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ENDOSCOPIC MANAGEMENT OF PANCREATIC DISEASES
R BAIJAL
Gastroenterology Centre, Jagjivanram Hospital, Mumbai.
Endoscopic techniques are used increasingly in the management of acute and chronic pancreatitis. In many instances surgery can be avoided by endoscopic intervention as in endoscopic drainage of pseudocysts. Other conditions that can be managed by endoscopy include biliary calculi in acute biliary pancreatitis, pancreatic duct disruptions, strictures or stones and treatment of potential causes of pancreatitis such as sphincter of Oddi dysfunction and pancreas divisum. Despite widespread use of these endoscopic techniques, there are few controlled studies comparing pancreatic endotherapy with either surgical intervention or medical treatment.
Management of patients with acute recurrent and chronic pancreatitis is hampered by our incomplete understanding of the pathogenesis of pancreatic inflammation and mechanism of pancreatic pain. The short term assessment of therapies is made more difficult due to the relapsing and remitting nature of pain in pancreatic disease. Therefore, a detailed understanding of the natural history of pancreatitis is required prior to undertaking endoscopic treatment of pancreatic diseases.
BILIARY PANCREATITIS
Gallstone disease is one of the most common causes of acute pancreatitis. Although most episodes are mild and resolve spontaneously, in some patients, severe pancreatitis with local and systemic complications develop and may lead to death in 10% to 15% patients.
A pathbreaking, randomized, controlled study by Neoptolemos and Carr-Locke[1] showed significantly lower complication (24% vs 61%) and mortality (4% vs 18%) rates and a shorter mean length of hospital stay (LOS; 9.5 vs 17 days) in patients with predicted severe pancreatitis who underwent ERCP with sphincterotomy and stone extraction within 72 hours compared with patients who received supportive medical management. Early ERCP had no beneficial effect on patients with mild pancreatitis. The mechanism by which patients with severe pancreatitis benefit from ERCP is unclear as ERCP cannot reverse the damage already done to the pancreas. It has been suggested that patients with severe pancreatitis have a high prevalence of residual common bile duct (CBD) stones which may lead to superimposed cholangitis or continue to irritate the pancreas. Endoscopic removal of these residual stones should benefit these patients.
Several other studies have shown different results. Fan et al[2] in a similar randomized trial from Hong Kong reported no significant difference in complication or mortality rate with respect to pancreatitis, but early ERCP did protect against cholangitis, which occurs in 9% to 10% of patients. In a German multicentre study[3] patients with biliary pancreatitis, excluding those with biliary obstruction or cholangitis, were randomized to ERCP within 72 hours or to noninvasive therapy. There was no significant difference in mortality or overall complication rate, but the ERCP group had more severe complications, especially respiratory failure. This study has been criticized because it excluded the patients most likely to benefit from endoscopic therapy, and because it was a multicentre study, not all hospitals had a high degree of experience in performing ERCP in acute settings.
Despite conflicting data, there is a strong consensus that patients who have predicted severe pancreatitis with evidence of a CBD stone or biliary obstruction benefit from urgent ERCP when performed by experienced operators. A meta-analysis[4] with pooled data showed a 34.6% relative risk reduction for complications and a 42.9% relative risk reduction for death in patients treated with urgent ERCP, sphincterotomy and stone extraction.
stent in case of chronic pancreatitis.
case of pancreas divisum.
cysto gastrostomy.
cystogastrostomy stent in situ.
chronic pancreatitis.
Occult Biliary Stone Disease or Crystals
Biliary microlithiasis is a significant cause of unexplained acute pancreatitis. In two prospective studies,[5,6] microscopic evaluation of bile was performed in patients convalescing from idiopathic pancreatitis who had no evidence of cholelithiasis. Two thirds of patients had microscopic evidence of cholesterol or calcium bilirubinate crystals; patients with bilirubinate crystals demonstrated sludge on transcutaneous sonography. Importantly patients with microlithiasis had significantly fewer recurrent attacks of pancreatitis when treated with cholecystectomy, endoscopic sphincterotomy, or ursodeoxycholic acid.
Idiopathic Pancreatitis
Gallstone disease and alcohol abuse cause 75% to 80% of all cases of pancreatitis. Including metabolic causes, drug-induced disease, trauma, and viral illness, only approximately 10% of cases of acute pancreatitis remain idiopathic or unexplained.[7] ERCP has an important role in the evaluation of patients with idiopathic disease. Because ERCP is an invasive procedure with well-defined complications, the following question arises: In which patients is ERCP indicated? Most authorities agree that ERCP is indicated:
After two or more mild attacks of acute pancreatitis.
After the first attack of severe acute pancreatitis.
After the first attack of pancreatitis if a patient is more than 45 years of age because the risk for neoplasm increases with age.
Acute, unexplained pancreatitis is the initial presentation in an estimated 3% of patients with pancreatic cancer.[8]
A wide variety of abnormalities may be found on ERCP as causes of pancreatitis and include:
Choledochocoele
Chronic pancreatitis
Intraductal papillary mucinous tumour (IPMT)
Occult stone disease
Pancreas divisum (PD)
Pancreatic cancer
Periampullary tumour
Sphincter of Oddi dysfunction (SOD)
A complete ERCP study in the setting of idiopathic pancreatitis includes:
1.Careful endoscopic examination of the papilla to rule out an ampullary neoplasm or a choledochocoele
2. Complete cholangiography and pancreatography to rule out occult biliary stone disease, chronic pancreatitis, aberrant biliary pancreatic junction, PD and malignant obstruction of the pancreatic duct.
3. Sphincter of Oddi manometry of the biliary and pancreatic sphincters.
In the largest endoscopic series of patients evaluated for idiopathic recurrent acute pancreatitis,[9] 44 of the 116 (38%) patients had an abnormality that could explain the pancreatitis:
72 (62%) No abnormality
17 (14.7%) SOD
11 (9.5%) PD
8 (6.9%) Cholelithiasis
4 (3.4%) Choledochocoele
3 (2.6%) Ampullary tumour
1 (0.8%) Pancreatic duct stricture
Sphincter of Oddi dysfunction
SOD is a common cause of unexplained pancreatitis in patients seen in referral centres.[9] Endoscopic manometry can demonstrate separate biliary and pancreatic sphincters and there can be a discordance between the basal pressures in the two sphincters, with one normal and the other elevated. Silverman et al[10] reviewed the results of manometry in 111 patients with pancreaticobiliary pain, most of whom had normal liver and pancreatic chemistries. Manometry was possible in both sphincters in 88 (79%) patients; 28 (32%) patients had elevated pressure in both sphincters; and 15 (17%) patients demonstrated a discordance, with elevated pressure in one of the two sphincters. The clinical implication is that dual-sphincter manometry may be required when evaluating for unexplained pancreatitis and pancreatic sphincterotomy rather than biliary sphincterotomy may be required in some patients to relieve the pain.
A classification of pancreatitis-associated SOD has been proposed that is analogous to biliary SOD[11] : type I patients have recurrent attacks of pancreatitis (confirmed clinically and biochemically) with a dilated pancreatic duct and slow drainage. These patients appear to have stenotic lesions, do not require sphincter of Oddi manometry for diagnosis, and have the best results from sphincterotomy. Type II patients have acute relapsing pancreatitis and no evidence for stenosis other than tonic sphincter of Oddi pressures more than 40 mm Hg on manometric testing. Type III patients have pancreatic type of pain and no evidence of pancreatitis but an abnormal sphincter of Oddi manometry. Type III patients are least likely to respond to sphincterotomy. Pancreatic sphincterotomy should not be undertaken lightly because it is associated with a postprocedural pancreatitis in 11% of patients and a 14% restenosis rate.
Pancreas Divisum
In pancreas divisum (PD) the ventral and dorsal pancreatic buds fail to fuse in utero, resulting in drainage of the bulk of pancreatic juice (80%-95%) via the duct of Santorini through the relatively small minor papilla. PD occurs in 6% of normal subjects in autopsy series compared to an incidence as high as 10%-20% of patients in some series of acute recurrent pancreatitis. As not all patients with PD develop pancreatitis, it is hypothesized that relative obstruction at the minor papilla results in ductal hypertension with consequent pancreatitis through poorly understood mechanisms. Pancreatic histology from patients with PD and recurrent pancreatitis has demonstrated changes of chronic pancreatitis in the dorsal duct distribution and normal parenchyma from the ventral portion. Manoeuvres aimed at facilitating flow through the minor papilla have been reported to reduce attacks of pancreatitis. Therapies have included minor papilla stenting, sphincterotomy, and surgical sphincteroplasty with improvement in 75% of patients.[12] The difficulty arises in identifying the patients who might benefit from endoscopic therapy. In some series prolonged dorsal duct dilatation after administration of secretin correlates with symptomatic improvement after endoscopic therapy. Endoscopic therapy on the minor papilla should be restricted to those patients who are troubled by frequent and moderately severe episodes of pancreatitis.
ENDOSCOPIC DRAINAGE OF PANCREATIC PSEUDOCYSTS
Pancreatic pseudocysts are contained collections of fluid rich in pancreatic enzymes not lined by an epithelium. They are relatively common and occur in up to 20% of patients with acute and chronic pancreatitis. The current practice is to drain pseudocysts that are symptomatic and observe those that are asymptomatic, independent of initial size.
Endoscopic drainage of pseudocysts can be performed via both transmural and transpapillary routes. The transmural route requires CT or ultrasonographic demonstration of close (less than 1 cm) apposition between the pseudocyst and the lumen of the neighbouring gut. Most commonly a fistula is created from the stomach or the duodenum into the pseudocyst using a needle alone or a cutting current via a needle knife or a fistulatome.[13] The tract is maintained with a guidewire while the fistula is enlarged via either incision with a sphincterotome or, more commonly, balloon dilatation which is less likely to cause haemorrhage. Fistula patency is maintained by multiple double pigtail stents until CT or ultrasonography demonstrates resolution of the cavity. If the content is infected or particulate, a nasocystic catheter may be placed initially to permit flushing of the cavity.
Complete resolution of the pseudocyst with endoscopic therapy occurs in 65% to 95% of patients. Complications occur in 10% to 35% of patients and include haemorrhage, postprocedural pancreatitis, retroperitoneal perforation, difficulty in locating a puncture site and infection or recurrence due to difficulty in maintaining an adequate fistula.
Endoscopic ultrasonography (EUS) may be used to determine the optimal site for endoscopic fistula formation. The advantage of EUS is that it allows identification of the area of maximal apposition, helps avoid intervening vessels, excludes the presence of pseudoaneurysms, and differentiates pseudocysts from cystic neoplasms with increased accuracy. Despite these advantages the use of EUS is not mandatory.
Transpapillary pseudocyst drainage by nasocystic drain or stents has been advocated for patients with a major communication between the pseudocyst and the pancreatic duct.[14] This is particularly useful in proximal duct stricture. The stent is left in situ for 4 to 16 weeks and removed when the pseudocyst has resolved. This technique avoids the potential complication of haemorrhage during cystenterostomy but carries the risk of stent induced duct damage, especially in patients without chronic pancreatitis.
Transenteric drainage also has also been described for management of organized necrosis after an episode of acute necrotizing pancreatitis. Baron et al[15] reported 90% success in drainage of partly liquefied, organized pancreatic necrosis when localized. It requires nasocystic lavage and infection is not necessarily a contraindication. Endoscopic therapy for necrosis remains investigational and should be used only by experienced endoscopists.
Pancreatic duct disruption
Major pancreatic duct disruption may occur in the setting of acute or chronic pancreatitis and present as (i) an external pancreatico-cutaneous fistula secondary to percutaneous tube drainage of pseudocysts or pancreatic resection, (ii) an internal fistula extending to the colon, small intestine, bile duct or pleural space, (iii) an internal sinus tract may collect as ascites, acute fluid collection or pseudocyst. Diagnosis is made easily via the high amylase activity in the fluid.
The principle of management is that patients must have complete continuity of their pancreatic duct, so as not to heal in two disconnected segments (disconnected duct syndrome). Large fluid collections are drained internally or externally and a transpapillary pancreatic stent is placed according to the duct anatomy identified. Stents may traverse the papilla alone when duct caliber is adequate to reduce the intraductal pressure at the level of the leak. When strictures are present they also should be traversed.
In addition to pseudocysts pancreatic duct stent placement across a ductal disruption has been described for the treatment of pancreatic ascites, pleural effusions, enteric fistulae and pancreatico-cutaneous fistulae.[16]
Large fluid collections, particularly those with necrotic debris, as well as disconnected glands, may best be handled with a combination of surgical and interventional radiologic techniques.
Pancreatic duct strictures
Obstruction to the flow of pancreatic juice is believed to be a major source of pain in patients with chronic pancreatitis. This concept is supported by the beneficial effect of pancreatic decompression by longitudinal pancreaticojejunostomy.
Evaluation of the patient with chronic pancreatitis and increased pain must include a search for various potential sources of pain by endoscopy and imaging studies. Pancreatic strictures are likely to be demonstrated at ERCP, when pancreatic juice analysis and brush cytology should be done to exclude malignancy.
Sequential steps include definition by pancreatography, stricture access with guide wires, strictures dilation, and stent placement. Pancreatic sphincterotomy is often performed to facilitate access to the pancreatic duct. Pancreatic sphincterotomy carries risks of 10% to 15% for early complications such as pancreatitis or cholangitis and 14% for late complications, primarily stenosis of the sphincterotomy site. Although initial improvement is quoted as between 75% and 95%, long term results are less promising with less than 60% sustained benefit at 12 and 28 months.[17] The interpretation of these results is complicated by the relapsing and remitting nature of chronic pancreatitis and the eventual reduction in pain in many patients. A major potential problem is the stents themselves which induce changes similar to chronic pancreatitis. Stents generally should be removed within 3 to 4 weeks. In summary, it appears that in the presence of dominant stricture, relief of obstruction may lead to considerable symptomatic and even functional benefit.
Pancreatic Calculi
Pancreatic calculi may be both the consequence and the cause of pain in chronic pancreatitis. Removal of calculi within the main pancreatic duct has been associated with decreased ductal diameter as well as improvement in chronic pain and relapsing attacks of pancreatitis. However, more than 50% of stones could not be removed without ancilliary manoeuvres like extra-corporeal shock wave lithotripsy (ESWL) to fragment pancreatic calculi. Kozarek et al has reported 40 patients at a mean follow-up of 28 months after lithotripsy and endotherapy.[18] Eighty per cent of these patients avoided subsequent surgery and there was a statistically significant decrease in preprocedure pain, narcotic ingestion and yearly hospitalizations. Data such as these suggest that certain patients with obstructing calculi respond to stone removal, but this does not imply that every patient should be treated endoscopically. Patients with multiple calculi and strictures within a pseudotumour of the pancreatic head may be better served by head resection.
Intraductal Papillary Mucinous Tumors (IPMT)
IPMTs include what used to be called mucinous ductal ectasia. Typically, these patients are older men who present with recurrent abdominal pain, acute pancreatitis, weight loss or pancreatic insufficiency. The diagnosis of IPMT can be suspected on CT scanning, but ERCP is the gold standard. The endoscopic image of mucus extruding through a patulous pancreatic orifice is pathognomonic and filling defects may be present on pancreatography. Accurate staging of the tumour is difficult as intraductal tumours can be multicentric within the pancreatic duct and endoscopic pancreatoscopy may be indicated to determine the extent of involvement.
IPMT should not be confused with mucinous cystic tumours, such as mucinous cyst adenoma. These usually are found incidentally in middle-aged women, with a single, large cyst in the body or tail of pancreas. As a rule, the cysts do not communicate with the pancreatic duct and pancreatography usually only shows displacement of the pancreatic duct by the cyst.
Pancreatic cancer
ERCP is 95% sensitive and 90% specific for the diagnosis of pancreatic cancer. The sensitivity of tissue sampling on ERCP varies from 44% to 72%. ERCP allows for sensitive pancreatography, direct tissue sampling, assessment of the patency of the duodenum and palliative stenting of obstructed bile and pancreatic ducts.
Approximately 80% of patients with pancreatic cancer have unresectable disease on diagnosis. These patients may experience jaundice, pruritus, pain, anorexia and maldigestion. Endoscopic biliary stenting provides excellent palliation of jaundice. In a controlled trial, Smith et al[19] found that the short-term relief of jaundice was similar in patients undergoing endoscopic stenting compared with surgery (92%) with significant lower rates of major complications (11% vs 29%) and procedure related mortality (3% vs 14%). The median stent patency was 4.5 months. Initial placement of an expandable metal stent provides significantly longer relief of jaundice. In one trial,[20] the median patency from metal stents was 273 days versus 126 days for large-caliber polyethylene stents. Also, endoscopic placement of an expandable enteric stent offers an effective nonsurgical palliation of duodenal obstruction in patients with advanced, terminal cancer.
One reasonable approach to patients with obstructive jaundice and cancer of the pancreas is to perform ERCP to establish an accurate diagnosis radiographically and with tissue sampling and to place a plastic stent while the patient is being evaluated for surgery. Stenting can serve as a selection tool for potentially respectable lesions because patients who become anicteric quickly do well after surgery, as opposed to some elderly patients with obstruction, who remain jaundiced despite biliary decompression.
Several reports have shown marked reduction in pain in these patients, with endoscopic pancreatic duct stenting in addition to biliary stent.[21] Although pancreatic stenting can be technically challenging in patients with cancer, it is reasonable to perform it to palliate the pain.
Interventional endoscopic techniques have made great inroads into the management of pancreatic disease over the past 10 years. The cost effectiveness and minimally invasive nature of endoscopic therapy compared with surgery ensure the continued development of these techniques. However, controlled, prospective data are required to validate these management strategies. Pancreatic endotherapy is potentially dangerous and should be restricted to those endoscopists with adequate expertise, number of patients and supporting multidisciplinary infrastructure to deal with complications that arise from these procedures.
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