Symptoms and General Pathology

All Conditions

Digestive System Diseases

Constriction, Pathologic

Calculi

Pancreatic Diseases

Gallbladder Diseases

Gallstones

Cholelithiasis

Cholecystolithiasis

Pathological Conditions, Anatomical

Gastrointestinal Diseases

Biliary Tract Diseases

Partial ampullary endoscopic mucosal resection

Standard oval-shaped, braided wire polypectomy snare with 10 mm or 20 mm loop diameter will be used. With the duodenoscope in a semi-long position, the tip of the snare will be anchored just below the transverse fold of the ampulla and opened above-downwards fashion until the orifice will be seen. The orifice will be strictly preserved to avoid the risk of PEP and approximately the upper two-thirds of the ampullary mound will be grabbed by the snare. The direction and the depth will be controlled by combined movements of the elevator and wheels of the duodenoscope. After removal of the mucosa, the wall of choledochus will be seen clearly and standard wire-guided cannulation (WGC) will be performed. If cannulation can not be achieved with WGC, an additional incision will be performed to the wall of the choledochus with a needle knife.

PA-EMR

The needle knife will be placed at the junction of the upper one-third and lower two-thirds of the papillary roof (bulging portion). Minimal, superficial incisions will be made in the 11-12 o'clock direction. The length of the fistulotomy will be at the endoscopist's discretion, depending on the shape of the papilla. The cut will be extended until bile juice, the pinkish bile duct mucosa, and/or the bulging of the white sphincter of the Oddi's muscle is visible.

Salih Tokmak, Assist. prof

The aims of this study are to compare the needle knife fistulotomy (NKF) technique versus the partial ampullary endoscopic mucosal resection (PA-EMR) technique in patients with difficult biliary cannulation and to assess the incidence rate of complications between these cannulation methods.

Cannulation success with standard techniques reported to be around 95% even in expert hands and despite all efforts, it can be challenging that needs an alternate intervention.

NKF is recommended as the initial technique for pre-cutting because the rate of post-ERCP pancreatitis (PEP) is significantly low but there is an ongoing debate about limiting its use in certain types of papillae with a long intra-mural segment

Indeed the shape of the papillae influences the success of bile duct cannulation and the choice of the pre-cutting technique. Type-2 and Type-3 papillae are more difficult to cannulate than Type-1. NKF can be performed as the initial technique for pre-cutting in protruded Type-2 and Type-3 papillae but it has some limitations.

First of all, the incision can be erratic because it is performed without a guidewire and uncontrolled. This can cause a tattered mucosa as the incision progress and the papillae lose anatomic contours. Some amount of bleeding may also unavoidably occur and the field of view further impaired. If the initial incision line is incorrect and additional incision is needed, more crumpled and deformed papillae with irregular margins may be encountered. These undesired results are frequently experienced and prevent a clean-cut, thus further complicate the cannulation. Even perforation can occur.

Recently the investigators described a novel technique, PA-EMR, for difficult biliary cannulation in patients with protruded Type-2, Type-3, and shar-pei papilla. The investigators hypothesized that with this new technique cannulation success will be higher, procedure time will be shorter and the adverse events will be lower versus NKF technique.

Needle Knife Fistulotomy Versus Partial Ampullary Endoscopic Mucosal Resection for Difficult Biliary Cannulation

Successful bilary cannulation, verified by fluoroscopic images of correct guidewire positioning in the CBD, and contrast media.

Time from first contact with cannula to papillae to deep cannulation

Cukurova University

Duzce University

Asisstant Professor

Neoplasms

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

brush cytology

PROTOCOL

Introduction: The introduction of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic sphincterotomy (ES) in 1974 has dramatically changed the treatment of biliary and pancreatic diseases. ES permits transection of Oddi's sphincter, allowing the endoscopist to remove stones and place stents.

The main indications for ERCP are: 1. Removal of common bile duct stones 2. Dilation of benign biliary ducts strictures 3. Stent placement in patients with malignancy 4. Acute biliary pancreatitis 5. Removal of stones and dilation of strictures of the main pancreatic duct in patients with chronic pancreatitis and 6. Treatment of biliary fistulae after surgical operations .

Complications of ES can be described as early (within one month after ES) and late. Early complications have approximately a 10% incidence and include: 1.acute pancreatitis (5,4%) 2.bleeding (2%) 3.acute cholangitis (1%) 4.acute cholecystitis (0,5%) 5. Perforation and others (1,1%). Late complications are mainly the recurrence of choledocholithiasis (2,5%), narrowing of the previous ES and recurrent acute cholangitis. Furthermore, there is a debate in the literature about late development of cholangiocarcinoma.

Carcinogenesis after surgical sphincteroplasty and biliary-enteric anastomosis has been described. Previous studies have shown late development of cholangiocarcinoma after transduodenal sphincteroplasty and biliary-enteric anastomosis for benign disease. The incidence is up to 7% in a twenty-year follow up, while in the general population is approximately 1/ 100.000 . In addition, Tocchi et al showed that the rate of cholangiocarcinoma after transduodenal sphincteroplasty and choledochoduodenal anastomosis is up to 5-7% and after other choledochi-enteric anastomoses approximately 1,9%. It seems that the ablation of sphincter function causes prolonged pancreatobiliary and duodenobiliary reflux. Proteolytic pancreatic enzymes are activated and bacterial intestinal flora colonizes the biliary epithelium, causing recurrent inflammation. Chronic inflammatory irritation may lead to hyperplasia, dysplasia and atypia of epithelium, ultimately inducing carcinogenesis.

Eleftheriadis et al, studied changes of the biliary epithelium in patients who underwent choledochi-duodenal anastomosis for benign disease, and hyperplasia of the biliary epithelium was demonstrated. The same results and atypia of biliary epithelium were reported by Kurumado et al, in mice models with choledochi-duodenal anastomosis. Anomalous pancreatobiliary junction and choledochal cysts produce the same histologic alterations of the biliary epithelium.

These facts raise a great amount of concern about late development of cancer after ES. Bergman et al in a small trial argues that after ES, the function of the biliary sphincter is permanently lost. On the other hand, Sugiyama et al demonstrated the reduction of pancreatobiliary reflux 1 year after ES. In addition, large population-based studies have shown no causal association between ES and cholangiocarcinoma, but with enough limitations in study design. In conclusion, the long term cytologic changes of the biliary epithelium after ES for benign disease are not well known.

During ERCP, brush cytology can be performed to evaluate bile duct strictures. The use of endoscopic brushing after ES has no reported complications .

Objective: To evaluate cytologic alterations of the biliary epithelium after previous endoscopic sphincterotomy for benign disease.

Informed consent will be obtained from all patients. ERCP will be conducted at the Endoscopic Unit of Aretaieion University Hospital and Tzaneio General Hospital, Athens, Greece. Pethidine, midazolam or propofol will be used for patient sedation. ERCP will be conducted with the use of a side viewing endoscope. After catheterization of the common bile duct through the previous sphincterotomy, cellular material will be obtained with the use of an endoscopic brush from the bile ducts. With the same way, brush cytology will be performed in the control group after performing ES.

Material obtained from each patient will be smeared on five glass slides. Four slides will be fixed with ethanol solution 95% and the fifth will be air dried. The brush will be fixed in suitable liquid for performing liquid phase cytology. Immunocytology with immunofluorescence p-53 antibody will be performed in samples with hyperplasia, dysplasia or atypia. The cytology department of Tzaneio Hospital will conduct examination and evaluation of all samples.

Samples based on their morphological characteristics will be classified in five categories: a. inadequate sample (very small cell number, presence of blood, inadequate fixation) b. negative for malignancy (adequate cell number with benign morphologic characteristics) c. reactive with or without atypia (cells with reactive/proliferative or inflammatory characteristics. Malignancy is rare but cannot be excluded) d. suspicious for malignancy e. positive for malignancy \[21,22\].

Examination and evaluation of the specimens will be done by two specialized cytologists, separately, in order to achieve more objective results.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Needle Knife Fistulotomy Versus Partial Ampullary Endoscopic Mucosal Resection for Difficult Biliary Cannulation	NCT05068739	Biliary Disease Common Bile Duc... Biliary Strictu... Malignant Hepat... Pancreatic Dise...	PA-EMR NKF	16 Years - 90 Years	Duzce University
Cytological Evaluation of Biliary Epithelium After Endoscopic Sphincterotomy	NCT01135732	Endoscopic Sphi... Cholangiocarcin...	brush cytology	18 Years -	University of Athens
Needle Knife Fistulotomy Versus Partial Ampullary Endoscopic Mucosal Resection for Difficult Biliary Cannulation	NCT05068739	Biliary Disease Common Bile Duc... Biliary Strictu... Malignant Hepat... Pancreatic Dise...	PA-EMR NKF	16 Years - 90 Years	Duzce University
Needle Knife Fistulotomy Versus Partial Ampullary Endoscopic Mucosal Resection for Difficult Biliary Cannulation	NCT05068739	Biliary Disease Common Bile Duc... Biliary Strictu... Malignant Hepat... Pancreatic Dise...	PA-EMR NKF	16 Years - 90 Years	Duzce University

Spots Global Cancer Trial Database for endoscopic sphincterotomy