WGC is a technically simple method. Normally, we use a hydrophilic tipped guidewire (diameter 0.035 or 0.025 inch), which is preloaded into a catheter or pull-type papillotome. The papillotome is oriented in the 11 to 12 o’clock position on the AV and is bent to ensure correct alignment with the axis of the bile duct. As a direct contact method, following minimal insertion of the papillotome into the orifice of the AV, the guidewire is carefully advanced into the common bile duct (CBD) under fluoroscopic guidance until it is seen to enter the CBD. For the noncontact method, biliary access is achieved using the slightly protruding 2 to 3 mm tip of the guidewire on the papillotome to make smooth contact with the AV orifice. This noncontact method may avoid direct contact injury caused by the tip of the cannula or papillotome. If the PD is entered unintentionally, the guidewire is simply withdrawn and a further attempt is made to negotiate the CBD. If unintentional PD insertion occurs repeatedly, early switching to another appropriate method, such as double guidewire cannulation (DGC) or prophylactic pancreatic stent (PS) insertion followed by precut or transpancreatic septostomy, should be considered to facilitate selective access or minimize complications. However, the insertion frequency, procedure time, and the number of PD insertions of the guidewire, including retrials, have not been defined clearly. A recent ESGE guideline recommended pancreatic WGC in patients where selective biliary cannulation was difficult and repeated unintentional PD access occurred [12]. It also recommended attempting the placement of a prophylactic PS in all patients in whom pancreatic guidewire-assisted attempts at biliary cannulation have failed.

Compared with CC, the WGC technique increases the primary selective biliary cannulation rate and reduces the frequency or severity of PEP. Numerous randomized controlled trials (RCTs) have demonstrated the benefits of WGC (Table 1) [6-11,15]. A systematic review and meta-analysis also reported that WGC reduced the frequency or severity of PEP compared with CC. In addition, WGC was shown to be associated with a higher selective biliary cannulation rate [5,13]. A recent meta-analysis of 12 RCTs showed that the WGC technique significantly reduced PEP compared with the CC technique (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.32 to 0.82). In addition, the WGC technique was associated with greater primary cannulation success, fewer precut sphincterotomies, and no increase in other ERCP-related complications [5]. Therefore, a recent ESGE guideline suggested that WGC should be employed as the initial selective cannulation method [12].

The mechanisms by which WGC reduces the risk of PEP risk can be explained by several ways. Masci et al. [14] identified several technical problems, including frequent contrast injections into the PD, difficult cannulation, precutting, pancreatic sphincterotomy, and balloon dilatation of the sphincter of Oddi, as risk factors for PEP in their meta-analysis study. The WGC technique may reduce the risk of pancreatitis by directly preventing unintentional contrast injection into the PD and pancreatic acinarization, facilitating early biliary cannulation, potentially limiting papillary trauma, or reducing the need to attempt precut sphincterotomies.

The definition of what constitutes “difficult” cannulation is still imprecise. Lee et al. [11] defined difficult as the failure to achieve biliary access after attempting to do so for 10 minutes, or after more than five unintentional PD cannulations. Artifon et al. [9] defined cannulation as difficult when 7 to 10 attempts were required to achieve successful biliary access. Recent studies suggested stricter criteria for difficult biliary cannulation. More RCTs are needed to establish cannulation difficulty criteria and arrive at a consensus on the definition of difficult. At present, more than five cannulation attempts, a cannulation time of more than 5 minutes, or unintentional cannulation of the PD on more than one occasion are considered to represent a difficult cannulation in experienced hands [12].

Although WGC may reduce the risk of PEP, it does not do so in patients with suspected sphincter of Oddi dysfunction (SOD) or in patients who are subjected to unintentional WGC into the PD. In high-risk patients, such as those with SOD, repeated unintentional WGC into the PD may trigger PEP via mechanical injury or because of increases in hydrostatic pressure due to edematous obstruction of the AV. Therefore, when unintentional PD guidewire cannulation occurs, WGC followed by temporary placement of a PS may be preferable to WGC alone to prevent increases in pancreatic enzyme levels and reduce the frequency or severity of PEP, especially in high-risk patients [3]. The ESGE also recommended the insertion of a prophylactic PS in all patients in whom pancreatic WGC attempts at biliary cannulation were made [12].

Since DGC was first described by Dumonceau et al. [16], it has shown promise in overcoming difficult biliary cannulation and has been commonly used in cases of repeated unintentional PD cannulations. Technically, DGC may be an effective alternative to frequent unintentional PD cannulation. In DGC, while the previously inserted PD guidewire is in place, an attempt is made to insert another guidewire in the direction of the CBD. The placement of the guidewire in the PD may facilitate selective biliary access, using another sphincterotome or a catheter in the same working channel as the first guidewire. The placement of the guidewire deep into the main PD may provide a variety of benefits, such as lifting the AV toward the working channel, straightening the PD and common channel, opening a stenotic papillary orifice, or potentially minimizing repeated guidewire insertions into the PD [17].

Compared with the CC method, DGC has been suggested as a useful approach for overcoming difficult biliary cannulation. However, two prospective RCTs that compared the use of DGC versus CC methods in patients with difficult biliary cannulation reported conflicting results in terms of technical success and complications [18,19]. Maeda et al. [18] reported that the cannulation rate using the DGC technique was higher than with the CC method (93% vs. 58%, respectively), with no PEP. In contrast, Herreros de Tejada et al. [19] showed that DGC was not superior to the CC technique in terms of technical success, and that PEP was more prevalent in the DGC group (17% for DGC and 8% for CC). More large-scale comparative studies are required to clarify the controversy and the role of DGC versus CC.

A comparison of DGC with transpancreatic precut sphincterotomy revealed that both techniques were useful in cases of unintentional PD cannulation [20-22]. The overall technical success and complications were not different in the reported studies. The use of a PS could significantly reduce the incidence of PEP. However, unlike transpancreatic sphincterotomy, persisting with DGC may extend the cannulation time. In cases of difficult cannulation or unintentional PD cannulation, to reduce the severity and incidence of PEP, a sequential algorithm (with crossover techniques) may be a useful alternative, rather than persisting with a single technique.

In addition to PEP, guidewire-related perforation may be an important complication. Although the tip of the guidewire is smooth and hydrophilic, perforation is a possibility. Common risk factors for guidewire-related perforation include Billroth II subtotal gastrectomy, endoscopic sphincterotomy, precut sphincterotomy, intramucosal injection of contrast agent, long procedure times, periampullary diverticulum, bile duct stricture, SOD, old age, and inexperience [23,24]. In terms of the instruments used, perforation may also be associated with the texture of the guidewire itself and the flexibility of the tip. In the presence of these risk factors, perforation often occurs locally around the AV or proximal biliary obstruction. When biliary cannulation is difficult and the operator or assistants force the entry of the guidewire into the bile duct, guidewire-induced perforation may occur as a result of the AV edema or injury and inflammation of periampullary lesions [25,26]. Moreover, the operator may not detect a microperforation created by the guidewire.

However, guidewire-related perforations are usually local microperforations and are clinically asymptomatic in most patients. Patients usually recover within 24 to 48 hours after conservative treatment, including fasting and broad-spectrum antibiotics [25,26]. However, if the perforation is not detected at an early stage, the patient may develop abdominal pain or fever. During insertion of a drainage tube, catheter, or dilatator, further damage may unwittingly be done to the microperforation, increasing its size to the extent that surgery is required.

In a retrospective study, Abu-Hamda et al. [53] compared three techniques: precut fistulotomy with occasional PS; precutting with a blended current without PS; and precutting with a pure cutting current and frequent PS. The success rates for each technique were not statistically different (95.5%, 95.7%, and 89.6%), and the PEP rates also did not differ significantly (0%, 6%, and 3%). Precut fistulotomy reduced the risk of PEP compared with the conventional precut method. Another retrospective study by Katsinelos et al. [54] compared precut fistulotomy, conventional precut, and transpancreatic sphincterotomy. In that study, the success rates were 92.3%, 97.7%, and 100% for the three techniques, respectively, and the PEP rates were 2.6%, 20.9%, and 22.4%, respectively (p=0.001). Precut fistulotomy resulted in a significantly lower rate of PEP compared with conventional precut or transpancreatic sphincterotomy. Another RCT by Mavrogiannis et al. [29] also showed that the occurrence of PEP was significantly lower with precut fistulotomy than with precut papillotomy (0% vs. 7.6%, p<0.05), without any difference in the technical success.

Theoretically, precut fistulotomy can prevent direct injury to the PD or edematous change of the AV compared with other conventional precut techniques where the precut starts at the orifice of the AV. Thus, according to the ESGE guideline, precut fistulotomy may be recommended as a precut technique [12].

Transpancreatic septotomy involves incision of the biliary-pancreatic septum, which separates the PD from the bile duct, through the PD orifice [55]. The septum is located between the PD and the CBD. Difficult biliary cannulation may be related to duct blockage by the ampulla septum in cases where the guidewire repeatedly enters the PD [56]. Unlike a freehand technique, such as an NK, papillary transpancreatic septotomy can be performed in patients where cannulation is difficult or PD cannulation occurs. In papillary transpancreatic septotomy, a papillotome is used, and there is no need to exchange devices after the introduction of the guidewire into the PD. When unintentional PD cannulation has occurred repeatedly, the septotomy or sphincterotomy is relatively easy. Wire-assisted septotomy can be performed after introducing a guidewire into the PD, followed by sphincterotomy, maintaining the direction of the bile duct at 11 o’clock. By cutting through the septum between the PD and bile duct, the biliary and pancreatic orifices are both rendered visible [56-58]. The overall technical success of this procedure was reported to range from 85% to 97.5%, with a lower incidence of complications [31,55,58-60]. Another useful and safe option for pancreatic sphincterotomy is to precut along the PS, following the placement of a prophylactic PS when unintentional PD cannulation occurs. In these cases, the second procedure (i.e., the precut from the orifice) is relatively easy and more comfortable for the operator than a freehand technique. Precut along the PS also prevents or minimizes PEP and acts as a guide to facilitate selective biliary access [3].

As described above, the precut-related complications, such as PEP, bleeding, and perforation, have now been reported to be similar to those associated with conventional sphincterotomy in experienced hands. PEP in particular, one of the most severe complications, is reported to have a similar rate to that in conventional sphincterotomy. However, prolonged and repeated cannulation procedures prior to precut with inexperienced hands may increase the risk of PEP. Among various techniques, precut fistulotomy reduced the risk of PEP compared with the conventional precut method, and precut following placement of prophylactic PS also reduced the rate of PEP [50-53,61]. However, still more comparative studies with transpancreatic septotomy, taking into account the type of devices and criteria such as difficult cannulation, will be needed to clarify the question of complications.