Incidence Of High-grade Dysplasia Research Articles

Systematic Four-Quadrant Biopsy Detects Barrett's Dysplasia in More Patients Than Nonsystematic Biopsy

To compare detection of Barrett's dysplasia and adenocarcinoma by systematic versus nonsystematic surveillance biopsy protocols. Upper GI consultation and open-access endoscopy are provided jointly at Glasgow Royal Infirmary by medical and surgical teams. The surgical team adopted annual systematic four-quadrant biopsy Barrett's surveillance in 1995. The medical team continued annual Barrett's surveillance with nonsystematic biopsy until 2004. We compare detection of Barrett's dysplasia and esophageal adenocarcinoma in unselected patients by these two biopsy strategies over 10 yr. All patients had > or = 3 cm Barrett's esophagus and histological proof of intestinal metaplasia. Patients referred for dysplasia management or with prevalent adenocarcinoma were excluded. Cohort A (N = 180) had four-quadrant biopsy every 2 cm while cohort B (N = 182) had nonsystematic biopsies. Cohort A versus cohort B: Median number of biopsies per endoscopy: 16 versus 4. Prevalence of low-grade dysplasia (per patient): 18.9% versus 1.6% (P << 0.001). Prevalence of high-grade dysplasia: 2.8% versus 0% (P = 0.03). Incidence of low-grade dysplasia: 2.2% versus 6.6% (NS). Incidence of high-grade dysplasia: 2.8% versus 0% (P = 0.03). Nine cohort A patients (total 5%, 1.4% per patient-year) were treated for HGD (eight endoscopically, one by esophagectomy). Two had intramucosal adenocarcinoma. No cohort A patient developed advanced cancer but three cohort B patients developed and died of invasive Barrett's adenocarcinoma (0.6% per patient-year). Patient age, gender, Barrett's segment length, and follow-up were similar (though not identical) in both cohorts, but confounding seems unlikely to account for a 13-fold difference in detection of prevalent dysplasia between the two groups. Our data support the hypothesis that systematic four-quadrant biopsy is considerably more effective than nonsystematic biopsy sampling in detecting Barrett's dysplasia and early adenocarcinoma. Greater biopsy numbers and the systematic pattern of biopsy taking may both contribute to this greater effectiveness.

Clinicopathologic Characteristics and Malignant Potential of Colorectal Flat Neoplasia Compared with that of Polypoid Neoplasia

Because of their potential for malignancy, flat colorectal neoplasias are a current topic of debate. This study was designed to investigate the clinicopathologic features of flat neoplasia and to compare them with those of polypoid neoplasia, as well as to identify the determinants of malignant transformation of both flat and polypoid colorectal neoplasia. A prospective, cross-sectional study of 3,360 patients diagnosed with adenomas via total colonoscopy and polypectomy was performed at 11 tertiary medical centers between July 2003 and July 2004. In this study, potential risk factors for malignant transformation were analyzed. If multiple adenomas were identified, then only the adenoma with the most advanced degree of histology was recorded for the patient. Of a total of 3,360 neoplasias identified, we found that the incidence of flat and polypoid neoplasias were 207 (6.2 percent) and 3,153 (93.8 percent), respectively. Patients with flat neoplasias tended to be older (59.6 vs. 57.1, P < 0.01), with the neoplasia located more frequently in the right colon than polypoid neoplasias (49.3 percent vs. 32 percent, P < 0.01). The incidence of high-grade dysplasia or cancer in flat neoplasias was similar to that of polypoid neoplasias (5.4 percent vs. 4.6 percent, P = 0.36). Multivariate analysis revealed that a size of > or =11 mm (odds ratio, 6.8; 95 percent confidence interval, 4.8-9.7) and location in the left colon (odds ratio, 1.6; 95 percent confidence interval, 1.1-2.4) were significant determinants for the malignancy potential of colonic neoplasias. The clinicopathologic indices for the propensity of malignant transformation in colorectal neoplasias were a size > or =11 mm and location in the left colon rather than flat gross morphology.

Chemopreventive effect of a vitamin D3 analog, alfacalcidol, on colorectal carcinogenesis in mice with ulcerative colitis

An increased incidence of colorectal carcinoma is known to occur in patients with ulcerative colitis (UC), which displays a cycle of recurrence-remission in the colorectal mucosa. Repeated oral doses of 3% dextran sulfate sodium subsequent to a single intraperitoneal injection of azoxymethane induced a chronic UC resulting in an increased incidence of high-grade dysplasia and submucosal-invasive adenocarcinomas in the mouse colorectum. The active form of vitamin D(3) is a calcium-regulating hormone that increases serum calcium levels and intestinal calcium absorption. It has been reported that there is an inverse correlation between serum levels of the active metabolite of vitamin D and colorectal carcinoma stage. The features of the colitis induced in this animal model are very similar to the UC in patients in terms of both clinical and histological characteristics. Treatment with a vitamin D(3) analog, alfacalcidol, in mice prevented colitis and carcinogenesis; this is shown by inhibition of the decrease in colorectal length and inhibition of the increased incidence of colorectal dysplasia, with a reduction in the mRNA expression of the DNA-synthesizing enzyme, thymidine kinase, in colorectal tissues.

Barrett’s Esophagus in Women: Demographic Features and Progression to High-Grade Dysplasia and Cancer

Barrett's esophagus is traditionally considered a disease of older white men. The aims of this study were to compare the demographic features of Barrett's esophagus in men and women and to determine the prevalence and incidence of high-grade dysplasia and cancer in these patients. All patients enrolled in the Cleveland Clinic Barrett's Esophagus Registry from 1979-2002 were studied. Age, ethnicity, number of endoscopies, hiatal hernia size, length of Barrett's segment, and prevalence and incidence of high-grade dysplasia and cancer were compared between men and women. There were 839 patients in the registry (628 men and 211 women). Barrett's segment length was greater in men than in women (mean, 5.06 +/- 4.2 vs 4.05 +/- 3.27 cm, respectively; P = .003). There were no significant differences for other parameters. There were 114 prevalence cases of high-grade dysplasia or cancer (96 men, 18 women). Women were less likely to have prevalent high-grade dysplasia or cancer than men (odds ratio, 0.52; 95% confidence interval, 0.31-0.88; P = .015). There were 13 incidence cases of high-grade dysplasia or cancer (11 men, 2 women) during a mean follow-up of 4.72 years, which was similar in both genders with an incidence rate of 1 in 179 patient-years of follow-up for women and 1 in 91 patient-years of follow-up in men. Twenty-five percent of patients in our registry are women. The length of Barrett's esophagus is greater in men than in women, but other features are similar. The prevalence of high-grade dysplasia/cancer in women is approximately half that of men. Incidence rates for high-grade dysplasia/cancer are similar in men and women, although the number of cases is small.

Should Complete Ablation of Barrett's Esophagus (BE) Be the Goal of Photodynamic Therapy (PDT)?

Background: PDT has been approved for the treatment of BE with high-grade dysplasia. The complete elimination of BE has been suggested as the goal of ablation therapy but the outcomes of complete ablation in a large cohort of patients with a long duration of follow-up has not been described. Aim: To compare the outcomes who achieved complete ablation of BE to those with residual BE after PDT. Methods: We reviewed the prospectively maintained database of patients treated with PDT for BE begun in 1991 in the Barrett's Esophagus Unit. Only patients followed for more than a year were included to allow a reasonable post-treatment surveillance period. Patients were treated with PDT using either sodium porfimer at a dose of 2 mg/kg. 48 hours after therapy, patient were photoradiated at a dose of 175-200 J/cm fiber at a power output of 400 mW/cm fiber using a 630 nm laser. Surveillance was done every 3-6 months by a single endoscopist with biopsies taken in four quadrants every centimeter of Barrett's esophagus. Two experienced gastrointestinal pathologists reviewed all pathology. Results: A total of 167 patients (139 males, mean age 64+/−1 years) were identified who had been followed for a mean of 54+/−3 months (range 12-148 months). These patients were treated for high-grade dysplasia in 90 (54%), adenocarcinoma in 22 (13%), low grade dysplasia in 42 (25%), and no dysplasia in 14 (8%). These patients had a mean BE length of 6+/−1 cm. 84 (50%) of the patients achieved complete ablation that was confirmed histologically 24+/−3 months after treatment. Of those that achieved a complete ablation, 93% (78) remained in histological remission during surveillance, 4% (3) developed non-dysplastic mucosa, 1% (1) developed low grade dysplasia, and 2% (2) developed high grade dysplasia. In the other 83 patients who had residual Barrett's mucosa, 6% (5) developed cancer and 8% (7) developed high-grade dysplasia. Patients who have complete elimination of Barrett's mucosa have a significantly lower likelihood of progressing to high-grade dysplasia or cancer (p<0.01). Conclusions: Complete ablation of BE is still associated with recurrence of Barrett's mucosa but the incidence of high grade dysplasia or cancer was only 2%. However, residual Barrett's mucosa after PDT was associated with a 14% incidence of high-grade dysplasia and cancer. Complete elimination of Barrett's mucosa should be the goal of ablation therapy as it reduces the risk of advanced neoplasia by 85%. Background: PDT has been approved for the treatment of BE with high-grade dysplasia. The complete elimination of BE has been suggested as the goal of ablation therapy but the outcomes of complete ablation in a large cohort of patients with a long duration of follow-up has not been described. Aim: To compare the outcomes who achieved complete ablation of BE to those with residual BE after PDT. Methods: We reviewed the prospectively maintained database of patients treated with PDT for BE begun in 1991 in the Barrett's Esophagus Unit. Only patients followed for more than a year were included to allow a reasonable post-treatment surveillance period. Patients were treated with PDT using either sodium porfimer at a dose of 2 mg/kg. 48 hours after therapy, patient were photoradiated at a dose of 175-200 J/cm fiber at a power output of 400 mW/cm fiber using a 630 nm laser. Surveillance was done every 3-6 months by a single endoscopist with biopsies taken in four quadrants every centimeter of Barrett's esophagus. Two experienced gastrointestinal pathologists reviewed all pathology. Results: A total of 167 patients (139 males, mean age 64+/−1 years) were identified who had been followed for a mean of 54+/−3 months (range 12-148 months). These patients were treated for high-grade dysplasia in 90 (54%), adenocarcinoma in 22 (13%), low grade dysplasia in 42 (25%), and no dysplasia in 14 (8%). These patients had a mean BE length of 6+/−1 cm. 84 (50%) of the patients achieved complete ablation that was confirmed histologically 24+/−3 months after treatment. Of those that achieved a complete ablation, 93% (78) remained in histological remission during surveillance, 4% (3) developed non-dysplastic mucosa, 1% (1) developed low grade dysplasia, and 2% (2) developed high grade dysplasia. In the other 83 patients who had residual Barrett's mucosa, 6% (5) developed cancer and 8% (7) developed high-grade dysplasia. Patients who have complete elimination of Barrett's mucosa have a significantly lower likelihood of progressing to high-grade dysplasia or cancer (p<0.01). Conclusions: Complete ablation of BE is still associated with recurrence of Barrett's mucosa but the incidence of high grade dysplasia or cancer was only 2%. However, residual Barrett's mucosa after PDT was associated with a 14% incidence of high-grade dysplasia and cancer. Complete elimination of Barrett's mucosa should be the goal of ablation therapy as it reduces the risk of advanced neoplasia by 85%.

Advanced diagnostic tools: virtual colonoscopy and magnifying chromoendoscopy

Early endoscopic diagnosis of colorectal cancers (CRCs) represents the best tool for the reduction of CRC mortality, but the conventional colonoscopic view seems unable to clarify faint changes of colorectal mucosa. For these reasons, during the last few decades, two new techniques have been developed in order to better define, diagnose and treat colorectal lesions: chromoendoscopy (CE) and magnifying chromoendoscopy (MC). The authors herein highlight the benefits of both and compare the results of conventional endoscopy and CE with 0.2% indigo carmine solution, evaluating 995 consecutive selected patients referred for colonoscopy between January 1999 and March 2003 at the International Health Union of Rome. CE showed new neoplastic patterns not detectable with conventional endoscopy in 102 patients (10.2%). The incidence of high-grade dysplasia and early carcinomas was 9.9% for protruded, 13.1% for flat and 60% for depressed lesions. Our comparative study on 995 consecutive selected patients confirmed the existence of flat and depressed neoplasms in Italy and shows the high accuracy rate of CE over conventional endoscopy for the detection of non-polypoid lesions. CE should be used routinely in order to enhance the early diagnosis of CRCs, while MC in experienced hands represents a significant advance in colonoscopic practice improving the diagnosis of every single lesion, enhancing therapeutic efficacy of colorectal tumours.

Significance of Atypical Squamous Cells of Undetermined Significance on ThinPrep Papanicolaou Smears

Gynecol Oncol 2000;79:44–49 The authors retrospectively reviewed the records of 126 patients with ASCUS using the ThinPrep system and subdivided them into ASCUS favor reactive and ASCUS favor HGSIL. The overall prevalence of dysplasia in this group was 15.9% and was higher among patients in the ASCUS favor HGSIL group. The incidence of high-grade dysplasia among the 63 patients in the ASCUS favor reactive group was 3.2%; the incidence in the ASCUS favor HGSIL group was 12.7%. Comment: This report appears to confirm that the finding of ASCUS favor HGSIL is associated with a significant risk of high-grade dysplasia. These findings are true both in conventional smears and in liquid-based cytology. The authors suggest that patients with ASCUS favor HGSIL should be offered colposcopic examination. (CJD)

Clinicopathological features of serrated adenoma of the colorectum: comparison with traditional adenoma.

AIM: Serrated adenoma is a recently described category of colorectal adenoma. The aim of this study was to determine whether serrated adenomas have clinicopathological findings distinct from "traditional" adenoma. METHODS:...

Serrated adenoma of the colorectum: colonoscopic and histologic features

Background: Serrated adenoma is a recently recognized epithelial neoplasm of the colorectum. The aim of this study is to clarify the colonoscopic features of serrated adenomas. Methods: The endoscopic findings for 52 serrated adenomas of the colorectum were investigated; these were then divided into three groups according to surface features. The histologic type (tubular, tubulovillous or villous) and the incidence of high-grade dysplasia were compared among the three groups. Results: The surface under chromoscopy showed a hyperplastic pattern in 17 lesions, a cerebriform pattern in 18 lesions and a combined pattern in 17 lesions. The tubular type of serrated adenoma was predominant in the hyperplastic pattern group (94%), whereas the tubulovillous or villous histologic types were frequent in the cerebriform pattern (89%) and combined pattern (82%) groups. High-grade dysplasia was found in 18% of the combined pattern adenomas; the incidence was lower in hyperplastic (6%) or cerebriform pattern (0%) adenomas. Conclusions: Surface features of serrated adenomas have a close correlation with their histologic type. A combined hyperplastic-cerebriform surface pattern under chromoscopy was seen only in serrated adenomas. (Gastrointest Endosc 1999;49:736-42.)

Surveillance for colonic carcinoma in ulcerative colitis

To evaluate the efficacy of surveillance colonoscopy with biopsy for the detection of high-grade dysplasia (HGD) or colonic carcinoma in patients with chronic ulcerative colitis, we undertook a retrospective review of 248 patients who underwent 370 examinations (mean duration of disease 12 yr). High-grade dysplasia or carcinoma was found in 24 examinations in 16 patients, with a mean duration of disease of 16 yr. There were 15 patients with HGD. Nine patients had HGD alone, 6 had HGD and carcinoma, and 1 had carcinoma without HGD. The overall incidence of HGD was 6%. Dysplasia-associated lesions or mass were the most consistent indicators of carcinoma, the combination being present in four instances. Of the 7 patients with cancer, 6 were recognized by colonoscopy, and 1 patient with negative visual endoscopie findings was discovered using surveillance biopsies. The conclusions of this study are that dysplasia is a reliable histopathologic marker and correlates with the presence of cancer in chronic ulcerative colitis; the absence of dysplasia correlates with the absence of cancer. The presence of dysplasia-associated lesions or mass with HGD is the strongest indication for operation. This study supports the use of surveillance colonoscopy in managing high-risk ulcerative colitis patients.