Author Affiliations: Department of Endoscopy and Motility Unit, G. Gennimatas General Hospital (Katsinelos P, Chatzimavroudis G, Tziomalos K, Beltsis A, Lazaraki G and Terzoudis S), and 2nd Department of Internal Medicine (Zavos C and Kountouras J), School of Medicine, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

Corresponding Author: Panagiotis Katsinelos, MD, PhD, Department of Endoscopy and Motility Unit, G. Gennimatas General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54635, Greece (Tel: 0030-2310-963341; Fax: 0030-2310-963341; Email: gchatzimav@yahoo.gr)

 

© 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.

doi: 10.1016/S1499-3872(13)60063-6

 

 

Contributors: KP proposed the study. KP, ZC and LG performed research and wrote the first draft. CG, BA and TS collected and analyzed the data. TK and KJ were major contributors in revising the manuscript critically for important intellectual content. All authors contributed to the design and interpretation of the study and to further drafts. KP is the guarantor.

Funding: None.

Ethical approval: The research proposal was approved by the Institutional Review Board of Research and Ethics Committee of G. Gennimatas General Hospital (Thessaloniki, Greece).

Competing interest: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

 

 

BACKGROUND:It is unclear whether the presence of periampullary diverticula (PAD) affects technical success and complication rates during endoscopic retrograde cholangio-pancreatography (ERCP). Moreover, the impact of PAD on fluoroscopy duration is still unknown. The present study aimed to investigate the success rate and difficulty of common bile duct (CBD) cannulation, post-procedure complications and fluoroscopy duration in patients with and without PAD.

 

METHODS:Patients from January 2008 to December 2010 with PAD (group A) and without PAD (group B) and similar indications for therapeutic ERCP were prospectively compared. The comparison included patient characteristics, findings of ERCP, and details of procedure and fluoroscopy time. The influence of papilla's location with respect to the diverticulum on procedure was also investigated.

 

RESULTS:A total of 428 consecutive patients who had undergone therapeutic ERCP for similar indications were divided in two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. The mean age and ASA score of the patients with PAD were significantly higher than those patients without PAD. The main indication was choledocholithiasis. Successful final CBD cannulation was achieved in 97.20% of the patients in group A vs 99.69% in group B (P=0.05). CBD diameter, number of stones and the largest stone size were significantly higher in group A than group B (P<0.001). Complete clearance of the CBD after the first attempt was achieved in 85.86% and 94.75% of the patients in groups A and B, respectively (P=0.03). In both groups, the time needed to complete the procedure and fluoroscopy time was significantly longer in patients with PAD (22.87 vs 18.99 minutes, P<0.001; 76.51 vs 47.42 seconds, P<0.001). There was no significant difference between the two groups in the complication rate. The type of papilla's location with respect to the diverticulum did not influence the total cannulation rate and post-procedure complications.

 

CONCLUSION: The presence of a PAD does not affect the success rate and complications of therapeutic ERCP in expert hands; however, the fluoroscopy time is significantly longer in patients with PAD.

 

(Hepatobiliary Pancreat Dis Int 2013;12:408-414)

 

KEY WORDS: endoscopic retrograde cholangiopancreatography; anatomy; ampulla of Vater

Periampullary diverticula (PAD) are located within 2 cm from the major duodenal papilla. The majority of PAD is acquired. Their prevalence increases with age, as they are rarely seen before 40 years of age, and may be as high as 32% in the elderly.^[1-8] PAD discovered incidentally during endoscopic retrograde cholangiopancreatography (ERCP) are frequently asymptomatic, but may be a cause of considerable morbidity.^[9] Despite common belief that the presence of PAD makes the procedure technically difficult, and probably increases the risk of post-ERCP complications, the published studies^[1-7] demonstrate inconclusive results. In this regard, a technically difficult ERCP is related to prolonged fluoroscopy time and consequently increased radiation exposure of patients and staff.^[10-13] Cumulative high doses of ionizing radiation have a harmful effect on health;^[14-16] although several studies^[10-13] have investigated the factors that affect the fluoroscopy time during therapeutic ERCP, the influence of PAD and the location of the major papilla with respect to the diverticulum on fluoroscopy time is unknown. The present study was undertaken to investigate the impact of PAD and their type on technical success, rate of post-ERCP complications, and fluoroscopy time during the procedure.

 

 

This was a prospective observational study, conducted between January 2008 and December 2010, in a tertiary referral center of therapeutic endoscopy in Northern Greece. After completion of the study, each patient with PAD and naïve papilla was compared with those patients without PAD and naïve papilla, with a similar indication for ERCP. The comparison included patients' characteristics, findings of ERCP, and data for the procedure and fluoroscopy time. The research proposal was approved by the Institutional Review Board of Research and Ethics Committee of our hospital.

 

Patients undergoing therapeutic ERCP on an inpatient or outpatient basis were eligible for enrollment in the study. Exclusion criteria were: age under 18 years, pregnancy or breast feeding, previous endoscopic sphincterotomy (ES), upper gastrointestinal obstruction, Billroth II operation, ampullary cancer, severe hypoxemia with ventilation/perfusion imbalance, acute myocardial infarction within three months prior to the procedure, coagulopathy and platelet count less than 50×10⁹/L, and refusal to participate in the study. Patients were also excluded if their papilla was not detectable after a thorough examination of the second part of the duodenum.

 

Medical history was recorded in all patients, including the indications for ERCP, presence of concomitant diseases, medication and history of acute pancreatitis. Comprehensive physical examination was also performed and American Society of Anesthesiology (ASA) scores were recorded for all patients.^[17] Each patient or his/her relatives gave written informed consent after receiving verbal and written explanations about ERCP and possible post-procedure complications.

 

ERCPs were performed by an experienced pancreato-biliary endoscopist (Katsinelos P) using a standard therapeutic duodenoscope under conscious sedation with midazolam and pethidine. Hyoscine-n-butyl (Buscopan, Boehringer, Ingelheim Ltd., UK) or glucagon was administered as needed. Arterial oxygen saturation, heart rate and blood pressure were monitored using automated devices. For ductal opacification, 50% sodium meglumine amide triazoate diluted in distilled water was used. Pancreatograms were graded according to the extent of pancreatic opacification: the main pancreatic duct, first class branches, secondary branches or acinarization. The cannulation of the common bile duct (CBD) was first attempted using a sphincterotome (Clever-Cut, Olympus, Athens, Greece) and if this was not successful within 5 minutes, a hydrophilic guidewire (Jagwire, Microvasive, Athens, Greece) was used for 5 minutes or more. If both techniques failed, precut papillotomy was performed. ES was undertaken using a hydrophilic guidewire to enable controlled cutting and prevent the "zipper cut" phenomenon. It was performed using blended current (cut 45 W, coagulation 30 W) with an Olympus electrosurgical unit (PSD-30, Olympus, Athens, Greece). The length of ES was small in patients undergoing stent placement, and the largest was possible in patients with choledocholithiasis. In patients with non-removable large stones, the placement of a plastic stent was planned.

 

The following parameters were recorded: presence of PAD, location of papilla in relation to PAD, time to deep CBD cannulation, CBD diameter, type of precut papillotomy (conventional needle knife, suprapapillary fistulotomy, transpancreatic septotomy), extent of pancreatic opacification, size and number of CBD stones, performed treatment, total procedure time and fluoroscopy duration.

 

The CBD diameter was the measured maximal duct diameter within 2 cm from the papilla adjusted for radiographic magnification. The size of stones was measured after correction for the magnification by using the known diameter of the duodenoscope on the same radiograph as a reference. The total procedure time was recorded via screen recording time, from endoscope insertion until its withdrawal. Fluoroscopy time was recorded by a radiologist. The location of the papilla with respect to the diverticulum was recorded in all patients and was divided into the following three categories: type I: papilla located at the rim of the diverticulum (Fig. A); type II: papilla located within 2 cm from the diverticulum (Fig. B); and type III: intradiverticular papilla or papilla located between 2 adjacent diverticula (Fig. C).

 

Venous blood was drawn from each patient for serologic testing of amylase levels using an automated analyzer at baseline, 6 and 24 hours after the procedure. The definition of post-ERCP complications and the grading of their severity were based on consensus criteria.^[18]

 

After ERCP, all patients were monitored in the ward by the endoscopist to assess whether the patient could be discharged. Patients and their escorts were provided with detailed written advice regarding potential post-ERCP complications. The patients' family physicians and local hospitals were also notified and were advised to call the investigators if any complication occurred. When discharged, the patients were instructed to fast (water allowed) until the next morning. Clear liquids could then be consumed, followed by regular diet. Finally, the patients were evaluated at the outpatient clinic or were contacted by the phone call on days 1, 10 and 30 after ERCP, to assess the occurrence of late complications.

 

The primary endpoint of the study was to investigate the influence of PAD on technical success, rate of complications and fluoroscopy time in therapeutic ERCP. The secondary endpoint was the effect of papilla's type with respect to the diverticulum on these parameters.

 

Statistical analysis was made using the Statistical Package for Social Sciences (SPSS 13.0, Chicago, IL., USA). Categorical variables were analyzed with the Chi-square test and Fisher's exact test, as appropriate, while continuous variables were expressed as mean±SD and analyzed using Student's t test. The level of statistical significance was set at P<0.05.

 

 

A total of 483 consecutive patients who had undergone an ERCP in the period between January 2008 and December 2010 were included in the study. From these patients, 55 were excluded for the following reasons: undetectable papilla (18 patients), upper gastrointestinal obstruction (9), ampullary malignancy (7), previous ES (7), previous Billroth II operation (5), and refusal to participate in the study (9). Finally, 428 patients who had undergone therapeutic ERCP were divided into two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. Patients' characteristics and indications for ERCP are shown in Table 1. Patients with PAD (group A) were older (77.36 vs 68.06 years, P<0.001) and had a worse general condition. The main indication for therapeutic ERCP was choledocholithiasis in both groups, and there was no significant difference in history of cholecystectomy.

 

Technical characteristics of ERCP are shown in Table 2. There was no significant difference in final CBD cannulation rates (P=0.05), nor in the effort and difficulty in achieving CBD cannulation (as estimated by using different techniques to cannulate).

 

The results of endoscopic treatment according to the indications for ERCP in the two groups are shown in Table 3. Complete clearance of the CBD was achieved more easily in group B than in group A (P=0.003), and this difference remained with all the techniques used (basket/balloon, mechanical lithotripsy, mechanical lithotripsy plus stent, all P<0.05). In two patients (2.02%) of group A and five patients of group B (1.64%) with choledocholithiasis, plastic stents were placed because of inability to use mechanical lithotripsy due to the presence of very large CBD stones (P=0.902). The time needed to complete the procedure and fluoroscopy time were significantly longer in patients with PAD (P<0.001) (Table 3).

 

The rates of complications are not significantly different between the two groups (Table 4). Hemorrhage and post-ERCP pancreatitis were mild or moderate in all patients and they were treated conservatively. One patient in group A and two patients in group B presented basket impaction during extraction of CBD stones and were treated endoscopically.

 

The effect of papilla's location with respect to PAD on technical characteristics of ERCP and patients treatment is shown in Table 5. Type III was associated with statistically significant smaller CBD diameter and stones' size in relation to types I and II. The total procedure and fluoroscopy times were significantly shorter in type III than in types I and II. The rate of post-procedure complications was not different among the three types of papilla's location.

 

 

In the present study, no significant differences were observed in final CBD cannulation rate and use of different techniques to achieve CBD cannulation between patients with (97.20%) and those without PAD (99.69%). In previous studies, CBD cannulation could be achieved in only 61% of the patients with PAD.^[2-5] However, more recently, CBD cannulation rates as high as 95.4% have been reported.^{[1, 6-8]} These conflicting results might be partly due to differences in study design, study population, operator's experience and the use of new duodenoscopes, special accessories and techniques that facilitate CBD cannulation even in patients with a papilla within a PAD or a floppy papilla on the edge of a diverticulum. We also observed no difference with respect to post-procedure complication between patients with and those without PAD. Even though, some studies suggested that the presence of PAD is associated with increased risk for post-ES bleeding and perforation,^{[4, 7, 19]} and that the majority of existing data does not support this association.^{[1-3, 6, 8]}

 

Furthermore, the classification of PAD into three types in the present study showed no difference in final CBD cannulation rate, and different techniques to achieve CBD cannulation. A higher rate of post-ERCP pancreatitis and bleeding in type I papilla vs types II and III was observed even if it was not significantly different. A study^[1] showed that paradiverticular papilla (PAD types I or II) are usually easy to cannulate; however, when the papilla is located deep inside the diverticulum (PAD type III), often lying at the bottom, the cannulation used to be difficult,^[20] and one has to use techniques that may help in this situation,^[21] thus increasing the risk for complications. Interestingly, in our series it was in type I papilla not in type III, in which there was a trend to higher complication rate, although it was not statistically significant. It remains to be seen in future studies with large samples whether this observation was random. The procedure was performed by an experienced endoscopist; this explains excellent results despite anatomical difficulties posed by a papilla located inside or on the edge of a diverticulum, or between two diverticula. But this might not be the case in the hands of an endoscopist with less experience.

 

This study demonstrated an association of choledocholithiasis with PAD. The association of PAD with primary and recurrent choledocholithiasis before^[22,23] or after ES has been described.^{[24, 25]} Proposed theories included an increased bacterial load in the duodenum^[26] and bile duct^[27] with a subsequent increase in lithogenic b-glucuronidase activity,^[28] a decrease of biliary clearance,^[29] or a mechanical obstruction of the CBD.^[30,31] We also observed a significant association of PAD with larger CBD stones, a number of stones and CBD dilation on cholangiogram. Our findings are consistent with those of other studies^{[21, 23]} that enrolled patients for an ERCP as an indication for choledocholithiasis. In contrast, a study^[8] on patients undergoing ERCP for a wider range of indications showed that the presence of PAD was not associated with the higher incidence of larger stones or CBD dilation. We also found an association of type III PAD with smaller CBD diameter and stones' size. No altered CBD anatomy (angulations, strictures) was noted in these patients except for the mild dilation (10.3 mm), indicating smaller CBD stones in this subgroup of patients. Since the incidence of stone disease is similar to that reported, it is impossible to make any other comment since no information is available on the relation among CBD dilation, stone size and papilla location within or near the diverticula. However, a group of patients with the papilla located within the PAD had a lower occurrence of biliary tract stone diseases than the other two groups.^[32]

 

The present study revealed a higher rate of type I PAD (the papilla located at the rim of the diverticulum). The published data on the prevalence of papilla location with respect to PAD are contradictory. A prospective study^[8] in a Greek cohort reported that PAD was most commonly located within 2 cm from the papilla. However, another two studies^{[7, 32]} found that PAD was rarely located within 2 cm from the papilla. These studies reported a slightly higher incidence of PAD with the papilla.

 

In this series, we investigated their classification and their relationship to fluoroscopy time. An audit^[33] of radiation exposure to personnel performing ERCP found that both patients and staff are exposed to significant radiation. This was equivalent to an estimated additional lifetime fatal cancer risk of between 1 in 300 and 1 in 700. Radiation dose has a direct linear relationship with fluoroscopy time and is theoretically dependent on many factors including the type of procedure (diagnostic or therapeutic), the skills of the endoscopist, the presence of an altered upper gastrointestinal anatomy (i.e., Billroth II operation), stent insertion, lithotripsy, biopsies, use of a needle-knife, guidewire, additional wires other than a standard balloon catheter, and involvement of a gastroenterology fellow, thereby prolonging fluoroscopy duration.^{[9-13, 34]} We observed that the presence of a diverticulum was associated with a significant increase in fluoroscopy time because increased size and number of stones, use of mechanical lithotripsy and mechanical lithotripsy plus stent placement were encountered in patients with PAD to a significantly greater extent. Type I diverticulum was associated with longer fluoroscopy time than types II and III, and this finding could be explained by larger stone size and more frequent use of mechanical lithotripsy plus stent placement in patients with type I diverticulum.

 

Our study has shown the following advantages. Firstly, the cohort of patients is more homogenous than those in previous studies, who have similar indications for ERCP. Secondly, prospective design allows accurate recording of the procedure, fluoroscopy duration and post-ERCP complications. Thirdly, all procedures were performed by an experienced pancreatobiliary endoscopist in a single center, eliminating the procedure's factors influencing the procedure and fluoroscopy duration. The limitation of our study is that these excellent results must be viewed in context of a single endoscopist with a high degree of expertise and cannot be extrapolated to less-experienced endoscopists.

 

In conclusion, a periampullary diverticulum, inde-pendently of type, does not affect the success rate of therapeutic ERCP in expert hands; however, its presence, especially type I diverticulum, is associated with a higher radiation exposure.

 

 

1 Chang-Chien CS. Do juxtapapillary diverticula of the duodenum interfere with cannulation at endoscopic retrograde cholangiopancreatography? A prospective study. Gastrointest Endosc 1987;33:298-300. PMID: 3115861

2 Vaira D, Dowsett JF, Hatfield AR, Cairns SR, Polydorou AA, Cotton PB, et al. Is duodenal diverticulum a risk factor for sphincterotomy? Gut 1989;30:939-942. PMID: 2503431

3 Lobo DN, Balfour TW, Iftikhar SY. Periampullary diverticula: consequences of failed ERCP. Ann R Coll Surg Engl 1998;80:326-331. PMID: 9849331

4 Zoepf T, Zoepf DS, Arnold JC, Benz C, Riemann JF. The relationship between juxtapapillary duodenal diverticula and disorders of the biliopancreatic system: analysis of 350 patients. Gastrointest Endosc 2001;54:56-61. PMID: 11427842

5 Rajnakova A, Goh PM, Ngoi SS, Lim SG. ERCP in patients with periampullary diverticulum. Hepatogastroenterology 2003;50:625-628. PMID: 12828047

6 Tham TC, Kelly M. Association of periampullary duodenal diverticula with bile duct stones and with technical success of endoscopic retrograde cholangiopancreatography. Endoscopy 2004;36:1050-1053. PMID: 15578293

7 Boix J, Lorenzo-Zúñiga V, Añaños F, Domènech E, Morillas RM, Gassull MA. Impact of periampullary duodenal diverticula at endoscopic retrograde cholangiopancreatography: a proposed classification of periampullary duodenal diverticula. Surg Laparosc Endosc Percutan Tech 2006;16:208-211. PMID: 16921297

8 Panteris V, Vezakis A, Filippou G, Filippou D, Karamanolis D, Rizos S. Influence of juxtapapillary diverticula on the success or difficulty of cannulation and complication rate. Gastrointest Endosc 2008;68:903-910. PMID: 18635174

9 Tyagi P, Sharma P, Sharma BC, Puri AS. Periampullary diverticula and technical success of endoscopic retrograde cholangiopancreatography. Surg Endosc 2009;23:1342-1345. PMID: 18818967

10 Uradomo LT, Lustberg ME, Darwin PE. Effect of physician training on fluoroscopy time during ERCP. Dig Dis Sci 2006; 51:909-914. PMID: 16718536

11 Larkin CJ, Workman A, Wright RE, Tham TC. Radiation doses to patients during ERCP. Gastrointest Endosc 2001;53:161-164. PMID: 11174284

12 Buls N, Pages J, Mana F, Osteaux M. Patient and staff exposure during endoscopic retrograde cholangiopancreatography. Br J Radiol 2002;75:435-443. PMID: 12036837

13 Campbell N, Sparrow K, Fortier M, Ponich T. Practical radiation safety and protection for the endoscopist during ERCP. Gastrointest Endosc 2002;55:552-557. PMID: 11923771

14 Berrington de González A, Darby S. Risk of cancer from diagnostic X-rays: estimates for the UK and 14 other countries. Lancet 2004;363:345-351. PMID: 15070562

15 Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med 2007;357:2277-2284. PMID: 18046031

16 Colang JE, Killion JB, Vano E. Patient dose from CT: a literature review. Radiol Technol 2007;79:17-26. PMID: 17848530

17 American Society of Anesthesiologists. ASA Relative Value Guide 2002. Code 99140. Park Ridge, IL: ASA; 2002: xii.

18 Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-393. PMID: 2070995

19 Chapman RW. Complications of ERCP. In: Green J. Guidelines on complications of gastrointestinal endoscopy. London: British Society of Gastroenterology;2006:20-25.

20 Shemesh E, Klein E, Czerniak A, Coret A, Bat L. Endoscopic sphincterotomy in patients with gallbladder in situ: the influence of periampullary duodenal diverticula. Surgery 1990;107:163-166. PMID: 2099745

21 Sherman S, Hawes RH, Lehman GA. A new approach to performing endoscopic sphincterotomy in the setting of a juxtapapillary duodenal diverticulum. Gastrointest Endosc 1991;37:353-355. PMID: 1906414

22 Chandy G, Hart WJ, Roberts-Thomson IC. An analysis of the relationship between bile duct stones and periampullary duodenal diverticula. J Gastroenterol Hepatol 1997;12:29-33. PMID: 9076619

23 Christoforidis E, Goulimaris I, Kanellos I, Tsalis K, Dadoukis I. The role of juxtapapillary duodenal diverticula in biliary stone disease. Gastrointest Endosc 2002;55:543-547. PMID: 11923769

24 Cheon YK, Lehman GA. Identification of risk factors for stone recurrence after endoscopic treatment of bile duct stones. Eur J Gastroenterol Hepatol 2006;18:461-464. PMID: 16607138

25 Kim DI, Kim MH, Lee SK, Seo DW, Choi WB, Lee SS, et al. Risk factors for recurrence of primary bile duct stones after endoscopic biliary sphincterotomy. Gastrointest Endosc 2001;54:42-48. PMID: 11427840

26 Skar V, Skar AG, Osnes M. The duodenal bacterial flora in the region of papilla of Vater in patients with and without duodenal diverticula. Scand J Gastroenterol 1989;24:649-656. PMID: 2510248

27 Sandstad O, Osnes T, Skar V, Urdal P, Osnes M. Structure and composition of common bile duct stones in relation to duodenal diverticula, gastric resection, cholecystectomy and infection. Digestion 2000;61:181-188. PMID: 10773723

28 Skar V, Skar AG, Bratlie J, Osnes M. Beta-glucuronidase activity in the bile of gallstone patients both with and without duodenal diverticula. Scand J Gastroenterol 1989;24:205-212. PMID: 2494696

29 Tzeng JJ, Lai KH, Peng NJ, Lo GH, Lin CK, Chan HH, et al. Influence of juxtapapillary diverticulum on hepatic clearance in patients after endoscopic sphincterotomy. J Gastroenterol Hepatol 2005;20:772-776. PMID: 15853993

30 san Román AL, Moreira VF, García M, Merono E, Boixeda D. Direct compression by a duodenal diverticulum causing common bile duct obstruction. Endoscopy 1994;26:334. PMID: 8076563

31 van der Linde K, van der Linden GH, Beukers R, Cleophas TA. Food impaction in a duodenal diverticulum as an unusual cause of biliary obstruction: case reports and review of the literature. Eur J Gastroenterol Hepatol 1997;9:635-639. PMID: 9222744

32 Yildirgan MI, Ba?o?lu M, Yilmaz I, Atamanalp SS, Balik AA, Aydinli B, et al. Periampullary diverticula causing pancreaticobiliary disease. Dig Dis Sci 2004;49:1943-1945. PMID: 15628730

33 Naidu LS, Singhal S, Preece DE, Vohrah A, Loft DE. Radiation exposure to personnel performing endoscopic retrograde cholangiopancreatography. Postgrad Med J 2005;81:660-662. PMID: 16210465

34 Kim E, McLoughlin M, Lam EC, Amar J, Byrne M, Telford J, et al. Prospective analysis of fluoroscopy duration during ERCP: critical determinants. Gastrointest Endosc 2010;72: 50-57. PMID: 20620272