Presence Of Synchronous Adenomas Research Articles

Surveillance Colonoscopies of Synchronous Colorectal Cancer: What Should We Do?

The aim of this study is to investigate the occurrence of metachronous neoplasms at 2-year surveillance colonoscopy for synchronous colorectal cancer patients and the relative risk factors. Synchronous colorectal cancer patients who underwent surgery or endoscopic resection for colorectal cancer between January 2008 and December 2019 were enrolled. All patients underwent surveillance colonoscopies at least twice within 2 years after operation. Univariate and multivariate analyses were conducted to assess the risk factors for the metachronous neoplasms. Totally 38 patients (male/female: 26/12) were included, with an average age of 64.6 years (±11.5 years) and a mean surveillance interval of 23.47 ± 4.39 months. In 21 of 38 patients (55.3%), metachronous adenoma was detected, including 6 metachronous advanced adenomas. Two patients were detected with metachronous carcinomas. In univariate analysis, male sex, elderly age at diagnosis, and the presence of synchronous adenomas/synchronous advanced adenoma at baseline colonoscopy were associated with the development of metachronous adenoma (P = .037, .047, .013, .039), but not associated with metachronous advanced adenoma (P = 0.455, .746, .503, .269). Patients tends to occur less metachronous advanced adenoma if index colorectal tumors were treated by endoscopic resection (P = .010), but the tendency was not discovered in metachronous adenoma (P = .289). Tumor location (with/ without rectum cancer) was not associated with the development of metachronous lesions (P = .526, .382). On multivariate analysis, the presence of synchronous adenomas at baseline colonoscopy was an independent risk factor for MA during follow-up (odds ratio = 15.0; 95% CI: 1.55-145.22). For postoperative synchronous colorectal cancer patients, doctors should design individual surveillance strategies according to sex, baseline colonoscopy, and operative (or endoscopic) approach of resection.

Loss of ZG16 is associated with molecular and clinicopathological phenotypes of colorectal cancer

BackgroundZymogen granule protein 16 (ZG16) is one of the most significantly down-regulated genes in colorectal cancer (CRC) tissues. This study aimed to further evaluate its expression changes and investigate its association with molecular and clinicopathological characteristics of CRC.MethodsWe applied quantitative RT-PCR to determine expression difference between tumor and matched normal tissues from 23 CRC patients. To further validate the down-regulation in tumor tissues, we performed immunohistochemistry (IHC) analysis in 40 paraffin-embedded normal-tumor pairs and 22 colon tissues with a variety of diseases. To evaluate if the ZG16 gene changes were associated with clinicopathological characteristics, we further analyzed the gene expression and copy number changes from The Cancer Genome Atlas (TCGA) and Oncomine datasets.ResultsQuantitative RT-PCR confirmed significant down-regulation (~ 130-fold) of ZG16 in all tumor tissues. ZG16 expression was in an organ-specific manner with an extremely high expression in normal epithelial cells of small intestine, colon and rectum. IHC analysis showed that ZG16 protein was completely lost in all of 40 CRC tissues, and partially lost in premalignant adenomatous polyps (adenomas) and chronic ulcerative colitis tissues. Gene expression and copy number changes were significantly associated with multiple molecular and clinicopathological features of CRC including microsatellite instability (MSI), MLH1 silencing, CpG island methylator phenotype, hyper-mutation status, gender, presence of synchronous adenomas, and histological type (P < 0.05). Patients with lower ZG16 gene expression showed shorter progression-free survival and overall survival than those with relatively higher expression (P < 0.05). Multivariate analysis suggested that the ZG16 expression was an independent prognosis factor (P = 0.012, HR = 6.286, 95% CI = 0.816–0.975).ConclusionFor the first time, our study demonstrated that ZG16 expression was sequentially reduced from normal, adenoma, to carcinoma. Association with multiple clinicopathological features indicates that ZG16 may play an important role in cancer initiation and progression. ZG16 may serve as a potential biomarker for diagnosis and prognosis of CRC.

15-Hydroxyprostaglandin Dehydrogenase in Colorectal Mucosa as a Potential Biomarker for Predicting Colorectal Neoplasms

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early stages of colorectal carcinogenesis. The aim of the present study was to investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and normal tissues from the surgical specimens of 32 sporadic colorectal cancer patients. mRNA expression of 15-PGDH was measured using a quantitative real-time PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal-appearing mucosa, the presence of synchronous adenoma, and the cumulative incidence of metachronous adenoma. The relative 15-PGDH expression of normal-appearing mucosa in patients with synchronous adenoma was significantly lower than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced stage colorectal cancer (P = 0.045). However, there was no significant difference in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal-appearing colorectal mucosa can be a useful biomarker of field effect for the prediction of sporadic synchronous neoplasms.

Drawing up an individual risk index for development of metachronous neoplastic lesions in resected colorectal cancer

to identify possible risk factors for the development of metachronous lesions in colorectal cancer (CRC) which would allow to establish a post-surgical individual prognostic index. three hundred eighty-two surgically treated CRC were reviewed. We compared the incidence of metachronous lesions in 40 variables concerning patient clinical data and initial neoplastic findings. An individual risk index for metachronicity was drawn up including those variables which presented significant differences in multivariate logistic regression, dividing patients into three groups. variables with prognostic value for metachronicity were distal cancer location: OR = 2.30 (1.03-5.13), alcohol intake: OR = 2.20 (1.08-4.48), presence of synchronous adenomas: isolated: OR = 2.47 (1.03-4.48), multiple: OR = 4.26 (1.78-10.17), and presence of synchronous advanced adenoma: OR = 2.91 (1.52-12.60). Tumor MUC-5 expression proved to have a protective role: OR = 0.23 (0.08-0.66). An individual risk score was established considering these variables and patients could be classified into three groups, with a discrimination power for metachronicity of p < 0.0000001. Classification in high and low risk groups had a sensitivity = 75.32%, specificity = 84.21%, positive predictive value = 75.34%, negative predictive value = 92.31% and global diagnostic accuracy = 80.75%. the identification of risk factors for the development of metachronous lesions allow to calculate, at the time of surgical treatment, an individual prognostic index and to classify patients into three different risk groups. In high and low risk groups, both specificity and accuracy were acceptable for the prognosis of metachronous lesions, being remarkable the negative predictive power of our classification, which could become relevant when planning a different endoscopic follow up of these patients.

Su1465 The Prevalence of Sessile Serrated Adenomas in a Fecal Immunochemical Test Positive Colorectal Cancer Screening Cohort

Su1465 The Prevalence of Sessile Serrated Adenomas in a Fecal Immunochemical Test Positive Colorectal Cancer Screening Cohort Nicholas J. Tutticci*, Barbara A. Leggett, Mark N. Appleyard, David G. Hewett Gastroenterology and Hepatology, Royal Brisbane and Womens Hospital, Brisbane, QLD, Australia; School of Medicine, University of Queensland, Brisbane, QLD, Australia Background: Sessile serrated adenomas (SSAs) are important, colonoscopicallysubtle precursor lesions in the serrated pathway of colorectal neoplasia. SSA prevalence rates have been described in cohorts undergoing colonoscopy for average risk screening and for clinical indications, but not in a high risk screening cohort (fecal immunochemical test positive, FIT ). We aimed to assess the prevalence of SSAs in participants from the Australian Bowel Cancer Screening Program, a national, population-based screening program offering fecal immunochemical testing to adults aged 50, 55 and 65, and colonoscopy for those returning a positive result. Methods: We enrolled 503 consecutive FIT screening program participants from a defined geographic catchment between 2008 and 2011. We assembled a comparison, non-screening control cohort of 1056 patients 50 years of age undergoing colonoscopy by matched colonoscopists for clinical indications from the same center. We used multiple logistic regression to analyze the predictors of SSAs in FIT screening participants, and compare the prevalence of SSAs between screening participants and controls, adjusting for age, sex, bowel preparation, colonoscopist and year of colonoscopy. Results: 164 SSAs were found in 64 (13%) of 503 FIT participants, representing 18% of all polyps; 114 (70%) of SSAs were proximal. Adenomas were found in 259 (52%) FIT screening program participants. Of these, 129 (26%) had advanced adenomas and 46 (5%) had synchronous SSAs. 10 cancers were found, none with synchronous SSAs. Among FIT screening participants, the presence of an SSA was significantly associated with the presence of synchronous adenomas (OR 2.67, p 0.002) and colonoscopist (OR 3.87, p 0.002) but not participant age, sex, year of procedure or bowel preparation. In the control group, adenomas were found in 284 (27%) patients, advanced adenomas in 80 (8%) and SSAs in 61 (6%). The crude prevalence of SSAs was 13% in FIT screening participants, compared with 6% in control patients. This difference was significant (adjusted OR 1.9, p 0.01) after controlling for age, sex, bowel preparation, colonoscopist and year, but not when controlling for the presence of an adenoma (adjusted OR 1.43, p 0.157). Conclusions: FIT screening program participants undergoing colonoscopy have a higher prevalence of SSAs than patients undergoing colonoscopy for clinical indications. However, this difference likely mirrors the higher prevalence of adenomas also seen in this screening cohort, rather than the detection of SSAs by FIT. Further, any differences need to be interpreted with caution given the variation in SSA prevalence between colonoscopists.

Análisis de la posible influencia de las lesiones sincrónicas en el pronóstico del cáncer colorrectal resecado

To analyze the relationship between synchronous lesions in patients with colorectal cancer and their prognostic value. We have retrospectively reviewed 369 patients with resected colorectal cancer. We compared the rate of apparently curative surgery, progression and tumoral relapse, development of extracolonic cancer and mortality between patients with and without synchronous cancer. Afterwards, we analyzed the same parameters in colorectal cancer with and without synchronous adenomas. Finally, we repeated the analysis after stratification of cancers in 2 groups according to pTNM staging: 0-I-II stage vs III-IV. We found synchronous adenomas in 54.7% of our patients and synchronous cancers in 7.6%. Follow-up period of groups with and without synchronous lesions were: 70.8 +/- 22.9 and 67.2 +/- 24.5 months (p = 0.55) respectively. Synchronous cancers showed higher mortality: 35.7 vs. 14.4%: p = 0.006; OR = 3.31 (1.33-8.13), higher tumoral progression : 39.3 vs. 19.1%: p = 0.011; OR = 2.75 (1.14-6.56) and higher relapse rate: 10.7 vs. 3.5%: p = 0.096. Stratifying according to stage, patients with stage 0-I-II and synchronous cancer showed worse prognosis: mortality = 27.7 vs. 8.1%, p = 0.019; OR = 4.45 (1.2-15.1), tumoral progression = 27.8 vs. 8.5%, p = 0.02; OR = 4.12 (1.14-14.19), and extracolonic cancer = 16.7 vs. 6.4% p = 0.095. There were no statistical differences between cases with and without synchronous adenomas. Synchronous cancers showed worse prognosis after resection, with higher rate of tumoral progression and mortality. This difference is focused on the cases diagnosed in stage 0-I-II, not being found in III-IV. The presence of synchronous adenomas doesn't influence prognosis.

The Frequency of Synchronous Adenomas Detected At Colonoscopic Removal of Early Colorectal Cancers

Background and Aims: Synchronous adenomas are often detected when colonoscopic removals of early colorectal cancers are carried out. The study aimed to evaluate whether or not the removed early cancers had any characteristics associated with the presence of synchronous adenoma. Methods: The study included a total of 253 early colorectal cancers (221 intramucosal and 32 submucosal invasive cancers), which were colonoscopically removed in our hospital during past 10 years. We analyzed the relationships between the following characteristics of resected early cancers and the presence of synchronous adenomas : location, tumor size, endoscopic configuration, histology, and depth of invasion. Results: The overall percentage of synchronous adenoma at colonoscopic removals of early colorectal cancers was 43.5%. Almost half of the resected early cancers were associated with synchronous adenoma(s) during colonoscopy. With regard to the location of removed cancers the prevalences of synchronous adenoma(s) were 45.2% (right colon), 45.8% (left colon), and 38.0% (rectum), respectively. No difference was statistically observed according to the location of original tumor. Regarding the size of removed cancers the prevalences of synchronous adenoma(s) were 56.4% (<10 mm), 38.4% (10 mm-20 mm), and 27.5% (>20 mm). Prevalence of adenoma(s) became to be lower according to the size up of removed tumor (p < 0.005). Regarding the endoscopic configuration of removed cancers the prevalences of synchronous adenoma(s) were 48.8% (pedunculated type), 45.1% (sessile type), 31.3% (flat type), and 24.2% (superficial spreading type), respectively. Polypoid type cancer (pedunculated or sessile type) had higher prevalences of synchronous adenoma(s) when compared to those of non-polypoid type (flat or superficial spreading type) (p < 0.05). As to the histology of removed cancers the prevalences of synchronous adenoma(s) were 43.4% (tubular adenocarcinoma), and 43.6% (villous adenocarcinoma), respectively. No statistical difference was observed between them. As to the depth of invasion the prevalences of synchronous adenoma (s) were 46.2% (m), and 25.0% (sm). Adenomas were less frequent with submucosal invasive cancers (p < 0.05). Conclusion: The characteristics of colonoscopically removed early cancers might influence on the prevalence of adenomas at colonoscopy. Size, configuration, and depth of invasion of removed cancers might be significant factors which influence on the frequency of synchronous adenomas.

Chromosomal changes in colorectal adenomas: Relationship to gene mutations and potential for clinical utility

Although the occurrence of both chromosomal aberrations and specific gene mutations in colorectal tumorigenesis is firmly established, the relationship between these different forms of genetic abnormality remains poorly understood. We have previously demonstrated, in colorectal adenocarcinomas, that mutations of APC, KRAS, and TP53 are each specifically associated with certain chromosomal aberrations. Using comparative genomic hybridization and mutational analysis of APC, KRAS, and TP53 to evaluate 78 colorectal adenomas, we have shown that several of the significant relationships between gene mutations and chromosomal abnormalities reported in colorectal adenocarcinomas also exist at the adenomatous stage. KRAS mutation correlated with 12p gain (P < 0.001) and TP53 mutation with both 20q gain and 18q loss (P = 0.03 for both). In addition, we have identified two chromosomal aberrations, gain of 13q and loss of 11q, that correlate with the presence of synchronous adenomas (P = 0.049 and P = 0.03, respectively) and several chromosomal changes (20p+, 20q+, 17p-, and 18q-) that are related to the onset of high-grade dysplasia. These data strengthen our previous contention that the co-occurrence of specific gene mutations and chromosomal changes is not random and significant relationships do exist. Our findings also raise the possibility that certain chromosomal aberrations may act as important clinical biomarkers.

What is the risk factor for metachronous colorectal carcinoma?

The purpose of this study was to determine the risk factors for developing metachronous colorectal carcinoma and to determine an adequate postoperative colonoscopic surveillance. Two hundred eighty-four patients, examined by routine colonoscopy after resection for colorectal carcinoma, were reviewed. Clinical and pathologic factors were assessed by multiple logistic regression analysis. One hundred eighty-three patients with synchronous adenoma or carcinoma at the initial operation had a significantly higher incidence of both metachronous adenoma and carcinoma than the 101 patients without a synchronous lesion. Other clinical factors including age, gender, tumor stage, tumor site, and tumor grade were not significant for an increased incidence of metachronous carcinoma. The presence of synchronous lesions proved to be the only risk factor (relative risk, 3.293; P = 0.0155) for developing metachronous carcinoma. Metachronous carcinoma was detected in 30 patients (10.6 percent) and completely removed from all patients. Mucosal carcinoma was found in 25 patients (8.8 percent) and invasive carcinoma in 5 patients (1.8 percent). All five invasive carcinomas were detected in asymptomatic patients having synchronous lesion. Four patients required a second operation for metachronous carcinoma more than 13 months following the first. The risk factor for developing metachronous carcinoma is the presence of synchronous adenoma or carcinoma at the initial operation. To detect metachronous carcinoma at a curable stage, annual colonoscopic surveillance should be performed for high-risk patients.

Colonoscopic follow-up of colorectal carcinoma

The value of routine colonoscopy in the prevention or early detection of metachronous carcinoma of the colon and rectum remains unproven. This study attempts to clarify this issue. An analysis of a personal series of 460 patients with primary colorectal carcinoma treated by the second author between 1972 and 1990 was reviewed. After various exclusions, there remained 231 patients who had been prospectively followed by colonoscopy with a mean follow-up period of 5.6 years. In 48 (21 percent) patients, there were synchronous adenomas present at the time of the initial resection for carcinoma and 35 (73 percent) of these patients subsequently developed metachronous adenomas, being recurrent in 22. Ninety-five (52 percent) of the 183 patients without synchronous adenomas eventually developed metachronous adenomas, so that overall 130 (56 percent) patients developed a metachronous adenomas. Four patients developed a metachronous carcinoma that was either Dukes A or B, and all remain well at the time of final follow-up. These metachronous carcinomas were found after a mean interval of seven and three-quarter years. All four patients had synchronous adenomas and all developed metachronous adenomas on multiple occasions before the metachronous carcinoma was detected. Thus, a subset consisting of only 22 patients produced all four metachronous malignancies--a rate of 18 percent. It would appear that the presence of synchronous adenomas with the subsequent development of recurring metachronous adenomas is significant and warrants a more intensive follow-up program to ensure the early diagnosis and more likely cure of any metachronous carcinoma.

Over-expression of the c-myc proto-oncogene in colorectal carcinoma.

Alterations in the c-myc proto-oncogene in colorectal cancer were studied at the level of RNA expression, gene amplification and rearrangements. One hundred cases of colorectal cancer, stratified by Dukes' stage were examined. The level of messenger RNA expression was measured in tumours and matched normal mucosa from the same patient. Between 5 and 400 fold over-expression was found in 66% of tumours. Neither the presence nor the level of over-expression correlated with tumour staging. A significant correlation (P < 0.01) was found between over-expression of c-myc in tumours and the presence of synchronous adenomas elsewhere in the colon. In contrast to other tumours, no rearrangements of the gene were found on Southern analysis of colorectal cancers. Similarly, amplification of the gene was not found in the cancers examined.