Medical Care: The goals of medical treatment are to modify behaviors that may exacerbate the natural history of the disease, to enable the pancreas to heal itself, to determine the cause of abdominal pain and alleviate it, to detect pancreatic exocrine insufficiency and restore digestion and absorption to normal, and to diagnose and treat endocrine insufficiency.
" Behavior modification
o 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 those abstaining. Recommending abstinence from alcohol usually is not sufficient; the physician must use available resources for evaluation and treatment of alcohol and chemical dependency. Simply telling patients that they must abstain from alcohol is neither effective nor satisfactory. Successful treatment requires a team approach, including the involvement and expertise of a chemical dependency counselor and a psychologist trained in cognitive therapy.
o 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.
" Pancreatic healing
o The benefit of antioxidants in the early stages of chronic pancreatitis is still controversial.
o Most patients can be managed medically safely. Even in patients with asymptomatic pseudocysts, relatively few develop serious complications (eg, bleeding, infection) requiring urgent surgery, and half never will require surgical intervention.
" Alleviation of abdominal pain
o A number of factors may contribute to the pain in chronic pancreatitis. 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, might cause pain that is relieved by duct decompression. Pancreatic and 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. The principal mechanisms of pain may change with the duration of disease.
o Diagnostic tests may be necessary to identify an anatomical explanation for the pain and to plan appropriate treatment. If no anatomical 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. The impetus for using exogenous pancreatic enzymes to reduce pain begins with the hypothesis that stimulation of the pancreas by food causes pain. CCK is one of the possible mediators of this response.
" This hypothesis is supported by one report that a CCK-receptor antagonist reduces pain in patients with chronic pancreatitis. Both the digestive products of a meal and the CCK-releasing factor stimulate CCK release from the duodenal mucosa. CCK acts directly on 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. 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.
o If conventional medical therapy is unsuccessful and the patient has severe, intractable pain, celiac ganglion blockade can be considered. 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. Using alcohol injections, 12 of 23 patients obtained complete relief and 6 of 23 patients obtained partial relief of pain. 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.
o CT-guided and EUS-guided celiac axis block may enhance safety and improve the efficacy of treatment in as many as 40% of cases.
" Restoration of digestion and absorption
o Although reduced fat intake is often recommended in patients with chronic pancreatitis, the clinical benefit is unknown. Indeed, in dogs, the efficiency of fat absorption increases with increased fat intake. Whether humans have a similar response is unknown.
o Medium chain triglycerides are directly absorbed by the small intestine without a requirement for digestion by lipase or micellar solubilization. To supply both 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 ofenzymes. In recent years, this adverse effect has not been seen; this is probably due to a reformulation of enzyme preparations.
o Colbalamin 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 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.
Surgical Care: Intervention is indicated when an anatomical complication that is correctable by a mechanical intervention exists. Generally, this is an acquired abnormality and includes 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, and variceal hemorrhage due to splenic vein thrombosis. Depending on the individual case, the appropriate intervention may involve endoscopic, radiologic, or surgical techniques.
" Endoscopic treatment of chronic pancreatitis
o Endoscopic therapy aimed at decompressing an obstructed pancreatic duct can be associated with pain relief in some patients. The rationale for this approach is based upon the hypothesis that ductal hypertension due to strictures of the main pancreatic duct leads to pain.
o 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 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.
o Endoscopic therapy might be beneficial in chronic pancreatitis with the following:
" 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, reduce ductal pressures, and may help 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 benefit clinically; pain relief correlates with a reduction in the diameter of the duct by more than 2 mm. Patients with recurrent pancreatitis are more likely to benefit than those with chronic daily pain. The stricture rarely disappears, and the stent invariably clogs; therefore, repeated procedures are required to exchange it. Prolonged or inappropriate stenting can injure the pancreatic duct.
" Pancreatic duct stones: While pancreatic duct stones are 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 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, complications occur in 20%, and 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, with a success rate of 83% and complication rate of 12%. 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, and 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%.
" Radiologic treatment of chronic pancreatitis: 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 ultrasound or CT guidance is an option. Transgastric pseudocyst drainage has been used to treat pancreatic pseudocysts successfully, but a high failure rate has been reported.
" Surgical treatment of chronic pancreatitis: The choice of operation depends on the clinical problem and preoperative assessment of the abnormality. In general, the approach aims either to improve pancreatic duct drainage or to resect the diseased organ.
o 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 as 42% of patients.
o 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, 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.
o Total pancreatectomy and islet autotransplantation: In selected patients, the long-term morbidity caused by diabetes following total pancreatectomy can be avoided. This involves harvesting the islets from the resected pancreas and injecting them into the portal system, which then lodges them in the liver. 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. Increasing severity of pancreatic fibrosis correlates positively with poor recovery of islets (<300,000) and insulin dependence.
Diet:
" A diet low in fat and high in protein and carbohydrates is recommended, especially in patients with steatorrhea. The degree of restriction depends upon the severity of fat malabsorption; generally, an intake of 20 grams per 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 50-75 g) 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.
DRUG TREATMENT :
1. ANALGESICS :
- ACETAMINOPHEN
- ACETAMINOPHEN WITH PROPOXYPHENE
- TRAMADOL
- MEPERIDINE
2. HORMONES : TO REDUCE PANCREATIC SECRETION
- OCTREOTIDE
3. ANTIDEPRESSANTS :
- AMITRIPTYLINE
4. PANCREATIC ENZYME SUPPLIMENTS :
- PANCREATIC LIPASE
- LIPASE
- AMYLASE
- PANCREAS
- PANCREATIN