Related Neoplasia Research Articles

P-0132 - Is a Complete Remission of Intestinal Metaplasia a Suitable Endpoint in Patients Undergoing Radiofrequency Ablation (RFA)? Long-Term Results of RFA Treatment in 62 Consecutive Patients

Introduction: Radiofrequency ablation (RFA) in combination with endoscopic resection (ER) is a method of choice for treatment of early esophageal neoplasia. Complete remission of intestinal metaplasia (CR-IM) and complete remission of dysplasia (CR-D) are commonly used as the endpoints of successful treatment. The relevance of CR-IM (in patients with macroscopically normal neo-Z-line) has recently been challenged. Methods: The aim of this prospective, single center study was to assess the long-term efficacy of RFA. Main outcome measurements were complete remission of intestinal metaplasia (CR-IM) or dysplasia (CR-D) in patients with/without a complete macroscopic eradication of Barrett's esophagus and recurrence rate of IM and dysplasia. Conover one-way analysis was used to calculate the risk factors for recurrence of intestinal metaplasia. Results: The study involved 62 consecutive patients (mean age 62, range 25-86; 55 males and 7 females) undergoing endoscopic treatment for esophageal neoplasia in our center during 2009–2013. Sixty patients were diagnosed with Barrett's esophagus related neoplasia, the remaining 2 patients had squamous neoplasia. The median follow-up was 25 months (range 3-60). In 19 patients (31%), RFA was a single treatment modality while in 43 patients (69%), RFA was combined with endoscopic resection or dissection of a visible lesion The indications for endoscopic treatment were as follows: early adenocarcinoma (EAC): 23 (37,1%), early squamous carcinoma (ESC): 2 (3,2%), high-grade intraepithelial neoplasia (HGIN): 20 (32,3%), low-grade intraepithelial neoplasia (LGIN): 17 (27,4%). A total of 117 RFA treatment sessions were performed (37 with HALO 360, 80 with HALO 90). The median number of treatment sessions per patient (ER + RFA) was 2 (1-6). CR-IM and CR-D were achieved in 69% (95% CI 61-81%) and 89% (95% CI 85-97%), respectively. In 80% of patients without CR-IM, the neo-Z-line was completely normal without macroscopically visible islands or tongues of metaplastic mucosa. During the follow-up, there were 6 recurrences at the level of neo-Z-line (out of 33 patients with BE with follow up of at least 18 months after finishing the treatment; 18%) of intestinal metaplasia. In 5 of these patients, the neo-Z-line was macroscopically normal. Low-grade dysplasia (within the Z-line) recurred in 2 patients (5%). High-grade dysplasia and/or carcinoma have not recurred. The risk factors for recurrence of intestinal metaplasia were male sex, younger age and diagnosis of cancer. We did not detect buried glands beneath the new neosquamous epithelium in any patient. Conclusion: Treatment of BE with RFA results in CR-D and CR-IM in a high proportion of patients with a low recurrence rate. A majority of patients without CR-IM or with a recurrence of IM have macroscopically normal neo-Z-line. CR-IM and a recurrence of IM might not be clinically relevant endpoints in patients with macroscopically normal neo-Z-line.

Tu1323 Five Year Outcomes for Patients Undergoing Endoscopic Therapy for Barrett's Related Neoplasia From the United Kingdom's Largest Single Centre Experience

The National Institute of Clinical Excellence (NICE) in the United Kingdom (UK) approved the use of minimally invasive endoscopic therapy for the treatment of Barrett's Eosphagus (BE) related neoplasia as an alternative to surgery in 2010. These high risk patients carry a 40-60% risk of progressing to Esophageal Adenocarcinoma (EAC), survival from which is poor. Over the past 5 years combined endoscopic mucosal resection (EMR) & Radiofrequency ablation (RFA) have become the preferred intervention for the curative treatment of patients with Barrett's related neoplasia.

Tu1340 Recurrence After Successful Radiofrequency Ablation for Barrett's Related Neoplasia Is More Likely in Males: Data From the United Kingdom Patient Registry

Barrett's esophagus (BE) is the pre-cursor to eosophageal adenocarcinoma (EAC). BE is more prevalent in males. Combined endoscopic mucosal resection (EMR) for visible lesions followed by Radiofrequency ablation (RFA) have become first line treatments for patients with BE related neoplasia. Recurrence after successful treatment can occur in up to 25% of cases.

Tu1328 Endoscopic Submucosal Dissection for Barrett's Esophagus: Efficacy and Safety Results in a Large Tertiary Center Series of Patients

Tu1328 Endoscopic Submucosal Dissection for Barrett's Esophagus: Efficacy and Safety Results in a Large Tertiary Center Series of Patients

In vivo endomicroscopy improves detection of Barrett's esophagus–related neoplasia: a multicenter international randomized controlled trial (with video)

Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE). To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. Multicenter, randomized, controlled trial. Academic medical centers. Adult patients with BE undergoing routine surveillance or referred for early neoplasia. Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. Diagnostic yield, performance characteristics, clinical impact. A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. Tertiary-care referral centers and expert endoscopists limit generalizability. Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( NCT01124214.).

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II)...

Increased expression of programmed death (PD)‐1 and its ligand PD‐L1 correlates with impaired cell‐mediated immunity in high‐risk human papillomavirus‐related cervical intraepithelial neoplasia

Impaired local cellular immunity contributes to the pathogenesis of persistent high-risk human papillomavirus (HR-HPV) infection and related cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms remain unclear. Recently, the programmed death 1/programmed death 1 ligand (PD-1/PD-L1; CD279/CD274) pathway was demonstrated to play a critical role in attenuating T-cell responses and promoting T-cell tolerance during chronic viral infections. In this study, we examined the expression of PD-1 and PD-L1 on cervical T cells and dendritic cells (DCs), respectively, from 40 women who were HR-HPV-negative (-) or HR-HPV-positive (+) with CIN grades 0, I and II-III. We also measured interferon-γ, interleukin-12 (IL-12) and IL-10 in cervical exudates. The most common HPV type was HPV 16, followed by HPV 18, 33, 51 and 58. PD-1 and PD-L1 expression on cervical T cells and DCs, respectively, was associated with HR-HPV positivity and increased in parallel with increasing CIN grade. The opposite pattern was observed for CD80 and CD86 expression on DCs, which decreased in HR-HPV+ patients in parallel with increasing CIN grade. Similarly, reduced levels of the T helper type 1 cytokines interferon-γ and IL-12 and increased levels of the T helper type 2 cytokine IL-10 in cervical exudates correlated with HR-HPV positivity and CIN grade. Our results suggest that up-regulation of the inhibitory PD-1/PD-L1 pathway may negatively regulate cervical cell-mediated immunity to HPV and contribute to the progression of HR-HPV-related CIN. These results may aid in the development of PD-1/PD-L1 pathway-based strategies for immunotherapy of HR-HPV-related CIN.

283 Patients Undergoing Radiofrequency Ablation (RFA) for Barrett's Related Neoplasia Have Improved Outcomes With Decreasing Length's of Baseline Barrett's Eosophagus (BE) and Increasing Number of RFA Sessions

283 Patients Undergoing Radiofrequency Ablation (RFA) for Barrett's Related Neoplasia Have Improved Outcomes With Decreasing Length's of Baseline Barrett's Eosophagus (BE) and Increasing Number of RFA Sessions

Endoscopic Mucosal Resection Results in Change of Histologic Diagnosis in Barrett’s Esophagus Patients with Visible and Flat Neoplasia: A Multicenter Cohort Study

There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett's esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. In this multicenter outcomes project, patients with Barrett's-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET.

Abstract 5217: Integrative sequencing reveals novel alterations in untreated and castration resistant prostate cancer.

Abstract Prostate cancer is the third most common source of male cancer deaths in developed countries. The standard of care for aggressive prostate cancer is androgen ablation, which prolongs survival until the tumor acquires a castration resistant phenotype. The molecular pathology underlying prostate cancer progression is not yet fully understood. We used integrative high throughput sequencing to study cancer-associated alterations in 53 prostate cancer related neoplasia at the DNA, RNA and epigenetic levels. The cohort included both hormone-naive and castration resistant prostate cancers, along with two neuroendocrine prostate cancers. We identified two new fusion genes, one of which associated with neuronal differentiation and castration resistance. We also identified a number of novel prostate cancer associated transcripts, including transcripts specific to castration resistant tumors. Based on ChIP-seq data from prostate cancer cell lines, many of the novel transcripts were regulated by known oncogenes such as ERG and AR. Methylation sequencing revealed a near-identical pattern of promoter hypermethylation in both hormone-naive and castration resistant tumors. Enrichment of hypermethylation was observed at EZH2 binding sites, supporting the role of EZH2 in the recruitment of DNA methyltransferase in prostate cancer. Promoter hypermethylation suppressed the expression of hundreds of genes, but a subset of genes characterized by promoter H3K27 trimethylation responded to hypermethylation with increased expression. Citation Format: Matti J. Annala, Kati K. Waltering, Antti Ylipää, Kimmo Kartasalo, Kirsi Tuppurainen, Serdar Karakurt, Leena Latonen, Outi Saramäki, Simo-Pekka Leppänen, Janne Seppälä, Hanna E. Rauhala, Teuvo LJ Tammela, Olli Yli-Harja, Wei Zhang, Tapio Visakorpi, Matti Nykter. Integrative sequencing reveals novel alterations in untreated and castration resistant prostate cancer. [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 5217. doi:10.1158/1538-7445.AM2013-5217

Accuracy and interrater reliability for the diagnosis of Barrett's neoplasia among users of a novel, portable high-resolution microendoscope

The high-resolution microendoscope (HRME) is a novel imaging modality that may be useful in the surveillance of Barrett's esophagus in low-resource or community-based settings. In order to assess accuracy and interrater reliability of microendoscopists in identifying Barrett's-associated neoplasia using HRME images, we recruited 20 gastroenterologists with no microendoscopic experience and three expert microendoscopists in a large academic hospital in New York City to interpret HRME images. They prospectively reviewed 40 HRME images from 28 consecutive patients undergoing surveillance for metaplasia and low-grade dysplasia and/or evaluation for high-grade dysplasia or cancer. Images were reviewed in a blinded fashion, after a 4-minute training with 11 representative images. All imaged sites were biopsied and interpreted by an expert pathologist. Sensitivity of all endoscopists for identification of high-grade dysplasia or cancer was 0.90 (95% confidence interval [CI]: 0.88-0.92) and specificity was 0.82 (95% CI: 0.79-0.85). Positive and negative predictive values were 0.72 (95% CI: 0.68-0.77) and 0.94 (95% CI: 0.92-0.96), respectively. No significant differences in accuracy were observed between experts and novices (0.90 vs. 0.84). The kappa statistic for all raters was 0.56 (95% CI: 0.54-0.58), and the difference between groups was not significant (0.64 vs. 0.55). These data suggest that gastroenterologists can diagnose Barrett's-related neoplasia on HRME images with high sensitivity and specificity, without the aid of prior microendoscopy experience.

Anal intraepithelial neoplasia progression to squamous cell carcinoma.

353 Background: In the U.K., the annual incidence of anal cancer is up to 1.5 per 100,000 per year. Anal intra-epithelial neoplasia (AIN) is believed to be a precursor to squamous cell carcinoma whose incidence is still undetermined. This cell transformation has been associated with human papillomavirus (HPV) infections, in particular HPV 16 and 18. Our aim was to determine the frequency of progression to squamous cell carcinoma (SCC) of the anus in patients with known AIN. Methods: Study subjects with diagnosis of AIN from January 1st 1997 to January 1st 2009 were identified from a prospective database in a single hospital trust. The incidence of a subsequent diagnosis of anal SCC was determined from the local pathology and anal cancer database and cross referenced with the regional cancer database, Thames Cancer Registry. Results: We identified 397 patients (303 males) diagnosed with AIN in the database and HPV infection was identified in n= 395 patients. 15 (4%) patients were diagnosed with anal SCC a median of 5 months, Interquartile range 27 (2- 29 months) after their initial diagnosis. The distribution of AIN 1, 2 and 3 at presentation was 2, 1 and 12 respectively. Of interest, number of patients developed other HPV related cancers during the study period, such as vulva (n=8), cervical (n=3) and penile cancers (n=1). Conclusions: The incidence of anal cancer is higher in patients with known AIN compared to the general population. This justifies surveillance of these patients for anal and other HPV related intraepithelial neoplasia, however the nature of this, anoscopy or clinical examination alone, has yet to be determined.

Prevalence of cervical intraepithelial neoplasia in relation to knowledge, attitudes/beliefs, and practices among university students in North-Eastern Nigeria

Background: The involvement of communities in control of cervical cancer cannot be overemphasized, but this must take cognizance of their current knowledge, attitudes/beliefs, and practices (KABP) of the people if it will be sustainable. This study assessed the prevalence of cervical intraepithelial neoplasia (CIN) among university students and their level of KABP concerning cervical screening in Maiduguri North-Eastern, Nigeria. Materials and Methods: Two hundred and fifty-two subjects (age range: 18-69 years) were screened using pap smear screening method and acetowhite method. A structured questionnaire was administered on each subject to elicit information on KABP that could predispose them to the disease. Results: CIN was recorded in 12.8% of subjects with low-grade squamous intraepithelial lesion in 10.8% and high-grade squamous intraepithelial lesion 2.0% of the women, respectively. The average general level of knowledge of various aspect of was 43.3% average positive attitudes/beliefs about the disease was recorded in 17.1% of subject, while positive practices that could lead to prevention of the disease was obtained in 30.0%. Conclusion: The level of knowledge of the disease and screening is very low and together with high levels of negative attitudes and practices, will adversely affect control measures and therefore have to be addressed.

Computed tomography of Crohn’s disease: The role of three dimensional technique

Crohn's disease, a transmural inflammatory bowel disease, remains a difficult entity to diagnose clinically. Over the last decade, multidetector computed tomography (CT) has become the method of choice for non-invasive evaluation of the small bowel, and has proved to be of significant value in the diagnosis of Crohn's disease. Advancements in CT enterography protocol design, three dimensional (3-D) post-processing software, and CT scanner technology have allowed increasing accuracy in diagnosis, and the acquisition of studies at a much lower radiation dose. The cases in this review will illustrate that the use of 3-D technique, proper enterography protocol design, and a detailed understanding of the different manifestations of Crohn's disease are all critical in properly diagnosing the full range of possible complications in Crohn's patients. In particular, CT enterography has proven to be effective in identifying involvement of the small and large bowel (including active inflammation, stigmata of chronic inflammation, and Crohn's-related bowel neoplasia) by Crohn's disease, as well as the extra-enteric manifestations of the disease, including fistulae, sinus tracts, abscesses, and urologic/hepatobiliary/osseous complications. Moreover, the proper use of 3-D technique (including volume rendering and maximum intensity projection) as a routine component of enterography interpretation can play a vital role in improving diagnostic accuracy.

Elevated Risk of Colorectal Neoplasia in Relatives of Patients with Colorectal Cancer: A Population-based Study in Utah

Purpose: Colorectal cancer (CRC) is the third most common cancer in the U.S. Prior studies have established that the risk of CRC is increased in first-degree relatives (FDR) of patients with CRC. Current guidelines recommend individuals with a FDR diagnosed with CRC or advanced adenoma before age 60 should undergo screening colonoscopy starting at age 40. Many of these studies rely on patient recall regarding family history and therefore lack verification of reported diagnoses. In this retrospective, population-based, case-control study we quantified the prevalence of adenomas in the relatives (FDR, second-degree-SDR or third-degree -TDR) of patients with CRC. Our study is the first population based assessment of the risk of adenomas in FDR, SDR or TDR of individuals with CRC. This study will provide evidence for or against the current screening guidelines. Methods: We performed a population-based retrospective case-control study of residents of the state of Utah, between 50 and 80 years of age, who underwent colonoscopy between February 15, 1995 and January 31, 2009 at Intermountain Healthcare or University of Utah Health System. De-identified medical information on patients undergoing colonoscopy was merged with cancer histories from the Utah Cancer Registry and overlaid on pedigrees from the Utah Population Database to investigate the familial aggregation of adenomas. Cox regression analysis was used to assess the relative risk of adenoma development in relatives. Results: There were 126,936 unique patients who underwent colonoscopy. 3,804 patients in this cohort were diagnosed with CRC and they defined the case population. For each case, one randomly selected, age- and sex-matched control was selected from the population who had CRC-free colonoscopy. The prevalence of adenomas was increased in FDRs (OR 1.82, 95% CI, 1.66-2.00), SDRs (OR 1.19, 95% CI, 1.08-1.31) and TDRs (OR 1.10, 95% CI, 1.04-1.17) of cases compared to controls. This risk was similar for FDRs whether index patients developed CRC below (OR 2.04, 95% CI: 1.74-2.39) or above 60 years old (OR 1.58, 95% CI: 1.37-1.83). Conclusion: In this study we report that FDRs, SDRs and TDRs of individuals with CRC had an increased risk of developing colorectal neoplasia themselves. The strength of the association showed a relationship based on the degree of kinship. Our data supports the current CRC screening guidelines and supports a genetic basis of inheritance for colorectal neoplasia.

VH27 Successful Endoscopic Treatment of Macroscopically Advanced Barrett′s Esophagus Related Neoplasias

Endoscopic treatment combining endoscopic resection (ER) and radiofrequency ablation (RFA) is a method of choice in management of patients with early Barrett′s esophagus related neoplasias. Our report describes a successful endoscopic treatment of two patients with macroscopically advanced neoplasias arising from Barrett′s esophagus.

PO.08 Colorectal cancer risk in Parkinson's disease: insights from a surgically treated cohort

BackgroundA number of epidemiologic studies show a decreased risk of non-melanoma cancer in Parkinson's disease (PD). Cigarette smoking is less prevalent in PD and hence the risk of smoking related...

Bile acids may have a role in GERD and related neoplasia

Bile acids may have a role in GERD and related neoplasia

MLL-SEPTIN gene fusions in hematological malignancies

The mixed lineage leukemia (MLL) locus is involved in more than 60 different rearrangements with a remarkably diverse group of fusion partners in approximately 10% of human leukemias. MLL rearrangements include chromosomal translocations, gene internal duplications, chromosome 11q deletions or inversions and MLL gene insertions into other chromosomes, or vice versa. MLL fusion partners can be classified into four distinct categories: nuclear proteins, cytoplasmatic proteins, histone acetyltransferases and septins. Five different septin genes (SEPT2, SEPT5, SEPT6, SEPT9, and SEPT11) have been identified as MLL fusion partners, giving rise to chimeric fusion proteins in which the N terminus of MLL is fused, in frame, to almost the entire open reading frame of the septin partner gene. The rearranged alleles result from heterogeneous breaks in distinct introns of both MLL and its septin fusion partner, originating distinct gene fusion variants. MLL-SEPTIN rearrangements have been repeatedly identified in de novo and therapy related myeloid neoplasia in both children and adults, and some clinicopathogenetic associations are being uncovered. The fundamental roles of septins in cytokinesis, membrane remodeling and compartmentalization can provide some clues on how abnormalities in the septin cytoskeleton and MLL deregulation could be involved in the pathogenesis of hematological malignancies.

Systematic review: the role of bile acids in the pathogenesis of gastro-oesophageal reflux disease and related neoplasia

Factors other than acid may play a role in gastro-oesophageal reflux disease (GERD) and its complications. To assessed the role of bile acids in the pathogenesis of GERD, Barrett's oesophagus and Barrett's-related neoplasia. We conducted a systematic review of computerised bibliographic databases for original articles involving humans or human oesophageal tissue or cells that assessed exposure to or manipulation of bile acids. Outcomes assessed included GERD symptoms; gross oesophageal injury; Barrett's oesophagus and related neoplasia; and intermediate markers of inflammation, proliferation or neoplasia. Eighty-three original articles were included. In in vivo studies, bile acids concentrations were higher in the oesophageal aspirates of patients with GERD than controls, and bile acids infusions triggered GERD symptoms, especially in high concentrations or in combination with acid. In ex vivo/in vitro studies, bile acids stimulated squamous oesophageal cells and Barrett's epithelial cells to produce inflammatory mediators (e.g., IL-8 and COX-2) and caused oxidative stress, DNA damage and apoptosis. They also induced squamous cells to change their gene expression pattern to resemble intestinal-type cells and caused Barrett's cells to increase expression of intestinal-type genes. In aggregate, these studies suggest that bile acids may contribute to the pathogenesis of symptoms, oesophagitis and Barrett's metaplasia with related carcinogenesis in patients with GERD. However, all study results are not uniform and substantial differences in study parameters may explain at least some of this variation.