Synchronous Colorectal Adenomas Research Articles

Mucosal Microbiota from Colorectal Cancer, Adenoma and Normal Epithelium Reveals the Imprint of Fusobacterium nucleatum in Cancerogenesis.

Microbiota were analyzed by NGS and by an ensemble of metagenomics analysis tools in a total of 69 tissues from 9 patients with synchronous colorectal neoplasia and adenomas (27 specimens: 9 from normal tissues, 9 adenomas, and 9 tumours), 16 patients with only colonic adenomas (32 specimens: 16 from normal tissues and 16 adenomas), and from healthy subjects (10 specimens of normal mucosa). Weak differences were observed in alpha and beta metrics among the synchronous tissues from CRC and controls. Through pairwise differential abundance analyses of sample groups, an increasing trend of Rikenellaceae, Pseudomonas and Fusobacterium, and decreasing trends of Staphylococcus, Actinobacillus and Gemmiger were observed in CRC, while Staphylococcus and Bifidobacterium were decreased in patients with only adenomas. At RT-qPCR analysis, Fusobacterium nucleatum was significantly enriched in all the tissues of subjects with synchronous colorectal neoplasia. Our findings provide a comprehensive view of the human mucosa-associated gut microbiota, emphasizing global microbial diversity mostly in synchronous lesions and proving the constant presence of Fusobacterium nucleatum, with its ability to drive carcinogenesis.

Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells

BackgroundColorectal cancer (CRC) is one of the most prevalent and life-threatening cancer among the world. Accumulated somatic mutations during malignant transformation process endow cancer cells with increased growth, invasiveness and immunogenicity. These highly immunogenic cancer cells develop multiple strategies to evade immune attack. Through post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer development and progression but also manipulate anti-cancer immune response. This study aims to identify miRNAs associated with the colorectal cell malignant transformation process and their association with immune cell population using synchronous adjacent normal, polyp and CRC specimens. MethodsWe conducted a Low Density Array to compare the miRNA expression profile of synchronous colorectal adenoma, adenocarcinoma and adjacent normal colon mucosa collected from 8 patients, in order to identify candidate miRNAs involved in CRC progression. These findings were further validated in 14 additional patients and GEO dataset GSE41655. The relative abundance of dendritic cells, natural killer cells, neutrophil and macrophage was determined and correlated with dysregulated miRNA levels. ResultsMicroRNA microarray identified 39 miRNAs aberrantly expressed during the colorectal cell transformation process. Seven novel miRNAs were shortlisted, and dysregulation of miR-149-3p, miR-192-3p, miR-335-5p and miR-425 were further validated by the qPCR validation experiment and data retrieved from the GEO dataset. Furthermore, these miRNAs demonstrated certain associations with level of dendritic cells, natural killer cells, neutrophil and macrophage within the polyp or CRC specimens. ConclusionThis study revealed miRNA dysregulated during stepwise malignant transformation of colorectal mucosal cells and their association with immune cell population.

Does Colonic Diverticulosis Raise the Risk of Colorectal Adenoma in Patients with Colorectal Cancer?

Background The aim of this study was to evaluate the risk of development of colorectal adenomas in patients with colorectal cancer (CRC) with and without colonic diverticulosis. Methods We performed a retrospective cohort study that included patients with CRC between 2008 and 2011. All patients underwent preoperative colonoscopic and barium enema examinations. Follow-up colonoscopic examinations were performed within 1 year and between 3 and 5 years postoperatively. The incidence of colorectal adenomas was compared based on the presence or absence of diverticulosis. Additionally, multivariate logistic regression analysis was performed to identify the factors independently associated with the development of synchronous and metachronous colorectal adenomas. Results Of the 168 patients with CRC included in the study, 55 showed colonic diverticulosis. Synchronous colorectal adenomas were more common in CRC patients with diverticulosis than in those without diverticulosis (P > 0.001). Multivariate regression analysis showed that colonic diverticulosis (odds ratio (OR) 3.874, 95% confidence interval (CI) 1.843–8.144, P > 0.001) and obesity (body mass index > 25.0 kg/m2, OR 2.395, 95% CI 1.089–5.270, P = 0.030) were associated with an increased risk of synchronous colorectal adenomas. The presence of synchronous colorectal adenomas increased the risk of metachronous colorectal adenomas (OR 4.407, 95% CI 1.855–10.473, P > 0.001). Conclusions Colonic diverticulosis was associated with synchronous colorectal adenomas in patients with CRC, which is eventually increasing the risk of metachronous adenomas.

Hyperglycemia combined Helicobacter pylori infection increases risk of synchronous colorectal adenoma and carotid artery plaque.

BackgroundCardiovascular disease and colorectal cancer have severe consequences to human health and may occur simultaneously or sequentially. Carotid artery plaque is a predictor of cardiovascular disease, and colorectal adenoma is a premalignant lesion of colorectal cancer. We investigated the core risk factors of carotid artery plaque and colorectal adenoma.ResultsIn total, 2361 subjects were enrolled. In multivariate analysis, age ≥ 60 years, male sex, BMI > 27, LDL > 130 mg/dL, HbA1c ≥ 6.5%, hs-CRP > 0.3 mg/L and H. pylori infection were independent risk factors for synchronous colorectal adenoma and carotid artery plaque formation. In the H. pylori-positive and -negative groups, the proportions and odds ratio (OR) for synchronous colon adenoma and carotid artery plaque increased with increasing HbA1c. OR for synchronous colon adenoma and carotid artery plaque was significantly higher in the participants with HbA1c levels of 5.7%–6.4% and HbA1c ≥ 6.5% than in those with normal HbA1c in the H. pylori-negative group. The OR was more significant increased for H. pylori-positive patients when HbA1c level ≥ 6.5% was 15.87 (95% CI 8.661–29.082, p < 0.0001).Materials and MethodsThe records of 4669 subjects aged > 40 years who underwent bidirectional gastrointestinal endoscopy and carotid artery ultrasound examination on the same day or within 12 months of endoscopy examination from January 2006 to December 2015 were reviewed. All subjects had a gastric biopsy specimen tested for Helicobacter pylori.ConclusionsHyperglycemia combined with H. pylori infection was an increased risk factor for synchronous colorectal adenoma and carotid artery plaque formation. Diabetes control and H. pylori eradication may be warranted in higher prevalence areas.

NSAIDs and EGFR Inhibitors for Duodenal Polyp Prevention.

Familialadenomatouspolyposis (FAP)andattenuatedFAP(AFAP) are relatedgeneticconditions thatarecharacterizedbymultiple synchronous and metachronous colorectal adenomas with a 70% to 100%riskofdevelopingcolorectal cancer (CRC)and, lessoften,duodenal neoplasia. Although both of these conditions are caused by mutations in the coding region of the adenomatous polyposis coli (APC) tumor suppressor gene, thephenotypespresentquitedistinctly in correlationwith the position of the mutation within the coding region. In classic FAP, which presents with amuch greater polyp burden at an earlier age and a greater risk of CRC than AFAP, the mutation occurs in the central region of the protein, whereas mutations in the Nor CterminusareassociatedwithAFAP.TheAmericanGastroenterological Association recommends an annual sigmoidoscopy, beginning at ages 10 to 12 years, for patients with a genetic diagnosis of FAP, or at-risk familymemberswhohavenotundergonegenetic testing.1 Genetic and endoscopic screening of patients and family members, followed by timely treatment, has led to a 55% reduction in the occurrence of CRC at diagnosis of FAP, and improved cumulative survival amongall FAPpatients. In fact, duodenal cancer is now amore common cause of death than CRC in this population. TreatJAMA

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

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.

Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.

Background/AimsMicrosatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms.MethodsConsecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers.ResultsIn total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987).ConclusionsThe presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.

Prevalence and management of colorectal neoplasia in surgically treated esophageal cancer patients

AimsThe existence of other primary tumors during the treatment of esophageal cancer patients has been an important issue. Our aim is to investigate the prevalence and management of colorectal neoplasia (CRN) in surgically treated esophageal cancer patients. MethodsBetween 2002 and 2008, 93 patients with esophageal cancer were surgically treated. Seventy-three patients underwent subtotal esophagectomy and 20 underwent lower esophagectomy for esophageal cancer. Colonoscopy was available for detecting CRN before and after surgery. ResultsEighty-nine (95.7%) of the 93 patients were screened by colonoscopy preoperatively or within a year from the operation. Thirty-nine patients (43.8%) with CRN were synchronously identified: adenoma in 34 (38.2%) and adenocarcinoma in 5 patients (5.6%). Eleven adenomas with high grade-dysplasia and 8 adenomas with low grade-dysplasia were removed endoscopically. Three superficial adenocarcinomas were endoscopically removed before surgery, and 2 adenocarcinomas were surgically removed. Seventy-four patients (83.1%) were followed using colonoscopy, and 11 subsequent CRN, including 2 superficial adenocarcinomas, were endoscopically detected in 8 patients (10.8%). The size of esophageal cancer was larger in the patients with than without CRN (p = 0.036). The body mass index in esophageal cancer patients with CRN tended to be higher than in those without CRN (p = 0.065). ConclusionsWe noted that esophageal cancer is frequently associated with synchronous and/or metachronous colorectal cancer and adenomas. Colonoscopy is useful to detect and manage CRN before and after esophagectomy, although a few limitations exist.

Abstract 1283: Prevalence of synchronous oligopolyposis in Hispanics with incident colorectal cancer: A population-based analysis

Abstract Background: In Puerto Rico (PR), colorectal cancer (CRC) is the 1st cause of cancer death and the 2nd most common cancer among men and women. Familial CRC accounts for 10-15% of all CRCs. Several studies suggest that inheritance has a significant impact in the pathogenesis of up to a third of all CRC cases. Little is known about the prevalence of polyposis syndromes among Hispanics and statistics are needed to quantify disease burden. Aim: To determine the prevalence of oligopolyposis (defined as ≥20 synchronous colorectal adenomas) among Hispanics with incident CRC. Methods: Pathological reports from patients with biopsies positive for CRC from 2007 to 2011 were retrieved from the PR Central Cancer Registry. A total of 4334 pathological reports were initially obtained. After taking into account the inclusion/exclusion criteria, 1685 reports were included in the final analysis. Reports were analyzed by age, gender, stage at diagnosis and colorectal location (proximal vs. distal). Colorectal polyp burden was calculated using pathology reports and normalization of data based on colon segment size (STATA 10.0). Results: A total of 1685 colectomy specimens with colonic adenocarcinoma were analyzed (46.5% were female). The mean patient age was 68 years (SD ± 11) with an age distribution of: &amp;lt;50 (6.3%), 50-64 (30.7%), 65-75 (72.3%), &amp;gt;75 (27.8%). Tumors were classified as Stage 0 (2.9%), Stage I (19.5%), Stage II (32.2%), Stage III (40.3%), and Stage IV (4.93%). The mean number of polyps was 11 (SD ± 9.6) after normalization. 10.2% of CRC patients had oligopolyposis. Most patients with oligopolyposis were &amp;gt;50 years (96.5%), had tumors located in the proximal colon (62.3%), and had an earlier stage at diagnosis (35.9%) compared to patients without oligopolyposis (p&amp;lt;0.001). Conclusion: In our cohort of Hispanics, oligopolyposis was seen in 10% of cases. Our observations suggest that genetic syndromes associated with colorectal polyposis may account for a higher than expected number of CRC cases. Characteristics&amp;lt;20 adenomas n (%)≥20 adenomas n (%)P-valueAge&amp;lt;50100 (6.6)6 (3.5)0.12350-64467 (30.9)50 (29.0)65-75536 (35.5)57 (33.1)&amp;gt;75408 (27.0)59 (34.3)GenderFemale710 (46.9)75 (43.6)0.408Male803 (53.0)97 (56.4)Stage0/I283 (20.7)56 (35.9)&amp;lt;0.001II442 (32.4)47 (30.1)III/IV640 (46.9)53 (34.0)GradeWell276 (21.4)36 (25.2)0.042Moderate942 (72.9)105 (73.4)Poor75 (5.8)2 (1.4)LocationDistal780 (55.5)62 (37.4)&amp;lt;0.001Proximal625 (44.5)104 (62.3) Citation Format: Carlos E. Bertran, Juan M. Marques, Vanessa Mendez, Katerina Freyre, Yaritza Diaz-Algorri, Luis R. Pericchi, Marievelisse Soto, Marcia R. Cruz-Correa. Prevalence of synchronous oligopolyposis in Hispanics with incident colorectal cancer: A population-based analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1283. doi:10.1158/1538-7445.AM2014-1283

Tu1016 Prevalence of Synchronous Oligopolyposis in Hispanics With Incident Colorectal Cancer: A Population-Based Analysis

Background: In Puerto Rico (PR), Colorectal Carcinoma (CRC) is the first cause of cancer death and the second most common cancer among men and women. Familial CRC accounts for 10-15% of all CRCs and several studies suggest that inheritance has a significant impact in the pathogenesis of up to a third of all CRC cases. Little is known about the prevalence of polyposis syndromes among Hispanic individuals and statistics are needed to help quantify disease burden. Aim: To determine the prevalence of oligopolyposis (defined as ≥20 synchronous colorectal adenomas) among Hispanics with incident CRC. Methods: Pathological reports from patients with biopsies positive for CRC from 2007 to 2011 were retrieved from the Puerto Rico Central Cancer Registry. A total of 4334 pathological reports were initially obtained, and after the inclusion/exclusion criteria were implemented, 1685 reports were included in the final analysis. Reports were analyzed by age, gender, stage at diagnosis and colorectal location (proximal vs. distal). Colorectal polyp burden was calculated using pathology reports and normalization of data based on colon segment size. Computer software STATA 10.0 was used for the analysis of data. Results: A total of 1685 colectomy specimens with colorectal carcinoma were analyzed. Of those 46.5% were female; 100% of pathologies were interpreted as colonic adenocarcinoma. The mean patient age was 68 years (SD ± 11) with an age distribution of: 75 (27.8%). The majority of tumors were classified as Stage III (40.3%), while the rest were Stage 0 (2.9%), Stage I (19.5%), Stage II (32.2%), and Stage IV (4.93%). The mean number of polyps was 11 (SD ± 9.6) after normalization of results; with a number of polyps per age group: 50 years (96.5%), had tumors located in the proximal colon (62.3%), and had earlier stage at diagnosis (35.9%) compared to patients without oligopolyposis (p<0.001). Conclusion: In our cohort of Hispanics with incident CRC, oligopolyposis (≥20 synchronous adenomas) was seen in 10%of cases. Our observations suggest that genetic syndromes associated with colorectal polyposis may account for a higher than expected number of CRC cases.

Metabolic syndrome is an independent risk factor for synchronous colorectal neoplasm in patients with gastric neoplasm

There are no data on how metabolic syndrome (MetS) affects the prevalence of synchronous colorectal neoplasm (CRN) in gastric neoplasm (GN) patients. The aim of this study was to investigate a model for risk stratification for colorectal screening by evaluating the clinical characteristics of synchronous CRN in GN patients classified according to the presence of MetS. A cross-sectional, case-control study of 492 patients (368 males and 124 females) with GN, and 492 age-matched healthy controls undergoing simultaneous upper endoscopy and colonoscopy, was conducted. The GN group involved 446 patients without MetS, and 46 patients with MetS. In total, 177 (39.7%) and 28 (60.9%) synchronous CRN were detected in GN patients without MetS and with MetS, respectively (P=0.006). A total of 143 (34.7%) synchronous colorectal adenomas were detected in GN patients without MetS, whereas 17 (48.6%) were detected in GN patients with MetS (P=0.101), as well as more synchronous colorectal cancers (11.2% vs 37.9%, P<0.001). A multivariate logistic regression analysis revealed that the presence of GN (OR=1.54, 95% CI: 1.18-2.00, P=0.001) and the presence of MetS (odds ratio=1.82, 95% confidence interval: 1.19-2.78, P=0.006) were significant independent risk factors associated with the prevalence of CRN. The frequency of synchronous CRN in GN patients with MetS was 1.96 times greater than that in the GN group without MetS. The risk of synchronous CRN is significantly increased by the presence of GN, especially in MetS patients. Screening for synchronous CRN is highly recommended for GN patients with MetS.

Synchronous colorectal adenomas

Colorectal adenomas which are discovered simultaneously or 6 months after the diagnosis of primary adenoma or colorectal cancer (CRC) are called synchronous adenomas. The presence of synchronous adenomas increases the probability of adenomas with severe dysplasia as well as CRC. The aim of the study is to show the characteristics of synchronous colorectal adenomas and to present the relation between the index rectal adenoma and the proximal synchronous tumours. The research included 114 synchronous colorectal adenomas diagnosed in 58 patients. Total colonoscopy was performed on all patients. The largest number of patients had two adenomas (p < 0.001). Synchronous adenomas were more often diagnosed in men older than 50 (p < 0.001). The largest number of adenomas was localized in the sigma (52 patients, 43.0%) (p < 0.001). The biggest number of tumours was localized in the combination of rectum-sigma segments (p < 0.001). There were 31 (25.6%) synchronous, that is index tumours of the rectum and 90 (74.4%) the so-called proximal synchronous tumours of the proximal part of the colon. In 33 (56.9%) patients, who did not have the index tumour, the prevalence of proximal synchronous tumours was the highest (57.0%) (p < 0.001). The probability of adenoma multiplication is higher in men, and it increases with age. Beside the fact that synchronous adenomas are more often found distally, a great probability of finding proximal tumours shows that total colonoscopy is the method of choice for the discovery of colorectal tumours. Complete colonoscopic mapping of all colorectal adenomas and their removal prevents the development of metachronous, overlooked benign CRC already present at the moment of initial diagnostics that could be the cause of the development of metachronous CRC.

The Risk of Colorectal Adenoma in Patients with Gastric Adenomas

Purpose: Gastric polyps are found frequently in various colonic polyposis syndromes. Genetic alterations of several genes are developed in gastric adenomas and colorectal adenomas. However, it is not established that patients with gastric adenomas are higher risk for colorectal adenomas. The aims of study were to investigate the prevalence rate of colorectal adenoma in patients with gastric adenomas and to determine the association between the presence of gastric adenomas and synchronous colorectal adenomas. Methods: We reviewed the clinical records including endoscopic findings of 87 patients with gastric adenomas and 174 sex-age-matched controls among 19,019 subjects who underwent esophagogastroduodenoscopy and colonoscopy simultaneously or within 6 months from January 2001 to December 2008 at the Center for Health Promotion of Samsung Medical Center. Results: There were 72 men and 15 women with gastric adenoma. Colorectal adenomas were identified in 42 (48.3%) of 87 cases and in 58 (33.3%) of 174 controls (p=0.022). The prevalence of colorectal adenoma was significantly higher in gastric adenoma group than in control group. The mean size and the number of colorectal adenomas were not significantly different between the two groups. The majority of colorectal adenoma was located in distal colonic segments in gastric adenoma group in contrast with proximal colonic segments in control group. According to the multivariate logistic regression analysis, independent risk factors of colorectal adenoma were increasing age over 55 years (odds ratio (OR)=2.107; 95% confidence interval (CI), 1.219-3.641) and the presence of gastric adenomas (OR=1.913; 95% CI, 1.101-3.325). Conclusion: The risk of colorectal adenoma increased significantly in patients with gastric adenomas and those over the age of 55. Our results suggest that screening colonoscopy may be necessary for patients with gastric adenomas to find colorectal adenomas. Am J Gastroenterol 2009; 104:S168-S190; doi:10.1038/ajg.2009.492

Extramammary Paget’s disease in Korea: its association with gastrointestinal neoplasms

Extramammary Paget's disease (EMPD) most commonly occurs in the perineal and genital areas of elderly people. The current treatment of choice is adequate surgical excision. Between 1990 and 2007, 28 patients (27 men and one woman) with EMPD were treated at Asan Medical Center, Seoul, Korea, by wide local excision (WLE) with a 2- to 3-cm normal skin margin. "Carcinoma in situ" (CIS) was defined as confinement of Paget cells to the epithelium, whereas "invasive carcinoma" was defined as infiltration of Paget cells into more than dermal connective tissue. Of the 28 lesions, 21 (75%) were located in the penoscrotal area. Six (21.4%) patients had associated gastrointestinal neoplasms, three with associated gastrointestinal malignancies and four with synchronous colorectal adenomas, including one with both. Surgical procedures included WLE with primary repair in 13 patients (46.4%), WLE with skin graft in 12 (42.9%), WLE with skin graft and Gracilis muscle transposition in two (7.1%), and combined abdominoperineal resection and distal gastrectomy in one (3.6%). Four patients (14.3%) also underwent inguinal lymph node dissection, with three found to have lymph node metastases. Of 11 patients with invasive carcinoma, three (27.3%) had lymph node metastases, compared with none of 17 patients with CIS. Patients with lymph node metastases showed a significantly lower disease-specific survival rate (P = 0.008). Patients with invasive carcinoma tended to have a lower disease-specific survival rate (P = 0.087). EMPD in Korea showed an absolute male predominance and an association with gastrointestinal neoplasms. Lymph node metastasis significantly affected, and depth of invasion tended to affect, disease-specific survival rate.

Villous adenoma of the appendix with dysplasia

Sir, A 35-year-old male patient reported to the surgeon with complaints of repeated attacks of pain in abdomen, associated with nausea and vomiting. He had clinical evidence of acute appendicitis. The patient was operated and an appendicectomy was done. The specimen was sent for histopathological examination. Grossly, the appendix measured 6 × 1.2 × 1 cm and showed a bulbous, globular and enlarged tip. The cut section showed localized thickened wall at the tip. Microscopic examination revealed mucosa with villous and papillary infoldings, mostly covered by a single layer of tall columnar mucous-producing cells [Figures ​[Figures11 and ​and2].2]. Stratification was seen in some areas. At places, mild dysplastic change was also seen in the basal half of the mucosa. Mucous secretion was present, but without distension of the lumen of appendix. The remaining layers showed presence of acute inflammation. These findings were mainly seen in the sections taken from the tip of the appendix. The base of the appendix (surgical margin) was normal. Based on the histopathological findings, a diagnosis of villous adenoma of appendix with mild dysplasia and acute appendicitis was made. Figure 1 Photomicrograph showing part of wall of appendix with inflammation and villous configuration of the mucosa (Haematoxylin and eosin, ×10) Figure 2 Photomicrograph of the epithelium of appendix showing villous configuration lined by mucus-producing cells (Haematoxylin and eosin, ×40) Appendiceal tumors account for less than 0.4% of neoplasms in the gastrointestinal tract and are found in less than 1% of appendectomies.[1,2] Adenoma of the appendix is a rare pathological entity, which may progress to invasive carcinoma. They rarely produce clinical symptoms, and are mostly discovered incidentally during histopathological examination. A few may present with acute appendicitis.[1,3] Villous adenoma of the appendix is a rare pathological condition.[4,5] Adenomas of the appendixes, like adenomas elsewhere in the large intestine, are neoplastic lesions, which may progress to invasive adenocarcinoma,[3] and, once diagnosed, indicates a need for further investigation due to an association with neoplasia elsewhere.[6] Appendiceal adenomas are diffuse villous lesions involving large areas of the appendiceal mucosa. They frequently have a villous configuration with papillary fronds covered by large number of mucus-producing cells, which often have a deceptively innocuous appearance. The dysplastic nature of the lesion is best appreciated by examining the epithelial characteristics in the basal half of the mucosa, where crowding and stratification of the cells with nuclear atypia will be appreciated. Areas with a serrated pattern may be seen. Excessive mucous production by the lining epithelial cells may occur, in which case a mucocoele of the appendix may form.[3] Adenomas of the appendix may be cured by appendicectomy,[1,3] provided the resection line at the base of the appendix is tumor-free. Careful scrutiny of the remainder of the large intestine is necessary in patients with appendiceal adenomas because of the strong association with synchronous or metachronous colorectal adenomas and carcinomas.[3] Our patient has been asymptomatic for the last 2 years.

Prevalence of Synchronous Colorectal Neoplasms Detected by Colonoscopy in Patients with Gastric Cancer

Our purpose was to study the characteristics of colorectal neoplasms in patients with gastric cancer (GC). The study group comprised GC patients who underwent colonoscopy before resection of their GC. We examined the prevalence, site, and histology of colorectal neoplasms, as well as the clinicopathological features and treatment of the patients who had synchronous colorectal cancers (CRC). The logistic regression model was applied to investigate the features of the GC patients with concurrent CRC. We studied 466 GC patients (mean age 64.5 years; 147 women, 319 men), 143 (31%) of whom had a family history of gastrointestinal cancer. Synchronous colorectal adenoma and cancer were detected in 182 (39%) and 18 (4%) patients, respectively. Among the 18 synchronous CRCs, 11 were in the early stages and 10 of these were resected endoscopically. The other eight required simultaneous open radical surgery. All the GC patients with synchronous CRC were older than 50 years. Statistical analysis did not show a significant difference between the features of the patients with and those without concurrent CRC. The possibility of synchronous colorectal neoplasms in GC patients cannot be disregarded in clinical practice; however, screening of the large bowel may not be necessary in GC patients younger than 50 years.

Detection of Metachronous Neoplasms in Colorectal Cancer Patients: Identification of Risk Factors

Patients with colorectal cancer have a high risk of developing metachronous neoplasms. Identification of predictive factors associated with such conditions would allow individualized follow-up strategies in these patients. This study was designed to identify individual and familial factors associated with the development of metachronous colorectal neoplasms in patients with colorectal cancer. In the context of a prospective, multicenter, general population-based study-the EPICOLON project-all patients with colorectal cancer attended in ten Spanish hospitals during a one-year period were included. Patients with familial adenomatous polyposis or inflammatory bowel disease were excluded. All patients were monitored by colonoscopy within two years of the diagnoses. Demographic, clinical, pathologic, molecular (microsatellite instability status and immunohistochemistry for MSH2 and MLH1), and familial characteristics (fulfillment of Amsterdam I or II criteria, and revised Bethesda guidelines) were analyzed. A total of 353 patients were included in the study. At two years of follow-up, colonoscopy revealed the presence of adenomas in 89 (25 percent) patients and colorectal cancer in 14 (3.9 percent) patients, in 7 cases restricted to anastomosis. Univariate analysis demonstrated that development of metachronous neoplasm (adenoma or colorectal cancer) was associated with personal history of previous colorectal cancer (odds ratio, 5.58; 95 percent confidence interval, 1.01-31.01), and presence of previous or synchronous adenomas (odds ratio, 1.77; 95 percent confidence interval, 1.21-3.17). Although nonstatistical significance was achieved, metachronisms were associated with gender (P<0.09) and differentiation degree (P<0.08). Multivariate analysis identified previous or synchronous adenomas (odds ratio, 1.98; 95 percent confidence interval, 1.16-3.38) as independent predictive factor. Neither presence of tumor DNA microsatellite instability nor family history correlated with the presence of metachronous neoplasms. Patients with previous or synchronous colorectal adenoma have an increased risk of developing metachronous colorectal neoplasms. Accordingly, this subgroup of patients may benefit from specific surveillance strategies.

Identification of MYH Mutation Carriers in Colorectal Cancer: A Multicenter, Case-Control, Population-Based Study

Whereas it has conclusively been demonstrated that biallelic MutY human homolog (MYH) mutations confer a significant risk for colorectal cancer (CRC), the influence of monoallelic mutations remains controversial. Characterization of MYH-associated CRC is critical to identify individuals who might benefit from preventive strategies. This prospective, multicenter, case-control, population-based study was aimed at (1) establishing the CRC risk associated with specific germline MYH mutations and (2) devising a set of clinical criteria to identify MYH carriers among newly diagnosed CRC. Genotyping for Y165C and G382D was performed by TaqMan technology. Single-stranded conformation polymorphism analysis was performed in heterozygotes to screen for mutations in the entire gene. All individuals were re-screened for any additional pathogenic variant. Biallelic and monoallelic MYH mutations were found in 8 (0.7%) and 19 (1.7%) of 1116 CRC patients, respectively. None of the 934 control subjects carried biallelic mutations, whereas 22 (2.3%) of them were monoallelic carriers. In a meta-analysis including all previous case-control studies, monoallelic MYH carriers were not at increased risk for CRC (odds ratio, 1.11; 95% confidence interval, 0.90-1.37), although a significant association was found with the Y165C mutation in either homozygotes or heterozygotes (odds ratio, 1.67; 95% confidence interval, 1.17-2.40). Furthermore, presence of more than 15 synchronous colorectal adenomas or CRC diagnosed before the age of 50 years was the most effective set of criteria for the identification of biallelic MYH mutation carriers. This study proposes the first set of clinical criteria designed to identify CRC patients with biallelic MYH mutations, and it argues against an increased risk for monoallelic carriers.

Role of computed tomographic colonoscopy of postoperative surveillance in patient with gastric cancer

To examine the diagnostic yield of colorectal neoplasia at computed tomographic colonoscopy (CTC) as well as the feasibility of contrast enhanced CTC in patients with gastric cancer. To examine the incidence of colon polyp we selected postoperative 188 gastric cancer patients, which we refer to as the 'colon polyp survey group'. To examine the feasibility of CTC for early detection of colon cancer or advanced colon adenoma, we selected 47 gastric cancer patients (M:F 29:18, mean age 53.8 years), which we call the 'CT colonoscopy group'. All the 47 patients underwent successive CTC and colonoscopy on the same day. Totally 109 colon polyps were observed from 59 out of 188 gastric cancer patients, the incidence rate of colon polyps in gastric cancer patients being 31.4%. The sensitivity of CTC in detecting individuals with at least 1 lesion of any size was 57.1%, the specificity was 72.7%, the positive predictive value was 47.1%, and the negative predictive value was 71.9%. When the cutoff size was decreased to 6 mm, the sensitivity and specificity were 80.0% and 92.9%, respectively, with positive and negative predictive values of 57.1% and 97.5%, respectively. Only one patient was classified as false negative by virtual colonoscopy. The diagnostic yield of colorectal polyp was 31.4% in patients with gastric cancer, and contrast enhanced CTC is an acceptable tool for the detection of synchronous colorectal advanced adenoma and postoperative surveillance of gastric cancer patients.

A Prospective Study of the Prevalence and Distribution of Colorectal Neoplasia in Asymptomatic Asian Population

Background/Aims: With the rapid increase in the incidence of colorectal cancer in some Asian countries, interest in screening test in asymptomatic individuals is increasing. However, few studies on this field have been conducted in Asia. We aim to evaluate the prevalence, distribution and predicting factors of colorectal neoplasia in asymptomatic Asian individuals. Methods: We conducted a prospective, cross-sectional study of 9018 consecutive patients undergoing colonoscopy in 17 centers of 11 Asian cities (Bangkok, Delhi, Guangzhou, Hong Kong, Jakarta, Kuala Lumpur, Manila, Seoul, Singapore, Taipei, Tokyo) between July 2004 and December 2004. Of those, colonoscopic results of 860 asymptomatic screening individuals were analyzed. Advanced neoplasia was defined as adenoma larger than 10 mm in diameter, adenoma with high grade dysplasia, villous adenoma, or invasive cancer. The proximal neoplasm was considered as neoplasia at and proximal to the splenic flexure. Results: The mean age of 860 asymptomatic subjects was 54.4 ± 11.6 years and 471 (54.8%) were male. The overall prevalence of colorectal adenoma, advanced neoplasm, and invasive cancer was 18.5%, 4.5%, and 1.0% respectively. The prevalence of distal, proximal, and synchronous colorectal adenoma (advanced neoplasm) was 8.8% (2.1%), 7.7% (2.0%), and 3.0% (0.3%) respectively. In multivariate logistic regression analysis, male gender (p = 0.021), older age (p = 0.005), and family history of colorectal cancer in the first degree relatives (p = 0.009) were associated with an increased risk of colorectal advanced neoplasia. The ethnicity of Korean and Japanese was associated with an increased risk of colorectal adenoma but not with advanced neoplasia. In analysis comparing the risk of proximal advanced neoplasm in patients with distal adenoma vs those with no distal polyps, the adjusted relative risk was 3.1 (95% CI, 1.1-8.4). In asymptomatic screening subjects with no distal polyps (n = 720), 7.9% and 1.8% of the subjects have adenoma and advanced neoplasia in proximal colon respectively, and in multivariate analysis, first degree relative with history of colorectal cancer was a significant predicting factor for proximal advanced neoplasm (p < 0.021). In addition, 65% (13/20) of patients with proximal advanced neoplasm had no distal polyp, and the proportion of patients with proximal adenoma or advanced neoplasm increased with age. Conclusions: In asymptomatic Asian populations, male gender, older age and family history of colorectal cancer were associated with an increased risk of colorectal neoplasm. Quite a portion of proximal colonic neoplasia was detected with no distal polyp, especially in the elderly.