Impact of the shape of the ampulla of Vater and biliary tree pathology on access technique and post-ERCP complications

Impact of the shape of the ampulla of Vater and biliary tree pathology on access technique and post-ERCP complications | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of the shape of the ampulla of Vater and biliary tree pathology on access technique and post-ERCP complications Jamry Andrzej This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4370114/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and aim: Difficulties and complications during endoscopic retrograde cholangiopancreatography (ERCP) can depend on the anatomy of the papillae, the pathology of the biliary tree, and proper selection of the endoscopic technique. However, knowledge about these relationships is limited. Methods: This single-center retrospective study included 1002 patients who underwent ERCP. The analyses included the impact of the existing anatomy (shape of the papillae [modified Haraldsson classification], periampullary diverticulum [PAD], common bile duct [CBD] diameter ≤9 mm, outflow obstruction level and choledocholithiasis]) on cannulation difficulty, access technique (classic sphincterotomy [CS], classic precut [CPC], needle precut [NPC], two-step access, unintended Wirsung duct cannulation) and complications (bleeding, hyperamylasemia, pancreatic pain and postendoscopic pancreatitis [PEP]). Results: According to the modified Haraldsson classification,47.4% of the papillae were type 1, 31.3% were type 2; 11.1% were type 3, and 10.2% were type 4. Cannulation was considered difficult in 56.9% (58/102; p=0.0014) of type 4 papillae and 46.4% (162/349; p= 0.001) and 49.5% (46/93; p=0.039) of patients with distal and medial CBD obstruction, respectively. CPC was used for 42.2% (43/102; p=0.017) of patients with type 4 papillae. NPC was used 38.7% (43/111; p<0.0001) of patients with type 3 papillae, and 26.0% (34/131; p=0.008) of patients with a CBD diameter ≤9 mm. Two-step access was used for 28.4% (29/102; p<0.0001) of type 4 papilla patients, 17.8% (53/315; (p= 0.002)) of type 2 papilla patients and 18.9% (66/349; p=0.002)of patients with distal CBD obstruction. Bleeding occurred for 21.9% (104/475; p=0.003) of type 1papilla patients. A total of 19.0% (85/448,p<0.0001) of patients with CBD diameters ≤9 mm had hyperamylasemia; 6.2% (28/449,p=0.025); had pancreatic pain and 4% (18/449; p=0.021)had PEP . Conclusion: The existing anatomy of the papillae and biliary tree affected the difficulty of cannulation, the selection of access technique, and the occurrence of side effects. Gastroenterology & Hepatology Endoscopic sphincterotomy Ampulla of Vater Common bile duct Risk factors Cannulation Complication. Introduction and Background During endoscopic retrograde cholangiopancreatography (ERCP), obtaining access to the biliary tree (via cannulation and sphincterotomy) is part of the procedure and can lead to complications such as postendoscopic pancreatitis (PEP), bleeding and perforation. Difficulties in this stage can depend not only on the anatomy of the papillae of Vater but also on the distal common bile duct (CBD) diameter, presence of periampullary diverticula (PADs) and biliary tree outflow obstruction level. Additionally, there are many different access techniques available (guidewire, precut classic, transpancreatic, precut needle, two-step access and many others), but knowledge about which is most appropriate for the anatomy of the patient is limited. Additionally, previous analyses did not included the existence of a diverticulum or pathology in the biliary tree itself [1-4 [5][6.][7]. Therefore, the purpose of this study was to analyze the relationships between the anatomy of Vaterian papillae, biliary tree pathology and access technique (classic sphincterotomy [CS], classic precut [CPC], needle precut [NPC], two-step access, and unintended Wirsung duct cannulation) and potential complications (bleeding during ERCP, blood and urine hyperamylasemia 4 hours after the procedure, pancreatic pain and PEP). Knowledge about these relationships can help create recommendations for choosing the ideal access technique, reduce the risk of complications and facilitate the learning process for ERCP. Ethical approval was issued and is formulated as the Ethics Committee at the Swietokrzyska Medical Chamber No. Ldz.SIL.KB/B.3/2024 Methods Data collection and patient population: This single-center study included 1002 consecutive (years 2010-2014, mean age 67 years, 61.6% (616) women) patients with naive Vaterian papillae for whom therapeutic ERCP was performed. The exclusion criteria were a previous papilla endoscopic or surgical procedure performed before ERCP and acute pancreatitis. The data were collected from the Endobase-Endoscopic Database and Oracle-Hospital Medical Database as well as from other hospitals. The patients were analyzed in terms of the following factors. Anatomy: The analyzed anatomical features included papilla shape, the existence of PAD and pathology in the biliary duct. To assess the shape of the Vaterian papillae, we used a modified Haraldsson classification system[1,2]. Initially, patients with neoplastic deformed papillae were excluded (approximately 10% of patients who undergo ERCP in everyday practice). Therefore, we modified Haraldson's classifications partly based on the study of the Human Anatomy Teaching Group from Cambridge.[8]. Finally, group 2 included patients with both small (Haraldson group 2) and rigid (Haraldson group 4) papillae. However, group 4 included patients with deformed/infiltrated papillae regardless of etiology (neoplastic or chronic pancreatitis). Finally, papillae were classified according to shape as type 1 (regular), type 2 (small and rigid), type 3 (protruding or pendulous), or type 4 (deformed papillae) as a result of infiltration. Additionally, other factors that can impact the access process, such as the presence of PAD, CBD diameter ≤9 mm (measured from X-ray images at a distance of 2.0 cm from the ampulla of Vater), outflow obstruction level based on imaging examinations preceding the procedure (distal, medial, hilum) and choledocholithiasis, were analyzed. Access technique: A classic sphincterotome with a guide wire was routinely used. Difficult cannulation was defined according to the 5-5-2 criteria: more than 5 contacts with the papilla, more than 5 minutes of cannulation and more than two unintended pancreatic duct cannulations [10]. In addition, if a guidewire passed into the pancreatic duct or underwent opacification, prophylactic pancreatic stenting was routinely performed. After more than 5 minutes of ineffective cannulation, we performed precut sphincterotomy via either the classic (CPC) or needle knife (NPC) approach. Two-stage access was defined as no catheterization of the target duct within approximately 20 minutes, despite the precut incision being performed, and the postponement of subsequent attempts for 4-5 days (until tissue edema subsides). Adverse events: Bleeding during ERCP was classified as the presence of bloody discharge after ES that impeded further cannulation and required additional endoscopic procedures to stop. Abdominal pain suggestive of pancreatitis was defined according to the revised Atlanta Classification [3]. PEP was defined as new or worsened abdominal pain combined with > 3 times the normal value of amylase or lipase at more than 24 hours after ERCP and a requirement for admission or the prolongation of a planned admission [4]. Statistical analysis: Quantitative variables are expressed herein as the mean and standard deviation. Categorical variables are presented as numbers and percentages. The normality of the data distribution was tested with the Kolmogorov‒Smirnov test. The χ2 test was used to test the interdependence of pairs of variables for double classifications. Univariate and multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% CIs and P values. In the case of multivariable models, the FORWARD (entering significant variables sequentially) and BACKWARD (first entering all variables into the model and subsequently removing the nonsignificant variables sequentially) options were used.A P value less than 0.05 was considered to indicate statistical significance. Statistical analysis was performed using Med-Calc Statistical Software 20, version 19.7. Results I. Grouping of patient characteristics: To determine the relationship between the anatomy of the biliary tract, the use of a particular access technique and possible complications, a group of 1002 patients was analyzed. The mean age was 67 years, and 61.5% (616) were female. Therefore, factors other than the appearance of the papillae themselves were also analyzed. According to the modified Haraldson classification, 474% of patients (475/1002) had type 1 papillae, 31.3% (314/1001) had type 2 papillae, 11.1% (111/1002) had type 3 papillae, and 10.2% (102/1002) had type 4 papillae. A total of 20.4% (204/1002) patients had a periampullary diverticulum (PAD). A total of 35.2% (349/1002) of patients had obstructions in the distal CBD, and 9.4% (93/1002) had obstructions in the middle part of the CBD (Table I). II. Access technique: 1. Difficult cannulation: Defining the factors influencing the difficulty in accessing the duct, which is the target of the therapeutic procedure, may enable the selection of an appropriate operator (in terms of experience) before starting any interventional endoscopic procedures. In the present study, difficult cannulation was observed in 56.9% (58/102; p=0.002) of patients with deformed (type 4) Vaterian papillae, 46.4% (162/349; p=0.001) of patients with distal CBD strictures and 49.5% (46/93; p=0.04) of patients with medial CBD strictures. In contrast, easier access was found in 34.3% (163/475; p=0.001) of patients with classic (type 1) Vaterian papillae, 31.7% (145/458; p≤0.0001) of patients with choledocholithiasis and in 29.4% (60/204; p= 0.001) of patients with PAD (Table II). 2. Endoscopic sphincterotomy (ES) technique: Knowledge about which type of sphincterotomy is most likely to provide access (depending on the existing anatomy) can improve recommendations for the procedure. Therefore, we analyzed the relationships between the existing anatomy and the type of sphincterotomy performed. Classic sphincterotomy (CS) was performed significantly more often in patients with type 1 Vaterian papillae (47.4%; 259/475; p=0.015), with PAD (54.4%; 117/204; p=0.028), or with choledocholithiasis (54.1%; 248/458; p=0.034). CPC was performed more frequently in patients with deformed (type 4) papillae (42.2%; 43/102; p=0.018). In addition, NPC was used more frequently for protruding (type 3) Vaterian papillae (38.7%; 43/111; p<0,0001) and for a CBD diameter ≤9 mm (26,0%, 34/131; p=0,008) but was chosen significantly less often for patients with PAD (9.3%; 29/204; p=0,0004). (Table III) 3. Two-step access: Despite the use of precut sphincterotomy, access to the target duct may still be impossible, and the risk of PEP and false pathway creation may increase, leading to a false diagnosis. In this situation, two-step access should be considered. In the present study, two-step access was implemented significantly more frequently for patients with deformed (type 4) papillae (28.4%; 29/102; OR 2.74; p<0.0001), small (type 2) papillae (17.8%; 56/315; p= 0.032) and distal outflow obstruction (18.9%; 66/349; p=0.002; Table IV). III. Adverse events: Assessing the relationship between the existing anatomy and the occurrence of complications during and after ERCP may enable the selection of the access technique with the lowest risk of complications (for example, Wirsung duct stenting) and the endoscopist with the most appropriate level of experience. Bleeding during ES was significantly more frequent in patients with classic (type 1) Vaterian papillae (21.9%; 104/475; p=0.003). In contrast, this complication was significantly less common in patients with small (type 2) papillae (12.7%; 40/315; p=0.003) and a CBD diameter ≤ 9 mm (13.4%; 60/449; p=0.0006). Hyperamylasemia 4 hours after ERCP was significantly more common in patients with a distal CBD diameter ≤9 mm (19.0%; 85/448; OR 2.6, p<0.0001). Pancreatic pain and PEP were observed more frequently in patients with a CDB diameter ≤ 9 mm (6.2%; 28/449; p=0.027 and 4.0%; 18/449; p=0.021, respectively) (Table V). Discussion The impact of the anatomy and pathology of Vaterian papillae and biliary tree pathology on the choice of access technique (cannulation difficulties, sphincterotomy technique, two-step access) and adverse events has not been fully explained. Few studies have examined all of these factors together [12]; most analyses have focused only on the relationship between papilla shape and cannulation difficulty and excluded deformed papillae, altered CBD anatomy and PADs[1,2,6,9,16,17,18], while other authors only examined access techniques without considering anatomy [5,7,9]. Therefore, in our study, we additionally included infiltrated ampullae of Vater (according to a modification of Haraldson's classification), the extent of biliary tree obstruction and the presence of PADs. This approach can improve the understanding of the relationship between difficulties during access and other factors, not only the shape of the papillae. Knowledge regarding this subject is important because it can facilitate the training process, enable proper selection of endoscopists (according to their level of experience) and ensure that the access technique (depending on the papilla shape and biliary tree pathology) has the lowest risk of complications. Difficult cannulation: Our results confirmed that the degree of difficulty during cannulation depends not only on the shape of the papillae but also on the level of bile outflow blockade. Taking other factors into account answers the question posted by Sinha as to why flat papillae were difficult to cannulate in Haraldson's studies [2,8]. According to the results of this study, cannulation was difficult in 56.9% (58/102) p=0.0002, of patients with deformed (type 4) papillae, 46.4%(162/349; p=0.0011 of patients with distal biliary tree flow obstruction and 49.5% (46/93)(p= 0.0407 of patients with medial biliary tree outflow obstruction. Therefore, it should be recommended that procedures in these patients be performed by experienced endoscopist In contrast, for patients with a low risk of cannulation difficulty, such as those with classic (type 1) papillae (34.3%; 163/475) (p=0.0014), choledocholithiasis (31.7%; 145/458) (p<0.0001), and perhaps even PAD (29.4%; 60/204) (p=0.001), this issue requires more detailed analysis; it may be possible for endoscopists to treat these patients during the learning process under supervision. Due to the lack of a uniform classification system for determining the shape of papillae and differences in the frequency of use of guidewires for various kinds of sphincterotomy and two-step access, comparing the obtained results with those of other studies is challenging. For example, apart from Haraldson, his classification system has been used only for analysis by Chen, Estela and Balan [6,11,12]. In a multicenter analysis, Haraldsson's team enrolled 1401 patients and reported that cannulation was more difficult in patients with small (type 2) papillae (52%; 95% CI, 45%-59%) and protruding (type 3) papillae (48%; 95% CI, 42%-53%) than in those with classic (type 1) papillae [2]. Chen analyzed 286 patients and obtained similar results. Small (type 2) papillae (OR 7.18, p = 0.045) and protruding (type 3) papillae (OR 7.44, p = 0.016) were more difficult to cannulate than classic (type 1) papillae [11]. A similar conclusion was reached by Balan, who showed that significantly more cannulation attempts (mean value of 5.5 attempts, p = 0.00108) and more time (mean value of 5.6 minutes, p = 0.00181) were needed for patients with small (type 2) papillae [12]. In the present study, these relationships were not significant (40.3%; 127/315; p= 0.73; OR 1.05; p=0.73); however, two-step access was used significantly more frequently for patients with small (type 2) papillae (17.8%; 56/315; p= 0.032; OR 1.49; p=0.032). Indirectly, these findings suggest difficulties in deep cannulation of the target duct in this group of patients. However, it should be emphasized that comparing these data with those of other studies is problematic because of the different definitions of type 2 papillae and leakage of the distal CBD with an altered anatomy. Other factors that may explain these differences are the frequency with which a guidewire was used and the use of different precut incision techniques. The Haraldson group used guidewires in approximately 50% of patients; classic access was impossible, and the precut technique was used in only 9% of patients [2]. In contrast, we used guidewires in more than 90% of patients, NPCs in 38.7%(43/111) p<0,0001 (OR 3.54 p <0.0001) of patients with protruded (type 3) papillae and CPC in 42.2%(43/102) p=0,017 (OR 1,65 p = 0,0183) of patients with deformed (type 4) papillae. Other results were published by Estela, who, in the analyzed group (230 patients), difficult cannulization was more common in type 3 (3.66%, 95% CI 2.49-5.84), type 4 (3.21%, 95% CI 1.82-5.75), and type 2 (1.95%, 95% CI 1.15-3.20) patients than in type 1 patients. These results are partially consistent with ours, but we did not confirm any difficulties during cannulation of type 2 papillae [6]. The differences may result from differences in the classification and access technique used. The next factor that could explain the differences was the exclusion criteria. Haraldsson, Chang, Balan and Estella excluded patients with tumors or other causes of deformity of the papillary region (meaning that approximately 10% of patients treated daily by ERCP were excluded). [2,6,11,12] In our study, according to the modified Haraldson classification, all patients with deformed papillae were classified as having type 4 papillae. In our series, this group had the highest probability of experiencing a difficult cannulation (56.9%; 58/102; p=0.0002; OR 2.19, p=0.0002). Most of our patients in group 4 had cancer-related deformed papillae. In this way, a similar result was presented by Chen, who reported that the presence of neoplasia was related to difficulty in cannulation (OR 4,45 p=0,014) [11]. Additionally, Chen reported that type 1 papillae required significantly less time for cannulation (56.78% of the patients could be cannulated within 5 minutes) and had the lowest cannulation failure rate (1.69%) 1,55 (1,19-2,02) [11]. Similarly, our study revealed that the risk of cannulation difficulties in patients with type 1 papillae was significantly lower (34.3%; 163/475; p= 0.0014; OR= 0.66; p= 0.0014). However, differences from Chen’s research exist in terms of PEP risk factors. We did not find a relationship between papilla shape and the risk of PEP. In contrast, Chen reported that type 2 papillae were correlated with a greater percentage of PEP (20%, p = 0.020). This difference may be due to Chen’s application of endoscopic papilla balloon dilatation (OR for PEP 4,51) [13], whereas we used two-stage access in 17.8% (56/315; p=0.032; OR 1.49; p= 0.032) of patients with type 2 papillae, which can reduce the risk of PEP. These results may justify the early use of a two-stage procedure in patients with type 2 or 4 papillae. The next factor analyzed was the presence of PADs, which may increase the risk of difficulties and complications [11,14]. However, the presence of a weak point in the duodenal wall can also facilitate access to the biliary duct. This relationship was also found in the present study, which showed that the presence of PADs made cannulation easier in 29.4% (60/204) of patients (p= 0.001; OR=0.57, p=0.01). Interesting data in this regard were presented by Mu in a meta-analysis [15]. In previous studies, the presence of a PAD was related to difficult cannulation (RR=1.46, 95% CI=1.27-1.67; p<.00001); however, within the last 20 years, these relationships were not statistically significant (RR=1.16, 95% CI=0.96-1.41; p=0.12). This is probably a consequence of the development of equipment and cannulation techniques. Additionally, in Mu’s study, PAD was also associated with a high risk of PEP (RR=1.32, 95% CI=1.10-1.59; p=0.003), perforation (RR=1.73, 95% CI=1.06-2.82; p=0.030), and bleeding (RR=1.48, 95% CI=1.13-1.93; p=0.005) [15]. We did not observe this relationship, and these differences are likely a consequence of the authors’ significantly less frequent use of NPC (9.3%; 19/204; p=0.0004; OR=0.41; p=0.0006) in PAD patients. Many other classifications of Vaterian papillae have been created but do not include patients with PADs; therefore, it is impossible to compare these results with those of other studies [16,17,18,19]. Access technique: We confirmed that the type of papillae, presence of PAD and biliary tree pathology have an impact on the technique chosen for performing sphincterotomy. CS was possible significantly more frequently in patients with type 1 papillae (47.4%; (259/475; p= 0.0155; OR 1.36; p= 0.0156); in patients with PAD (54.4%; (117/204); p=0.028; OR 1.41; p=0.028); and in patients with choledocholithiasis (54.1%; (248/458); p=0.0341; OR 1.31; p=0.0341). CPC was chosen significantly more often in patients with type 4 papillae (42,2%; 43/102; p= 0.0171; OR 1.65; p=0.0183), and NPC was chosen more often in patients with type 3 papillae (38.7%; 43/111; p<0.0001; OR 3.54; p<0.0001). Only two studies have analyzed the sphincterotomy technique chosen in relation to papilla shape; unfortunately, other papilla shape classifications were used in these studies [16,20]. The Canena (2021) classification includes 7 types: type 1 (flat), type 2A (prominent with 2 folds), type 2C (bulging), type 3A (interdiverticular), type 3B (diverticular border type), and type 4 (unclassified). The authors analyzed 361 patients who underwent only needle knife fistulotomy (NKF). According to multivariate analysis, flat (type 1) and prominent (< 1-fold) (2B) papillae were risk factors for difficult cannulation, and types 2B, 3A and 3B were associated with the lowest cannulation rates post-NKF [16]. In our study, the preferred technique for all patients with PAD was CS (54.4%; 117/204;p=0.028; OR 1.41; p=0.029), and we used NPC significantly less often (9.3%; 19/204; p=0,004;OR 0.41;, p=0.0006). In contrast, in Canena’s study, NKF was used significantly more often for type 2c papillae (similar to type 3 in Haraldsson’s classification). This finding is consistent with our results, as we used NPC significantly more often in patients with type 3 papillae (38.7%; 43/111; OR 3.54; p< 0.0001). A study conducted by Horiuchi in 2007 analyzed 86 patients. The effectiveness of the three-type precut technique on the basis of papilla shape was assessed: for small (Haraldsson type 2)- trans pancreatic (CPC),for large (Haraldsson type 1) - needle knife precut (NKP) , and for swollen (Haraldsson type 3) needle knife fistulotomy (NKF) . Successful access to the biliary tree was achieved in 96%, 90%, and 100% of patients, respectively. The overall complication rate was 4.7% (4 of 86) (2 patients with mild bleeding and 2 with mild pancreatitis) [20]. These criteria for choosing the ES technique agree with our own technique for swollen (Haraldson type 3) papillae, for which the most common technique was NPC (38.7%; 43/111; p<0,001; OR 3.54; p< 0.0001). In contrast, for the small papillae (Haraldson type 2) in our study, the CPC technique for sphincterotomy was used significantly less often (27.0%; 85/315; OR=0.72; p = 0.0287). The above comparison highlights the lack of uniform rules for the use of various access techniques according to the existing anatomy; therefore, to reach a consensus, this issue requires further research. The limitations of the present study include its single-center nature and the fact that the analyzed procedures were performed by one operator. Therefore, there is a risk of bias in the technique of assessing the shape of the papillae and the selection of access techniques. Another limitation was the low number of participants in each group (with different anatomies of the bile ducts) after division according to the access technique used. The existing number of patients made it impossible to perform a statistical analysis of the relationships between the detailed anatomy and access technique used and side effects. Conclusions The results revealed a relationship between the anatomy of the papillae and bile ducts, the access technique selected and the occurrence of side effects. This knowledge may facilitate the training process by helping endoscopists assess the degree of difficulty of the procedure and the risk of complications based on the appearance of the papillae and the level of biliary outflow obstruction in imaging tests. This approach will make it possible to determine whether the procedure can be safely performed by an endoscopist during training or whether it requires the intervention of an expert. Additionally, if other studies confirm the existence of a relationship between the anatomy and the access technique used (type of sphincterotomy and need to implement a two-stage procedure), recommendations in this area can be created. The results obtained in this study justify the consideration of multicenter studies defining the access technique (such as the rules for using a guidewire, CPC, NPC, protective PD stenting or two-step access) and covering a larger group of patients, which would enable a more detailed analysis of complications in each group of patients treated through different access techniques depending on the existing anatomy. References Haraldsson E, Lundell L, Swahn F, et al. Endoscopic classification of the papilla of Vater. Results of an inter- and interobserver agreement study. United European Gastroenterology Journal 2017, Vol. 5(4) 504–510 PMID: 28588881; DOI: 10.1177/2050640616674837 Haraldsson E, Kylänpää L, Grönroos J, et al. 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PMID: 32586551 DOI: 10.1016/j.gie.2020.02.005 Adler, D.G. ERCP biliary cannulation difficulty as a function of papillary subtypes: A tale of shapes and Shar-Pei dogs. Gastrointest. Endosc. 2019, 90, 964–965 PMID: 31759420 DOI: 10.1016/j.gie.2019.07.030 Testoni A, Mariani A, Aabakken L,et all. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline , Endoscopy 2016 Jul;48(7):657-83. PMID: 27299638 DOI: 10.1055/s-0042-108641 Chen Q,Li Z, Li S. et al.. Diagnosis and treatment of juxta-ampullary duodenal diverticulum Clin Invest Med. 2010 Oct 1;33(5):E298-303. PMID: 20926036 DOI: 10.25011/cim.v33i5.14355 Balan G, Arya M, Catinean A, Sandru V et al.. Anatomy of Major Duodenal Papilla Influences ERCP Outcomes and Complication Rates: A Single Center Prospective Study J. Clin. Med. 2020, 9, 1637; PMID: 32481755 DOI: 10.3390/jcm9061637 Chandrasekhara, V.; Khashab, M.A.; Muthusamy, V.R,et al. Adverse events associated with ERCP. Gastrointest. Endosc. 2017, 85, 32–47. PMID: 27546389 DOI: 10.1016/j.gie.2016.06.051 AvisseC, Flament J, Delattre J ,,Ampulla of Vater. Anatomic, embryologic, and surgical aspects,, Surg Clin North Am 2000 Feb;80(1):201-12. PMID: 10685149 DOI: 10.1016/s0039-6109(05)70402-3 Mu P, Yue P, Li F, et al. Does periampullary diverticulum affect ERCP cannulation and postprocedure complications? an up-to-date meta-analysis. Turk J Gastroenterol 2020; 31(3): 193-204. PMID: 32343231 DOI: 10.5152/tjg.2020.19058 Canena J, Lopes L, Fernandes J et al.. Influence of a novel classification of the papilla of Vater on the outcome of needle-knife fistulotomy for biliary cannulation BMC Gastroenterol (2021) 21:147 PMID: 33794778 DOI: 10.1186/s12876-021-01735-3 MohamedR , LethebeC, Gonzalez-MorenoE et al.. Morphology of the major papilla predicts ERCP procedural outcomes and adverse events Surg Endosc 2020 Nov 4. PMID: 33146812 DOI: 10.1007/s00464-020-08136-9 WangX, ZhaoJ, WangL et al.. Relationship between papilla-related variables and post endoscopic retrograde cholangiopancreatography pancreatitis: A multicenter, prospective study J Gastroenterol Hepatol 2020 Jun 8. PMID: 32511794 DOI: 10.1111/jgh.15135 Watanabe M, Okuwaki K, Kida M. et al.. Transpapillary biliary cannulation is difficult in cases with large oral protrusion of the duodenal papilla. Digestive Diseases and Sciences (2019) 64:2291–229 PMID: 30746630 DOI: 10.1007/s10620-019-05510-z Horiuchi A, Najayama Y, Kajjyama M ,Tanaka N .Effect of Precut Sphincterotomy on Biliary Cannulation Based on the Characteristics of the Major Duodenal Papilla Clinical Gastreoenterology and Hepatology 2007;5:1113–1118 PMID: 17689295 DOI: 10.1016/j.cgh.2007.05.014 Next recommended study: 1. A more detailed description of the step-by-step access technique (classic caniulotomy, short- versus long-nose needle, guidewires, and protective PD stenting or two-step access) is needed. 2. A larger group of patients may allow a statistical analysis of side effects depending on the papillary shape, biliary pathology and access technique. Tables Tables 1 to 5 are available in the Supplementary Files section Additional Declarations The authors declare no competing interests. Supplementary Files JamryTable.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4370114","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298789616,"identity":"a491ce5f-82f0-4990-b9ea-b9e2f1f1d7bc","order_by":0,"name":"Jamry Andrzej","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAqklEQVRIiWNgGAWjYBACxgYQWcEgA+Y9IF7LGQMeMC+BeKvaSNHC3H467TPvvD88/NINbA+I0sLYk7t5Nu82Ax7JOQfYDYjT0pC7mRmkxeBGApsEcVr63wK1zDHgsSdeywyQLQ1AWySI1/J2M+OcY8Y8EjcS24nzi2F/7maGNzVycvwzko89+ECUlgYGBiZIpDC2EaOBgUEepPYHhM1GnJZRMApGwSgYcQAACRktsr/ZyU4AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-7015-2462","institution":"Distrcit Hospital Starachowice Surg Dep.","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jamry","middleName":"","lastName":"Andrzej","suffix":""}],"badges":[],"createdAt":"2024-05-05 03:09:19","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-4370114/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4370114/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":56836099,"identity":"83a9be8d-8358-495f-a291-bfe79d6b2b22","added_by":"auto","created_at":"2024-05-21 05:59:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":224009,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4370114/v1/8691fbab-6be0-4181-9dc4-9ba2f4ed33c1.pdf"},{"id":56836066,"identity":"d701078e-1bd3-4efe-9e87-ddd16836f582","added_by":"auto","created_at":"2024-05-21 05:59:04","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18385,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"JamryTable.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4370114/v1/bc66c02d8d8da636b4c3d53a.xlsx"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eImpact of the shape of the ampulla of Vater and biliary tree pathology on access technique and post-ERCP complications\u003c/p\u003e","fulltext":[{"header":"Introduction and Background","content":"\u003cp\u003eDuring endoscopic retrograde cholangiopancreatography (ERCP), obtaining access to the biliary tree (via\u0026nbsp;cannulation and sphincterotomy)\u0026nbsp;is\u0026nbsp;part of the procedure\u0026nbsp;and\u0026nbsp;can\u0026nbsp;lead to complications such\u0026nbsp;as postendoscopic pancreatitis (PEP), bleeding and perforation.\u0026nbsp;Difficulties in this stage can\u0026nbsp;depend\u0026nbsp;not only\u0026nbsp;on the\u0026nbsp;anatomy of the papillae of Vater but also\u0026nbsp;on the\u0026nbsp;distal common bile duct (CBD) diameter, presence of periampullary diverticula (PADs) and biliary tree outflow obstruction level. Additionally, there are many different access techniques\u0026nbsp;available\u0026nbsp;(guidewire, precut classic, transpancreatic, precut needle, two-step\u0026nbsp;access and many others),\u0026nbsp;but knowledge about which is most appropriate for the anatomy of the patient is limited. Additionally, previous analyses\u0026nbsp;did\u0026nbsp;not\u0026nbsp;included\u0026nbsp;the existence of\u0026nbsp;a\u0026nbsp;diverticulum\u0026nbsp;or\u0026nbsp;pathology in the biliary tree itself\u0026nbsp;[1-4 [5][6.][7].\u0026nbsp;Therefore,\u0026nbsp;the\u0026nbsp;purpose of\u0026nbsp;this\u0026nbsp;study\u0026nbsp;was to\u0026nbsp;analyze\u0026nbsp;the relationships\u0026nbsp;between\u0026nbsp;the\u0026nbsp;anatomy of\u0026nbsp;Vaterian\u0026nbsp;papillae, biliary tree pathology\u0026nbsp;and\u0026nbsp;access technique (classic sphincterotomy [CS], classic precut [CPC], needle precut [NPC], two-step access, and unintended Wirsung duct cannulation)\u0026nbsp;and\u0026nbsp;potential complications\u0026nbsp;(bleeding during ERCP, blood and urine hyperamylasemia 4 hours after\u0026nbsp;the\u0026nbsp;procedure, pancreatic pain and PEP).\u0026nbsp;Knowledge about these relationships\u0026nbsp;can help create recommendations for\u0026nbsp;choosing the\u0026nbsp;ideal access technique, reduce the risk of complications and facilitate the learning process for ERCP.\u003c/p\u003e\n\u003cp\u003eEthical approval was issued and is formulated as the \u0026nbsp;Ethics Committee at the Swietokrzyska Medical Chamber No. Ldz.SIL.KB/B.3/2024\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eData collection and\u0026nbsp;patient population:\u0026nbsp;This single-center\u0026nbsp;study\u0026nbsp;included\u0026nbsp;1002 consecutive (years 2010-2014, mean age\u0026nbsp;67 years, 61.6% (616) women)\u0026nbsp;patients\u0026nbsp;with naive Vaterian papillae\u0026nbsp;for whom\u0026nbsp;therapeutic ERCP\u0026nbsp;was performed. The exclusion\u0026nbsp;criteria were\u0026nbsp;a previous\u0026nbsp;papilla\u0026nbsp;endoscopic or surgical procedure\u0026nbsp;performed\u0026nbsp;before ERCP\u0026nbsp;and\u0026nbsp;acute pancreatitis.\u0026nbsp;The data\u0026nbsp;were collected from\u0026nbsp;the Endobase-Endoscopic Database and Oracle-Hospital Medical Database\u0026nbsp;as well as from other hospitals.\u0026nbsp;The patients were\u0026nbsp;analyzed\u0026nbsp;in terms of\u0026nbsp;the following factors.\u0026nbsp;Anatomy:\u0026nbsp;The analyzed\u0026nbsp;anatomical features included papilla shape,\u0026nbsp;the\u0026nbsp;existence of PAD and pathology in\u0026nbsp;the\u0026nbsp;biliary duct. To assess\u0026nbsp;the\u0026nbsp;shape of the Vaterian papillae, we\u0026nbsp;used\u0026nbsp;a\u0026nbsp;modified Haraldsson classification\u0026nbsp;system[1,2].\u0026nbsp;Initially,\u0026nbsp;patients with neoplastic deformed papillae\u0026nbsp;were excluded\u0026nbsp;(approximately 10% of patients who undergo ERCP in everyday practice). Therefore,\u0026nbsp;we modified Haraldson's classifications partly based on the study of the Human\u0026nbsp;Anatomy Teaching Group\u0026nbsp;from Cambridge.[8].\u0026nbsp;Finally, group 2 included patients with both small (Haraldson\u0026nbsp;group 2) and rigid (Haraldson group 4) papillae.\u0026nbsp;However, group 4 included patients with deformed/infiltrated papillae regardless of etiology (neoplastic or chronic pancreatitis). Finally,\u0026nbsp;papillae\u0026nbsp;were\u0026nbsp;classified\u0026nbsp;according to shape as\u0026nbsp;type 1\u0026nbsp;(regular),\u0026nbsp;type 2\u0026nbsp;(small and rigid),\u0026nbsp;type 3\u0026nbsp;(protruding or pendulous),\u0026nbsp;or\u0026nbsp;type 4\u0026nbsp;(deformed\u0026nbsp;papillae)\u0026nbsp;as\u0026nbsp;a result of\u0026nbsp;infiltration. Additionally, other factors\u0026nbsp;that\u0026nbsp;can impact\u0026nbsp;the\u0026nbsp;access process,\u0026nbsp;such\u0026nbsp;as\u0026nbsp;the presence\u0026nbsp;of PAD,\u0026nbsp;CBD diameter ≤9 mm (measured from\u0026nbsp;X-ray images at a distance of 2.0 cm from the ampulla of Vater),\u0026nbsp;outflow obstruction level based on imaging examinations preceding the procedure\u0026nbsp;(distal,\u0026nbsp;medial,\u0026nbsp;hilum)\u0026nbsp;and choledocholithiasis, were analyzed.\u003c/p\u003e\n\u003cp\u003eAccess technique:\u0026nbsp;A classic\u0026nbsp;sphincterotome with\u0026nbsp;a\u0026nbsp;guide wire was routinely used.\u0026nbsp;Difficult cannulation was defined according to\u0026nbsp;the\u0026nbsp;5-5-2\u0026nbsp;criteria:\u0026nbsp;more than 5 contacts with the papilla,\u0026nbsp;more than 5 minutes\u0026nbsp;of cannulation\u0026nbsp;and more than two unintended pancreatic duct\u0026nbsp;cannulations\u0026nbsp;[10].\u0026nbsp;In addition, if a\u0026nbsp;guidewire\u0026nbsp;passed\u0026nbsp;into the pancreatic duct or\u0026nbsp;underwent opacification, prophylactic pancreatic stenting was routinely performed.\u0026nbsp;After more than\u0026nbsp;5 minutes of ineffective cannulation,\u0026nbsp;we\u0026nbsp;performed\u0026nbsp;precut sphincterotomy\u0026nbsp;via\u0026nbsp;either\u0026nbsp;the\u0026nbsp;classic (CPC) or needle knife (NPC)\u0026nbsp;approach.\u0026nbsp;Two-stage access was defined as no catheterization of the target duct within\u0026nbsp;approximately\u0026nbsp;20 minutes, despite\u0026nbsp;the\u0026nbsp;precut incision\u0026nbsp;being\u0026nbsp;performed, and the postponement of subsequent attempts for 4-5 days (until tissue edema subsides).\u003c/p\u003e\n\u003cp\u003eAdverse events: Bleeding during ERCP was classified as the presence of bloody discharge after ES that\u0026nbsp;impeded\u0026nbsp;further cannulation and required\u0026nbsp;additional endoscopic procedures to stop. Abdominal pain suggestive of pancreatitis was defined according to\u0026nbsp;the\u0026nbsp;revised Atlanta Classification\u0026nbsp;[3].\u0026nbsp;PEP was defined as\u0026nbsp;new or worsened abdominal pain combined with \u0026gt; 3 times the normal value of amylase or lipase at more than 24 hours after ERCP and\u0026nbsp;a\u0026nbsp;requirement\u0026nbsp;for\u0026nbsp;admission or the prolongation of a planned admission\u0026nbsp;[4].\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analysis: Quantitative variables\u0026nbsp;are\u0026nbsp;expressed herein as\u0026nbsp;the\u0026nbsp;mean and standard deviation. Categorical variables\u0026nbsp;are\u0026nbsp;presented as numbers and percentages. The normality of\u0026nbsp;the\u0026nbsp;data distribution was tested with the\u0026nbsp;Kolmogorov‒Smirnov\u0026nbsp;test. The χ2 test was used to test the interdependence of pairs of variables for double classifications.\u0026nbsp;Univariate\u0026nbsp;and multivariate logistic regression models were used to estimate odds ratios\u0026nbsp;(ORs)\u0026nbsp;with 95% CIs and P values. In\u0026nbsp;the\u0026nbsp;case of multivariable models, the FORWARD (entering significant variables sequentially)\u0026nbsp;and BACKWARD (first entering all variables into the model and subsequently removing the nonsignificant variables sequentially) options\u0026nbsp;were used.A P value less than 0.05 was considered to indicate statistical significance. Statistical analysis was performed using Med-Calc Statistical Software 20, version 19.7.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eI. Grouping of patient characteristics: To determine the relationship between the anatomy of the biliary tract, the use of a particular access technique and possible complications, a group of 1002 patients was analyzed. The mean age was 67 years, and 61.5% (616) were female. Therefore, factors other than the appearance of the papillae themselves were also analyzed. According to the modified Haraldson classification, 474% of patients (475/1002) had type 1 papillae, 31.3% (314/1001) had type 2 papillae, 11.1% (111/1002) had type 3 papillae, and 10.2% (102/1002) had type 4 papillae. A total of 20.4% (204/1002) patients had a periampullary diverticulum (PAD). A total of 35.2% (349/1002) of patients had obstructions in the distal CBD, and 9.4% (93/1002) had obstructions in the middle part of the CBD (Table I).\u003c/p\u003e\n\u003cp\u003eII. Access technique: \u003cbr\u003e1. Difficult cannulation: Defining the factors influencing the difficulty in accessing the duct, which is the target of the therapeutic procedure, may enable the selection of an appropriate operator (in terms of experience) before starting any interventional endoscopic procedures. In the present study, difficult cannulation was observed in 56.9% (58/102; p=0.002) of patients with deformed (type 4) Vaterian papillae, 46.4% (162/349; p=0.001) of patients with distal CBD strictures and 49.5% (46/93; p=0.04) of patients with medial CBD strictures. In contrast, easier access was found in 34.3% (163/475; p=0.001) of patients with classic (type 1) Vaterian papillae, 31.7% (145/458; p≤0.0001) of patients with choledocholithiasis and in 29.4% (60/204; p= 0.001) of patients with PAD (Table II). 2. Endoscopic sphincterotomy (ES) technique: Knowledge about which type of sphincterotomy is most likely to provide access (depending on the existing anatomy) can improve recommendations for the procedure. Therefore, we analyzed the relationships between the existing anatomy and the type of sphincterotomy performed. Classic sphincterotomy (CS) was performed significantly more often in patients with type 1 Vaterian papillae (47.4%; 259/475; p=0.015), with PAD (54.4%; 117/204; p=0.028), or with choledocholithiasis (54.1%; 248/458; p=0.034). CPC was performed more frequently in patients with deformed (type 4) papillae (42.2%; 43/102; p=0.018). In addition, NPC was used more frequently for protruding (type 3) Vaterian papillae (38.7%; 43/111; p\u0026lt;0,0001) and for a CBD diameter ≤9 mm (26,0%, 34/131; p=0,008) but was chosen significantly less often for patients with PAD (9.3%; 29/204; p=0,0004). (Table III) 3. Two-step access: Despite the use of precut sphincterotomy, access to the target duct may still be impossible, and the risk of PEP and false pathway creation may increase, leading to a false diagnosis. In this situation, two-step access should be considered. In the present study, two-step access was implemented significantly more frequently for patients with deformed (type 4) papillae (28.4%; 29/102; OR 2.74; p\u0026lt;0.0001), small (type 2) papillae (17.8%; 56/315; p= 0.032) and distal outflow obstruction (18.9%; 66/349; p=0.002; Table IV).\u003c/p\u003e\n\u003cp\u003eIII. Adverse events: Assessing the relationship between the existing anatomy and the occurrence of complications during and after ERCP may enable the selection of the access technique with the lowest risk of complications (for example, Wirsung duct stenting) and the endoscopist with the most appropriate level of experience. Bleeding during ES was significantly more frequent in patients with classic (type 1) Vaterian papillae (21.9%; 104/475; p=0.003). In contrast, this complication was significantly less common in patients with small (type 2) papillae (12.7%; 40/315; p=0.003) and a CBD diameter ≤ 9 mm (13.4%; 60/449; p=0.0006). Hyperamylasemia 4 hours after ERCP was significantly more common in patients with a distal CBD diameter ≤9 mm (19.0%; 85/448; OR 2.6, p\u0026lt;0.0001). Pancreatic pain and PEP were observed more frequently in patients with a CDB diameter ≤ 9 mm (6.2%; 28/449; p=0.027 and 4.0%; 18/449; p=0.021, respectively) (Table V). \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe impact of the anatomy and pathology of Vaterian papillae and biliary tree pathology on the choice of access technique (cannulation difficulties, sphincterotomy technique, two-step access) and adverse events has not been fully explained. Few studies have examined all of these factors together [12]; most analyses have focused only on the relationship between papilla shape and cannulation difficulty and excluded deformed papillae, altered CBD anatomy and PADs[1,2,6,9,16,17,18], while other authors only examined access techniques without considering anatomy [5,7,9]. Therefore, in our study, we additionally included infiltrated ampullae of Vater (according to a modification of Haraldson's classification), the extent of biliary tree obstruction and the presence of PADs. This approach can improve the understanding of the relationship between difficulties during access and other factors, not only the shape of the papillae. Knowledge regarding this subject is important because it can facilitate the training process, enable proper selection of endoscopists (according to their level of experience) and ensure that the access technique (depending on the papilla shape and biliary tree pathology) has the lowest risk of complications. Difficult cannulation: Our results confirmed that the degree of difficulty during cannulation depends not only on the shape of the papillae but also on the level of bile outflow blockade. Taking other factors into account answers the question posted by Sinha as to why flat papillae were difficult to cannulate in Haraldson's studies [2,8]. According to the results of this study, cannulation was difficult in 56.9% (58/102) p=0.0002, of patients with deformed (type 4) papillae, 46.4%(162/349; p=0.0011 of patients with distal biliary tree flow obstruction and 49.5% (46/93)(p= 0.0407 of patients with medial biliary tree outflow obstruction. Therefore, it should be recommended that procedures in these patients be performed by experienced endoscopist In contrast, for patients with a low risk of cannulation difficulty, such as those with classic (type 1) papillae (34.3%; 163/475) (p=0.0014), choledocholithiasis (31.7%; 145/458) (p\u0026lt;0.0001), and perhaps even PAD (29.4%; 60/204) (p=0.001), this issue requires more detailed analysis; it may be possible for endoscopists to treat these patients during the learning process under supervision. Due to the lack of a uniform classification system for determining the shape of papillae and differences in the frequency of use of guidewires for various kinds of sphincterotomy and two-step access, comparing the obtained results with those of other studies is challenging. For example, apart from Haraldson, his classification system has been used only for analysis by Chen, Estela and Balan [6,11,12]. In a multicenter analysis, Haraldsson's team enrolled 1401 patients and reported that cannulation was more difficult in patients with small (type 2) papillae (52%; 95% CI, 45%-59%) and protruding (type 3) papillae (48%; 95% CI, 42%-53%) than in those with classic (type 1) papillae [2]. Chen analyzed 286 patients and obtained similar results. Small (type 2) papillae (OR 7.18, p = 0.045) and protruding (type 3) papillae (OR 7.44, p = 0.016) were more difficult to cannulate than classic (type 1) papillae [11]. A similar conclusion was reached by Balan, who showed that significantly more cannulation attempts (mean value of 5.5 attempts, p = 0.00108) and more time (mean value of 5.6 minutes, p = 0.00181) were needed for patients with small (type 2) papillae [12]. In the present study, these relationships were not significant (40.3%; 127/315; p= 0.73; OR 1.05; p=0.73); however, two-step access was used significantly more frequently for patients with small (type 2) papillae (17.8%; 56/315; p= 0.032; OR 1.49; p=0.032). Indirectly, these findings suggest difficulties in deep cannulation of the target duct in this group of patients. However, it should be emphasized that comparing these data with those of other studies is problematic because of the different definitions of type 2 papillae and leakage of the distal CBD with an altered anatomy. Other factors that may explain these differences are the frequency with which a guidewire was used and the use of different precut incision techniques. The Haraldson group used guidewires in approximately 50% of patients; classic access was impossible, and the precut technique was used in only 9% of patients [2]. In contrast, we used guidewires in more than 90% of patients, NPCs in 38.7%(43/111) p\u0026lt;0,0001 (OR 3.54 p \u0026lt;0.0001) of patients with protruded (type 3) papillae and CPC in 42.2%(43/102) p=0,017 (OR 1,65 p = 0,0183) of patients with deformed (type 4) papillae. Other results were published by Estela, who, in the analyzed group (230 patients), difficult cannulization was more common in type 3 (3.66%, 95% CI 2.49-5.84), type 4 (3.21%, 95% CI 1.82-5.75), and type 2 (1.95%, 95% CI 1.15-3.20) patients than in type 1 patients. These results are partially consistent with ours, but we did not confirm any difficulties during cannulation of type 2 papillae [6]. The differences may result from differences in the classification and access technique used. The next factor that could explain the differences was the exclusion criteria. Haraldsson, Chang, Balan and Estella excluded patients with tumors or other causes of deformity of the papillary region (meaning that approximately 10% of patients treated daily by ERCP were excluded). [2,6,11,12] In our study, according to the modified Haraldson classification, all patients with deformed papillae were classified as having type 4 papillae. In our series, this group had the highest probability of experiencing a difficult cannulation (56.9%; 58/102; p=0.0002; OR 2.19, p=0.0002). Most of our patients in group 4 had cancer-related deformed papillae. In this way, a similar result was presented by Chen, who reported that the presence of neoplasia was related to difficulty in cannulation (OR 4,45 p=0,014) [11]. Additionally, Chen reported that type 1 papillae required significantly less time for cannulation (56.78% of the patients could be cannulated within 5 minutes) and had the lowest cannulation failure rate (1.69%) 1,55 (1,19-2,02) [11]. Similarly, our study revealed that the risk of cannulation difficulties in patients with type 1 papillae was significantly lower (34.3%; 163/475; p= 0.0014; OR= 0.66; p= 0.0014). However, differences from Chen’s research exist in terms of PEP risk factors. We did not find a relationship between papilla shape and the risk of PEP. In contrast, Chen reported that type 2 papillae were correlated with a greater percentage of PEP (20%, p = 0.020). This difference may be due to Chen’s application of endoscopic papilla balloon dilatation (OR for PEP 4,51) [13], whereas we used two-stage access in 17.8% (56/315; p=0.032; OR 1.49; p= 0.032) of patients with type 2 papillae, which can reduce the risk of PEP. These results may justify the early use of a two-stage procedure in patients with type 2 or 4 papillae. The next factor analyzed was the presence of PADs, which may increase the risk of difficulties and complications [11,14]. However, the presence of a weak point in the duodenal wall can also facilitate access to the biliary duct. This relationship was also found in the present study, which showed that the presence of PADs made cannulation easier in 29.4% (60/204) of patients (p= 0.001; OR=0.57, p=0.01). Interesting data in this regard were presented by Mu in a meta-analysis [15]. In previous studies, the presence of a PAD was related to difficult cannulation (RR=1.46, 95% CI=1.27-1.67; p\u0026lt;.00001); however, within the last 20 years, these relationships were not statistically significant (RR=1.16, 95% CI=0.96-1.41; p=0.12). This is probably a consequence of the development of equipment and cannulation techniques. Additionally, in Mu’s study, PAD was also associated with a high risk of PEP (RR=1.32, 95% CI=1.10-1.59; p=0.003), perforation (RR=1.73, 95% CI=1.06-2.82; p=0.030), and bleeding (RR=1.48, 95% CI=1.13-1.93; p=0.005) [15]. We did not observe this relationship, and these differences are likely a consequence of the authors’ significantly less frequent use of NPC (9.3%; 19/204; p=0.0004; OR=0.41; p=0.0006) in PAD patients. Many other classifications of Vaterian papillae have been created but do not include patients with PADs; therefore, it is impossible to compare these results with those of other studies [16,17,18,19]. Access technique: We confirmed that the type of papillae, presence of PAD and biliary tree pathology have an impact on the technique chosen for performing sphincterotomy. CS was possible significantly more frequently in patients with type 1 papillae (47.4%; (259/475; p= 0.0155; OR 1.36; p= 0.0156); in patients with PAD (54.4%; (117/204); p=0.028; OR 1.41; p=0.028); and in patients with choledocholithiasis (54.1%; (248/458); p=0.0341; OR 1.31; p=0.0341). CPC was chosen significantly more often in patients with type 4 papillae (42,2%; 43/102; p= 0.0171; OR 1.65; p=0.0183), and NPC was chosen more often in patients with type 3 papillae (38.7%; 43/111; p\u0026lt;0.0001; OR 3.54; p\u0026lt;0.0001). Only two studies have analyzed the sphincterotomy technique chosen in relation to papilla shape; unfortunately, other papilla shape classifications were used in these studies [16,20]. The Canena (2021) classification includes 7 types: type 1 (flat), type 2A (prominent with \u0026lt;1 fold), type 2B (prominent and \u0026gt;2 folds), type 2C (bulging), type 3A (interdiverticular), type 3B (diverticular border type), and type 4 (unclassified). The authors analyzed 361 patients who underwent only needle knife fistulotomy (NKF). According to multivariate analysis, flat (type 1) and prominent (\u0026lt; 1-fold) (2B) papillae were risk factors for difficult cannulation, and types 2B, 3A and 3B were associated with the lowest cannulation rates post-NKF [16]. In our study, the preferred technique for all patients with PAD was CS (54.4%; 117/204;p=0.028; OR 1.41; p=0.029), and we used NPC significantly less often (9.3%; 19/204; p=0,004;OR 0.41;, p=0.0006). In contrast, in Canena’s study, NKF was used significantly more often for type 2c papillae (similar to type 3 in Haraldsson’s classification). This finding is consistent with our results, as we used NPC significantly more often in patients with type 3 papillae (38.7%; 43/111; OR 3.54; p\u0026lt; 0.0001). A study conducted by Horiuchi in 2007 analyzed 86 patients. The effectiveness of the three-type precut technique on the basis of papilla shape was assessed: for small (Haraldsson type 2)- trans pancreatic (CPC),for large (Haraldsson type 1) - needle knife precut (NKP) , and for swollen (Haraldsson type 3) needle knife fistulotomy (NKF) . Successful access to the biliary tree was achieved in 96%, 90%, and 100% of patients, respectively. The overall complication rate was 4.7% (4 of 86) (2 patients with mild bleeding and 2 with mild pancreatitis) [20]. These criteria for choosing the ES technique agree with our own technique for swollen (Haraldson type 3) papillae, for which the most common technique was NPC (38.7%; 43/111; p\u0026lt;0,001; OR 3.54; p\u0026lt; 0.0001). In contrast, for the small papillae (Haraldson type 2) in our study, the CPC technique for sphincterotomy was used significantly less often (27.0%; 85/315; OR=0.72; p = 0.0287). The above comparison highlights the lack of uniform rules for the use of various access techniques according to the existing anatomy; therefore, to reach a consensus, this issue requires further research. The limitations of the present study include its single-center nature and the fact that the analyzed procedures were performed by one operator. Therefore, there is a risk of bias in the technique of assessing the shape of the papillae and the selection of access techniques. Another limitation was the low number of participants in each group (with different anatomies of the bile ducts) after division according to the access technique used. The existing number of patients made it impossible to perform a statistical analysis of the relationships between the detailed anatomy and access technique used and side effects.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe results revealed a relationship between the anatomy of the papillae and bile ducts, the access technique selected and the occurrence of side effects. This knowledge may facilitate the training process by helping endoscopists assess the degree of difficulty of the procedure and the risk of complications based on the appearance of the papillae and the level of biliary outflow obstruction in imaging tests. This approach will make it possible to determine whether the procedure can be safely performed by an endoscopist during training or whether it requires the intervention of an expert. Additionally, if other studies confirm the existence of a relationship between the anatomy and the access technique used (type of sphincterotomy and need to implement a two-stage procedure), recommendations in this area can be created. The results obtained in this study justify the consideration of multicenter studies defining the access technique (such as the rules for using a guidewire, CPC, NPC, protective PD stenting or two-step access) and covering a larger group of patients, which would enable a more detailed analysis of complications in each group of patients treated through different access techniques depending on the existing anatomy.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHaraldsson E, Lundell L, Swahn F, et al. Endoscopic classification of the papilla of Vater. Results of an inter- and interobserver agreement study. United European Gastroenterology Journal 2017, Vol. 5(4) 504\u0026ndash;510 PMID: 28588881; DOI: 10.1177/2050640616674837\u003c/li\u003e\n \u003cli\u003eHaraldsson E, Kyl\u0026auml;np\u0026auml;\u0026auml; L, Gr\u0026ouml;nroos J, et al. The macroscopic appearance of the major duodenal papilla influences bile duct cannulation: a prospective multicenter study by the Scandinavian Assocization for Digestive Endoscopy study group for ERCP. Gastrointest. Endosc. 2019;90:957\u0026ndash;63 PMID: 31326385;DOI: 10.1016/j.gie.2019.07.014\u003c/li\u003e\n \u003cli\u003eBanks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis 2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62(1): 102\u0026ndash;111 PMID: 23100216 DOI: 10.1136/gutjnl-2012-302779\u003c/li\u003e\n \u003cli\u003eDumonceau J, Kapral C Aabakken L,et al. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline Endoscopy 2020 Feb;52(2):127-149. PMID: 31863440 ;DOI: 10.1055/a-1075-4080\u003c/li\u003e\n \u003cli\u003eL\u0026ouml;hr M, Aabakken L , Arnelo U, et all. How to cannulate? A survey of the Scandinavian Association for Digestive Endoscopy (SADE) in 141 endoscopists, Scandinavian Journal of Gastroenterology. 2012 47:7, 861-869, DoI: 10.3109/00365521.2012.672588\u003c/li\u003e\n \u003cli\u003eEstelaE.L, Tovar N.R, MaldonadoF.A et al. Association between type of major duodenal papilla and difficult biliary cannulation at first endoscopic retrograde cholangiopancreatography in adults: a cross-sectional study with bootstrap method Ann Gastroenterol. 2023 Mar-Apr;36(2):216-222. doi: 10.20524/aog.2023.0775. Epub 2023 Jan 25\u003c/li\u003e\n \u003cli\u003eFacciorussoA, RamaiD, GkolfakisP et al.. Comparative efficacy of different methods for difficult biliary cannulation in ERCP: systematic review and network meta-analysis Gastrointest Endosc 2022 Jan;95(1):60-71.e12. doi: 10.1016/j.gie.2021.09.010. Epub 2021 Sep 17.\u003c/li\u003e\n \u003cli\u003eSinhaA, ThiaryaD PatelP et al.. Macroscopic appearance of the major duodenal papilla Gastrointest Endosc 2020 Jul;92(1):227-229. doi: 10.1016/j.gie.2020.02.005. PMID: 32586551 DOI: 10.1016/j.gie.2020.02.005\u003c/li\u003e\n \u003cli\u003eAdler, D.G. ERCP biliary cannulation difficulty as a function of papillary subtypes: A tale of shapes and Shar-Pei dogs. Gastrointest. Endosc. 2019, 90, 964\u0026ndash;965 PMID: 31759420 DOI: 10.1016/j.gie.2019.07.030\u003c/li\u003e\n \u003cli\u003eTestoni A, Mariani A, Aabakken L,et all. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline , Endoscopy 2016 Jul;48(7):657-83. PMID: 27299638 DOI: 10.1055/s-0042-108641\u003c/li\u003e\n \u003cli\u003eChen Q,Li Z, Li S. et al.. Diagnosis and treatment of juxta-ampullary duodenal diverticulum Clin Invest Med. 2010 Oct 1;33(5):E298-303. PMID: 20926036 DOI: 10.25011/cim.v33i5.14355\u003c/li\u003e\n \u003cli\u003eBalan G, Arya M, Catinean A, Sandru V et al.. Anatomy of Major Duodenal Papilla Influences ERCP Outcomes and Complication Rates: A Single Center Prospective Study J. Clin. Med. 2020, 9, 1637; PMID: 32481755 DOI: 10.3390/jcm9061637\u003c/li\u003e\n \u003cli\u003eChandrasekhara, V.; Khashab, M.A.; Muthusamy, V.R,et al. Adverse events associated with ERCP. Gastrointest. Endosc. 2017, 85, 32\u0026ndash;47. PMID: 27546389 DOI: 10.1016/j.gie.2016.06.051\u003c/li\u003e\n \u003cli\u003eAvisseC, Flament J, Delattre J ,,Ampulla of Vater. Anatomic, embryologic, and surgical aspects,, Surg Clin North Am 2000 Feb;80(1):201-12. PMID: 10685149 DOI: 10.1016/s0039-6109(05)70402-3\u003c/li\u003e\n \u003cli\u003eMu P, Yue P, Li F, et al. Does periampullary diverticulum affect ERCP cannulation and postprocedure complications? an up-to-date meta-analysis. Turk J Gastroenterol 2020; 31(3): 193-204. PMID: 32343231 DOI: 10.5152/tjg.2020.19058\u003c/li\u003e\n \u003cli\u003eCanena J, Lopes L, Fernandes J et al.. Influence of a novel classification of the papilla of Vater on the outcome of needle-knife fistulotomy for biliary cannulation BMC Gastroenterol (2021) 21:147 PMID: 33794778 DOI: 10.1186/s12876-021-01735-3\u003c/li\u003e\n \u003cli\u003eMohamedR , LethebeC, Gonzalez-MorenoE et al.. Morphology of the major papilla predicts ERCP procedural outcomes and adverse events Surg Endosc 2020 Nov 4. PMID: 33146812 DOI: 10.1007/s00464-020-08136-9\u003c/li\u003e\n \u003cli\u003eWangX, ZhaoJ, WangL et al.. Relationship between papilla-related variables and post endoscopic retrograde cholangiopancreatography pancreatitis: A multicenter, prospective study J Gastroenterol Hepatol 2020 Jun 8. PMID: 32511794 DOI: 10.1111/jgh.15135\u003c/li\u003e\n \u003cli\u003eWatanabe M, Okuwaki K, Kida M. et al.. Transpapillary biliary cannulation is difficult in cases with large oral protrusion of the duodenal papilla. Digestive Diseases and Sciences (2019) 64:2291\u0026ndash;229 PMID: 30746630 DOI: 10.1007/s10620-019-05510-z\u003c/li\u003e\n \u003cli\u003eHoriuchi A, Najayama Y, Kajjyama M ,Tanaka N .Effect of Precut Sphincterotomy on Biliary Cannulation Based on the Characteristics of the Major Duodenal Papilla Clinical Gastreoenterology and Hepatology 2007;5:1113\u0026ndash;1118 PMID: \u003cstrong\u003e17689295\u003c/strong\u003e DOI: 10.1016/j.cgh.2007.05.014\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eNext recommended study:\u003c/p\u003e\n\u003cp\u003e1. A more detailed description of the step-by-step access technique (classic caniulotomy, short- versus long-nose needle, guidewires, and protective PD stenting or two-step access) is needed.\u003c/p\u003e\n\u003cp\u003e2. A larger group of patients may allow a statistical analysis of side effects depending on the papillary shape, biliary pathology and access technique.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 5 are available in the Supplementary Files section\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"DIstrict Hospital Starachowice","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endoscopic sphincterotomy, Ampulla of Vater, Common bile duct, Risk factors, Cannulation, Complication.","lastPublishedDoi":"10.21203/rs.3.rs-4370114/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4370114/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and aim:\u003c/strong\u003e Difficulties and complications during endoscopic retrograde cholangiopancreatography (ERCP) can depend on the anatomy of the papillae, the pathology of the biliary tree, and proper selection of the endoscopic technique. However, knowledge about these relationships is limited. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This single-center retrospective study included 1002 patients who underwent ERCP. The analyses included the impact of the existing anatomy (shape of the papillae [modified Haraldsson classification], periampullary diverticulum [PAD], common bile duct [CBD] diameter ≤9 mm, outflow obstruction level and choledocholithiasis]) on cannulation difficulty, access technique (classic sphincterotomy [CS], classic precut [CPC], needle precut [NPC], two-step access, unintended Wirsung duct cannulation) and complications (bleeding, hyperamylasemia, pancreatic pain and postendoscopic pancreatitis [PEP]). Results: According to the modified Haraldsson classification,47.4% of the papillae were type 1, 31.3% were type 2; 11.1% were type 3, and 10.2% were type 4. Cannulation was considered difficult in 56.9% (58/102; p=0.0014) \u0026nbsp;\u0026nbsp;of type 4 papillae and 46.4% (162/349; p= 0.001) and 49.5% (46/93; p=0.039) of patients with distal and medial CBD obstruction, respectively. CPC was used for 42.2% (43/102; p=0.017) of patients with type 4 papillae. NPC was used 38.7% (43/111; p\u0026lt;0.0001) of patients with type 3 papillae, and 26.0% (34/131; p=0.008) of patients with a CBD diameter ≤9 mm. Two-step access was used for 28.4% (29/102; p\u0026lt;0.0001) of type 4 papilla patients, 17.8% (53/315; (p= 0.002)) of type 2 papilla patients and 18.9% (66/349; p=0.002)of patients with distal CBD obstruction. Bleeding occurred for 21.9% (104/475; p=0.003) of type 1papilla patients. A total of 19.0% (85/448,p\u0026lt;0.0001) \u0026nbsp;of patients with CBD diameters ≤9 mm had hyperamylasemia; 6.2% (28/449,p=0.025); had pancreatic pain and 4% (18/449; p=0.021)had PEP . \u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The existing anatomy of the papillae and biliary tree affected the difficulty of cannulation, the selection of access technique, and the occurrence of side effects.\u003c/p\u003e","manuscriptTitle":"Impact of the shape of the ampulla of Vater and biliary tree pathology on access technique and post-ERCP complications","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-21 05:59:00","doi":"10.21203/rs.3.rs-4370114/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fad40a6d-d899-4f4d-b1a3-52669f33c44d","owner":[],"postedDate":"May 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32181906,"name":"Gastroenterology \u0026 Hepatology"}],"tags":[],"updatedAt":"2024-05-21T05:59:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-21 05:59:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4370114","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4370114","identity":"rs-4370114","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}