1. Case information [Case 1] Male, 55 years old. He was admitted to our hospital on 2011-02-23 due to abdominal pain and yellowish staining of skin and sclera for 15 d. The patient was admitted to our hospital 15 d ago with no obvious cause of epigastric distension and pain, dark urine, thick tea-like, no fever and chills, no abdominal distension and diarrhea. The patient was diagnosed by abdominal ultrasound as dilated intra- and extrahepatic bile ducts and occupying pancreatic lesion, and by CT as diffuse enlargement of the pancreas and occupying lesion in the head of the pancreas. He was admitted to our hospital for further diagnosis and treatment. Past history: no history of diabetes mellitus, hypertension, coronary heart disease. No smoking and alcohol addiction. He was admitted with a temperature of 36.4°C, pulse rate of 75 beats/min, respiration of 18 breaths/min, and blood pressure of 118/75 mmHg. The skin and sclera were mildly yellowish. There were no obvious positive signs of heart and lungs. The abdomen was flat, no gastrointestinal type or peristaltic wave was seen; the liver and spleen were not detected under the ribs, there was no significant pressure pain throughout the abdomen, Murphy’s sign was negative, no mass was palpated, and the mobile turbid sounds were negative. Laboratory findings: normal leukocytes and granulocytes percentage; glutathione 377 U/L, total bilirubin 50.8 mmol/L, direct bilirubin 23.1 mmol/L, g-glutamyl transpeptidase 405 U/L, alkaline phosphatase 258 U/L; normal blood and urine amylase; hepatitis virus serum markers (-), glycogen antigen CA 19-9 63.0 U/L (normal value 0 ~ 39.0 g/L), other tumor markers are not abnormal. The CT diagnosis: autoimmune pancreatitis (AIP), not excluding occupying lesions in the jugular abdomen, serum immunology or aspiration biopsy is recommended for further examination. MRI biliary water imaging (MRCP) showed: low level biliary obstruction with obstruction at the lower end of the common bile duct; pancreatic thickening.MRCP diagnosis: combined with CT considered AIP, not excluding peri-pot belly cancer. Serum immunological test: immunoglobulin IgG 19.2 g/L (normal value 6.0 ~ 16.0 g/L), IgA and IgM were normal. In view of the jaundice, elevated IgG, and diffuse swelling of the pancreas, the patient was clinically diagnosed with AIP, and hormone therapy was started after 1 week of hospitalization: prednisone acetate tablets, 30 mg, orally 1/day, along with liver protection. After 4 d of hormone therapy, the clinical symptoms were significantly relieved, and the total bilirubin 19.4 mmol/L, direct bilirubin 8.4 mmol/L, and IgG 16.0 g/L were all reduced to normal levels. 2 weeks later, the CT scan showed that the gallbladder was significantly reduced, and the widening of the intra- and extrahepatic bile ducts was reduced, but the pancreas was still thickened, and the posterior margin of the pancreatic body and the anterior margin of the tail of the pancreas were similar to the CT scan 2 weeks before. After 2 weeks of oral hormone administration, prednisone acetate tablets were reduced to 20 mg/day. 1 month later, the CT scan showed that the widening of the intra- and extrahepatic bile ducts was significantly reduced and the enlargement of the pancreas had subsided. After 6 months, the patient’s oral hormone therapy was continued, and the treatment was maintained after decreasing 5mg/week to 5mg/d. After 6 months, the CT scan showed no significant dilatation of the intra- and extra-hepatic bile ducts, and the pancreatic volume was basically normal. At the follow-up of nearly 2 years, the patient was in good general condition with no recurrence. [Case 2] Female, 49 years old. She was admitted to our hospital on 2012-03-19 due to epigastric distention for 1 month, aggravated with epigastric pain for 1 week. The patient felt distention and discomfort in the upper abdomen 1 month ago, which worsened after eating. 1 week ago, she developed pain in the left upper abdomen with no obvious cause, radiating to the left lower back and left shoulder. He was treated at a local hospital, and took oral pain medication. The diagnosis of abdominal CT was that the pancreas was full and swollen, which was considered to be an occupying lesion; a low-density lesion was seen in the liver, which did not exclude the possibility of liver metastasis. For further diagnosis and treatment, he was admitted to our hospital. Past history: no history of diabetes mellitus, hypertension, coronary heart disease. He was not addicted to smoking or alcohol and did not overeat. The body temperature was 36.7°C, pulse rate was 78 beats/min, respiration was 17 breaths/min, blood pressure was 129/82 mmHg. The skin and sclera were not yellowish. There were no obvious positive signs in the heart and lungs, mild pressure pain in the left upper abdomen, no rebound pain or muscle tension, and no palpable mass. Laboratory findings: white blood cell and granulocyte percentage were normal; glutaminase 377 U/L, total bilirubin 15.7 mmol/L, direct bilirubin 7.5 mmol/L, g-glutamyl transpeptidase 187 U/L, alkaline phosphatase 94 U/L; total cholesterol and triglycerides were normal; blood and urine amylase were normal; hepatitis virus serum markers were (-), tumor markers were (-); autoantibodies 15 tests were not abnormal. ultrasound showed There was no dilatation of the bile ducts inside and outside the liver, and the right lobe of the liver showed 0.9 cm diameter echogenicity. The head of the pancreas was normal in size, the body of the pancreas was 2.9 cm, widened, the tail of the pancreas was 2.2 cm, the echogenicity of the caudal part of the body was uneven, no clear image of the mass was seen, and the main pancreatic duct was not dilated. CT diagnosis: 1, cyst in the right lobe of the liver; 2, pancreatic thickening, not excluding atypical pancreatitis. Serum immunological tests were performed: immunoglobulin IgG 17.0 g/L, IgA and IgM were normal. In view of the patient’s left upper abdominal pain, imaging showed enlargement of the pancreatic neck, no clear hypodense lesions, no evidence of pancreatic cancer and elevated serum IgG, the clinical diagnosis of AIP was made. After 3 d of hormone therapy, the patient’s general condition improved significantly, and the abdominal pain symptoms were significantly relieved. After 1 week of treatment, serum IgG 12.6 g/L was rechecked, and after 2 weeks, CT showed that the thickening of the neck of the pancreas was reduced compared with the previous one. After 2 weeks of oral hormone treatment, prednisone acetate tablets were reduced by 5 mg per week to 5 mg/d, and the treatment was maintained for 3 months. At 1 year follow-up, the patient was in good general condition with no recurrence. 2, Discussion 2.1, Pathogenesis Autoimmune pancreatitis (AIP) is a specific type of chronic pancreatitis mediated by autoimmune inflammation and characterized by diffuse or localized enlargement of the pancreas and irregular stenosis of the pancreatic duct. Sarles et al. first described this disease in 1961, and Yoshida et al. formally introduced the concept of AIP in 1995. in 2001 AIP has been used as an independent subtype of chronic pancreatitis. The etiology of AIP is not fully understood, and the two cases in this group do not have the common causes of pancreatitis such as gallstone disease, alcoholism, hyperlipidemia, overeating, and drugs. The literature reports that AIP may be related to the following factors: (1) immune factors. Immune-mediated pathogenesis has been the focus of research on AIP, and a large body of literature has confirmed that most patients with AIP have hyperglobulinemia and elevated serum IgG4 levels, and positive expression of autoantibodies such as antinuclear antibodies, human type II carbonic anhydrase antibodies (ACA-II) and anti-amylase a-2A antibodies can be detected, and deposits of complement C3 and IgG can be seen on the basement membrane of the pancreatic duct [5 ]. Meanwhile, the proportion of CD4+ T cells and CD8+ T cells in peripheral blood and pancreatic tissues of AIP patients was increased while CD45RA+ regulatory T cells were significantly decreased, suggesting that both cellular and humoral immune mechanisms are involved in the occurrence and development of AIP. (2) Genetic factors. Immune system diseases may often have genetic mutations involved in disease development, and AIP may occur along with other autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease), so it is assumed that genetic factors are involved in the development of the disease. (3) Infectious factors. H. pylori infection can induce autoimmune response and apoptosis through recognition by ACA-II, which can promote AIP and accelerate pancreatic damage in chronic pancreatitis. 2.2. Typing and nomenclature of AIP There are 2 different types of AIP according to histology and clinical manifestations, and the International Pancreatic Society has agreed on its histopathological diagnostic criteria. One type is lymphoplasmacytic sclerosing pancreatitis (LPSP) or autoimmune pancreatitis without granulocytic epithelial damage (GEL), with the following 4 histopathological features of the pancreas: (1) dense infiltration of plasma cells and lymphocytes, especially around the pancreatic duct. (2) Specific peculiar storiform fibrosis. (3) Small phlebitis with lymphocytes and plasma cells, often causing occlusion of the involved veins. (4) Large numbers of immunoglobulin G4 (IgG4)-positive plasma cells (> 10/HPF). Clinically, this type appears to be a manifestation of pancreatic lesions in IgG4-associated systemic diseases, which are characterized by elevated serum IgG4 levels and extra-pancreatic lesions such as sclerosing cholangitis, sclerosing salpingitis, and retroperitoneal fibrosis with massive IgG4-positive plasma cell infiltration. Another type is spontaneous ductocentric pancreatitis (IDCP) or autoimmune pancreatitis with granulocytic epithelial damage (GEL), which is prevalent in the United States and Europe.LPSP shares some of the same histopathologic features as IDCP, such as peripancreatic ductal lymphoplasmacytic infiltration and patterned fibrosis, but one feature of IDCP that distinguishes it from LPSP is granulocytic epithelial damage: pancreatic alveoli IDCP has no or little IgG4-positive plasma cell infiltration (< 10/HPF), and the clinical data of patients with histologically confirmed type II AIP suggest that it is not a systemic disease, but more like a unique pancreatic lesion without elevated serum IgG4 and other organ involvement. However, about 30% of patients with IDCP reported in the literature have inflammatory bowel disease such as ulcerative colitis. Currently, the International Pancreatic Society classifies LPSP as type I AIP and IDCP as type II AIP. 2.3 Clinical characteristics Reviewing the literature, AIP has the following clinical characteristics: (1) insidious onset, type I AIP patients are predominantly male, usually with an age of onset greater than 50 years; type II AIP patients have no significant gender differences, with an age of onset of about 40 years. (2) Clinical symptoms are mainly progressive or intermittent jaundice with or without abdominal pain, and abdominal pain is mostly epigastric discomfort or mild pain, with few episodes of acute pancreatitis-like severe abdominal pain. In our case 1, the symptoms were abdominal pain and mild jaundice, and in case 2, the main manifestation was left upper abdominal pain, both without acute pancreatitis-like symptoms of severe abdominal pain. Wang Kewei et al. reported one case and searched the literature to collect 107 cases of AIP reported in China from January 2001 to December 2010, and analyzed the clinical symptoms of 108 cases of AIP, of which 74% (80/108) had obstructive jaundice, 46% (50/108) had epigastric discomfort or pain, and about 1% (1/108) were asymptomatic. In addition, AIP patients have weight loss and may be accompanied by fatigue, nausea, vomiting and abdominal distension. (3) Other immune system diseases may be associated. The literature reports that 20% to 50% of AIP is associated with other autoimmune diseases, such as Sj?gren syndrome (dry mouth and eyes arthritis syndrome), primary sclerosing cholangitis (PSC), sclerosing salpingitis, ulcerative colitis, systemic lupus erythematosus and diabetes mellitus (mainly type II), interstitial lung fibrosis, autoimmune thyroid disease, retroperitoneal fibrosis and so on. A small number of AIP patients may be accompanied by two autoimmune diseases at the same time. (3) Laboratory tests: elevated levels of g-globulin, IgG, especially IgG4; elevated bilirubin, abnormal liver enzymes; normal or elevated serum amylase, about half of the patients with AIP have elevated blood amylase, but it is rare that the value is three times higher than normal; normal or mildly elevated blood lipase; elevated blood glucose; positive expression of various autoantibodies in serum; some cases may have mild elevation of CA19-9. (4) Imaging shows diffuse or limited enlargement of the pancreas, limited AIP usually involves the head of the pancreas, pancreatic calcification, pancreatic duct stones and pseudocysts are rare. CT is the most commonly used imaging method to diagnose AIP, which has the following CT features: 1. The pancreas is commonly enlarged in a bologna-like fashion on CT examination of diffuse AIP. The density of the lesioned pancreatic tissue is homogeneous, and the density of the AIP lesion is relatively homogeneous in CT scan, arterial phase, venous phase and delayed phase, which is different from pancreatic cancer that shows inhomogeneous density.2. Delayed enhancement of the AIP lesioned pancreas is relatively hypodense in the early phase on enhanced CT scan, while the density gradually increases in the delayed phase with progressive enhancement, which is different from the enhancement characteristics of the normal pancreas.Enhanced CT of AIP The characteristics of delayed enhancement are caused by the characteristics of its lesion: the proliferating fibrous tissue compresses the microvessels in the pancreas, narrowing the vascular lumen and slowing down the blood flow, and the contrast agent slowly enters the lesion tissue and slowly flows out.3. Capsule-like rim is seen around the pancreas. This may be due to fibrotic changes containing peripancreatic adipose tissue. Magnetic resonance cholangiopancreatography (MRCP)/retrograde cholangiopancreatography (ERCP) shows diffuse or segmental stenosis of the main pancreatic duct, and sometimes biliary stenosis is seen, mostly involving the pancreatic segment. (5) Histopathologically type I AIP mainly presents as LPSP; type I AIP mainly presents as IDCP.(6) Hormonal therapy is effective. 2.4. Diagnosis and differential diagnosis The initial diagnostic criteria for AIP were the JPS criteria developed by the Japanese Pancreatic Society in 2002. Since then there are modified Japanese criteria and Korean Kim criteria, as well as HISORT criteria (histology, imaging, serology, involvement of other organs, response to hormone therapy) in the U.S. In 2008, Japanese and Korean scholars jointly introduced Asian diagnostic criteria for AIP: (1) Imaging changes: diffuse or limited enlargement of the pancreas, sometimes with masses and/or hypodense margins. Diffuse or restrictive stenosis of the pancreatic duct, often accompanied by biliary stenosis. (2) Serologic examination: elevated serum IgG or IgG4 and positive for other autoantibodies. (3) Histological examination: lymphocytic infiltration with fibrosis at the site of pancreatic lesion. (4) Selectable criteria: effective for hormone therapy. In 2011, the International Society of Pancreatic Diseases published the international diagnostic criteria for AIP, which are based on P (pancreatic parenchymal image), D (pancreatic ductal image), S (serology), OOI (other organ involvement), H (pancreatic histology), and R (hormone treatment response) to classify type I AIP. response) to classify type I AIP into grade 1 and grade 2; type II AIP was classified into grade 1 and grade 2 according to P, D, OOI, and H. Because of the lack of serologic markers for type II AIP, the international diagnostic criteria for type II AIP emphasize the importance of histologic pathologic examination. Clinically, AIP needs to be associated with pancreatic cancer. clinical manifestations of AIP are mostly jaundice or abdominal discomfort and abdominal pain that gradually worsen, similar to the clinical manifestations of pancreatic cancer; imaging manifestations are diffuse enlargement of the pancreas or limited enlargement, especially when the head of the pancreas is enlarged, which is extremely similar to pancreatic cancer in appearance; some patients have elevated CA19-9. Therefore, clinically, AIP is easily misdiagnosed as pancreatic head cancer. Some authors reported that the misdiagnosis rate of AIP in hepatobiliary surgery is as high as 96%, and other literature reported that 91% of patients underwent surgery due to misdiagnosis of this disease. For the differentiation of the two, we should pay attention to the clinical symptoms (including extra-pancreatic organ lesions) and carefully analyze the imaging features, especially the CT examination results of the pancreas, which are mostly without diffuse enlargement of the pancreas. It is common. The aforementioned CT features of AIP, as well as the significantly higher CT values in the venous phase of enhanced CT at the site of AIP-involved pancreas than pancreatic cancer, the non-dilated or slightly dilated distal pancreatic duct of the involved pancreas, and the rare invasion of peripancreatic vessels, can provide important information for the differential diagnosis of pancreatic (head) cancer and AIP. In addition, attention should be paid to the detection of serological globulin, IgG or IgG4 levels, autoantibodies and tumor markers. The sensitivity and specificity of serum IgG>1777mg/L for the diagnosis of AIP were 57.1% and 93.7%, respectively, and 73.3% and 95.1% for IgG4 levels>1410mg/L. The sensitivity and specificity of IgG4 levels>2800mg/L were 53% and 99%, respectively. The literature reports that combined serum IgG4 and CA19-9 tests can be used for the differential diagnosis of AIP and pancreatic cancer. In our group, two exceptions were diagnosed with pancreatic occupying lesions on hospital imaging. Our CT examination example 1 showed diffuse enlargement of the pancreas with salami-like changes, and example 2 showed localized enlargement of the pancreatic neck with uniform enhancement on enhancement scan, which were not consistent with imaging features of pancreatic cancer. The possibility of AIP was considered after detecting elevated IgG, and the diagnosis was finally confirmed by effective hormone therapy. Analysis of the reasons for the misdiagnosis of the 2 patients as pancreatic occupations in the external hospital was mainly related to the fact that AIP (especially the localized type of AIP) resembles pancreatic occupational lesions in appearance and is easily misdiagnosed on imaging. Through the treatment of these two patients with AIP, we learned that the diagnosis of AIP is mainly made by comprehensive analysis of imaging manifestations, laboratory tests and the effect of hormonal therapy. The key to the correct diagnosis of AIP is to understand its clinical features, to be familiar with the clinical symptoms, signs and imaging features of AIP, especially CT features, and to be alert to the possibility of AIP during the diagnosis and treatment of atypical occupying pancreatic lesions. AIP also needs to be differentiated from common chronic pancreatitis to avoid missing the opportunity of hormone therapy. Most patients with common chronic pancreatitis have a history of alcoholism or biliary disease. Imaging is commonly associated with pancreatic parenchymal atrophy, irregular dilatation of the main pancreatic duct, often with intrapancreatic duct stones, mucin emboli, pancreatic parenchymal calcification and peripancreatic pseudocyst formation. 2.5. Treatment The clinical effect of glucocorticoid treatment for AIP is good, which can relieve clinical symptoms, improve laboratory and pancreatic imaging findings, and also improve the condition of the pancreas and extra-pancreatic involved organs. The dose and duration of hormone application vary, but usually the starting dose is 30-40mg/d, and after 2-4 weeks of treatment, the dose is reduced by 5mg every 1-2 weeks, and the total course of treatment is usually six months. Kamisawa et al. found no significant relationship between the degree of improvement of AIP and the starting dose of hormone through long-term follow-up, and therefore recommended a starting dose of 30 mg/d. The duration of hormone therapy for AIP is mostly advocated as a long course of treatment, which is usually discontinued when the pancreatic imaging pattern returns to normal. The recurrence rate after hormone therapy for AIP is 6% to 26%. For patients with AIP recurrence, they can be treated with a large amount of hormone again, and about 6% of patients need small dose (2.5~5.0 mg/d) maintenance therapy, and there are also a small number of patients who can remit on their own without hormone therapy. Ursodeoxycholic acid has also been reported to have a therapeutic effect on AIP in some cases, but further studies are needed to follow up. In our case 1, prednisone acetate tablets, 30 mg, were administered orally 1/day, and the jaundice subsided after 4 days of treatment, and the IgG decreased to normal level; after 2 weeks of treatment, the dilatation of the intra- and extrahepatic bile ducts was reduced, indicating that the inflammation of the pancreatic tissue was reduced; after 1 month of treatment, the enlargement of the pancreas had subsided. In case 2, because the clinical symptoms were relatively mild and the pancreas was not diffusely enlarged, the hormone dose was smaller than that of case 1. After 3 days of hormone treatment, the patient’s symptoms were significantly relieved; the serum IgG returned to normal after 1 week; the thickening of the pancreatic neck was reduced after 2 weeks compared with the previous one. The duration of hormone treatment was six months in case 1 and three months in case 2, both of which were discontinued after CT examination showed that the size of the pancreas had basically returned to normal. Through the treatment of the two AIP cases in this group, we believe that AIP hormone therapy can take individualized doses, and patients should be closely observed for symptom relief during treatment, and blood biochemistry and serum immunological indexes and pancreatic imaging should be strictly and regularly rechecked, and the drug should be stopped after the serum IgG and pancreatic imaging patterns basically return to normal, to avoid premature discontinuation or insufficient hormone maintenance doses leading to disease recurrence. The jaundice subsided quickly after hormone therapy, which indicates that if the diagnosis of AIP is clear, the jaundice can not be reduced. When applying hormone therapy, patients with combined diabetes mellitus should have their blood glucose controlled in the normal range. If clinical symptoms persist and hormone therapy is ineffective or if malignancy is suspected, surgical treatment must be performed.