Dysplasia-associated Lesions Or Masses Research Articles

P-052 Sessile Serrated Adenoma Prevalence in Inflammatory Bowel Disease Patients Is Independent of Age

Sessile serrated adenomas (SSA) are pre-neoplastic lesions that is felt to represent a carcinogenic sequence distinct from that of conventional adenomas and dysplasia-associated lesions or masses (DALMs). SSA can occur in the general population, as well as, in inflammatory bowel disease (IBD) patients. However, the risk for SSA in IBD patients has not been characterized. This study evaluated the prevalence of SSA in IBD patients. A retrospective chart review was performed using electronic health records. Patients included were those who presented to an urban academic medical center during a one-year period for IBD surveillance colonoscopy. Patients were excluded if the colonoscopy report could not be matched to an outpatient medical record. Data regarding patients' age, demographics, IBD history, and colonoscopic and pathologic findings were collected. A database was created using Microsoft Excel maintaining patient confidentiality. Identifying information was excluded to ensure anonymity. Statistical analysis was performed using Fisher's Exact Test, with statistical significance set at P < 0.05. There were 136 patients who received IBD surveillance colonoscopy; 58 (42.6%) with Crohn's disease and 78 (57.4%) with ulcerative colitis. Among them, 74 (54.4%) were <50 years old and 62 (45.6%) were >50 years old. Sporadic adenomas included sessile serrated, tubular, villous, and tubulovillous histologies. Twelve patients (6 Crohn's, 6 ulcerative colitis) had sporadic adenomas, resulting in an adenoma detection rate of 8.8%. Five of the patients were >50 years and 7 were <50 years. There was no significant difference in the rate of sporadic adenomas based upon disease type (P = 0.7613) or age (P = 1.0000). Eight (5.8%) of the patients (3 Crohn's, 5 ulcerative colitis) had SSAs, 5 of whom were <50 years and 3 were >50 years. There was no significant difference in the rate of SSA based upon disease type (P = 1.000) or age (P = 0.7273). The prevalence of sessile serrated adenomas in the general population increases with age. However, there have been limited studies focused on the rate of SSAs in patients with inflammatory bowel disease. This study revealed an adenoma detection rate of 8.8% with sessile serrated adenomas occurring in 5.9%. There was no significant difference in the rate of SSAs based upon disease type or age. The similarity in SSA rates across ages in IBD patients may suggest that an IBD-related physiologic pathway may result in early SSA formation. Alternatively, as the sessile serrated pathway is distinct from that of conventional adenomas, age may exert less influence on the development of SSA than it does the sporadic adenomas. Because the average-risk screening colonoscopy population is predominantly >50 years old, this is difficult to ascertain. Although this is a small, single institution study, the similar prevalence of SSA in younger and older IBD patients raises interesting questions about the nature of these lesions both in IBD patients and in the general population.

Ileal DALM in Crohnʼs Disease: An Overlooked Entity?

Background: Patients with inflammatory bowel disease (IBD) are at an increased risk for developing neoplasia. Dysplasia associated lesions or masses (DALMs) are traditionally described in the colon and may represent underlying malignancy. Current surveillance protocols for malignancy generally require colonic biopsies. Small bowel malignancy among patients with Crohn's Disease (CD) has been described, but surveillance protocols for these patients have not been well defined. Case Report: We report here a 62 year old male with a history of umbilical hernia repair who presented with abdominal pain, nausea, and vomiting. He was previously diagnosed with mixed-pattern irritable bowel syndrome and had two episodes of small bowel obstructions (SBO) that were attributed to adhesions and managed conservatively. He had a heavy smoking and NSAID use history. The patient had never had a colonoscopy before and denied a family history of IBD or GI malignancy. Physical exam was significant for a distended abdomen. CRP was elevated at 3.82 mg/dL (normal < 0.5 mg/dL) and ESR was normal. A CT scan showed partial SBO with a long segment of ileal wall thickening. Colonoscopy showed fistulae at 45 and 55 cm from the anal verge. Abnormal polypoid lesions were seen in the terminal ileum (Fig 1) and biopsies showed tubulovillous-like lesion with low grade dysplasia, located within the distal portion of inflamed ileum compatible with DALM (Fig 3). A definitive diagnosis of CD could not be made and hence no medical therapy was started. CT enterography showed inflammation involving 20 cm of the distal ileum. A retrograde double balloon enteroscopy was performed, but the ileum could not be reached.Figure 1Figure 3As malignancy could not be ruled out, the decision was made for exploratory laparotomy that showed creeping fat and severe distal ileitis with enter-entero and entero-sigmoid fistulas. The patient underwent ileosigmoid fisula closure, and ileocolic resection with primary ileo-ascending colon anastomosis. Gross pathology confirmed severe Crohn's ileitis with tubulovillous-like lesions in TI with low grade dysplasia compatible with DALM in the distal ileum (Fig 2,3). No colitis was appreciated.Figure 2Conclusion: This case report demonstrates a DALM that affected the distal ileum in the setting of severe untreated ileal Crohn's. This brings into question the role for endoscopic surveillance and possible need for obtaining tissue to evaluate for malignancy among patients with CD with small bowel involvement.

Präkanzerosen im Kolon

Preneoplastic lesions of colorectal carcinoma can be divided in non-serrated and serrated lesions. Non-serrated lesions include conventional adenomas (tubular, tubulovillous and villous) and dysplasias associated with inflammatory bowel disease like flat intraepithelial neoplasia, dysplasia-associated lesions or masses (DALM) and adenoma-like masses (ALM). Conventional adenomas are mostly sporadic, but also found in hereditary adenomatous-polyposis syndromes. Hamartous polyposis syndromes are also associated with colorectal cancer. Serrated lesions include hyperplastic polyps, sessile serrated adenomas and traditional serrated adenomas. Based on these precancerous colorectal lesions different molecular subtypes were identified. Histological subtype, size and grade of dysplasia of polyps are essential for risk assessment of colorectal cancer.

Non-Polypoid Colorectal Neoplasms in Ulcerative Colitis

The incidence of colorectal cancer associated with ulcerative colitis (UC) increases with time. It is imperative to identify dysplasia-associated lesions or masses (DALM) and non-polypoid colorectal neoplasms (NP-CRN) to reduce the morbidity and mortality from colorectal cancer associated with UC. Recent findings suggest most dysplastic lesions in UC can be considered as visible under careful endoscopic observation. To find NP-CRN in UC, the careful examination of well-prepared mucosa and noting subtle differences is necessary. Magnifying chromoendoscopy, therefore, can be useful to endoscopically diagnose these subtle findings. The authors believe that targeted biopsies during chromoendoscopy will increasingly be used and replace random biopsies in the future.

Variability in the diagnosis and management of adenoma-like and non-adenoma-like dysplasia-associated lesions or masses in inflammatory bowel disease: an Internet-based study

Dysplasia-associated lesions or masses (DALMs) in inflammatory bowel disease (IBD) are a heterogeneous group of tumors with different natural histories. Our purpose was to determine the ability of gastroenterologists (GE) to distinguish adenoma-like (ALD) from non-adenoma-like DALMs (NALD) in patients with ulcerative colitis (UC) and to evaluate management practices with regard to these lesions. Randomly chosen academic and private practice members of the American Society for Gastrointestinal Endoscopy and a group of IBD experts. All GEs answered a series of questions related to UC-associated DALMs and were asked to classify 13 digitally transmitted endoscopic images (5 ALD, 5 NALD, and 3 inflammatory polyps [IP]). Internet-based survey. Not applicable. Not applicable. Percentage of respondents who answered management questions and classified endoscopic images correctly. ALD, NALD, and IP were correctly diagnosed by 68%, 75%, and 82% of IBD experts; 58%, 56%, and 57% of academic gastroenterologists; and 60%, 73%, and 60% of private practice GEs, respectively. Overall, there were no significant differences in rates of correct diagnosis for the 3 types of polyps (P=.603). IBD experts showed a significantly higher correct diagnosis rate (P=.048) and interobserver agreement (P<.01) compared with the other two GE groups. Many GEs were not aware of the currently recommended management guidelines for patients with IBD with DALMs. Only a single endoscopic image was used in this study. The response rate was 32%. These data suggest that academic GEs and private practice GEs have more difficulty than IBD experts do in distinguishing between and managing DALMs in patients with UC.

Computer-assisted quantitative analysis of Ki-67 antigen in dysplasia: Associated lesions or masses in ulcerative colitis

The aim of this study was to apply computer-assisted methodology in assessment of Ki-67 positivity in "adenoma-like" dysplasia associated lesions or masses (DALMs), and carcinoma in ulcerative colitis (UC), and to determine a new approach to grading of Ki-67 staining intensity. Immunohistochemical slides were quantitatively analyzed for estimation of proportion and intensity of Ki-67 positive-stained cells in a total of 50 "adenoma-like" DALMs (27 with low-grade dysplasia and 23 with high-grade dysplasia), and 17 adenocarcinomas associated with UC. The four grades of immunohistochemical staining intensity were established by an automated classification of nuclear optical densities. The Ki-67 labeling index (LI) in low-grade dysplasia was significantly lower than in high-grade dysplasia, and carcinoma (p < 0.001). The Ki-67 LI of carcinomas was not significantly different from the value obtained in high-grade dysplasia (p > 0.05), however having the difference in percentage values of the moderate stained nuclei (p < 0.05). The overall average values of chromogene nuclear optical density, showed statistically significant differences between DALMs and carcinoma (p < 0.05), although not between normal mucosa and low-grade dysplasia (p > 0.05). The obtained results imply, according to the overall percentage of labeled nuclei, that high-grade dysplasia is very close to carcinoma, while there is the difference in the percentage of moderately stained nuclei. We showed that Ki-67 positivity have a different internal distribution which could be useful in analysing these lesions. These findings also, indicate the important biological differences between low-grade dysplasia and carcinoma in UC, and a low proliferative potential of the former. Automated image analysis permits an objective [corrected] estimation of Ki-67 immunohistochemical staining in UC-associated dysplasia and carcinoma.

Long-term follow-up after polypectomy treatment for adenoma-like dysplastic lesions in ulcerative colitis

Background & Aims: A previously published study by our group suggested that adenoma-like dysplasia-associated lesions or masses (DALMs) in ulcerative colitis (UC) may be treated adequately by polypectomy and continued endoscopic surveillance. The length of follow-up evaluation in these patients averaged only 42 months. The purpose of this study was to evaluate the long-term outcome of our previously defined group of UC patients, all with adenoma-like DALMs, who were treated by polypectomy. Methods: The clinical, endoscopic, and pathologic outcome of 34 UC patients, 24 with an adenoma-like DALM, and 10 with a coincidental sporadic adenoma, 28 of whom were treated by polypectomy and continued endoscopic surveillance, and 6 by colonic resection, were compared with the outcome of 49 non-UC patients who were treated similarly for a sporadic adenoma. The mean length of follow-up evaluation averaged 82.1 months and 71.8 months for the 2 UC subgroups, respectively, and 60.4 months for the non-UC controls. Results: Overall, 20 of 34 UC patients (58.8%) developed at least one further adenoma-like DALM on follow-up evaluation. One patient had flat low-grade dysplasia present in the colon, which was resected within 6 months of the initial polypectomy, and another patient, with primary sclerosing cholangitis, developed adenocarcinoma 7.5 years after her initial polypectomy. There was no significant difference in the prevalence of polyp formation on follow-up evaluation between UC patients with an adenoma-like DALM (62.5%) and UC patients with a sporadic adenoma (50%), or between either of these 2 UC patient subgroups and the non-UC sporadic adenoma patient group (49%; P > 0.05). Conclusions: UC patients who develop an adenoma-like DALM may be treated adequately by polypectomy with complete excision and continued endoscopic surveillance.

Inflammatory bowel disease in Ashkenazi Jews: implications for familial colorectal cancer

Inflammatory bowel disease (IBD) has a multifactorial etiology and includes ulcerative colitis (UC) and Crohn's disease (CD). Powerful epidemiologic and genetic studies have provided ample evidence that a subset of both CD and UC are attributable to a likely primary genetic etiology. This is evidenced by the recent identification of the IBD1 gene ( NOD2 ) mutations which show an association with susceptibility to CD. The IBD complex shows a significant increased frequency in Jews when compared to non-Jews. While there is an increased incidence of colorectal cancer (CRC) in patients with IBD, it nevertheless is important to realize that IBD likely accounts for no more than 1-3% of all cases of CRC in Ashkenazi Jews. Importantly, however, awareness of the increased CRC risk in IBD may aid immeasurably in preventive interventions. The molecular pathway leading to CRC in IBD appears to differ from the well-known adenoma-to-CRC sequence, given the fact that these cancers appear to arise from either flat, dysplastic tissue or dysplasia-associated lesions or masses (DALMs). An important model, but by no means an absolute one, for colon carcinogenesis in IBD follows progression from an absence of dysplasia, to indefinite dysplasia, to low-grade dysplasia, on to high-grade dysplasia, and ultimately to invasive CRC. This carcinogenic process relates to the disease duration with respect to the extent of colonic involvement and may also involve primary sclerosing cholangitis. Given this knowledge of an increased risk for CRC in UC and CD, surveillance colonoscopy should initially be performed 8-10 years after onset of symptoms as opposed to diagnosis, and it should be performed 1-2 years after 8 years of disease in patients with pancolitis or after 15 years in those with left-sided colitis. A search for dysplasia of colonic mucosa with biopsies performed in all four quadrants every 10 cm throughout the colon is exceedingly important. Additional biopsies should be taken of any flat lesions, masses, or strictures. Prophylactic colectomy may then be indicated when severe dysplasia is confirmed by knowledgeable pathologists.

Management of neoplastic polyps in inflammatory bowel disease.

Dysplasia-associated lesions or masses (DALMs) are a heterogeneous population of lesions with different endoscopic and morphologic features. Non-adenoma-like DALMs should be removed via colectomy. Adenoma-like DALMs that occur outside areas of colitis can be treated like sporadic adenomas and removed by polypectomy. Recent data suggest that adenoma-like DALMs located within areas of colitis should be removed by polypectomy with complete excision and multiple biopsies of the site. As long as there is no flat dysplasia or adenocarcinoma elsewhere in the colon, a colectomy is not required. However, this group of patients requires increased colonoscopic surveillance.

Expression of survivin, YB-1, and KI-67 in sporadic adenomas and dysplasia-associated lesions or masses in ulcerative colitis.

Sporadic adenomas are said to exhibit an orderly growth pattern with a reversal of proliferative and apoptotic cell distribution as compared with normal colonic crypts. Dysplastic polyps of patients with ulcerative colitis (UC) may represent dysplasia-associated lesions or masses (DALM) with a high associated cancer risk, or, alternatively, may represent sporadic adenomas. Histologic criteria to differentiate between sporadic adenomas and DALM have not focused on the balance between cell renewal and cell loss. The expression of the novel anti-apoptosis gene product, survivin, and the proliferation markers, Ki-67 and Y-box binding protein (YB-1), were investigated by immunohistochemical localization in sporadic adenomas and DALM lesions of patients with UC. In adenomas, KI-67 was expressed preponderantly at the luminal aspect of the polyp, whereas its expression was diffuse in DALM. Survivin was detected diffusely in both adenomas and DALM. YB-1 showed positive staining in the deep aspect of adenomatous glands but only to a minor degree at the surface, whereas both deep and diffuse expression patterns of YB-1 were seen in DALM. The authors conclude that DALM and sporadic adenomas exhibit different patterns of cellular proliferation and that molecular markers of cell proliferation, Ki-67 and YB-1, may be useful to distinguish sporadic adenomas from DALM. However, the similar expression of survivin suggests that the underlying mechanisms that regulate apoptotic cell death are uniform in these lesions.

Polypectomy may be adequate treatment for adenoma-like dysplastic lesions in chronic ulcerative colitis

Background & Aims: Chronic ulcerative colitis (CUC)-associated adenoma-like DALMs (dysplasia-associated lesions or masses) pose a difficult clinical problem to both gastroenterologists and pathologists because they are difficult to distinguish endoscopically and pathologically from sporadic adenomas that develop coincidentally in patients with CUC. The aim of this study was to evaluate the outcome of CUC patients with an adenoma-like DALM treated conservatively and to compare the findings with CUC patients with a coincidental sporadic adenoma. Methods: Clinical, endoscopic, and pathological features and outcome of 24 CUC patients with an adenoma-like DALM were compared with those of 10 CUC patients with a coincidental sporadic adenoma and 49 non-CUC (control) patients with a sporadic adenoma. Patients were followed up for a mean of 42.4 and 41.2 months for the 2 CUC groups, respectively, and 37.0 months for the non-CUC controls by endoscopic surveillance. Results: Of the 24 CUC patients with adenoma-like DALMs (male/female ratio, 14/10; mean age, 61.5 years; mean duration of colitis, 10.4 years), 14 (58%) developed further adenoma-like DALMs within the follow-up interval. Only 1 patient (4%) developed an isolated focus of low-grade dysplasia, and none developed adenocarcinoma. Five of 10 (50%) CUC patients with sporadic adenomas developed further adenomas, and none of the patients in this group developed either dysplasia or adenocarcinoma. Of the 49 non-CUC control patients, 39% developed further adenomas. Conclusions: CUC patients who develop an adenoma-like DALM that endoscopically and histologically resembles a sporadic adenoma, regardless of its location (either within or outside areas of documented colitis), may be treated with polypectomy and endoscopic surveillance because of its relatively benign course. GASTROENTEROLOGY 1999;117:1288-1294