自身免疫性胰腺炎的诊断与治疗

Diagnosis and treatment of autoimmune pancreatitis

目的：总结自身免疫性胰腺炎（AIP）的临床特征、诊断与治疗方法。 方法：采用回顾性描述性研究方法。收集2010年1月至2014年12月中国医科大学附属第一医院收治的43例AIP患者的临床资料。全部患者行实验室和影像学检查。对诊断明确者采取皮质类固醇激素治疗，对怀疑胰腺恶性肿瘤的患者采取手术治疗。观察指标：（1）临床表现。（2）实验室检查结果。（3）影像学表现。（4）治疗情况。（5）病理学表现。（6）随访情况。采用门诊和住院方式进行随访，随访内容包括实验室和影像学检查，随访时间截至2016年1月。偏态分布的计量资料以平均数（范围）表示。 结果：（1）临床表现：43例患者中，33例有梗阻性黄疸，19例体质量减轻，18例腹上区胀痛，5例急性轻型胰腺炎发作（同一患者合并多种症状）。43例患者中23例胰腺外组织器官受累，合并局灶性肾炎15例、干燥综合征7例、肺部受累5例、自身免疫性甲状腺炎5例、肝门部IgG4相关性胆管炎3例、腹膜后纤维化3例、溃疡性结肠炎1例（同一患者合并多种疾病）。（2）实验室检查结果：17例患者行IgG4检测，15例浓度升高。（3）影像学表现：43例患者均行腹部CT检查，胰腺弥漫性肿大、呈香肠样外观34例，胰腺局灶性肿大9例。20例患者胰周血管受累，其中包括脾静脉狭窄或闭塞，肠系膜上静脉、门静脉和脾静脉汇合部狭窄，导致区域性门静脉高压继发胃周静脉曲张和脾肿大。3例可见肠系膜上动脉被软组织肿块包绕伴大量腹腔积液。5例可见胰腺假性囊肿伴脾静脉受累和胰周渗出。15例肾脏受累的患者腹部CT检查表现为肾皮质楔形或结节样病变。 5例出现肺部炎性假瘤和间质性肺炎，肺部CT检查显示实性的肺部结节或肺泡间质弥漫性毛玻璃样斑片影。32例行MRCP检查。28例行ERCP检查，其结果显示：主胰管局灶性、弥漫性或节段性狭窄28例（弥漫性狭窄23例、局限性狭窄5例），胰腺内胆总管狭窄32例，肝门部胆管狭窄3例。9例行EUS检查，其结果显示：胰头部低回声肿块3例，胰腺实质弥漫性或非均质低回声改变6例。（4）治疗情况：43例患者中，30例接受激素初始治疗。经类固醇激素治疗后，27例患者相关临床症状逐渐好转，实验室、影像学表现均有所好转。11例患者未接受激素初始治疗，其中2例因梗阻性黄疸行内镜胆管支架植入术，7例行外科胆管内引流术，2例未接受内镜治疗和外科手术治疗。2例因怀疑胰腺腺癌而行胰十二指肠切除术，术后病理学确诊为AIP，术后接受激素治疗。（5）病理学表现：43例患者中，22例行病理学检查，其中5例浅表淋巴结标本活组织病理学检查显示淋巴结内活跃的淋巴滤泡增生，免疫组织化学染色检测显示淋巴结内含有大量IgG4阳性的浆细胞，支持AIP相关淋巴结病的诊断。15例行细针抽吸细胞学检查，其中14例无恶性肿瘤细胞学证据，1例怀疑有恶性肿瘤上皮细胞而行胰腺切除。2例胰腺切除手术标本病理学检查显示致密的淋巴结细胞，免疫组织化学染色检测显示IgG4阳性的浆细胞浸润，明确了AIP的诊断。（6）随访情况：41例患者获得随访，平均随访时间为28个月（12～71个月）。30例接受激素初始治疗的患者中，27例治疗完全有效，3例部分有效。27例完全有效的患者，随访期间4例复发，继续应用激素治疗并延长疗程治愈，3例未再复发，1例再次复发，需要长期小剂量激素维持治疗。3例激素治疗部分有效的患者，加用霉酚酸酯分别治疗6、4、4个月后影像学检查异常完全消失。11例未接受激素初始治疗的患者中，2例失访， 1例行胆总管空肠吻合术患者术后1年死亡，其余8例患者影像学异常自发性缓解或经激素治疗后临床和影像学表现均好转，未见复发。2例行胰十二指肠切除术的患者术后接受激素治疗，未见复发。 结论：AIP的确诊应综合临床表现、血清学检查、影像学检查结果和组织病理学检查，应与胰腺癌鉴别诊断，避免误诊而施行不必要的手术治疗。

Objective：To summarize the clinical characteristics, diagnosis and treatment of autoimmune pancreatitis（AIP）. Methods：The retrospective descriptive study was adopted. The clinical data of 43 patients with AIP who were admitted to the First Affiliated Hospital of China Medical University between January 2010 and December 2014 were collected. All patients underwent laboratory tests and imaging examinations. For the patients who had the definite diagnosis of AIP, corticosteroid therapy was adopted, and for the patients who had the suspicion of pancreatic cancer, surgical operation was carried out. Observed indexes included clinical manifestations, laboratory findings, imaging findings, treatment, pathological findings and followup status. The followup of imaging examinations and laboratory tests via outpatient and inpatient examinations was performed on the patients until January 2016. Measurement data with skewed distribution were presented as average （range）. Results：（1） Clinical manifestations： of the 43 patients, 33 demonstrated obstructive jaundice, 19 had loss of weight, 18 had upper abdominal pain and 5 had acute mild pancreatitis （the same patient with a variety of symptoms）. Extrapancreatic organ involvement was detected in 23 of the 43 patients, including focal nephritis in 15 patients, sicca syndrome in 7 patients, pulmonary involvement in 5 patients, autoimmune thyroiditis in 5 patients, hilar IgG4associated cholangitis in 3 patients, retroperitoneal fibrosis in 3 patients and ulcerative colitis in 1 patient （the same patient with a variety of diseases）. （2） Results of laboratory tests： 17 patients underwent serum IgG4 detection and increased expression of IgG4 was found in 15 patients. （3） Imaging findings： all the 43 patients underwent enhanced computed tomography （CT） scan of pancreas. Diffused enlargement of pancreas with appearance of sausage was observed in 34 patients and localized pancreatic head enlargement was observed in 9 patients. Twenty patients had peripancreatic vascular involvement including stenosis or occlusion of splenic vein, stricture at the confluence of superior mesenteric vein, portal vein and splenic vein resulting in regional portal hypertension which led to gastric venous varices and splenomegaly. Three patients showed that superior mesenteric artery was surrounded by tissue masses with massive ascites. Five patients had pancreatic pseudocyst with splenic vein involvement and peripancreatic effusion. The abdominal CT examination of 15 patients with renal involvement showed renal cortical wedge or nodular lesions. Pulmonary inflammatory pseudotumor and interstitial pneumonia appeared in 5 patients, CT of whom showed solid pulmonary nodules or diffuse groundglass opacities and patchy shadows in pulmonary interstitium. Thirtytwo patients underwent magnetic resonance cholangiopancreatography and 28 patients underwent endoscopic retrograde cholangiopancreatography. The results showed the focal and diffuse or segmental stenosis of the main pancreatic duct were detected in 28 patients （diffuse stenosis in 23 patients, local stenosis in 5 patients）, stenosis of the intrapancreatic common bile duct in 32 patients, stenosis of hilar bile duct in 3 patients. Nine patients underwent endoscopic ultrasonography examination. The results showed 3 patients had hypoechoic mass in the head of pancreas and 6 patients had diffuse or heterogeneous hypoechoic of the pancreatic parenchyma. （4） Treatment status： of 43 patients, 30 patients received initial steroid treatment. After steroid treatment, the clinical symptoms of 27 patients gradually improved and laboratory and imaging findings were both improved. Eleven patients didn＇t receive initial steroid treatment, of whom 2 patients with obstructive jaundice underwent endoscopic biliary stent implantation, 7 patients underwent surgical biliary drainage and 2 received neither endoscopic treatment nor surgical treatment. Two patients underwent pancreatoduodenectomy due to suspicion of pancreatic adenocarcinoma and were diagnosed as AIP based on postoperative pathological results and treated with steroid after operation. （5） Pathological examination： of the 43 patients, 22 underwent pathological examination. Results of pathological examination of superficial lymph nodes showed lymph follicles hyperplasia, and immunohistochemistry staining showed massive IgG4 positive plasmocytes in 5 patients, supporting the diagnosis. Results of fine needle aspiration cytology in 15 patients showed no cytological evidence were detected in 14 patients and epithelial cells of malignant tumors in 1 patient. Results of pathological examination of surgical specimens showed dense infiltration of lymphocyte and immunohistochemistry staining showed massive IgG4 positive plasmocytes. （6） Followup status： of 43 patients, 41 were followed up for an average time of 28 months （range, 12-71 months）. Of the 30 patients who received steroid treatment, 27 had complete response and 3 had partial response. Of the 27 with complete response, 4 patients relapsed during followup and were cured by continuous steroid treatment and extending treatment course, 3 patients did not relapse, 1 patient relapsed again, and longterm low dose steroid maintenance therapy was needed. The 3 patients with partial response were treated with mycophenolate mofetil for 6, 4, 4 months and imaging abmormalities disappeaved absolutely. Eleven patients received no steroid for the initial treatment, in whom 2 patients were lost to followup, 1 patient with common bile duct jejunum anastomosis died in 1 year after surgery. In the other 8 patients, the imaging abnormalities were spontaneous remission or clinical and imaging manifestations were improved after steroid treatment and no recurrence was found. Two patients who underwent pancreatoduodenectomy due to suspicion of pancreatic adenocarcinoma received steroid treatment after operation and no recurrence was observed. Conclusion：Clinicians should combine clinical manifestations, serological examination, imaging findings and pathological examination to make definite diagnosis of AIP and make differential diagnosis of pancreatic cancer to avoid unnecessary surgical treatment by misdiagnosis.