Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Barrett Esophagus

Hyperplasia

Disease Attributes

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

patients with DHG on Barrett's esophagus on endoscopic biopsies followed by endoscopic resection

Pathological revision

Influence of histological concordance on the risk of recurrence:

the histological concordance being the comparison between the biopsies and the endoscopic resection piece and its concordant response rate.

Impact of Histologic Concordance Between Biopsies and the Endoscopic Resection Specimen, in the Treatment of Barrett's Esophagus in Dysplasia, on the Recurrence of Dysplasia

the histological concordance being the comparison between the biopsies and the endoscopic resection piece and its concordant response rate.

Identification of histological factors of recurrence.

Institut Paoli-Calmettes

Adenocarcinoma

Patients who have undergone an EMR for Barretts Oesophagus

Michael J Bourke, MBBS

Analysis of long term outcomes of patients undergoing endoscopic mucosal resection for Barrett's oesophagus with high grade dysplasia and/or early intramucosal carcinoma (IMC).

Long Term Barrett's Endoscopic Mucosal Resection Study

Long Term Outcomes of Patients Undergoing Endoscopic Resection of Barrett's Oesophagus (BO) With High Grade Dysplasia (HGD) and Early Adenocarcinoma

Patients will be contacted via phone and will be required to answer questions over the phone. Health questionnaires may also be sent at the patients request to complete and post back.

Professor Michael Bourke

Director of Gastrointestinal Endoscopy

Rare Diseases

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Esophageal Cancer

Patient with Barrett's Esophagus with a history of High grade dysplasia or early esophageal adenocarcinoma

Endoscopy with biopsy 6 weeks after the initial endoscopy

Upper endoscopy with biopsy

Louis M WongKeeSong, MD

This study is being done to determine if a new endoscope will help doctors identify pre-cancer or early cancer lesions in patients who have Barrett's esophagus. This new endoscope allows the doctor to look at the lining of the esophagus in 3 different ways by modifying light.

Patients with Barrett's esophagus are advised to undergo periodic endoscopic surveillance with random biopsies in an attempt to identify high-grade dysplasia (HGD) or early adenocarcinoma (ACA) at a time when intervention can be curative. This approach, however, can be time-consuming and is hindered by low sampling yield and random sampling error. Endoscopic Tri-Modal Imaging (ETMI) is a novel diagnostic modality that encompasses three advanced imaging features in one system: high-resolution endoscopy (HRE), autofluorescence imaging (AFI) and narrow-band imaging (NBI). HRE and AFI provide a bird's-eye view of 'red flag' areas which are then assessed by NBI for focused and more specific tissue characterization. The aim of this prospective, multi-center study is to compare the diagnostic performance of ETMI with that of standard white-light endoscopy (WLE) for identifying high-grade dysplasia (HGD) and early adenocarcinoma (ACA) in BE. A total of 84 BE patients will be recruited for the study and they will undergo both ETMI and WLE examinations in a randomized, crossover fashion. Standard surveillance biopsies and ETMI-targeted biopsies will be performed. The primary outcome will compare the number of patients and lesions with HGD or early ACA detected with WLE and ETMI. It is anticipated that ETMI will enhance the detection of high-grade Barrett's lesions relative to WLE.

Endoscopic Tri-Modal Imaging in Patients With Barrett's Esophagus

Endoscopic Tri-Modal Imaging for the Detection of High-Grade Dysplasia and Early Adenocarcinoma in Patients With Barrett's Esophagus: A Randomized Crossover Multi-center Study

Mayo Clinic

Principal Investigator

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Liquid nitrogen spray with a cryospray catheter through an upper endoscope that enables the direct visualization of mucosal freeze (cryoburn) of the mucosa treated which avoids the need for direct tissue contact. Frozen state is defined as mucosa appearing white. Cryofreeze is preformed in cycles of 10 second sprays with a minimal thaw of 60 seconds each spray. This cycle is repeated 4 times in each area of treatment.

Cryospray Ablation

John A. Dumot, D.O.

This is a single center study to evaluate the efficacy and safety of a new ablation technique involving the spray of liquid nitrogen through a catheter (cryotherapy) via an upper endoscopy (EGD) to ablate Barrett's esophagus with changes of high-grade dysplasia (HGD) or intramucosal cancer (IMCA) and patients with esophageal cancer limited to the esophageal wall, in whom there are no standard treatment options available.

The Cryo-Ablator System is a cryosurgical unit with a liquid nitrogen cooled cryocatheter and accessories to destroy tissue during surgical procedures by applying extreme cold.

Patients will prepare for esophagogastroduodenoscopy (EGD) in the standard fashion using an overnight fast with only clear liquids and required medications allowed up to 2 hours before the procedure. The EGD will be performed using a therapeutic Olympus endoscope. The cryocatheter is passed into the therapeutic channel of the endoscope. Liquid nitrogen is sprayed through the cryocatheter for a duration of 10 seconds as measured by the device integrated timer. This process will be repeated four times in piecemeal fashion such that for any given area treated it will be maintained in a frozen state for a total of 40 seconds. Following circumferential treatment, the process will be repeated again applying the spray to the same section of mucosa for a duration of 20 seconds. Patients will be contacted the following day to assess for any immediate complications.

Patients will repeat treatment every 6 weeks if no evidence of esophageal mucosal injury, until complete ablation of the Barrett's mucosa has been achieved. Follow up period of five years to monitor healing and progression.

Cryotherapy for Barrett's Esophagus and Early Esophageal Cancers

A Pilot Study of Cryotherapy for Barrett's Esophagus With High-Grade Dysplasia and Early Esophageal Cancers

Determined by the end of protocol biopsies: incremental (absence of HGD and IMCA in all specimens); partial (residual IMCA with absence of any dysplasia); complete (absence of any intestinal metaplasia or dysplasia)

Toxicity is defined as death or esophageal perforation

Number of patient with each response determined by the end of protocol biopsies: incremental (absence of HGD and IMCA in all specimens); partial (residual IMCA with absence of any dysplasia); complete (absence of any intestinal metaplasia or dysplasia); no response

Case Comprehensive Cancer Center

Gastrointestinal Agents

All Drugs and Chemicals

Omeprazole

Proton Pump Inhibitors

Antacids

Anti-Ulcer Agents

Enzyme Inhibitors

treatment with high-power argon plasma coagulation (90 Watt) followed by acid suppression with high-dose oral omeprazole (40 mg t.i.d)

treatment with high-power argon plasma coagulation (90 Watt) followed by acid suppression with standard dose oral omeprazole (40 mg q.d)

treatment with standard-power argon plasma coagulation (60 Watt) followed by acid suppression with high-dose oral omeprazole (40 mg t.i.d)

Argon Plasma Coagulation 90W power

Argon Plasma Coagulation 60W power

Omeprazole 120 mg

Omeprazole 40 mg

Background and study aims. To evaluate the impact of power setting and proton pump inhibitor (PPI) dose on the efficacy and safety of argon plasma coagulation (APC) of Barrett's esophagus (BE) with low-grade dysplasia (LGD).

Patients and methods. Investigator initiated, single-center, parallel-group randomized controlled trial (RCT) conducted in a tertiary referral center in Poland. Consecutive patients with BE and LGD were randomly assigned to APC with power set at 90 Watt (90W) or 60 Watt (60W) followed by 120 mg or 40 mg omeprazole for six weeks. The primary outcome of the study was the rate of complete (endoscopic and histologic) ablation of BE at six weeks. Secondary outcomes included safety and long-term efficacy (at two years and at the end of a long-term follow-up of over 4 years.

Investigator initiated, single-center, parallel-group RCT conducted in a tertiary referral center in Poland.

Patients were blinded to the power settings used for APC, but they knew the PPI dose they received. The endoscopist performing APC ablation was blinded to participant allocation and APC power setting (the power was set up by an assistant who knew the group allocation and the power display remained covered during the entire procedure). The endoscopist and pathologist involved in efficacy assessment were blinded to participant allocation.

Argon Plasma Coagulation for Barrett's Esophagus

Argon Plasma Coagulation for Barrett's Esophagus With Low Grade Dysplasia: A Randomized Trial With Long Term Follow-up Evaluating the Impact of Power Setting and Proton Pump Inhibitor Dose

Complete ablation was defined as no endoscopic and histologic evidence of Barrett's mucosa, dysplasia, and buried metaplastic glands

Centre of Postgraduate Medical Education

Maria Sklodowska-Curie National Research Institute of Oncology

Stomach Neoplasms

Atrophy

Adenoma

Duodenal Neoplasms

Polyps

Gastritis, Atrophic

Metaplasia

Gastritis

Stomach Diseases

Gastroenteritis

Intestinal Neoplasms

Duodenal Diseases

Intestinal Diseases

Stomach Cancer

Patients referred for clinically indicated EGD, without known precancerous condition. Patients will receive endoscopy with standardised biopsy and photodocumentation protocol

Massimiliano Di Pietro, MD

Bincy Alias

Ines Modolell, MD

Andreas V Hadjinicolaou

Cancers of the upper gastro-intestinal tract, including esophagus (gullet), stomach and small bowel, are amongst the deadliest malignancies. The main reason for their high mortality rate is that they are usually diagnosed late when curative treatments are no longer effective. However, these types of cancer generally arise from well-described pre-cancerous diseases, such as Barrett's esophagus and gastric intestinal metaplasia. This provides an opportunity for clinicians to detect these pre-cancerous conditions early and offer adequate cure or clinical monitoring before they progress to cancer. A camera test (gastroscopy) is the gold-standard test to detect pre-cancerous diseases in these organs.

There has been limited research to set the standards for performance of a gastroscopy, especially with regards to diagnosis of pre-cancerous conditions, which require knowledge and skills by the physician performing the test (endoscopist). Therefore, the hypothesis behind this study is that the aforementioned pre-cancerous diseases are understudied and often go undetected. This study aims to understand how often endoscopists should diagnose these pre-cancerous diseases on routine gastroscopy and help define the standards to measure performance. The investigators will assess the following rates: i. how often endoscopists diagnose these pre-cancerous lesions during endoscopy; ii. How often these conditions are diagnosed on biopsies taken according to a standardized protocol; iii. How often these condition should have been diagnosed by the endoscopists based on the review of pictures by expert endoscopists. The investigators will also compare the rates of correct diagnosis by endoscopists with different levels of experience and based on the times spent to complete the diagnostic test.

Investigating these aspects will enhance the understanding of the medical community with regards to the diagnosis of these pre-cancerous lesions and set endoscopy standards to improve their early detection and treatment before they progress to cancer. This will translate to improved cancer prevention and benefit for patients.

BACKGROUND Esophagogastroduodenoscopy (EGD) is the gold-standard test for investigating upper gastrointestinal (GI) tract pathology. The learning curve for EGD is generally steep and it is often performed by trainees at the mid stages of core training as well as nurse endoscopists. Currently the Joint Advisory Group for GI endoscopy (JAG) recommends a minimum number of 200 procedures to acquire the skills and perform endoscopy independently. However, there has been very little research done to set the standard required to measure EGD performance. The only validated quality indicators in EGD include the successful J-manoeuvre rate and D2 intubation rate, which reflect very basic skills and do not measure diagnostic ability. This contrasts with key performance indicators (KPI) for colonoscopy, for which extensive research has led to development of formal quality performance indicators. In colonoscopy formal quality indicators include (i) cecal intubation rate, (ii) adenoma detection rate, (iii) rectal retroversion rate, (iv) colonoscopy withdrawal time, (v) polyp retrieval rate, (vi) post-colonoscopy colorectal cancer rate and (vii) perforation rate. This has allowed researchers to demonstrate that poor quality colonoscopy leads to an increase in the incidence of interval cancers.

Similar benchmarks have not been set for the upper GI tract. A recent UK study revealed that 7.7% cases of upper GI cancers were missed on previous EGD and that there was a correlation between missed cancer and high number of procedures per lists and hence, arguably, those performed under user time pressure. This is in line with studies on other Western populations indicating that between 5.3% and 13.9% of patients with upper GI cancers have had normal EGD reported within the previous 3 years. Given that gastroscopy is the most commonly performed procedure in endoscopy units in the UK and its demand is increasing, there is an urge to identify diagnostic KPI to measure diagnostic skills, to improve quality of the endoscopies and to reduce the rate of missed diagnoses. Furthermore, such minimum quality standards are extremely important to counteract the potential negative effects on the performance of the pressure faced by endoscopy departments to deliver diagnostic and therapeutic procedures in a timely fashion. The importance of adequate procedure time for diagnostic accuracy has been demonstrated both in the detection of oesophageal and gastric neoplastic lesions. For detection of upper GI neoplasia, it has been demonstrated that a minimum of 7 minutes per procedure should be spent in order to ensure adequate visualisation and allow detection of high-risk lesion . In a Korean study, that compared faster with slower endoscopists, all of whom had adequate training and experience, the slower endoscopists (withdrawal time from duodenum \>3min) had a significantly higher detection rate of upper GI neoplasia. Finally, in the context of Barrett's oesophagus (BO), longer inspection times during EGD correlated with increase detection rate.

Pre-malignant lesions in the upper GI tract are generally understudied when compared to those in the lower GI tract. Furthermore, their epidemiology seems to vary with geography, and this has not been inadequately investigated in the UK. Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma. The population prevalence is difficult to estimate given that the condition can be asymptomatic, and the diagnosis is only made by endoscopy and biopsy. It is estimated that the prevalence in the general population in Western Countries is 1-2% with significant geographic variation, but increases in patients undergoing endoscopic procedures (4.0% in Dutch population, 5.6% USA). However, the majority of studies looking at BE prevalence are confounded by the fact that most procedures were performed for GERD symptoms generating selection bias. In studies performed in patients referred for colonoscopy (n=1500 approximately) the prevalence of BE varied between 6.8% and 16.7%.

Similar to oesophageal cancer, gastric cancer has its own pre-malignant precursors including gastric intestinal metaplasia (GIM) and gastric atrophy (GA) . The endoscopic diagnosis of GA and GIM however is not straightforward as the colorimetric shift from normal to pathological mucosa is subtle and additional endoscopic signs such as disappearance of gastric folds can be affected by the degree of air insufflation. The prevalence of GA can reach up to 33.3% in Western Europeans and is higher in East Asia. For GIM, the reported population prevalence in Western Countries ranges from 7 to 28.6%. These rates are however probably affected by selection bias, such as enrichment of individuals affected by H. pylori infection. In a Dutch study on patient referred for colonoscopy 0.8% had GA, 7.1% had both GA and GIM and 1.4% had gastric dysplasia.

For esophageal squamous dysplasia, the precursor lesion of oesophageal squamous cell carcinoma, prevalence estimates are between 3 and 38%. This reflects the variation in endoscopic methods, histopathological scoring and the studied populations from high-risk geographic regions such has Korea. The prevalence of squamous dysplasia in Western Countries in not well known, since it is generally very difficult to diagnose on white light endoscopy. It can be argued that squamous dysplasia is vastly underdiagnosed in clinical practice as the ratio between oesophageal adenocarcinoma and squamous cell carcinoma in the UK is just over 2:1, however squamous dysplasia is rarely diagnosed.

Duodenal adenoma is another understudied pre-malignant lesion that can in fact undergo malignant transformation in 30-85% of cases and as such, needs to be recognised and treated early and definitively . These occur very often in the context of familial adenomatous polyposis (FAP) syndrome, whereas sporadic duodenal adenomas are much rarer with a prevalence of 0.03-0.4% (32, 33).

The majority of studies looking at prevalence of pre-malignant upper GI conditions in the general population referred for EGD are limited by the lack of standardised endoscopy and biopsy protocols. In addition, none of the studies looked at variation of prevalence based on experience. Furthermore, no expert review of endoscopic images has been performed to ensure quality of the diagnosis. Although quality standards in upper GI endoscopy have been proposed by the British Society of Gastroenterology and European Society of Gastrointestinal Endoscopy, the majority of the statements in these guidelines have a low level of evidence and weak to moderate strength of the recommendation. Most importantly, none of the statements refer to diagnostic KPI, given that the expected detection rate of the upper GI pre-neoplastic and early neoplastic lesions at endoscopy is unknown. This represents a gap that our study aims to tackle.

HYPOTHESIS The hypothesis is that the prevalence of upper Gi pre-malignant condition is underestimated based on available literature data and that the detection rate of pre-cancerous upper GI lesions improves with a more rigorous and systematic approach to performing EGD. In the future, using diagnostic KPI to monitor performance of upper GI endoscopists will result in improved outcomes of oesophago-gastric cancer.

STUDY OBJECTIVES The aim of this study is to assess endoscopic and pathological outcomes during routine EGD using standard photo-documentation and biopsy protocol.

The primary objective is to define the prevalence of pre-malignant or early malignant upper GI tract lesions as measured by a standardised endoscopy and biopsy protocol. This is further broken down into categories of pre-malignant pathology, namely: 1) Barrett's esophagus with and without dysplasia; 2) squamous dysplasia;, 3) gastric atrophy/gastric intestinal metaplasia; , 4) gastric adenoma; and 5) duodenal adenoma.

The secondary objectives are:

1. Missed rate of endoscopic diagnosis compared to pathological diagnosis
2. Missed rate of endoscopic diagnosis compared to expert review of endoscopic photos
3. Correlation between duration of the endoscopy and detection of pre-neoplastic and neoplastic lesions
4. Quality of the endoscopic pictures taken in routine endoscopy
5. Correlation between endoscopist experience and rate of detection
6. Correlation between use of image enhanced endoscopy and rate of detection
7. Interobserver agreement among expert and not expert endoscopists
8. Correlation between life-style factors and pathological outcomes

STUDY DESIGN This will be a multicenter population study. Recruiting centers will be a range of Teaching and District General Hospitals in England. 1000 patients referred for urgent or routine endoscopy to evaluate upper GI symptoms will be recruited. The detection rates of upper GI tract pre-malignant lesions in our study procedures will be compared to standard historical data from each participating institution. An equivalent population from the year prior to the start of recruitment, matched for age, sex, indication for endoscopy and referral pathway, will be retrieved from the archives of each participating NHS Trust and directly contrasted to this study population to evaluate whether the detection rate of pre-malignant upper GI tract lesions improves with a more rigorous and systematic approach to performing EGD using a standardized photo documentation and biopsy protocol. In this way, the investigators can evaluate the immediate impact of our study and the utility of the proposed diagnostic KPI. As an example, the investigators already have date to show that in 2019 over 8,500 EGD were performed in Cambridge alone, of which 53% had biopsies taken. Based on matched pathology record, only 29 new diagnoses of GA or GIM were made during the same time period, suggesting the possibility of large under-detection of premalignant stomach. The endoscopic pictures will be evaluated by two expert endoscopists with interest in detection and treatment of upper GI pre-malignant and early malignant conditions. The quality of the pictures will be scored on a visual analogue scale based on two parameters: optical quality and representation of the intended section of the upper GI tract. The endoscopists will note the presence of premalignant conditions. In case of disagreement, a third investigator will review the picture to achieve a gold standard endoscopic diagnosis.

Clinical samples from biopsies taken during endoscopic procedures for the purpose of tissue diagnosis

Diagnostic Performance Indicators in Upper GI Endoscopy:PROSPERO Study

PROspective Multicentre Study to Identify Diagnostic Key PERfOrmance Indicators in Upper GI Endoscopy (PROSPERO)

The primary outcome is calculating the proportion of patients diagnosed with pre-malignant pathology in the upper GI tract. This is further broken down into categories of pre-malignant pathology, namely; 1) duodenal adenoma, 2) gastric atrophy/gastric intestinal metaplasia (IM), 3) gastric adenoma, 4) Barrett's oesophagus and 5) squamous dysplasia.

The detection rates of upper GI tract pre-malignant lesions in our study procedures will be compared to standard historical data currently available to update and guide future practice guidelines.

(defined as any pathological diagnosis that was not suspected by the endoscopist on visualisation alone)

(defined as endoscopic lesions identified by expert review and not reported by primary endoscopist)

Assessment of whether duration of the endoscopy associates with diagnosis of pre-neoplastic lesions

defined as quantitative assessment of photo on a Visual Analogue Scale by expert endoscopists

Assessment of whether year of endoscopy practice correlate with the rate of detection of pre-malignant lesions

Assessment of whether use of dye or electronic chromoendoscopy improves detection of lesions

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Impact of Histologic Concordance Between Biopsies and the Endoscopic Resection Specimen, in the Treatment of Barrett's Esophagus in Dysplasia, on the Recurrence of Dysplasia	NCT03685799	Barretts Esopha...	Pathological re...	18 Years -	Institut Paoli-Calmettes
Long Term Barrett's Endoscopic Mucosal Resection Study	NCT02200250	Barretts Esopha...		18 Years - 99 Years	Western Sydney Local Health District
Endoscopic Tri-Modal Imaging in Patients With Barrett's Esophagus	NCT00586989	Barretts Esopha... High Grade Dysp... Early Esophagea...	Upper endoscopy...	18 Years - 85 Years	Mayo Clinic
Cryotherapy for Barrett's Esophagus and Early Esophageal Cancers	NCT00650988	Barretts Esopha... Esophageal Canc...	Cryospray Ablat...	18 Years -	Case Comprehensive Cancer Center
Endoscopic Tri-Modal Imaging in Patients With Barrett's Esophagus	NCT00586989	Barretts Esopha... High Grade Dysp... Early Esophagea...	Upper endoscopy...	18 Years - 85 Years	Mayo Clinic
Argon Plasma Coagulation for Barrett's Esophagus	NCT04154748	Barretts Esopha...	Argon Plasma Co... Argon Plasma Co... Omeprazole 120 ... Omeprazole 40 m...	18 Years -	Maria Sklodowska-Curie National Research Institute of Oncology
Diagnostic Performance Indicators in Upper GI Endoscopy:PROSPERO Study	NCT04843397	Esophageal Canc... Gastric Cancer Barrett Esophag... Gastric Atrophy Gastric Intesti... Duodenal Adenom... Esophageal Dysp... Duodenum Cancer Gastric Polyp Barretts Esopha...		18 Years -	University of Cambridge
Long Term Barrett's Endoscopic Mucosal Resection Study	NCT02200250	Barretts Esopha...		18 Years - 99 Years	Western Sydney Local Health District

Spots Global Cancer Trial Database for barretts esophagus