhythmic drugs: adenosine iv three times (at doses of 6 mg, 12mg, 12mg bolus) and esmolol iv twice (at doses 28.5 mg). This approach resulted in disappearance of the delta wave and tachycardia for the whole surgery period. In this case report we discuss the role of induction of anesthesia and presence of toxic adenoma in a patient with WPW. PMID:19561784

Thyroid-stimulating hormone pituitary adenomas.

PubMed

Clarke, Michelle J; Erickson, Dana; Castro, M Regina; Atkinson, John L D

2008-07-01

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing < 2% of all pituitary adenomas. The authors conducted a retrospective analysis of patients with TSH-secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for

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

PubMed

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

2015-09-29

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.

[Extracapsular hepatic adenoma. Case report and literature review].

PubMed

Vargas-Flores, Edgar; Pérez-Aguilar, Francisco; Valdez-Mendieta, Yanet

Hepatic adenomas are uncommon epithelial tumours. They usually appear in women between 20 and 44 years old. They are commonly located in the right hepatic lobe and are typically solitary masses. Multiple adenomas can present in patients with prolonged use of oral contraceptive pills, glycogen storage diseases and hepatic adenomatosis. A 35 year-old woman without any significant past medical history, with a chief complaint that started in December 2012 with oppressive, mild intensity abdominal pain located in right upper quadrant in the abdomen on deep palpation. With an abdominal ultrasound showing a mass of 91×82×65cm located in the right flank, isoechogenic with internal vascularity. Contrast computed tomography scan showing an ovoid tumour with circumscribed borders, with heterogenic intense reinforcement and displacement of adjacent structures with dimensions of 88×71×80cm. In laparotomy, excision of the tumour and cholecystectomy with the trans surgical findings of an 8cm tumour with a pedicle containing one artery and one vein coming from the hepatic free border with strong adhesions to the gallbladder. Pathologic diagnosis: Extracapsular hepatic adenoma. Incidence of hepatic adenomas has increased in the last decades, in a parallel fashion with the introduction of oral contraceptive pills, showing association with glycogen storage diseases and to a lesser degree with diabetes and pregnancy. Diagnosis is clinical with the aid of imaging studies. Prognosis of hepatic adenomas is not well established, therefore, management depends on symptoms, size, number, location and certainty of diagnosis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Gigantism caused by growth hormone secreting pituitary adenoma.

PubMed

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi; Kim, Chan Jong

2014-06-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings.

Gigantism caused by growth hormone secreting pituitary adenoma

PubMed Central

Rhee, Noorisaem; Jeong, Kumi; Yang, Eun Mi

2014-01-01

Gigantism indicates excessive secretion of growth hormones (GH) during childhood when open epiphyseal growth plates allow for excessive linear growth. Case one involved a 14.7-year-old boy presented with extreme tall stature. His random serum GH level was 38.4 ng/mL, and failure of GH suppression was noted during an oral glucose tolerance test (OGTT; nadir serum GH, 22.7 ng/mL). Magnetic resonance imaging (MRI) of the brain revealed a 12-mm-sized pituitary adenoma. Transsphenoidal surgery was performed and a pituitary adenoma displaying positive immunohistochemical staining for GH was reported. Pituitary MRI scan was performed 4 months after surgery and showed recurrence/residual tumor. Medical treatment with a long-acting somatostatin analogue for six months was unsuccessful. As a result, secondary surgery was performed. Three months after reoperation, the GH level was 0.2 ng/mL and insulin-like growth factor 1 was 205 ng/mL. Case two involved a 14.9-year-old boy, who was referred to our department for his tall stature. His basal GH level was 9.3 ng/mL, and failure of GH suppression was reported during OGTT (nadir GH, 9.0 ng/mL). Pituitary MRI showed a 6-mm-sized pituitary adenoma. Surgery was done and histopathological examination demonstrated a pituitary adenoma with positive staining for GH. Three months after surgery, the GH level was 0.2 ng/mL and nadir GH during OGTT was less than 0.1 ng/mL. Pituitary MRI scans showed no residual tumor. We present two cases of gigantism caused by a GH-secreting pituitary adenoma with clinical and microscopic findings. PMID:25077093

Simultaneous above and below approach to giant pituitary adenomas: surgical strategies and long-term follow-up

PubMed Central

D’Ambrosio, Anthony L.; Grobelny, Bartosz T.; Freda, Pamela U.; Wardlaw, Sharon; Bruce, Jeffrey N.

2012-01-01

Introduction Giant pituitary adenomas of excessive size, fibrous consistency or unfavorable geometric configuration may be unresectable through conventional operative approaches. We present our select case series for operative resection and long-term follow-up for these unusual tumors, employing both a staged procedure and a combined transsphenoidal-transcranial above and below approach. Method A retrospective chart review was performed on patients operated via the staged, and combined approaches by the senior author (J.N·B.). Pre-operative characteristics and postoperative outcomes were reviewed. A detailed description of the operative technique and perioperative management is provided. Results Between 1993 and 1996, two patients harboring giant pituitary adenomas underwent an intentionally staged resection, and between 1997 and 2006, nine patients harboring giant pituitary adenomas underwent surgery via a single-stage above and below approach. Nine patients (82%) presented with non-secreting adenomas and two patients (18%) presented with prolactinomas refractory to medical management. Gross total resection was achieved in six patients (55%), near total resection in 1 (9%), and subtotal removal in 4 (36%). Seven patients (64%) experienced visual improvement postoperatively and no major complications occurred. Long-term follow-up averaged 51.6 months. Panhypopituitarism was observed in four patients, partial hypopituitarism in four, persistent DI in two, and persistent SIADH in one. Conclusions The addition of a transcranial component to the transsphenoidal approach offers additional visualization of critical neurovascular structures during giant pituitary adenoma resection. Complications rates are similar to other series in which complex pituitary adenomas are resected by other means. The above and below approach is both safe and effective and the immediate and long-term advantages of a single-stage approach justify its utility in this select group of patients

Clinical characteristics of patients with thyrotropin-secreting pituitary adenoma.

PubMed

Wu, Yung-Yen; Chang, Hung-Yu; Lin, Jen-Der; Chen, Kwang-Wen; Huang, Yu-Yao; Jung, Shih-Ming

2003-03-01

Thyroid-stimulating hormone (thyrotropin, TSH)-secreting pituitary adenoma is a very rare cause of hyperthyroidism. Diagnosis of this condition is often delayed due to lack of availability of TSH radioimmunoassay (RIA), the failure to recognize the utility of RIA and the incorrect attribution of the condition to other causes of thyrotoxicosis. This retrospective study analyzed the clinical characteristics of patients with this disorder treated from 1991 to 2002. Seven patients (6 females, 1 male; mean age, 48 years; range, 33 to 72 years) with a diagnosis of TSHsecreting pituitary adenoma based on detectable TSH levels with high serum free thyroid hormone or triiodothyronine concentrations and pituitary lesions found on neuroimaging were included in this study. Patient records including clinical features, endocrine studies, immunohistochemistry studies, and response to treatment were reviewed. All 7 patients had hyperthyroidism, elevated free thyroxine or triiodothyronine levels, and unsuppressed levels of TSH. Imaging studies demonstrated a pituitary mass or lesion in all patients. Six patients had macroadenomas and 1 patient had a microadenoma. One of the patients had coexisting acromegalic features and hypersecretion of growth hormone was diagnosed. All of the patients had been treated with thionamides or thyroidectomy for presumed primary hyperthyroidism. Serum alpha-subunit level was uncharacteristically normal in 2 patients and elevated in 1 patient. Alpha-subunit/TSH molar ratios were elevated in 3 patients. Five patients underwent transsphenoidal adenomectomy but only one of them remained well-controlled at follow-up. Three patients received administration of somatostatin analogs and they achieved normalization of serum TSH and free thyroid hormones during the period of therapy. TSH immunoassay has an important role in the evaluation of hyperthyroid patients to determine the presence of inappropriate secretion. TSH-secreting pituitary adenoma exhibits

Pictures of focal nodular hyperplasia and hepatocellular adenomas

PubMed Central

Sempoux, Christine; Balabaud, Charles; Bioulac-Sage, Paulette

2014-01-01

This practical atlas aims to help liver and non liver pathologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocellular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for paraffin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glutamine synthase and according to the above results additional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocellular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated. PMID:25232451

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

PubMed

Berker, Dilek; Isik, Serhat; Aydin, Yusuf; Tutuncu, Yasemin; Akdemir, Gokhan; Ozcan, Hatice Nursun; Guler, Serdar

2011-01-01

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

Double separate versus contiguous pituitary adenomas: MRI features and endocrinological follow up.

PubMed

Roberts, Sammie; Borges, Manuel Thomas; Lillehei, Kevin O; Kleinschmidt-DeMasters, B K

2016-10-01

Double pituitary adenomas are defined as two adenomas within a gland. These have distinct light microscopic and immunohistochemical features and may be clearly-separate or contiguous. Most reports have focused on the various hormonal combinations in double tumors rather than on any potential increased risk for residual mass or endocrinopathy. Departmental files were searched to identify all double adenomas from 1/1/2000 to 3/1/2016, with review of magnetic resonance imaging (MRI) to determine if the dual nature of the lesions could be discerned retrospectively after histologic diagnosis of double adenoma. All cases were immunostained for standard anterior pituitary hormones. Eight cases were identified: 2 follicle-stimulating hormone (FSH)/alpha subunit (ASU) + prolactinoma (PRL); 1 PRL + corticotroph (ACTH); 1 hormone-negative + PRL; 1 ACTH + ASU/growth hormone (GH)/PRL; 1 GH/PR + PRL; 1 FSH/ASU, + ACTH; 1 GH + luteinizing hormone (LH). One patient had clearly-separate lesions identified preoperatively and required two surgical procedures for gross total resection. A second patient had 2 lesions recognized at surgery and afterwards on retrospective neuroimaging. The remaining 6 patients had double adenomas discovered at the time of histologic examination that were not resolvable at surgery or on retrospective neuroimaging. Four patients, 2 with clearly-separate and 2 with contiguous double adenomas, had persistent MRI abnormalities, and one had continued endocrine abnormalities. Double contiguous pituitary adenomas are difficult to anticipate preoperatively or to resolve intraoperatively. Although double contiguous adenomas are much more common than double separate lesions, both have a risk for subtotal resection and, thus, residual mass and/or endocrinopathy may ensue.

Surgical Outcomes of Cavernous Sinus Syndrome in Pituitary Adenomas.

PubMed

Fu, Weilun; Duan, Lian; Geng, Sumin

2017-11-01

The type of pituitary adenoma with a manifestation that includes cavernous sinus syndrome is rare. Based on the clinical data of 70 patients, this study investigated the pathogenesis, imaging characteristics, and prognostic factors of pituitary adenoma with cavernous sinus syndrome. We conducted a retrospective analysis of the characteristics of patients with pituitary adenoma with cavernous sinus syndrome who received surgical treatment. The patients were classified into different prognosis groups according to the time required for them to recover from the cavernous sinus syndrome. Univariate analyses were conducted for the correlations between the prognosis and factors. Of the 3598 cases of pituitary adenomas, 70 (1.95%) presented cavernous sinus syndrome. Of the patients, 55.7% recovered within 2 weeks of surgery, 24.3% recovered from 2 weeks to 1 year after surgery, and 20% had not returned to normal after more than 1 year after surgery. Univariate analyses showed that shorter disease duration (P < 0.001), lower Knosp grade (P = 0.045), a transsphenoidal approach (P < 0.001), and associated pituitary apoplexy (P = 0.012) were predictive factors of early postoperative recovery. The prognosis of cavernous sinus syndrome differs depending on the mechanism of the syndrome. There was no significant difference in the prognosis between patients with total pituitary adenoma resection and subtotal resection. Timely surgery within 100 days of symptom occurrence, Knosp grade 0-2, and associated pituitary apoplexy are predictive factors of good prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Pleomorphic adenoma cells vary in their susceptibility to SV40 transformation depending on the initial karyotype.

PubMed

Kazmierczak, B; Thode, B; Bartnitzke, S; Bullerdiek, J; Schloot, W

1992-07-01

Chromosomal aberrations involving 8q12 or 12q13-15 characterize two cytogenetic subgroups of salivary gland pleomorphic adenomas. As the tumors of the two groups differ in their clinical and histologic characteristics, we decided to determine their susceptibility to SV40 transformation. We transfected cell cultures from 13 adenomas with aberrations involving 8q12 and from seven adenomas with involvement of 12q13-15 using an SV40 plasmid coding for the early region of the viral genome. Whereas all cultures with aberrations of 12q13-15 showed transformed foci, only 4 of the 13 cultures with 8q12 abnormalities showed foci of transformed cells. We also observed a much higher immortalization rate in the first group (3/7 vs. 1/13). All successfully transformed tumor cell cultures showed a relatively stable karyotype in the pre-crisis stage and a high mitotic index, were T-antigen positive, and had an extended life span in vitro.

Uneven Distribution of Regional Blood Supply Prompts the Cystic Change of Pituitary Adenoma.

PubMed

Zhang, Jianhe; Gu, Jianjun; Ma, Yiming; Huang, Yinxing; Wang, Jiaxing; Wu, Zhifeng; Zhong, Qun; Wang, Shousen

2017-07-01

Previous studies have suggested that the cystic change of pituitary adenoma might be related to the blood supply and metabolism of the tumor; however, the exact pathologic mechanism underlying the cystic change remains unknown. We aimed to assess the features of regional blood supply of pituitary adenoma and examine its relationship with the cystic change of pituitary adenoma. Patients (N = 79) with pituitary adenoma admitted to our hospital were divided into the parenchyma group (n = 40) or the cystic change group (n = 39). Dynamic contrast-enhanced magnetic resonance imaging of the pituitary adenoma was conducted for the parenchyma group and the steepest slopes (SS max , reflecting regional blood supply) at different areas were calculated. The location of cystic change of the pituitary adenoma was recorded and analyzed for the cystic change group. The parenchyma group showed an upper SS max of 2.52 ± 1.18, a lower SS max of 2.89 ± 1.46, a left SS max of 2.71 ± 1.31, and a right SS max of 2.66 ± 1.29. The difference between the upper and lower SS max was statistically significant (P < 0.001), with no difference between the left and right regions (P = 0.668). The location of cystic change of the pituitary adenoma was mainly in the upper region, accounting for 48.7% of cases. Regional blood supply is unevenly distributed in the parenchymal pituitary adenoma, with reduced blood supply in the upper than the lower region. Cystic change mainly occurs in the upper region of pituitary adenoma. Copyright © 2017 Elsevier Inc. All rights reserved.

Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case–Control Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhiyuan; Ellis, Scott; Lee, Cheng-Chia

Purpose: To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non–adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA). Methods and Materials: The clinical features and outcomes of 104 NFA patients treated with SRS in our center between September 1994 and August 2012 were evaluated. Among them, 34 consecutive patients with a confirmatory SCA were identified. A control group of 70 patients with other subtypes of NFA were selected for review based on comparable baseline features, including sex, age at the time of SRS, tumor size, marginmore » radiation dose to the tumor, and duration of follow-up. Results: The median follow-up after SRS was 56 months (range, 6-200 months). No patients with an SCA developed Cushing disease during the follow-up. Tumor control was achieved in 21 of 34 patients (62%) in the SCA group, compared with 65 of 70 patients (93%) in the NFA group. The median progression-free survival (PFS) was 58 months in the SCA group. The actuarial PFS was 73%, 46%, and 31% in the SCA group and was 94%, 87%, and 87% in the NFA group at 3, 5, and 8 years, respectively. Silent corticotroph adenomas treated with a dose of ≥17 Gy exhibited improved PFS. New-onset loss of pituitary function developed in 10 patients (29%) in the SCA group, whereas it occurred in 18 patients (26%) in the NFA group. Eight patients (24%) in the SCA group experienced worsening of a visual field deficit or visual acuity attributed to the tumor progression, as did 6 patients (9%) in the NFA group. Conclusion: Silent corticotroph adenomas exhibited a more aggressive course with a higher progression rate than other subtypes of NFAs. Stereotactic radiosurgery is an important adjuvant treatment for control of tumor growth. Increased radiation dose may lead to improved tumor control in SCA patients.« less

Management of clinically non-functioning pituitary adenoma.

PubMed

Chanson, Philippe; Raverot, Gerald; Castinetti, Frédéric; Cortet-Rudelli, Christine; Galland, Françoise; Salenave, Sylvie

2015-07-01

Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Down-regulation of E-cadherin and catenins in human pituitary growth hormone-producing adenomas.

PubMed

Sano, Toshiaki; Rong, Qian Zhi; Kagawa, Noriko; Yamada, Shozo

2004-01-01

Growth hormone (GH)-producing pituitary adenomas can be ultrastructurally divided into two major types: densely granulated and sparsely granulated. The latter type of adenoma characteristically exhibits globular accumulations of cytokeratin filaments known as fibrous bodies, which are immunohistochemically identifiable as juxtanuclear dot-like immunoreactivity. We hypothesize that the formation of fibrous body might be related to dysfunction of adhesion molecules, because of the functional relationship between intermediate filaments and the cadherin-catenin complex and frequent observation of loss of cohesiveness of the adenoma cells. Our recent immunohistochemical study showed that expression of E-cadherin and its undercoat proteins, alpha-, beta- and gamma-catenin, in GH cell adenomas with prominent fibrous bodies was significantly reduced compared with GH cell adenomas without fibrous bodies and the normal adenohypophysial cells. Although no mutation of exon 3 of the beta-catenin gene was found in any GH cell adenomas with fibrous bodies, methylation-specific polymerase chain reaction analysis revealed that the E-cadherin promoter region was methylated in 37.5% of these adenomas, two of which displayed total methylation, but not in GH cell adenomas without fibrous bodies. We conclude that the decreased expression of the E-cadherin-catenin complex and methylation of the E-cadherin gene promoter region are events associated with the formation of fibrous bodies in GH cell adenomas. It remains to be clarified to explain the mechanism by which down-regulation of adhesion molecules is involved in the abnormal assembly of intermediate filaments.

PUFA levels in erythrocyte membrane phospholipids are differentially associated with colorectal adenoma risk.

PubMed

Rifkin, Samara B; Shrubsole, Martha J; Cai, Qiuyin; Smalley, Walter E; Ness, Reid M; Swift, Larry L; Zheng, Wei; Murff, Harvey J

2017-06-01

Dietary intake of PUFA has been associated with colorectal neoplasm risk; however, results from observational studies have been inconsistent. Most prior studies have utilised self-reported dietary measures to assess fatty acid exposure which might be more susceptible to measurement error and biases compared with biomarkers. The purpose of this study was to determine whether erythrocyte phospholipid membrane PUFA percentages are associated with colorectal adenoma risk. We included data from 904 adenoma cases and 835 polyp-free controls who participated in the Tennessee Colorectal Polyp Study, a large colonoscopy-based case-control study. Erythrocyte membrane PUFA percentages were measured using GC. Conditional logistic regression was used to calculate adjusted OR for risk of colorectal adenomas with erythrocyte membrane PUFA. Higher erythrocyte membrane percentages of arachidonic acid was associated with an increased risk of colorectal adenomas (adjusted OR 1·66; 95 % CI 1·05, 2·62, P trend=0·02) comparing the highest tertile to the lowest tertile. The effect size for arachidonic acid was more pronounced when restricting the analysis to advanced adenomas only. Higher erythrocyte membrane EPA percentages were associated with a trend towards a reduced risk of advanced colorectal adenomas (P trend=0·05). Erythrocyte membrane arachidonic acid percentages are associated with an increased risk of colorectal adenomas.

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging.

PubMed

Lee, John Y K; Cho, Steve S; Zeh, Ryan; Pierce, John T; Martinez-Lage, Maria; Adappa, Nithin D; Palmer, James N; Newman, Jason G; Learned, Kim O; White, Caitlin; Kharlip, Julia; Snyder, Peter; Low, Philip S; Singhal, Sunil; Grady, M Sean

2017-08-25

OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent

Pyloric gland adenoma of gallbladder—reports of two cases and a brief review of literature

PubMed Central

Yang, Guang; Qin, Haixia; Raza, Anwar; Saukel, George W.; Solomon, Naveenraj; Michelotti, Marcos

2016-01-01

Adenomas of the gallbladder are uncommon benign epithelial neoplasms. Rarely, they can give rise to gallbladder cancer, which is the most common malignancy of the biliary tract, carrying a poor prognosis and decreased survival. Here we report the case histories of two patients, 40-year-old and 53-year-old males who presented with >1 cm gallbladder polyps, which were detected and confirmed using various imaging studies. Cholecystectomy was performed on both patients and the subsequent pathologic exam revealed 1.2 and 1.6 cm polyps in the lumen. Histopathologically, both polyps showed features reminiscent of “pyloric” gland type of adenoma. The differences between the two cases in regard to histopathological and immunohistochemical characteristics will be discussed. We will also briefly review the latest nomenclature on such low-grade polypoid gallbladder entities. PMID:27034818

Steroidogenic Factor 1, Pit-1, and Adrenocorticotropic Hormone: A Rational Starting Place for the Immunohistochemical Characterization of Pituitary Adenoma.

PubMed

McDonald, William C; Banerji, Nilanjana; McDonald, Kelsey N; Ho, Bridget; Macias, Virgilia; Kajdacsy-Balla, Andre

2017-01-01

-Pituitary adenoma classification is complex, and diagnostic strategies vary greatly from laboratory to laboratory. No optimal diagnostic algorithm has been defined. -To develop a panel of immunohistochemical (IHC) stains that provides the optimal combination of cost, accuracy, and ease of use. -We examined 136 pituitary adenomas with stains of steroidogenic factor 1 (SF-1), Pit-1, anterior pituitary hormones, cytokeratin CAM5.2, and α subunit of human chorionic gonadotropin. Immunohistochemical staining was scored using the Allred system. Adenomas were assigned to a gold standard class based on IHC results and available clinical and serologic information. Correlation and cluster analyses were used to develop an algorithm for parsimoniously classifying adenomas. -The algorithm entailed a 1- or 2-step process: (1) a screening step consisting of IHC stains for SF-1, Pit-1, and adrenocorticotropic hormone; and (2) when screening IHC pattern and clinical history were not clearly gonadotrophic (SF-1 positive only), corticotrophic (adrenocorticotropic hormone positive only), or IHC null cell (negative-screening IHC), we subsequently used IHC for prolactin, growth hormone, thyroid-stimulating hormone, and cytokeratin CAM5.2. -Comparison between diagnoses generated by our algorithm and the gold standard diagnoses showed excellent agreement. When compared with a commonly used panel using 6 IHC for anterior pituitary hormones plus IHC for a low-molecular-weight cytokeratin in certain tumors, our algorithm uses approximately one-third fewer IHC stains and detects gonadotroph adenomas with greater sensitivity.

Magmas Overexpression Inhibits Staurosporine Induced Apoptosis in Rat Pituitary Adenoma Cell Lines

PubMed Central

Gentilin, Erica; Minoia, Mariella; Molè, Daniela; delgi Uberti, Ettore C.; Zatelli, Maria Chiara

2013-01-01

Magmas is a nuclear gene that encodes for the mitochondrial import inner membrane translocase subunit Tim16. Magmas is overexpressed in the majority of human pituitary adenomas and in a mouse ACTH-secreting pituitary adenoma cell line. Here we report that Magmas is highly expressed in two out of four rat pituitary adenoma cell lines and its expression levels inversely correlate to the extent of cellular response to staurosporine in terms of apoptosis activation and cell viability. Magmas over-expression in rat GH/PRL-secreting pituitary adenoma GH4C1 cells leads to an increase in cell viability and to a reduction in staurosporine-induced apoptosis and DNA fragmentation, in parallel with the increase in Magmas protein expression. These results indicate that Magmas plays a pivotal role in response to pro-apoptotic stimuli and confirm and extend the finding that Magmas protects pituitary cells from staurosporine-induced apoptosis, suggesting its possible involvement in pituitary adenoma development. PMID:24069394

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

Adult weight gain and colorectal adenomas-a systematic review and meta-analysis.

PubMed

Schlesinger, S; Aleksandrova, K; Abar, L; Vieria, A R; Vingeliene, S; Polemiti, E; Stevens, C A T; Greenwood, D C; Chan, D S M; Aune, D; Norat, T

2017-06-01

Colorectal adenomas are known as precursors for the majority of colorectal carcinomas. While weight gain during adulthood has been identified as a risk factor for colorectal cancer, the association is less clear for colorectal adenomas. We conducted a systematic review and meta-analysis to quantify the evidence on this association. We searched Medline up to September 2016 to identify observational (prospective, cross-sectional and retrospective) studies on weight gain during adulthood and colorectal adenoma occurrence and recurrence. We conducted meta-analysis on high weight gain versus stable weight, linear and non-linear dose-response meta-analyses to analyze the association. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using a random effects model. For colorectal adenoma occurrence, the summary OR was 1.39 (95% CI: 1.17-1.65; I2: 43%, N = 9 studies, cases = 5507) comparing high (midpoint: 17.4 kg) versus stable weight gain during adulthood and with each 5 kg weight gain the odds increased by 7% (2%-11%; I2: 65%, N = 7 studies). Although there was indication of non-linearity (Pnon-linearity < 0.001) there was an increased odds of colorectal adenoma throughout the whole range of weight gain. Three studies were identified investigating the association between weight gain and colorectal adenoma recurrence and data were limited to draw firm conclusions. Even a small amount of adult weight gain was related to a higher odds of colorectal adenoma occurrence. Our findings add to the benefits of weight control in adulthood regarding colorectal adenoma occurrence, which might be relevant for early prevention of colorectal cancer. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk.

PubMed

Huang, Brian Z; Tsilidis, Konstantinos K; Smith, Michael W; Hoffman-Bolton, Judith; Visvanathan, Kala; Platz, Elizabeth A; Joshu, Corinne E

2018-05-26

We previously investigated the association between single nucleotide polymorphisms (SNPs) in genes related to obesity and inflammation and colorectal cancer in the CLUE II cohort. However, the relationships between these SNPs and colorectal adenomas have not been well evaluated. In a nested case-control study of 135 incident adenoma cases and 269 matched controls in the CLUE II cohort (1989-2000), we genotyped 17 candidate SNPs in 12 genes (PPARG, TCF7L2, ADIPOQ, LEP, IL10, CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and 19 tagSNPs in three genes (IL10, CRP, and TLR4). Conditional logistic regression was used to calculate odds ratios (OR) for adenomas (overall and by size, histology, location, number). Polymorphisms in the inflammatory-related genes CRP, ADIPOQ, IL6, and TLR4 were observed to be associated with adenoma risk. At rs1205 in CRP, T (minor allele) carriers had a higher risk (OR 1.67, 95%CI 1.07-2.60; reference: CC) of adenomas overall and adenomas with aggressive characteristics. At rs1201299 in ADIPOQ, the AC genotype had a higher risk (OR 1.58, 95%CI 1.00-2.49) of adenomas, while the minor AA genotype had a borderline inverse association (OR 0.44, 95%CI 0.18-1.08; reference: CC). At rs1800797 in IL6, the AA genotype had a borderline inverse association (OR 0.53, 95%CI 0.27-1.05; reference: GG). Three TLR4 tagSNPs (rs10116253, rs1927911, rs7873784) were associated with adenomas among obese participants. None of these SNPs were associated with colorectal cancer in our prior study in CLUE II, possibly suggesting a different genetic etiology for early colorectal neoplasia. © 2018 Wiley Periodicals, Inc.

Investigation of a cluster of pituitary adenomas in workers in the aluminum industry.

PubMed

Cullen, M R; Checkoway, H; Alexander, B H

1996-11-01

Four cases of pituitary adenoma among employees at a primary aluminum production factory were identified over a five year period by a community physician. The objective of this investigation was to determine whether there has been a comparable high incidence in other aluminum factories, and if particular jobs, departments, or activities in the industry are associated with higher rates of the disease. Pituitary adenoma in employees at all United States factories of the company for the years 1989-94 was assessed by a search of a health data information bank and an insurance data base covering present and past employees of the corporation. The incidence in the aluminum workers was estimated and compared with the workers in the index plant. A nested case control study was conducted to compare employment histories of identified cases with those of age and sex matched controls selected from the health information data base. 25 cases, including the index cases, were identified which had been diagnosed during the period 1989-94. The resulting rate of 10.4/100,000 person-years was much lower than that at the index plant. Case-control analysis showed no coherent pattern of location, department, or job significantly associated with risk. In particular, jobs and departments associated with exposures common to aluminum smelting-such as coal tar pitch volatiles and fluorides-were shown to be uncommon among cases compared with age and sex matched controls. Overall, despite the unprecedented cluster at a single plant, no strong evidence was found that the rate of pituitary adenoma is increased in aluminum workers generally. We found no association with any work activity or location in the industry to suggest a work related or exposure related cause for the disease.

Prognostic implications of telomerase expression in pituitary adenomas.

PubMed

Tortosa, F; Webb, S M

2018-04-01

To analyse the prognostic value of telomerase expression in patients with pituitary adenomas (PAs) followed-up for at least 8 years. A retrospective study was conducted of samples from 51 PAs (40 typical and 11 atypical) from patients who underwent transsphenoidal surgery between 2006 and 2008 and from 10 normal pituitary glands obtained by autopsy. Telomerase expression was assessed by immunohistochemistry, correlating the expression with that of Ki-67 and p53. We observed telomerase expression in 43 PAs (84.3%, 32 of the 40 typical PAs and in the 11 atypical PAs), which was higher in the clinically nonfunctioning cases (P=.0034) and very rare in the patients with acromegaly (P=.0001). There was a significant association between the percentage of tumour cells (>10%) and the recurrence of the adenoma (P=.039). There was no correlation with the expression of Ki-67 and p53 (P=.4986), and there were no differences according to age, sex, tumour size and invasiveness. A telomerase expression rate greater than 10% in the pituitary tumour tissue was associated with recurrence or progression of the PA, especially in the nonfunctioning cases. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Carbohydrate, glycemic index, and glycemic load and colorectal adenomas in the Prostate, Lung, Colorectal, and Ovarian Screening Study.

PubMed

Flood, Andrew; Peters, Ulrike; Jenkins, David J A; Chatterjee, Nilanjan; Subar, Amy F; Church, Timothy R; Bresalier, Robert; Weissfeld, Joel L; Hayes, Richard B; Schatzkin, Arthur

2006-11-01

It is possible that high-glycemic-load diets, through their hyperinsulinemic effects, can increase the risk of colorectal cancer. We analyzed data from a cancer screening study to determine whether persons with high-glycemic-load diets would be at an increased risk of distal adenomas. We included subjects with no prior adenoma or cancer from the Prostate, Lung, Colorectal, and Ovarian screening trial and whose results from flexible sigmoidoscopy exams indicated either no lesions (n = 34 817) or >/=1 distal adenoma (n = 3696). We used a 137-item food-frequency questionnaire to assess usual dietary intake over the preceding 12 mo. Using logistic regression analysis, we calculated, separately for men and women, prevalence odds ratios (ORs) and 95% CIs of sigmoidoscopy-detected, distal adenomas for quintiles of energy-adjusted dietary carbohydrate, glycemic index, and glycemic load. ORs decreased with increasing intakes of carbohydrate for both the men and the women in unadjusted models, but these associations were attenuated in multivariate-adjusted models. Among the men, the association remained significant after adjustment (OR: 0.71; 95% CI 0.60, 0.84; P for trend < 0.0001), but in the women it did not (OR: 0.89; 95% CI: 0.73, 1.10; P for trend = 0.30). The results for glycemic index showed no associations in either men or women. Results for glycemic load closely mirrored those for carbohydrate. Despite expectations that increasing glycemic load and glycemic index would increase the risk of adenoma, we observed no association in women and even an inverse association in men.

Gallbladder adenoma with focal adenocarcinoma.

PubMed

Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

2008-01-01

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

Nelfinavir induces radiation sensitization in pituitary adenoma cells

PubMed Central

Zeng, Jing; See, Alfred P.; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P.; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K.; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T.; Lim, Michael

2017-01-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir’s effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 d, 17 d with nelfinavir treatment, 27 d with radiation 6 Gy, and 41 d with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on protein gel blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies. PMID:21811091

Nelfinavir induces radiation sensitization in pituitary adenoma cells.

PubMed

Zeng, Jing; See, Alfred P; Aziz, Khaled; Thiyagarajan, Saravanan; Salih, Tarek; Gajula, Rajendra P; Armour, Michael; Phallen, Jillian; Terezakis, Stephanie; Kleinberg, Lawrence; Redmond, Kristen; Hales, Russell K; Salvatori, Roberto; Quinones-Hinojosa, Alfredo; Tran, Phuoc T; Lim, Michael

2011-10-01

Pituitary adenomas with local invasion and high secretory activity remain a therapeutic challenge. The HIV protease inhibitor nelfinavir is a radiosensitizer in multiple tumor models. We tested nelfinavir as a radiosensitizer in pituitary adenoma cells in vitro and in vivo. We examined the effect of nelfinavir with radiation on in vitro cell viability, clonogenic survival, apoptosis, prolactin secretion, cell cycle distribution, and the PI3K-AKT-mTOR pathway. We evaluated tumor growth delay and confirmed nelfinavir's effect on the PI3K-AKT-mTOR pathway in a hind-flank model. Nelfinavir sensitized pituitary adenoma cells to ionizing radiation as shown by viability assays and clonogenic assay with an enhancement ratio of 1.2 (p < 0.05). There is increased apoptotic cell death, as determined by annexin-V expression and cleaved caspase-3 levels. Nelfinavir does not affect prolactin secretion or cell cycle distribution. In vivo, untreated tumors reached 4-fold volume in 12 days, 17 days with nelfinavir treatment, 27 days with radiation 6 Gy, and 41 days with nelfinavir plus radiation (one-way ANOVA p < 0.001). Decreased phospho-S6 on Western blotting in vitro and immunohistochemistry in vivo demonstrated nelfinavir inhibition of the PI3K-AKT-mTOR pathway. Our data suggests a promising combination therapy with nelfinavir plus radiation in pituitary adenomas, which should be investigated in clinical studies.

The Relation of Smoking, Alcohol Use and Obesity to Risk of Sigmoid Colon and Rectal Adenomas

PubMed Central

Kono, Suminori; Shinchi, Koichi; Wakabayashi, Kazuo; Todoroki, Isao; Sakurai, Yutaka; Imanishi, Koji; Nishikawa, Hiroshi; Ogawa, Shinsaku; Katsurada, Mitsuhiko

1995-01-01

We conducted a case‐control study, using 429 cases with histologically confirmed sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal colonoscopy at least up to 60 cm from the anus. The subjects were male Self‐Defense Forces personnel aged 48–56 who received a retirement health examination including a routine sigmoid‐ or colonoscopy. Lifestyle characteristics were ascertained by a self‐administered questionnaire. Smoking in the recent past (ġ 10 years preceding the colonoscopy) and smoking in the remote past (>10 years before the colonoscopy) were both significantly associated with risk of sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal adjustment for smoking in the two periods, only smoking in the recent past was associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1‐150, 151‐250 and ġ251 cigarette‐years were 1.0 (reference), 1.9 (1.3‐2,8), 2.1 (1.4‐3.0) and 3.0 (1.9‐4.7), respectively (P for trend < 0.01), and those for rectal adenoma were 1.0 (reference), 1.2 (0.4‐3.2), 3.5 (1.4‐8.5) and 2.0 (0.6‐6.7), respectively (P for trend = 0.03). Alcohol use was significantly positively associated with sigmoid adenoma, and insignificantly associated with rectal adenoma. Body mass index was significantly positively associated with sigmoid adenoma, especially large ones. No such association was found for rectal adenoma. These findings suggest that smoking, especially in the recent past, and alcohol use are common risk factors for sigmoid colon and rectal adenomas while obesity may be exclusively related to the growth of sigmoid adenoma. PMID:8567391

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

PubMed

Losa, M; Fortunato, M; Molteni, L; Peretti, E; Mortini, P

2008-12-01

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

The role of aryl hydrocarbon receptor (AhR) in the pathology of pleomorphic adenoma in parotid gland.

PubMed

Drozdzik, Agnieszka; Kowalczyk, Robert; Lipski, Mariusz; Łapczuk, Joanna; Urasinska, Elzbieta; Kurzawski, Mateusz

2016-01-01

Pleomorphic adenoma (benign mixed tumor) is one of the most common salivary gland tumors. However, molecular mechanisms implicated in its development are not entirely defined. Therefore, the study aimed at definition of aryl hydrocarbon receptor (AhR) involvement in pleomorphic adenoma pathology, as the AhR controlled gene system was documented to play a role in development of various human tumors. The study was carried out in pleomorphic adenoma and control parotid gland tissues where gene expression of AHR, AhR nuclear translocator (ARNT), AhR repressor (AHRR), as well as AhR controlled genes: CYP1A1 and CYP1B1, at mRNA and protein (immunohistochemistry) levels were studied. Functional evaluation of AhR system was evaluated in HSY cells (human parotid gland adenocarcinoma cells) using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as AhR specific inducer. Pleomorphic adenoma specimens showed cytoplasmic and nuclear AhR expression in epithelial cells as well as in mesenchymal cells. In parotid gland AhR was expressed in cytoplasm of duct cells. Quantitative expression at mRNA level showed significantly higher expression of AHR, ARNT and CYP1B1, and comparable levels of CYP1A1 in pleomorphic adenoma tissue in comparison to healthy parotid gland. The HSY cell study revealed significantly higher expression level of AHRR in HSY as compared with MCF-7 cells (human breast adenocarcinoma cell line used as reference). Upon TCDD stimulation a drop in AHRR level in HSY cells and an increase in MCF-7 cells were observed. The HSY and MCF-7 cell proliferation rate (measured by WST-1 test) was not affected by TCDD. Summarizing both in vitro and in vivo observations it can be stated that AhR system may play a role in the pathology of pleomorphic adenoma. Copyright © 2015. Published by Elsevier Ltd.

Histomolecular interpretation of pleomorphic adenomas of the salivary gland by matrix-assisted laser desorption ionization imaging and spatial segmentation.

PubMed

Ernst, Günther; Guntinas-Lichius, Orlando; Hauberg-Lotte, Lena; Trede, Dennis; Becker, Michael; Alexandrov, Theodore; von Eggeling, Ferdinand

2015-07-01

Despite efforts in localization of key proteins using immunohistochemistry, the complex proteomic composition of pleomorphic adenomas has not yet been characterized. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI imaging) allows label-free and spatially resolved detection of hundreds of proteins directly from tissue sections and of histomorphological regions by finding colocalized molecular signals. Spatial segmentation of MALDI imaging data is an algorithmic method for finding regions of similar proteomic composition as functionally similar regions. We investigated 2 pleomorphic adenomas by applying spatial segmentation to the MALDI imaging data of tissue sections. The spatial segmentation subdivided the tissue in a good accordance with the tissue histology. Numerous molecular signals colocalized with histologically defined tissue regions were found. Our study highlights the cellular transdifferentiation within the pleomorphic adenoma. It could be shown that spatial segmentation of MALDI imaging data is a promising approach in the emerging field of digital histological analysis and characterization of tumors. © 2014 Wiley Periodicals, Inc.

Phenotypical and Pharmacological Characterization of Stem-Like Cells in Human Pituitary Adenomas.

PubMed

Würth, Roberto; Barbieri, Federica; Pattarozzi, Alessandra; Gaudenzi, Germano; Gatto, Federico; Fiaschi, Pietro; Ravetti, Jean-Louis; Zona, Gianluigi; Daga, Antonio; Persani, Luca; Ferone, Diego; Vitale, Giovanni; Florio, Tullio

2017-09-01

The presence and functional role of tumor stem cells in benign tumors, and in human pituitary adenomas in particular, is a debated issue that still lacks a definitive formal demonstration. Fifty-six surgical specimens of human pituitary adenomas were processed to establish tumor stem-like cultures by selection and expansion in stem cell-permissive medium or isolating CD133-expressing cells. Phenotypic and functional characterization of these cells was performed (1) ex vivo, by immunohistochemistry analysis on paraffin-embedded tissues; (2) in vitro, attesting marker expression, proliferation, self-renewal, differentiation, and drug sensitivity; and (3) in vivo, using a zebrafish model. Within pituitary adenomas, we identified rare cell populations expressing stem cell markers but not pituitary hormones; we isolated and expanded in vitro these cells, obtaining fibroblast-free, stem-like cultures from 38 pituitary adenoma samples. These cells grow as spheroids, express stem cell markers (Oct4, Sox2, CD133, and nestin), show sustained in vitro proliferation as compared to primary cultures of differentiated pituitary adenoma cells, and are able to differentiate in hormone-expressing pituitary cells. Besides, pituisphere cells, apparently not tumorigenic in mice, engrafted in zebrafish embryos, inducing pro-angiogenic and invasive responses. Finally, pituitary adenoma stem-like cells express regulatory pituitary receptors (D2R, SSTR2, and SSTR5), whose activation by a dopamine/somatostatin chimeric agonist exerts antiproliferative effects. In conclusion, we provide evidence that human pituitary adenomas contain a subpopulation fulfilling biological and phenotypical signatures of tumor stem cells that may represent novel therapeutic targets for therapy-resistant tumors.

Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

PubMed Central

Jaszewski, Richard; Misra, Sabeena; Tobi, Martin; Ullah, Nadeem; Naumoff, Jo Ann; Kucuk, Omer; Levi, Edi; Axelrod, Bradley N; Patel, Bhaumik B; Majumdar, Adhip PN

2008-01-01

AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas, the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps. METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years. RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation. CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia. PMID:18680228

The efficacy of fractionated radiotherapy and stereotactic radiosurgery for pituitary adenomas: long-term results of 125 consecutive patients treated in a single institution.

PubMed

Kong, Doo-Sik; Lee, Jung-Il; Lim, Do Hoon; Kim, Kwang Won; Shin, Hyung Jin; Nam, Do-Hyun; Park, Kwan; Kim, Jong Hyun

2007-08-15

The objective of this retrospective cohort study was to define the efficacy and safety of fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) for the treatment of patients with pituitary adenoma. Between January 1995 and April 2006, 125 consecutive patients with pituitary adenomas (54 hormone-secreting adenomas and 71 nonsecretory adenomas) received FRT or underwent SRS. Sixty-four patients received FRT, for which the mean total dose was 50.4 grays (Gy) (range, 48-54 Gy), and 61 patients underwent gamma-knife SRS with mean marginal dose of 25.1 Gy (range, 9-30 Gy). After mean follow up of 36.7 months, the tumor volume was increased in only 4 patients (3.2%). The overall actuarial progression-free survival rate was 99% at 2 years and 97% at 4 years. No difference was observed between the FRT group and the SRS group in the control of tumor growth. Based on the endocrinologic results in the patients who had secretory adenomas, the overall hormone complete remission rate was 26.2% at 2 years and 76.3% at 4 years. The median time to complete remission was 26 months in the SRS group and 63 months in the FRT group (P = .0068). Hypopituitarism developed as a delayed complication in 11.5% of patients at a median of 84 months. Both FRT and SRS were efficient treatment modalities for the control of tumor growth in patients with pituitary adenomas. The current results indicated that single-dose radiosurgery more promptly produces an effect on the hypersecretion of pituitary hormones and may be recommended over FRT for suitable patients.

Long-term treatment with bromocriptine of a plurihormonal pituitary adenoma secreting thyrotropin, growth hormone and prolactin.

PubMed

Shimatsu, A; Murabe, H; Nakamura, Y; Mizuta, H; Ihara, C; Nakao, K

1999-02-01

A 48-year-old female presented with acromegaly, amenorrhea and hyperthyroidism associated with high serum free T4 levels and measurable TSH concentrations. The administration of GHRH induced significant increases in GH, PRL and TSH. Conversely, intravenous infusion of dopamine or oral administration of bromocriptine effectively inhibited GH, PRL and TSH secretion. Serum alpha-subunit levels were neither affected by GHRH, dopamine nor bromocriptine. Transsphenoidal surgery was performed and immunostaining of the tissue showed that the adenoma cells were positive for GH, PRL or TSH. The patient was treated with bromocriptine at a daily oral dose of 10 mg after surgery. Serum TSH were initially suppressed but returned within reference intervals with persistent normalized free T4 levels. Serum PRL became undetectable and GH levels were stable around 6 ng/ml except the periods of poor drug compliance, when serum TSH, GH and PRL levels rose considerably. The patient was followed-up for 10 years without any change in the residual adenoma tissues as detected by magnetic resonance imaging. These findings suggest that long-term bromocriptine therapy is effective in treating the hypersecretory state of a plurihormonal adenoma secreting TSH, GH and PRL.

Dietary Choline and Betaine and the Risk of Distal Colorectal Adenoma in Women

PubMed Central

Cho, Eunyoung; Willett, Walter C.; Colditz, Graham A.; Fuchs, Charles S.; Wu, Kana; Chan, Andrew T.; Zeisel, Steven H.; Giovannucci, Edward L.

2008-01-01

Background Choline and betaine are involved in methyl-group metabolism as methyl-group donors; thus, like folate, another methyl-group donor, they may be associated with a reduced risk of colorectal adenomas. No epidemiologic study has examined the association of intake of these nutrients and colorectal adenoma risk. Methods We investigated the relationship between intakes of choline and betaine and risk of colorectal adenoma in US women enrolled in the Nurses' Health Study. Dietary intake was measured by food-frequency questionnaires, and individual intakes of choline and betaine were calculated by multiplying the frequency of consumption of each food item by its choline and betaine content and summing the nutrient contributions of all foods. Logistic regression models were used to calculate adjusted odds ratios (as approximations for relative risks) and 95% confidence intervals (CIs) of colorectal adenoma. All statistical tests were two-sided. Results Among 39 246 women who were initially free of cancer or polyps and who had at least one endoscopy from 1984 through 2002, 2408 adenoma cases were documented. Increasing choline intake was associated with an elevated risk of colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake, relative to the lowest quintile, were 1.03 (0.90 to 1.18), 1.01 (0.88 to 1.16), 1.23 (1.07 to 1.41), and 1.45 (1.27 to 1.67; Ptrend<.001). Betaine intake had a nonlinear inverse association with colorectal adenoma; the multivariable relative risks (95% CIs) for increasing quintiles of intake were 0.94 (0.83 to 1.07), 0.85 (0.75 to 0.97), 0.86 (0.75 to 0.98), and 0.90 (95% CI = 0.78 to 1.04; Ptrend = .09). Among individual sources of choline, choline from phosphatidylcholine and from sphingomyelin were each positively related to adenoma risk. Conclusions Our findings do not support an inverse association between choline intake and risk of colorectal adenoma. The positive association between choline

Top 100 Most-cited Articles on Pituitary Adenoma: A Bibliometric Analysis.

PubMed

Guo, Xiaopeng; Gao, Lu; Wang, Zihao; Feng, Chenzhe; Xing, Bing

2018-06-02

Many articles have been published on pituitary adenomas. Bibliometric analyses are helpful for determining the most impactful studies within a field. To identify the top 100 most-cited articles on pituitary adenomas using the bibliometric analysis method. We searched the Thomson Reuters Web of Science on March 31, 2018. Articles were listed in descending order by the total citation (TC) number, and the most-cited articles on pituitary adenomas were identified and analyzed. The most-cited articles were published between 1970 and 2014, with 1999 as the most prolific year. Growth hormone-secreting pituitary adenoma was the most commonly studied tumor subtype (43%), and in clinical studies, treatment options and follow-up were the most important research focuses (62%). The average number of TCs was 326, and the average number of annual citations (ACs) was 17. More review articles were published in the last decade, and the average number of ACs was higher for this decade than for previous decades. Twenty-one articles were recognized as "Citation Classics" with a TC number>400. Twenty-five journals published the top 100 works; the Journal of Clinical Endocrinology and Metabolism published the most articles (25%). The most articles (43%) were published in the United States. S. Melmed authored the greatest number of publications (14%). Departments of Medicine (32%) and Endocrinology (32%) contributed to the largest number of articles. This study identified the research focuses and trends regarding pituitary adenoma and provides key references for investigators in guiding future pituitary adenoma research. Copyright © 2018 Elsevier Inc. All rights reserved.

Obesity, Weight Gain and Risk of Colon Adenomas in Japanese Men

PubMed Central

Handa, Koichi; Hayabuchi, Hitomi; Kiyohara, Chikako; Inoue, Hisako; Marugame, Tomomi; Shinomiya, Sachiko; Hamada, Hiroaki; Onuma, Kazuya; Koga, Hiroko

1999-01-01

Obesity has been related to increased risk of colon cancer or adenomas, but the epidemiologic findings are not entirely consistent. We examined the relation of not only body mass index (BMI) but also waist‐to‐hip ratio (WHR) and weight gain to colon adenoma risk in men who received a preretirement health examination at the Japan Self Defense Forces (SDF) Fukuoka and Kumamoto Hospitals during the period from 995 to 1996. In the series of 803 men at age 47–55 years, 189 cases of colon adenomas and 226 controls with normal total colonoscopy were identified. Weight at 10 years before was ascertained by referring to the recorded data. After allowance for hospital, rank in the SDF, smoking and alcohol use, weight gain over the past 10 years was significantly associated with increased risk of colon adenomas (odds ratio for ≥ 6 kg versus ≤−2 kg = 2.2; 95% confidence interval 1.0–4.8). High BMI and high WHR were each associated with increased risk, but only WHR was related to the risk independently of weight gain. In particular, weight gain accompanied with a high WHR was associated with a significant increase in the risk. Men with high physical activity tended to have lower risk. Associations with obesity‐related variables and physical activity were not materially differential as regards the location and size of adenoma. The findings indicate that weight gain in middle age leading to abdominal obesity increases the risk of colon adenomas, and consequently of colon cancer. PMID:10543250

Thrombospondin expression in aldosterone-producing adenomas.

PubMed

Hatakeyama, Haruhiko; Nishizawa, Makoto; Nakagawa, Atsushi; Nakano, Shigeru; Kigoshi, Toshikazu; Miyamori, Isamu; Uchida, Kenzo

2002-07-01

Thrombospondin (TSP) 1 and 2 are extracellular matrix proteins that appear to play a role in cell adhesion and cell migration. It has been demonstrated that the pattern of TSP expression is shifted from TSP1 to TSP2 under adrenocorticotrophic hormone treatment in bovine adrenocortical cells. We investigated the expression in human adrenal tissues by Northern blot analysis and correlated these data with the expression of the adrenocorticotrophic hormone-receptor (ACTH-R). All adrenal tissues (control adrenals, nonfunctional adenomas and ACTH-dependent aldosterone-producing adenomas (APA)) expressed both TSP1 and TSP2 mRNAs. Compared to control adrenals (TSP1 and TSP2 expression = 100 +/- 12%, respectively), TSP1 expression was negatively (51 +/- 10%, p < 0.01) and TSP2 expression was positively (289 +/- 36%, p < 0.01) regulated in APA. No significant differences in TSP1 and TSP2 expressions were found between control adrenals and nonfunctional adenomas. In APA, TSP1 (r = -0.86, p<0.01) and TSP2 (r = 0.88, p < 0.01) expressions correlated closely with the expression of ACTH-R. These results suggest that ACTH activity plays an important role in regulating the expression of TSPs in human adrenal tissues. We speculate that the shift of expression observed in APA may be associated with the phenotype of the tumors.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

PubMed

Artico, M; Bianchi, E; Magliulo, G; De Vincentiis, M; De Santis, E; Orlandi, A; Santoro, A; Pastore, F S; Giangaspero, F; Caruso, R; Re, M; Fumagalli, L

2012-01-01

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

Meat consumption and the risk of incident distal colon and rectal adenoma

PubMed Central

Ferrucci, L M; Sinha, R; Huang, W-Y; Berndt, S I; Katki, H A; Schoen, R E; Hayes, R B; Cross, A J

2012-01-01

Background: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis. Methods: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17 072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression. Results: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04–2.36), well or very well-done meat (OR=1.59, 95% CI=1.05–2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17–2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06–2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03–2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56–0.86) and iron from supplements (OR=0.65, 95% CI=0.44–0.97) were inversely associated with any distal colorectal adenoma. Conclusion: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma. PMID:22166801

Hepatic Cell Adenoma: A Report of Four Cases

PubMed Central

Albritton, David R.; Tompkins, Ronald K.; Longmire, William P.

1974-01-01

Four patients with hepatic cell adenoma have been treated at the UCLA Hospital since 1965. The most recent was a 22-year-old woman who underwent subtotal resection of a giant hepatic cell adenoma after an unusual and confusing clinical presentation. The tumor may be the largest reported to date and may have excreted metabolically-active substances. Increased familiarity with the varying clinical and radiographic presentations of these rare tumors may facilitate earlier diagnosis and management. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 6.Fig. 7. PMID:4366047

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

PubMed

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

2016-07-15

To investigate the microRNA (miRNA) expression during histological progression from colorectal normal mucosa through adenoma to carcinoma within a lesion. 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. 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. 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.

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

PubMed

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

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. 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. 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. 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. Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e

Fecal Microbiota Characteristics of Patients with Colorectal Adenoma Detected by Screening: A Population-based Study

PubMed Central

Goedert, James J.; Gong, Yangming; Hua, Xing; Zhong, Huanzi; He, Yimin; Peng, Peng; Yu, Guoqin; Wang, Wenjing; Ravel, Jacques; Shi, Jianxin; Zheng, Ying

2015-01-01

Background Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low. Methods Microbiota metrics were determined by Illumina sequencing of 16S rRNA genes amplified from DNA extracted from feces self-collected in RNAlater. Among fecal immunochemical test-positive (FIT +) participants, colonoscopically-defined normal versus CRA patients were compared by regression, permutation, and random forest plus leave-one-out methods. Findings Of 95 FIT + participants, 61 had successful fecal microbiota profiling and colonoscopy, identifying 24 completely normal patients, 20 CRA patients, 2 CRC patients, and 15 with other conditions. Phylum-level fecal community composition differed significantly between CRA and normal patients (permutation P = 0.02). Rank phylum-level abundance distinguished CRA from normal patients (area under the curve = 0.767, permutation P = 0.006). CRA prevalence was 59% in phylum-level cluster B versus 20% in cluster A (exact P = 0.01). Most of the difference reflected 3-fold higher median relative abundance of Proteobacteria taxa (Wilcoxon signed-rank P = 0.03, positive predictive value = 67%). Antibiotic exposure and other potential confounders did not affect the associations. Interpretation If confirmed in larger, more diverse populations, fecal microbiota analysis might be employed to improve screening for CRA and ultimately to reduce mortality from CRC. PMID:26288821

Role of supplemental calcium in the recurrence of colorectal adenomas: a metaanalysis of randomized controlled trials.

PubMed

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J

2005-02-01

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Diagnostic value of stool DNA testing for multiple markers of colorectal cancer and advanced adenoma: a meta-analysis.

PubMed

Yang, Hua; Xia, Bing-Qing; Jiang, Bo; Wang, Guozhen; Yang, Yi-Peng; Chen, Hao; Li, Bing-Sheng; Xu, An-Gao; Huang, Yun-Bo; Wang, Xin-Ying

2013-08-01

The diagnostic value of stool DNA (sDNA) testing for colorectal neoplasms remains controversial. To compensate for the lack of large-scale unbiased population studies, a meta-analysis was performed to evaluate the diagnostic value of sDNA testing for multiple markers of colorectal cancer (CRC) and advanced adenoma. The PubMed, Science Direct, Biosis Review, Cochrane Library and Embase databases were systematically searched in January 2012 without time restriction. Meta-analysis was performed using a random-effects model using sensitivity, specificity, diagnostic OR (DOR), summary ROC curves, area under the curve (AUC), and 95% CIs as effect measures. Heterogeneity was measured using the χ(2) test and Q statistic; subgroup analysis was also conducted. A total of 20 studies comprising 5876 individuals were eligible. There was no heterogeneity for CRC, but adenoma and advanced adenoma harboured considerable heterogeneity influenced by risk classification and various detection markers. Stratification analysis according to risk classification showed that multiple markers had a high DOR for the high-risk subgroups of both CRC (sensitivity 0.759 [95% CI 0.711 to 0.804]; specificity 0.883 [95% CI 0.846 to 0.913]; AUC 0.906) and advanced adenoma (sensitivity 0.683 [95% CI 0.584 to 0.771]; specificity 0.918 [95% CI 0.866 to 0.954]; AUC 0.946) but not for the average-risk subgroups of either. In the methylation subgroup, sDNA testing had significantly higher DOR for CRC (sensitivity 0.753 [95% CI 0.685 to 0.812]; specificity 0.913 [95% CI 0.860 to 0.950]; AUC 0.918) and advanced adenoma (sensitivity 0.623 [95% CI 0.527 to 0.712]; specificity 0.926 [95% CI 0.882 to 0.958]; AUC 0.910) compared with the mutation subgroup. There was no significant heterogeneity among studies for subgroup analysis. sDNA testing for multiple markers had strong diagnostic significance for CRC and advanced adenoma in high-risk subjects. Methylation makers had more diagnostic value than mutation

Dietary meat intake in relation to colorectal adenoma in asymptomatic women

PubMed Central

Ferrucci, Leah M.; Sinha, Rashmi; Graubard, Barry I.; Mayne, Susan T.; Ma, Xiaomei; Schatzkin, Arthur; Schoenfeld, Philip S.; Cash, Brooks D.; Flood, Andrew; Cross, Amanda J.

2009-01-01

Introduction No previous study has concurrently assessed the association between meat intake, meat cooking methods and doneness levels, meat mutagens (heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons), heme iron, and nitrite from meat and colorectal adenoma in asymptomatic women undergoing colonoscopy. Methods Of 807 eligible women in a cross-sectional multi-center colonoscopy screening study, 158 prevalent colorectal adenoma cases and 649 controls satisfactorily completed validated food frequency and meat questionnaires. Using an established meat mutagen database and new iron and nitrite databases, we comprehensively investigated components of meat that may be involved in carcinogenesis. Using logistic regression we estimated odds ratios (OR) and 95% confidence intervals (CI) within quartiles of meat-related variables. Results Red meat was positively associated with colorectal adenoma (OR fourth versus first quartile = 2.02; 95% CI = 1.06–3.83; P trend = 0.38). Intake of pan fried meat (OR = 1.72; 95% CI = 0.96–3.07; P trend = 0.01) and the HCA: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (OR = 1.90; 95% CI = 1.05–3.42; P trend = 0.07) were also associated with increased risk of colorectal adenoma. The new databases yielded lower estimates of heme iron and nitrite than previous assessment methods, although the two methods were highly correlated for both exposures. Although not statistically significant, there were positive associations between iron and heme iron from meat and colorectal adenoma. Conclusions In asymptomatic women undergoing colonoscopy, colorectal adenomas were associated with high intake of red meat, pan fried meat, and the HCA MeIQx. Other meat-related exposures require further investigation. PMID:19367270

Dietary meat intake in relation to colorectal adenoma in asymptomatic women.

PubMed

Ferrucci, Leah M; Sinha, Rashmi; Graubard, Barry I; Mayne, Susan T; Ma, Xiaomei; Schatzkin, Arthur; Schoenfeld, Philip S; Cash, Brooks D; Flood, Andrew; Cross, Amanda J

2009-05-01

No previous study has concurrently assessed the associations between meat intake, meat-cooking methods and doneness levels, meat mutagens (heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons), heme iron, and nitrite from meat and colorectal adenoma in asymptomatic women undergoing colonoscopy. Of the 807 eligible women in a cross-sectional multicenter colonoscopy screening study, 158 prevalent colorectal adenoma cases and 649 controls satisfactorily completed the validated food frequency and meat questionnaires. Using an established meat mutagen database and new heme iron and nitrite databases, we comprehensively investigated the components of meat that may be involved in carcinogenesis. Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) within quartiles of meat-related variables. Red meat was associated positively with colorectal adenoma (OR fourth vs. first quartile = 2.02; 95% CI = 1.06-3.83; P trend = 0.38). Intake of pan-fried meat (OR = 1.72; 95% CI = 0.96-3.07; P trend = 0.01) and the HCA: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) (OR = 1.90; 95% CI = 1.05-3.42; P trend = 0.07) were also associated with an increased risk of colorectal adenoma. The new databases yielded lower estimates of heme iron and nitrite than previous assessment methods, although the two methods were highly correlated for both exposures. Although not statistically significant, there were positive associations between iron and heme iron from meat and colorectal adenoma. In asymptomatic women undergoing colonoscopy, colorectal adenomas were associated with high intake of red meat, pan-fried meat, and the HCA MeIQx. Other meat-related exposures require further investigation.

Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women.

PubMed

Woodson, Karen; Flood, Andrew; Green, Lisa; Tangrea, Joseph A; Hanson, Jeffrey; Cash, Brooks; Schatzkin, Arthur; Schoenfeld, Phillip

2004-03-03

Loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that is polymorphic in the population, and its presence may predispose an individual to the development of colorectal cancer. We evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. Among 40 participants, 11 (27.5%) had LOI of IGF-II in their normal colonic mucosal tissue. After adjusting for body mass index and family history of colorectal cancer, LOI status was associated with a fivefold increased risk of adenoma formation (odds ratio = 5.2, 95% confidence interval = 1.0 to 26.7). On average, IGF-II expression was more than threefold higher among women with LOI of IGF-II than among women with normal imprinting status. Our findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer. These findings are intriguing and need to be confirmed in larger studies.

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans.

PubMed

Sanapareddy, Nina; Legge, Ryan M; Jovov, Biljana; McCoy, Amber; Burcal, Lauren; Araujo-Perez, Felix; Randall, Thomas A; Galanko, Joseph; Benson, Andrew; Sandler, Robert S; Rawls, John F; Abdo, Zaid; Fodor, Anthony A; Keku, Temitope O

2012-10-01

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn's disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1-V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.

Chronic administration of phenytoin and pleomorphic adenoma: A case report and review of literature.

PubMed

Maharshi, Vikas; Nagar, Pravesh

2017-01-01

Adverse drug effects that are uncommon or appear only on chronic administration of a drug may not be detected in clinical trials. This explains the need of strict post-marketing vigilance on drug use. Phenytoin administration has been shown in the literature to be associated with development of neoplasia (benign/malignant). In our knowledge current work represents the first case of pleomorphic-adenoma of sub-mandibular salivary gland developed following chronic phenytoin use. A 40 year old male having a history of head trauma twenty years back, had been on tablet phenytoin 100 mg thrice daily since then. One year back he noticed a small swelling in left sub-mandibular region and gradually increasing in size. FNAC and CECT revealed the diagnosis of pleomorphic-adenoma of sub-mandibular salivary gland. Other causes were ruled out. Surgical excision was performed successfully and continuing follow-up with no recurrence at the end of 6 months. Histo-pathogical examination of the tissue did not show any malignant changes.

Serum Interleukin-6, insulin, and HOMA-IR in male individuals with colorectal adenoma.

PubMed

Sasaki, Yu; Takeda, Hiroaki; Sato, Takeshi; Orii, Tomohiko; Nishise, Shoichi; Nagino, Ko; Iwano, Daisuke; Yaoita, Takao; Yoshizawa, Kazuya; Saito, Hideki; Tanaka, Yasuhisa; Kawata, Sumio

2012-01-15

It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma. In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast. In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association. Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR. ©2011 AACR.

Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.

PubMed

Obari, Abdulkader; Sano, Toshiaki; Ohyama, Kenichi; Kudo, Eiji; Qian, Zhi Rong; Yoneda, Akiko; Rayhan, Nasim; Mustafizur Rahman, Muhammad; Yamada, Shozo

2008-01-01

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.

Detecting the sampling rate through observations

NASA Astrophysics Data System (ADS)

Shoji, Isao

2018-09-01

This paper proposes a method to detect the sampling rate of discrete time series of diffusion processes. Using the maximum likelihood estimates of the parameters of a diffusion process, we establish a criterion based on the Kullback-Leibler divergence and thereby estimate the sampling rate. Simulation studies are conducted to check whether the method can detect the sampling rates from data and their results show a good performance in the detection. In addition, the method is applied to a financial time series sampled on daily basis and shows the detected sampling rate is different from the conventional rates.

Complementary role of parathormone washout test to 99mTc-MIBI parathyroid scintigraphy and histopathologic analysis of cell types in parathyroid adenomas.

PubMed

Ince, Semra; Emer, Ozdes; Deveci, Salih; Okuyucu, Kursat; Alagoz, Engin; San, Huseyin; Ayan, Aslı; Karacalioglu, Ozgur; Haymana, Cem; Gunalp, Bengul; Arslan, Nuri

2018-05-02

Parathyroid scintigraphy (PS) can be negative or equivocal (N/E) in a considerable number of cases with highly suspicious clinical findings and biochemical results for parathyroid adenoma (PA). The aims of this study were to investigate the complementary role of parathormone washout test (PWT) to PS in patients with primary hyperparathyroidism (PHPT) and evaluate histopathologic aspects of PAs in comparison with PS results. Thirty-eight patients with PHPT referred for PS were included in the study. Seventeen patients had both scintigraphic and ultrasonographic findings concordant with PA (Group A). Twenty-one patients having N/E PS, but suspected lesions for PA on ultrasonography (US) formed Group B. PWT was performed for all patients and they underwent the surgical intervention. An adenoma was removed in all patients and the histopathologic cell characteristics were established. The tumor size on US was larger in those patients whose adenomas were seen on the PS (P<.001). The percentages of chief (or principal), oxyphilic and clear cells in PAs were not statistically different between the groups. Serum parathormone level and PWT were not statistically significant between Group A and Group B (P=.095 and P=.04, respectively). Although there is not a definitive threshold value, the sensitivity of PS increases with lesion size. While chief cell and oxyphilic cell content of PAs tend to deplete in N/E PS, clear cell rate increases substantially. Combining PS with both US and PWT increases the sensitivity of detection and localization of PAs. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Sestamibi scan-directed parathyroid surgery: potentially high failure rate without measurement of intraoperative parathyroid hormone.

PubMed

Westerdahl, Johan; Bergenfelz, Anders

2004-11-01

The present study evaluated sestamibi scan-directed parathyroidectomy with intraoperative parathyroid hormone (PTH) assessment (ioPTH). The preoperative sestamibi scintigraphies were compared with the intraoperative findings for 103 patients undergoing first exploration for sporadic primary hyperparathyroidism (pHPT). Data were collected prospectively. Ninety-nine patients (96%) were cured. Patients with persistent pHPT (n = 4) all had an incorrect scintigram as well as an insufficient decline of ioPTH. At operation, 90 patients (87%) had solitary parathyroid adenoma; 12 patients had multiglandular disease. In one patient no enlarged parathyroid gland was found. Overall 77 of 118 abnormal glands (65%) were correctly identified by sestamibi scintigraphy. The sensitivity for localizing a single parathyroid adenoma was 80%. Patients with incorrect scintigrams had a higher proportion of upper pole adenomas than patients with correct scans. High glandular weight and high level of serum PTH were important factors for detectability. Sestamibi scintigraphy did not predict multiglandular disease. However, the use of ioPTH identified 8 of the 9 patients with a positive scan (a solitary focus) and multiglandular disease. In contrast, false-negative ioPTH led to four unnecessary bilateral explorations in the 63 patients with a scan-identified adenoma. With the help of ioPTH, a focused parathyroidectomy was accomplished in 43% of scan-negative patients with a solitary adenoma. In conclusion, sestamibi scintigraphy is an acceptable method for localizing a solitary parathyroid adenoma. However, the technique alone does not reliably predict multiglandular disease. Potentially the failure rate in scan-directed parathyroidectomy could increase, with up to 10% of patients without ioPTH.

Prevalence of advanced adenomas in small and diminutive colon polyps using direct measurement of size.

PubMed

Tsai, Franklin C; Strum, Williamson B

2011-08-01

Most studies reporting polyp size use visual estimates. Determining the prevalence of advanced histology based on direct measurement of polyp size may help guide the management of polyps found at optical colonoscopy (OC) and CT colonography (CTC). We designed a large, prospective study to assess the prevalence of advanced adenomas based on direct measurement of polyp size by a certified pathologists' assistant as reported in the pathology report. Patients between 40 and 89 years of age who presented for screening colonoscopy were included in our study. Advanced adenomas were defined as ≥10 mm or ≥25% villous features, high grade dysplasia or cancer. Polyps were divided by size into three groups: diminutive (≤5 mm), small (6-9 mm) and large (≥10 mm). If more than one adenoma was present, the most advanced was used for analysis. We evaluated 6,905 consecutive patients referred for colonoscopy between January 2005 and December 2006. Of the 4,967 who met the inclusion criteria, the mean age was 58.8 and consisted of 59% women. Overall, 930 (18.7%) had an adenoma; 248 (5%) were advanced adenomas including 8 (0.16%) cancers. Of 89 polyps≥10 mm, 76 (85%) had advanced histology; of 247 polyps 6-9 mm, 67 (27%) were advanced; of 1,025 polyps ≤5 mm, 105 (10%) were advanced. Thus, 172 of 248 (69%) patients with advanced adenomas had small or diminutive adenomas. Our data indicate the majority (69%) of advanced adenomas are <10 mm. Even among polyps≤5 mm, there was an appreciable prevalence of advanced adenomas (10%). These findings may help guide the management of sub-centimeter colon polyps found by OC or CTC.

Differential diagnosis between gallbladder adenomas and cholesterol polyps on contrast-enhanced harmonic endoscopic ultrasonography.

PubMed

Park, Chan Hyuk; Chung, Moon Jae; Oh, Tak Geun; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Kim, Hyunki; Hwang, Ho Kyoung; Lee, Woo Jung; Song, Si Young

2013-04-01

Differential diagnosis between gallbladder (GB) adenomas and cholesterol polyps based on ultrasonography or endoscopic ultrasonography (EUS) is challenging because they have similar echogenicity and morphology. We evaluated the usefulness of contrast-enhanced harmonic EUS (CEH-EUS) for differentiating between GB adenomas and cholesterol polyps. Between June 2010 and December 2011, a total of 87 patients with GB polyps who underwent a CEH-EUS were reviewed retrospectively. Of the 87 patients, 57 had a cholecystectomy. Of these, 34 patients were diagnosed with adenoma, cholesterol polyp, adenocarcinoma, or adenomyomatosis pathology. The remaining 23 patients were not diagnosed with GB polyps because their lesions separated from the GB mucosal layer during pathological sampling. On CEH-EUS, homogeneous and heterogeneous enhancement was shown in 6 and 2 patients with adenoma and in 4 and 8 patients with cholesterol polyps, respectively. Sensitivity and specificity of CEH-EUS for differential diagnosis of GB adenomas from cholesterol polyps based on the enhancement pattern were 75.0 and 66.6 %, respectively. CEH-EUS might be useful for distinguishing GB adenomas and cholesterol polyps based on enhancement patterns. However, an additional technique such as quantitative perfusion analysis is necessary because visual assessment of CEH-EUS images is subjective.

The management of aldosterone-producing adrenal adenomas--does adrenalectomy increase costs?

PubMed

Reimel, Bethann; Zanocco, Kyle; Russo, Mark J; Zarnegar, Rasa; Clark, Orlo H; Allendorf, John D; Chabot, John A; Duh, Quan-Yang; Lee, James A; Sturgeon, Cord

2010-12-01

Most experts agree that primary hyperaldosteronism (PHA) caused by an aldosterone-producing adenoma (APA) is best treated by adrenalectomy. From a public health standpoint, the cost of treatment must be considered. We sought to compare the current guideline-based (surgical) strategy with universal pharmacologic management to determine the optimal strategy from a cost perspective. A decision analysis was performed using a Markov state transition model comparing the strategies for PHA treatment. Pharmacologic management for all patients with PHA was compared with a strategy of screening for and resecting an aldosterone-producing adenoma. Success rates were determined for treatment outcomes based on a literature review. Medicare reimbursement rates were calculated to estimate costs from a third-party payer perspective. Screening for and resecting APAs was the least costly strategy in this model. For a reference patient with 41 remaining years of life, the discounted expected cost of the surgical strategy was $27,821. The discounted expected cost of the medical strategy was $34,691. The cost of adrenalectomy would have to increase by 156% to $22,525 from $8,784 for universal pharmacologic therapy to be less costly. Screening for APA is more costly if fewer than 9.6% of PHA patients have resectable APA. Resection of APAs was the least costly treatment strategy in this decision analysis model. Copyright © 2010 Mosby, Inc. All rights reserved.

Multifocal canalicular adenoma of the minor labial salivary glands

PubMed Central

Samar, María Elena; Avila, Rodolfo Esteban; Fonseca, Ismael Bernardo; Anderson, William; Fonseca, Gabriel M; Cantín, Mario

2014-01-01

Canalicular adenoma (CA) is an uncommon benign neoplasia of salivary glands which is clinically difficult to recognise. Despite having an excellent prognosis, the histological diagnosis and clinical management of this entity can be troublesome. While the main differential diagnosis to consider is basal cell adenoma (BCA), similar histological patterns and multifocality have been observed in adenoid cystic carcinoma (ACC) and polymorphous low-grade adenocarcinoma (PLGA), both locally-aggressive malignancies which require radically different treatment to CA. An emphasis has been placed on the value of immunohistochemistry in avoiding diagnostic and surgical errors. CA is positive for AE1/AE3, CD117 and S-100 protein, and negative for p63, α-SMA, Ki 67 and vimentin. Here we discuss the case of a 61-year-old female with CA in her right upper lip, showing multifocal growth histologically. The differential diagnosis with other adenomas is discussed in addition to the role of immunohistochemical studies that can confirm the clinical and surgical findings. PMID:25550873

Helicobacter pylori infection with intestinal metaplasia: An independent risk factor for colorectal adenomas

PubMed Central

Yan, Ye; Chen, Yi-Na; Zhao, Qian; Chen, Chao; Lin, Chun-Jing; Jin, Yin; Pan, Shuang; Wu, Jian-Sheng

2017-01-01

AIM To explore the association between Helicobacter pylori (H. pylori) infection status, intestinal metaplasia (IM), and colorectal adenomas. METHODS We retrospectively reviewed 1641 individuals aged ≥ 40 years who underwent physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy, and an interview to ascertain baseline characteristics and general state of health. Histopathological results were obtained by gastric and colorectal biopsies. RESULTS The prevalence of H. pylori infection and adenomas was 51.5% (845/1641) and 18.1% (297/1641), respectively. H. pylori infection was significantly correlated with an increased risk of colorectal adenomas (crude OR = 1.535, 95%CI: 1.044-1.753, P = 0.022; adjusted OR = 1.359, 95%CI: 1.035-1.785, P = 0.028). Individuals with IM had an elevated risk of colorectal adenomas (crude OR = 1.664, 95%CI: 1.216-2.277, P = 0.001; adjusted OR = 1.381, 95%CI: 0.998-1.929, P = 0.059). Stratification based on H. pylori infection stage and IM revealed that IM accompanied by H. pylori infection was significantly associated with an increased risk of adenomas (crude OR = 2.109, 95%CI: 1.383-3.216, P = 0.001; adjusted OR = 1.765, 95%CI: 1.130-2.757, P = 0.012). CONCLUSION H. pylori-related IM is associated with a high risk of colorectal adenomas in Chinese individuals. PMID:28293091

Risk factors cannot explain the higher prevalence rates of precancerous colorectal lesions in men

PubMed Central

Waldmann, Elisabeth; Heinze, Georg; Ferlitsch, Arnulf; GessI, Irina; Sallinger, Daniela; Jeschek, Philip; Britto-Arias, Martha; Salzl, Petra; Fasching, Elisabeth; Jilma, Bernd; Kundi, Michael; Trauner, Michael; Ferlitsch, Monika

2016-01-01

Background: Prevalence of (pre)cancerous colorectal lesions are higher in men than in women, although transition rates from advanced lesions to cancer is similar in both sexes. Our aim was to investigate whether the sex-specific difference in incidence of premalignant colorectal lesions might be explained by the impact of risk factors. Methods: A cross-sectional study analysing health check-up examinations and screening colonoscopies performed within a national quality assurance program. Results: A total of 25 409 patients were included in this study, 50.8% were women. Median age for both sexes was 60 years (interquartile range (IQR) 54–67). A multivariable model showed that risk factors mediated only 0.6 of the 10.4% gender gap in adenoma and 0.47 of the 3.2% gender gap in advanced adenoma detection rate. Smoking was the only independent risk factor with a varying sex-specific effect (men OR 1.46, CI 1.29, 1.64, women OR 1.76, CI 1.53, 2.06) and advanced adenomas (men OR 1.06, CI 0.80–1.42; women OR 2.08, CI 1.52–2.83). Independent risk factors for adenomas were BMI (OR 1.35 per IQR, CI 1.25–1.47) and triglyceride level (OR 1.03 per IQR, CI 1.00–1.06); for advanced adenomas physical activity (none vs regular: OR 1.54, CI 1.18–2.00, occasional vs regular: OR 1.17, CI 1.00–1.38), cholesterol level (OR 1.13 per IQR, CI 1.02–1.25), blood glucose level (OR 1.05 per IQR, CI 1.01–1.09) and alcohol score (OR 1.09 per IQR, CI 1.01–1.18). Conclusions: Risk factors cannot explain higher prevalence rates in men. Results of this study strongly underline the need for sex-specific screening recommendations. PMID:27764840

An unusual cause of hypercalcemic crisis: Water-clear cell double parathyroid adenoma.

PubMed

Yazar, Fatih Mehmet; Karaağaç, Mustafa; İşler, Ali; Bülbüloğlu, Ertan; Ezberci, Fikret

2017-01-01

To evaluate the clinical characteristics of a patient operated for water-clear cell adenoma and to discuss these in the light of relevant literature. PubMed and Google Scholar were searched to identify articles related to water-clear cell adenoma using the following keywords: parathyroid tissue, parathyroid gland, parathyroid cells, parathyroid adenoma, parathyroid hyperplasia, water-clear-cell, and water clear cell. The search included case reports, review articles, and original articles that had been published between January 1990 and November 2014 without any restrictions on language. All articles that contained information on the study population and treatment related data were identified and retrieved. In addition, an evaluation was of a case of a 47-year-old male patient with PHC who was treated at our clinic was conducted. A total of 19 patients, including our new case, (age range: 18 to 81 years, mean±SD: 57.47±16.31 years) were included in the analysis. Eleven patients were female. Information about adenoma location was available from studies involving 17 patients and they indicated the following distribution of locations: left inferior (n=10), right superior (n=4). When preoperative imaging methods were examined, a false negative result was given by ultrasonography in 28.5% of patients and only 57.1% were positive on scintigraphy. Concomitant thyroid papillary carcinoma was determined in 1 patient. The mean tissue dimensions were 3.47±1.73 cm (range, 0.8-6.8 cm). Water-clear cell adenoma, which shows similar clinical characteristics to other parathyroid adenomas, is an uncommon cause of hyperparathyroidism.

Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers

PubMed Central

Hernández-Ramírez, Laura C.; Gabrovska, Plamena; Dénes, Judit; Stals, Karen; Trivellin, Giampaolo; Tilley, Daniel; Ferraù, Francesco; Evanson, Jane; Ellard, Sian; Grossman, Ashley B.; Roncaroli, Federico; Gadelha, Mônica R.

2015-01-01

Context: Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease. Objective: To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members. Design: This was an observational, longitudinal study conducted over 7 years. Setting: International collaborative study conducted at referral centers for pituitary diseases. Participants: FIPA families (n = 216) and sporadic young-onset (≤30 y) pituitary adenoma patients (n = 404) participated in the study. Interventions: We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant. Main Outcome Measure(s): We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis. Results: Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening. Conclusions: A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas. PMID

Telangiectatic adenoma - computed tomography and magnetic resonance findings: a case report and review of the literature.

PubMed

Takayassu, Tatiana Chinem; Marchiori, Edson; Eiras, Antonio; Cabral, Rafael Ferracini; Cabral, Fernanda Caseira; Batista, Raquel Ribeiro; Zanetti, Gláucia; Dias, Paula Cristina Pereira

2009-01-07

Telangiectatic adenoma is a new classification of a hepatic lesion. It was previously named telangiectatic focal nodular hyperplasia but it is in fact true adenoma with telangiectatic features. We report here a case of telangiectatic adenoma in a 72-year-old woman. The image features are lack of a central scar, a heterogeneous lesion, hyperintensity in T1-weighted MR images, strong hyperintensity in T2-weighted MR images, and persistent contrast enhancement in delayed-phase contrast-enhanced CT or T1-weighted MR images. It is a monoclonal lesion with potential of malignancy. The treatment of telangiectatic adenoma is surgery, the same way as hepatic adenoma. Focal nodular hyperplasia may be managed by clinical follow-up alone.

Expression of the pituitary transcription factor Ptx-1, but not that of the trans-activating factor prop-1, is reduced in human corticotroph adenomas and is associated with decreased alpha-subunit secretion.

PubMed

Skelly, R H; Korbonits, M; Grossman, A; Besser, G M; Monson, J P; Geddes, J F; Burrin, J M

2000-07-01

We have studied the expression of the pituitary transcription factors Ptx-1 and Prop-1 in a series of 34 pituitary adenomas fully characterized for in vitro hormone secretion and histological staining. In studies involving mammalian cell lines, the pituitary transcription factor Ptx-1 has been shown to be a pituitary hormone panactivator, whereas more recent studies have shown that it plays an important role in alpha-subunit gene expression. Its expression has not been examined previously in human pituitary adenomas characterized by in vitro hormone secretory profiles. Of the 34 pituitary adenomas studied, Ptx-1 expression was reduced by more than 50% compared to that of the housekeeping gene human glyceraldehyde-3-phosphate dehydrogenase in the 6 corticotroph adenomas, which also had significantly reduced alpha-subunit production (all 6 tumors secreting < or =0.5 ng/24 h). Mutations of the pituitary transcription factor Prop-1, which is responsible for the syndrome of Ames dwarfism in mice, are being increasingly recognized as a cause of combined pituitary hormone deficiency in humans, although ACTH deficiency has been described only once. Prop-1 expression was detected in all 34 pituitary adenomas, including 6 corticotroph adenomas and 5 gonadotroph adenomas. The expression of Prop-1 has not been described previously in these cell phenotypes.

Follicular adenoma in ectopic thyroid. A case-report.

PubMed

Consalvo, Vincenzo; Barbieri, Gerarda; Rossetti, Amalia Rosaria Rita; Romano, Mafalda; Contieri, Rosaria; Tramontano, Salvatore; Rescigno, Carmela; Infranzi, Massimo; Lombardi, Domenico

2017-01-01

The term ectopic thyroid refers to the presence of thyroid tissue located far from its usual anatomic placement and with no vascular connection to the main gland. The presence of swelling in atypical locations is diagnostically differentiated from other pathologies like pleomorphic adenoma or carcinoma, inflammatory lesions like sialadenitis, neurogenic tumors, paraganglioma, fibrolipoma and lymphadenopaties of diverse etiologies. Here we present the case of a submandibular ectopic thyroid in a 67year old woman. She came to our attention for a left submandibular swelling. The anamnesis did not show related pathologies, as well as blood tests. Diagnostic image studies and a FNAC were performed. The mass was surgically removed and histopatology showed a follicular adenoma in the contest of the capsulated lesion. It is important to not underestimate these types of lesions and procede with hematochemical, instrumental tests and above all surgery that can eliminate any diagnostic uncertainty and on the whole be therapeutic. It should not be forgotten that ectopic thyroid tissue can be a site for adenoma or papillary carcinoma and thus any watch and wait strategy should be avoided. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Traditional serrated adenoma (TSA): morphological questions, queries and quandaries.

PubMed

Chetty, Runjan

2016-01-01

Traditional serrated adenoma (TSA) is an uncommon type of serrated adenoma that can be a precursor to biologically aggressive colorectal cancer that invokes the serrated (accelerated) pathway. The purpose of this review is to address some of the more contentious issues around nomenclature, diagnostic criteria, histological variants, coexistence with other polyp types, the occurrence of dysplasia and the differential diagnosis. While the vast majority of TSAs are exophytic villiform polyps composed of deeply eosinophilic cells, flat top luminal serrations and numerous ectopic crypt foci, histological variants include flat TSA, filiform TSA and one composed of large numbers of mucin-containing cells. It is unlikely that there is any biological difference between the histological variants. There is a contention that TSAs are not dysplastic ab initio and that the majority do not show cytological atypia. Two types of dysplasia are associated with TSA. Serrated dysplasia is less well recognised and less commonly encountered than adenomatous dysplasia. TSA with dysplasia must be separated from TSA with coexisting conventional adenoma. TSA is a characteristic polyp that may be extremely exophytic, flat or composed of mucin-rich cells and is typified by numerous ectopic crypt foci. They may coexist with other serrated polyps and conventional adenomas. Approximately 20-25% will be accompanied by adenomatous dysplasia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Brunner’s gland adenoma of duodenum: report of two cases

PubMed Central

Lu, Li; Li, Ruotong; Zhang, Guojing; Zhao, Zhicheng; Fu, Weihua; Li, Weidong

2015-01-01

Brunner’s gland adenoma is a rare tumor of the duodenum and might also be an unusual cause of gastrointestinal bleeding or obstruction. The pathogenesis of Brunner gland hamartoma of the duodenum is unknown. We report two cases of Brunner’s gland adenoma. Surgical resection was carried out because the tumor size was big in both cases and one accompanied with bleeding. Pathological examination revealed submucosal nodular hyperplasia of the Brunner’s glands. PMID:26261670

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention

PubMed Central

Lance, Peter; Alberts, David S.; Thompson, Patricia A.; Fales, Liane; Wang, Fang; Jose, Jerilyn San; Jacobs, Elizabeth T.; Goodman, Phyllis J.; Darke, Amy K.; Yee, Monica; Minasian, Lori; Thompson, Ian M.; Roe, Denise J.

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as alpha tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90–1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared to placebo (RR = 1.03, 95% CI, 0.96–1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. PMID:27777235

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...

Quantitative evaluation of vision-related and health-related quality of life after endoscopic transsphenoidal surgery for pituitary adenoma.

PubMed

Wolf, Amparo; Coros, Alexandra; Bierer, Joel; Goncalves, Sandy; Cooper, Paul; Van Uum, Stan; Lee, Donald H; Proulx, Alain; Nicolle, David; Fraser, J Alexander; Rotenberg, Brian W; Duggal, Neil

2017-08-01

OBJECTIVE Endoscopic resection of pituitary adenomas has been reported to improve vision function in up to 80%-90% of patients with visual impairment due to these adenomas. It is unclear how these reported rates translate into improvement in visual outcomes and general health as perceived by the patients. The authors evaluated self-assessed health-related quality of life (HR-QOL) and vision-related QOL (VR-QOL) in patients before and after endoscopic resection of pituitary adenomas. METHODS The authors prospectively collected data from 50 patients who underwent endoscopic resection of pituitary adenomas. This cohort included 32 patients (64%) with visual impairment preoperatively. Twenty-seven patients (54%) had pituitary dysfunction, including 17 (34%) with hormone-producing tumors. Patients completed the National Eye Institute Visual Functioning Questionnaire and the 36-Item Short Form Health Survey preoperatively and 6 weeks and 6 months after surgery. RESULTS Patients with preoperative visual impairment reported a significant impact of this condition on VR-QOL preoperatively, including general vision, near activities, and peripheral vision; they also noted vision-specific impacts on mental health, role difficulties, dependency, and driving. After endoscopic resection of adenomas, patients reported improvement across all these categories 6 weeks postoperatively, and this improvement was maintained by 6 months postoperatively. Patients with preoperative pituitary dysfunction, including hormone-producing tumors, perceived their general health and physical function as poorer, with some of these patients reporting improvement in perceived general health after the endoscopic surgery. All patients noted that their ability to work or perform activities of daily living was transiently reduced 6 weeks postoperatively, followed by significant improvement by 6 months after the surgery. CONCLUSIONS Both VR-QOL and patient's perceptions of their ability to do work and

Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

PubMed

Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

1979-12-01

A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.

Dual Pathologies of Parathyroid Adenoma and Papillary Thyroid Cancer on Fluorocholine and Fluorodeoxyglucose PET/CT.

PubMed

Thanseer, N T K; Bhadada, Sanjay Kumar; Sood, Ashwani; Parihar, Ashwin Singh; Dahiya, Divya; Singh, Priyanka; Basher, Rajender Kumar; Das, Ashim; Mittal, Bhagwant R

2018-04-01

18 F-Fluorocholine (FCH) PET/CT is evolving as a functional imaging modality for the preoperative imaging of abnormal parathyroid tissue(s) helping to localize eutopic and ectopic parathyroid tissue and limit the extent of surgery. FCH PET/CT may show incidental uptake in various thyroid lesions necessitating further evaluation, whereas the role of 18 F-fluorodeoxyglucose (FDG) PET/CT in the detection of incidental thyroid nodules is well documented. The case of a middle-aged woman with dual pathology of parathyroid adenoma and papillary thyroid cancer detected on FCH and FDG PET/CT is presented.

Five-year follow-up of a 13-year-old boy with a pituitary adenoma causing gigantism--effect of octreotide therapy.

PubMed

Schoof, Ellen; Dörr, Helmuth G; Kiess, Wieland; Lüdecke, Dieter K; Freitag, Eduard; Zindel, Volker; Rascher, Wolfgang; Dötsch, Jörg

2004-01-01

In children, there is little experience with octreotide therapy for pituitary tumors, especially growth hormone (GH) producing adenomas. We report on a 13-year-old boy with gigantism due to a GH-producing pituitary adenoma caused by a Gsalpha mutation on the basis of McCune-Albright syndrome. At the age of 6.5 years a GH- and prolactin-producing pituitary adenoma was diagnosed. The adenoma was surgically removed. Immediately thereafter, the small adenoma residuum was treated with octreotide (2 x 100 microg/day s.c.). During therapy with octreotide, the growth rate dropped to normal values; however, rose again after 2 years of treatment. The insulin-like growth factor I (IGF-I) levels remained above the 95th percentile, the GH level mostly >2 microg/l. After 5 years of octreotide therapy, GH (6.9 microg/l), IGF-I (620 microg/l), IGF-binding protein 3 (5.4 mg/l), and prolactin (17.0 ng/ml) levels were still elevated. The growth velocity was +2.4 SDS (standard deviation score), the pubertal status was mature, and the bone age was 14.3 years (prospective final height 208 cm). A magnetic resonance imaging scan showed an unchanged residual 4-mm rim of adenoma at the pituitary site. Side effects from octreotide therapy were not reported by the patient or his family. The therapy was changed to the long-acting release octreotide analog octreotide-LAR. After 1 year of treatment with octreotide-LAR, the GH level was 1.0 microg/l, and the prospective final height dropped by 10 cm. This case demonstrates that combined surgical and medical treatment can influence the prognosis of childhood gigantism; however, the prognosis of this rare condition remains uncertain. Copyright 2004 S. Karger AG, Basel

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 Resources Genetic Testing (1 link) Genetic Testing Registry: ...

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

Colorectal Adenomas in Participants of the SELECT Randomized Trial of Selenium and Vitamin E for Prostate Cancer Prevention.

PubMed

Lance, Peter; Alberts, David S; Thompson, Patricia A; Fales, Liane; Wang, Fang; San Jose, Jerilyn; Jacobs, Elizabeth T; Goodman, Phyllis J; Darke, Amy K; Yee, Monica; Minasian, Lori; Thompson, Ian M; Roe, Denise J

2017-01-01

Selenium and vitamin E micronutrients have been advocated for the prevention of colorectal cancer. Colorectal adenoma occurrence was used as a surrogate for colorectal cancer in an ancillary study to the Selenium and Vitamin E Cancer Prevention Trial (SELECT) for prostate cancer prevention. The primary objective was to measure the effect of selenium (as selenomethionine) on colorectal adenomas occurrence, with the effect of vitamin E (as α-tocopherol) supplementation on colorectal adenoma occurrence considered as a secondary objective. Participants who underwent lower endoscopy while in SELECT were identified from a subgroup of the 35,533 men randomized in the trial. Adenoma occurrence was ascertained from the endoscopy and pathology reports for these procedures. Relative Risk (RR) estimates and 95% confidence intervals (CI) of adenoma occurrence were generated comparing those randomized to selenium versus placebo and to vitamin E versus placebo based on the full factorial design. Evaluable endoscopy information was obtained for 6,546 participants, of whom 2,286 had 1+ adenomas. Apart from 21 flexible sigmoidoscopies, all the procedures yielding adenomas were colonoscopies. Adenomas occurred in 34.2% and 35.7%, respectively, of participants whose intervention included or did not include selenium. Compared with placebo, the RR for adenoma occurrence in participants randomized to selenium was 0.96 (95% CI, 0.90-1.02; P = 0.194). Vitamin E did not affect adenoma occurrence compared with placebo (RR = 1.03; 95% CI, 0.96-1.10; P = 0.38). Neither selenium nor vitamin E supplementation can be recommended for colorectal adenoma prevention. Cancer Prev Res; 10(1); 45-54. ©2016 AACR. ©2016 American Association for Cancer Research.

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. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Immunohistochemichal Assessment of the CrkII Proto-oncogene Expression in Common Malignant Salivary Gland Tumors and Pleomorphic Adenoma.

PubMed

Askari, Mitra; Darabi, Masoud; Jahanzad, Esa; Mostakhdemian Hosseini, Zahra; Musavi Chavoshi, Marjan; Darabi, Maryam

2015-01-01

Background and aims. Various morphologies are seen in different salivary gland tumorsor within an individual tumor, and the lesions show divers biological behaviors. Experimental results support the hypothesis that increased CrkII proto-oncogene is associated with cytokine-induced tumor initiation and progression by altering cell motility signaling pathway. The aim of this study was to assess the CrkII expression in common malignant salivary gland tumors and pleomorphic ade-noma. Materials and methods. Immunohistochemical analysis of CrkII expression was performed on paraffin blocks of 64 car-cinomas of salivary glands, 10 pleomorphic adenomas, and 10 normal salivary glands. Biopsies were subjected to immu-nostaining with EnVision detection system using monoclonal anti-CrkII. Evaluation of immunoreactivity of CrkII was based on the immunoreaction intensity and percentage of stained tumor cells which were scored semi-quantitatively on a scale with four grades 0 to 3. Kruskal-wallis test and additional Mann-Whitney statistical test were used for analysis of CrkII expression levels. Results. Increased expression of CrkII was seen (P=0.005) in malignant tumors including: mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic adenoma, but CrkII expression in acinic cell carcinoma was weak. CrkII expression in pleomorphic adenoma was weak or negative. A weak staining was sparsely seen in normal acinar serous cell. Conclusion. Increased expression of CrkII and its higher intensity of staining in tumors with more aggressive biologic behavior in carcinomas of salivary gland is consistent with a role for this proto-oncogene in salivary gland tumorigenesis and cancer progression.

Hypoxia induces hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

PubMed

Xiao, Zhengzheng; Liu, Qin; Zhao, Boxi; Wu, Jun; Lei, Ting

2011-12-01

The hypoxia inducible factor 1 α (HIF-1α) activity has been associated with various hemorrhagic events. The biological role of HIF-1α in the hemorrhagic transformation of pituitary adenomas remains unknown. We hypothesized that fast growing tumor cells tend to predispose themselves to sublethal hypoxia and activate the HIF-1α signaling pathway, leading to hemorrhagic transformation in pituitary adenomas. Here, we used apoplectic and non-apoplectic pituitary adenomas to determine the involvement of HIF-1α signaling in intratumoral hemorrhage. We employed HIF-1α overexpression/knockdown strategies to examine the association between HIF-1α signaling and hemorrhagic presentation in vitro and in vivo. In support of our hypothesis, compared with non-hemorrhagic pituitary adenomas, higher cellular proliferation was observed in hemorrhagic ones and it correlated with increased HIF-1α signaling. HIF-1α overexpression activated its downstream genes, vascular endothelial growth factor and the proapoptotic BNIP3, in MMQ pituitary adenoma cells and this up-regulation was attenuated by HIF-1 siRNA. In vivo studies using MMQ cell xenografts in nude mice showed that HIF-1α overexpression significantly promoted hemorrhagic transformation. Our study indicates that tumor hypoxia, following rapid tumor growth, may promote hemorrhagic transformation in pituitary adenomas via the HIF-1α signaling pathway.

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma

Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.

PubMed

Shimizu, Masahito; Fukutomi, Yasushi; Ninomiya, Mitsuo; Nagura, Kazuo; Kato, Tomohiro; Araki, Hiroshi; Suganuma, Masami; Fujiki, Hirota; Moriwaki, Hisataka

2008-11-01

Experimental studies indicate the chemopreventive properties of green tea extract (GTE) on colorectal cancer. Epidemiologically, green tea consumption of > 10 cups daily reduced colorectal cancer risk in Japanese. Because colorectal adenomas are the precursors to most sporadic colorectal cancers, we conducted a randomized trial to determine the preventive effect of GTE supplements on metachronous colorectal adenomas by raising green tea consumption in the target population from an average of 6 cups (1.5 g GTE) daily to > or = 10 cups equivalent (2.5 g GTE) by supplemental GTE tablets. We recruited 136 patients, removed their colorectal adenomas by endoscopic polypectomy, and 1 year later confirmed the clean colon (i.e., no polyp) at the second colonoscopy. The patients were then randomized into two groups while maintaining their lifestyle on green tea drinking: 71 patients supplemented with 1.5 g GTE per day for 12 months and 65 control patients without supplementation. Follow-up colonoscopy was conducted 12 months later in 125 patients (65 in the control group and 60 in the GTE group). The incidence of metachronous adenomas at the end-point colonoscopy was 31% (20 of 65) in the control group and 15% (9 of 60) in the GTE group (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < 0.05). The size of relapsed adenomas was also smaller in the GTE group than in the control group (P < 0.001). No serious adverse events occurred in the GTE group. GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas.

Differentiation between Cystic Pituitary Adenomas and Rathke Cleft Cysts: A Diagnostic Model Using MRI.

PubMed

Park, M; Lee, S-K; Choi, J; Kim, S-H; Kim, S H; Shin, N-Y; Kim, J; Ahn, S S

2015-10-01

Cystic pituitary adenomas may mimic Rathke cleft cysts when there is no solid enhancing component found on MR imaging, and preoperative differentiation may enable a more appropriate selection of treatment strategies. We investigated the diagnostic potential of MR imaging features to differentiate cystic pituitary adenomas from Rathke cleft cysts and to develop a diagnostic model. This retrospective study included 54 patients with a cystic pituitary adenoma (40 women; mean age, 37.7 years) and 28 with a Rathke cleft cyst (18 women; mean age, 31.5 years) who underwent MR imaging followed by surgery. The following imaging features were assessed: the presence or absence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, an off-midline location, the presence or absence of an intracystic nodule, size change, and signal change. On the basis of the results of logistic regression analysis, a diagnostic tree model was developed to differentiate between cystic pituitary adenomas and Rathke cleft cysts. External validation was performed for an additional 16 patients with a cystic pituitary adenoma and 8 patients with a Rathke cleft cyst. The presence of a fluid-fluid level, a hypointense rim on T2-weighted images, septation, and an off-midline location were more common with pituitary adenomas, whereas the presence of an intracystic nodule was more common with Rathke cleft cysts. Multiple logistic regression analysis showed that cystic pituitary adenomas and Rathke cleft cysts can be distinguished on the basis of the presence of a fluid-fluid level, septation, an off-midline location, and the presence of an intracystic nodule (P = .006, .032, .001, and .023, respectively). Among 24 patients in the external validation population, 22 were classified correctly on the basis of the diagnostic tree model used in this study. A systematic approach using this diagnostic tree model can be helpful in distinguishing cystic pituitary adenomas from Rathke cleft cysts

Familial acromegaly with pituitary adenoma. Report of three affected siblings.

PubMed

Abbassioun, K; Fatourehchi, V; Amirjamshidi, A; Meibodi, N A

1986-03-01

The authors report the cases of three brothers with pituitary adenomas who had classical findings of acromegaly and gigantism. Two had irreducibly elevated growth hormone (GH) values and underwent transsphenoidal microsurgical extirpation of their tumors. The third acromegalic brother had a normal GH value and evidence of panhypopituitarism; he had a small intrasellar tumor and a partially empty sella. The pattern of inheritance was probably autosomal recessive. A review of literature indicated that familial incidence of isolated acromegaly with pituitary adenomas is rare.

Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas.

PubMed

Yoon, Jung Hwan; Song, Jae Hwi; Zhang, Cao; Jin, Meishan; Kang, Young Hwi; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

2011-04-01

Gastrokine 1 (GKN1) plays a role in the gastric mucosal defence mechanism and may be a gastric tumour suppressor. We have investigated whether inactivation of the GKN1 gene is involved in the development and/or progression of gastric cancers. GKN1 protein expression was examined in gastric adenomas and cancer and we also analysed GKN1 mutation and epigenetic alteration, DNA copy number change and mRNA transcript expression. The effect of GKN1 on cell proliferation and death was examined in wild-type GKN1-transfected AGS gastric cancer cells. Reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathological parameters, including depth of invasion, location and lymph node metastasis (χ(2) test, p > 0.05). In western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumours, and hypermethylation of GKN1 gene was found in two tumours. DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Collision tumors of the sella: coexistence of pituitary adenoma and craniopharyngioma in the sellar region

PubMed Central

2013-01-01

Collision tumors of the sellar region are relatively uncommon and consist mainly of more than one type of pituitary adenoma or a cyst or cystic tumor. The association of a pituitary adenoma and a craniopharyngioma is particularly rare. This study describes a rare occurrence in which a pituitary adenoma and a craniopharyngioma coexisted in the sellar region. The case involves a 47-year-old woman who underwent transsphenoidal surgery with subtotal tumor resection and reoperation using an interhemispheric transcallosal approach for total microsurgical resection of the tumor because the visual acuity in her left eye had re-deteriorated. Histopathological and immunohistochemical examinations of the excised tissue revealed a pituitary adenoma in the first operation and a craniopharyngioma in the second operation. Retrospective analysis found the coexistence of a pituitary adenoma and a craniopharyngioma, known as a collision tumor. Instead of the transsphenoidal approach, a craniotomy should be performed, to explore the suprasellar region. PMID:23919255

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas

PubMed Central

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M.; Gahete, Manuel D.; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C.; Gálvez, María A.; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J.; Maraver-Selfa, Silvia; Japón, Miguel A.; García-Arnés, Juan A.; Soto-Moreno, Alfonso; Webb, Susan M.; Kineman, Rhonda D.; Culler, Michael D.; Castaño, Justo P.; Luque, Raúl M.

2017-01-01

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3–5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760. PMID:28181484

BIM-23A760 influences key functional endpoints in pituitary adenomas and normal pituitaries: molecular mechanisms underlying the differential response in adenomas.

PubMed

Ibáñez-Costa, Alejandro; López-Sánchez, Laura M; Gahete, Manuel D; Rivero-Cortés, Esther; Vázquez-Borrego, Mari C; Gálvez, María A; de la Riva, Andrés; Venegas-Moreno, Eva; Jiménez-Reina, Luis; Moreno-Carazo, Alberto; Tinahones, Francisco J; Maraver-Selfa, Silvia; Japón, Miguel A; García-Arnés, Juan A; Soto-Moreno, Alfonso; Webb, Susan M; Kineman, Rhonda D; Culler, Michael D; Castaño, Justo P; Luque, Raúl M

2017-02-09

Chimeric somatostatin/dopamine compounds such as BIM-23A760, an sst2/sst5/D 2 receptors-agonist, have emerged as promising new approaches to treat pituitary adenomas. However, information on direct in vitro effects of BIM-23A760 in normal and tumoral pituitaries remains incomplete. The objective of this study was to analyze BIM-23A760 effects on functional parameters (Ca 2+ signaling, hormone expression/secretion, cell viability and apoptosis) in pituitary adenomas (n = 74), and to compare with the responses of normal primate and human pituitaries (n = 3-5). Primate and human normal pituitaries exhibited similar sst2/sst5/D2 expression patterns, wherein BIM-23A760 inhibited the expression/secretion of several pituitary hormones (specially GH/PRL), which was accompanied by increased sst2/sst5/D2 expression in primates and decreased Ca 2+ concentration in human cells. In tumoral pituitaries, BIM-23A760 also inhibited Ca 2+ concentration, hormone secretion/expression and proliferation. However, BIM-23A760 elicited stimulatory effects in a subset of GHomas, ACTHomas and NFPAs in terms of Ca 2+ signaling and/or hormone secretion, which was associated with the relative somatostatin/dopamine-receptors levels, especially sst5 and sst5TMD4. The chimeric sst2/sst5/D 2 compound BIM-23A760 affects multiple, clinically relevant parameters on pituitary adenomas and may represent a valuable therapeutic tool. The relative ssts/D 2 expression profile, particularly sst5 and/or sst5TMD4 levels, might represent useful molecular markers to predict the ultimate response of pituitary adenomas to BIM-23A760.

Risk of colorectal adenomas in patients with celiac disease: a systematic review and meta-analysis.

PubMed

Lasa, J; Rausch, A; Zubiaurre, I

Whether celiac disease increases the risk of presenting with colorectal adenoma or not, has not been extensively evaluated. This question becomes relevant when considering early screening methods in patients with the disease. The aim of our article was to determine the risk of colorectal adenomas in celiac disease patients. A computer-assisted search of the MEDLINE-Pubmed, EMBASE, LILACS, Cochrane Library, and Google Scholar databases was carried out, encompassing the time frame of 1966 to December 2016. The search strategy consisted of the following MESH terms: 'celiac disease' OR 'celiac sprue' AND 'colorectal' OR 'colorectal neoplasia' OR 'colorectal adenoma'. A fixed-effect model was used for the analyses. The first analysis dealt with the prevalence of all presentations of colorectal adenoma in patients with celiac disease and the second was on the prevalence of advanced adenomas. The outcomes were described as odds ratios (OR) with their 95% confidence intervals. The search identified 480 bibliographic citations, 17 of which were chosen for evaluation. Fourteen of those studies were rejected, leaving a final total of three for the analysis. Those studies included 367 cases of celiac disease and 682 controls. No significant heterogeneity was observed (I 2 =26%). There was no increased prevalence of colorectal adenomas in the celiac disease patients, when compared with the controls (OR: 0.94 [0.65-1.38]), and no significant difference was observed when assessing the prevalence of advanced adenomas (OR: 0.97 [0.48-1.97]). Celiac disease was not associated with an increased risk of colorectal adenomas. However, due to the limited evidence available, more studies are necessary to determine whether there is an actual association. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Acromegaly due to a Macroinvasive Plurihormonal Pituitary Adenoma and a Rectal Carcinoid Tumor

PubMed Central

Chin, Sang Ouk; Hwang, Jin-Kyung; Rhee, Sang Youl; Chon, Suk; Oh, Seungjoon; Lee, Misu; Pellegata, Natalia S.

2015-01-01

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor. PMID:25559714

Rate based failure detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Brett Emery Trabun; Gamage, Thoshitha Thanushka; Bakken, David Edward

This disclosure describes, in part, a system management component and failure detection component for use in a power grid data network to identify anomalies within the network and systematically adjust the quality of service of data published by publishers and subscribed to by subscribers within the network. In one implementation, subscribers may identify a desired data rate, a minimum acceptable data rate, desired latency, minimum acceptable latency and a priority for each subscription. The failure detection component may identify an anomaly within the network and a source of the anomaly. Based on the identified anomaly, data rates and or datamore » paths may be adjusted in real-time to ensure that the power grid data network does not become overloaded and/or fail.« less

Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy).

PubMed

Zorzi, Manuel; Senore, Carlo; Da Re, Filippo; Barca, Alessandra; Bonelli, Luigina Ada; Cannizzaro, Renato; de Pretis, Giovanni; Di Furia, Lucia; Di Giulio, Emilio; Mantellini, Paola; Naldoni, Carlo; Sassatelli, Romano; Rex, Douglas K; Zappa, Marco; Hassan, Cesare

2017-07-01

To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Induction of Adenomas by the Irradiation of Salivary Glands of Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glücksman, A.; Cherry, C. P.; Glucksman, A.

1962-08-01

Local irradiation induces adenomas in the three major salivary glands of rats. Their incidence varies with dose, over-all time of treatment, and sex of the animals. The sublingual gland is most and the parotid the least prone to adenoma formation; the submandibular gland is intermediate. With fractionated protracted doses of x rays the tumor formation is greater than with concentrated smaller doses in the parotid, the submandibular, and the skin, but lower in the sublingunal. For the same dose of x rays the sublingual produces 100% adenomas in males and 50% in females, but none in castrated females. Adenomae occurmore » only in regions in which the acini have disappeared. They are of acinar type in the sublingual and submandibular, formed by the proliferative activity of intercalated ducts. In the parotid they are of tubular type and formed by dedifferentiated ducts. Radiation causes compensatory secretory activity in the intercalated ducts of the sublingunal and the tubules of the submandibular gland but the disappearance of secretory granules in the intercalated ducts of the parotid. Adenoma formation follows the stimulation of regenerative activity in intercalated ducts and in the parotid of excretory ducts by the progressive disappearance of acini and the compensatory activity of the secretory tubules. It is influenced by the sex of the rats and by the type of radiation treatment, but is not a function of radiation dose.« less

Fetal adenoma of the pigmented ciliary epithelium associated with persistent hyperplastic primary vitreous.

PubMed

Doro, S; Werblin, T P; Haas, B; Iwamoto, T; Jakobiec, F A

1986-10-01

A 1.5-year-old girl presented with a peripheral iris mass. When the girl was 3 years old, the lesion was excised after it had manifested significant growth. A stalk of fibrovascular tissue was noted to extend from the lesion to the optic disc. Histopathologically, the tumor was a well-circumscribed, pigmented ciliary body adenoma. Electron microscopy revealed characteristic neuroepithelial melanosomes, distinct from those of choroidal melanocytes, and occasional annulate lamellae. A fibrovascular membrane extended over the tumor surface and was adherent to lens capsule. The association of this adenoma with a persistent stalk of primary vitreous indicates a congenital origin of this tumor. Both adenoma and adenocarcinoma of the pigmented and nonpigmented ciliary epithelium tend to be disorders of adults. The authors report the youngest presentation of a pigment epithelium adenoma, the only well-documented case associated with persistent hyperplastic primary vitreous, and the only documentation of annulate lamellae in a ciliary body tumor.

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases.

PubMed

Horvath, E; Kovacs, K; Smyth, H S; Cusimano, M; Singer, W

2005-01-01

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.

A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

PubMed

Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

2016-06-01

A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

PubMed Central

Bobe, Gerd; Sansbury, Leah B.; Albert, Paul S.; Cross, Amanda J.; Kahle, Lisa; Ashby, Jason; Slattery, Martha L.; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Marshall, James R.; Schatzkin, Arthur; Lanza, Elaine

2008-01-01

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non–steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; Ptrend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. PMID:18559549

Cushing's syndrome associated with a bronchial adenoma. Possible periodic hormonogenesis.

PubMed

Shapiro, M S; Gutman, A; Bruderman, I; Myers, B; Griffel, W B

1975-09-01

Diagnostic and therapeutic problems in a patient with ectopic ACTH syndrome caused by a malignant bronchial adenoma are discussed. Persistent Cushing's syndrome was present following apparent total adrenalectomy, but radioactive scanning with 131I-19-iodocholesterol showed the presence of residual adrenal tissue in the right suprarenal bed. Amelioration of the hypercortisolism occurred after removal of the bronchial adenoma. A paradoxical elevation of adrenocortical activity followed administration of dexamethasone and data are presented which suggest that periodic secretion of ACTH accounted for this phenomenon.

Telangiectatic adenoma – computed tomography and magnetic resonance findings: a case report and review of the literature

PubMed Central

2009-01-01

Telangiectatic adenoma is a new classification of a hepatic lesion. It was previously named telangiectatic focal nodular hyperplasia but it is in fact true adenoma with telangiectatic features. We report here a case of telangiectatic adenoma in a 72-year-old woman. The image features are lack of a central scar, a heterogeneous lesion, hyperintensity in T1-weighted MR images, strong hyperintensity in T2-weighted MR images, and persistent contrast enhancement in delayed-phase contrast-enhanced CT or T1-weighted MR images. It is a monoclonal lesion with potential of malignancy. The treatment of telangiectatic adenoma is surgery, the same way as hepatic adenoma. Focal nodular hyperplasia may be managed by clinical follow-up alone. PMID:19128493

Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery

PubMed Central

Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

2016-01-01

Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients’ ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. PMID:27106613

Quantitative analysis in spontaneous canine anal sac gland adenomas and carcinomas.

PubMed

Simeonov, Radostin; Simeonova, Galina

2008-12-01

Stained cytological specimens from 7 canine anal sac gland adenomas and 11 canine anal sac gland carcinomas were analyzed by computer-assisted nuclear morphometry. In each case, the nuclei of at least 100 neoplastic cells were measured, and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND) and nuclear roundness (NR) were calculated. The study aimed to evaluate (1) the possibility of using nuclear cytomorphometry as an auxiliary diagnostic method to differentiate between canine anal sac gland adenomas and adenocarcinomas, and (2) the prognostic value of nuclear morphometry in canine anal sac gland adenocarcinomas. The results indicated that (1) MNA, MNP, MND and NR could be used as effective auxiliary tools for differential diagnosis between canine anal sac gland adenomas and adenocarcinomas, and (2) MNA, MNP and MND are reliable prognostic indicators for canine anal sac gland adenocarcinomas.

Plurihormonal pituitary adenoma immunoreactive for thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, and prolactin.

PubMed

Luk, Cynthia T; Kovacs, Kalman; Rotondo, Fabio; Horvath, Eva; Cusimano, Michael; Booth, Gillian L

2012-01-01

To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment. A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved. Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.

Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk

PubMed Central

Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

2012-01-01

Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort. PMID:22724046

Polymorphisms in heterocyclic aromatic amines metabolism-related genes are associated with colorectal adenoma risk.

PubMed

Eichholzer, Monika; Rohrmann, Sabine; Barbir, Aline; Hermann, Silke; Teucher, Birgit; Kaaks, Rudolf; Linseisen, Jakob

2012-01-01

Colorectal adenoma (CRA) and colorectal cancer (CRC) risks have been linked to the intake of red and processed meat. Heterocyclic aromatic amines (HCA) formed herein during high temperature cooking, are metabolized by a variety of enzymes, and allelic variation in the coding genes could influence individual CRA risk. Associations of polymorphisms in NAT1, NAT2, GSTA1, SULT1A1, CYP1A2, UGT1A7, UGT1A9, GSTP1 genes with colorectal adenoma risk were investigated in a nested case-control study of the EPIC-Heidelberg cohort including 428 cases matched by age, sex and year of recruitment with one or two controls (n=828) with negative colonoscopy per case. Genoyping was preformed with the Sequenom MassArray system and the LightCycler 480. Conditional logistic regression was used to compute odds ratios (OR) and corresponding 95% confidence intervals (CI). For rs15561 (NAT1) and rs1057126 (NAT1), the rarer allel was significantly inversely associated with adenoma risk OR=0.80 (95% CI 0.65-0.97) and (OR=0.81 (95% CI 0.65-0.99) and, respectively). For the combined NAT2 alleles encoding for enzymes with medium (versus slow) activity we also observed a significantly inverse association with adenoma risk (OR=0.75; 95% CI 0.85-0.97). In addition, homozygous carriers of the A allele of rs3957357 (GSTA1), i.e., those with a decreased enzyme activity, had a decreased risk of colorectal adenoma with an OR of 0.68 (95% CI 0.50-0.92; AA versus GG/GA). Polymorphisms in the other tested genes did not modify the risk of colorectal adenomas. In conclusion, polymorphisms in NAT1, NAT2, and GSTA1 are related to colorectal adenoma risk in this German cohort.

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. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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

Cell-surface markers for colon adenoma and adenocarcinoma.

PubMed

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

2016-04-05

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.

Age of the host and other factors affecting the production with urethane of pulmonary adenomas in mice.

PubMed

ROGERS, S

1951-05-01

Young, rapidly growing mice are greatly more responsive to the adenoma-inducing influence of urethane than are those just arriving at maturity. This is manifest both in the proportion of animals developing the tumors and in their number per individual. An amount of urethane per gram body weight which suffices to induce adenomas in only an occasional 8-week-old animal will cause them to appear in quantity in more than half the 3-week-old mice injected. There is an almost absolute inverse correlation between the rate of growth of the pulmonary tissue between the ages of 2 and 10 weeks and the response to urethane in terms of adenomas. Hence the conclusion seems justified that the natural proliferative activity of the alveolar cells during youth plays a major part in the formation of the tumors. After the 6th week the age differences become relatively slight, yet there is reason to think that they continue in some degree as life goes on. Urethane has no effect to promote multiplication of the cells it has rendered neoplastic, its whole role being to initiate neoplastic change. The abnormalities induced by urethane in the nucleus of normal and neoplastic cells, as observed by previous workers, have suggested that the substance brings about the adenomatous state by acting upon the nucleus. But colchicine, also a karyolytic poison causing pronounced nuclear changes, does not alter in the least the yield of adenomas to urethane when administered concurrently. Nor does fasting influence the yield, though it markedly reduces mitotic activity. The meaning of these facts is discussed.

Changing pathological diagnosis from hyperplastic polyp to sessile serrated adenoma: systematic review and meta-analysis.

PubMed

Niv, Yaron

2017-12-01

The WHO published a new classification of colonic polyps in 2010, including the group of serrated polyps, which can be divided into hyperplastic polyps (HP), traditional serrated adenomas, and sessile serrated adenomas (SSA) or polyps. To assess the rate of re-diagnosis of HP to SSA and to look for possible predictors for changing the diagnosis. English Medical literature searches were performed for 'reassessment' OR 'reclassification' AND 'hyperplastic polyp' OR 'sessile serrated adenoma' till 31 January 2017. PRISMA guidelines for systematic reviews were followed. Studies that included a precise re-diagnosis of HP into SSA were included. We also looked for predictors of SSA diagnosis such as polyp location and size, patient sex and age, and synchronous advanced adenoma. Altogether, we found 220 eligible studies; 212 were excluded as they did not fulfill the inclusion criteria and we were left with eight studies including 2625 patients. The odds ratio for the number of polyps with changed pathological diagnosis from HP to SSA was 0.112 with 95% confidence interval (CI): 0.099-0.126 (P<0.0001) or 11.2%. Heterogeneity between studies was significant with Q=199.4, d.f. (Q)=9, P<0.0001, and I=95.486%. The odds ratio for changing the pathological diagnosis from HP to SSA for polyp proximal location and polyp size more than 5 mm were 4.401, 95% CI: 2.784-6.958, P<0.0001, and 8.336, 95% CI: 4.963-15.571, P<0.0001, respectively. Endoscopists and pathologists should be aware of the SSA diagnosis when finding HPs larger than 5 mm in the right colon. The diagnosis of HP in these cases should be reassessed by experienced gastrointestinal pathologists.

Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery.

PubMed

Abe, T; Tara, L A; Lüdecke, D K

1999-07-01

Pituitary tumors causing gigantism are rare in childhood and adolescence. In a review of 2367 patients with pituitary adenomas who were treated between 1970 and 1997, we found 15 cases (0.63%, 9 male and 6 female patients) of growth hormone-secreting pituitary adenomas in patients who were less than 20 years of age at the time of surgery, and we compared their characteristics with those of adenomas in an adult group. Patients were grouped according to their ages at the first operation, with five patients (33.3%) in the prepubescent group (0-11 yr), eight (53.3%) in the pubescent group (12-17 yr), and two (13.3%) in the postpubescent group (18-19 yr). All 15 patients exhibited the typical symptoms of growth hormone oversecretion. The incidence of hyperprolactinemia among patients with prepubescent onset was 66.7%. Radiological examinations demonstrated microadenomas in 4 patients (26.7%) and macroadenomas in 11 patients (73.3%). The mean follow-up period was 73.5 months. Direct transnasal explorations were performed for all patients. Tumor invasion into the cavernous sinus was observed in six patients (40%). Radical tumor resection was performed for four patients (80%) in the prepubescent group, for five patients (62.5%) in the pubescent group, and for neither patient in the postpubescent group. Surgical morbidity was caused by permanent diabetes insipidus in three patients (20%). Rapid growth was postoperatively improved in 80% of the prepubescent age group. The recurrence rate was 13.3% (2 of 15 patients). Transnasal pituitary surgery was found to be as safe in pediatric patients with gigantism as in adults. Growth hormone-secreting pituitary adenomas in childhood and adolescence were more likely to be invasive or aggressive than were those in adulthood. The clinical biological characteristics for children were different from those for adults.

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.

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

PubMed Central

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

2014-01-01

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

ESR1 and its antagonist fulvestrant in pituitary adenomas.

PubMed

Gao, Hua; Xue, Yake; Cao, Lei; Liu, Qian; Liu, Chunhui; Shan, Xiaosong; Wang, Hongyun; Gu, Yi; Zhang, Yazhuo

2017-03-05

Estrogen has a key role in the pathogenesis of pituitary adenomas (PAs). The study was to evaluate the estrogen receptor alpha (ESR1) level in 289 PAs cases, its association with clinicopathologic features and serving as a target of cancer treatment. In this study, the ESR1 level was evaluated by tissue microarray (TMA). The effect of fulvestrant was determined by an animal model of prolactinoma established by subcutaneous injection of 17β-estradiol in F344 rats. The volume and weight of the pituitary were assessed in the different groups. The effects of fulvestrant on cell proliferation and cell invasion were explored in the pituitary adenoma cell lines GH3 and JT1-1. The ESR1-positive cells rates of 191/289 cases were more than 50%. And ESR1 high level cases (age≥50) were 103/133, and 88/156 in cases (age<50) (X 2  = 14.17, p = 0.0001). The average weight of the pituitary gland in F344 rat tumor model induced by 17-β-estradiol was 38.6 ± 11.2 mg, almost 6 times higher than control group (6.2 ± 1.7 mg). Fulvestrant significantly reduced the weight of the pituitary and its inhibition rate was 68.4 ± 8.3%. TUNEL assay and Western blotting showed that fulvestrant induced apoptotic cell death in vivo and in vitro. PTEN/MAPK signaling pathways were activated in response to fulvestrant treatment in GH3 cells. U0126 partly rescued cell viability of GH3 cells after fulvestrant exposure. ESR1 can be a potential target for PAs, especially for elder GHomas and NFPAs. Fulvestrant may be a new choice for the treatment of PAs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

PubMed

Prendergast, Nicole; Goldstein, Jeffrey D; Beier, Alexandra D

2018-04-01

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Gallium-67 uptake by a benign adrenocortical adenoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jackson, J.A.; Naul, L.G.; Montgomery, J.L.

1988-08-01

A 55-yr-old man presented with an atypical relapsing meningitis and was found to have intense unilateral adrenal uptake by /sup 67/Ga imaging. Computed tomography showed a 4-cm right adrenal mass which was hypointense on the T1-weighted images and mildly hyperintense on the T2-weighted images of a magnetic resonance (MR) scan. At surgery, a coincidental benign adrenocortical adenoma was found. Because /sup 67/Ga uptake is usually associated with inflammatory or malignant lesions and malignant adrenal lesions are hyperintense on T2-weighted MR images, these findings contributed to diagnostic uncertainty in this patient. Thus, a nonhyperfunctional adrenocortical adenoma may be associated with abnormalmore » /sup 67/Ga uptake and atypical MR findings.« less

Preoperative clonidine use in trans-sphenoidal pituitary adenoma surgeries - a randomized controlled trial.

PubMed

Bajaj, Jitin; Mittal, Radhe Shyam; Sharma, Achal

2017-02-01

Pituitary masses are common lesions accounting for about 15-20% of all brain tumours. Oozing blood is an annoyance in microscopic sublabial trans-sphenoidal approach for these masses. There have been many ways of reducing the ooze, having their own pros and cons. To find out the efficacy and safety of clonidine in reducing blood loss in pituitary adenoma surgery through a randomized masked trial. It was a prospective randomized controlled trial done. Total 50 patients of pituitary adenomas were randomized into two groups. Group A (25 patients) was given 200 μg clonidine orally, while Group B (25 patients) was given placebo. Surgeon, anaesthesiologist and patient were blinded for the trial. Sublabial trans-septal trans-sphenoidal approach to sella and excision of mass was performed in each patient. Patients were studied for pre-, intra- and post-operative blood pressure and heart rate, pre- and post-operative imaging findings, intra-operative blood loss, bleeding grading by surgeon, surgeon's satisfaction about condition of specific part and quality of surgical field, operative time and extent of resection. Blood loss during the surgery, operative time and bleeding grading by the surgeon were found significantly less in the clonidine group, while quality of surgical field, condition of the specific part and extent of resection were found significantly better in the clonidine group (p value <.05). There was no untoward adverse effect of the drug in the test group. Clonidine is a safe and effective drug to reduce bleeding in trans-sphenoidal microscopic pituitary adenoma surgeries.

Endoscopic ultrasound evaluation in the surgical treatment of duodenal and peri-ampullary adenomas

PubMed Central

Azih, Lilian C; Broussard, Brett L; Phadnis, Milind A; Heslin, Martin J; Eloubeidi, Mohamad A; Varadarajulu, Shayam; Arnoletti, Juan Pablo

2013-01-01

AIM: To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection. METHODS: Records of 111 patients seen at our institution from November 1999 to July 2011 with the post-operative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed. RESULTS: Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included

Endoscopic ultrasound evaluation in the surgical treatment of duodenal and peri-ampullary adenomas.

PubMed

Azih, Lilian C; Broussard, Brett L; Phadnis, Milind A; Heslin, Martin J; Eloubeidi, Mohamad A; Varadarajulu, Shayam; Arnoletti, Juan Pablo

2013-01-28

To investigate endoscopic ultrasound (EUS) for predicting depth of mucosal invasion and to analyze outcomes following endoscopic and transduodenal resection. Records of 111 patients seen at our institution from November 1999 to July 2011 with the post-operative pathological diagnosis of benign ampullary and duodenal adenomas were reviewed. Records of patients who underwent preoperative EUS for diagnostic purposes were identified. The accuracy of EUS in predicting the absence of muscular invasion was assessed by comparing EUS reports to the final surgical pathological results. In addition, the incidence of the post-operative complications over a period of 30 d and the subsequent long-term outcome (recurrence) over a period of 30 mo associated with endoscopic and transduodenal surgical resection was recorded, compared and analyzed. Among 111 patients with benign ampullary and duodenal adenomas, 47 underwent preoperative EUS for 29 peri-ampullary lesions and 18 duodenal lesions. In addition, computed tomography was performed in 18 patients, endoscopic retrograde cholangio-pancreatography in 10 patients and esophagogastroduodenoscopy in 22 patients. There were 43 patients with sporadic adenomas and 4 patients with familial adenomatous polyposis (FAP)/other polyposis syndromes. In 38 (81%, P < 0.05) patients, EUS reliably identified absence of submucosal and muscularis invasion. In 4 cases, EUS underestimated submucosal invasion that was proven by pathology. In the other 5 patients, EUS predicted muscularis invasion which could not be demonstrated in the resected specimen. EUS predicted tumor muscularis invasion with a specificity of 88% and negative predictive value of 90% (P < 0.05). Types of resection performed included endoscopic resection in 22 cases, partial duodenectomy in 9 cases, transduodenal ampullectomy with sphincteroplasty in 10 cases and pancreaticoduodenectomy in 6 cases. The main post-operative final pathological results included villous adenoma (n = 5

A functional thyrotropin- and growth hormone-secreting pituitary adenoma with a ultrastructurally monomorphic feature: a case study.

PubMed

Ozawa, Y; Kameya, T; Kasuga, A; Naritaka, H; Kanda, N; Maruyama, H; Saruta, T

1998-04-01

A 38-yr-old female with a TSH- and GH-secreting pituitary adenoma is described, who had both overt symptoms, hyperthyroidism and acromegaly. Her serum TSH was not suppressed despite high concentrations of free T3 and free T4, and her alpha-subunit/TSH molar ratio was high. Her serum GH was consistently high, and was not suppressed by an oral glucose tolerance test. Preoperative testing revealed that, although the TSH response was impaired, TSH, alpha-subunit and GH were increased by TRH injection, and that these hormones were reduced by bromocriptine or somatostatin analog. Although she did not have hyperprolactinemia, the in vitro culture and immunohistochemical studies revealed that the adenoma cells produced and released PRL, in addition to TSH, alpha-subunit and GH. Immunohistochemical studies showed the presence of GH in the cytoplasm of many adenoma cells. TSH beta-positive adenoma cells were less frequently seen than GH-positive adenoma cells. No cells showed the coexistence of GH and TSH beta, and a few cells were positive for PRL. By electron microscopy, the adenoma was found to be composed of a single cell type resembling thyrotrophs, and did not have any characteristics of somatotrophs. This case was considered to be of interest, because the adenoma was ultrastructurally monomorphous, but immunohistochemically polymorphous.

Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

PubMed Central

Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

2015-01-01

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA).

PubMed

Torlakovic, Emina Emilia; Gomez, Jose D; Driman, David K; Parfitt, Jeremy R; Wang, Chang; Benerjee, Tama; Snover, Dale C

2008-01-01

The morphologic distinction between various serrated polyps of the colorectum may be challenging. The distinction between sessile serrated adenoma (SSA) and traditional serrated adenoma (TSA) may be difficult using currently available criteria mostly based on cytologic characteristics. We have evaluated 66 serrated polyps including 29 SSA, 18 TSA, and 19 hyperplastic polyps for overall shape of the polyps, architectural features of individual crypts, the presence of eosinophilic cytoplasm, size and distribution of the proliferation and maturation zones, as well as Ki-67 and CK20 expression. The extent of the expression of CK20 and Ki-67 could not distinguish between the 3 types of serrated polyps, but the distribution of their expression was very helpful and differences were statistically significant. The distribution of Ki-67+ cells was the single most helpful distinguishing feature of the serrated polyp type (P<0.0001, chi test). Hyperplastic polyps had regular, symmetric, and increased Ki-67 expression. SSA had irregular, asymmetric, and highly variable expression of Ki-67. TSA had low Ki-67 expression, which was limited to "ectopic crypts" and admixed tubular adenomalike areas. In serrated polyps, ectopic crypt formation (ECF) defined by the presence of ectopic crypts with their bases not seated adjacent to the muscularis mucosae was nearly exclusive to TSA and was found in all cases, while the presence of cytologic atypia and eosinophilia of the cytoplasm were characteristic, but not limited to TSA. No evidence of ECF, but nevertheless abnormal distribution of proliferation zone was characteristic of SSA, whereas HP had neither. The presence of the ECF defines TSA in a more rigorous fashion than previous diagnostic criteria and also explains the biologic basis of exuberant protuberant growth associated with TSA and the lack of such growth in SSA. Recognition of this phenomenon may also help in exploring the genetic and molecular basis for differences between

Clinical outcomes in male patients with lactotroph adenomas who required pituitary surgery: a retrospective single center study.

PubMed

Liu, Winnie; Zahr, Roula Shraiky; McCartney, Shirley; Cetas, Justin S; Dogan, Aclan; Fleseriu, Maria

2018-06-23

Lactotroph adenomas (LA) are the most frequently encountered pituitary tumors. Although more frequently observed in women, LAs in men were recently included in a more aggressive category regardless of histological grading, by the WHO. We aimed to perform a rigorous retrospective review of a single center's pre-operative evaluation, patient characteristics and outcomes of male LAs patients requiring pituitary surgery. A retrospective review, over 11 years, of patients who underwent resection of a pituitary adenoma at a single center was conducted. Predictors of persistent disease in male LAs patients along with a comparison to predictors of silent corticotroph adenomas (SCAs) patients who also underwent surgery at the center was also conducted. Thirty-one male patients with LAs were identified. When compared to SCAs patients, LAs male patients were younger (41 vs. 50 years of age, p = 0.01). Men with LAs had more invasive tumors (75% vs. 44.7% p = 0.02). More LAs in men had residual tumor after surgery than patients with SCA (92.6% vs. 42.1%, p < 0.001). Male patients with LAs and patients with SCA had similar rates of requiring additional surgery (28.9% vs. 24.1%, p = NS) and radiation therapy (18.4% vs. 19.4%, p = NS). High rates of DA resistance, invasive tumors and postoperative residual disease in male patients with LA who required surgery are shown. Surgery improved optic chiasm compression, PRL level and central hypogonadism but, not surprisingly, failed to normalize other pituitary hormones and/or eliminate need for DA therapy.

Electrical stimulation treatment for facial palsy after revision pleomorphic adenoma surgery.

PubMed

Goldie, Simon; Sandeman, Jack; Cole, Richard; Dennis, Simon; Swain, Ian

2016-04-22

Surgery for pleomorphic adenoma recurrence presents a significant risk of facial nerve damage that can result in facial weakness effecting patients' ability to communicate, mental health and self-image. We report two case studies that had marked facial weakness after resection of recurrent pleomorphic adenoma and their progress with electrical stimulation. Subjects received electrical stimulation twice daily for 24 weeks during which photographs of expressions, facial measurements and Sunnybrook scores were recorded. Both subjects recovered good facial function demonstrating Sunnybrook scores of 54 and 64 that improved to 88 and 96, respectively. Neither subjects demonstrated adverse effects of treatment. We conclude that electrical stimulation is a safe treatment and may improve facial palsy in patients after resection of recurrent pleomorphic adenoma. Larger studies would be difficult to pursue due to the low incidence of cases. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

Altered saturated and monounsaturated plasma phospholipid fatty acid profiles in adult males with colon adenomas

PubMed Central

Pickens, C. Austin; Lane-Elliot, Ami; Comstock, Sarah S.; Fenton, Jenifer I.

2016-01-01

Background Altered lipid metabolism and plasma fatty acid (FA) levels are associated with colorectal cancer (CRC). Obesity and elevated waist circumference (WC) increase the likelihood of developing precancerous colon adenomas. Methods Venous blood was collected from 126 males, ages 48 to 65 years, who received routine colonoscopies. Plasma phospholipid (PPL) FAs were isolated, derivatized, and then analyzed using gas chromatography. Odds ratios (ORs) and 95% confidence intervals were determined using polytomous logistic regression after adjusting for confounding factors (i.e. age, smoking, WC, and BMI). Results PPL palmitic acid (PA) was inversely correlated with the presence of colon adenomas (p = 0.01). For each unit increase in palmitoleic acid (OR: 3.75, p = 0.04) or elaidic acid (OR: 2.92, p = 0.04) an individual was more likely to have adenomas relative to no colon polyps. Higher enzyme activity estimates (EAEs) of stearoyl-CoA desaturase-1 (SCD-1, p = 0.02) and elongation of very long chain-6 (Elovl-6, p = 0.03) were associated with an individual being approximately 1.5 times more likely to have an adenoma compared to no polyps. Conclusions PPL FAs and EAEs, which have previously been associated with CRC, are significantly different in those with adenomas when compared to those without polyps. PPL PA, elaidic acid, and SCD-1 and Elovl-6 EAEs are associated with adenomas independent of BMI and WC. Impact PPL PA, elaidic acid, and SCD-1 and Elovl-6 EAEs are associated with adenomas even after adjusting for obesity-related risk factors and may function as novel biomarkers of early CRC risk. PMID:26721667

Comparing the outcomes of two strategies for colorectal tumor detection: policy-promoted screening program versus health promotion service.

PubMed

Wu, Ping-Hsiu; Lin, Yu-Min; Liao, Chao-Sheng; Chang, Hung-Chuen; Chen, Yu-Hung; Yang, Kuo-Ching; Shih, Chia-Hui

2013-06-01

The Taiwanese government has proposed a population-based colorectal tumor detection program for the average-risk population. This study's objectives were to understand the outcomes of these screening policies and to evaluate the effectiveness of the program. We compared two databases compiled in one medical center. The "policy-promoted cancer screening" (PPS) database was built on the basis of the policy of the Taiwan Bureau of National Health Insurance for cancer screening. The "health promotion service" (HPS) database was built to provide health check-ups for self-paid volunteers. Both the PPS and HPS databases employ the immunochemical fecal occult blood test (iFOBT) and colonoscopy for colorectal tumor screening using different strategies. A comparison of outcomes between the PPS and HPS included: (1) quality indicators-compliance rate, cecum reaching rate, and tumor detection rate; and (2) validity indicators-sensitivity, specificity, positive, and negative predictive values for detecting colorectal neoplasms. A total of 10,563 and 1481 individuals were enrolled in PPS and HPS, respectively. Among quality indicators, there was no statistically significant difference in the cecum reaching rate between PPS and HPS. The compliance rates were 56.1% for PPS and 91.8% for HPS (p < 0.001). The advanced adenoma detection rates of PPS and HPS were 1.0% and 3.6%, respectively (p < 0.01). The carcinoma detection rates were 0.3% and 0.4%, respectively (p = 0.59). For validity indicators, PPS provides only a positive predictive value for colorectal tumor detection. HPS provides additional validity indicators, including sensitivity, specificity, positive predictive value, and negative predictive value, for colorectal tumor screening. In comparison with the outcomes of the HPS database, the screening efficacy of the PPS database is even for detecting colorectal carcinoma but is limited in detecting advanced adenoma. HPS may provide comprehensive validity indicators and will

The association of calcium and vitamin D with risk of colorectal adenomas.

PubMed

Hartman, Terryl J; Albert, Paul S; Snyder, Kirk; Slattery, Martha L; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Marshall, James; Shike, Moshe; Weissfeld, Joel; Brewer, Brenda; Schatzkin, Arthur; Lanza, Elaine

2005-02-01

The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dietary calcium intake [odds ratio (OR) for the 5th compared with the lowest quintile = 0.91; 95% CI = 0.67-1.23; P-trend = 0.68], total calcium intake (OR = 0.86; 95% CI = 0.62-1.18; P-trend = 0.20), or dietary vitamin D intake (OR = 0.93; 95% CI = 0.69-1.25; P-trend = 0.43) averaged over follow-up. Total vitamin D intake was weakly inversely associated with adenoma recurrence (OR = 0.84; 95% CI = 0.62-1.13; P-trend = 0.03). Supplemental calcium and vitamin D use during follow-up also were inversely associated with adenoma recurrence (OR for any compared with no use = 0.82; 95% CI = 0.68-0.99; and OR = 0.82; 95% CI = 0.68-0.99; for calcium and vitamin D, respectively). Slightly stronger associations were noted for the prevention of multiple recurrences. Our analyses did not suggest a significant effect modification between total calcium and total vitamin D intake (P = 0.14) on risk for adenoma recurrence. This trial cohort provides some evidence that calcium and vitamin D may be inversely

Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing's disease: a case report.

PubMed

Takiguchi, Tomoko; Koide, Hisashi; Nagano, Hidekazu; Nakayama, Akitoshi; Fujimoto, Masanori; Tamura, Ai; Komai, Eri; Shiga, Akina; Kono, Takashi; Higuchi, Seiichiro; Sakuma, Ikki; Hashimoto, Naoko; Suzuki, Sawako; Miyabayashi, Yui; Ishiwatari, Norio; Horiguchi, Kentaro; Nakatani, Yukio; Yokote, Koutaro; Tanaka, Tomoaki

2017-09-02

A functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing's disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD. In our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing's disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture. Here we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD.

Intraosseous pleomorphic adenoma: case report and review of the literature.

PubMed

Aver-De-Araujo, L M; Chaves-Tarquinio, S B; Neuzling-Gomes, A P; Etges, A

2002-01-01

Pleomorphic adenoma is the most common neoplasm of the salivary glands, affecting mainly the parotid gland. The preferential intraoral site of this tumor is the palate. A case of a 31-year-old woman with an intraosseous pleomorphic adenoma located in the maxilla (left paramedian region), showing an approximate evolution of one year is reported. The present intraosseous case represents a rare location, with the tumor probably originating from glandular epithelial remnants captured during embryogenesis. In a review of the literature of 142 cases of intragnathic localization (24% in the maxilla) are identified. A slight predominance of women was observed (56%), with 55% of the patients being affected during the 5th to 7th decade of life. The tumors were malignant in 94% of the cases, with special predominance of mucoepidermoid carcinoma (65%). Intraosseous pleomorphic adenomas are rare, with the present patient being the 6th case reported in the literature and the second found in the maxilla. Mean age of the 5 previously reported cases was 58.8 years.

Hypophysopexy technique for radiosurgical treatment of cavernous sinus pituitary adenoma.

PubMed

Couldwell, William T; Rosenow, Joshua M; Rovit, Richard L; Benzil, Deborah L

2002-01-01

Stereotactic radiosurgery is being used with increased frequency in the treatment of residual or recurrent pituitary adenomas. The major risk associated with radiosurgical treatment of residual or recurrent pituitary tumor adjacent to normal functional pituitary gland is radiation of the pituitary, which frequently leads to the development of hypopituitarism. The authors describe a technique of pituitary transposition to reduce the radiation dose to the normal pituitary gland in cases of planned radiosurgical treatment of residual pituitary adenoma within the cavernous sinus. A sellar exploration for tumor resection is performed, the pituitary gland is transposed from the region of the cavernous sinus, and a fat and fascia graft is interposed between the normal pituitary gland and the residual tumor in the cavernous sinus. The residual tumor may then be treated with stereotactic radiosurgery. The increased distance between the normal pituitary gland and the residual tumor facilitates treatment of the tumor with radiosurgery and reduces the radiation to the normal pituitary gland. An illustrative case of a young female with recurrent acromegaly and a pituitary adenoma invading the cavernous sinus is described.

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

[A systematic review of worldwide natural history models of colorectal cancer: classification, transition rate and a recommendation for developing Chinese population-specific model].

PubMed

Li, Z F; Huang, H Y; Shi, J F; Guo, C G; Zou, S M; Liu, C C; Wang, Y; Wang, L; Zhu, S L; Wu, S L; Dai, M

2017-02-10

Objective: To review the worldwide studies on natural history models among colorectal cancer (CRC), and to inform building a Chinese population-specific CRC model and developing a platform for further evaluation of CRC screening and other interventions in population in China. Methods: A structured literature search process was conducted in PubMed and the target publication dates were from January 1995 to December 2014. Information about classification systems on both colorectal cancer and precancer on corresponding transition rate, were extracted and summarized. Indicators were mainly expressed by the medians and ranges of annual progression or regression rate. Results: A total of 24 studies were extracted from 1 022 studies, most were from America ( n =9), but 2 from China including 1 from the mainland area, mainly based on Markov model ( n =22). Classification systems for adenomas included progression risk ( n =9) and the sizes of adenoma ( n =13, divided into two ways) as follows: 1) Based on studies where adenoma was risk-dependent, the median annual transition rates, from ' normal status' to ' non-advanced adenoma', 'non-advanced' to ' advanced' and ' advanced adenoma' to CRC were 0.016 0 (range: 0.002 2-0.020 0), 0.020 (range: 0.002-0.177) and 0.044 (range: 0.005-0.063), respectively. 2) Median annual transition rates, based on studies where adenoma were classified by sizes, into <10 mm and ≥10 mm ( n =7), from ' normal' to adenoma <10 mm, from adenoma <10 mm to adenoma ≥10 mm and adenoma ≥ 10 mm to CRC, were 0.016 7 (range: 0.015 0-0.037 0), 0.020 (range: 0.015-0.035) and 0.040 0 (range: 0.008 5-0.050 0), respectively. 3) Median annual transition rates, based on studies where adenoma, were classified by sizes into diminutive (≤5 mm), small (6-9 mm) and large adenoma (≥10 mm) ( n =6), from ' normal' to diminutive adenoma,'diminutive' to ' small','small' to ' large', and large adenoma to CRC were 0.013 (range: 0.009-0.019), 0.043 (range: 0

Dietary patterns and risk of colorectal adenoma: a systematic review and meta-analysis of observational studies.

PubMed

Godos, J; Bella, F; Torrisi, A; Sciacca, S; Galvano, F; Grosso, G

2016-12-01

Current evidence suggests that dietary patterns may play an important role in colorectal cancer risk. The present study aimed to perform a systematic review and meta-analysis of observational studies exploring the association between dietary patterns and colorectal adenomas (a precancerous condition). Pubmed and EMBASE electronic databases were systematically searched to retrieve eligible studies. Only studies exploring the risk or association with colorectal adenomas for the highest versus lowest category of exposure to a posteriori dietary patterns were included in the quantitative analysis. Random-effects models were applied to calculate relative risks (RRs) of colorectal adenomas for high adherence to healthy or unhealthy dietary patterns. Statistical heterogeneity and publication bias were explored. Twelve studies were reviewed. Three studies explored a priori dietary patterns using scores identifying adherence to the Mediterranean, Paleolithic and Dietary Approaches to Stop Hypertension (DASH) diet and reported an association with decreased colorectal adenoma risk. Two studies tested the association with colorectal adenomas between a posteriori dietary patterns showing lower odds of disease related to plant-based compared to meat-based dietary patterns. Seven studies identified 23 a posteriori dietary patterns and the analysis revealed that higher adherence to healthy and unhealthy dietary patterns was significantly associated risk of colorectal adenomas (RR = 0.81, 95% confidence interval = 0.71, 0.94 and RR = 1.24, 95% confidence interval = 1.13, 1.35, respectively) with no evidence of heterogeneity or publication bias. The results of this systematic review and meta-analysis indicate that dietary patterns may be associated with the risk of colorectal adenomas. © 2016 The British Dietetic Association Ltd.

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

PubMed

Murchie, Brent; Tandon, Kanwarpreet; Hakim, Seifeldin; Shah, Kinchit; O'Rourke, Colin; Castro, Fernando J

2017-04-01

Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

Cyclooxygenase-2 expression in human gastric tubular adenomas and carcinomas; correlation with intratumoral microvessel density and apoptotic index.

PubMed

Honjo, Soichiro; Kase, Satoru; Osaki, Mitsuhiko; Ardyanto, Tonang Dwi; Kaibara, Nobuaki; Ito, Hisao

2004-01-01

Cyclooxygenase (COX)-2 plays an important role in carcinogenesis in various human malignancies. This study examined the relationship among COX-2 expression, angiogenesis and apoptosis in human gastric adenoma and carcinoma. We examined the expression of COX-2 in 30 tubular adenomas and 11 carcinomas, comparing it with intratumoral microvessel density (IMVD) and apoptotic index (AI) by immunohistochemistry and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxygenin nick-end labeling (TUNEL) procedure. Immunohistochemistry demonstrated positive expression of COX-2 in 15 (50.0%) adenomas and in 50 (53.1%) carcinomas, respectively. The frequency of COX-2 expression was significantly higher in intestinal-type carcinomas than in diffuse-type, regardless of the tumor stage. The IMVD was significantly higher in the early and advanced carcinomas than in the adenomas and also higher in the COX-2-positive adenomas and carcinomas than in the negative ones. The AI was significantly higher in the adenomas than in the carcinomas and also in the COX-2-negative adenomas and intestinal-type early carcinomas than in their positive counterparts, respectively (p < 0.05). The IMVD and AI showed significant inverse correlation in both the adenomas (p=0.02, r=-0.64) and carcinomas (p=0.04, r=-0.18). COX-2 expression might be an early event in gastric tumorigenesis and provide a preferential advantage for tumor cell proliferation because of its vascular-rich microenvironment and escape from tumor cell apoptosis, especially in intestinal-type gastric carcinomas.

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

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

PubMed

Hull, Mark A; Sandell, Anna C; Montgomery, Alan A; Logan, Richard F A; Clifford, Gayle M; Rees, Colin J; Loadman, Paul M; Whitham, Diane

2013-07-29

The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of

SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas.

PubMed

Semaan, Alexander; van Ellen, Anne; Meller, Sebastian; Bergheim, Dominik; Branchi, Vittorio; Lingohr, Philipp; Goltz, Diane; Kalff, Jörg C; Kristiansen, Glen; Matthaei, Hanno; Pantelis, Dimitrios; Dietrich, Dimo

2016-01-01

Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of SEPT9 and SHOX2 has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions. Assessment of promoter methylation of SEPT9 distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (all p  < 0.001). Correspondingly, SHOX2 methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues ( p  < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the SEPT9 gene locus. SEPT9 / SHOX2 methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.

Geographic-Related Differences of Pituitary Adenomas Hormone Profile: Analysis of Two Groups Coming from Southeastern and Eastern Europe.

PubMed

Cimpean, Anca Maria; Melnic, Eugen; Bălinişteanu, Bogdan; Corlan, Ana; Coculescu, Mihail; Rusu, Sergiu; Raica, Marius

2015-01-01

We compared the immunoprofile of pituitary adenomas from Romania and Moldova. One hundred and eighty cases coming from Romania (94 cases, group 1) and Moldova (86 cases, group 2) were assessed by immunohistochemistry regarding all six basic hormones expressed in pituitary adenomas. Specific differences and similarities were found and stated for both groups. In group 1, 70% of cases were pituitary adenomas positive for one hormone, 13% were plurihormonal, while 17% were negative. In group 2, 50,3% of the cases expressed only one hormone and 12,5% were negative for all hormones. The highest difference was observed for plurihormonal adenomas, found in about 37,2% of cases for group 2 (2.86 times higher for group 2 compared with group 1). A higher incidence of GH-secreting adenomas characterized group "1," while group "2" had the highest percent of LH-secreting adenomas, 55% of cases being positive. Triple association was noticed in 4.25% of cases of group 1 and in 8,13% out of total cases, from group 2. Four-hormone association was found only in group 2, noticed in 15,56% of the cases. The present paper highlights strong evidences of a particular and different immunoprofile of pituitary adenomas coming from Romania and Moldova.

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

PubMed Central

Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

2016-01-01

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

ICA Occlusion by an ACTH-secreting pituitary adenoma post-TSS and irradiation

PubMed Central

El-Zammar, Diala; Akagami, Ryojo

2011-01-01

Occlusion of intracranial arteries by a pituitary adenoma with ensuing infarction is a rare occurrence. In this case study, we show the instance of a pituitary macroadenoma and apoplexy causing mechanical obstruction of the internal carotid artery with consequent infarction following transphenoidal surgery (TSS) and radiation therapy in a patient with Cushing's disease. We report a 44-year-old woman presented with amenorrhea and headaches. Necessary investigations, resection by TSS, and microscopic examination revealed an adenocorticotropin (ACTH)-secreting pituitary macroadenoma. The pituitary tumour recurred in subsequent years, resulting in the development of Cushing's disease and syndrome. Despite two more transphenoidal surgeries, radiotherapy, and medical suppressive therapy, the pituitary adenoma continued to enlarge, and the hypercortisolemia and Cushingoid symptoms persisted. A craniotomy was arranged as the next step in the treatment strategy. Only hours prior to the scheduled surgery, the patient developed left-sided hemiplegia, was diagnosed with acute occlusion of the right ICA and underwent an emergency bifrontal craniotomy with evacuation of the tumour and decompression. Pathological examination revealed evidence of apoplexy in the ACTH-secreting pituitary adenoma. This case demonstrates the vast scope of complications that can arise from pituitary adenomas despite combination therapy and forewarns clinicians to be prepared to manage these infrequent but conceivable occurrences. PMID:22399870

Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.

PubMed

Liu, Yen-Ling; Wu, Jin-Shang; Yang, Yi-Ching; Lu, Feng-Hwa; Lee, Chih-Ting; Lin, Wan-Ju; Chang, Chih-Jen

2018-04-01

Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Giant tubular adenoma with malignancy clinical characteristics in a female teenager: Case report and a review of the literature.

PubMed

Mărginean, Cristina Oana; Mărginean, Maria Oana; Simu, Iunius; Horvath, Adrienne; Meliţ, Lorena Elena

2016-10-01

Adenomas of the colon are usually benign tumors which carry a tendency for malignancy. These tumors can be villous, tubular, tubulovillous, or sessile serrated. Those with adenomatous structure can develop malignant characteristics in 1.5% to 9.4% of cases. We present a case report of a 16-year-old female adolescent with an adenoma of the descending colon. History revealed prolonged diarrheic syndrome for the past 6 months, repeated headache, and a weight loss of ∼5 kg in the past month. One week before the admission, the patient presented an episode of inferior digestive hemorrhage. On admission laboratory tests revealed iron deficiency anemia, and a mildly increased erythrocyte sedimentation rate. The abdominal ultrasound revealed an inhomogeneous mass of the descending colon and 2 hyperechoic lesions in the liver. The colonoscopy showed a tumor of the descending colon, a tubular adenoma according to the pathological examination. Additionally, we noted an atypical presentation of the tumor and the signs of mild dysplasia identified at the pathological examination. Weight loss, bowel transit alterations, loss of appetite, and inferior hemorrhage in an adolescent can be symptoms of a benign or malignant tumor of the colon.

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats.

PubMed

Rubio, Carlos A

2017-12-01

Recent studies have disclosed novel histological phenotypes of colon tumours in carcinogen-treated rats. The aim of this study was to update the current histological classification of colonic neoplasias in Sprague-Dawley (SD) rats. Archival sections from 398 SD rats having 408 neoplasias in previous experiments were re-evaluated. Of the 408 colonic neoplasias, 11% (44/408) were adenomas without invasive growth and 89% (364/408) invasive carcinomas. Out of the 44 adenomas, 82% were conventional (tubular or villous), 14% traditional serrated (TSA; with unlocked serrations or with closed microtubules) and 5% gut-associated lymphoid tissue (GALT)-associated adenomas. Out of 364 carcinomas, 57% were conventional carcinomas, 26% GALT carcinomas, 8% undifferentiated, 6% signet-ring cell carcinomas, and 4% traditional serrated carcinomas (TSC). Thus, conventional adenomas, conventional carcinomas and GALT-associated carcinomas predominated (p<0.05). The updated classification of colonic tumours in SD rats includes conventional adenomas, TSA, GALT-associated adenomas, conventional carcinomas, TSC, GALT-associated carcinomas, signet-ring cell carcinomas and undifferentiated carcinomas. Several of the histological phenotypes reported here are not included in any of the current classifications of colonic tumours in rodents. This updated classification fulfils the requirements for an animal model of human disease, inasmuch as similar histological phenotypes of colon neoplasias have been documented in humans. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Ethnic disparities in the risk of colorectal adenomas associated with lipid levels: a retrospective multiethnic study.

PubMed

Davis-Yadley, Ashley H; Lipka, Seth; Shen, Huafeng; Devanney, Valerie; Swarup, Supreeya; Barnowsky, Alex; Silpe, Jeff; Mosdale, Josh; Pan, Qinshi; Fridlyand, Svetlana; Sreeharshan, Suhas; Abraham, Albin; Viswanathan, Prakash; Krishnamachari, Bhuma

2015-03-01

Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.

Hyperfunctioning thyroid nodules in toxic multinodular goiter share activating thyrotropin receptor mutations with solitary toxic adenoma.

PubMed

Tonacchera, M; Chiovato, L; Pinchera, A; Agretti, P; Fiore, E; Cetani, F; Rocchi, R; Viacava, P; Miccoli, P; Vitti, P

1998-02-01

Toxic multinodular goiter is a cause of nonautoimmune hyperthyroidism and is believed to differ in its nature and pathogenesis from toxic adenoma. Gain-of-function mutations of the TSH receptor gene have been identified as a cause of toxic adenoma. The pathogenesis at the molecular level of hyperfunctioning nodules in toxic multinodular goiter has yet not been reported. Six patients with a single hot nodule within a multinodular goiter and 11 patients with toxic thyroid adenoma were enrolled in our study. At histology five hyperfunctioning nodules in multinodular goiters showed the features of adenomas, and one was identified as a hyperplastic nodule. The entire exon 10 of the TSH receptor gene was directly sequenced after PCR amplification from genomic DNA obtained from surgical specimens. Functional studies of mutated receptors were performed in COS-7 cells. Five out of 6 (83%) hyperfunctioning nodules within toxic multinodular goiters harbored a TSH receptor mutation. A TSH receptor mutation was also evident in the hyperfunctioning nodule that at histology had the features of noncapsulated hyperplastic nodule. Among toxic adenomas, 8 out of 11 (72%) nodules harbored a TSH receptor mutation. All the mutations were heterozygotic and somatic. Nonfunctioning nodules, whether adenomas or hyperplastic nodules present in association with hyperfunctioning nodules in the same multinodular goiters, had no TSH receptor mutation. All the mutations identified had constitutive activity as assessed by cAMP production after expression in COS-7 cells. Hyperfunctioning thyroid nodules in multinodular goiters recognize the same pathogenetic event (TSH receptor mutation) as toxic adenoma. Other mechanisms are implicated in the growth of nonfunctioning thyroid nodules coexistent in the same gland.

One-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas-a technical report.

PubMed

Wen, Guodao; Tang, Chao; Zhong, Chunyu; Li, Junyang; Cong, Zixiang; Zhou, Yuan; Liu, Kaidong; Zhang, Yong; Tohti, Mamatemin; Ma, Chiyuan

2016-11-15

Binostril endoscopic transsphenoidal approach (BETA) provides sufficient manipulation space and wide endoscopic vision, although it increases the trauma of nose. Mononostril endoscopic transsphenoidal approach (META) has minimal trauma of nose, at the expense of space within the operation. We describe a one-and-a-half nostril endoscopic transsphenoidal approach (OETA) that combines the advantages of BETA and META. We introduced OETA for pituitary adenomas with a detailed technical description. A retrospective analysis was also performed on 57 consecutive patients who underwent one-and-a-half nostril endoscopic transsphenoidal surgery between March 2014 and June 2015 at Jinling hospital. The gross total resection rate was 79%. The gross complete resection rate of Knosp grade 3 tumors were 63.6, and 27.3% in grade 4 tumors. Postoperative hormone remission was achieved in 14 out of 18 (77.8%) patients with secreting adenomas. Postoperative abnormal visual function improvement was achieved in 23 out of 32 patients (73%) with preoperative visual dysfunction. The overall intra-operative CSF leak was 17.5%, with the postoperative CSF leak decreased to 3.5% after the sellar reconstruction with the unilateral "rescue" nasoseptal flap procedure. The main sinonasal complaints 2 weeks after surgery were: loss of sense of smell (28%), decrease in sense of taste (4%), trouble breathing during the day (18%), thick nasal discharge (36%), post nasal discharge (8%), dried nasal material (6%), and headache (6%). Three months after surgery, there were no reports of decrease of taste, post nasal discharge, or dried nasal material. Other complaints were decreased significantly. Six months after surgery, the main complaints of sinonasal quality of life were negligible, and overall health status was near complete recovery to preoperative status. The one-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas is a simple and reliable technique. It provides not only a

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

Intraoperative Ultrasound in Patients Undergoing Transsphenoidal Surgery for Pituitary Adenoma: Systematic Review [corrected].

PubMed

Marcus, Hani J; Vercauteren, Tom; Ourselin, Sebastien; Dorward, Neil L

2017-10-01

Transsphenoidal surgery is the gold standard for pituitary adenoma resection. However, despite advances in microsurgical and endoscopic techniques, some pituitary adenomas can be challenging to cure. We sought to determine whether, in patients undergoing transsphenoidal surgery for pituitary adenoma, intraoperative ultrasound is a safe and effective technologic adjunct. The PubMed database was searched between January 1996 and January 2016 to identify relevant publications that 1) featured patients undergoing transsphenoidal surgery for pituitary adenoma, 2) used intraoperative ultrasound, and 3) reported on safety or effectiveness. Reference lists were also checked, and expert opinions were sought to identify further publications. Ultimately, 10 studies were included, comprising 1 cohort study, 7 case series, and 2 case reports. One study reported their prototype probe malfunctioned, leading to false-positive results in 2 cases, and another study' prototype probe was too large to safely enter the sphenoid sinus in 2 cases. Otherwise, no safety issues directly related to use of intraoperative ultrasound were reported. In the only comparative study, remission occurred in 89.7% (61/68) of patients with Cushing disease in whom intraoperative ultrasound was used, compared with 83.8% (57/68) in whom it was not. All studies reported that surgeons anecdotally found intraoperative ultrasound helpful. Although there is limited and low-quality evidence available, the use of intraoperative ultrasound appears to be a safe and effective technologic adjunct to transsphenoidal surgery for pituitary adenoma. Advances in ultrasound technology may allow for more widespread use of such devices. Copyright © 2017 Elsevier Inc. All rights reserved.

Adrenergic factors regulating cell division in the colonic crypt epithelium during carcinogenesis and in colonic adenoma and adenocarcinoma.

PubMed

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-01

Evidence exists implicating adrenergic factors in the control of intestinal epithelial cell proliferation in both normal and diseased states. In this report, attention is focussed on changes in the amine requirements of proliferating cells during the chemical induction of tumours in the colon of mouse. Cell proliferation rates were measured stathmokinetically. Tumours were induced by s.c. injection of dimethylhydrazine (DMH). Results with a series of adrenoceptor agonists and antagonists suggest that there is an alpha 2-adrenoceptor mediated excitatory effect in normal colon but an alpha 2 adrenoceptor mediated inhibitory effect in adenoma and carcinoma. Alpha 1 adrenoceptors, on the other hand, have an inhibitory effect in normal crypts and in adenomas, and an excitatory effect in carcinomas. Beta adrenoceptors have an inhibitory effect in the normal and DMH-treated crypt, and in adenomas, but not in carcinomas. In the crypt epithelium of DMH-treated mice, two regions on cell proliferation, with differing regulatory factors, could be identified. In the upper region of the carcinogen-exposed crypt is a zone where cell proliferation is stimulated by an alpha 2 adrenergic mechanism, thus resembling the basal region of the normal crypt. By contrast, in the basal region of these crypts, cell proliferation is stimulated by an alpha 1 mechanism, thus resembling a malignant tumour.

Water-clear cell adenoma of the parathyroid. A case report with immunohistochemistry and electron microscopy.

PubMed

Grenko, R T; Anderson, K M; Kauffman, G; Abt, A B

1995-11-01

We report a water-clear cell adenoma of the parathyroid gland, a lesion which to our knowledge has not been described previously. Like its rare but well-described hyperplastic counterpart, water-clear cell hyperplasia, this adenoma is composed of cells with abundant foamy-to-granular cytoplasm and mild nuclear pleomorphism. The cells form glandular structures and cell nests separated by fine fibrovascular septae. The tumor cells stain positively with anti-parathyroid hormone and show characteristic glassy and flocculate material by electron microscopy. Unlike water-clear cell hyperplasia, water-clear cell adenoma is a solitary lesion that compresses the residual nonneoplastic parathyroid gland.

Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps.

PubMed

Zarandi, Ashkan; Irani, Shiva; Savabkar, Sanaz; Chaleshi, Vahid; Ghavideldarestani, Maryam; Mirfakhraie, Reza; Khodadoostan, Mahsa; Nazemalhosseini-Mojarad, Ehsan; Asadzadeh Aghdaei, Hamid

2017-01-01

The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Epigenetic silencing of mismatch repair genes, such as MLH1 , by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis. Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation. Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients. The frequency of  MLH1  promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC.

Vitamin D Receptor Genotype, Vitamin D3 Supplementation, and Risk of Colorectal Adenomas

PubMed Central

Barry, Elizabeth L.; Peacock, Janet L.; Rees, Judy R.; Bostick, Roberd M.; Robertson, Douglas J.; Bresalier, Robert S.; Baron, John A.

2017-01-01

IMPORTANCE Despite epidemiological and preclinical evidence suggesting that vitamin D and calcium inhibit colorectal carcinogenesis, daily supplementation with these nutrients for 3 to 5 years was not found to significantly reduce the risk of recurrent colorectal adenomas in a recent randomized clinical trial. OBJECTIVE To investigate whether common variants in 7 vitamin D and calcium pathway genes (VDR, GC, DHCR7, CYP2R1, CYP27B1, CYP24A1, and CASR) modify the effects of vitamin D3 or calcium supplementation on colorectal adenoma recurrence. DESIGN, SETTING, AND PARTICIPANTS We examined 41 candidate single-nucleotide polymorphisms (SNPs) in 2259 participants in a randomized, double-blind, placebo-controlled trial conducted at 11 clinical centers in the United States. Eligibility criteria included a recently diagnosed adenoma and no remaining colorectal polyps after complete colonoscopy. The study’s treatment phase ended on August 31, 2013, and the analysis for the present study took place from July 28, 2014, to October 19, 2016. INTERVENTIONS Daily oral supplementation with vitamin D3 (1000 IU) or calcium carbonate (1200 mg elemental calcium) or both or neither. MAIN OUTCOMES AND MEASURES The outcomes assessed were the occurrence of 1 or more adenomas or advanced adenomas (estimated diameter, ≥ 1 cm; or with villous histologic findings, high-grade dysplasia, or cancer) during follow-up. Treatment effects and genotype associations and interactions were estimated as adjusted risk ratios (RRs) and 95% confidence intervals (CIs). The effective number of independent SNPs was calculated to correct for multiple testing. RESULTS Among the 2259 participants randomized, 1702 were non-Hispanic whites who completed the trial and had genotype data for analysis (1101 men; mean [SD] age 58.1 [6.8] years). The effect of vitamin D3 supplementation on advanced adenomas, but not on adenoma risk overall, significantly varied according to genotype at 2 VDR SNPs (rs7968585 and rs

The incidence of cerebrovascular accidents and second brain tumors in patients with pituitary adenoma: a population-based study.

PubMed

Brown, Paul D; Blanchard, Miran; Jethwa, Krishan; Flemming, Kelly D; Brown, Cerise A; Kline, Robert W; Jacobson, Debra J; St Sauver, Jennifer; Pollock, Bruce E; Garces, Yolanda I; Stafford, Scott L; Link, Michael J; Erickson, Dana; Foote, Robert L; Laack, Nadia N I

2014-03-01

To assess the risk of cerebrovascular accidents (CVAs) and second brain tumors (SBTs) in patients with pituitary adenoma after surgery or radiotherapy. A cohort of 143 people from Olmsted County, who were diagnosed with pituitary adenoma between 1933 and 2000, was studied. Only patients from Olmsted County were included because of the unique nature of medical care in Olmsted County, which allows the ascertainment of virtually all cases of pituitary adenoma for this community's residents and comparisons to the general population in the county. Surgical resection was performed in 76 patients, 29 patients underwent radiotherapy (with 21 undergoing both surgery and radiotherapy), 5 patients were reirradiated, and 59 patients were managed conservatively and observed. Median follow-up was 15.5 years. There was no difference in CVA-free survival between treatment groups. On univariate analysis age > 60 years (hazard ratio [HR], 11.93; 95% CI, 6.26-23.03; P < .001); male sex (HR, 3.67; 95% CI, 2.03-6.84; P < .001), and reirradiation (HR, 3.41; 95% CI, 1.05-9.68; P = .04) were associated with worse CVA-free survival. In multivariate analysis, only age > 60 years was associated with worse CVA-free survival. Compared with the general population, there was a 4-fold increase in the rate of CVAs in pituitary adenoma patients (HR, 4.2; 95% CI, 2.8-6.1). Two patients developed SBT (an irradiated patient and a surgically managed patient). CVA is a significant risk for patients with pituitary tumors, but treatment does not seem to impact the risk. Even with long-term follow-up, SBTs are a rare event regardless of treatment modality.

Application of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology for the diagnosis of colorectal adenoma.

PubMed

Zhou, Zhong-Yin; Tao, DI-DI; Cao, Ji-Wang; Luo, He-Sheng

2013-06-01

The aim of the present study was to identify a specific biological marker for the diagnosis of colorectal adenomas through the analysis of variations in serum protein profiling in colorectal adenoma patients. The study was conducted at the Renmin Hospital of Wuhan University (Wuhan, China) between September 2011 and May 2012. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was performed to compare the serum protein profiles of 50 patients with colorectal adenoma and 50 healthy individuals. The obtained protein profiles were analyzed using Biomarker Wizard software. Twenty protein peaks were identified to exhibit differences in average intensity between colorectal adenomas compared with normal controls, including peaks 8,565.84, 8,694.51 and 5,910.50 Da, in which the intensity between the patients and control individuals was significantly different. Two peaks, 8,565.84 and 8,694.51 Da, were observed to be highly expressed in the colorectal adenomas, however, expression was low in the control samples. By contrast, 5,910.50 Da expression was low in the colorectal adenomas and high in the controls. The results of the current study indicate that the three protein peaks may represent specific biomarkers for colorectal adenomas.

Time to Revive the Value of the Pseudocapsule in Endoscopic Endonasal Transsphenoidal Surgery for Growth Hormone Adenomas.

PubMed

Xie, Tao; Liu, Tengfei; Zhang, Xiaobiao; Chen, Lingli; Luo, Rongkui; Sun, Wei; Hu, Fan; Yu, Yong; Gu, Ye; Lu, Zhiqiang

2016-05-01

To investigate the role of endoscopic endonasal transsphenoidal surgery and the pseudocapsule in the treatment of growth hormone adenomas. The study included 43 patients (age range, 21-64 years) with growth hormone adenomas treated with an endoscopic endonasal approach. We compared the tumor characteristics and surgical outcomes of cases with (group A, 21 cases, from November 2013 to January 2015) and without (group B, 22 cases, from October 2011 to October 2013) extra-pseudocapsule resection. The preoperative demographics, tumor characteristics, and surgical complications were not significantly different between groups A and B. Postoperative remission without adjuvant therapy was achieved in 18 of 21 cases (85.7%) in group A, which was significantly greater than that observed in group B (12 of 22 cases [54.4%]). In group A, the pseudocapsules were verified by endoscopy and histopathology. The pseudocapsule was removed en bloc with the whole adenoma in only 5 cases (23.8%). For the remaining 16 patients (76.2%), following extra-pseudocapsule dissection, incomplete pseudocapsule removals with intracapsule procedures were achieved. The combination of extra-pseudocapsule resection and endoscopy led to a high rate of gross total tumor resection and endocrinologicl remission in acromegalic patients compared with the group with intracapsular resection. Extra-pseudocapsule resection resulted in no additional postoperative complications. Copyright © 2016. Published by Elsevier Inc.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism.

PubMed

Thawani, Jayesh P; Bailey, Robert L; Burns, Carrie M; Lee, John Y K

2014-01-01

Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes.

Change in the immunophenotype of a somatotroph adenoma resulting in gigantism

PubMed Central

Thawani, Jayesh P.; Bailey, Robert L.; Burns, Carrie M.; Lee, John Y. K.

2014-01-01

Background: Examining the pathologic progression of a pituitary adenoma from the point of a prepubescent child to an adult with gigantism affords us an opportunity to consider why patients may develop secretory or functioning tumors and raises questions about whether therapeutic interventions and surveillance strategies could be made to avoid irreversible phenotypic changes. Case Description: A patient underwent a sublabial transsphenoidal resection for a clinically non-functioning macroadenoma in 1999. He underwent radiation treatment and was transiently given growth hormone (GH) supplementation as an adolescent. His growth rapidly traversed several percentiles and he was found to have elevated GH levels. The patient became symptomatic and was taken for a second neurosurgical procedure. Pathology and immunohistochemical staining demonstrated a significantly higher proportion of somatotroph cells and dense granularity; he was diagnosed with a functional somatotroph adenoma. Conclusions: While it is likely that the described observations reflect the manifestations of a functional somatotroph adenoma in development, it is possible that pubertal growth, GH supplementation, its removal, or radiation therapy contributed to the described endocrine and pathologic changes. PMID:25396071

Trophic and neurotrophic factors in human pituitary adenomas (Review).

PubMed

Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio

2017-10-01

The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.

The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing's Disease.

PubMed

Perez-Rivas, Luis G; Theodoropoulou, Marily; Ferraù, Francesco; Nusser, Clara; Kawaguchi, Kohei; Stratakis, Constantine A; Faucz, Fabio Rueda; Wildemberg, Luiz E; Assié, Guillaume; Beschorner, Rudi; Dimopoulou, Christina; Buchfelder, Michael; Popovic, Vera; Berr, Christina M; Tóth, Miklós; Ardisasmita, Arif Ibrahim; Honegger, Jürgen; Bertherat, Jerôme; Gadelha, Monica R; Beuschlein, Felix; Stalla, Günter; Komada, Masayuki; Korbonits, Márta; Reincke, Martin

2015-07-01

We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease. To determine the prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease. We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies. A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma. Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities. We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8-mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 ± 7 mm and were inversely associated with the development of postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells. USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age.

The Gene of the Ubiquitin-Specific Protease 8 Is Frequently Mutated in Adenomas Causing Cushing's Disease

PubMed Central

Perez-Rivas, Luis G.; Theodoropoulou, Marily; Ferraù, Francesco; Nusser, Clara; Kawaguchi, Kohei; Stratakis, Constantine A.; Faucz, Fabio Rueda; Wildemberg, Luiz E.; Assié, Guillaume; Beschorner, Rudi; Dimopoulou, Christina; Buchfelder, Michael; Popovic, Vera; Berr, Christina M.; Tóth, Miklós; Ardisasmita, Arif Ibrahim; Honegger, Jürgen; Bertherat, Jerôme; Gadelha, Monica R.; Beuschlein, Felix; Stalla, Günter; Komada, Masayuki; Korbonits, Márta

2015-01-01

Context: We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease. Objective: To determine the prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease. Design: We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies. Patients: A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma. Main Outcomes Measures: Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities. Results: We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8-mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 ± 7 mm and were inversely associated with the development of postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells. Conclusions: USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age. PMID:25942478

Endonasal endoscopic surgery in pituitary adenomas: Surgical results in a series of 86 consecutive patients.

PubMed

López-García, R; Abarca-Olivas, J; Monjas-Cánovas, I; Picó Alfonso, A M; Moreno-López, P; Gras-Albert, J R

2018-03-23

The endoscopic endonasal approach has become the gold standard for the surgical treatment of pituitary adenomas. The aim of this study is to present the results obtained in our hospital in purely endoscopic surgery of pituitary adenomas. From February 2011 to August 2016, we conducted a prospective study on a series of 86 patients with pituitary adenoma, all of whom underwent surgery with a purely endoscopic endonasal approach. The 'four hands-two nostrils' technique was performed in all cases by a surgical team composed of an ENT surgeon and a neurosurgeon. Mean follow-up was 32 months. All patients were evaluated according to clinical, radiological and endocrinological criteria. In our series, 53% were women and 47% men. The age ranged from 14 to 84 years of age, with a mean of 54 years of age. The most common initial symptom was visual deficit (42%), followed by hormonal hyperfunction (21%), with acromegaly being the most common clinical syndrome. The most common tumours were non-functioning tumours (73%), while GH-secreting tumours (65%) were the most common functioning adenoma. Regarding tumour size, 76% were macroadenomas, 11% microadenomas and 13% giant adenomas. Approximately 63% of the adenomas exhibited suprasellar extension and 37% involved invasion of the cavernous sinus (Knosp grade ≥3). Total excision was achieved in 77% of the cases. After the intervention, visual improvement was achieved in 91% and remission of endocrine hyperfunction in up to a 73% of cases. The most common complication was anterior pituitary insufficiency of at least one axis (9%). There were no cases of postoperative cerebrospinal fluid fistula. In terms of surgical quality, our results are similar to those of published series, and demonstrate the efficacy and safety of the endoscopic endonasal approach as the surgical treatment of choice for pituitary adenomas. However, further studies with a higher sample size are necessary to obtain clinically significant results. Copyright

A Case Report of Rare Carcinoma Ex Pleomorphic Adenoma of Submandibular Gland and its Detailed Description

PubMed Central

Deshmukh, Ajinkya Amritrao; Deshmukh, Atul A.

2017-01-01

A 65-year-old female patient reported with a chief complaint of swelling in the left lower region of the jaw since two years. On clinical examination, the swelling was present on the mandibular left posterior region and measuring approximately 6.2 cm antero-posteriorly × 6.2 cm mediolaterally × 8.7 cm superioinferiorly. Initially, it was non tender but eventually it became tender. Fine needle aspiration was done to rule out any salivary gland pathology and report obtained was carcinoma ex pleomorphic adenoma. Then, excisional biopsy was taken and tissue sent for histopathology. Histopathological diagnosis was benign adenoma with carcinoma. Later serial sections of tissue were studied and came to the conclusion of carcinoma ex pleomorphic adenoma which was non invasive type and showed bizarre cells with neoplastic changes. Benign part was composed of myxomatous area with partial capsule. Neoplastic cells showed invasion into capsule and few necrotic areas were also present. Overall interpretation was favoured Non invasive carcinoma ex pleomorphic adenoma. So here, we reported a case of Carcinoma ex Pleomorphic Adenoma (CAEXPA) which is a deadly and rare variant of salivary gland malignancy. PMID:28658924

Quantitative Value of Aldosterone-Renin Ratio for Detection of Aldosterone-Producing Adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) Study.

PubMed

Maiolino, Giuseppe; Rossitto, Giacomo; Bisogni, Valeria; Cesari, Maurizio; Seccia, Teresa Maria; Plebani, Mario; Rossi, Gian Paolo

2017-05-21

Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration. We interrogated 2 large data sets of prospectively collected patients studied with the same predefined protocol, which included the captopril challenge test. We used an unambiguous diagnosis of aldosterone-producing adenoma as reference index. We also assessed whether the post-captopril ARR and plasma aldosterone concentration fall furnished a diagnostic gain over baseline ARR values. We found that the false-positive rate fell exponentially, and, conversely, the specificity increased with rising ARR values. At receiver operating characteristics curves and diagnostic odds ratio analysis, the high baseline ARR values implied very high positive likelihood ratio and diagnostic odds ratio values. The baseline and post-captopril ARR showed similar diagnostic accuracy (area under the receiver operating characteristics curve) in both the exploratory and validation cohorts, indicating lack of diagnostic gain with this confirmatory test (between-area under the curve difference, 0.005; 95% CI, -0.031 to 0.040; P =0.7 for comparison, and 0.05; 95% CI, -0.061 to 0.064; P =0.051 for comparison, respectively). These results indicate that the ARR conveys key quantitative information that, if properly used, can simplify the diagnostic workup, resulting in saving of money and resources. This can offer the chance of diagnosis and ensuing adrenalectomy to a larger number of hypertensive patients, ultimately resulting in better control of blood pressure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Comparison of the clinicopathological features of flat and polypoid colorectal adenomas that are smaller than or equal to five millimeters.

PubMed

Yener, Neşe Arzu; Midi, Ahmet; Ataizi Çelikel, Ciğdem

2014-02-01

Colorectal flat adenomas (FAs) may represent a different histogenesis, since their malignant potential is thought to be higher than polypoid adenomas of the same size. In this study, we classified FAs of ≤5 mm into three subgroups-superficially elevated adenomas (SEAs), completely flat adenomas (CFAs), and depressed adenomas (DAs)-based on their low microscopic shapes and compared their clinicopathological features with polypoid tubular adenomas (pTAs) with the same size. One hundred one pTAs and 46 FAs with tubular morphology with the same size (≤5 mm) were studied. The percentages of high-grade dysplasia in FAs and pTAs were 19.56% and 12.87%, respectively. The percentages of the high-grade dysplasia were 28.57%, 13.63%, and 20.00% in the DA, SEA, and CFA subgroups, respectively. FAs had a significantly higher number of normal epithelium at the basal crypts of the lesion than the pTAs (p=0.001). The presence of pericryptal mesenchymal cells was higher in pTAs than the FAs (78.21% vs 10.86%) (p<0.001). Flat adenoma represents a distinct type of colorectal adenoma with special histopathological properties-existence of a normal epithelium at the basal crypts, lack of pericryptal mesenchymal cells, and a high percentage of high-grade dysplasia-especially when it has a depressed shape at low magnification.

Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy.

PubMed

Moody, J A; Lingeman, J E

2001-02-01

Options for treatment of large (greater than 100 gm.) prostatic adenomas have until now been limited to open surgery or transurethral resection by skilled resectionists. Considerable blood loss, morbidity, extended hospital stay and prolonged recovery occur with open surgery for large prostatic adenomas. Endoscopic surgery for benign prostatic hyperplasia has evolved during the last decade to offer the patient and surgeon significant advantages of transurethral removal of prostatic adenomas. Holmium laser enucleation of the prostate with transurethral tissue morcellation provides significant reductions in morbidity, bleeding and hospital stay for patients with large prostate adenomas. A retrospective review of data on 10 cases of holmium laser enucleation and 10 open prostatectomies for greater than 100 gm. prostatic adenomas was performed from 1998 to 1999 at our institution. Patient demographics, indication for surgery, preoperative and postoperative American Urological Association (AUA) symptom scores, operating time, serum hemoglobin, resected prostatic weight, pathological diagnosis, length of stay and complications were compared. Patient age, indications for surgery (retention, failed medical therapy, high post-void residual, bladder calculi, bladder diverticula and azotemia) and preoperative AUA symptom scores were similar in both groups. Postoperative AUA symptom scores were significantly decreased (p <0.004) in both groups. Operating times were not significantly different. Serum sodium was unchanged by holmium laser enucleation (not significant), and postoperative hemoglobin was not significantly reduced in the holmium laser enucleation group but decreased significantly in the open prostatectomy group (mean decrease 2.9 +/- 0.7 gm., p = 0.0003). Resected weight was greater in the holmium laser enucleation group (151 versus 106 gm., p = 0.07). Length of stay was significantly shorter in the holmium laser enucleation group (2.1 versus 6.1 days, p <0

[Sonoelastography, B-mode sonography, and color Doppler sonography findings of pleomorphic adenomas and Warthin tumors of parotid gland].

PubMed

Yerli, Hasan; Eşki, Erkan

2015-01-01

This study aims to investigate the sonoelastography (SE), B-mode sonography, and color Doppler sonography findings of the pleomorphic adenomas and Warthin tumors of the parotid gland. A total of 84 parotid masses (23 pleomorphic adenomas, 25 Warthin tumors) in 72 patients (37 males, 35 females; mean age 59 years; range 30 to 79 years) were retrospectively analyzed. For each lesion, B-mode sonography, color Doppler sonography, and SE images were evaluated. Vascularity and elasticity scores of the tumors during color Doppler sonography and SE examinations were calculated by 4-scoring method. Lobulated contour and cystic areas were more common in the pleomorphic adenomas and Warthin tumors during the B-mode sonography examination (p<0.05). Peripheral vascularity was common in more than half of the pleomorphic adenoma patients, whereas central or mixed vascularity was seen in a large group of the Warthin tumor patients (p<0.05). The mean scores on color Doppler sonography examination were 1.13±0.81 for pleomorphic adenomas and 1.96±0.97 for Warthin tumors (p<0.05). The mean scores on SE examination were 2.69±0.70 for pleomorphic adenomas and 1.83±0.63 for Warthin tumors (p<0.05). Score 1 on SE examination was found in three of five Warthin tumor patients with peripheral vascularity on color Doppler sonography. B-mode, color Doppler and elastography examinations by sonography provide some helpful findings in the differentiation of pleomorphic adenomas and Warthin tumors.

Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?

PubMed

Castinetti, Frederic; Brue, Thierry

2010-08-01

Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting. Transsphenoidal neurosurgery is the gold standard treatment; however, it is not always effective. Gamma Knife radiosurgery is a specific modality of stereotactic radiosurgery, a precise radiation technique. Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment. As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period. Hypopituitarism is the main side effect, observed in 20-40% cases. Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).

Development of pituitary adenoma in women with hyperprolactinaemia: clinical, endocrine, and radiological characteristics.

PubMed Central

Pontiroli, A E; Falsetti, L

1984-01-01

Sixty eight women referred for treatment of hyperprolactinaemia entered a three year follow up study to determine the clinical and endocrine course of the disease and its association with microadenoma of the pituitary. Details recorded before treatment included medical history, gonadotrophin and ovarian hormonal concentrations, and release of prolactin in response to protirelin (thyrotrophin releasing hormone), benserazide, cimetidine, and nomifensine. Sellar tomography was then performed yearly for three years in all women, 54 of them also undergoing computed coronal and sagittal tomography. At baseline evaluation 27 women showed radiological evidence of pituitary adenoma; at the end of the follow up period the number had increased to 41. Amenorrhoea, steady and raised serum prolactin concentrations, a low ratio of luteinising hormone to follicle stimulating hormone, a longer duration of disease, and low serum progesterone concentrations were more common in women with a final diagnosis of pituitary adenoma than in those whose sella remained normal. Tests for release of prolactin had yielded abnormal results from the outset in all 41 women with radiological evidence of pituitary adenoma and in about half of those whose sella had remained radiologically normal. Response to medical treatment (metergoline in 20 patients, bromocriptine in 21) was similar and showed no difference between patients with tumorous and non-tumorous hyperprolactinaemia. These findings suggest that a large proportion of women with hyperprolactinaemia may harbour a prolactin secreting pituitary adenoma which becomes apparent over a relatively short period. Amenorrhoea and steady and raised serum prolactin concentrations are more common in these women. Tests for release of prolactin are of predictive value in identifying women who will develop a pituitary adenoma. PMID:6421360

A unique case of isolated sebaceous adenoma of the bulbar conjunctiva.

PubMed

Ilhan, Hatice Deniz; Turkoglu, Elif Betul; Bilgin, Ahmet Burak; Bassorgun, Ibrahim; Dogan, M Erkan; Unal, Mustafa

2016-01-01

Our patient was a 34 year-old male who presented with a painless conjunctival mass that had developed 3 months before his first visit. On performing slit-lamp biomicroscopy, a lobulated pink-yellowish solid mobile mass was observed on the nasal bulbar conjunctival surface of his left eye. The tumor was excised, and histopathologic examination of the tumor revealed a sebaceous adenoma. Systemic examination was normal. No recurrence was observed during the 24-month follow-up period. Sebaceous adenoma of the bulbar conjunctiva is an extremely rare benign tumor, which may be observed to be isolated in the absence of malignancy.

Pleomorphic adenoma of minor salivary gland with therapeutic misadventure: a rare case report.

PubMed

Thakur, Jagdeep S; Mohindroo, Narinder K; Mohindroo, Shobha; Sharma, Dev R; Thakur, Anamika

2010-01-08

The benign tumors of nasopharynx are least encountered tumors in otolaryngology, as nasopharynx is considered one of notorious anatomical site for the malignant tumors. Pleomorphic adenoma of the minor salivary gland of nasopharynx and parapharyngeal space is rare. We present a pleomorphic adenoma of minor salivary gland which was mismanaged. An adult male presented with left nostril obstruction for five months. The examination found big mass extending from nasopharynx to oropharynx. On CT scan, this tumor was quite big and extending to the parapharyngeal space. The FNAB found it a carcinoma but it did not respond to radiotherapy. The excision biopsy of tumor revealed it as pleomorphic adenoma. We found only five published reports on this tumor arising from nasopharynx. Although, in this case report exact origin of the tumor could not be ascertained as it also appeared to be a parapharyngeal tumor but we kept the possibility of a nasopharyngeal tumor on the basis of clinical features. The pleomorphic adenoma of nasopharynx is rare. It can be misdiagnosed as malignant epithelial tumor on histopathology. The differentiation from its malignant variant is also difficult. A possibility of benign tumor should always be kept in nasopharyngeal growth with no evidence of metastasis, and histopathological diagnosis of growth should be available before any definitive treatment.

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. Design The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2 × 2 factorial ‘efficacy’ study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55–73 year-old patients, who have been identified as ‘high risk’ (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and ‘advanced’) per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as ‘intermediate risk’ for future

Identification of Kininogen 1 as a Serum Protein Marker of Colorectal Adenoma in Patients with a Family History of Colorectal Cancer.

PubMed

Yu, Jiekai; Huang, Yanqin; Lin, Chen; Li, Xiaofen; Fang, Xuefeng; Zhong, Chenhan; Yuan, Ying; Zheng, Shu

2018-01-01

The serum protein markers of colorectal adenoma in patients with a family history of colorectal cancer have been rarely reported. Serum samples from colorectal adenoma patients with or without a family history of colorectal cancer and healthy controls were profiled using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). The model to distinguish colorectal adenoma patients with a family history of colorectal cancer from atypical hereditary colorectal families (CRA-H) and sporadic colorectal adenoma patients without a family history of colorectal cancer (CRA-S) was established with 85.0% accuracy. The model distinguishing CRA-H from healthy individuals was established with 90.0% specificity and 86.7% sensitivity. Additionally, five peaks (2202, 5821, 3260, 2480, and 2218) showing differential expression in advanced colorectal adenoma patients with a family history of colorectal cancer were selected. The protein Kininogen 1 (KNG1) was identified in colorectal adenoma patients and validated using Western Blotting. KNG1 may be a biomarker for colorectal adenoma patients with a family history of colorectal cancer.

Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.

PubMed

Palles, Claire; Cazier, Jean-Baptiste; Howarth, Kimberley M; Domingo, Enric; Jones, Angela M; Broderick, Peter; Kemp, Zoe; Spain, Sarah L; Guarino, Estrella; Guarino Almeida, Estrella; 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 C; 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 J W; McVean, Gilean; Houlston, Richard S; Tomlinson, Ian

2013-02-01

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 variants associated with susceptibility, POLE p.Leu424Val and POLD1 p.Ser478Asn, have high penetrance, and POLD1 mutation was also associated with endometrial cancer predisposition. The mutations map to equivalent sites in the proofreading (exonuclease) domain of DNA polymerases ɛ and δ and are predicted to cause a defect in the correction of mispaired bases inserted during DNA replication. In agreement with this prediction, the tumors from mutation carriers 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 mutations affecting the exonuclease domain.

Hepatocellular carcinoma arising in a pigmented telangiectatic adenoma with nuclear β-catenin and glutamine synthetase positivity: case report and review of the literature.

PubMed

Hechtman, Jaclyn F; Raoufi, Mohammad; Fiel, M Isabel; Taouli, Bachir; Facciuto, Marcelo; Schiano, Thomas D; Blouin, Amanda G; Thung, Swan N

2011-06-01

Telangiectatic hepatocellular adenoma is a rare, recently recognized subtype of hepatocellular adenoma that is often underrecognized by pathologists. We report a case of hepatocellular carcinoma arising within a pigmented telangiectatic hepatocellular adenoma in a noncirrhotic man with diffuse glutamine synthetase and nuclear β-catenin positivity. This case highlights malignant transformation of telangiectatic adenomas, and describes a previously unreported association between pigment deposition and telangiectatic adenoma. Radiology, gross pathology, and histopathology are shown. Review of the literature with attention to β-catenin and glutamine synthetase staining, malignant transformation, patient characteristics, the presence of Dubin-Johnson-like pigment, and genetic characteristics of telangiectatic adenomas are discussed.

ADC histogram analysis for adrenal tumor histogram analysis of apparent diffusion coefficient in differentiating adrenal adenoma from pheochromocytoma.

PubMed

Umanodan, Tomokazu; Fukukura, Yoshihiko; Kumagae, Yuichi; Shindo, Toshikazu; Nakajo, Masatoyo; Takumi, Koji; Nakajo, Masanori; Hakamada, Hiroto; Umanodan, Aya; Yoshiura, Takashi

2017-04-01

To determine the diagnostic performance of apparent diffusion coefficient (ADC) histogram analysis in diffusion-weighted (DW) magnetic resonance imaging (MRI) for differentiating adrenal adenoma from pheochromocytoma. We retrospectively evaluated 52 adrenal tumors (39 adenomas and 13 pheochromocytomas) in 47 patients (21 men, 26 women; mean age, 59.3 years; range, 16-86 years) who underwent DW 3.0T MRI. Histogram parameters of ADC (b-values of 0 and 200 [ADC 200 ], 0 and 400 [ADC 400 ], and 0 and 800 s/mm 2 [ADC 800 ])-mean, variance, coefficient of variation (CV), kurtosis, skewness, and entropy-were compared between adrenal adenomas and pheochromocytomas, using the Mann-Whitney U-test. Receiver operating characteristic (ROC) curves for the histogram parameters were generated to differentiate adrenal adenomas from pheochromocytomas. Sensitivity and specificity were calculated by using a threshold criterion that would maximize the average of sensitivity and specificity. Variance and CV of ADC 800 were significantly higher in pheochromocytomas than in adrenal adenomas (P < 0.001 and P = 0.001, respectively). With all b-value combinations, the entropy of ADC was significantly higher in pheochromocytomas than in adrenal adenomas (all P ≤ 0.001), and showed the highest area under the ROC curve among the ADC histogram parameters for diagnosing adrenal adenomas (ADC 200 , 0.82; ADC 400 , 0.87; and ADC 800 , 0.92), with sensitivity of 84.6% and specificity of 84.6% (cutoff, ≤2.82) with ADC 200 ; sensitivity of 89.7% and specificity of 84.6% (cutoff, ≤2.77) with ADC 400 ; and sensitivity of 94.9% and specificity of 92.3% (cutoff, ≤2.67) with ADC 800 . ADC histogram analysis of DW MRI can help differentiate adrenal adenoma from pheochromocytoma. 3 J. Magn. Reson. Imaging 2017;45:1195-1203. © 2016 International Society for Magnetic Resonance in Medicine.

Thyroid hyperfunctioning adenomas with and without Gsp/TSH receptor mutations show similar clinical features.

PubMed

Arturi, F; Capula, C; Chiefari, E; Filetti, S; Russo, D

1998-01-01

Activating mutations of Gs alpha protein (gsp) and TSH receptor (TSH-R) identified in autonomously hyperfunctioning thyroid adenomas have been proposed as the primary event responsible for this disease. Since mutations have not been detected in 100% (ranging from less than 10% to 90%) of the patients, we evaluated whether the presence of gsp and TSH-R mutations cause differences in the clinical and biochemical parameters of the affected patients. Fifteen consecutive patients (11 women and 4 men) with autonomously hyperfunctioning thyroid adenomas who underwent thyroidectomy, previously examined for the presence of gsp or TSH-R mutations, were investigated. In all of the patients we examined plasma free T3, free T4, TSH levels and ultrasound volume of the nodules. The patients with mutations in gsp or TSH-R were similar to the patients without mutations for clinical presentation, sex distribution and mean age. Furthermore, basal serum FT3, TSH and tumor volume in the patients with mutations were not significantly different from the group without mutations. Our preliminary data demonstrate that no significant differences are present in the two groups of patients examined, suggesting that factors other than gsp or TSH-R mutations play a role in the clinical presentation of the disease.

Predictive factors suggesting an underestimation of gastric lesions initially diagnosed as adenomas by forceps biopsy.

PubMed

Ko, Sung Jun; Yang, Min A; Yun, So Hee; Park, Moon Sik; Han, Shang Hoon; Cho, Jin Woong

2016-03-01

The endoscopic forceps biopsy of gastric lesion may provide inadequate specimens for a correct diagnosis of the entire lesion. Therefore, a histologic discrepancy may exist between specimens obtained by forceps biopsy and by endoscopic resection. The aim of this study was to evaluate the endoscopic characteristics of an underestimation in gastric carcinomas initially diagnosed as adenomas by forceps biopsy. We retrospectively reviewed 431 lesions diagnosed as gastric adenomas by forceps biopsy and resected by endoscopic submucosal dissection (ESD) between January 2008 and December 2011. The endoscopic findings were reviewed for location, size, gross appearance, ulceration, and surface color. We compared these variables between the adenoma group and the carcinoma group, as defined by the post-resection pathological findings. The mean patient age was 65.63±9.30 years in the adenoma group and 64.75±10.30 years in the carcinoma group. The mean size of the lesion was 21.04±8.65 mm in the adenoma group and 22.06±7.46 mm in the carcinoma group. In the multivariate analysis, high-grade dysplasia from endoscopic forceps biopsy and red discoloration were significant variables associated with carcinoma in post-resection histology. Gastric adenomatous lesions with endoscopic characteristics of surface redness and high-grade dysplasia on forceps biopsy should be resected completely by ESD because of the high possibility of an underestimation after ESD.

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

PubMed

Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Barclay, Ella; Casey, Graham; Saunders, Brian; Thomas, Huw; Clark, Sue; Tomlinson, Ian

2015-02-01

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.

Mammosomatotroph adenoma of the pituitary associated with gigantism and hyperprolactinemia. A morphological study including immunoelectron microscopy.

PubMed

Felix, I A; Horvath, E; Kovacs, K; Smyth, H S; Killinger, D W; Vale, J

1986-01-01

A 29-year old giantess with growth hormone excess and hyperprolactinemia underwent transsphenoidal surgery to remove her pituitary tumor. Electron microscopy revealed a mammosomatotroph adenoma composed of one cell type. Immunoelectron microscopy, using the immunogold technique, demonstrated predominantly growth hormone or prolactin or a varying mixture of both growth hormone and prolactin in the adenoma cells. The presence of growth hormone and prolactin was found not only in the cytoplasm of the same adenoma cells but also in the same secretory granules. In the nontumorous adenohypophysis, somatotrophs and lactotrophs showed ultrastructural signs of hyperactivity. This finding is in contrast with the presence of suppressed somatotrophs and lactotrophs seen in nontumorous portions of adult pituitaries harboring growth hormone or prolactin-secreting adenomas. Our morphological study reinforces the view that growth hormone-producing pituitary tumors, originating in childhood, are different from those of the adult gland.

Sessile Serrated Polyps: Detection, Eradication, and Prevention of the Evil Twin

PubMed Central

Obuch, Joshua C.; Pigott, Courtney M.; Ahnen, Dennis J.

2015-01-01

Opinion Statement The sessile serrated polyp (SSP), also known as sessile serrated adenoma, is the evil twin among the colorectal cancer precursors. As will be described, these lesions have multiple aliases (serrated adenoma, serrated polyp or serrated lesion among others), they hang out in a bad neighborhood (the poorly prepped right colon), they hide behind a mask of mucus, they are difficult for witnesses (pathologists) to identify, they are difficult for police (endoscopists) to find, they are difficult to permanently remove from society (high incomplete resection rate), they can be impulsive (progress rapidly to CRC) and enforcers (gastroenterologists) don’t know how best to control them (uncertain surveillance recommendations). There is no wonder that there is a need to understand these lesions well, learn how best to prevent the colonic mucosa from going down this errant path or, if that fails, to detect these deviants and eradicate them from colonic society. These lesions should be on the endoscopists’ most wanted list. PMID:25623474

Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

PubMed Central

Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Cázares, Hugo Guerrero; Burger, Peter; Salvatori, Roberto; Quiñones-Hinojosa, Alfredo

2014-01-01

Purpose Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. Results GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Conclusion Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis. PMID:24402129

Nephrogenic adenoma of the urinary tract: A 6-year single center experience.