**3. Chronic pancreatitis**

## **3.1 Endoscopic diagnosis of chronic pancreatitis**

Diagnosis of CP derives from a combination of clinical symptoms, as abdominal pain, malabsorption, diabetes mellitus, and pancreatic function tests, as fecal elastase and morphological pancreatic abnormalities, and as calcifications, atrophy, ductal dilatation or strictures, and pseudocysts. At advanced stages of the disease, when both symptoms and morphological alterations are present, reaching the diagnosis is generally easy. On the contrary, it is much more challenging in earlier stages, given both to the low sensitivity and specificity of usual diagnostic methods and to the absence of a widely shared definition of early CP. According to a recent consensus, the term "early" describes the disease state rather than the disease duration; thus, it refers to a condition in which features of advanced CP are lacking [38].

Imaging has a fundamental role in the diagnosis and therapeutic management of patients with CP, and the most frequently used imaging modalities for CP are EUS, ERCP, MRI, computed tomography (CT), and abdominal ultrasound (US). EUS and ERCP showed the highest sensitivity (81 and 82%, respectively) and specificity (90 and 94%, respectively) [39]. Nevertheless, guidelines recommend using US, CT, and MRI as first imaging diagnostic approach, due to their larger availability and noninvasiveness, reserving EUS only to cases in which cross-sectional imaging is not conclusive [40]. ERCP should be used for therapeutic purposes only.

EUS diagnosis of CP is based on the assessment of ductal and parenchymal morphologic features, which correspond to histopathological changes. They initially embraced 11 criteria, then become 9, which are summarized in **Table 2**. In the absence of any criteria, a diagnosis of chronic pancreatitis is unlikely, whereas when five or more criteria out of nine are present, chronic pancreatitis is likely [41].

Since the different pathological characteristics in CP have not the same importance in terms of diagnostic value, the "nine criteria classification," giving to each criterion the same relevance, has not a high diagnostic accuracy. Thus, another scheme,


### **Table 2.**

*Nine classic criteria for establishing a diagnosis of chronic pancreatitis on EUS.*


### **Table 3.**

*The Rosemont classification for endoscopic ultrasound-based criteria for the diagnosis of chronic pancreatitis.*

named Rosemont classification, proposed by the International Consensus, divides parenchymal and ductal criteria in major and minor features. Major criteria for CP are hyperechoic foci with shadowing and main pancreatic duct (PD), calculi and lobularity with honeycombing. Minor criteria for CP are cysts, dilated ducts, irregular pancreatic duct contour, dilated side branches, hyperechoic duct wall, strands, nonshadowing hyperechoic foci, and lobularity with noncontiguous lobules (**Table 3**) [42]. Basing on these consensus criteria, the EUS diagnosis could be consistent with CP, suggestive of CP, indeterminate for CP or normal (**Table 4**).

### **3.2 Endoscopic management of obstructive pancreatic ductal stone**

Pancreatic stones seem to arise either as direct and evenly calcified stones or as radiolucent protein plugs that may or may not become calcified during the course

**Consistent with CP** A. 1 major A feature (+) ≥ 3 minor features B. 1 major A feature (+) major B feature C. 2 major A features **Suggestive of CP** A. 1 major A feature (+) <3 minor features B. 1 major B feature (+) ≥3 minor features C. ≥5 minor features (any) **Indeterminate for CP** A. 3 to 4 minor features, no major features B. Major b features alone or with <3 minor features **Normal** ≤ 2 minor features, no major features

### **Table 4.**

*EUS diagnosis of CP on the basis of consensus criteria.*

### *Endoscopic Management of Acute and Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.105930*

of the disease [43]. The majority of pancreatic stones are calcified and radiopaque. Their prevalence increased with time and was detected in approximately 62% of patients with CP [44]. The best candidates for the successful treatment of painful CP are patients with solitary stones, with distal obstruction of the main pancreatic duct (located in the pancreatic head), and with a mean size of 10 mm and associated with strictures [4, 45].

ERCP and extraction are recommended for smaller (< 5 mm), nonimpacted stones of the main pancreatic duct [46]. ERCP can achieve main pancreatic duct drainage by sphincterotomy of the major and/or minor papilla, by short-term stent placement, or by pancreatic stone extraction using basket or balloon. Endoscopic therapy is also preferable in patients with risk factor (older age, co-morbidities) instead of surgery.

ESWL is recommended for fragmentation of large (> 5 mm), radiopaque stone(s) located preferentially in the pancreatic head [45]. For radiolucent calculi (difficult to target with X-ray), a nasopancreatic tube can be placed to facilitate targeting of the stones during ESWL [47].

Endoscopy alone allows stone extraction in a minority of CP patients (9–14%) [48, 49]; ESWL prior to endoscopy therapy allowed extraction of pancreatic stone in >80% of patients after failed stone extraction at primary endoscopy [48]. Pancreatic mechanical lithotripsy is burdened by major complications compared to biliary mechanical lithotripsy, and these included trapped or broken basket, traction wire fracture, and pancreatic ductal leak.

Pancreatic stone fragmentation after ESWL is obtained in 90% of patients (after multiple sessions) [50].

In a recent meta-analysis, ESWL alone allowed complete/partial main pancreatic duct clearance in 70%/22% of patients, respectively; pain was absent or mild–moderate during the 2 years following treatment in 52.7% and 33.4% of patients, respectively; quality of life improved in 88.2% of patients [51].

ESWL in not free from complications: most frequent is pancreatitis (up to 4.2%). The most severe complications are infection, acute stone incarceration in the papilla, bleeding, and perforation. Other minor adverse events reported are asymptomatic hyperamylasemia, hematuria, gastrointestinal mucosal injury, skin erythema, and tenderness in the region of contact with the shockwave head [52].

The systematically addition of endoscopic therapy after ESWL is not recommend by the European Society of Gastrointestinal Endoscopy (ESGE) [45]. Some studies and retrospective series reported similar decreases in main pancreatic duct diameter and no differences in pain resolution, instead of longer hospital stay and higher costs for patients who had ESWL combined with ERCP [53, 54].

Per-oral pancreatoscopy (POP)-assisted electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) is an emerging technology to fragment large intraductal stone(s). In a recent review and meta-analysis, technical success and overall fragmentation success were 91.2% and 85.5%, respectively [55]. Furthermore, stone fragmentation and ductal clearance could be achieved in 62% of patients in a single session; this suggests that POP may be an effective alternative to ESWL. Currently, with the newer version of cholangioscopes (SpyGlass-DS, Boston Scientific, Marlborough, MA), this technique will increase in the next few years.

The safety of POP-guided lithotripsy has been confirmed in two systematic reviews [55, 56]. The most common adverse events were post-ERCP pancreatitis (7%), pain (4.7%), perforation (4.3%), and hemorrhage (3.4%); overall, the incidence of adverse events was 11.2% with EHL and 13.1% with LL. Moreover, the technique has many advantages: it allows direct visualization of the stones (reducing ductal injury),

it can identify radiolucent stones, and it can confirm ductal clearance after lithotripsy [57]. However, the weaknesses of POP include need of expertise, additional costs, and need to dilated pancreatic duct (to allow insertion of pancreatoscope).

ESGE suggests to consider POP-guided lithotripsy when ESWL is not available or for stones that were not fragmented after adequately performed ESWL [45].

### **3.3 Endoscopic management of pancreatic stricture**

Strictures of the main pancreatic duct may be a complication of a previously embedded stone or a consequence of acute inflammatory changes around the main pancreatic duct [58]. Strictures may be classified as either nondominant or dominant. Dominant main pancreatic duct strictures are defined by the presence of at least one of the following characteristics: 1) upstream main pancreatic duct dilatation (≥6 mm in diameter), 2) prevention of contrast medium outflow beside a 6-Fr catheter inserted upstream from the stricture, and/or 3) abdominal pain during continuous infusion of a nasopancreatic catheter inserted upstream from the stricture with 1 L saline for 12–24 h [45, 59].

Before endoscopic treatment of man pancreatic duct strictures, malignancy should be excluded, by cross-sectional imaging and cytology brushing (especially for patients without pancreatic calcification) [60].

Endoscopic management of pancreatic duct stricture includes pancreatic sphincterotomy, dilatation of the stricture using bougie, balloon or Soehendra stent retriever, followed by placement of one or multiple plastic stents [61]. Technical success is defined by stent insertion across a dominant main pancreatic duct stricture (or most proximal one in case of multiple strictures), and it aims to 1) decompress the main pancreatic duct and improve pain and 2) dilate the stricture(s). Less frequent indication includes facilitation of main pancreatic duct stone clearance in association with ESWL [62].

Dominant strictures are single in >80% of the patients, and insertion of single 10-Fr plastic stent can be used as the initial endoscopic therapy. In responders, endotherapy should be continued for at least 1 year before permanently removing the stent. Stent should be replaced if necessary (every 6 month or on demand), based on symptoms or signs of stent dysfunction [45].

Stricture resolution was achieved in 9–50% of patients [58, 63]; long-term pain relief is experienced by about two-thirds of patients (67.5%) after stenting. However, resolution of the stricture after stent removal was observed only in a minority of patients [64]. The follow-up after stent removal in most study was >24 months.

Refractory pancreatic duct stricture is defined as a symptomatic dominant stricture that persists or relapses after a single pancreatic stent placement indwelling for 1 year [45]. A substantial proportion of pancreatic duct stricture may not respond to conventional endoscopic therapy (single plastic stent). Treatment options for these strictures are multiple side-by-side plastic stents, self-expandable metal stents (SEMSs), or surgery. The use of multiple plastic stenting during multiple sessions of endotherapy allowed stricture resolution in 89.5% of patients and pain relief in 77.1% of patients after 9.5 years follow-up [65, 66].

More recently, the use of SEMS and biodegradable stents has been described for refractory pancreatic strictures. With respect to SEMS, only fully covered SEMS (FCSEMS) has provided acceptable results: pain improvement in 37–88% of patients (follow-up of 3–4 years) [67, 68]. However, there were no differences in pain relief between multiple plastic stenting and FCSEMS (84.2% vs. 85.2%). The main advantage of FCSEMS over multiple stenting is a lower number of endoscopic sessions [69]. *Endoscopic Management of Acute and Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.105930*

Regarding complication with plastic stent, the most commonly reported in the short term were mild pancreatitis (severe pancreatitis was very rare) or worsening of pancreatic pain, followed by sepsis (2.6%), cholangitis (2.3%), and post-sphincterotomy bleeding (1.5%). During follow-up, distal (3.6%) or proximal (2.7%) stent migration and stent obstruction (almost all stent become obstructed for3 months) are reported. Furthermore, stent-induced ductal lesions were described in 18% of patients and mortality in 0.4% [45].

Adverse events reported with the use of FCSEMS include pain (7–20%), stent migration (15–46%), de novo strictures (16–27%), pancreatitis, cholestasis, and cholangitis [45, 70].

In symptomatic patients with main pancreatic duct obstruction and failure of conventional transpapillary drainage, endosonography-guided (EUS-guided) therapy can be a chance. The technic consists of puncturing the main pancreatic duct through duodenal or gastric wall, and a guidewire is inserted in the pancreatic duct to proceed with transpapillary (rendezvous technique) or transmural drainage using a stent [71]. This is a difficult technique that should be performed only in tertiary centers after multidisciplinary discussion [45]. In successful procedure, immediate pain relief has been reported in a majority of patients (50–100%); during long-term follow-up, pain relief was achieved in 70–90% of patients. In large series, failure of EUS-guided technique occurs approximately in 10% of cases and complications occur in about 10% that include severe pancreatitis, bleeding, hematoma, and perforation [72, 73]. Frequently (20–55%), stent migration or occlusion needs endoscopic reintervention.

### **3.4 Endoscopic management of chronic pancreatitis complications**

### *3.4.1 Biliary stricture*

Biliary strictures occur in about 10–15% of patients with CP [74]. Strictures can be asymptomatic or present with jaundice, cholangitis, choledocholithiasis, or asymptomatic elevation of ALP and/or bilirubin [75]. Before endoscopic treatment, malignancy should be reasonably excluded.

Biliary strictures related with CP are resistant to endoscopic treatment due to periductal fibrosis and calcification [74]. Endoscopic treatment consists of an ERCP with stent(s) placement to achieve biliary decompression. Only a small percentage of patients respond to a single plastic stent placement [76]. The suggested approach for benign biliary stricture consists of temporarily dilating the stricture using multiple side-by-side plastic stents (exchange every 3–6 months) or FCSEMS [77, 78]. Both approach provided similar results 2 years after stent removal (88% vs. 90.9%, respectively) and similar treatment-related morbidity [79]. Short biliary strictures respond better to endoscopic therapy [80], and severe CP and long length stricture are predictors for stricture recurrence [81]. After 1 year of unsuccessful endoscopy therapy, surgery should be considered.

### *3.4.2 Pseudocyst and pancreatic duct leak*

Approximately one-third of patients with CP develop pancreatic pseudocyst (PPC) during the course of their disease, and less than 10% of these cases will resolve spontaneously [82]. PPCs should be differentiated from cystic neoplasm.

The indications for PPC drainage are the presence of symptoms (abdominal pain, gastric obstruction, early satiety, weight loss, and jaundice), progressively cyst enlargement, or complications (infection, bleeding, rupture, and fistulization to adjacent hollow structures) [45, 83]. Asymptomatic pseudocysts can safely be kept under observation, provided they are carefully monitored and do not increase in size.

Endoscopic therapy of PPCs consists of transmural drainage (EUS-guided or conventional) with plastic or dedicated stents (PPCs ≥5 cm, no communication with pancreatic duct), endoscopic transpapillary drainage (PPC < 5 cm, communicating with pancreatic duct), or using a combination of these techniques [84]. Technical success is defined as insertion of the stent between the PPC and the digestive lumen [85]; instead clinical success is defined as disappearance of symptoms with resolution of the PPC or a decrease to less than 2 cm [86]. Compared with percutaneous drainage, endoscopic drainage is associated with higher clinical success rate, fewer reinterventions, shorter hospital stay, similar morbidity, and recurrence rate [87].

For an adequate treatment planning CT scan, MRI, EUS, and/or ERCP should be performed before PPC drainage to diagnose 1) the presence of necrotic debris inside the fluid collection (this may impede endoscopic drainage), 2) main pancreatic duct rupture (partial or complete), and 3) the presence of pseudoaneurysms close to the pseudocyst. If no ductal rupture is present, only transmural drainage can be performed; if partial ductal rupture is present, stent placement bridging the rupture is associated with the treatment success; if complete ductal rupture is present, long-term indwelling of transmural stents should be considered to avoid PPC recurrence [45, 88, 89]. Other technical aspects are underlined in Section 2.4.2.

### *3.4.3 Vascular complications*

During CP progression, patients can develop, although rare, vascular complications that are difficult to treat and are responsible for significant morbidity and mortality. The CP-related vascular complications can be classified into arterial and venous (splanchnic thrombosis with splenic vein thrombosis) [90]. For the management of vascular complications, both surgical and nonsurgical interventions (endovascular, percutaneous, and endoscopic using EUS) are available. Nowadays, nonsurgical treatment options are the first-line therapy for these complications [90]. Obviously in this paragraph, we will focus on endoscopic technique.

Arterial complications are reported in 1.3–10% of patients with CP, and pseudoaneurysm is the most common arterial complications (approximately 70% of bleeding complications in CP, with a reported mortality rate of 15–50%) [91, 92]. They can be asymptomatic or present with hemorrhage due to rupture (hemosuccus pancreaticus, gastrointestinal bleeding, or intra-retroperitoneal hemorrhage), pain, or obstructive symptoms [92]. All pseudoaneurysms diagnosed on imaging require treatment irrespective of size as they have a high risk of rupture and life-threatening hemorrhage. The endoscopic approach is used for pseudoaneurysms detected on EUS. Hence, EUSguided injection of the embolic agent (thrombin) is reserved for pseudoaneurysms arising from splenic and gastroduodenal arteries [90, 93].

The reported prevalence of venous thrombosis in patients with CP ranges from 3 to 41.7% with a pooled prevalence of 11.6%. Of the splanchnic veins, splenic vein thrombosis is the most common due to its proximity to the pancreas (prevalence ranging from 1.5 to 41.7%). Splenic vein thrombosis can extend to the portal vein in 1.5–4% of patients. Mesenteric venous thrombosis is uncommon and is reported in 0.8–1.1% of patients with CP [94]. In patients presenting with gastrointestinal variceal bleeding, endoscopic or surgical intervention of the gastroesophageal varices is required. Endoscopic therapy is preferred for patients without significant pancreatic symptoms as they do not require surgery for CP [90]. Esophageal varices can be treated either with banding or sclerotherapy with conventional sclerosants. For gastric or fundal varices, these are not effective, and recent studies have reported reasonable success rates with cyanoacrylate glue injection [95].
