Endoscopic diagnosis and therapy of pancreatic diseases

Table II.

EUS criteria	Histological correlate
Parenchymal abnormalities
Hyperechoic foci	Focal fibrosis
Hyperechoic strands	Bridging fibrosis
Lobular contour	Interlobular fibrosis
Cysts	Cyst / pseudocyst
Ductal abnormalities
Main duct dilation	>3-mm head, >2-mm body, >1-mm tail
Duct irregularity	Focal dilation / narrowing
Hyperechoic margins	Periductal fibrosis
Visible side branches	Side-branch dilation
Stones	Calcified stones

What other diseases, conditions, or complications should I look for in patients with pancreatic disease?

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What is the right therapy for the patient with chronic pancreatitis?

Indications for endoscopic treatment

• Treatment of abdominal pain

• Treatment of loco-regional complications (pseudocyst, biliary obstruction)

• Treatment of pancreatic fistula (pancreatico-pleural, pancreatic ascites)

Treatment of abdominal pain

Abdominal pain is a very common problem in chronic pancreatitis. There are different grades, from mild to severe, chronic pain. The pathogenesis of pain in chronic pancreatitis is multifactorial and poorly understood: it may diminish with treatment but rarely disappears.

All patients should be advised to stop alcohol and tobacco use as a first step in management.

Imaging studies such as CT scan have to be performed to rule out other conditions such as persistent acute inflammation (inflammatory mass) in the pancreas, pancreatic and peripancreatic fluid collections, biliary obstruction, duodenal stenosis, gallbladder disease, or pancreatic cancer.

Medical therapy includes low-fat diet, use of high-dose pancreatic enzymes, and acid suppression. Opioid analgesics have been tried, however, with little benefit.

Endoscopic management of pain

• a. EUS-guided celiac plexus blockade

  – Safe and well tolerated; unfortunately, only a proportion of patients respond (around 30%) and for a short-period of time (around 3 months).

  – Should be limited for flares of chronic pain in patients with pain refractory to medical therapy and limited therapeutic options.

• b. Drainage of main pancreatic duct (MPD)

  – Should be considered early in the course of calcifying chronic pancreatitis associated with pain that has not responded to narcotics therapy and marked decrease in quality of life.

  – Etiology of main pancreatic duct obstruction: 1) pancreatic stones (18%); 2) ductal stenosis (47%);  3) combination of stones and stenosis (32%).

  – Stones can be fragmented by extracorporeal shock wave lithotripsy (ESWL) and removed after pancreatic sphincterotomy during ERCP with a response rate of about 50%.

  – Similar response rates can be achieved with placement of pancreatic stents for pancreatic strictures; however, it Is recommended that pancreatic duct stents should stay for short periods of time. This can also help to recognize those patients that have better chances of benefitting from surgery.

• c. Drainage of pancreatic pseudocysts, if present (either transpapillary or transmurally)

• d. Surgical vs. endoscopic therapy. Surgical therapy (lateral pancreatico-jejunostomy) has better long-term results than endoscopic therapy.

About 15% of patients treated endoscopically will be pain-free after 5 years, compared with 35% to 40% of patients treated surgically. However, surgery has higher morbidity and mortality than endoscopic treatment. Endoscopic therapy may be considered as the first treatment option. Surgery should be considered in case of treatment failure or recurrence.

What is the most effective initial therapy?

Pancreatic stones management

ERCP

Patients with intraductal pancreatic stones and abdominal pain can benefit from endoscopic management.

• – Pancreatic sphincterotomy and stone extraction for <5mm noncalcified ductal stones without associated stricture in the pancreatic duct.

• – Stone extraction can be achieved endoscopically with a pancreatic extraction basket or a balloon extraction catheter.

• – In 70% to 90% of cases: failed extraction without previous non-ERCP fragmentation by ESWL.

Endoscopic duct decompression may be preferred over surgery as an initial therapy because of its fast recovery rates and low morbidity and mortality, when compared to surgery. However, long-term results are better with surgery.

ESWL (extra-corporeal shockwave lithotripsy)

• – High success rate of pancreatic stone fragmentation (70-90%)

• – If multiple stones are present: first, try to target the stone closest to the head of the pancreas

• – There is no need to target stones in secondary ducts.

• – ERCP with stone extraction after ESWL: if there is lack of spontaneous elimination after a follow-up abdominal imaging (CT, plane films)

Pancreatic duct stenosis management

• – If an MPD stenosis is present, first exclude pancreatic cancer, especially in the absence of stones. The work-up may include tumor markers such as Ca 19-9, pancreatic duct brushing, and EUS-guided biopsy.

• – Dilation of stenosis and insertion of plastic stent:

To achieve large-diameter-dilation placement of plastic stents, first, with Soehendra catheters and then placing multiple 7 Fr diameter stents, or if the duct is large enough, try to insert 8.5 or 10 Fr stents. Definite stent removal is difficult to achieve because of the high rate of relapse: a high proportion of patients (>80%) experience pain relapse within the first year after stent removal.

• – Recent evidence shows promising results with the insertion of multiple stents in the MPD, with resolution of stenosis in about 95% of patients.

• – Complications of stent insertion are uncommon and include

Classification

Pancreatic pseudocysts are more common after chronic than acute pancreatitis, and more common in alcohol-related pancreatitis. Classification is based on the underlying etiology (acute or chronic), ductal anatomy, and the presence of communication between the cyst and pancreatic duct:

Type I. Acute “postnecrotic” pseudocysts occur after an episode of acute pancreatitis and are rarely communicated with the pancreatic duct.

Type II. Postnecrotic pseudocyst occur after an episode of acute on chronic pancreatitis (no stenosis at pancreatic duct and often with a duct-pseudocyst communication).

Type III. Retention pseudocysts: occur in chronic pancreatitis and are associated with duct stenosis and pseudocyst-duct communication.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

Endoscopic drainage

• – Less invasive than surgery; no need for external drains, high long-term success rate.

• – The test of choice to determine the size, location, and thickness of pseudocyst wall is endoscopic ultrasound (EUS).

• – A distance between the cyst and gastric or duodenal wall of more than 1 cm and presence of large vessels or varices are relative contraindications for endoscopic drainage.

• – Transgastric or transduodenal (transmural) drainage. Site depends on location in relation to the stomach or duodenum.

• – A contrast-enhanced abdominal CT allows assessment of the precise location of the pseudocyst in relation to the stomach and duodenum and potential intervening vascular structures for transmural drainage.

• – Endoscopic ultrasound is the preferred method to localize and direct pseudocyst drainage in the absence of an endoscopically visible bulge.

The collection is entered at a point of endoscopically visible extrinsic compression, using electrocautery or needle. Once entry is confirmed, the transmural tract balloon is dilated to 8 to 10 mm to allow placement of one or two 10-Fr stents.

Successful drainage is achieved in approximately 75% to 100% of cases, with complication rates of about 5% to 10% and recurrence rates of 5% to 20%.

Double pigtail stents are placed because they are less prone to migrate into or out of the collection, and straight stents are associated with delayed bleeding complications.

When the pseudocyst communicates with the main pancreatic duct, a pancreatic endoprosthesis can be placed with or without pancreatic sphincterotomy. This approach is useful for drainage of pseudocysts measuring less than 6 cm that are not approachable transmurally.

If EUS is not being used, procedures may be done with a side-viewer duodenoscope. Endoscopic drainage can be performed using fluoroscopy or EUS-guidance.

Types of endoscopic drainage

Transpapillary approach with ERCP

– When pseudocyst communicates with main pancreatic duct

– In patients with pancreatic duct disruption

Direct drainage across the stomach or duodenal wall

– When pseudocyst is adjacent to the gastroduodenal wall

Infected pancreatic necrosis

Pancreatic necrosis develops within the first 4 days of acute pancreatitis; initially, the necrosis is sterile but infected necrosis develops in 40% to 70% of cases, and mortality increases to 30% in this group of patients.

It is diagnosed by fine-needle aspiration or with evidence of gas in retroperitoneum on CT scan.

Intervention should be delayed for at least 3 to 4 weeks until the necrosis is organized (walled-off pancreatic necrosis or WOPN).

Endoscopic drainage

Necrosis has to be walled-off (WOPN) for successful management. To perform this procedure, local expertise is mandatory.

Transmural drainage is performed to evacuate solid material. Options include direct endoscopic debridement/necrosectomy, which can be performed with a forward-viewing therapeutic endoscope that is advanced through the duodenal/gastric wall into the necrotic fluid collection.

The endoscope can access the paracolic, retroduodenal, and perinephric spaces. Necrosis that is closely adhered to the posterior gastric wall or medial duodenal wall is often ideal for endoscopic necrosectomy.

EUS helps in exactly imaging the necrosis location and making sure that the necrosis can be approached safely from the posterior stomach / medial duodenal wall.

Advantages of endoscopic drainage. Avoidance of morbidity of open surgery debridement, avoidance of external fistulae, therapeutic potential in poor surgical candidates.

Disadvantage. Necessity for the necrosis to be walled-off, limited ability to evacuate large areas of less-well liquefied necrotic debris, need for repeated procedures for adequate drainage.

Direct necrosectomy is superior to standard transmural endoscopic drainage, which uses transmural drainage and irrigation, although recent data support a combined endoscopic/percutaneous approach. In the majority of cases, successful resolution of the necrotic cavity obviates the need of surgical drainage.

Patients with extensive extrapancreatic necrosis not approachable from posterior stomach/medial duodenal wall are often not suitable for endoscopic drainage; however, a recent report has used a percutaneous tract to place a large diameter, self-expandable stent followed by insertion into these types of collections for endoscopic debridement.

Acute recurrent pancreatitis

Acute recurrent pancreatitis (ARP) is defined by more than one acute episode of acute pancreatitis. Patients with a second attack are at high risk of recurrence; they need an extensive work-up to determine etiology.

In about 10% to 22% of cases, the underlying cause cannot be found. Multiple factors may be involved, including alcohol use, microlithiasis, sphincter of Oddi dysfunction (SOD), pancreas divisum, hereditary pancreatitis, gene mutations, cystic fibrosis, choledochocele, annular pancreas, anomalous pancreatobiliary junction, ampullary lesions, pancreatic tumors, and autoimmune pancreatitis (AIP).

EUS detection of gallstones, sludge, microlithiasis

EUS can direct the treatment toward cholecystectomy or ERCP. In addition, diagnostic suspicion and confirmation of AIP with EUS findings and FNA or tru-cut biopsy results. Additionally, if EUS shows findings of chronic pancreatitis, the patient likely has a different course than those with normal pancreas and ARP.

In patients with unexplained ARP after exhaustive evaluation, including EUS, measurement of pancreatic sphincter pressure by pancreaticobiliary manometry can allow the diagnosis of pancreatic sphincter of Oddi dysfunction. If this diagnosis is confirmed, biliary and pancreatic sphincterotomy may prevent recurrent attacks of pancreatitis. The risk of post-ERCP pancreatitis in this group of patients is high.

Pancreas divisum: failure of the dorsal and ventral pancreatic ducts to fuse.

The role of pancreas divisum as a cause of ARP pancreatitis is controversial, but it is believed that in a subset of patients, the minor papilla produces functional obstruction to the flow of pancreatic secretions.

Pancreas divisum can be diagnosed by CT, MRI/MRCP (with secretin stimulation), or EUS. Endoscopic minor papilla sphincterotomy with or without pancreatic stenting in properly selected patients without extensive changes of chronic pancreatitis can reduce or prevent further attacks of acute pancreatitis.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

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Listing of these, including any guidelines for monitoring side effects.

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How should I monitor the patient with pancreatic disease?

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What's the evidence?

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DiMagno, M. “Chronic pancreatitis”. Curr Opin Gastroenterol. vol. 26. 2010. pp. 490-8.

Draganov, P. “Pancreatic pseudocyst”. World J Gastroenterol. vol. 15. 2009. pp. 38-47.

Navaneethan, U. “Minimally invasive techniques in pancreatic necrosis”. Pancreas. vol. 38. 2009. pp. 867-75.

Sugumar, A. “Diagnosis and treatment of autoimmune pancreatitis”. Curr Opin Gastroenterol. vol. 26. 2010. pp. 513-18.

Liao, Z. “A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum”. Endoscopy. vol. 41. 2009. pp. 439-44.

Baron, TH. “Endoscopic drainage of pancreatic pseudocysts”. J Gastrointest Surg. vol. 12. 2008. pp. 369-72.

Baron, TH. “Treatment of pancreatic pseudocysts, pancreatic necrosis, and pancreatic duct leaks”. Gastrointest Endosc Clin N Am. vol. 3. 2007. pp. 559-79.

Kozarek, RA. “Endoscopic management of pancreatic necrosis: not for the uncommitted”. Gastrointest Endosc. vol. 1. 2005. pp. 101-4.

Papachristou, GI. “Peroral endoscopic drainage/debridement of walled-off pancreatic necrosis”. Ann Surg. vol. 6. 2007. pp. 943-51.

Gullo, L. “An update of acute recurrent pancreatitis: data from five European countries”. Am J Gastroenterol. vol. 8. 2002. pp. 1959-62.

Gardner, TB. “Direct endoscopic necrosectomy for the treatment ofwalled-off pancreatic necrosis: results from a multicenter U.S. series”. Gastrointest Endosc. vol. 73. 2011. pp. 718-26.

Gardner, TB. “Acomparison of direct endoscopic necrosectomy with transmural endoscopicdrainage for the treatment of walled-off pancreatic necrosis”. Gastrointest Endosc. vol. 69. 2009. pp. 1085-94.

Gluck, M. “Endoscopic and percutaneous drainage of symptomatic walled-offpancreatic necrosis reduces hospital stay and radiographic resources”. Clin Gastroenterol Hepatol. vol. 8. 2010. pp. 1083-8.

Gachago, K, Draganov, P. “Pain management in chronic pancreatitis”. World J Gastroenterol. vol. 14. 2008. pp. 3137-48.

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