Chronic Pancreatitis
PKGhatak, MD
Chronic pancreatitis is a devastating disease. Episodic severe unrelenting abdominal pain is the chief symptom. Progressive loss of weight and diarrhea of foul smelling stool are chronic symptoms. Alcoholism is the prime cause of this illness and cigarette smoking is an additive factor to alcoholism.
Hereditary causes:
Hereditary predisposition to chronic pancreatitis is an important factor but the incidence of hereditary pancreatitis is low. The CFTR (cystic fibrosis transmembrane conductance regulator) gene mutation causes abnormal ductal secretion. CFTR is inherited as an autosomal recessive mode, and primarily affects bronchial glands producing thick sticky mucus but CFTR also affects the pancreas and other glands. SPINK 1 protein (serine protease inhibitor Kazal1) is a potent trypsin inhibitor. Mutation of the SPINK 1 protein gene prolongs the action of trypsin and damages the pancreas. Mutation of the PRSS I gene causes premature activation of Trypsinogen to Trypsin - a potent protein digestive enzyme of the pancreas. SPINK 1 gene is inherited as an autosomal dominant mode with 80 % penetration. Autodigestion of pancreatic tissue produces pancreatic insufficiency and the inflammation of the peritoneum causes pain. Progressive damage of Beta cells of the pancreas causes insulin deficiency and hyperglycemia.
Chronic pancreatitis, unlike pyelonephritis and bronchitis, is not due to an infection by viruses or bacteria. It is due to alcohol. A combination of pancreatic duct obstruction by stones or carcinoma of the head of the pancreas, sarcoma, lymphoma, etc. and alcohol abuse is the next important cause. About 40 % of chronic pancreatitis is due to alcohol, of the rest another 30 % are from a combination of pancreatic duct obstruction and alcohol, and in 10% no cause can be found.
How alcohol causes chronic pancreatitis.
Alcohol increases the protein content of the pancreatic secretion and decreases bicarbonate concentration resulting in the coagulation of protein. The coagulated protein globes block the pancreatic ducts. Alcohol increases the permeability of the cells lying in the ducts, and the pancreatic secretion sips into the pancreatic glands. Trypsin neutralizing enzyme production is decreased and trypsin action is prolonged. These result in chronic pancreatitis.
When this damage is repeated over 5 to 10 years the damage to the pancreas becomes overwhelming and recovery becomes rare or impossible.
Other risk factors:
Increased incidence of chronic pancreatitis is seen in hypertriglyceridemia (usually 1000 mg +), hypercalcemia, abdominal surgery and trauma, and a Cardio-Pulmonary bypass procedure. ERCP (endoscopic retrograde cholangiopancreatography) and use of certain drugs. Rare incidences of autoimmune pancreatitis and systemic vasculitis are known.
Incidence:
About 50 in 100,000 people suffer from chronic pancreatitis and the rate has been going up since 1990. Men are more susceptible; the peak incidence is 40 to 45 years. The risk is proportional to the cumulative amount of alcohol consumed over the years.
Clinical Presentation. The First attack of pancreatitis.
The first incidence is acute pancreatitis. An attack starts after an episode of heavy drinking. Nausea and vomiting were soon followed by the onset of severe burning abdominal pain in the epigastrium and below the left ribcage. The pain is deep inside towards the back of the torso. At times the pain is felt on the left flank. The pain is so severe that the patient arrives at the ER immediately.
All the main signs of an acute abdomen are present on examination. The board like rigidity of the anterior abdominal wall indicates peritonitis. Depending on the severity and duration of the attack, cardiovascular compromise may be present.
Laboratory and imaging:
Indication of acute inflammation is evident by the presence of leukocytosis with a left shift, hemoconcentration, increased levels of liver enzymes, bilirubin, and alkaline phosphatase are indications of common bile duct obstruction. Proteinuria and the presence of sugar in the urine are usual findings. The severity of inflammation is judged by LDH over 350 units, AST over 250 units, CPK to 1000 + units, Creatinine over 1. 8 mg, C-R protein to 1,500 mg/l. Low serum calcium of less than 8 mg indicates the binding of calcium with fatty acid produced by the digestion of body fat. A high Lactic acid, high LDH, high AST, and PaO2 less than 50 mmHg are bad prognostic signs.
Specific tests for acute pancreatitis are elevated serum Lipase and Amylase. Amylase begins to rise in 3 hrs. and may reach 250 units and persist for 72 hrs., the Lipase increases in 50% of cases and may remain high for 14 days. High blood sugar is usually present.
Imaging: Ultrasound of the abdomen may not be the best test because the gas filled colon and small intestine interfere with image quality. MRI is more accurate and safer. MRI shows edematous pancreas and pancreatic duct dilatation. The dilated duct is due to obstruction of the duct by pancreatic stones or stones impacted at the sphincter of Oddi or a tumor of the head of the pancreas. Atelectasis of the lower lobes of the left lung and left sided pleural effusion may be present.
Clinical Presentation of Repeated attacks.
This first episode may not be the last in the majority of chronic pancreatic cases. Episodes of acute attacks, several times a year, are not uncommon. Repeated attacks damage the pancreatic exocrine (digestive) and endocrine (insulin production) functions to various degrees depending on the duration and frequency of acute attacks.
Acute abdominal pain may last several hours to 2 -3 days at a time. Marked weight loss and diarrhea of fatty stool are common symptoms. Signs of protein malnutrition are evident in the presence of hollowed out temples, sunken cheeks, skinny legs and arms.
Laboratory findings:
Laboratory findings in chronic pancreatitis are variable depending on the remaining functioning pancreatic tissue. Blood sugar levels are generally high, increased fecal fat points to malabsorption of fat and fat soluble vitamins A, D, E, and K.
Imaging;
MRI or CT of the abdomen is the initial test. 30% show various degrees of pancreatic calcification, and stones. The pancreas is generally atrophic and the pancreatic ducts are dilated. Secretin enhanced MRCP (special MRI) to evaluate hepatobiliary pancreatic system) maybe performed in difficult cases. Stones, stricture of the sphincter of Oddi and tumors are better detected by ERCP. Ultrasound study during ERCP increases visual evidence when cancer of the pancreas is suspected. Skinny needle biopsy done through ERCP scope provides a definitive diagnosis of malignancy. In chronic pancreatitis the pancreatic tissues are in various degrees of degeneration, atrophic and replaced with fibrous tissue, the Beta cell islands are much reduced in numbers. The main pancreatic duct is dilated.
Management of Chronic pancreatitis:
The goals are pain control, prevention of future attacks, pancreatic enzyme replacement, and control of blood sugar by insulin. Pain control is crucial, success and failure depend on it.
Medical therapy:
The multidisciplinary team is better at managing pain and exocrine and endocrine deficiency brought on by chronic pancreatitis. Pancreatic enzyme replacement and insulin administration are effective in some patients but not universally. To control pain non-opioid medications are tried to begin with but in the end, the majority of patients require opioids to control the intractable pain. Opioid addiction is a usual occurrence and becomes a major problem.
Non-conventional treatments:
Mind-body therapy, acupuncture, chiropractic manipulation of the spine, touch therapy, dietary manipulation, supplements and antioxidant administration, etc. are tried and failed to show any improvement in pain and are disappointing.
Surgery for Pain control:
The sympathetic nerve fibers carry the pain sensation from the pancreas and the fibers originate from T5 to T12 segment of the spinal cord. The preganglionic fibers make a synaptic connection in the Celiac ganglion. The postganglionic fibers innervate the Pancreas, Liver- biliary system, vasculature of the small intestine and adrenal glands.
The head of the pancreas is considered the Pacemaker of Pain in chronic pancreatitis.
To assess the effect of sympathetic denervation, celiac ganglion block is performed. If effective then surgery is performed. The procedure is done by minimum invasive Laparoscopic method and is known as Bilateral thoracoscopic splanchnicectomy (BTS). The outcome of BTS is effective but the improvement may not last long. The main adverse effect of BTS is postural hypotension.
Drainage of Pancreas.
During ERCP, the dilatated main pancreatic duct may be seen. If a stone is a cause, then the removal of the stone can be accomplished at the same time. If the stone is large or impacted, Extracorporeal Shockwave Lithotripsy is indicated. If dilatation of the sphincter of Oddi is performed, a stent is placed in the main pancreatic duct and drained for 6 to 8 weeks. In some cases, the drainage produces a significant decrease in pain. In those cases, an appropriate surgical procedure can result in a long term improvement.
Whipple Operation:
In 1935 Whipple was the first surgeon to remove the head of the pancreas along with the duodenum. If the patients were able to abstain from alcohol and smoking for at least for one year, they had significant relief from pain. However, the Whipple operation produced significant morbidity and mortality. Development of type 1 Diabetes mellitus, nutritional, iron, calcium and vitamin B12 deficiency followed the operation. The antrum and duodenum are not just conduits but both have exocrine and endocrine functions.
The diagram above shows the Postoperative picture of a Whipple operation.
Modifications of the Whipple operation were undertaken by many groups in order to preserve as much duodenum as possible and save the tail of the pancreas and islets cells at the same time. To ensure adequate drainage of pancreatic secretion pancreatojejunostomy was performed.
Puestow modification 1958.
Puestow did not remove the head of the pancreas, instead opened the main pancreatic duct from the head to the tail followed by a side to side anastomosis of the main pancreatic duct and jejunum.
Berger modification of Puestow operation.
The above is a diagram of Berger's modification of the Puestow operation.
Burger modification preserved the duodenum and removed as much of the pancreatic head as possible by blunt dissection.
In 1960 Partington and Rochelle modified Puestow's operation by not including distal pancreatectomy.
Most recent modification.
In this operation, a total pancreatectomy followed by Islet cell autologous transplantation was performed to retain autonomous insulin production.
Various comparative studies were completed in order to find an operation that would control pain and produce minimum morbidity and mortality. Overall, all surgical procedures show some good control of pain but relapse in a year is common if patients go back to drinking and smoking.
Pain is the main reason the patient seeks medical attention for chronic pancreatitis. Medical and surgical treatment modalities are difficult to impose on patients because of significant morbidity. Patients with surgically correctable conditions like pancreatic stones, stricture of sphincter Oddi, and biliary obstruction have the best prognosis. Medically treatable conditions - hypertriglyceridemia and hypercalcemia also have a better prognosis. Overall pain control is achieved in 30-35 % of cases provided the patients abstained from drinking alcohol and stopped smoking. Opioid addiction is very difficult to avoid because of constant and unrelenting pain and when other methods are ineffective. About 4 % of patients with chronic pancreatitis develop cancer of the pancreas but in the hereditary condition, the cancer rate increases to 20%. Increased incidence of venous thromboembolism, increased risk of CAD and other acute vascular events are known because of changes in coagulation factors and platelet function.
Written in memoriam of Sanjay Banerjee. 1965 - 2012.
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