Incidence Of High-grade Dysplasia Research Articles

Risk factor analysis of malignant adenomas detected during colonoscopy.

Several studies have shown that colorectal adenomas are the most important precancerous lesions. The colonoscopic identification of groups with the high risk of malignant colorectal adenomas remains a controversial issue for clinicians. To evaluate the basic characteristics of colorectal adenomas with malignancy risk using high-grade dysplasia (HGD) as an alternative marker for malignant transformation. Data from Shanghai General Hospital between January 2017 and December 2021 were retrospectively analyzed. The primary outcome was the incidence of HGD in adenomas, which was used as a surrogate marker for the risk of malignancy. Odds ratios (ORs) for the HGD rate in adenomas were analyzed in relation to adenoma-related factors. A total of 9,646 patients identified with polyps during 57,445 screening colonoscopies were included in the study. Patients with flat polyps, sessile polyps, and pedunculated polyps represented 27.3% (N = 2,638), 42.7% (N = 4,114), and 30.0% (N = 2,894) of the total number, respectively. HGD was found in 2.41% (N = 97), 0.92% (N = 24), and 3.51% (N = 98) of sessile adenomas, flat adenomas, and pedunculated adenomas, respectively (P < 0.001). Multivariable logistic regression showed that polyp size (P < 0.001) but not shape (P > 0.8), was an independent predictor of HGD. Contrast to the diameter ≤1 cm, the OR value for diameters 1-2, 2-3, and >3 cm was 13.9, 49.3, and 161.6, respectively. The HGD incidence also increased in multiple adenomas (>3 vs. >1, ORs 1.582) and distal adenomas (distal vs. proximal adenomas, OR 2.252). Adenoma morphology (pedunculated vs. flat) was statistically significant in univariate analysis but not when size was included in the multivariate analysis. Besides, the incidence of HGD was also significantly higher in older patients (>64 vs. <50 years old, OR = 2.129). Sex (P = 0.681) was not statistically significant. All these associations were statistically significant (P < 0.05). The malignant potential of polyps is mostly affected by their size but not by their shape. In addition, distal location, multiple adenomas, and advanced age were also correlated with malignant transformation.

Risk stratification of patients with gastric lesions indefinite for dysplasia.

Background/AimsThere are no definite guidelines for the management of gastric lesions diagnosed as indefinite for dysplasia (IND) by endoscopic forceps biopsy (EFB). Therefore, this study aimed to evaluate the clinical outcomes of gastric IND and predictive factors for gastric neoplasm.MethodsThis study included 457 patients with a first diagnosis of gastric IND by EFB between January 2005 and December 2013. Patient characteristics and endoscopic and pathological data were reviewed and compared.ResultsOf the 457 gastric IND patients, 128 (28%) were diagnosed with invasive carcinoma, 21 (4.6%) with high-grade dysplasia, 31 (6.8%) with low-grade dysplasia, and 277 (60.6%) as negative for dysplasia. Of lesions observed, 180 (39.4%) showed upgraded histology. Multivariate analysis revealed that surface erythema (odds ratio [OR], 2.804; 95% confidence interval [CI], 1.741 to 4.516), spontaneous bleeding (OR, 2.618; 95% CI, 1.298 to 5.279), lesion size ≥ 1 cm (OR, 5.762; 95% CI, 3.459 to 9.597), and depressed morphology (OR, 2.183; 95% CI, 1.155 to 4.124) were significant risk factors for high-grade dysplasia or adenocarcinoma. The ORs associated with 2 and ≥ 3 risk factors were 7.131 and 34.86, respectively.ConclusionsPrecautions should be taken in the management of gastric IND patients, especially when risk factors, including surface erythema, spontaneous bleeding, lesion size ≥ 1 cm, and depressed morphology are present. Considering the combined effect of the presence of multiple risk factors on the incidence of high-grade dysplasia or adenocarcinoma, endoscopic resection should be recommended if a gastric IND patient has at two or more of these factors.

Importance of each high-risk stigmata and worrisome features as a predictor of high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas

BackgroundHigh-risk stigmata (HRS) and ‘worrisome features’ (WFs) are defined as predictive factors for malignancies of intraductal papillary mucinous neoplasms (IPMNs). We performed this study to determine the importance and odds ratio (OR) of each HRS and WFs as predictors for high-grade dysplasia (HGD). MethodsWe analyzed 295 patients who underwent pancreatectomy for branch duct and mixed-type IPMN, and evaluated the association between HRS and WFs (as defined by the ‘2017 Fukuoka Consensus Guidelines’) and HGD. ResultsThe proportions of patients with low-grade dysplasia (LGD), HGD, and invasive carcinoma were 47%, 28%, and 25%, respectively. Multivariate analysis comparing patients with LGD and HGD using all HRS and WFs revealed that an enhancing mural nodule ≥5 mm (OR: 4.1), pancreatitis (OR: 2.2), and thickened/enhancing cyst walls (OR: 2.2) were independent predictive factors for HGD. Based on the OR (the former factor is two points and the latter two factors are each one point), the incidence of HGD in patients with none (n = 43), one (n = 82), two (n = 25), three (n = 52), and four (n = 19) of these predictive factors were 9%, 26%, 52%, 62%, and 63%, respectively. Assuming a score of one or higher as a surgical indication, the sensitivity, specificity, positive predict value, and negative predict value of HGD were 95, 38, 44, and 91%. ConclusionsOur derived scoring system using more important factors in HRS and WFs may be useful for predicting HGD and determining surgical indications of IPMN.

Sa1149 – Incidence of High Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients with Irregular Z Line

Sa1149 – Incidence of High Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients with Irregular Z Line

Incidence of Progression of Persistent Nondysplastic Barrett’s Esophagus to Malignancy

The risk of esophageal adenocarcinoma (EAC) in patients with non-dysplastic Barrett's esophagus (NDBE) is low, so there is debate over the role of ongoing surveillance for patients with NDBE. It is important to identify patients at low risk for progression. We assessed cancer risk based on the subsequent number of endoscopies showing persistence of NDBE in a nationwide study in the Netherlands. In a population-based study, patients with a first diagnosis of NDBE were selected from the Dutch nationwide registry of histopathology. We calculated incidence rates and incidence rate ratios (IRR) for high-grade dysplasia (HGD) and EAC to determine whether the number of endoscopies negative for dysplasia and the persistence of NDBE over time associate with progression to malignancy. We identified 12,728 patients with NDBE during 2003 and 2013. HGD or EAC developed in 436 patients (3.4%) during 64,537 person-years of follow up (median, 4.9 years). The rate of progression to HGD or EAC was 0.68 (95% CI, 0.61-0.74) per 100 person-years. In patients with 2 consecutive endoscopies showing NDBE, the rate of progression to HGD or EAC decreased to 0.55 (95% CI, 0.46-0.64) per 100 person-years (IRR, 0.72; 95% CI, 0.60-0.87). Overall, the incidence of HGD or EAC decreased by 14% for each year of progression-free follow-up (IRR, 0.86; 95% CI, 0.81-0.92). In a population-based study in the Netherlands, we found patients with stable NDBE to have a low risk of progression to HGD or EAC. These findings indicate that surveillance intervals might be lengthened or even discontinued in subgroups patients with persistent NDBE.

Review of Cervical Carcinoma Screening Program in Tamil Nadu – Current Trend and Recommendations from a Histopathologist’s Viewpoint

ABSTRACT Objectives Cervical carcinoma, the commonest carcinoma affecting Indian females, is caused by human papilloma virus (HPV) infection. Primordial prevention and primary prevention with HPV vaccine and cancer screening respectively, can go a long way in preventing this carcinoma. The health system project in Tamil Nadu has done a commendable job in reducing the disease burden by introducing screening programs for cervical carcinoma at the grassroots level, way back in 2005. This study was done to evaluate the cervical biopsy specimens received as a part of this program to compute its incidence, compare the incidence among various districts, and suggest future directions based on our observations. Materials and methods From visual inspection with acetic acid/visual inspection with Lugol’s iodine positive cervical biopsy specimens, 506 were chosen randomly from various districts. Based on histopathological examination, incidence of individual lesions and district-wise incidence were calculated. Predictive factors that determine the progression of these lesions were analyzed based on the literature. Results Out of the 506 cervical biopsy specimens, 34 were unsatisfactory. The incidence of high-grade dysplasia peaked around 31 to 40 years, and squamous cell carcinoma peaked among 51 to 60 years. Madurai ranked high in the incidence of both high-grade dysplasia and carcinoma. Conclusion Incidence of dysplasia and carcinoma in our study was comparable to those seen in the literature. Integration of HPV deoxyribonucleic acid studies into the program can increase the detection rate, detect the progressors, help to identify the HPV species prevalent in an area, and aid in formulating cost-effective HPV vaccine cocktail. How to cite this article Ibrahim SS, Kesavaraj K, Arun M, Ameen SAM, Sankar R. Review of Cervical Carcinoma Screening Program in Tamil Nadu – Current Trend and Recommendations from a Histopathologist’s Viewpoint. J South Asian Feder Menopause Soc 2017;5(1):1-7.

Patients With Barrett's Esophagus and Persistent Low-grade Dysplasia Have an Increased Risk for High-grade Dysplasia andCancer.

In some patients with Barrett's esophagus (BE) and a confirmed diagnosis of low-grade dysplasia (LGD), the LGD is not detected during follow-up examinations. We would like to avoid the unnecessary risks and costs of ablative treatment for these patients. Therefore, we investigated whether persistent LGD increases risk for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and what proportion of patients are no longer found to have dysplasia after an initial diagnosis of LGD. In a retrospective study, we collected information on 1579 patients with BE and LGD from 2005 through 2010 by using a nationwide registry of histopathology diagnoses in the Netherlands (PALGA). Confirmed LGD was defined as a diagnosis of LGD that was confirmed by any other pathologist. Persistent LGD was defined as LGD detected at the first and follow-up endoscopy. Datawere collected on patients until treatment for HGD, detection of EAC, or the last endoscopy at which a biopsy was collected (through July 2014). We evaluated whether persistent LGD was a risk factor for malignant progression by using univariable and multivariable Cox regression analyses. Of individuals with BE and LGD in the database, the diagnosis of LGD was confirmed for 161 patients (10% of total). In these patients, the incidence of HGD and/or EAC was 5.18/100 person-years (95% confidence interval [CI], 4.32-8.10/100 person-years) compared with 1.85/100 person-years (95% CI, 1.52-2.22/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. The incidence of EAC alone in patients with confirmed LGD was 2.51/100 person-years (95% CI, 1.46-3.99/100 person-years), compared with 1.01/per 100 person-years (95% CI, 0.41-2.10/100 person-years) in patients for whom LGD was not confirmed at the first endoscopy. Of patients in whom LGD was confirmed at the first endoscopic examination, 51% were not found to have dysplasia at the first follow-up endoscopy, and 30% had persistent LGD. In patients with persistent LGD, the incidence of HGD and/or EAC was 7.65/100 person-years (95% CI, 4.45-12.34) and of only EAC was 2.04/100 person-years (95% CI, 0.65-4.92); in patients without persistent LGD, the incidence of HGD and/or EAC was 2.32/100 person-years (95% CI, 1.08-4.40/100 person-years) and of only EAC was 1.45 (95% CI, 0.53-3.21/100 person-years). Persistent LGD was found to be an independent risk factor for the development of HGD and/or EAC, with hazard ratio of 3.5 (95% CI, 1.48-8.28). In a large population-based cohort study of patients with BE and LGD, the risk of progression to HGD and/or EAC was higher in patients with confirmed LGD and highest in those with confirmed and persistent LGD.

Low risk of adenocarcinoma and high-grade dysplasia in patients with non-dysplastic Barrett's esophagus: Results from a cohort from a country with low esophageal adenocarcinoma incidence.

The risk of esophageal adenocarcinoma (EAC) in non-dysplastic Barrett's esophagus (NDBE) is considered to be approximately 0.3% per year or even lower, according to population-based studies. Data from countries with low EAC incidence are scarce. Our principal aim was to determine the incidence of high-grade dysplasia (HGD) and EAC in NDBE. Our secondary aims were to identify the predictors of progression and to calculate the incidence of HGD/EAC, by using the calculation method for surveillance time in population-based studies. A cohort of NDBE patients was prospectively followed up. Cases of HGD and EAC (study end points) diagnosed during the first year of follow-up were considered as prevalent. Only cases with an endoscopic surveillance time > 1 year were included in our analysis. We enrolled 331 patients (251 men) in the surveillance program. Their median age was 59 years (interquartile range (IQR): 47-67 years). Their median NDBE length was 3 cm (IQR: 2-4 cm). Of these patients, 80 died during the follow-up (one from EAC) and two were lost to follow-up. After 2284 patient-years of endoscopic follow-up (median surveillance time, 5 years (IQR: 2-10 years)), we found that five cases of HGD and two cases of EAC were diagnosed. The incidence of HGD/EAC was 3.1 cases per 1000 patient-years (95% CI: 1.3-6.0) and that of EAC was 0.9 (95% CI: 0.2-2.9). The incidence of HGD/EAC in short segments (≤ 3 cm) was 0.7 cases per 1000 patient-years (95% CI: 0.3-3.4). The sole variable that we found associated with progression was NDBE length. If the total surveillance time was considered (3537 patient-years), the incidence of HGD and EAC was only slight lower. The incidence of HGD and EAC was very low in NDBE. Therefore, current surveillance guidelines must be reassessed, at least for short-segment BE.

Significance of a white opaque substance under magnifying narrow-band imaging colonoscopy for the diagnosis of colorectal epithelial neoplasms

The aim of this study was to examine the significance of a white opaque substance (WOS) found on magnifying narrow-band imaging (M-NBI) for the diagnosis of colorectal neoplastic lesions. We retrospectively reviewed colonoscopy records from 2006 to 2012 at our institution and identified cases of endoscopically or surgically resected colorectal epithelial neoplasms observed by M-NBI colonoscopy. The colonoscopic and histologic characteristics of the lesions were compared between WOS-positive and WOS-negative lesions. We further classified the WOS as regular or irregular and compared the histologic characteristics between the two types of lesions. There were 105 WOS-positive lesions and 451 WOS-negative lesions. The former were subdivided into lesions with regular and irregular WOS. The incidence of high-grade dysplasia or carcinoma was significantly higher in WOS-positive lesions (61.9%) than in WOS-negative lesions (28.6%) (P < .05). Among the WOS-positive lesions, massive submucosal invasion was more frequent in lesions with irregular WOS (82.4%) than in those with regular WOS (1.4%) (P < .05). Among cancers with massive submucosal invasion, lymph node metastasis was more frequent in cancers with irregular WOS (17.4%) than in those with regular WOS or without the WOS (0%) (P < .05). A WOS in colorectal neoplasms may be an optical marker for high-grade dysplasia and cancer. An irregular WOS may be indicative of massive submucosal invasion and lymph node metastasis.

OC-088 Risk of oesophageal neoplasia in barrett’s oesophagus with indefinite for dysplasia or low grade dysplasia at index biopsy: a 10-year cohort study

Introduction Barrett’s oesophagus (BO) is the only recognised precursor for oesophageal adenocarcinoma (OAC). Accurate prediction of progression to high grade dysplasia (HGD) or OAC is important. The literature reports progression rates for indefinite for dysplasia (IND) at 1.2% per patient-year and low grade dysplasia (LGD) at 9% per patient-year. Our study aims to determine incidence of HGD or OAC in patients with confirmed histopathological diagnosis of IND or LGD at index biopsy. Method Retrospective review of all patients diagnosed with IND or LGD over a 10-year period from January 2003 to September 2014. Two specialist pathologists in Barrett’s oesophagus and neoplasia reviewed all histology. Primary end point was progression to HGD or OAC. Patient demographics and grade of endoscopist were recorded. Patients with HGD or OAC at index biopsy were excluded. Results 85 patients (78.8% male, 100% White British) had LGD; 138 (65.9% males, 100% White British) patients had IND. 47% (n = 40) patients with LGD and 10.1% (n = 14) patients with IND progressed to HGD or OAC in the 10-year period. Median age at progression was 71 years (IQR 61.5 to 75.3) and 68 years (IQR 60.25 to 73.5) for LGD and IND, respectively. Median time of progression from first diagnosis to HGD or OAC was 16 months for both IND and LGD. Median BO length was 7 cm (IQR 5 to 9.75) in LGD and 6 cm (IQR 4.25 to 6.75) in IND. 35% (n = 14) patients with LGD who progressed had an expert upper GI endoscopist performing the endoscopy; in these 14 patients, median time for progression was 5.5 months (IQR 3.25 to 12.75). 67.5% (n = 27) patients with LGD were diagnosed with HGD or OAC 12 months after their last biopsy; the median time to biopsy in the LGD group was 5 months (IQR 1.5 to 6). But 16.8% (n = 15) patients were diagnosed with HGD/OAC at the first follow-up biopsy; the median time to this diagnosis was 5 months (IQR 2.5 to 6). Excluding 5 IND patients who developed OAC within 12 months, median time to progression for IND was 46 months (IQR 18 to 66); 7 patients with IND progressed to HGD, 5 patients progressed to intramucosal adenocarcinoma, and 2 died of inoperable adenocarcinoma. Conclusion The majority of LGD who progressed occurred in less than 12 months, and median time to diagnosis was 5 months. An expert upper GI endoscopist follow up is warranted for earlier diagnosis and treatment in IND and LGD. Current BSG Guidelines suggest a follow-up surveillance endoscopy should be done at 6 months for confirmed LGD prior to radio-frequency ablation. Our findings suggest these patients should be followed up earlier. LGD should be recognised as a marker of more advanced neoplasia. Disclosure of interest None Declared.

Dietary Selenium Deficiency Exacerbates DSS-Induced Epithelial Injury and AOM/DSS-Induced Tumorigenesis

Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis.

Mo1110 A Systematic Review of Patient Provider, and System Barriers to Colorectal Cancer Screening With Colonoscopy in African-Americans

Introduction: African-Americans (AAs) are 20% less likely than Caucasians to undergo appropriate colorectal cancer (CRC) screening. The group also carries the greatest burden of disease, as evidenced by the highest: 1) incidence of CRC of any ethnic group; 2) CRC mortality rate; 3) prevalence of polyps at screening colonoscopy; 4) incidence of high-grade dysplasia at age ,50; and 5) incidence of advanced stage at disease presentation. While studies have explored barriers to uptake for screening colonoscopy among AAs, existing literature lacks a comprehensive conceptual framework that synthesizes the contributing patient, provider, and system factors. We sought to systematically review the literature to inform a conceptual framework governing all barriers to colonoscopic screening in AAs. Methods: We conducted a systematic review of Medline and Cochrane databases for studies addressing barriers to colonoscopic CRC screening. Search results were reviewed manually and included if they addressed barriers to uptake of screening colonoscopy, included AAs in the U.S, and were published in English between 1/1/90 and 11/1/12. We then employed a modified Andersen Behavioral Model of Health Service Use as a conceptual framework to construct a model for uptake for screening colonoscopy among AAs in the U.S. ( Table). Results: We identified and reviewed 409 abstracts by two authors; 127 were included in the full-text review process. Of these studies, 34 met criteria for inclusion. 20 (59%) studies presented patient-level barriers to screening uptake, 13 (38%) addressed provider-level barriers, and 8 (24%) presented system-level factors. 16 (47%) studies reported rates of colonoscopy uptake for AAs, which ranged from 14% to 65%. Prominent patient-level barriers were low education level, lack of knowledge about CRC screening, fear of cancer diagnosis, anxiety about procedure discomfort, self-perception of low cancer risk, and direct and indirect costs. Provider-level factors included knowledge deficits about guidelines and lack of screening recommendation. System-level factors included lack of insurance coverage, poor access to care, insufficient time with primary care physicians, inaccessibility of specialist services, absence of reminder systems, and insufficient reimbursement for discussing screening. Conclusions: We identified multiple, modifiable patient, provider, and system-level barriers to CRC screening among average-risk AAs. Heeding these barriers, future interventions should target patient knowledge about the efficacy of colonoscopy screening for preventing CRC, physician knowledge about screening guidelines for AAs, and access to healthcare services. Using focused interventions at the level of the patient, provider, and healthcare system, we may reduce the morbidity and mortality from CRC in this high-risk, under-screened population. Patient, Provider, and System-level Barriers to Colorectal Cancer Screening Among AfricanAmericans. Based on a modified Andersen Model of Health Services Use.

Abstract 178: Vitamin D reduces lung cancer progression the N-nitroso-tris-chloroethylurea model of mouse lung squamous cell carcinoma.

Abstract Vitamin D, an essential mediator of calcium homeostasis, acts through the vitamin D receptor to promote cellular differentiation and inhibit proliferation. Epidemiologic studies indicate that low serum levels of 25(OH)D3 are associated with increased risk and poor prognosis of lung cancer. Pre-clinical studies in mice show that dietary vitamin D and calcium deficiency promote carcinogenesis in mouse models of cancer. These data suggest that vitamin D may have a role as a chemopreventive agent. To investigate the role of vitamin D in lung cancer, a carcinogen-induced model of lung squamous cell carcinoma (SCC) was employed. N-nitroso-tris-chloroethylurea (NTCU) was applied topically each week to the back of SWR/J mice. Following ∼15 weeks of NTCU treatment, mice on a standard diet begin to develop flat atypia, which progresses through dysplasia to invasive lung SCC by 35 to 40 weeks. We investigated the effects of vitamin D on cancer progression using different levels of dietary vitamin D3 and injections of the most active metabolite 1,25(OH)2D3 (calcitriol) in the NTCU model (80 mM/week). After 24 weeks of NTCU, mice on a deficient diet had more advanced disease than those on a sufficient diet. However, that study demonstrated that the 80 mM/week of NTCU was too toxic and resulted in premature death. A second vitamin D intervention study has now been completed using a less toxic dose of 40 mM/week of NTCU. In this study mice were randomized to 6 treatment groups (Table 1). Disease burden, as measured by histology (Table 1), was similar to that seen with higher dose NCTU. This study supports our earlier findings that vitamin D deficient mice develop disease at a more rapid rate when compared to mice that are sufficient. This also suggests that calcitriol administration may reduce the progression of lung SCC in mice that are vitamin D deficient. Further studies are on going to elucidate the mechanism by which vitamin D acts to slow the progression of lung SCC in this model. Table 1. Serum 25(OH)D3 levels &amp; incidence of high-grade dysplasia and lung SCC. Group Carcinogen (NTCU) Diet Vitamin D (IU/kg) Serum 25(OH)D3 Level (ng/ml) High-grade Dysplasia (%) Lung SCC (%) D deficient − 0 &amp;lt;4 0/11 (0) 0/11 (0) D deficient +NTCU + 0 &amp;lt;4 13/13 (100) 11/13 (85) D deficient +NTCU &amp; calcitriol (i.p. 80 ug/kg/w) + 0 &amp;lt;4 14/14 (100) 8/14 (57) D sufficient − 2,000 21 0/14 (0) 0/14 (0) D sufficient +NTCU + 2,000 19 13/14 (92) 4/14 (29) D sufficient +NTCU &amp; calcitriol (i.p. 80 ug/kg/w) + 2,000 10 10/13 (76) 3/13 (20) Citation Format: Sarah A. Mazzilli, Mary Reid, Paul Bogner, Donald Trump, Candace Johnson. Vitamin D reduces lung cancer progression the N-nitroso-tris-chloroethylurea model of mouse lung squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 178. doi:10.1158/1538-7445.AM2013-178

Re: Risk of Malignant Progression in Barrett's Esophagus Patients: Results from a Large Population-Based Study

Bhat’s article (1) and its accompanying editorial (2) addressed the screening and/or surveillance strategies for Barrett’s esophagus (BE). We agree that the incidence of Barrett’s adenocarcinoma (BAc) is lower than that previously claimed (1,3). Consistent with data, variable endoscopy/biopsy protocols and inconsistent endoscopist–pathologist interactions substantially affect the assessment and reported prevalence of this disease (4,5). Unequivocal definitions, educational programs, and audited interdisciplinary teamwork are needed to obtain more reliable information, as demonstrated by our seven-year experience with a multicenter BE registry (the Esofago di Barrett e Rischio di Adenocarcinoma [EBRA] in Northeast Italy) (4,5). This registry, which is restricted to the records of intestinalized-BE patients and excludes patients with cancers that were diagnosed within a year of enrollment, currently includes 841 patients, with a median followup of 44.6 months or 3 058 patient-years (6). The incidence of high-grade dysplasia (HGD) is 4.9 (95% confidence interval [CI] = 2.7 to 8.1) patients per 1 000 person-years, and the incidence of BAc is 2.3 (95% CI = 0.9 to 4.7) patients per 1 000 person-years. Among patients with low-grade dysplasia, 32.0 (95% CI = 12.7 to 65.3) per 1 000 patient-years will progress to HG-D or BAc. These prospectively collected data lie between the earlier “enthusiastic” figures and Bhat’s “pessimistic” findings. Interestingly, Bhat’s findings and our own experience with the EBRA consistently demonstrate that the BE planet has so far been only partially explored.

Patients With Nondysplastic Barrett's Esophagus Have Low Risks for Developing Dysplasia or Esophageal Adenocarcinoma

The risks of dysplasia and esophageal adenocarcinoma (EAC) are not clear for patients with nondysplastic Barrett's esophagus (NDBE); the rate of progression has been overestimated in previous studies. We studied the incidences of dysplasia and EAC and investigated factors associated with progression of BE. The BE study is a multicenter outcomes project of a large cohort of patients with BE. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Patients followed up for at least 1 year after the index endoscopy examination were included, whereas those diagnosed with dysplasia and EAC within 1 year of diagnosis with BE (prevalent cases) were excluded. Of 3334 patients with BE, 1204 met the inclusion criteria (93.7% Caucasian; 88% male; mean age, 59.3 y) and were followed up for a mean of 5.52 years (6644.5 patient-years). Eighteen patients developed EAC (incidence, 0.27%/y; 95% confidence interval [CI], 0.17-0.43) and 32 developed HGD (incidence, 0.48%/y; 95% CI, 0.34-0.68). The incidence of HGD and EAC was 0.63%/y (95% CI, 0.47-0.86). There were 217 cases of low-grade dysplasia (incidence, 3.6%/y; 95% CI, 3.2-4.1). Five and 10 years after diagnosis, 98.6% (n = 540) and 97.1% (n = 155) of patients with NDBE were cancer free, respectively. The length of the BE was associated significantly with progression (EAC <6 cm, 0.09%/y vs EAC ≥ 6 cm, 0.65%/y; P = 0.001). There is a lower incidence of dysplasia and EAC among patients with NDBE than previously reported. Because most patients are cancer free after a long-term follow-up period, surveillance intervals might be lengthened, especially for patients with shorter segments of BE.

Barrettʼs Surveillance Interval Repeat Ratio: A Novel Utilization Metric

Purpose: Surveillance endoscopy (EGD) programs in patients with Barrett's Esophagus (BE) are recommended to detect development of dysplasia or early esophageal adenocarcinoma (EAC). Current guidelines recommend repeat EGD within one year for patients without dysplasia and interval EGD every 3 years subsequently; and for patients with low grade dysplasia repeat EGD within 6 months and annually subsequently. The number of patients diagnosed with BE has increased in the recent decades and this increase has significant implications for health care resource utilization and costs. Currently there are no objective criteria which can be used as a utilization measure. We proposed to devise a novel metric of BE Interval Repeat Ratio (BEIRR) to optimize utilization of surveillance EGD in BE. Methods: Retrospective review of medical records for a cohort of patients (≥ 18 years) who had EGD which detected mucosal changes suspicious for BE between January 2004 to December 2006 done by 6 well experienced gastroenterologists at the University setting. These patients were followed till May 2010. BEIRR was calculated as Total number of repeat EGD's + Total number of Initial EGD's/Total number of Initial EGD's for 6 providers separately and statistical analysis was performed. Patients diagnosed to have EAC and patients whose pathology reports could not be obtained were excluded from the final analysis. Results: 151 patients were identified with mucosal changes suspicious for BE (111 Male; Mean Age 61.1 years) and 13 were excluded. 82 patients had BE without dysplasia, 4 patients had BE with low grade dysplasia and 52 patients did not have microscopic changes of BE. 136 EGD's were repeated over 6 years for patients with BE without dysplasia with a cumulative BEIRR of 2.8. Individual BEIRR for 6 providers were 3, 2.26, 3.5, 2.1, 2.1 and 2.3, respectively, with a mean of 2.54, SD 0.57; 95% CI 1.4-3.68. For 4 patients with low grade dysplasia 24 EGD's were repeated with cumulative BEIRR of 7. For patients without BE on microscopy 54 EGD's were repeated of which 33 (61%) were repeated for surveillance and none of the subsequent EGD's showed any evidence of metaplasia, dysplasia or cancer. One patient with LGD progressed to have high grade dysplasia and one patient progressed to have adenocarcinoma. Conclusion: BEIRR's can be used as a benchmark metric to optimize utilization of surveillance EGD's for BE. We found a very low incidence of high grade dysplasia and adenocarcinoma in our cohort of patients consistent with prior reported data. Surveillance EGD for patients with no microscopic evidence of BE did not detect even a single case of metaplasia, dysplasia or cancer.

Detection of Oncogenic Human Papillomavirus Impacts Anal Screening Guidelines in Men Who Have Sex With Men

It has been shown that testing for oncogenic human papillomavirus (HPV+) improves the sensitivity of cytologic diagnosis of atypical cells of undetermined significance in the cervix and anus, reducing the number of patients requiring colposcopy or high-resolution anoscopy. Some recommend that men who have sex with men with any abnormal cytology undergo high-resolution anoscopy. We endeavored to determine whether HPV testing could predict future high-grade dysplasia (high-grade squamous intraepithelial lesions) and modify screening internals. This investigation was conducted via a retrospective chart review of subjects with atypical cells of undetermined significance anal cytology, high-resolution anoscopy, and HPV testing. Records were abstracted for prior and subsequent screenings. Four hundred men who have sex with men (285 HIV-) underwent 2224 screenings. Of 224 subjects monitored for >2 years, the hazard ratio for developing high-grade dysplasia was 77% less for men who have sex with men who never had oncogenic HPV (HPV-) vs those who stayed HPV+ (P < .013). The hazard ratio for high-grade dysplasia in those who were HPV- vs those who became HPV- was not different. Risk of high-grade dysplasia was 28% within 6 months of becoming HPV+. The 3-year high-grade dysplasia risk was 15% and 54% for HPV- vs HPV+ subjects (P = .0006). Frequency of high-grade dysplasia in subjects who remained HPV- with predominantly atypical cells of undetermined significance cytology for 1, 2, or 3 years was 2%, 0% and 0% and was 17%, 0%, and 0% in HIV+ subjects. Kaplan-Meier analysis for HIV- subjects with HPV- predominantly atypical cells of undetermined significance cytology for 1 year showed <5% incidence of high-grade dysplasia at 4 years. Change in HPV status can predict the risk of high-grade dysplasia. Subjects with predominantly HPV- atypical cells of undetermined significance cytology for 2 years have a decreased risk of high-grade dysplasia. HPV testing when screening for anal dysplasia could alter screening parameters.

Outcome of endoscopy surveillance for Barrett's oesophagus

Endoscopic surveillance of individuals with Barrett's oesophagus is undertaken to detect early stage oesophageal malignancy. The impact of a surveillance programme on endoscopy resources and disease detection is uncertain. In 2004, we commenced a structured Barrett's oesophagus surveillance programme. The surveillance protocol specifies surveillance interval and number of oesophageal biopsies required according to previous endoscopy and biopsy findings. The first 3 years of surveillance were reviewed to assess programme adherence, impact on endoscopy resources and the incidence of high-grade dysplasia and adenocarcinoma in patients undergoing surveillance. Four hundred five patients were enrolled in the surveillance programme, and 776 patient years of endoscopy follow-up were analysed. Four-quadrant biopsies every 2 cm throughout the Barrett's oesophagus were performed in 89.8% of endoscopies. A total of 93.7% of patients had surveillance endoscopy performed at the appropriate time interval. Formalizing surveillance was followed by a decrease in the mean time interval for endoscopy surveillance from 16 months to 15 months, although the mode endoscopy surveillance interval lengthened from 1 year to 2 years. The mean number of biopsies per endoscopy increased from 5.9 to 7. In four patients, T1 stage oesophageal adenocarcinoma was identified, and in six patients, high-grade dysplasia was identified (combined incidence of adenocarcinoma/high-grade dysplasia 1 per 77.6 endoscopy years of follow-up). Structured Barrett's surveillance detects malignant progression at an early stage, which provides opportunities for curative surgical or endoscopic intervention. Formalizing surveillance resulted in a high rate of adherence to agreed guidelines and rationalized the use of endoscopy resources without significantly increasing workload.

Medication Usage and the Risk of Neoplasia in Patients With Barrett's Esophagus

Experimental evidence indicates that proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin, and statins can protect patients with Barrett's esophagus (BE) from developing neoplasias. However, only limited data are available on chemoprevention in patients with BE. A retrospective observational study was performed using data from patients with documented BE. Prescription information was collected from pharmacy records. Cox regression analyses were performed to examine the association between prescriptions for PPIs, NSAIDs/aspirin, or statins and the risk of developing esophageal dysplasia or adenocarcinoma during follow-up (from 1982 to 2005). We examined 344 patients diagnosed with BE (mean age 61 years, 90.4% Caucasian, 94.2% male). After BE diagnosis, 67.2% of the patients were prescribed PPIs for a mean duration of 5.1 years; 49.1% were prescribed NSAIDs for a mean duration of 3.6 years, and 25.3% were prescribed statins for a mean duration of 2.8 years. During 2620 patient-years, high grade dysplasia or esophageal adenocarcinoma developed in 33 patients. PPI treatment after BE diagnosis was associated with a reduced risk of high grade dysplasia or cancer; this association persisted after adjustment for gender, age, and the length of BE. NSAID and/or aspirin therapy were associated with a nonsignificant trend toward lower incidence of high grade dysplasia or esophageal cancer. PPI therapy reduces the risk of neoplasms in patients with BE. NSAIDs/aspirin appear to reduce cancer risk whereas statin use is not significantly associated with the risk of neoplasia in patients with BE.

Barrett′s esophagus: Where do we stand?

Barrett's esophagus (BE) is a precursor for esophageal adenocarcinoma, which has an increased incidence rate over the last few decades. Its importance stems from the poor five-year survival of esophageal adenocarcinoma and current data that suggest a survival benefit when surveillance programs are implemented. In this review, we will cover the pathophysiology and natural history of BE and the different endoscopic findings. The prevalence of BE in different geographic areas and the incidence of high-grade dysplasia and adenocarcinoma in this patient population is reviewed. Recent recommendation for screening and surveillance of BE has been covered in this review as well as the efficacy of nonconventional imaging modalities and endoscopic ablation therapies.