Characterized by pancreatic endocrine and exocrine insufficiency, along with resistance, and sometimes unrelenting pain.
It is a progressive fibroinflammatory disease.
Pancreatic insufficiency can be managed with pharmacological intervention, but the pain associated, is difficult to control.
Obstruction of the pancreatic duct is considered an important etiologic factor.
Prevalence is about 50 /100,000.
A progressive disease with an annual incidence of 5-8 and prevalence of 42-73 cases per 100,000 adults in the US.
Affects all ages, and the affected age group depends on etiology.
In patients without preceding clinical acute pancreatitis, the progression to chronic pancreatitis is assumed to be via asymptomatic subclinical parenchymal injury and inflammation.
It is usually associated with alcohol use, smoking, certain gene mutations, and typically begins with recurrent painful bouts of pancreatitis, followed by the insidious development of chronic, debilitating pain during the next 3 to 5 years after the initial episode.
CP due to alcohol typically presents between ages 40 and 60 years, and 2/3 of patients are men.
Black patients have CP more commonly than do white patients.
Patients with CP due to genetic mutations typically percent between ages of 10 and 40 years.
Patients with idiopathic CP have bimodal presentation.
Prevalence varies from 36-125 per hundred thousand population from Japan, China, India, of which India has the highest prevalence.
An inflammatory disease with anatomic destruction and physiologic impairment leading to pancreatic duct disruption.
It develops slowly, starting with cellular injury, followed by inflammation and fibrosis.
It involves the acinar cells, the predominant site of initial injury or stress, leading to inflammatory cascade.
Clinical manifestations of exocrine insufficiency or related to maldigestion, which can cause steatorrhea, weight loss, and fat soluble vitamin deficiencies.
Approximately 70% of adults with CP have at least one episode of acute pancreatitis and 50% have recurrent acute pancreatitis during the clinical course of CP.
CP is associated with osteoporosis and osteopenia and a higher rate of low trauma related fractures.
Acinar cells constitute the majority of pancreatic volume.
Acinar cells synthesizeand secrete digestive enzymes into the pancreatic ductal system.
Alcohol causes acinar cell injury.
Patients with early onset CP and those with an alcohol etiology are more likely to have abdominal pain and at least one episode of acute pancreatitis.
Acinar cell injury and death resulted in inflammation possibly related to damage seen in acute alcoholic pancreatitis.
Patients with him prior acute pancreatitis are susceptible to recurrent episodes due to chronic toxic insults or genetic susceptibility.
Recurrent pancreatitis episodes result in parenchymal injury and chronic inflammation with fibrosis.
Fibrosis involves pancreatic ducts that lead to focal duct structures with dilatation of the duct proximal to the obstruction.
Calculi form because the stasis of secretions and calcification of proteins plugs.
Ductal obstruction and repeated injury lead to loss of pancreatic tissue resulting in atrophy.
Nuclear factor kN plays a key role initiation of the inflammatory cascade and is promoted by innate immune cells, predominantly macrophages.
Oxidative stress is involved in the pathophysiology of chronic Pancreatitis.
Alcohol has adverse effects on pancreatic duct a and pancreatic stellate cells contributing to chronic pancreatitis.
Characterized by fibrosis and inflammation of the pancreas in individuals with genetic, environmental, and other risk factors such as hypertriglyceridemia, auto immune disorders such as celiac disease, and inflammatory bowel disease.
Risk factors include alcohol in 42 to 77% of patients, smoking in greater than 60% of patients, and genetic mutations in 10% of patients.
genetic mutations most commonly involve cystic fibrosis transmembrane conductance regulator, serine protease inhibitor Kayzal type1 or chymotrypsin C: more than 90% of these cases manifest as sporadic early onset, of age less than 35 years, pancreatitis.
One percent of cases of hereditary pancreatitis is accounted for by cationic trypsinogen gene mutation.
Chronic pancreatitis is considered to be idiopathic in 28% patients.
Alcohol use of 80 g per day or greater for 6 to 12 years, and smoking with a history of greater than 35 pack years increases the risk of chronic pancreatitis by a factor of five and have synergistic effects.
2/3 of patients with chronic pancreatitis are men, and the risk is higher among black persons among white individuals.
Characterized by pancreatic atrophy, fibrosis, ductile structures, ductal distortion, calcifications, dysplasia, exocrine insufficiency, diabetes and chronic pain.
Pancreatic stellate cells are quiescent and on activation upon stimulation and become mediators of chronic inflammation and fibrosis in chronic pancreatitis.
Transforming growth factors beta is the most important cytokine associated with fibrosis.
Chronic pancreatitis is still personality shows interlobular an intralobular fibrosis, acinar cell loss distorted architecture, and dilated ducts.
Approximately 80-90% of patients with chronic pancreatitis have pain, that is thought to be caused by obstruction of the pancreatic duct.
Ductal decompression advocated for patients with pain and markedly dilated duct.
30-75% of patients ultimately undergo surgery, usually in the end stage of the disease.
Early ductal drainage surgery compared with endoscopy as the first approach to treatment resulted in lower pain scores over 18 months.
Most common presentation is chronic or recurrent abdominal pain.
Approximately 70% of patients present with episodic upper abdominal pain, nausea, and vomiting.
Pain attacks may be intermittent with or without pancreatitis that occur early in the course of the disease (typeA) or persistent chronic pain between intermittent severe attacks (type B) , and chronic severe pain without severe attacks which is the most debilitating pain pattern (typeC).
The chronic pain in chronic pancreatitis is attributed to peripheral and central neural sentization that results in visceral sensitivity, pain elicited by stimulus that normally does not produce pain, and hyperalgesia.
chronic severe disabling pain requires narcotic use, and is often disruptive to patients lives and compounded by alcohol use and psychosocial factors.
A sub group of patients, nearly 30% have no pain, and 50% do not have a previous diagnosis of acute pancreatitis.
Abdominal pain usually in the epigastria, but may occur in the right or left upper quadrants.
Nausea common.
Pain may radiate to the back.
Diagnosis is clinically based.
Amylase and lipase levels are not predictive of chronic pancreatitis, and may be normal to up to 3 times normal.
Symptoms include relapsing pain and loss of endocrine and exocrine insufficiency.
May result in exocrine and endocrine pancreatic insufficiency and an increased risk of pancreatic cancer.
Recurrent episodes of abdominal pain, elevated lipase and amylase levels, pancreatic insufficiency and malnutrition.
Diagnosis associated with calcifications of the pancreas on imaging studies, abnormal pancreatogram based on ERCP or MRI cholangiopancreatography with beading of the pancreatic duct or ductal stones, endoscopic ultrasound demonstrating changes in the pancreatic duct, including hyperechoic walls, stones, and ductal dilation, calcifications, lobules consistent with pancreatitis and abnormal secretin pancreatic function or a tissue diagnosis confirming the diagnosis.
Classic findings on imaging include one of more findings of distal calcifications, ductal dilatation, and parenchymal atrophy.
A contrast CT scan is the initial diagnostic test and should be performed in all patients with suspicious CP.
Abdominal CT scans have an overall sensitivity of 75% for diagnosing chronic pancreatitis.
The presence of either calcifications, marked pancreatic duct changes or both on CT establish the diagnosis of CP.
Amylase and lipase tests are helpful for diagnosing acute pancreatitis but not CP.
Alcohol abuse is the most common etiology.
The three major causes of CP are alcohol, idiopathic, and genetic mutations.
Alcohol abuse is diagnosed with 42-77% of patients with chronic pancreatitis.
Idiopathic chronic pancreatitis is the second most common type of cause for chronic pancreatitis and affects 28-80% of people with this condition.
There are many treatment options that exist for chronic pancreatitis pain, but the response is often unpredictable, inconsistent, and inadequate.
Chronic pancreatitis may be associated with multi-level neuropathic pain syndrome.
Chronic pancreatitis pain levels affect the cerebral cortex with cortical reorganization and central sensitization, spinal / peripheral nerve sensitization, and neuropathic mechanisms and nociception.
Treatment includes analgesics, tricyclic antidepressants, SSRSs combined serotonin and norepinephrine reuptake inhibitors, pancreatic enzymes, and octreotide.
Patients with chronic pancreatitis should be advised to stop smoking and cease alcohol consumption.
Smoking is associated with the risk of chronic pancreatitis in a dose dependent fashion.
Smoking contribute to acinar cell injury due to its toxic metabolite nicotine.
Some patients may require pancreatic rest with nasogastric tube feedings or Total parenteral Nutrition.
Narcotic analgesics for short periods of time may be required.
Surgical drainage is accomplished by longitudinal pancreaticojejunostomy with a complication rate of 6-30%, a mortality rate of 0-2% and a success rate of improving pain of 65-85%.
Endoscopic drainage involves sphincterotomy, dilation of strictures and removal of stones and has a success rate of 30-100%.
Endoscopic drainage involves sphincterotomy, dilation of strictures and removal of stones and has a success rate of 30-100%.
With pancreatic duct obstruction surgical drainage is more effective than endoscopic management during 2 years of follow-up.
Surgical benefits were more rapid, effective and associated with sustained pain relief compared to endoscopic treatment.
While drainage procedures are utilized for dilated duct disease resective procedures such as a Whipple pancreaticoduodenectomy and subtotal pancreatectomy are used for small duct disease when pain control is refractory to medical and nonresectional surgery or resistant to surgical drainage.
Total pancreatectomy can improve or alleviate pain in 80% of case.
Total pancreatectomy with islet cell auto transplantation can result in insulin independence in about 80% of patients.
Total pancreatectomy with islet cell auto transplantation for pain results in the removal of all pain associated tissue, eliminates the possibility of pancreaticoenteric anastomotic leaks and avoids surgical diabetes.
Total pancreatectomy with islet cell auto transplantation may be a reasonable first line therapy for severe recurrent disease, especially when small to moderate size ducts are involved.
Structural causes include pancreatic duct obstruction due to stones, strictures, ampullary or periampullary mechanical or functional stenosis, neoplasms or intraductal papillary mutinous tumors.
Nonstructural causes include hypercalcemia, hypertriglyceridemia, toxins, infections, drugs and genetic mutations.
Genetic mutations associated with chronic pancreatitis can cause cellular injury in a trypsin-dependent or trypsinin-independent manner.
Increase intracellular trips in activation leads to cellular injury through endoplasmic reticulum stress oxidative stress and impaired autophagy.
Most common cause secondary to alcohol abuse, but can be seen with medications, ampullary obstruction, pancreatic duct interventions and other causes.
Alcohol abuse represents about 19-45% of such patients.
Islet cell yield from patients with alcohol induced chronic pancreatitis is poorer than from other etiologies.
Can be caused by pancreatic duct strictures following trauma or necrotizing pancreatitis.
Most commonly seen in men in their thirties and forties.
The prevalence of new onset diabetes of 15% within 36 months and 33% of the 16 months after a diagnosis of CP.
Complications of chronic pancreatitis: pseudocysts, bile duct stricture, duodenal stricture, splanchnic venous thrombosis, pancreatic cancer, glucose intolerance, exocrine pancreatic dysfunction with steatorrhea, and increased mortality.
Definitive diagnosis rest heavily on imaging findings, and laboratory assessment.
Imaging techniques include: CT, MRI cholangiopancreatography (MRCP), endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography: ERCP is no longer recommended due to complications.
MANAGEMENT:
Management includes pain medication, pancreatic enzymes, behavioral therapy, endoscopic treatment, and surgery.
Management of pain and the recognition of central sensitization in the role of psychological social factors associated with chronic pain causes for expansion of management approaches to non-structural behavioral interventions: analgesics, antioxidants, and neuromodulators such as gabapentinoifs and tricyclic antidepressants.
Endoscopic therapy involving removal of stones in the pancreatic duct, dilatation of strictures or interventions for moderate to severe pain that does not respond to medical therapy.
for structures in a pancreatic duct dilatation with stents is warranty with a pain relief percentage of 70%.
Extracorporeal shockwave lithotripsy is used to break up stones or is it a junk to ERCP.
Surgical management includes drainage procedures with attachment of the main pancreatic duct to the intestine or resection of involve pancreas.
Surgical options for pain relief include pancreatic resection for persistent focal inflammation, drainage of an obstructed duct, or even total pancreatectomy with or without islet cell transplantation.
Pain relief with surgery is higher than with the endoscopy, with similar complications and mortality agree to use every interventions in the endoscopy group.
The Dutch Pancreatitis Study Group found:early surgery versus endoscopy that it was associated with better relief of pain.
In patients with a dilated pancreatic duct, decompression via endoscopy with stone removal, pancreatic duct stents, or surgery can correct interstitial pressure resulting in diminished pain.