Chronic Pancreatitis Treatment & Management

The goals of medical treatment are as follows:

• Modify behaviors that may exacerbate the natural history of the disease

• Enable the pancreas to heal itself

• Determine the cause of abdominal pain and alleviate it

• Detect pancreatic exocrine insufficiency and restore digestion and absorption to normal

• Diagnose and treat endocrine insufficiency

The benefit of antioxidants in the early stages of chronic pancreatitis is still controversial. Most patients can be managed medically. Even in patients with asymptomatic pseudocysts, relatively few develop serious complications (eg, bleeding, infection) requiring urgent surgery, and half will never require surgical intervention.

See the Guidelines section for recommendations on the diagnosis and management of chronic pancreatitis, guidelines for the understanding and management of pain in chronic pancreatitis, as well as for  the diagnosis and management of asymptomatic neoplastic pancreatic cysts.

Inpatient care

The need for hospitalization and further inpatient management of patients with an attack of chronic pancreatitis depends on the severity of the disease.

Patients with mild pancreatitis are kept on nothing by mouth and administered intravenous (IV) fluid hydration. Narcotic analgesics generally are required for pain control. Nutritional supplementation is recommended in patients with malnutrition and in patients who are not able to take oral medication after a long hospitalization.

A small percentage of patients with severe pancreatitis may become critically ill, especially early in the natural history of recurrent acute or chronic pancreatitis. Intensive care management is required, and the clinician must look for developing complications, such as shock, pulmonary failure, renal failure, gastrointestinal bleeding, and multiorgan system failure.

Surgical care

Intervention is indicated when an anatomical complication that is correctable by a mechanical intervention exists. Generally, this is an acquired abnormality, such as one of the following:

• Pancreatic pseudocyst

• Abscess

• Fistula

• Ascites

• Fixed obstruction of the intrapancreatic portion of the distal common bile duct

• Stenosis of the duodenum with gastric outlet obstruction

• Variceal hemorrhage due to splenic vein thrombosis

Depending on the individual case, the appropriate intervention may involve endoscopic, radiologic, or surgical techniques.

Radiologic evaluation and drainage

Prior to percutaneous drainage, performing pancreatography is important in order to understand the anatomy of the pancreatic ductal system and plan appropriate treatment. If a communication exists between the pancreatic ductal system and the pseudocyst, percutaneous drainage may create a persistent pancreaticocutaneous fistula, especially if the duct has a stricture downstream from the site of the disruption.

If the anatomy of the pseudocyst does not lend itself to transpapillary, transgastric, or transduodenal endoscopic drainage, then percutaneous drainage under ultrasonographic or CT scan guidance is an option. Transgastric pseudocyst drainage has been used to treat pancreatic pseudocysts successfully, but a high failure rate has been reported.

Consultations

Successful treatment of alcoholism and tobacco addiction requires a team approach, including the involvement and expertise of a chemical dependency counselor and a psychologist trained in cognitive therapy.

In patients with uncontrolled abdominal pain, early referral to a pain management specialist may allow better pain control.

Cessation of alcohol consumption and tobacco smoking are important. In early stage alcohol-induced chronic pancreatitis, lasting pain relief can occur after abstinence from alcohol, but in advanced stages, abstinence does not always lead to symptomatic improvement. Patients continuing to abuse alcohol develop either marked physical impairment or have a death rate 3 times higher than do patients who abstain.

Recommending abstinence from alcohol usually is not sufficient; the physician must use available resources for evaluation and treatment of alcohol and chemical dependency. Successful treatment requires a team approach, including the involvement and expertise of a chemical dependency counselor and a psychologist trained in cognitive therapy.

Tobacco smoking is a strong and independent risk factor for chronic alcoholic pancreatitis. Because much of the reported excess morbidity and mortality in these patients is related to smoking tobacco, patients also need to overcome their tobacco addiction.

See the Guidelines section for guidelines for the understanding and management of pain by the Working Group for the International Consensus Guidelines for Chronic Pancreatitis. ^[15]

A number of factors may contribute to the pain in chronic pancreatitis, and the principal mechanisms of pain may change with the course of the disease. Sources of pain can include the following:

• Acute disease with inflammation and pseudocyst formation may be superimposed on chronic disease

• Obstruction of the pancreatic duct by strictures or stones may cause increased duct pressure and pain

• Pancreatic ischemia, with decreased pancreatic oxygenation and a decreased tissue pH, caused by a compartment syndrome may cause pain that is relieved by duct decompression

• Pancreatic nerves become enlarged, lose some of their cellular sheath, and are inflamed

• Obstruction of the duodenum or biliary tract may worsen with acute episodes and improve with time

Diagnostic tests may be necessary to identify an anatomic explanation for the pain and to plan appropriate treatment. If no anatomic explanation for abdominal pain can be found, medical therapy can be attempted. This therapy includes pain control with analgesic agents and a trial of noncoated pancreatic enzymes.

Exogenous pancreatic enzymes and CCK

The impetus for using exogenous pancreatic enzymes to reduce pain begins with the hypothesis that stimulation of the pancreas by food causes pain. Cholecystokinin (CCK) is one of the possible mediators of this response.

CCK releasing factor (CRF) typically is secreted into the duodenum. During the interdigestive period, proteolytic enzymes within the pancreatic juice rapidly degrade CRF. After a meal, the proteolytic enzymes are occupied with digesting dietary proteins, and enough CRF escapes to bind to duodenocytes, which stimulates CCK release, in turn stimulating pancreatic secretion.

In severe chronic pancreatitis with exocrine insufficiency, CCK levels may be high because proteolytic enzymes are low. When pancreatic enzyme supplements are administered in high doses, degradation of CRF is restored and the stimulus for CCK release is reduced.

This hypothesis is supported by one report that a CCK-receptor antagonist reduces pain in patients with chronic pancreatitis. The digestive products of a meal and the CCK-releasing factor stimulate CCK release from the duodenal mucosa. CCK acts directly on the pancreatic cells and indirectly through neural pathways to stimulate the pancreas. Through unknown mechanisms, such stimulation has been hypothesized to cause pain.

When exogenous pancreatic enzymes are taken with a meal, CCK-releasing factors are degraded and CCK release in response to a meal is reduced, as indicated by the smaller CCK response. This decreases pancreatic stimulation and pain. Any benefit from this treatment is likely limited to nonalcoholic patients with early chronic pancreatitis and requires the use of uncoated preparations.

Clinical trials investigating the benefits of this approach have provided mixed results. While four trials using enteric-coated enzyme preparations demonstrated no effect, these studies may have been flawed if the coating failed to release the enzymes into the feedback-sensitive portion of the duodenum. Two studies using non–enteric-coated tablets have demonstrated a reduction in pain compared with placebo. Female patients and those with idiopathic chronic pancreatitis appear to respond best.

Celiac ganglion blockade

If conventional medical therapy is unsuccessful and the patient has severe, intractable pain, celiac ganglion blockade can be considered. ^[1] This approach tries to alleviate pain by modifying afferent sensory nerves in the celiac plexus, using agents that anesthetize, reduce inflammation, or destroy nerve fibers.

In a study in which alcohol injections were administered, 12 of 23 patients obtained complete pain relief, and 6 of 23 patients obtained partial pain relief. However, the mean pain-free interval was only 2 months; the longest pain-free interval was only 4 months. Repeated blocks generally were not effective.

Because of the risks of paralysis resulting from a transverse myelopathy and catastrophic hemorrhage resulting from injury to major abdominal vasculature, the use of alcohol blocks should be restricted to patients with intractable, severe pain due to terminal pancreatic cancer.

Percutaneous or endoscopic celiac nerve blocks with either alcohol or steroids have had only limited success in chronic pancreatitis and should be considered an unproven therapy.

Although reduced fat intake is often recommended in patients with chronic pancreatitis, the clinical benefit is unknown. Indeed, the efficiency of fat absorption in dogs increases with increased fat intake. Whether humans have a similar response is unknown.

Medium chain triglycerides are directly absorbed by the small intestine without a requirement for digestion by lipase or micellar solubilization. To supply lipids and calories, medium-chain triglycerides can be used in patients with severe fat malabsorption. There is occasionally sufficient loss of fat-soluble vitamins to cause disease.

Enteric-coated preparations protect lipase from inactivation by gastric acid. Uncoated preparations are often less costly and adequate to relieve steatorrhea. Reducing gastric acid secretion may enhance the effectiveness of uncoated preparations. Enzyme preparations with high lipase content are available and recombinant lipase preparations will probably soon be marketed. Some of the recombinant enzymes are resistant to acidic denaturation. To provide adequate mixing with food, enzymes should be ingested during and just after a meal.

The most serious adverse effects (ie, colonic strictures) were observed with coated preparations that contained high concentrations of enzymes. In recent years, this adverse effect has not been seen, probably due to a reformulation of enzyme preparations.

Cobalamin or vitamin B-12 is absorbed complexed to intrinsic factor in the terminal ileum. Some vitamin B-12 absorption that is independent of intrinsic factor occurs throughout the small bowel. When vitamin B-12 enters the stomach, it binds to a protein known as haptocorrin or R-protein. The haptocorrin is proteolytically degraded in the small intestine by pancreatic enzymes, and the released vitamin B-12 then binds to intrinsic factor. In patients with pancreatic insufficiency, vitamin B-12 can remain bound to haptocorrin and is not available for absorption by the terminal ileum. Although vitamin B-12 malabsorption can be demonstrated in patients with chronic pancreatitis, it rarely causes clinical vitamin B-12 deficiency.

Endoscopic therapy aimed at decompressing an obstructed pancreatic duct can be associated with pain relief in some patients (see the images below). The rationale for this approach is based on the hypothesis that ductal hypertension due to strictures of the main pancreatic duct leads to pain. ^{[2, 3]}

Chronic pancreatitis. A nasopancreatic tube courses through the esophagus, stomach, and duodenum and into the pancreatic duct. Externally, the end of the tube is attached to a suction bulb to decompress the ductal system and monitor its function on a daily basis. In contrast to patients treated with transpapillary stents, none of these patients ever has failed to return for a follow-up appointment. In addition, while stent obstruction and subsequent infection can occur with transpapillary stents, the author has not observed this complication while using nasopancreatic tubes.

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Chronic pancreatitis. Nine days after placement of a nasopancreatic tube, a pancreatogram obtained via the tube showed that the disruption had healed (see the above image). The tube then was removed.

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Chronic pancreatitis. This follow-up CT scan (see the above 2 images) shows a percutaneous tube in the left upper quadrant that was used to drain a fluid collection. It was removed after 4 weeks. The patient returned to work, regained his weight, and had no recurrence of abdominal pain or signs of a recurrent pancreatic leak.

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At best, endoscopic treatment can offer pain relief in up to 60% of well-selected patients after 5 years of follow-up care. The one report with long-term follow-up included 1018 patients treated at 8 different centers who were followed for an average of 5 years. Obstruction of the pancreatic duct was due to strictures (47%), stones (18%), or strictures plus stones (32%). Patients were treated using various endoscopic techniques.

At the end of follow-up, 60% had completed the endoscopic therapy, while 16% were still undergoing some form of endoscopic therapy and 24% had undergone surgery. Pain relief (based upon a structured questionnaire) was achieved in 65% of patients on intention-to-treat analysis. Pancreatic function did not improve. The techniques involved can be technically challenging, and complications have been described. Currently, it should be performed only in centers with expertise in this area on carefully selected patients.

Endoscopic therapy may be beneficial in chronic pancreatitis in any of the following situations:

• Papillary stenosis

• Pancreatic duct strictures

• Pancreatic duct stones

• Pancreatic pseudocysts

Papillary stenosis

In a subset of patients with chronic pancreatitis, the papillary sphincter pressure and pancreatic ductal pressure are increased. In appropriately selected patients, a pancreatic duct sphincterotomy will facilitate drainage and reduce ductal pressures and may help to alleviate pain.

Pancreatic duct strictures

Suitable candidates for endoscopic therapy are patients with a dominant distal pancreatic stricture and upstream ductal dilatation. The procedure involves placing a guidewire through the stricture into the proximal duct, performing a pancreatic sphincterotomy, dilating the stricture, and placing a stent. While technical success is achieved in more than 90% of patients, nearly 20% will have a complication and less than two thirds of patients will benefit clinically. Pain relief correlates with a reduction in the diameter of the duct by more than 2mm. Patients with recurrent pancreatitis are more likely to benefit than are those with chronic daily pain.

The stricture rarely disappears, and the stent invariably clogs; therefore, repeated procedures are required to exchange the stent. Prolonged or inappropriate stenting can injure the pancreatic duct.

Pancreatic duct stones

While pancreatic duct stones are a sequelae of chronic pancreatitis, they also may be responsible for recurrent acute pancreatitis or exacerbations of chronic pain related to ductal obstruction and increased ductal pressure. Stones usually form proximal to the ductal strictures and usually require a pancreatic duct sphincterotomy and stricture dilation to enable their extraction. In addition to various endoscopic techniques, extracorporeal shockwave lithotripsy often is necessary to break up impacted or large stones into smaller pieces suitable for removal.

Technical success is achieved in approximately 60% of patients and complications occur in 20%. Approximately 70% of patients report improvement in their symptoms.

Pancreatic pseudocysts

Advances in interventional endoscopy now enable endoscopic treatment of many pseudocysts. In the appropriate clinical setting, obtain a pancreatogram to determine whether the pancreatic duct communicates with the pseudocyst. Ideally, communicating pseudocysts found in the head or body can be treated with transpapillary stents (see the images below), with a success rate of 83% and a complication rate of 12%.

This pancreatogram shows a pseudocyst communicating with the main pancreatic duct in a patient with chronic pancreatitis and recurrent abdominal pain. He was treated endoscopically with a transpapillary stent placed into the pancreatic duct.

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Four weeks after placement of a transpapillary stent, a patient with a pseudocyst communicating with the main pancreatic duct (chronic pancreatitis with recurrent abdominal pain) had not had a recurrence of pain. The CT scan showed resolution of the cyst, and the follow-up pancreatogram showed marked improvement. Transpapillary stenting of the pancreatic duct should be reserved for patients with established chronic pancreatitis.

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Noncommunicating pseudocysts that bulge into the foregut and have a mature wall less than 1 cm thick are treatable by endoscopic transduodenal or transgastric pseudocystostomy. The success rate is 85%, with a 17% complication rate. The transduodenal approach has fewer complications and recurrences than the transgastric approach. The long-term success rate of the initial procedure is reported at 62%.

The choice of operation depends on the clinical problem and the preoperative assessment of the abnormality. In general, the approach aims either to improve pancreatic duct drainage or to resect the diseased organ. Data suggest that surgical drainage of the pancreatic duct is more effective than endoscopic drainage in patients with obstruction of the pancreatic duct due to chronic pancreatitis.

Pancreatic duct drainage

In patients with a dilated pancreatic duct, a Roux-en-Y side-to-side pancreaticojejunostomy is indicated. The operative mortality rate is about 3%, and pain relief is obtained in approximately 75% of patients (patients' cases were followed for a mean of 8 y). Pancreatic dysfunction progresses similarly in surgical and nonsurgical groups, suggesting that drainage procedures do not affect the natural evolution of the disease significantly. The long-term result for pain relief is reported in 42% of patients.

Pancreatic resection

If the disease is limited to the head of the pancreas, a Whipple operation (pancreaticoduodenectomy) can produce good results. In patients with intractable pain and diffuse disease with nondilated ducts, a subtotal or total pancreatectomy can be offered; however, the pancreatic function and quality of life are impaired after these procedures, and the operative mortality rate of total pancreatectomy is about 10%. Pain is treated successfully in approximately 70% of cases. (See the images below.)

Chronic pancreatitis. This patient had a persistent postoperative leak from the site of a distal pancreatectomy. In the mid-1990s, the author sought to facilitate enteric drainage using transpapillary stents placed into the pancreatic duct. While this changed the fluid dynamics in favor of healing the disrupted duct, some patients developed complications from this technique.

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Chronic pancreatitis. The persistent postoperative leak from the site of a distal pancreatectomy has healed at 1-month follow-up (see the image above). However, after 4 weeks of transpapillary stenting, the pancreatogram now shows a stent-induced stenosis near the surgical genu (arrow). Based on this experience, the author stopped using pancreatic stents in this setting.

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Total pancreatectomy and islet autotransplantation

In 46 patients undergoing near-total pancreatectomy, pain relief occurred in 82% (resolved in 39% and improved in 43%). Although 51% were insulin independent initially, this decreased to 34% (one third) from 2-10 years after transplantation.

In selected patients, the long-term morbidity caused by diabetes following total pancreatectomy can be avoided. Doing so involves harvesting the islets from the resected pancreas and injecting them into the portal system, which then lodges them in the liver. Increasing severity of pancreatic fibrosis correlates positively with poor recovery of islets (< 300,000) and insulin dependence.

A diet low in fat and high in protein and carbohydrates is recommended, especially in patients with steatorrhea. The degree of fat restriction depends on the severity of fat malabsorption; generally, an intake of 20 g/day or less is sufficient. Patients who continue to suffer from steatorrhea following fat restriction require medical therapy.

Clinically significant protein and fat deficiencies do not occur until over 90% of pancreatic function is lost. Steatorrhea usually occurs prior to protein deficiencies, since lipolytic activity decreases faster than proteolysis.

Specific recommendations include a daily diet of 2000-3000 calories, consisting of 1.5-2 g/kg of protein, 5-6 g/kg of carbohydrates, and 20-25% of total calories consumed as fat (about 50-75g) per day.

Malabsorption of the fat soluble vitamins (A, D, E, and K) and vitamin B-12 may also occur. Oral supplementation of these enzymes is recommended.