Neoplasms

All Conditions

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Performing adenoma resection through standardized endoscopic mucosectomy of duodenal adenoma.

Endoscopic mucosectomy

Philippe GRANDVAL, MD/PhD

Philippe Grandval, MD/PhD

Urielle DESALBRES

Sporadic duodenal adenomas are rare. As they are highly pre neoplastic, they should be removed and endoscopic mucosectomy is recommended during digestive endoscopy. However, this technique, albeit less dangerous than surgery, is associated with complications such as haemorrhages, perforations, and more relapse than that can be observed for colorectal adenomas. As no prospective data have been published this French multicenter study aim to analyze results of this technique under standardized and secured procedure.

All investigators are expert in therapeutic endoscopy in tertiary centers and are member of a group of clinical researcher involved in that field (" GRAPHE " (Groupe de Recherche et d'Action des Praticiens Hospitaliers en Endoscopie interventionnelle). Results are highly expected among the international society of gastroenterologists who need to confirm the efficacy of endoscopy and define optimal conditions for performing adenomas resection in this location Primary End Point is the two years recurrence rate. Secondary End Points are frequency and type of complication after standardized endoscopic mucosectomy of duodenal adenomas, frequency and type of complications after a second endoscopic mucosectomy and patient's characteristics Patients with sporadic duodenal adenomas larger than 5 mm requiring endoscopic mucosectomy will be included. Non-inclusion criteria concern patients with previous endoscopic resection, lesion involving the major papilla, sub mucosal lesions, familial adenomatous polyposis and use of antiplatelet agent during the five last days.

Hundred and twenty patients will be included and followed 2 years after mucosectomy.

French Register of Duodenal Adenomas Characterization and Evaluation of Endoscopic Mucosectomy

Assistance Publique Hopitaux De Marseille

Digestive System Diseases

Duodenal Diseases

Intestinal Diseases

Gastrointestinal Diseases

Patients who consent to participate in this study will have a small sample of their adenoma and normal tissue sent for molecular testing.

A small sample of the duodenal adenoma will be obtained for molecular testing. The remaining adenoma will be sent for regular histological testing.

Tissue Sampling

Michael Bourke, MBBS, FRACP

The purpose is to investigate whether polyps that look different at endoscopy, have formed via different mutations and have different risks of turning into cancer.

Laterally spreading tumours (LSTs), are polyps that have a lateral extension along the duodenal wall with minimal vertical growth. It has become evident over the last few years that rather than being a single entity requiring an accumulation of mutations, Duodenal and ampullary cancer is in fact a heterogenous disease forming via multiple distinct genetic pathways. It is therefore hypothesised that different polyp types have different genetic abnormalities, and potentially form via distinct genetic pathways, although this theory has not been widely examined.

This knowledge would be important in furthering our understanding of the development of cancer. There is accumulating evidence that genetic abnormalities may be a better predictor of cancer behaviour than histological grade. Additionally, guidelines for endoscopy surveillance are currently a one size fits all approach that do not reflect the genetic heterogeneity of the disease and the knowledge that only 5% of polyps progress to cancer. Genetic studies may assess future cancer risk to a person in polyps once removed and plan surveillance endoscopy frequency.

Adenoma tissue sample and control "regular" tissue sample

Endoscopic Characteristics of Duodenal and Ampullary Lesions

A Correlation of the Endoscopic Characteristics of Duodenal and Ampullary Laterally Spreading Tumours With Their Somatic or Germline Mutations.

The aim of this project is to look for statistically significant differences in molecular abnormalities from the three known genetic pathways, between the two different morphological types, granular and non-granular, to potentially demonstrate that these different polyps form via different genetic pathways.

Professor Michael Bourke

Director of Gastrointestinal Endoscopy

Endoscopic full-thickness resection of the duodenal adenoma with the 'duodenal Full-Thickness resection device' (dFTRD).

Endoscopic Mucosal Resection (EMR) of the duodenal adenoma (=standard therapy).

dFTRD

Markus Bauder, MD

Karel Caca, MD, PhD

Karel Caca, Prof. Dr. med.

Sandra Wennemuth

Prospective, randomized multi-center trial. Comparison of Endoscopic Mucosal Resection (EMR) versus Endoscopic Full-Thickness Resection with the duodenal Full-Thickness Resection Device (dFTRD) of non-ampullary duodenal adenomas.

Endoscopic Resection of Non-ampullary Duodenal Adenomas: Endoscopic Mucosal Resection (EMR) vs. Endoscopic Full-thickness Resection With the 'Duodenal Full-thickness Resection Device' (dFTRD)

Composite endpoint of perforations and relevant bleeding

time span of the procedure according to sedation protocol

Kliniken Ludwigsburg-Bietigheim gGmbH

performed pancreatic duct stent placement after endoscopic papillectomy

have not performed pancreatic duct stent placement after endoscopic papillectomy

performed common bile duct stent placement after endoscopic papillectomy

have not performed common bile duct stent placement after endoscopic papillectomy

Post-resection, endoscopic retrograde cholangiopancreatography (ERCP) was performed for stent placement in pancreatic or bile ducts as needed, with X-ray confirmation of stent positioning.

Stent Placement in Pancreatic and Bile Ducts

Fujing Lv, M.D.

This is a retrospective study, including 79 patients with duodenal papillary adenoma, who treated with Endoscopic Papillectomy (EP) at Beijing friendship hospital. The cohort included patients who underwent EP with or without Pancreatic Duct (PD) and Common Bile Duct (CBD) stent placement. The investigators assessed the outcomes of EP and the impact of stent placement on complications and recurrence rates.

Duodenal papillary adenoma, a potentially malignant benign tumor is primarily treated with endoscopic papillectomy. Despite its efficacy, endoscopic papillectomy has a high complication rate. This study investigates whether pancreatic duct and common bile duct stent placement can mitigate these complications. In a retrospective analysis, 79 patients with duodenal papillary adenoma, treated with endoscopic papillectomy at our center, were studied. The cohort included patients who underwent endoscopic papillectomy with no stents placement, common bile duct stent placement alone, pancreatic duct stent placement alone, or stents placement in both ducts. Complete resection rates did not significantly differ between patients with or without stent placement. Early complication rates were similar across groups. However, significant reduction in common bile duct stenosis was observed in the stenting group. Furthermore, stent placement correlated with lower adenoma recurrence rates during follow-up. Thus, Pancreatic duct and common bile duct stent placement in endoscopic papillectomy may decrease late complications, particularly common bile duct stenosis, and reduce the recurrence of duodenal papillary adenoma.

Effectiveness of Endoscopic Papillectomy With Stent for Treating Duodenal Papillary Adenoma

Effectiveness of Endoscopic Papillectomy With Stent Placement in Pancreatic and Bile Ducts for Treating Duodenal Papillary Adenoma

Complications related with Endoscopic Papillectomy (EP), including pancreatitis, cholangitis, bleeding, perforation, hyperamylasemia, stenosis. The results of intraoperative endoscopic observation, postoperative symptoms and signs, blood routine examination, amylase, lipase, and imaging and endoscopic examination during follow-up were measured.

The pathological margins results were used to determine whether the lesion was completely resected.

Endoscopic observation and biopsy results were used to find recurrence.

Beijing Friendship Hospital

Symptoms and General Pathology

Rare Diseases

Esophageal Neoplasms

Stomach Neoplasms

Atrophy

Duodenal Neoplasms

Polyps

Barrett Esophagus

Gastritis, Atrophic

Metaplasia

Precancerous Conditions

Gastritis

Gastrointestinal Neoplasms

Digestive System Neoplasms

Stomach Diseases

Head and Neck Neoplasms

Esophageal Diseases

Gastroenteritis

Intestinal Neoplasms

Esophageal Cancer

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
French Register of Duodenal Adenomas Characterization and Evaluation of Endoscopic Mucosectomy	NCT03031704	Duodenal Adenom...	Endoscopic muco...	18 Years -	Assistance Publique Hopitaux De Marseille
Endoscopic Characteristics of Duodenal and Ampullary Lesions	NCT01556399	Duodenal Diseas...	Tissue Sampling	18 Years - 85 Years	Western Sydney Local Health District
Endoscopic Resection of Non-ampullary Duodenal Adenomas: Endoscopic Mucosal Resection (EMR) vs. Endoscopic Full-thickness Resection With the 'Duodenal Full-thickness Resection Device' (dFTRD)	NCT03559231	Duodenal Adenom...	dFTRD EMR	18 Years -	Kliniken Ludwigsburg-Bietigheim gGmbH
French Register of Duodenal Adenomas Characterization and Evaluation of Endoscopic Mucosectomy	NCT03031704	Duodenal Adenom...	Endoscopic muco...	18 Years -	Assistance Publique Hopitaux De Marseille
Endoscopic Characteristics of Duodenal and Ampullary Lesions	NCT01556399	Duodenal Diseas...	Tissue Sampling	18 Years - 85 Years	Western Sydney Local Health District
French Register of Duodenal Adenomas Characterization and Evaluation of Endoscopic Mucosectomy	NCT03031704	Duodenal Adenom...	Endoscopic muco...	18 Years -	Assistance Publique Hopitaux De Marseille
Effectiveness of Endoscopic Papillectomy With Stent for Treating Duodenal Papillary Adenoma	NCT06301048	Duodenal Adenom... Complication of...	Stent Placement...	18 Years -	Beijing Friendship Hospital
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

Spots Global Cancer Trial Database for duodenal adenoma