Malignant Potential Pancreatic Cancer

Although pancreatic cancer is often associated with surrounding pancreatitis, the risk of carcinoma developing in a setting of chronic pancreatitis is not known. Histology in patients with advanced chronic pancreatitis revealed duct epithelial hyperplasia in 31%, focal squamous metaplasia in 21%, cellular dysplasia in 8%, and dysplastic acinar nodules in 21%; overall, extensive pancreatic fibrosis was associated with epithelial anomalies in 66% of patients.
Pathology Acinar atrophy, acinar dilation, and intralobular fibrosis are typical histologic findings, although a diagnosis of chronic pancreatitis is not always straightforward, even for pathologists.
Autopsies in patients with chronic alcohol abuse reveal two distinct pathologic patterns of fibrosis: either perilobular or intralobular, suggesting different etiologic factors. The perilobular type is irregular, occasionally patchy, and when advanced extended into intralobular regions to the point of completely replacing pancreatic tissue by fibrosis. Intralobular fibrosis, on the other hand, is uniform in distribution. Such ancillary findings as protein plugs, pancreatic duct hyperplasia and stones, extensive intra- and peripancreatic fibrosis, splenic vein and bile duct involvement, and pseudocyst formation are more common with perilobular fibrosis.Associated liver cirrhosis is greater with intralobular fibrosis.
Imaging
The imaging differential of chronic pancreatitis includes changes found in the elderly; one should keep in mind that some degree of pancreatic atrophy and scaring and dilation of pancreatic ducts occur in elderly patients with no previous history of pancreatitis. Also, residual duct scarring after a bout of severe acute pancreatitis is not a sign of chronic pancreatitis.
In a setting of chronic pancreatitis the gland atrophies, pancreatic ducts dilate, and stasis of pancreatic secretions occurs, even without obstruction. The etiology for such stasis and duct dilation is incompletely understood, but
includes chronic duct wall inflammation, dilation of capillaries, and loss of duct epithelium; duct obstruction results in reflux of luminal content into extracellular space. A tortuous and beaded duct appearance is common. Endoscopic US is considerably more sensitive than abdominal US in diagnosing chronic pancreatitis. Sensitivity for ERCP is only about 75%, but specificity approaches 100%.Whether CT or MRI is more sensitive in detecting early changes of chronic pancreatitis is arguable; CT detects subtle calcifications better, but MRI is better at identifying fibrosis.
Computed Tomography
A CT finding of focal pancreatic enlargement often raises the possibility of a pancreatic malignancy. Pancreatic duct dilation is nonspecific and is found in pancreatitis or malignancy, or is a normal finding in the aged.
Ultrasonography
Sonographic pancreatic texture in chronic pancreatitis ranges from hypoechoic to hyperechoic, with the latter representing calcifications. A controversy in endoscopic circles is whether in chronic pancreatitis endoscopic US is preferred over ERCP. Abnormal findings may be detected earlier with endoscopic US than with ERCP. In a setting of chronic pancreatitis, endoscopic US and ERCP show good correlation in measuring the size of the duct of Wirsung. Duct dimensions on ERCP tend to be larger than those obtained with other imaging modalities because of x-ray magnification and distention with contrast. Endoscopic US reveals dilatation
of the main pancreatic duct, heterogeneous echogenicity of the pancreatic parenchyma, and small cysts. Endoscopic US detects pseudocysts and occasionally may suggest a superimposed pancreatic carcinoma.
Magnetic Resonance Imaging
Atrophy, a heterogeneous appearance, and a dilated pancreatic duct are common MR findings in chronic pancreatitis. Fibrosis tends to decrease the signal intensity on T1-weighted fat-suppression images. Decreased heterogenous arterial phase contrast enhancement is common; nevertheless, gadolinium enhanced MRI in patients with chronic pancreatitis and pancreatic carcinoma can show similar abnormal pancreatic enhancement in both entities. The two cannot be distinguished based on degree and time of enhancement. Magnetic resonance  cholangiopancreatography tends to overestimate pancreatic duct stenosis and underestimate the dilation of secondary branches and filling defects in the pancreatic duct, but it is superior to ERCP in depicting that part of the pancreas distal to an obstruction.
Pancreatography
Pancreatography findings in patients with chronic pancreatitis and an inflammatory tumor range from a smooth or irregular stenosis, to obstruction or a patent duct; the length of
stenosis varies. The pancreatic duct distal to the tumor is dilated in about three fourths of patients. Irregular dilation of secondary pancreatic ducts develops throughout the pancreas in some patients with diffuse mild chronic pancreatitis. When localized, similar changes are also found with neoplasms or simply reflect changes seen with age.
The secretin-pancreozymin test and ERCP concur in most patients with chronic pancreatitis. A majority of patients with an abnormal ERCP but normal secretin-pancreozymin test have a prior history of acute pancreatitis, but no clinical or laboratory evidence of chronic pancreatitis. Thus both tests complement each other when chronic pancreatitis is suspected because ERCP tends to overdiagnose this condition. Secretin-stimulated MRP in patients with chronic pancreatitis visualizes more pancreatic uct segments and secondary ducts and more stenoses and intraluminal defects than presecretin. At times acinar filling develops postsecretin in chronic pancreatitis. This test also aids in assessing pancreatic exocrine function. Thus reduced duodenal filling postsecretin in patients with chronic pancreatitis achieved a 72% sensitivity and 87% specificity in detecting decreased function.
Calcifications
The only reliable and almost pathognomonic imaging finding of chronic pancreatitis is pancreatic calcifications, readily identified by both CT and conventional radiography. A majority of these calcifications are intraductal
in location, in either the main duct or side branches. These calcifications are multiple and vary in size. They may be limited to a portion of the pancreas or be scattered throughout. With time, these calcifications remain static or increase in extent, although in an occasional patient they may decrease. The extent of calcification has a poor correlation with the degree of pancreatic exocrine dysfunction. Occasionally similar calcifications develop
in severe protein malnutrition. Pancreatic parenchymal calcifications may also develop after direct trauma to the pancreas and possibly after ischemia. Biliary and pancreatic calcifications have been reported in schistosomiasis. It has been observed that patients with chronic pancreatitis have a higher prevalence of aortic calcification than a control population.
image
Radiology images of chronic pancreatitis.Computed tomography reveals extensive calcifications that have replaced most of the pancreatic parenchyma.

Therapy Most therapy in chronic pancreatitis revolves around attempts to control pain. Confounding treatment is that pain disappears spontaneously in some of these patients.
Endoscopic One source of pain in these patients is increased pancreatic duct pressure. Endoscopic sphincterotomy or main pancreatic duct stenting reduces this pressure, and these patients have rapid pain resolution; in many of these patients such therapy is only temporary, however, and they will need to undergo more definitive procedures. A stent can be inserted in most patients even with pancreatic duct disruption. With a stricture or stone distal to the disruption and pseudocyst formation, a cystoenterostomy (either gastric or duodenal) is also necessary.
Endoscopic catheter and balloon techniques have evolved to the point that a number of main pancreatic duct concretions can be removed; currently this is not possible with calculi located in secondary branches. Therefore, if stone therapy is contemplated, it is useful
to know a specific concretion location. This information can be provided by CT and subsequent
3D reconstruction. Two patients with chronic pancreatitis and multiple calcifications in the main and accessory pancreatic ducts underwent intraductal infusion of citrates through a nasopancreatic catheter; the stones fragmented and dissolved.
Extracorporeal Shock-Wave Lithotripsy
Extracorporeal shock-wave lithotripsy (ESWL) is viable initial therapy in patients with chronic pancreatitis and stones in the main pancreatic duct unretrievable by ERCP. Published results are encouraging. Stones are disintegrated and complete stone clearance obtained in 75% to 80% of patients. A combined endoscopic-ESWL approach is often used. Clinical pancreatitis is rare after ESWL therapy. Not all patients are cured of their pain, and some eventually required a Whipple or Puestow procedure for relief of symptoms or persistent obstruction.
Surgical Partial common bile duct obstruction is common in chronic pancreatitis.Without relief of obstruction, these surgical high-risk patients progress to cholangitis and cirrhosis. Biliary maging provides a road map for surgical planning. Common surgical procedures to relieve intrapancreatic biliary obstruction are choledochoduodenostomy or choledochojejunostomy.
A Puestow procedure consists of a lateral side-to-side pancreaticojejunostomy, useful to decompress a dilated pancreatic duct.
image
Radiology images appearance of a lateral side-to-side pancreaticojejunostomy (Puestow procedure).

If no pancreatic tissue is resected, little change in existing endocrine or exocrine function should be evident. Computed tomography identifies most of these pancreaticojejunal anastomoses located anterior to the pancreatic body or tail; fluid, gas, or oral contrast is evident next to the anastomosis in some. Such fluid or gas either close to the anastomosis or in an adjacent Roux-en-Y loop should not be confused with an abscess. Complications of a Puestow procedure include fluid collections, abscess, pseudocyst, hematoma, and small-bowel or Roux-en-Y obstruction.
Partial pancreatic resection is considered for a failed pancreaticojejunostomy, localized disease, or if the pancreatic duct is not dilated. With resection of pancreatic head and duodenum (Whipple procedure), a Roux-en-Y is performed and the common bile duct and residual pancreatic duct anastomosed to the jejunum. A complication after this operation is breakdown at the pancreaticojejunostomy. As a result, pancreatic duct anastomosis into the stomach has become common; an anastomotic breakdown here is less likely. A duodenum-preserving pancreatic head resection together with a pancreaticogastric or pancreaticojejunal anastomosis is a viable alternative in some centers .
A distal pancreatectomy is performed if disease is limited to the body or tail of the pancreas. Patients undergoing a distal pancreatectomy have a better outcome than those with a pancreaticoduodenectomy or pancreaticojejunostomy).
image
Radiology images of eaticoduodenectomy (Whipple procedure). A: A pancreaticojejunostomy is proximal to the choledochojejunostomy and a gastrojejunostomy is more distal. B: A similar procedure to that in part A, except that a pylorus-sparing duodenojejunostomy is substituted for the gastrojejunostomy. The biliary anastomosis can be studied via a T-tube and the gastric anastomosis with oral contrast, but the pancreaticojejunostomy is not readily accessible. Indirect evidence of a breakdown of this nastomosis is provided by CT detection of an abscess in this region. In place of a pancreaticojejunostomy some surgeons perform a pancreaticogastrostomy.

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