Esophageal High-grade Dysplasia Research Articles

Endoscopic Calcium Electroporation in Patients with Barrett’s Esophagus High-Grade Dysplasia: A First-in-Man Phase I Study

Endoscopic Calcium Electroporation in Patients with Barrett’s Esophagus High-Grade Dysplasia: A First-in-Man Phase I Study

Endoscopic Screening for Second Primary Tumors of the Esophagus Among Head and Neck Cancer Patients.

Malignancies of the head and neck (HN) region and esophagus are among the most common cancers worldwide. Due to exposure to common carcinogens and the theory of field cancerization, HN cancer patients have a high risk of developing second primary tumors (SPTs). In our review of 28 studies with 51,454 HN cancer patients, the prevalence of SPTs was 12%. The HN area is the most common site of SPTs, followed by the lungs and esophagus, and 13% of HN cancer patients have been reported to have esophageal high-grade dysplasia or invasive carcinoma. The prognosis of HN cancer patients with concomitant esophageal SPTs is poor, and therefore identifying esophageal SPTs as early as possible is of paramount importance for risk stratification and to guide the treatment strategy. Image-enhanced endoscopy, especially using narrow-band imaging endoscopy and Lugol’s chromoendoscopy, has been shown to improve the diagnostic performance in detecting esophageal neoplasms at an early stage. Moreover, the early detection and minimally invasive endoscopic treatment of early esophageal neoplasm has been shown to improve the prognosis. Well-designed prospective studies are warranted to establish appropriate treatment and surveillance programs for HN cancer patients with esophageal SPTs.

Predictive value of p53, Ki67 and TLR5 in neoplastic progression of Barrett’s esophagus: a matched case–control study

Barrett’s esophagus progresses to high-grade dysplasia or cancer along the well-established metaplasia-dysplasia-adenocarcinoma sequence. The aim of this study was to evaluate the value of p53, Ki67, and toll-like receptor 5 (TLR5) in prediction of malignant progression of Barrett’s metaplasia and low-grade dysplasia. This was a retrospective matched case–control study based on Northern and Central Finland population. Patients diagnosed with esophageal high-grade dysplasia or adenocarcinoma were included. From these patients, all previous endoscopy samples were obtained along with original diagnostic HE-slides and clinical data. Age- and sex-matched patients with non-progressing Barrett’s metaplasia and low-grade dysplasia confirmed with follow-up endoscopies were used as controls. Two gastrointestinal pathologist re-reviewed all original HE-slides, and newly made sections to confirm representative tissue material blinded from clinical data. p53, Ki67, and TLR5 were immunohistochemically stained. Final cohort included 45 patients with progressive Barrett’s metaplasia (n = 21) or low-grade dysplasia (n = 24), and 92 patients with non-progressive Barrett’s metaplasia (n = 52) or low-grade dysplasia (n = 40). In Barrett’s metaplasia, aberrant p53 expression was observed in 6% of samples in progressors and 0% in non-progressors. In low-grade dysplasia, aberrant p53 was seen in 56% of samples in progressors and 17% in non-progressors (Odd’s ratio 6.7, 95% CI 1.8–24.6). Ki67 or TLR5 showed no association with disease progression. In this matched case–control study, p53 expression associated with a high risk of malignant progression in Barrett’s low-grade dysplasia. Routine staining of p53 is indicated in expert confirmed low-grade dysplasia.

Long-term results of an endoscopic screening program for superficial esophageal cancer in patients with head and neck squamous cell carcinoma.

Background and study aims Patients with head and neck squamous cell carcinoma (HNSCC) are at risk of a second primary tumor in the gastrointestinal tract, most commonly in the esophagus. Screening these patients for esophageal carcinoma may help detect asymptomatic dysplasia and early cancer, thus allowing curative treatment and more prolonged survival, but the impact of endoscopic screening remains uncertain. Here we aimed to describe the long-term results of an esophageal SCC screening program in patients with head and neck cancer in terms of prevalence, associated risk factors, and survival. Patients and methods We performed an observational study of a prospectively collected database including patients with HNSCC who had undergone high-definition endoscopy with chromoscopy between 2010 and 2018 at a Brazilian tertiary academic center. Results The study included 1,888 patients. The esophageal SCC prevalence was 7.9 %, with the majority (77.8 %) being superficial lesions. Significant risk factors for esophageal high-grade dysplasia (HGD) and invasive cancer included tumors of the oral cavity and oropharynx and the presence of low-grade dysplasia (LGD). Overall survival (OS) was significantly shorter among patients in whom esophageal cancer was diagnosed at an advanced stage ( P < .001). OS did not significantly differ between patients with HGD and early esophageal cancer versus those without esophageal cancer ( P = .210) Conclusions Endoscopic screening for superficial esophageal neoplasia in patients with HNSCC improves esophageal cancer detection. Screening could potentially benefit patients with primary cancer located at the oropharynx or oral cavity. In addition, the detection of esophageal LGD indicates a need for endoscopic surveillance.

Expression of CXCL12 in esophageal high grade dysplasia characterized pathologically by lymphocyte accumulation directly under the lesion.

Squamous dysplasia of the esophagus is an unequivocal neoplastic alteration of the esophageal squamous epithelium without invasion. Esophageal high grade dysplasia (EHGD) is characterized by >50% epithelial involvement or severe cytological atypia. Frequently, lymphocytes accumulate below EHGD lesions even though there is no invasion. If this lymphocytic accumulation is active, a transmitter should exist between the EHGD cells and the lymphocytes. C-X-C motif chemokine ligand (CXCL) 12, CXCL10 and C-C motif chemokine ligand 18 (CCL18) are all lymphocyte chemoattractants in vivo, but there are no reports on the relationship between these chemokines and EHGDs. In this study, we investigated these chemokines and C-X-C motif chemokine receptor 4 (CXCR4) (receptor for CXCL12) in 30 EHGDs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we enrolled 30 samples of normal esophageal squamous epithelium (NESE). We confirmed CXCL12 expression (H-score≥50 points) in 70% of EHGD and 0% of NESE samples, CXCL10 expression in 3% of EHGD and 3% of NESE samples, CCL18 expression in 3% of EHGD and 0% of NESE samples, and CXCR4 expression in 53% of EHGD and 0% of NESE samples by immunohistochemistry. EHGD and NESE cases were significantly different in their expressions between the tissue types (CXCL12, p<0.001; CXCR4, p<0.001). We examined CXCL12 and CXCR4 mRNA expressions of 3 representative EHGD samples, each having their respective immunostained areas detected by RT-PCR. Finding CXCL12 expression may indicate that this chemokine plays a part in the lymphocyte accumulation that occurs directly under EHGDs.

674 TRANSITION FROM ESOPHAGECTOMY TO ENDOSCOPIC THERAPY FOR EARLY ESOPHAGEAL CANCER

Abstract To assess the outcomes of patients with early esophageal cancer (EEC) and high-grade dysplasia (HGD) comparing esophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET). Methods Retrospective cohort study of consecutive patients with EEC/HGD, treated between 2000 and 2018 at a tertiary referral centre. Primary outcomes were all-cause and disease-specific mortality assessed by multivariable Cox regression and a propensity score matching sub analysis, providing hazard ratios (HR) with 95% confidence intervals (CIs), adjusted for age, tumor grade (G1/2 vs G3), tumor stage and lymphovascular invasion(LVI). Secondary outcomes included complications, hospital stay, and overall costs. Results Among 269 patients, 133 underwent esophagectomy and 136 received endoscopic mucosal resection (EMR)+/−further EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85,95%CI 0.73,4.72) and disease-specific mortality (HR 1.10,95%CI 0.26,4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien-Dindo ≥3 26.3% vs EMR 0.74%), longer in-patient stay (median 14 vs 0 days EMR) and higher hospital costs ($20.426 vs $10.988 per patient). Conclusion This series of patients with EEC/HGD treated during a transition period from surgery to EET, demonstrates a primary endoscopic approach does not compromise oncological outcomes with the benefit of fewer complications, shorter hospital stays, and lower costs compared to surgery. EET should be available as the gold standard treatment for patients with early esophageal cancer. Those with adverse prognostic features may still benefit from esophagectomy.

Influence of Tea Consumption on the Development of Second Esophageal Neoplasm in Patients with Head and Neck Cancer.

Alcohol is an important risk factor for the development of second esophageal squamous-cell carcinoma (ESCC) in head and neck squamous-cell carcinoma (HNSCC) patients. However, the influence of tea consumption is uncertain. We prospectively performed endoscopic screening in incident HNSCC patients to identify synchronous esophageal neoplasm. In total, 987 patients enrolled between October 2008 and December 2017 and were analyzed. In vitro studies were conducted to investigate the effect of epigallocatechin gallate (EGCG) on the betel alkaloid, arecoline-stimulated carcinogenesis in two ESCC cell lines. There were 151 patients (15.3%) diagnosed to have synchronous esophageal neoplasm, including 88 low-grade dysplasia, 30 high-grade dysplasia and 33 squamous-cell carcinoma (SCC). Tea consumption was associated with a significantly lower risk of having esophageal high-grade dysplasia or SCC in HNSCC patients, especially those who were betel nut chewers, alcohol drinkers or cigarette smokers (all adjusted odds ratio were 0.5; p-values: 0.045, 0.045 and 0.049 respectively). In vitro studies indicated that EGCG suppressed arecoline-induced ESCC cell proliferation and colony formation through the inhibition of the Akt and ERK1/2 pathway in a reactive oxygen species-independent manner. In conclusion, tea consumption may protect against the development of second esophageal neoplasms among HNSCC patients, especially those who regularly consume betel nuts, alcohol and cigarettes.

Esophageal High-Grade Squamous-Cell Dysplasia

This case presentation of a 56 year old female with high grade squamous cell dysplasia of her distal, normal appearing esophagus is extremely rare. A review of the medical literature found no other similar case reports, making decisions on treatment options challenging. A 56 year-old female presented to her outpatient gastroenterologist with a one month history of worsening acid reflux-like symptoms and atypical non-cardiac chest pain. She reported a substernal burning sensation that was non-radiating in nature. Her symptoms did not exacerbate with food and while originally intermittent, the heartburn had become more constant. She denied similar symptoms in the past. The patient had no past medical history and denied taking any medications. She denied smoking history, alcohol, and illicit drug abuse. Family history was significant for her father with Barrett's esophagus, but otherwise unremarkable for gastrointestinal pathology. Her physical examination was unremarkable and vital signs were within normal limits. She was prescribed a 6 week trial of 40mg Protonix daily without any resolution of her symptoms. A non-emergent EGD was scheduled. It revealed a normal appearing esophagus with no clear evidence of Barrett's epithelium. Random biopsies were taken which showed foci of high grade squamous metaplasia on the subsequent pathologic report. There was no consensus among multiple esophageal specialists on how to treat her. Recommended treatment options included a partial esophagectomy or a thermal ablation. The patient opted for a thermal ablation with biopsies afterwards still showing high grade squamous dysplasia. Over the course of the next 3 years, despite having 3 more thermal ablations, repeat biopsies continued to show low grade dysplasia. She opted to undergo observation with 6 month intervals between EGDs. Squamous cell dysplasia is a histological lesion confined to the epithelium and characterized by cytologic and architectural abnormalities. It is considered to be the only pre-malignant lesion of esophageal squamous cell carcinoma. The few studies conducted to evaluate esophageal squamous dysplasia have all been conducted in the high-risk Taihang Mountain region in China. The difference in patient populations and lack of follow up made it hard to compare treatment strategies. With no consensus among multiple specialists on how to proceed with treatment, this can be used as an example for future similar cases.

PS02.096: ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ESOPHAGEAL HIGH-GRADE SQUAMOUS DYSPLASIA: A CASE REPORT

Abstract Background Endoscopic resection is a novel therapeutic technique for early esophageal cancer and it is indicated in well differentiated superficial M1 or M2 lesion. The selection criteria have been expanded to selected M3 and SM1 lesion with the advancement of endoscopic technology and detailed study of relation between depth of lesion and lymphatic spread. Methods We report a case of endoscopic submucosal dissection (ESD) for esophageal high grade dysplasia. Results Madam S, a 50-year-old lady with no known medical illness, presented with gradual dysphagia for 1 year. She had no prior history of corrosive ingestion or reflux disease. She was diagnosed with esophageal stricture and underwent esophageal dilatation twice, before she was referred to our center. Clinical examination revealed no abnormality and her BMI was 25. OGDS revealed a 1cm superficial ulcerative lesion at proximal esophagus (25cm from incisor) with abnormal capillary pattern on narrow band imaging. Biopsy revealed high grade intraepithelial neoplasia. PET-CT showed metabolically active esophageal lesion with no distant metastasis. She decided for ESD after given the option of endoscopic treatment versus esophagectomy. ESD was done (Figure 1) and she had an uneventful recovery. Histopathology revealed complete resection of high grade squamous dysplasia. Conclusion Endoscopic treatment is less invasive option for early esophageal tumour which spares patients from esophagectomy and the related morbidities. However, it carries the risk of incomplete resection, recurrence and under-staging of the disease. It also requires highly specialized center and has a steep learning curve. Careful patient selection and proper pre-operative counseling are crucial in endoscopic treatment of early esophageal cancer. Long term surveillance is needed for early detection of recurrence. Disclosure All authors have declared no conflicts of interest.

The role of Hedgehog protein and gene methylation in the pathogenesis of esophageal cancer

Objective To explore the role of the Hedgehog singaling in the pathogenesis of esophageal cancer. Methods Tissue samples of normal esophageal mucosa, low-grade dysplasia, high-grade dysplasia and esophageal cancer were collected.Immunohistochemical stain, Western-blot and RT-PCR were employed to detect the expression of Hedgehog protein and gene, methylation special PCR was used to detect the methylation status of Hedgehog gene. Results There was no difference in the expression of SHh protein among nornaml esophageal and low-grade dysplasia, high-grade dysplasia and esophageal cancer (LGD vs.N: t=1.96, P=0.67; HGD vs.EC: t=1.59, P=0.53). However, the expression of SHh protein in high-grade dysplasia and esophageal cancer was higher than that in normal esophageal mucosa and low-grade dysplasia(HGD vs.N: t=0.593, P=0.004; HGD vs.LGD: t=1.308, P=0.325; EC vs.N: t=0.292, P=0.000; EC vs.LGD: t=0.734, P=0.004). The expression of Hedgehog gene in esophageal cancer was higher than that in normal esophageal mucosa, low-grade dysplasia and high-grade dysplasia(EC vs.N: t=0.909, P=0.019, EC vs.LGD: t=0.398, P=0.007; EC vs.HGD: t=0.843, P=0.012). The gene methylation in esophageal cancer was lower than that in normal esophageal mucosa, low-grade dysplasia and high-grade dysplasia(EC vs.N: t=0.0340, P=0.000; EC vs.LGD: t=0.102, P=0.000; EC vs.HGD: t=0.367, P=0.018). Conclusion Hedgehog signaling may play a role in the pathogenesis and development of esophageal cancer, however, demethylation of Hedgehog gene may be one of the mechanism that cause the activity of oncogene in esophageal cancer. Key words: Esophageal Neoplasms; Hedgehog Proteins; DNA Methylation

Coding of Barrett’s oesophagus with high-grade dysplasia in national administrative databases: a population-based cohort study

ObjectivesThe International Classification of Diseases 10th Revision (ICD-10) system used in the English hospital administrative database (Hospital Episode Statistics (HES)) does not contain a specific code for oesophageal high-grade dysplasia...

Whole-genome sequencing of nine esophageal adenocarcinoma cell lines.

Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines-ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4-all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC.

Sa1262 Annual Incidence of Esophageal Adenocarcinoma and High-grade Dysplasia in Barrett's Esophagus Containing Confirmed Low-Grade Dysplasia: A Systematic Review and Meta-Analysis

Sa1262 Annual Incidence of Esophageal Adenocarcinoma and High-grade Dysplasia in Barrett's Esophagus Containing Confirmed Low-Grade Dysplasia: A Systematic Review and Meta-Analysis

Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett's esophagus.

Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies, this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.

Laparoscopic transgastric esophageal mucosal resection: a treatment option for patients with high-grade dysplasia in Barrett's esophagus

BackgroundWe present long-term follow-up data on patients with esophageal high-grade dysplasia and/or carcinoma in situ who were treated with laparoscopic transgastric esophageal mucosal resection (LTEMR). MethodsPatient demographics, operative outcomes, and follow-up results were tabulated. ResultsLTEMR was performed in 11 patients (9 male, 2 female). The median age was 54 (44 to 75) years. The 30-day morbidity or mortality was zero. The median follow-up was 5.2 (2 to 12) years. Upper endoscopy was performed at 3, 6, and 12 month, and yearly thereafter. All patients regenerated squamous epithelium at 6 months. One patient developed a recurrence of Barrett's epithelium 2 years after resection. No recurrences of high-grade dysplasia or carcinoma were observed in any of the patients. Two patients developed an esophageal stricture; both were treated successfully with endoscopic balloon dilation and have suffered no further sequelae. ConclusionsLTEMR is safe and effective alternative method to treat patients with Barrett's esophagus with high-grade dysplasia.

340 Proportion of Missed Cancer and High-grade Dysplasia During Barrett's Esophagus Diagnosis: a Systematic Review and Meta-Analysis

340 Proportion of Missed Cancer and High-grade Dysplasia During Barrett’s Esophagus Diagnosis: a Systematic Review and MetaAnalysis Kavel Visrodia*, Siddharth Singh, Rajesh Krishnamoorthi, Prasad G. Iyer, David A. Katzka Mayo Clinic Rochester, Rochester, MN Background: Esophageal adenocarcinoma (EAC) and/or high-grade dysplasia (HGD) detected within one year of Barrett’s esophagus (BE) diagnosis is considered prevalent disease and therefore likely to have been “missed” during the initial endoscopy. Recent large BE surveillance studies suggest a sizeable portion of all EAC/HGD is found within this timeframe. This stands in contrast to the emphasis on BE surveillance occurring years after diagnosis. Aim: We conducted a systematic review and meta-analysis comparing the proportion of missed vs incident EAC/HGD detected after a negative index exam (IE). Methods: We performed a systematic literature search of the PubMed, EMBASE, and Web of Science databases (August 2014) for studies reporting the timing of EAC/HGD development in patients with BE during a follow-up of R 2 years. Missed EAC/HGD was defined as those developing within 12 years of BE diagnosis, after a negative IE. Incident EAC/HGD was defined as those occurring after the timeframe used in each study to define missed EAC/HGD. Prevalent EAC/HGD was defined as those diagnosed at the time of IE, regardless of presence or absence of symptoms. Pooled estimates for proportions of missed vs incident EAC/HGD, and prevalent+missed vs incident EAC/HGD were calculated for all studies; sensitivity analysis was performed for studies with BE cohorts comprised of only patients with baseline non-dysplastic BE (NDBE) or low-grade dysplasia (LGD). Results: 53 studies met the inclusion criteria; 51 had a missed EAC/HGD cutoff% 12 months. Meta-analysis of 38 studies and 1,321 patients with EAC showed that after a negative IE, 1/3 were classified as having missed EAC (pooled prevalence, 33.5%; 95% CI, 27.5-40.5) and the remainder as having incident EAC. Results from analysis of 20 studies including 1,481 patients with EAC/HGD were identical (33.5%; 95% CI, 23.9-44.7). On restricting analysis to a subset of patients with NDBE or LGD, the proportions of missed EAC (26.4%; 95% CI, 16.1-40.0) or EAC/HGD (34.8%; 95% CI, 24.7-46.5) were slightly lower or similar, respectively. As expected, with increasing duration of follow-up, the proportion of all EAC classified as incident cases increased: 2-5 years (nZ20 studies): 39.0% vs 61.0%; 5-8 years (nZ12 studies): 26.7% vs 73.3%; O 8 years (nZ4 studies): 12.8% vs 87.2%. In studies reporting data on prevalent, missed, and incident EAC (nZ20 studies and 615 patients with EAC), the majority of EAC were classified as prevalent or missed (83.5%; 95% CI, 77.4-88.2) vs incident (16.5%, 95% CI, 11.8-22.6). Conclusions: One-fourth EAC and 1/3 EAC/ HGD detected during surveillance are potentially present and missed at the time of initial BE diagnosis. Therefore, efforts to improve detection of EAC/HGD at or soon after BE diagnosis should be increased and perhaps even shifted from long-term surveillance. Table 1A. Proportion of missed and incident EAC and EAC/HGD in all BE cohorts, independent of baseline grade of dysplasia www.giejournal Missed (% Missed+Incident EAC)

Barrett's Oesophagus Surveillance versus endoscopy at need Study (BOSS): protocol and analysis plan for a multicentre randomized controlled trial.

The absolute annual risk of patients with Barrett's oesophagus (BO) developing oesophageal adenocarcinoma (OAC) is ≤ 0.5%. Screening BO patients for malignant progression using endoscopic surveillance is widely practised. To assess the efficacy and cost-effectiveness of this, we developed a protocol for a randomized controlled trial of surveillance versus 'at need' endoscopy. In a multicentre trial, 3400 BO patients randomized to either 2-yearly endoscopic surveillance or 'at need' endoscopy will be followed up for 10 years. Urgent endoscopy will be offered to all patients who develop symptoms of dysphagia, unexplained weight loss > 7lb (3.2 kg), iron deficiency anaemia, recurrent vomiting, or worsening upper gastrointestinal symptoms. Participants must have endoscopically and histologically confirmed BO, with circumferential BO ≥ 1 cm or maximal tongue/island length ≥ 2 cm. Candidates with existing oesophageal high-grade dysplasia or cancer, or previous upper gastrointestinal cancer will be excluded. Primary outcome will be overall survival. Secondary outcomes will be cost effectiveness (cost per life year saved and quality adjusted life years); cancer-specific survival; time to OAC diagnosis and stage at diagnosis; morbidity and mortality related to any interventions; and frequency of endoscopy. This randomized trial will provide data to evaluate the efficacy and cost-effectiveness of screening BO patients for OAC.

Morbidity and mortality as outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): An Italian multicentric retrospective study

Study objective: Biopsy-proven esophageal high grade dysplasia and/ or cancer, until a few years ago, was normally staged with CT and referred for esophagectomy, a procedure with high morbility and mortality rates. Recent evidence has suggested how EMR could be a more accurate grading tool for esophageal lesions and can be also employed as a definitive treatment option for a considerable amount of these patients. The aim of this study is to analyze our experience on the role of EMR as a diagnostic tool and to evaluate the long term outcome of the procedure when performed as a therapeutic treatment. Material and methods: We retrospectively reviewed data on 80 consecutive patients that underwent EMR for biopsy proven HGD (n 1⁄4 30), SCC (n 1⁄4 33) or EAC (n 1⁄4 17) at our Department. Complications that developed during the procedure, changes in histologic diagnosis, rate of submucosal invasion and additional treatments were recorded. Rates of metachronous lesions and recurrences at the EMR site throughout the follow-up and their treatment were recorded as well. Main results: EMR histology resulted in altered grading or staging in 42.5% patients (17.65% upstaging, 82.35% downstaging). Moreover, downstaging occurred in 30% patients with cancer and upstaging in 20% patients with HGD. Complications during the procedure occurred in 8.75% patients (5 hemorrhages that were treated with hemostatic forceps and 2 perforations that required surgery). Submucosal invasion was revealed in 37.14% patients with EMR-proven cancer. Of these 23.07% were referred to surgery, the others were treated conservatively due to comorbidities that contraindicated surgery or patient refusal. During the follow up of patients without submucosal invading cancer (58 patients, mean follow-up duration 40.22 months, SD 39.13) metachronous lesions developed in 6 patients (10.34%) and recurrences in 4 (6.90%). Of these, 4 were referred to surgery, 3 underwent an additional EMR session and 3 received other treatments due to inoperability. Conclusion: EMR histology changes the diagnosis in 42.5% patients and can also be used as an effective and safe treatment option, thus it reduces dramatically the need for esophagectomy. It should be employed regularly in the diagnostic work-up and as a treatment option for patients with esophageal lesions.

The role of endoscopic mucosal resection as a diagnostic and therapeutic procedure in patients with high grade dysplasia and early esophageal cancer

Study objective: Biopsy-proven esophageal high grade dysplasia and/ or cancer, until a few years ago, was normally staged with CT and referred for esophagectomy, a procedure with high morbility and mortality rates. Recent evidence has suggested how EMR could be a more accurate grading tool for esophageal lesions and can be also employed as a definitive treatment option for a considerable amount of these patients. The aim of this study is to analyze our experience on the role of EMR as a diagnostic tool and to evaluate the long term outcome of the procedure when performed as a therapeutic treatment. Material and methods: We retrospectively reviewed data on 80 consecutive patients that underwent EMR for biopsy proven HGD (n 1⁄4 30), SCC (n 1⁄4 33) or EAC (n 1⁄4 17) at our Department. Complications that developed during the procedure, changes in histologic diagnosis, rate of submucosal invasion and additional treatments were recorded. Rates of metachronous lesions and recurrences at the EMR site throughout the follow-up and their treatment were recorded as well. Main results: EMR histology resulted in altered grading or staging in 42.5% patients (17.65% upstaging, 82.35% downstaging). Moreover, downstaging occurred in 30% patients with cancer and upstaging in 20% patients with HGD. Complications during the procedure occurred in 8.75% patients (5 hemorrhages that were treated with hemostatic forceps and 2 perforations that required surgery). Submucosal invasion was revealed in 37.14% patients with EMR-proven cancer. Of these 23.07% were referred to surgery, the others were treated conservatively due to comorbidities that contraindicated surgery or patient refusal. During the follow up of patients without submucosal invading cancer (58 patients, mean follow-up duration 40.22 months, SD 39.13) metachronous lesions developed in 6 patients (10.34%) and recurrences in 4 (6.90%). Of these, 4 were referred to surgery, 3 underwent an additional EMR session and 3 received other treatments due to inoperability. Conclusion: EMR histology changes the diagnosis in 42.5% patients and can also be used as an effective and safe treatment option, thus it reduces dramatically the need for esophagectomy. It should be employed regularly in the diagnostic work-up and as a treatment option for patients with esophageal lesions.

Symptoms and Endoscopic Features at Barrett's Esophagus Diagnosis: Implications for Neoplastic Progression Risk

Risk stratification of Barrett's esophagus (BE) patients based on clinical and endoscopic features may help to optimize surveillance practice for esophageal adenocarcinoma (EAC) development. The aim of this study was to investigate patient symptoms and endoscopic features at index endoscopy and risk of neoplastic progression in a large population-based cohort of BE patients. A retrospective review of hospital records relating to incident BE diagnosis was conducted in a subset of patients with specialized intestinal metaplasia from the Northern Ireland BE register. Patients were matched to the Northern Ireland Cancer Registry to identify progressors to EAC or esophageal high-grade dysplasia (HGD). Cox proportional hazards models were applied to evaluate the association between endoscopic features, symptoms, and neoplastic progression risk. During 27,997 person-years of follow-up, 128 of 3,148 BE patients progressed to develop HGD/EAC. Ulceration within the Barrett's segment, but not elsewhere in the esophagus, was associated with an increased risk of progression (hazard ratio (HR) 1.72; 95% confidence interval (CI): 1.08-2.76). Long-segment BE carried a significant sevenfold increased risk of progression compared with short-segment BE; none of the latter group developed EAC during the study period. Conversely, the absence of reflux symptoms was associated with an increased risk of cancer progression (HR 1.61; 95% CI: 1.05-2.46). BE patients presenting with a long-segment BE or Barrett's ulcer have an increased risk of progressing to HGD/EAC and should be considered for more intense surveillance. The absence of reflux symptoms at BE diagnosis is not associated with a reduced risk of malignant progression, and may carry an increased risk of progression.