Juxtapapillary duodenal diverticula early and late clinical and therapeutical implications

The structure according to gender is of great interest in knowing the risk and frequency of the association of JPDD with the biliary - pancreatic pathology in males as against females. The description of the structure of the cases analyzed according to age groups is of major interest for the health care system as well, since the morbidity and mortality pattern differ from one age group to another. (Table 3, Table 4)

The indications which led to the performance of ERCP + ES (Table 5) were represented by:
- pain - biliary colic;
- jaundice with significant alteration of cholestasis samples;
- biliary colic, fever, shiver ± jaundice;
- painless jaundice;
- postoperative bile leakage into the drain tube.
One of the main criteria was the percentage of difficult ERCP ± ES, complications and cannula insertion failures. We considered ERCP difficult either because of the impossibility of cannulation, or because of the time elapsed between the highlighting of the papilla and the opacification of CBD or of Wirsung’s canal. This period of time exceeded 20 minutes in the case of difficult ERCP. Moreover, the complications which occurred were also taken into account:
- post endoscopic sphincterotomy hemorrhaging controlled by injecting 1/10,000 units of adrenaline or by administrating 1-2 units of blood;
- the occurrence of acute pancreatitis;
- others – impaction of Dormia probe, cholangitis. (Fig. 3, 4, 5, Table 6).

The 65 cases with JPDD required 79 examination procedures of CBD and of Wirsung’s duct, in 47 cases being followed by ES and calculi elimination, sometimes in a sequential manner (14 cases). A number of 11 failures was recorded, 8 of which caused by interposed JPDD. A number of 10 modal presentations of the cystic canal and of the common bile duct was recorded. (Fig. 6, 7)
Sphincterotomies – a total of 399 procedures – used for 601 cases, out of which 353 procedures were performed on 536 non-carrier JPDD patients and 47 procedures on the 65 “JPDD beneficiary” patients. The rate of complications was also different: a rate of 5.75% complications in patients without JPDD who underwent sphinterectomy and a rate of 14.89% in patients with JPDD who underwent sphinterectomy. (Fig. 8)

In both groups of patients, those without JPDD - 536 cases (89.1%) with 596 procedures and those with JPDD – 65 cases (10.81%) with 79 procedures, the following were examined:
- the rate of catheterization failure
- the rate of immediate complications
Thus, the number of catheterization failures was 71 (11.9%) in patients without JPDD, and 11 in patients with JPDD (16.92%). In the cases of CBD lithiasis (migrated, recurrent or native), a number of 74 procedures (ERCP ± ES) were repetitive endoscopic methods for obtaining the vacuity of the main biliary duct.
Serious complications may occur after endoscopic sphincterotomy, such as: hemorrhage, perforation, pancreatitis, cholangitis. These complications may be connected with the presence of “duodenal window” diverticula in terms of an increased rate of complications, the most frequent being hemorrhage, and possibly perforation caused by the presence of interposed diverticula. In such cases, endoscopic papillo-sphincterotomy should be avoided. Hemorrhage, the most frequent complication, can be avoided by making controlled incisions. However, in most cases, bleeding stops spontaneously or is solved by endoscopy, surgery being seldom necessary. Pancreatitis and cholangitis may occur after endos-copic sphincterotomy if an adequate biliary drainage is not made.
Out of the total of 47 endoscopic papillosphincterotomies performed on patients with JPDD, 6 were incomplete papillosphincterotomies, out of which 4 because of the interposed window diverticula, which limited the endosurgical intervention, and 2 because of the hemorrhage.
The 5 patients who hemorrhaged during the papillo-sphincterotomy had a minor hemorrhage, as the hemoglobin did not fall below 3 g/dl as compared to preoperative hemoglobin. In only one case, the blood loss was slightly greater, and the transfusion of two units of blood was necessary, especially because the patient was old. In two cases ES was definitive and performed as repeated sphincterotomy 4, respectively 7 days after the first surgical intervention, followed by endoscopic hemostasis.
Acute pancreatitis was recorded in 2 cases post ERCP, consisting in the tripling of the serum amylases compared to normal values, clinically accompanied by medium intensity pain in the clinical bar, in the superior abdominal level, which subsided after 3 - 4 days.
We cannot talk about infection after performing the endoscopy, respectively ERCP, since in most cases patients either presented clinical signs of cholangitis or were under antibiotic treatment which covered any form of digestive pollution during the endoscopic therapeutic maneuver.
However, it is imperative to remember that in spite of the papillosphincterotomy, lithotomy, i. e. by providing vacuity and biliary drainage, there were three cases which, despite the antibiotic protection, progressed with a prolonged febrile syndrome ranging between 37.5 - 38°C during the 7 - 10 days post ERCP and ES.
The method of endoscopic exploration of the biliary ducts was used on the whole sample included in the study, which was completed with therapeutic measures, papillo-sphincterotomy, with lithotomy or mechanical lithotripsy in the cases of lithiasis and concluded in a sequential manner using the laparoscopic method or converting it to a conventional procedure, in case of failure. It should be noted that the incidence of JPDD in late biliary pathology following surgery for cholelithiasis (remaining and native lithiasis) was of 17.61%.
Local anesthesia was used associated with an alert intravenous one. In fact, the patients were selected and those with severe respiratory failure, hemophilia, esophageal diverticula, severe kyphosis of the cervical spine were excluded, because this associated pathology represents a contraindication of the method, which may cause accidents during the endoscopy.
The investigation using contrast material lead to the diagnosis of the examined cases. A certain degree of disagreement with the preoperative examinations was noticed, mainly with percutaneous ultrasonography, i.e. approximately 33%, regarding the size of the extrahepatic biliary ducts and the number and size of the calculi. The low sensitivity of percutaneous ultrasonography of the terminal choledoch was also recorded. The number of evaluations using magnetic resonance imaging was too low to enable a comparison within the present study.

Results and Discussions
JPDD are found in a ratio of 5 -23% in endoscopically-examined patients, a completely different percentage from the results presented in necropsy studies (2.2 - 21%) or radiological ones (6%). (13,14,15) The frequency determined by our study was of 10.81% in the cases examined through ERCP for biliopancreatic diseases over a period of 10 years, from 1997 to 2007.
The importance of the presence of JPDD in the pathogenesis of biliary diseases or symptoms is well founded, but it was impossible to identify an exact causal connection between the presence of JPDD and diseases of the pancreas. Authors like Kim and al., (16), Van Basten and Stockbrugger (7), Van Spuy (16), demonstrated that there is a close connection between cholelithiasis and the presence of diverticula. Thus, Van Basten and Stockbrugger showed that 53% of the patients with JPDD also have CBD lithiasis, irrespective of the variant, in comparison with only 22% of the patients without JPDD.
It has been suggested that JPDD interferes with biliary drainage due to the extrinsic compression of CBD, a factor which makes the patient susceptible to biliary stasis and lithogenesis. This hypothesis is supported by the deformation of the anatomy of the inferior part of the choledoch, as a result of the presence of JPDD. In these patients the biliary tree is dilated, suggesting the existence of an extrinsic obstruction. Lotveit and al. (9) suggested a physio-pathologic model based on data from Oddi’s manometer which indicated that the pressure at the level of the oddian sphincter is lower in patients with JPDD. This relaxation of the sphincter allows the pathogenic microorganisms at the intestinal level, such as Escherichia Colli, to enter the CBD where they produce b-glycuronidase which initiates lithogenesis through the decomposition of biliary salts. Moreover, besides sphincterial incompetence, the CBD stasis predisposes to infections.
JPDD are acquired lesions. They are rare in patients under the age of 40, a fact also supported by the data in this paper, but their frequency increases with age. (11) In our study, according to age groups, the largest number of cases comprised patients aged 60 – 80. This connection with age suggests a degenerative process affecting the local resistance structures. The above mentioned dynamic process also interferes with biliary drainage, stimulating lithogenesis either by establishing an unfavourable pressure gradient in the biliary outflow, or by direct obstruction of biliary drainage due to the contraction of duodenal muscles and choledochal sphincters. Choledochal obstruction may be secondary to the impaction of food wastes inside the diverticula (18) determining the occurrence of secondary inflammatory phenomena. These, in turn, cause stasis in both the biliary and the pancreatic ducts, inducing the superinfection and increasing the capacity of the bile to determine the formation of calculi. (Fig. 9)

JPDD has immediate and late clinical implications, which affect the diagnosis of the diseases of the biliary-duodeno-pancreatic block. Among the immediate clinical implications, it is worth mentioning the multiple cases with obvious biliary-pancreatic symptomatology, an apparently "sine materia" symptomatology, which cannot be seen by using imaging techniques and which is considered a consequence of neurovegetative disorders. Transient jaundices of unknown origin are also important, being considered the result of hepatopathies, chronic pancreatitis, or of a malfunction of Oddi’s sphincter, none of these possible causes being objectified. The late clinical implication, but with major influences on both the liver and the pancreas, is represented by recurrent lithiasis, occurring at a distance after precise and correctly performed surgical interventions in the biliary area. (19)
In terms of treatment, JPDD can represent a significant risk factor when performing retrograde biliary-pancreatic endoscopy (ERCP), as it is an additional risk associated with the already known risks entailed by this method. Endoscopic sphincterotomy (ES) is also difficult to perform in the presence of juxtaposed diverticula, particularly interposed diverticula, in such a case even papillar cannulation being impossible to perform. The most frequently reported complications as a result of ERCP ± ES are acute pancreatitis, retroperitoneal perforation, hemorrhage and angiocholitis, such complications being more frequent in the presence of JPDD.
Last but not least, the importance of JPDD derives from late therapeutic implications. JPDD, unrecognised lesions prior to performing classical surgery, may lead to intra-operative incidents because the surgical procedures specific to the inferior part of CBD have a higher rate of complications in JPDD carrier patients. Sometimes, their presence is noticed too late, after having concluded a therapeutic maneuver requiring the extension of the surgical intervention, thus increasing the incidence of mortality.
In some circumstances, the discovery of the presence of JPDD being accidental, the diagnosis initially referred to determining the cause of the biliary obstruction. In this respect, the three consecutive diagnostic stages should be mentioned. The first stage is the clinical evaluation which distinguishes between obstructive jaundice and hepatocellular jaundice, based on the study of case history data, i.e. clinically objective or laboratory findings. The next stage is represented by percutaneous ultrasonography and computerized tomography (CT), focussing on the site of the obstruction. Ultrasound diagnosis has become a compulsory method used in any painful abdomen, being non-invasive and repetitive, although limited in the case of the terminal choledoch. The same limitations also apply to computerized tomography. During this stage, endoscopic exploration (ERCP) intervenes, allowing the opacification of the biliary ducts, followed or not by a therapeutic maneuver. This is also the time when JPDD are discovered, the anatomical type is determined, the size and pathology associated with or caused by them is evaluated. In our opinion, this makes the endoscopic examination the fundamental exploration method based on which, according to the associated lesions, the non-invasive or, on the contrary, the surgical treatment of the lesions is selected. For the diagnosis of the diseases associated with the biliary tree area, cholangio-MRI is used, in superposable conditions in point of specificity and biliary sensitivity. Due to its relatively non-invasive character, this procedure avoids the complications caused by ERCP/ES, but, at the same time, it cannot provide therapeutic possibilities to treat the diagnosed pathology. (20)
Papilla cannulation in patients with JPDD is significantly more difficult than cannulation in the absence of the diverticula. In the literature, failures ranging between 5.8 - 44.7% have been recorded in patients with JPDD as against 5.4 -3.3% in patients without JPDD. (21,22) In the studied cases, the percentage was of 16.92% as against 11% in patients without JPDD, probably also due to the considerable number of interposed JPDD which were found. Because the papilla was situated in the innermost part of the diverticulum, the externalization and catheterization of the papilla could not be performed. In this respect, many authors have reported exceptional technical methods to overcome the obstacle standing before an accurate diagnosis using ERCP and to perform consecutive therapeutic maneuvers. Fogel and al. (13) offer solutions involving the placing of an intrapancreatic stent and the use of the pre-cut method; Naotaka Fujita and al. use two instruments inserted through a broad working canal of 4.2 mm of the lateroendoscope. (23) Thus, a biopsy forceps is introduced to externalize the papilla and a sphincterotome on a catheter guide to perform ERCP/ES. Ilias Scotiniotis and al. (24) perform the externalization of the papilla with the biopsy foceps and the fixation of the duodenal mucosa with an endoclip, which will be removed after the endoscopic procedure.
The complications of sphincterotomy are exacerbated in patients with JPDD. Authors like Vaira and al. (21), Peter Cotton and al. (25), etc., have reported a rate of complications of 8.8% in patients with JPDD as against 2.4% in those without JPDD. The number of complications is not as frequent as that found by Boerde and al., namely 16.8% in patients with JPDD as against 2.7% in those without JPDD. (26)
In the cases we studied we assessed the following three (3) elements:
- Impossible cannulation - 70% in patients with interposed JPDD;
- Difficult cannulation consisting in procedures exceeding 20 minutes, and reaching 40 – 50 minutes;
- ES typical complications, out of which the most numerous were hemorrhages along the section, which stopped after injecting 1/10000 adrenaline or electrocauterization and pancreatic reactions manifested through pain and significant increases of amylases, but which, under treatment, did not require surgical intervention. (Table 7)
All these complications led to a significantly increased rate of morbidity in comparison with that of JPDD non-carrier-patients.
As far as the clinical implications are concerned, we have identified two important moments related to the influence of the presence of JPDD on the symptomatology reported by patients, namely:
a) immediate clinical implications determined by the investigation of patients with biliary-pancreatic symptomatology:
- patients with symptoms suggesting the impairment of the extrahepatic biliary tree, which apparently are “sine materia” – the investigations did not reveal a clear and objective cause;
- patients with transient jaundice of unknown etiology, which cannot be made objective using any screening method, except by endoscopy.
b) late clinical implications consisting in the recurrence of lithiasis in patients who benefited initially from an accurate diagnosis obtained by using complex methods of investigation of the vesicolithiasis lesions or mixed vesicocholedochal lesions. These patients had previously been treated either by classical or laparoscopic means. The intra-operative exploration involved both the radiological and the instrumental investigation of the CBD without revealing any migrated or local lithiasis elements or any other type of lesions of the extrahepatic biliary tree. In these circumstances, the frequency of lithiasis lesions at the level of CBD is surprising and cannot be explained by any pathologic element found prior to the surgical intervention, which was performed with accurate indications and techniques.
As far as the therapeutic implications are concerned, they also refer to two moments:
a) immediate therapeutic implications related to the endoscopic approach of the papilla and the CBD, which depend, on the one hand, on the difficulty of the catheterization in the presence of JPDD, and, on the other hand, on the worsening of the complications occurring during the performance of ES and of the therapeutic procedures on the CBD and subsequently.
b) late therapeutic implications related to the accidental discovery of JPDD at the level of the biliary duct, during classical surgical interventions, when both the attitude and the surgical procedure had to be modified in order to avoid retroduodenal perforation, acute pancreatitis or hemorrhage through a direct intervention on the papilla, which intervention was required by the nature of the upper lesions.

Conclusions
1. The duodenal “buttonhole” as an anatomical functional area is of crucial importance, because the achievement of normal biliary hydrodynamics depends on its integrity, since it is a component of the duodenal canal antireflux system (choledoch and Wirsung). The defects of the “buttonhole“ affect the hydro-dynamics of the biliary and pancreatic-duodenal discharges, but also allow the duodenal canal reflux during the “big sets” of duodenal contractions, when the pressure exceeds 70 mmHg, while the biliary (15 mm Hg) and pancreatic (18 mm Hg) pressure are at a much lower level.
2. There is a consistent pathology belonging to the duodeno-biliary reflux diseases, comparable to some extent with the duodenogastric reflux mechanisms occurring in the context of pylorus dissynergia or failure of the pylorus. An apparently superposable situation can be found in the determinism of the gastro-esophageal reflux following heart failure.
3. Besides the alteration of the antireflux functions, the diverticulum produces a series of mechanical disorders in the ampullar area, whose main consequences are the biliary stasis and the occurrence of lithogenesis conditions.
4. We have been noticed that duodenal diverticula are frequently unknown. Biliary pain is treated (cholecystectomy), but later on new diseases (of the CBD) will develop, be they lithiasis or nonlithiasis.
5. Late diseases in patients after cholelithiasis surgery, present un unexpectedly high incidence of DJPP, an incidence of 17.61 % as shown in our study, which is superposable to the data in the literature.
6. The recurrence of biliary diseases, such as cholangitis, after a cholecystectomy or a biliary desobstruction, requires mandatory endoscopic exploration to identify a diverticulum of the “duodenal window”. If such a diverticulum is found, it is legitimate to perform a choledochojejunal derivation on the “Y”-shaped ansa, to place the Oddian area at rest and to prevent the reflux and the stasis on the biliary ducts.

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