Chronic pancreatitis is an irreversible chronic inflammatory disease of the pancreatic tissue and function caused by various etiologies, which is pathologically characterized by atrophy and destruction of the pancreatic alveoli and interstitial fibrosis. The main clinical manifestations are recurrent epigastric pain and/or pancreatic exocrine and endocrine insufficiency, which may be accompanied by pancreatic parenchymal calcification, pancreatic duct dilatation, pancreatic duct stones and pancreatic pseudocyst formation.
I. Epidemiology of CP
The prevalence of CP in the United States is 8.1/100,000, in France is 26/100,000, in Japan is 33/100,000, and in India is the highest prevalence of (114-200)/100,000. According to the survey of 2008 cases of CP in 22 hospitals in China from 1994 to 2004, the prevalence rate was about 13/100,000, and the trend is increasing year by year.
Second, the pathogenic factors of CP
Chronic pancreatitis has many causative factors and is often the result of multiple factors. Alcoholism is one of the main factors, accounting for more than 60% in Western countries and about 35% in China. Other causative factors include hyperlipidemia, hypercalcemia, congenital abnormalities of the pancreas, pancreatic trauma or surgery, autoimmune diseases, genetic mutations or deficiencies, etc. The causative factors are not clear in 20% to 30% of patients.
III. Diagnosis of CP
(I) Clinical manifestations According to the course of CP, the clinical manifestations can be divided into 4 types. Although abdominal pain is the main clinical symptom of CP, 3% to 20% of patients can have no obvious abdominal pain and are diagnosed with CP only on physical examination or when type III or IV symptoms appear.
(II) Physical signs
Epigastric pressure pain and signs of peritoneal irritation may be present during acute attacks. When complicated by a huge pseudocyst, a mass can be retrieved. When the pancreatic head is significantly fibrotic or the pseudocyst compresses the lower part of the common bile duct, jaundice may appear. Wasting may occur due to impaired digestion and absorption, and signs associated with other complications may also appear.
(C) Diagnostic imaging
X-ray: calcified foci and positive stone shadows in the pancreatic region are seen in some patients. Abdominal ultrasound: Based on the morphology of the pancreas, echogenicity and pancreatic duct changes, it can be used as a primary screening test for CP, but the sensitivity of diagnosis is not high. CT/MRI/MRCP:CT shows changes such as enlarged or shrunken pancreas, irregular contour, pancreatic calcification, irregular dilatation of pancreatic duct or pancreatic pseudocyst.MRI has similar diagnostic value to CT for CP, but it does not show calcification and stones as well as CT.MRCP can show the degree of pancreatic duct dilatation and stone location, and can clarify the etiology of some CP.
Endoscopic ultrasound (EUS): The diagnosis of CP is better than that of abdominal ultrasound, with a diagnostic sensitivity of about 80%. The main manifestations are pancreatic parenchymal echogenicity enhancement, main pancreatic duct stenosis or irregular dilatation and branch pancreatic duct dilatation, pancreatic duct stones, pseudocysts, etc.
Endoscopic retrograde cholangiopancreatography ( ERCP): It is an important basis for the diagnosis of CP, which shows pancreatic duct stenosis and dilatation and stones. Mild CP: pancreatic duct lateral branch dilatation or obstruction (more than 3), normal main pancreatic duct; moderate CP: main pancreatic duct stenosis and dilatation; severe CP: main pancreatic duct obstruction, stenosis, stone, calcification, with pseudocyst formation.
(IV) Laboratory tests
Elevated serum amylase is seen during acute attacks, and if combined with chest and ascites, the amylase content in chest and ascites is often significantly elevated. CP may also show an increase in serum CA19-9, and if it is significantly elevated, the possibility of combined pancreatic cancer should be alerted. Pancreatic exocrine function test: The pancreatic exocrine function test is mostly non-invasive and is a reference for diagnosis, but the sensitivity of the test currently conducted is poor. Other related tests: IgG4, blood calcium, blood lipids, parathyroid hormone, virus and other tests are feasible when available to clarify the etiology of CP.
(E) Pathological changes of CP
The basic pathological changes of CP include different degrees of alveolar destruction, interstitial fibrosis of the pancreas, ductal dilatation and cyst formation. According to its pathological changes, it can be divided into chronic calcific pancreatitis, chronic obstructive pancreatitis and chronic inflammatory pancreatitis. Chronic calcific pancreatitis is the most common and manifests as sporadic interstitial fibrosis and protein emboli and stone formation in the glandular ducts and damage to the glandular ducts; chronic obstructive pancreatitis due to local obstruction of the main pancreatic duct, ductal stenosis leading to proximal dilatation and atrophy of the alveolar cells, which are replaced by fibrous tissue; chronic inflammatory pancreatitis mainly manifests as fibrosis and atrophy of the pancreatic tissue and infiltration of mononuclear cells. Pathological changes in extra-pancreatic organs, such as bile duct obstruction, portal vein compression, and thrombosis, are also seen in the presence of complications.
Acquisition of pancreatic specimens: surgical biopsy is the ideal specimen, which can also be obtained by EUS, CT or abdominal ultrasound-guided puncture biopsy.
IV. Diagnostic criteria and staging of CP
(a) Diagnostic criteria Main diagnostic bases: ① typical clinical manifestations (recurrent epigastric pain or acute pancreatitis, etc.); ② imaging examinations suggesting pancreatic calcification, pancreatic duct stones, pancreatic duct stenosis or dilatation, etc.; ③ characteristic pathological changes; ④ pancreatic exocrine insufficiency manifestations.
② or ③ can confirm the diagnosis; ①+④ proposed diagnosis.
(II) Clinical staging
Staging according to the clinical manifestations and comorbidities of CP (Table 2) is of guiding significance for treatment selection.
Table 2 Clinical staging of chronic pancreatitis
Clinical staging
Clinical manifestations
Stage l
Type I or II clinical manifestations only
Stage 2
Type III clinical manifestations appear
Stage 3
Appearance of type IV clinical manifestations
V. Diagnostic process of CP
The diagnosis of CP is to clarify the etiology as much as possible, and to make staging and prognosis judgment. The diagnostic process is shown in Figure 1.
VI. Treatment principles of CP
The treatment principles of CP are to eliminate the cause, control the symptoms, improve the function of the pancreas, treat complications and improve the quality of life.
(I) General treatment
Patients with CP must abstain from alcohol, smoking and excessive high-fat and high-protein diet. Patients with long-term steatorrhea should pay attention to supplementation of fat-soluble vitamins and vitamin B12 and folic acid, and appropriate supplementation of various trace elements.
(B) Internal treatment 1. treatment of acute exacerbation: the treatment principle is the same as acute pancreatitis. 2. treatment of pancreatic exocrine insufficiency: the main application of exogenous pancreatic enzyme preparation replacement therapy and auxiliary diet therapy. Pancreatic enzyme preparations also have a role in relieving pancreatic-derived pain. The first choice is the ultra-micronized pancreatic enzyme capsule containing highly active lipase, and it is recommended to take it during meals. In case of poor efficacy, acid-suppressing drugs such as proton pump inhibitors and H2 receptor blockers can be added. 3. Diabetes: Intensive conventional insulin therapy is used to maintain the optimal metabolic status of CP patients. Since patients with CP combined with diabetes mellitus are more sensitive to insulin, attention should be paid to prevent the occurrence of hypoglycemia. 4. Treatment of pain: ①General treatment: mild patients can be relieved by alcohol cessation and diet control. ②Medication: painkillers, pancreatic enzyme preparations and growth inhibitors and their analogues. ③Endoscopic treatment is feasible for obstructive pain, and CT and EUS-guided abdominal nerve block is feasible for non-obstructive pain. ④Surgical treatment can be considered when the above methods are ineffective.
(C) Endoscopic interventional treatment
Endoscopic treatment of CP is mainly used for pancreatic duct decompression and lithotripsy to relieve pancreatic-derived pain and improve quality of life, and the procedures include pancreatic duct dilatation, stent placement, lithotripsy, lithotripsy and cyst drainage. The success rate of ESWL lithotripsy is over 95%, and the stone removal rate can reach 70%-85% when combined with endoscopic treatment.
(iv) Surgical treatment
Surgical treatment is divided into emergency surgery and elective surgery.
Indications for emergency surgery: CP complications caused by infection, bleeding, cyst rupture, etc. Indications for elective surgery: (1) those with ineffective medical and interventional treatment; (2) those with biliary and duodenal obstruction due to compression of adjacent organs and ineffective endoscopic treatment, as well as those with left-sided portal hypertension with bleeding; (3) those with pseudocyst, pancreatic fistula or pancreatic-derived ascites and ineffective medical and interventional treatment; (4) those who cannot exclude malignant changes.
Surgery: The principle of surgical treatment is to relieve pain, control complications, delay the progression of pancreatic inflammation and protect endocrine and exocrine functions with the simplest possible surgical procedure. The choice of surgical procedure requires comprehensive consideration of inflammatory pancreatic mass, pancreatic duct obstruction and complications. If the main pancreatic duct is dilated and there is no inflammatory mass in the head of the pancreas, lateral anastomosis of the pancreatic duct and jejunum can be used; if there is inflammatory mass in the head of the pancreas, multiple branch pancreatic duct stones in the head of the pancreas, combined with pancreatic duct, bile duct or duodenal obstruction, standard pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy can be considered; while preserving the integrity of the duodenum and bile duct, pancreatic head resection with preservation of the duodenum can remove both Inflammatory masses and can also relieve obstruction of the pancreatic duct and biliary tract, the main procedures include Beger’s surgery, Frey’s surgery and Beme’s surgery; inflammatory lesions or main pancreatic duct stenosis concentrated in the tail of the pancreatic body can be treated by resection of the spleen or spleen-preserving tail of the pancreatic body; for extensive inflammatory changes in the whole pancreas and multiple branching pancreatic duct stones that cannot be treated by partial pancreatectomy or pancreatic duct dissection, etc. Total pancreatectomy and autologous islet transplantation can be considered.
(E) Treatment process of CP
The treatment of CP should be a multidisciplinary and comprehensive treatment of internal medicine, surgery, endoscopy, anesthesia and nutrition (Figure 2), and given the advantages of minimally invasive and reproducible endoscopic intervention, it can be used as the first-line treatment.