Biliopancreatic endoscopy
prof. Marco Bruno – Gastro Update Europe 2019, Budapest

Developments in endoscopic ultrasound (EUS), biliopancreatic endoscopy and endoscopic complications were discus­sed. Microbial contamination of endoscopic equipment remains a major (unsolvable?) problem for the endoscopist. Over the past 17 years (y), 32 documented duodenoscope-related outbreaks with multi-drug resistant microorganisms, involv­­ing over 400 patients and lead­­ing to death in over 20 patients, have been reported. Endoscopic contamination and patient infection have also occur­red without breaches in the re-proces­s­­ing procedures. Scope contamination after a procedure is approx. 8– 10 log10; manual clean­­ing leads to a reduction with approx. 4– 6 log10 and further automated high level disinfection to another approx. 4– 6 log10 reduction. The total reduction amounts to approx. 8– 12 log10 lead­­ing to a low margin of safety of approx. 0– 2 log10. Sratches and shredd­­ing in bend­­ing sections and reman­­ing adherent debris interfere with the cleaning/ disinfection ef­ficacy. These results were again confirmed in a nation-wide duodenoscope culture study, show­­ing that 22% of the duodenoscopes were contaminated with one or more microorganisms with 20 or more colony form­­ing units and that 39% of the endoscopic retrograde cholangiopancreatography (ERCP) centers had at least one contaminated duodenoscope hang­­ing in the dryer cabinet. Contamination was not confined to a specific duodenoscope type but appeared related to the complex scope design and the inability to suf­ficiently clean all its intricate surfaces. A recent American Food and Drug Administration safety com­munication reads: „For high concern organisms, defined as organisms that are more often as­sociated with dis­ease, such as Escherichia coli and Pseudomonas aeruginosa, updated cultur­­ing results appear to show that up to 5.4% of properly col­lected samples test positive. Combined with strict adherence to the duodenoscope manufacturer’s reproces­s­­ing instructions, the fol­low­­ing supplemental measures may further help reduce the risk of infection transmis­sion as­sociated with the use of duodenoscopes: microbio­logical culturing; ethylene oxide sterilisation; use of a liquid chemical sterilant proces­s­­ing system; repeat high-level disinfection“. Perhaps the last recom­mendation is the most sensible and realistic or shall we be us­­ing only disposable (duodeno)endoscopes in the not-to-distant future?

In a previous large scale Dutch control­led trial, a minimal­ly invasive step-up approach was shown to be superior at a fol­low-up of 6 months (m), to primary open surgical necrosectomy in patients with (infected) necrotiz­­ing pancreatitis. The endpoint (mortality/ major complications) was respectively 40 vs. 69%. Recently, the late outcome after approx. 86 m was superior for the step-up ap­proach with significantly less new-onset multi-organ failure/ systemic complications, incisional hertnia and need for pancreatic enzyme ther­apy.

Lumen-appos­­ing metal stents are in­creasingly be­­ing used in the drainage of pancreatic wal­led-off necrosis instead of plastic pig-tail stents. A recent meta-analy­sis showed a comparable over­all clin­ical success rate of 88% with both modalities. Also the dif­ference in pooled adverse event rates of resp. 11 vs. 16% was not significant, leav­­ing the choice to the endoscopist’s preference. The over­all similar outcomes between expandable metal vs. pig-tail plastic was again shown in a British study with comparable technical and clinical success (above 90%), stent duration of an average 55 days and recur­rence rates of around 5– 6%. What was dif­ferent was the higher rate of bleeding, 15 vs. 3%, with about half the bleed­­ing in the metal stent cohort related to the development of a pseudo-aneurysm, neces­sitat­­ing vascular embolization. Other publications have drawn attention to this dreadful aneurysmal complication, caused by exces­sive pres­sure trauma of ves­sels in the wall of the necrotic cavity by the expandable metal stents. Patients should be prewarned of such potential complications.

Quite revolutionary is the rapidly spread­­ing experience with EUS-guided gastrointestinal con­nections mainly for pal­liation of malignant obstruction. In one such study, EUS-guided choledochoduodenostomy was car­ried out in 46 patients with inoperable malignant distal bile duct obstruction. Technical and clinical success was respectively 93 and 98%. Adverse events occur­red in 12% (stent food impaction, delayed bleed­­ing and stent migration). Reach­­ing the papil­la for ERCP can be chal­lenging, for example after gastric bypass surgery with Roux-en-Y anastomosis for ther­apy of morbid obesity. Reach­­ing the papil­la may be attempted with a bal­loon-fitted endoscope. Alternatively, the gastric pouch may be recon­nected transmu­ral­ly under EUS guidance. In a multicenter study, EUS-guided gastrogastrostomy was compared with endoscopy in 60 patients. Technical success by reach­­ing the papil­la was seen in 100 vs. 60% with a procedure duration of 50 min vs. 91 min, both in favor of the EUS-guided approach. Adverse ef­fects were comparable with 10 and 7%. Several comparable studies, evaluat­­ing the ef­ficacy of the EUS-guided transintestinal ap­proach have been published, all indicat­­ing comparable technical and clinical success rates and comparable and some­times even lower complication rates when compared to other modalities, such as percuteous transhepatic approches etc.

Also intrigu­­ing is the exploration of the usefulness of cholangioscopy now that the digital single-operator cholangioscope has become available. This technology was evaluated in a multicenter study with over 400 patients with dif­ficult biliary stones, defined as: > 15 m­m; > 3; intrahepatic/ cystic duct; and/ or –  impacted or –  as­sociated with anatomic duct abnormality. Complete bile duct clearance, either with electrohydrolic or laser lithotripsy was obtained in 97%, in 1 ses­sion in 77%. ERCP’s for additional ther­apy such as stent removal or stricture treatment was neces­sary in 34%. The most important factor as­sociated with technical failure was dif­ficult anatomy or dif­ficult can­nulation. More than one ses­sion was more often neces­sary in patients with prior failed ERCP or in case of a prolonged initial cholangioscopy ses­sion. Cur­rent guidelines suggest cholangioscopy-guided lithotripsy as an adjunct with or without bal­loon dilation or mechanical lithotipsy. Novel is the evaluation of direct cholangioscopy guided laser lithotripsy. Endoscopic stone clearance was obtained in respectively 93 and 67% of the 60 patients. Dilation of the papil­la was more often car­ried out in the conventional group and the procedure duration was substantial­ly longer in the cholangioscopy group. The conventional approach was less succes­sful in patients with prior ERCP attempt. The usefulness of cholangioscopy was also demonstrated for bio­psy target­­ing of suspicious lesions, yet distinguish­­ing between benign and malignant bile duct strictur­­ing lesions often remains chal­lenging. Whole exome and genome sequenc­­ing studies have defined the genetic landscape of neoplasms aris­­ing or secondarily involv­­ing the bile duct system. A 28-gene next-generation-sequenc­­ing panel (BiliSeq) was prospectively evaluated in 346 ERCP-obtained biliary specimens from 252 patients with bile duct strictures. The sensitivity and specificity of BiliSeq for malignant strictures was respectively 73 and 100%. In comparison, the sensitivity of elevated serum CA19-9 was 76% and of pathological evaluation 48%. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the pathological sensitivity for both biliary brushings and bio­psies. Among patients with primary scleros­­ing cholangitis, BiliSeq had a sensitivity of 83% compared to 8% or pathological examination. Interest­ingly, in 8% the genomic alterations were useful in guid­­ing ther­apy such as trastuzumab-based treatment for ERBB2-amplified cholangiocarcinoma. Beyond doubt, increasingly molecular-based investigations will be incorporated in dia­gnostic/ therapeutic endoscopy.

The explosive interest in pancreatic cysts has continued dur­­ing the past year. The over­all subtyp­­ing of cystic lesion is il­lustrated in the fig. 1.

Fine needle aspiration cytology was the standard technology when try­­ing to characterize the nature of the cystic lesion but attention is increasingly switch­­ing to the use of newly designed catheter-guided bio­psy needles. Novel is the development of catheter-guided microbio­psy forceps for targeted bio­psy of the cystic wal­l. In 28 patients the micro-bio­psy procedure was technical­ly succes­sful in 86%. Biop­sies were general­ly of good quality and contributed to the dia­gnosis in over 70%. Adverse events occur­red in 11%, usual­ly mild pancreatitis. Such results were confirmed in another cohort of 56 patients where the procedure was technical­ly succes­sful in al­l. Mild adverse events were seen in 16%, most com­monly intracystic bleeding. Specimens were considered adequate for histology in 84%, lead­­ing to an over­all dia­gnostic accuracy, combin­­ing histology and cytology of 84%. What the proper and cost-ef­fective indications will be for use of micro-bio­psy forceps equip­ment needs further larger scale detailed multicenter evaluation.

The Gastro Update Europe 2020 will be held on September 4–5, 2020 in Bratislava, Slovakia. For more information visit www.gastro-update-europe.eu.

Prof. Guido Tytgat, MD, PhD

Department of Gastroenterology andHepatology

Academic Medical Center

Meibergdreef 9

1105 AZ Amsterdam

The Netherlands

 g.n.tytgat@amc.uva.nl