Хронічний панкреатит

1. 1. Whitcomb DC: Central role of the sentinel acute pancreatitis event (SAPE) model in understanding recurrent acute pancreatitis (RAP): Implications for precision medicine. Front Pediatr 10:941852, 2022. doi: 10.3389/fped.2022.941852

1. 1. Yadav D, Gawes RH, Brand RE, et al: Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch Intern Med 169:1035–1045, 2009. doi: 10.1001/archinternmed.2009.125. Clarification and additional information. Arch Intern Med 171(7):710, 2011. doi:10.1001/archinternmed.2011.124

In a patient with a typical history of heavy alcohol consumption and recurrent episodes of acute pancreatitis, detection of pancreatic calcification on plain x-rays of the abdomen may be sufficient. However, such calcifications typically occur late in the disease and then are visible in only about 30% of patients. CT can also be used in patients with a history of heavy alcohol consumption and in whom plain x-rays are not diagnostic.

In patients without a typical history but with symptoms suggesting chronic pancreatitis, abdominal CT is typically recommended to exclude pancreatic cancer as the cause of pain. Abdominal CT can be used to detect calcifications and other pancreatic abnormalities (eg, pseudocyst or dilated ducts) but still may be normal early in the disease.

MRI coupled with magnetic resonance cholangiopancreatography (MRCP) is now frequently used for diagnosis and can show masses in the pancreas as well as provide more optimal visualization of ductal changes consistent with chronic pancreatitis. Administration of IV secretin during MRCP increases sensitivity for detecting ductal abnormalities and also allows for functional assessment in patients with chronic pancreatitis. MRI is more accurate than CT and does not expose patients to radiation.

Endoscopic retrograde cholangiopancreatography (ERCP) is invasive and rarely used for the diagnosis of chronic pancreatitis. ERCP findings could be normal in patients with early chronic pancreatitis. ERCP should be reserved for patients who may need therapeutic intervention.

Endoscopic ultrasonography is less invasive and enables detection of subtle abnormalities in the pancreatic parenchyma and in the pancreatic duct. This imaging modality has a high sensitivity but limited specificity.

The most common pancreatic function tests do not detect mild to moderate exocrine pancreatic insufficiency with adequate accuracy. Late in the disease, tests of pancreatic exocrine function more reliably become abnormal.

Pancreatic function tests are classified as

• Direct: Monitor the actual secretion of pancreatic exocrine products (bicarbonate and enzymes).

• Indirect: Measure the secondary effects of the lack of pancreatic enzymes (eg, fat malabsorption).

Direct pancreatic function tests are most useful in patients who have an earlier stage of chronic pancreatitis in whom imaging studies are not diagnostic. Direct tests involve intravenous infusion of the hormone cholecystokinin to measure the production of digestive enzymes or infusion of the hormone secretin to measure the production of bicarbonate. The duodenal secretions are collected using double-lumen gastroduodenal collection tubes or an endoscope. Direct tests are cumbersome, are time-consuming, and have not been well standardized. Direct pancreatic function tests have mostly been phased out of clinical practice and are done in only a few specialized centers.

Indirect pancreatic function tests are less accurate in diagnosing earlier stages of chronic pancreatitis. These tests involve blood or stool samples. The serum trypsinogen test is an inexpensive test and is available through commercial laboratories. Very low levels of serum trypsinogen (< 20 ng/mL) are highly specific for chronic pancreatitis. A 72-hour test for stool fecal fat in patients who are following a high-fat diet is diagnostic for steatorrhea. This test is fairly reliable but cannot establish the cause of malabsorption. In other tests, fecal concentration of chymotrypsin and elastase may be decreased. The indirect tests are widely available, less invasive, inexpensive, and easier to do than the direct tests.

1. 1. Gardner TB, Adler DG, Forsmark CE, et al: ACG Clinical Guideline: Chronic Pancreatitis. Am J Gastroenterol 115(3):322-339, 2020. doi: 10.14309/ajg.0000000000000535

2. 2. Greenhalf W, Lévy P, Gress T, et al: International consensus guidelines on surveillance for pancreatic cancer in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 20(5):910-918, 2020. doi: 10.1016/j.pan.2020.05.011

Pain control is the most challenging task in the management of patients with chronic pancreatitis (1). First, vigorous efforts and appropriate referrals to encourage smoking cessation and alcohol abstinence should be made for patients with chronic pancreatitis in an effort to slow the disease progression as early as possible. Second, treatable complications of chronic pancreatitis such as duodenal or biliary obstruction that can cause similar symptoms should be sought. Patients should consume a low-fat (< 25 g/day) diet to reduce secretion of pancreatic enzymes. Patients with chronic pancreatitis should be educated about healthy lifestyle practices, and this should be reinforced at each visit.

Pancreatic enzyme supplementation may reduce chronic pain by suppressing the release of cholecystokinin from the duodenum, thereby reducing the secretion of pancreatic enzymes. Enzyme therapy is more likely to be successful in patients with less advanced disease, in women, and in patients with idiopathic pancreatitis than in patients with alcohol-associated pancreatitis. Although enzyme therapy is often tried because of its safety and minimal adverse effects, it may not provide substantial benefit in improving pain.

Often these measures do not relieve pain, requiring increased amounts of opioids, which increases the risk of addiction. Adjunctive pain medications, such as tricyclic antidepressants, gabapentin, pregabalin, and selective serotonin reuptake inhibitors, have been used alone or combined with opioids to manage chronic pain; results are variable. Pharmacologic treatment of pain in chronic pancreatitis is often unsatisfactory.

Glucocorticoids may be used to treat autoimmune pancreatitis (2).

Other treatment modalities include endoscopic therapy, lithotripsy, celiac plexus nerve block, and surgery.

Endoscopic therapy is aimed at decompressing a pancreatic duct obstructed by stricture, stones, or both and may provide pain relief in carefully selected patients with appropriate ductal anatomy. If there is significant stricture at the papilla or distal pancreatic duct, endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy, stent placement, or dilation may be effective (3). Pseudocysts can cause chronic pain. Some pseudocysts can be drained endoscopically (4).

Lithotripsy (extracorporeal shock wave lithotripsy or intraductal lithotripsy) is usually needed to treat large or impacted pancreatic stones.

Percutaneous or endoscopic ultrasound-guided nerve blockade of the celiac plexus with a corticosteroid and long-acting anesthetic may provide short-term pain relief in some patients with chronic pancreatitis.

Surgical treatment may be effective for pain relief. Surgical options should be reserved for patients who have stopped using alcohol and who can manage diabetes that may be intensified by pancreatic resection. A variety of surgical options involve resection and/or decompression (5). The choice of surgical procedure depends on the anatomy of the pancreatic duct, consideration of local complications, the surgical history of the patient, and local expertise. For example, if the main pancreatic duct is dilated > 5 to 8 mm, a lateral pancreaticojejunostomy (Puestow procedure) or Partington-Rochelle modification of the Puestow procedure relieves pain in about 70 to 80% of patients who are well-selected (eg, without an inflammatory mass) (6). If the pancreatic duct is not dilated, a variation of the modified Puestow procedure called a V-plasty or Hamburg procedure can be done.

Other surgical approaches include a partial resection such as a distal pancreatectomy (for extensive disease at the tail of the pancreas), a Whipple procedure (for extensive disease at the head of the pancreas), a pylorus-sparing pancreaticoduodenectomy (similar to a Whipple procedure), a duodenum-preserving pancreatic head resection (Beger procedure), or a total pancreatectomy with autotransplantation of islets. Overall, surgical drainage is more effective than endoscopic approaches in relieving obstruction and achieving pain relief (7).

In patients with exocrine pancreatic insufficiency, malabsorption of fat is more severe than malabsorption of proteins and carbohydrates. Fat malabsorption also results in a deficit of fat-soluble vitamins (A, D, E, and K). Pancreatic enzyme replacement therapy (replacement of deficient hormones to treat pancreatic insufficiency) is used to treat steatorrhea (8). Various preparations are available, and a dose of 75,000 to 150,000 United States Pharmacopeia units (25,000 to 50,000 international units) lipase per meal and half that amount with snacks is needed for appropriate fat absorption. The treatment should be started at these (low) doses with subsequent titration based on clinical response. The preparations should be taken with meals. An H2 blocker or proton pump inhibitor should be given to patients taking nonenteric–coated preparations to prevent acid breakdown of the enzymes.

Favorable clinical responses include weight gain, fewer bowel movements, elimination of oil droplet seepage, increases in levels of fat-soluble vitamins, and improved well-being. Clinical response can be documented by showing a decrease in stool fat after enzyme replacement therapy. If steatorrhea is particularly severe and refractory to these measures, medium-chain triglycerides can be provided as a source of fat because they are absorbed without pancreatic enzymes and other dietary fats should be reduced proportionally. Supplementation with fat-soluble vitamins A, D, and K should be given, including vitamin E, which may minimize inflammation.

The patient should be referred to an endocrine specialist for the management of diabetes. Insulin should be given cautiously because the coexisting deficiency of glucagon secretion by alpha cells can result in unopposed and prolonged hypoglycemia, which is the hallmark of pancreatogenic diabetes (type 3c diabetes). Oral hypoglycemic drugs rarely help treat diabetes caused by chronic pancreatitis.

1. 1. Gardner TB, Adler DG, Forsmark CE, et al: ACG Clinical Guideline: Chronic Pancreatitis. Am J Gastroenterol 115(3):322-339, 2020. doi: 10.14309/ajg.0000000000000535

2. 2. Okazaki K, Chari ST, Frulloni L, et al: International consensus for the treatment of autoimmune pancreatitis. Pancreatology 17(1):1-6, 2017. doi: 10.1016/j.pan.2016.12.003

3. 3. Kitano M, Gress TM, Garg PK, et al: International consensus guidelines on interventional endoscopy in chronic pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club. Pancreatology 20(6):1045-1055, 2020. doi: 10.1016/j.pan.2020.05.022

4. 4. ASGE Standards of Practice Committee; Muthusamy VR, Chandrasekhara V, et al: The role of endoscopy in the diagnosis and treatment of inflammatory pancreatic fluid collections. Gastrointest Endosc 83(3):481-488, 2016. doi: 10.1016/j.gie.2015.11.027

5. 5. Kempeneers MA, Issa Y, Ali UA, et al: International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis. Pancreatology 20(2):149-157, 2020. doi: 10.1016/j.pan.2019.12.005

6. 6. Bouwense SAW, Kempeneers MA, van Santvoort HC, et al: Surgery in Chronic Pancreatitis: Indication, Timing and Procedures. Visc Med 35(2):110-118, 2019. doi: 10.1159/000499612

7. 7. Yang CJ, Bliss LA, Freedman SD, et al: Surgery for chronic pancreatitis: The role of early surgery in pain management. Pancreas 44(5):819–823, 2015. doi: 10.1097/MPA.0000000000000333

8. 8. Whitcomb DC, Buchner AM, Forsmark CE: AGA Clinical Practice Update on the Epidemiology, Evaluation, and Management of Exocrine Pancreatic Insufficiency: Expert Review. Gastroenterology 165(5):1292-1301, 2023. doi: 10.1053/j.gastro.2023.07.007