Small Tubular Adenomas Research Articles

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

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 surveillance interval included family history of colorectal cancer and detection of 1-2 serrated polyps at the index examination. In comparisons of outcomes, we found no significant differences between the 3-year vs 5-year recommendation groups in proportions of subjects found to have 1 or more adenomas (38.8% vs 41.7% respectively; P=.27), advanced adenomas (7.7% vs 8.2%; P=.73) or clinically significant serrated polyps (10.0% vs 10.3%; P= .82) at the follow-up colonoscopy. Possibly influenced by patients' family history, race, quality of bowel preparation, or number or size of polyps, endoscopists frequently recommend 3-year surveillance intervals instead of guideline-recommended intervals of 5 years or longer for individuals with LRAs. However, at the follow-up colonoscopy, similar proportions of participants have 1 or more adenomas, advanced adenomas, or serrated polyps. These findings support the current guideline recommendations of performing follow-up examinations of individuals with LRAs at least 5 years after the index colonoscopy.

Genetic instability, CpG island methylator phenotype, and proliferative activity are distinct differences between diminutive and small tubular adenoma of the colorectum

It is recommended that small (6-10 mm) lesions be treated with endoscopic resection (ER), whereas diminutive (≤5 mm) lesions are not currently an indication for ER according to the Japanese guidelines. The aim of this study was to evaluate the molecular alterations, and therefore treatment indications, in diminutive versus small tubular adenoma (TA). We prospectively analyzed genetic instability, including microsatellite instability and loss of heterozygosity, methylation status, KRAS/BRAF mutations, and Ki-67 staining in 96 TAs without a villous component. Although no microsatellite instability was identified in either diminutive or small TAs, genetic instability was seen in small TAs (9.1%) but not diminutive TAs (P = .04). In addition, the low-level CpG island methylator phenotype (CIMP-L) was more frequently observed in small TAs (31.8%) than in diminutive TAs (P = .01). Thus, genetic instability and CIMP-L were associated with small TAs, and only CIMP-L was an independent predictive marker for small TAs (odds ratio, 3.29; P = .03). Intriguingly, the Ki-67 proliferative index tended to be higher in small TAs than in diminutive TAs (P = .06) and higher in TAs with CIMP-L than in those without CIMP (P = .08). KRAS mutations were seen in codon 12 in 5.2% of TAs, but no BRAF gene mutations were found. As the molecular events and proliferative activity for the progression may increase from diminutive to small TAs, small TAs should be treated with ER, whereas a "predict, resect, and discard" strategy may be acceptable in most diminutive lesions except flat and depressed-type lesions, in keeping with the current strategy in the West.

Veteransʼ Attitudes Towards De-intensification of Surveillance Colonoscopy for Low-Risk Adenomas: 2016 ACG Fellows-In-Training Award (CRC Prevention Category) 2016 ACG Presidential Poster Award

Introduction: Patients with low risk adenomas (LRAs - i.e., 1-2 small tubular adenomas) are at low risk for colorectal cancer (CRC). As a result, current U.S. Multi-Society Task Force guidelines recommend a surveillance interval of up to 10 years in such patients. But endoscopists rarely recommend an interval greater than 5 years, even in those who are unlikely to benefit (e.g., those with limited life expectancy). The purpose of this study was to assess Veterans' attitudes towards de-intensification of surveillance (i.e., less frequent surveillance) for LRAs. Methods: We developed a 39-item multiple-choice, scenario-based survey to assess patient attitudes towards de-intensification of surveillance colonoscopy. Inclusion criteria were: (1) age 60-89; and, (2) LRAs on screening colonoscopy performed at a single academic VA center from 2010-2015. Patients with any other indication for colonoscopy or those at increased risk for CRC (i.e., history of CRC, inflammatory bowel disease, or a polyposis syndrome), were excluded. The primary outcome was comfort waiting 10 years (versus 5 years) for surveillance colonoscopy (measured on a 7-point unidirectional Likert-type scale). Multivariable linear regression was used to identify predictors of comfort with waiting. The survey was mailed with a $10 gift card incentive. Results: 345 of 491 surveys (70%) were returned for analysis. Respondents were predominantly white (88%) and male (98%). The median age was 68 years and 63% completed education beyond high school. Health literacy was adequate in 90%. The vast majority of respondents (85%) were interested in undergoing routine surveillance at a 5-year interval if recommended by their physician. Despite this high interest in 5-year surveillance, nearly half (45%) reported that they would also be comfortable waiting 10 years. In multivariable linear regression, trust in physician was associated with more comfort waiting 10 years. Concern about developing CRC and perceived effectiveness of screening were both associated with less comfort waiting 10 years. No other factors, including demographics, education, or health literacy, were associated with comfort waiting. Conclusion: Patients with LRAs have diverse preferences for when to undergo surveillance colonoscopy. Given the clinical uncertainty about the optimal surveillance interval in these patients, decisions about the timing of surveillance should incorporate patient preferences rather than simply enforce the preferences of endoscopists.

Gastric Tubular Adenomas Five Years After Total Proctocolectomy in Familial Adenomatous Polyposis

Familial Adenomatous Polyposis (FAP) is an autosomal dominant syndrome caused by mutations in the Adenomatous polyposis c (APC) gene. The prevalence of FAP ranges from 1 in 6, 850 to 1 in 31,250 births.Guidelines suggest FAP patients should start the surveillance process for colorectal cancer around age 10-12.However, endoscopy to look for FAP-like extra-colonic manifestations is recommended to start at age 25-30. Patients with FAP frequently have gastric polyps which could be fundic gland polyps and tubular adenomas, however it is uncommon to have mostly gastric tubular adenomas. A 23-yearold female with a past medical history of FAP presented for gastrointestinal surveillance. The patient's mother had FAP and thus the patient was screened for APC gene mutation which turned out to be positive. She underwent endoscopic surveillance of the gastrointestinal tract at age 18 when she found to have multiple colonic tubulovillous adenomas and subsequently had a total proctocolectomy with a J-pouch ileoanal anastomosis. She also had an abdominal wall desmoid tumor that was removed. The patient's first endoscopy was at age 19. The first three endoscopies (age 19, 20, and 21) showed fundic gland polyps in the stomach and tubular adenomas in the small bowel. The patient's most recent endoscopy showed multiple diminutive fundic gland like gastric polyps (figure 1, A) which turned to be tubular adenomas on histology. She also was noted to have duodenal tubular adenomas, figure 1, B. The prevalence of gastric adenomas is estimated to be about 9.2%- 23% in FAP. The risk for gastric cancer in FAP patients is 0.6% and seems to be more common in attenuated FAP than in FAP. Although we do not have a true estimate for the rate of transformation from gastric adenoma to malignancy, endoscopic surveillance is still recommended. Endoscopic surveillances have better metric measures in small bowel tubular adenomas than in gastric adenomas using the Spigelman staging system. This case had gastric and duodenal polyps at a much earlier age (19) than the recommended age of screening endoscopy (25-30). This case reminds us of the importance of surveillance EGDs in FAP patients and taking multiple biopsies from polyps which may look like fundic gland polyps on endoscopic evaluation but may be tubular adenomas on histology.Figure 1Figure 2

Screening colonoscopy and colorectal cancer: a single center long term study.

In Germany, colonoscopy has been introduced as a screening instrument more than 10 years ago. Immediate outcome (complications and adenoma detection) is well documented in a nation wide register, but there is only limited information on the decisive end points: long term incidence and mortality of colorectal carcinoma.We therefore tried to contact all those 495 subjects (296 women and 199 men, mean age 63.9 years) that had been screened between 2003 and 2005 at our institution. We were able to trace 472 persons (96 %), 5.1 to 7.8 years after colonoscopy; a total of 2730 person years were analysed. Data were collected by direct telephone calls and follow up colonoscopy reports were retrieved.Four malignant lesions were identified at screening. Another two colorectal carcinomas were diagnosed three and seven years after adenoma-negative colonoscopies: an advanced rectum carcinoma (index endoscopy described inadequate bowel preparation) and a coecum tumor. The patient with the rectum tumor subsequently died from the disease. The other five patients with colorectal carcinoma are disease-free. - Compliance with surveillance was limited, only 38 of 60 patients with advanced benign lesions and 49 out of 82 patients with a small tubular adenoma had a repeat colonoscopy, and this was performed a mean of 1.1 years later than advised. About half of the screened subjects were completely unaware of a recommended control interval or grossly wrong about it.We conclude that colorectal carcinomas can occur despite screening colonoscopy, but this seems to be a rare event. Subjects screened are insufficiently informed as to recommendations on post-polypectomy surveillance. This is particularly worrying in the high risk group with benign, but advanced adenomas.

Evaluation of pro-inflammatory markers plasma C-reactive protein and urinary prostaglandin-E2 metabolite in colorectal adenoma risk.

C-reactive protein (CRP) is a pro-inflammatory protein with potential as a biomarker in predicting colon cancer risk. However, little is known regarding its association with risk of colorectal adenomas, particularly by subtypes. We conducted a colonoscopy-based matched case-control study to assess whether elevated plasma CRP levels may be associated with colorectal adenoma risk and further whether this association may be modified by urinary prostaglandin E2 metabolite (PGE-M), a biomarker of systemic prostaglandin E2 production. Included in the study were 226 cases with a single small tubular adenoma, 198 cases with multiple small tubular adenomas, 283 cases with at least one advanced adenoma, and 395 polyp-free controls. No apparent association between CRP level and risk of single small tubular adenomas was found (ptrend = 0.59). A dose-response relationship with CRP level was observed for risk of either multiple small tubular adenomas (OR = 2.01, 95%CI = 1.10-3.68 for the highest versus lowest tertile comparison; ptrend = 0.03) or advanced adenomas (OR = 1.81, 95%CI = 1.10-2.96 for the highest versus lowest tertile comparison; ptrend = 0.02). In a joint analysis of CRP level and PGE-M, risk of multiple or advanced adenoma was greatest among those with highest levels of both CRP and PGE-M in comparison to those with low CRP and low PGE-M (OR = 3.72, 95%CI = 1.49-9.72). Our results suggest that elevated CRP, particularly in the context of concurrent elevated PGE-M, may be a biomarker of multiple or advanced adenoma risk in a screening age population. © 2015 Wiley Periodicals, Inc.

Gastric Fundic Gland Adenocarcinoma With Chief Cell Differentiation

A previously healthy sixty-six year old Caucasian man was referred for an outpatient upper endoscopy and colonoscopy for mild iron deficiency anemia. He had episodic heartburn for which he occasionally took calcium carbonate. He denied any weight loss. His family history was positive for colon cancer in his mother at age 74. He had a twenty pack year tobacco history but quit one year ago. His colonoscopy identified two small tubular adenomas. On upper endoscopy, his esophagus and duodenum appeared normal. On retroflexion in the stomach, there was an irregular 7mm erythematous polypoid lesion in the fundus (Figure 1). Image enhanced endoscopy with narrow band imaging identified increased vascularity and a gyrus-like mucosal pit pattern (Figure 2). Band EMR was performed after initial biopsy revealed dysplasia and the polypoid lesion was removed en bloc. Histologic examination (hematoxylin and eosin stain, Figure 3) revealed well-differentiated gastric adenocarcinoma with chief cell differentiation arising from oxyntic mucosa and invading into the superficial submucosa (arrows). Mucosal and deep resection margins were clear of carcinoma and there was no lymphovascular or perineural invasion. The patient did well post procedure and will undergo a repeat upper endoscopy within six months. Figure 1 Figure 2 Figure 3 While gastric adenocarcinoma is not an uncommon cancer worldwide, gastric adenocarcinoma with chief cell differentiation is a recently described rare epithelial neoplasm of the stomach with unique clinicopathologic characteristics. Unlike conventional types of gastric adenocarcinoma, which typically present with advanced, including metastatic, disease, gastric adenocarcinoma with chief cell differentiation may be a locally curable entity. The initial description in the literature was a case series of twelve Japanese patients.1 More recently, a second case series identified ten additional patients, two of whom were Caucasian.2 Like our patient, all reported patients to date had a solitary polyp, and in the majority, the polyp was located in the gastric fundus. Invasion limited to the submucosa was seen in the initial case series in the majority of patients, but was not identified in the second series, although in that study, specimens examined were superficial biopsy samples only and the submucosa was not evaluated. In both studies, none of the patients developed tumor recurrence or metastasis, leading authors to question if the term oxyntic gland polyp is more appropriate for this lesion, rather than gastric adenocarcinoma with chief cell differentiation. Regardless of the nomenclature, our case highlights that this rare variant of gastric adenocarcinoma may occur in non-Asian patients and emphasizes the utility of narrow band imaging and the importance of endoscopic mucosal resection, given the possibility of submucosal invasion and the ability to achieve curative resection of this rare and unique type of gastric neoplasm.

Mo1992 Weight or BMI Gain in Adulthood Is Associated With Risk of Multiple Small Tubular Adenomas but Not Advanced Adenomas, and May Differ by Smoking Status, NSAID Use and Sex

Mo1992 Weight or BMI Gain in Adulthood Is Associated With Risk of Multiple Small Tubular Adenomas but Not Advanced Adenomas, and May Differ by Smoking Status, NSAID Use and Sex

Risk of adenomas with high-risk characteristics based on two previous colonoscopy.

The recommended intervals between surveillance colonoscopies are based on the most recent examination findings. However, whether the two previous colonoscopies affect second surveillance colonoscopic findings is not established. The aim of this study is to estimate the risk of obtaining high-risk findings (HRF) on the next surveillance colonoscopy using the results of two previous colonoscopies, and to estimate the appropriate time interval for the next surveillance colonoscopy. Among subjects who underwent screening colonoscopy during January 2002-December 2009, patients who underwent second surveillance colonoscopy before June 2012 were enrolled. "No adenoma" was defined as a hyperplastic polyp or no polyp, "low-risk findings (LRF)" as one or two small (< 1 cm) tubular adenomas, and "HRF" as advanced adenoma, cancer, or any sized multiple (≥ 3) adenomas. Among enrolled 852 subjects, 65 (7.6%) had HRF at second surveillance colonoscopy. Multivariate analysis showed that HRF on second surveillance colonoscopy were associated with male and HRF on screening colonoscopy (all, P < 0.01). In subjects with LRF on first surveillance colonoscopy, HRF on the screening colonoscopy significantly affected the detection of HRF on second surveillance colonoscopy (P < 0.01). Patients with HRF on screening colonoscopy and LRF on the first surveillance colonoscopy had no different risk of HRF on second surveillance colonoscopy from those with HRF on first surveillance colonoscopy (P > 0.05). The HRF on second surveillance are significantly associated with previous two colonoscopic results. In patients with LRF on first surveillance, screening colonoscopic findings should be considered to determine the optimal surveillance interval.

Role of Endoscopy and PET Imaging in Anorectal Melanoma: A Call for More Aggressive Diagnostic and Follow-up Strategy for Mucosal Melanomas

Purpose: A 63-year-old man presented to his primary care physician with pelvic pain and blood in stool in October, 2008. He underwent esophagogastroduodenoscopy (EGD) which was reportedly normal, and colonoscopy which showed hemorrhoids and two small tubular adenomas (TA). Due to continued rectal bleeding, he was referred to us for further management. Repeat colonoscopy revealed multiple small TA polyps, and a large 4x4-cm distal rectal polypoid mass above the dentate line. Pathology of rectal mass revealed small superficial fragments of tubulovillous adenoma (TVA) and a separate fragment of ulcerated and focally necrotic epithelioid neoplasm, with cells arranged in sheets, columns and rosettes and containing melanin appearing pigment. The specimen was moderately positive for S-100 but strongly positive for Melan A (melanin). EUS was also performed to assess depth of invasion of melanoma, and it was confined to submucosa. Patient chose chemoradiotherapy with fluorouracil and temozolamide followed by abdomino-perineal resection of rectal mass in November, 2009. The tumor demonstrated extensive infiltration of the muscle wall of the rectum with tumor deposits in perirectal soft tissue. Intramucosal adenocarcinoma arising in TVA was seen. Invasive melanoma was confined to the polyp (lamina propria). 11/36 lymph nodes positive for melanoma. He was started on the sorafenib and continued to have surveillance CT and PET scans. In 9/2012 he underwent EGD for evaluation of thickened gastric folds seen on surveillance CT, which showed 2 pigmented nodules in gastral body. Biopsy confirmed melanoma with immunophenotype similar to rectal mass. Chemotherapy with sorafenib was continued. EGD was repeated 5/2013 which showed one new lesion along with increasing size of 2 previous gastral melanomas despite being on the chemotherapy. Primary mucosal melanomas account for 1.4% of total melanomas in the U.S. The most common sites of primary GI melanomas are anorectal (31.4% anal canal and 22.2% rectum) and oropharyngeal region (32.8%), followed by esophagus (5.9%), stomach (2.7%), small bowel (2.3%), gallbladder (1.4%), and colon (0.9%). Besides the rarity of finding an already rare mucosal melanoma co-existing with adenocarcinoma within a TVA, our case emphasizes on some important clinical issues in management of mucosal melanomas. While cutaneous melanoma management is a well described science with most follow-up largely radiology based, there are no concrete guidelines for mucosal melanomas. It is plausible that synchronous mucosal melanomas occurred in rectum and stomach earlier than diagnosed and were missed by CT/PET imaging, which urges for endoscopic follow-up of mucosal melanomas, rather than solely imaging based.

Optimizing Risk Stratification in Individuals With a Personal History of Colorectal Adenomas

Optimizing Risk Stratification in Individuals With a Personal History of Colorectal Adenomas

Small intestinal tubular adenoma in a pediatric patient with Turner syndrome

Turner syndrome (TS) is a female chromosomal disorder caused by the lack of an X chromosome. The loss of this chromosome may result in the deficiency of tumor-suppressive or DNA repair genes, leading to tumorigenesis. Recombinant human growth hormone (GH) has been popularly used for treatment in TS patients for growth promotion. Although treatment with GH has been correlated with precancerous and cancerous lesions in TS children, its associations with gastric or colonic tumors, especially ileal tubular adenomas, have not been reported frequently. We here report a case of a 16-year-old patient with TS and tubular adenoma of the small intestine. Whether the ileal adenoma was caused by TS itself or GH therapy was discussed.

Antioxidant supplement and long-term reduction of recurrent adenomas of the large bowel. A double-blind randomized trial

Patients who undergo polypectomy are at increased risk of adenoma recurrence. The preventive potential of vitamins (A, C and E) and selenium supplementation represent an interesting opportunity for colorectal cancer prevention. To assess the efficacy of a combination of these micronutrients in reducing the incidence of recurrent adenomas in subjects on post-polypectomy endoscopic follow-up, a double-blind placebo-controlled randomized trial was started in Italy in 1988. A total of 411 patients were randomized to receive either an active compound (200 μg selenium, 30 mg zinc, 2 mg vitamin A, 180 mg vitamin C, 30 mg vitamin E) or a placebo daily for 5 years. Of them, 330 had follow-up colonoscopy (164 in the intervention and 166 in the placebo group). After a median follow-up of 4 years (range 1-15 years), 100 patients had recurrence: 38 in the intervention and 62 in the placebo arm. The 15-year cumulative incidence of recurrence was 48.3% in the intervention and 64.5% in the placebo arm (HR = 0.59; log-rank P = 0.009). A 39% reduction of the risk of recurrence was observed in the intervention compared to the placebo group (adjusted HR = 0.61; 95% CI 0.41-0.92): the risk reduction was similar for small tubular (adjusted HR = 0.61; 95% CI 0.37-0.99) and advanced adenomas (adjusted HR = 0.50; 95% CI 0.24-1.01). Our study showed a statistically significant effect of antioxidant supplementation on adenoma recurrence. Further clinical trials are needed to address the role of antioxidants in subgroups of subjects at increased risk for colorectal cancer.

Survey of Primary Care Residents to Assess Awareness of Updated 2008 ACG Guidelines for Colorectal Cancer Screening

Purpose: To assess the awareness of updated 2008 American College of Gastroenterology (ACG) guidelines for colorectal (CRC) screening among primary care internal medicine (PCIM) residents. Methods: This study is a descriptive analysis of an anonymous, 2-minute, written survey consisting of 18 multiple-choice questions, particularly including changes from the 2000 ACG guidelines, administered simultaneously to all university-based PCIM residents. Questions focused on age to begin screening in average- & high-risk groups, available cancer prevention and cancer detection tests with their recommended intervals. Survey was collected on completion and data analyzed with respect to percentage response and compared among different levels of training. Results: 83% (40/48) residents completed the survey. Per current guidelines, screening is recommended in African Americans beginning at age 45 years; however, no resident selected this response. No resident selected younger age to begin CRC screening in smokers and obese patients which may be beneficial, though not recommended by ACG at this time. All residents correctly identified family history of CRC or adenoma at age >60 years, or small tubular adenoma as average risk factor. Regarding screening tests: 100% residents selected colonoscopy every 10 years, sigmoidoscopy every 5 years. Only 52% residents (19%, 37%, and 75% of PGY 1, 2 & 3 respectively; p<0.05) identified double barium contrast as no longer recommended. 80% residents were aware that CT colonography (CTC) is recommended every 5 years. All residents selected guiac-based fecal occult blood testing annually, though it is no longer recommended by ACG. 78% residents said fecal DNA testing is recommended annually; only 22% correctly responded as every 3 years. All residents correctly identified colonoscopy, sigmoidoscopy and CTC as cancer prevention tests but all wrongly selected these as cancer detection tests also. Almost all the residents wrongly identified fecal immunochemical test (FIT) (88%) and fecal DNA testing (100%) as cancer prevention tests. 100% residents selected colonoscopy as the preferred cancer prevention test, but all wrongly selected colonoscopy as the preferred cancer detection test. None selected FIT as preferred cancer detection test. Conclusion: Primary care residents' awareness seems in dissension with the current CRC screening guidelines. As they are mainly focused in primary care and many would be future primary care physicians, efforts should be made to improve awareness and practice of evidence-based medicine. Additional multicentric study is warranted for validation of our results, and to design intervention to increase knowledge and adherence to guidelines to improve CRC screening.

Urinary Prostaglandin E2 Metabolite and Risk for Colorectal Adenoma

COX-2 is upregulated in most colorectal cancers. Most of the COX-2 tumor-inducing effects are believed to be mediated through overproduction of prostaglandin E(2) (PGE(2)), which can be measured using a urinary metabolite of PGE(2), PGE-M. Urinary PGE-M was assessed in a case-control study of colorectal adenoma. Included in the analysis were 224 cases with at least one advanced adenoma, 152 cases with multiple small tubular adenomas, 300 cases with only a single small tubular adenoma, and 364 polyp-free controls. There were no statistical differences in PGE-M levels between controls and cases with a single small tubular adenoma. However, cases with either an advanced adenoma or multiple small tubular adenomas had more than 25% higher levels of PGE-M than controls. Participants with the highest quartile level of PGE-M were approximately 2.5-fold more likely to have advanced or multiple small tubular adenoma in comparison with those with the lowest level of PGE-M [OR = 2.53; 95% confidence interval (CI), 1.54-4.14; P(trend) < 0.001]. The association was strongest among women. PGE-M level was associated with increased risk for multiple or advanced adenoma but not single small adenoma. Our study suggests that PGE-M may be a useful risk marker for assessing the risk of harboring clinically more important versus less important colorectal neoplasia.

Localization of Nerve Fibers in Colonic Polyps, Adenomas, and Adenocarcinomas by Immunocytochemical Staining for PGP 9.5

PGP 9.5 is a cytoplasmic protein and is a specific marker for neurites and neurons. Using anti-PGP 9.5, this study aimed to localize nerve fibers in normal colons, polyps, adenomas and adenocarcinomas. Colonic polyps, adenomas and T(1) to T(3) adenocarcinomas with adjacent normal colon were immunostained for PGP 9.5 using rabbit anti-PGP 9.5. In normal colon, numerous nerve fibers were localized in inner and outer muscles, from which submucosa and lamina propria were innervated. In hyperplastic polyps and tubular adenomas, the stalk revealed Meissner's plexus and large-diameter nerve fibers, and fine nerve fibers innervated abundantly in lamina propria of hyperplastic polyps and small tubular adenomas. In villous adenomas, large-diameter nerve fibers and Meissner's plexus were localized in the stalk whereas a few or no fine nerve fibers were localized in fine stroma. In adenocarcinomas, more fine fibers were localized in submucosal stroma adjacent to the invading carcinoma in T(1) carcinomas but there were no nerve fibers in the midst of tumors in T(2) and T(3) carcinomas. There were focally and sporadically increased nerve fibers adjacent to invading cancer nests in 5 of 8 T(2) cases. In T(3) carcinomas, fragmented Auerbach's plexus were noted in cancer-invaded colonic muscles and there were no increased fine nerve fibers in the cancer-invaded subserosa in the majority of cases. PGP 9.5 immunostaining revealed tumor-associated neurogenesis in submucosa but no obviously increased nerve fibers within cancer-invaded muscles. This lack of tumor-associated neurogenesis supports insidious and often silent clinical presentation of colonic carcinomas until invading through the colonic wall to adjacent organs.

How Can the Over-Use of Surveillance Colonoscopy After Polypectomy Be Modified?

It is evident that colorectal cancer screening programs have contributed to a decrease in mortality [1–3]. Since professional groups, especially gastroenterologists, generally prefer colonoscopy as the most effective tool for colorectal cancer prevention [2], a considerable proportion of people with adenomatous polyps are discovered at the time of screening. Accordingly, a large number of people require post-polypectomy surveillance, which places a huge burden on medical resources [4, 5]. Recent data showing that 20% of colonoscopies performed in practice were for surveillance after polypectomy [6] indicate the importance of appropriate allocation of medical resources. Therefore, efficient and safe guidelines on surveillance colonoscopy are needed to decrease the cost, risk and over-use of colonoscopy. Before the 1990s, because there was no available guidelines, annual follow-up colonoscopy was common practice after polypectomy. The National Polyp Study, showing that it was safe to defer the first follow-up colonoscopy for 3 years [7], raised the issue of the cost and burden of postpolypectomy surveillance, and eventually led to develop a guideline in 1997 that recommended a 3-year interval of colonoscopy after removal of adenomas [8, 9]. In 2003, the updated guideline recommended extended intervals of surveillance colonoscopy and introduced the concepts of risk stratification according to the results of index colonoscopy [10]. The observations of Atkin et al. [11] using sigmoidoscopy over 3to 6-year intervals showed that persons with adenoma of less than 1-cm size and with no high-grade dysplasia were not at a higher risk for developing colorectal cancer. This data clearly showed that patients could be stratified into low-risk or high-risk groups according to the size of adenoma in index colonoscopy. Based on these observations, the guideline published in 2003 recommended the first follow-up colonoscopy after 5 years for low-risk patients [10]. In 2006, the updated guideline further emphasized risk stratification at index colonoscopy to encourage a shift from intense surveillance to surveillance based on risk [12]. Recent guidelines recommend the first follow-up colonoscopy after 3 years in people at high risk (three or more adenomas, high-grade dysplasia, villous features, or an adenoma 1 cm or larger in size). Follow-up colonoscopy after 5–10 years is recommended for people at lower risk who have one or two small (\1 cm) tubular adenomas with no high-grade dysplasia. Surveillance examination for hyperplastic polyps was first included in a 2006 guideline, and 10-year follow-up evaluation is recommended. However, recent surveys have shown that a large proportion of clinicians do not follow the recommended guidelines. One national survey of surveillance colonoscopy after polypectomy in 1999 and 2000 showed that 54% of gastroenterologists and 86.5% of general surgeons recommend surveillance examinations every 3 years or even more often for a small adenoma [13]. For a hyperplastic polyp, 24% of gastroenterologists and 54% of surgeons recommend surveillance. Another national survey in 2004 showed that 61% of primary care physicians (family medicine and internal medicine) recommend surveillance for a hyperplastic polyp after 5 years or less, and 71% recommend surveillance for a single tubular adenoma after 3 years or less [14]. A recent self-reported patient survey showed that 46.7% of subjects with one or two nonadvanced adenomas received a surveillance colonoscopy S. P. Hong W. H. Kim (&) Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Korea e-mail: kimwonho@yuhs.ac

Current Postpolypectomy Surveillance Guidelines Supported

The most recent postpolypectomy surveillance guidelines from the U.S. Multisociety Task Force on Colorectal Cancer and the American Cancer Society recommend that patients with one to two small tubular adenomas undergo a repeat colonoscopy in 5 to 10 years (Gastroenterology 2006; 130:1872). In the U.S., the majority of this population undergoes follow-up colonoscopy in ≤5 years. To estimate 5-year cumulative incidence of adenoma after baseline screening colonoscopy, investigators prospectively enrolled 3803 asymptomatic Koreans …

Findings on Serial Surveillance Colonoscopy in Patients With Low-risk Polyps on Initial Colonoscopy

This study describes the prevalence of adenomatous polyps at serial follow-up exams after a colonoscopy finding 1 to 2 small tubular adenomas. We conducted a retrospective cohort of patients with 1 to 2 small tubular adenomas on an initial colonoscopy who underwent at least 2 additional surveillance examinations. Our primary outcome was any or advanced adenomas on the third colonoscopy. Eighty-eight patients met inclusion criteria. At the second and third colonoscopy, 31/88 (35.2%) patients and 26/88 (29.6%) patients had at least 1 adenoma, respectively. Among the 28 patients with 1 to 2 small tubular adenomas on colonoscopy no. 2, the prevalence of any adenomas on colonoscopy no. 3 was 39.3% [95% confidence interval (CI): 21.5%-59.4%]. Among the 56 patients without adenomas at colonoscopy no. 2, the prevalence of any and advanced adenomas on colonoscopy no. 3 was 25% (95% CI: 14.4%-38.4%), and 3.6% (95% CI: 0.4%-12.3%), respectively. In patients with 1-2 small tubular adenomas on initial colonoscopy the prevalence of adenomas and advanced lesions on the third colonoscopy remains high even if no adenomas are found on the second colonoscopy.

Association of Large Serrated Polyps With Synchronous Advanced Colorectal Neoplasia

Serrated polyps of the colorectum are a histologically and genetically heterogeneous group of lesions, which include classic hyperplasic polyps, sessile serrated adenomas (SSAs), and traditional serrated adenomas. Accumulating evidence suggests that they may have different malignancy potentials. This study sought to determine the association between the presence of large serrated colorectal polyps and synchronous advanced colorectal neoplasia. Among 4,714 asymptomatic subjects who underwent screening colonoscopy, cases of advanced colorectal neoplasia (tubular adenoma > or =1 cm, adenoma with any villous histology, adenoma with carcinoma in situ / high-grade dysplasia, or invasive adenocarcinoma) were compared with controls without advanced neoplasia with respect to candidate predictors, including age, sex, family history of colorectal cancer, body mass index, the presence and number of small tubular adenomas (<1 cm), the presence of multiple small serrated polyps (<1 cm), and the presence of large serrated polyps (> or =1 cm). Independent predictors of advanced neoplasia were determined by multivariate logistic regression analysis. Among 467 cases and 4,247 controls, independent predictors of advanced colorectal neoplasia were increasing age (odds ratio (OR)=4.51; 95% confidence interval (CI), 1.43-14.3; P=0.01 for subjects > or =80 years vs. 50-54 years of age); non-advanced tubular adenomas (OR=2.33; 95% CI 1.37-3.96, P=0.0017 for 3 or more); and large serrated polyps (OR=3.24; 95% CI 2.05-5.13, P<0.0001). In total, 109 subjects (2.3% of the study population) had large serrated polyps. Right- and left-sided large serrated polyps had a similar association with advanced colorectal neoplasia (OR=3.38 vs. 2.66, P=0.62). Large serrated polyps are strongly and independently associated with synchronous advanced colorectal neoplasia. Our results suggest that large serrated polyps may be a marker for advanced colorectal neoplasia. Further studies are needed to determine whether the association with advanced neoplasia differs among subsets of serrated polyps, particularly SSAs and classic hyperplastic polyps.