坏死性胰腺炎合并胰管断裂的诊治进展

坏死性胰腺炎是胰管断裂最常见的病因,可引起胰腺液体积聚反复发作、胰瘘等严重并发症。目前,坏死性胰腺炎患者合并胰管断裂是否需要早期常规诊断、首选的干预方式、最佳的干预时机等问题仍无定论。本文就坏死性胰腺炎合并胰管断裂的诊治进展作一综述。     

Corticosteroid-responsive pancreatic cyst found in autoimmune pancreatitis

There have been only a few reports of autoimmune pancreatitis complicated with pancreatic cyst and such cysts are rare, probably due to the absence of severe tissue necrosis and/or lack of stasis of the pancreatic juice in this condition. However, during a follow-up of 48 patients with this disease, we found 3 patients with pancreatic cysts, and this enabled us to evaluate their clinicopathological findings. Between September 1994 and July 2003, we treated and followed 48 patients with autoimmune pancreatitis, and found 3 patients with pancreatic cyst formation that was responsive to corticosteroid therapy. All of the patients with cysts had high serum IgG4 concentrations. After corticosteroid therapy, rapid resolution of the pancreatic cysts was observed. Immunostaining with goat polyclonal antibody for each IgG subclass showed severe infiltration of IgG4-positive plasma cells in the cyst wall in one patient. The high serum IgG4 concentration and favorable response to corticosteroid therapy suggests that a highly active state of the inflammatory process is closely associated with cyst formation, and that a corticosteroid-responsive pancreatic cyst is a characteristic feature of autoimmune pancreatitis.     

Effectiveness of steroid therapy for pancreatic cysts complicating autoimmune pancreatitis and management strategy for cyst-related complications

Abstract

Objectives: Autoimmune pancreatitis (AIP) sometimes becomes complicated with pancreatic cysts, although their detailed characteristics and management strategy have not been fully determined. We aimed to clarify the efficiency of steroid therapy and the risk factors for cyst formation and cyst-related complications.

Methods: One hundred sixty-three AIP patients were retrospectively analyzed for relevant factors of cyst formation. We compared subjects with and without steroids to evaluate drug effectiveness on cyst size change and investigated the factors associated with cyst-related complications.

Results: Thirty-two patients (19.6%) had complicating pancreatic cyst formation, and 40 cystic lesions of ≥10?mm in size were detected. Multivariate analysis revealed a drinking habit, abdominal/back pain, and elevated serum amylase to be significantly associated with cyst formation. Steroid-treated cysts became significantly reduced in size in the short-term and disappeared significantly more frequently within 1-year as compared with non-treated ones, which was confirmed by multivariate analysis. Six of 40 cysts exhibited cyst-related complications significantly associated with multilocular morphology and larger size.

Conclusions: Steroid therapy is an effective choice for cysts developing in AIP to promote the release of pancreatic juice stasis. Larger lesions with multilocular morphology should be monitored closely for cyst-related complications and be considered strong candidates for steroid therapy.     

A case of pancreatic carcinoma with suspected autoimmune pancreatitis

We present a case of pancreatic carcinoma with strongly suspected coexisting autoimmune pancreatitis (AIP). The patient presented with a chief complaint of icterus and weight loss, and was referred to our institution after a pancreatic lesion was found. Blood test showed elevation of serum bilirubin, hepato-biliary enzyme, glucose and tumor markers, and also high levels of serum IgG4 (344 mg/dl, normal 4.8–105 mg/dl) and anti-DNA antibody (14 IU/ml, normal <6.0 IU/ml). Ultrasonography demonstrated an enlarged pancreas with smooth borders and low internal echo density. Enhanced computed tomography (CT) showed a sausage-shaped pancreas without definitive metastasis to the surrounding lymph nodes and liver. Imaging of the pancreatic duct, including endoscopic retrograde pancreatography (ERP) and magnetic resonance cholangiopancreatography (MRCP), showed stenosis of the main pancreatic duct at the pancreatic head as well as a long segment of narrowing at the body and no dilatation at the tail. Tissues from these stenotic sites and open biopsy from pancreatic body showed infiltrating adenocarcinoma and dense fibrosis. To date, only a small number of reports have described pancreatic carcinoma accompanied with AIP. It is important to confirm diagnosis with histology in cases of suspicious autoimmune pancreatitis, even when the clinical images are compatible with AIP.     

自身免疫性胰腺炎与胰腺癌的鉴别诊断

自身免疫性胰腺炎（AIP）是慢性胰腺炎的一种特殊类型。尽管关于 AIP 的各种临床指南相继推行,但在临床上,AIP 与胰腺癌的鉴别仍十分困难。参考 AIP 的指南及最新的相关文献,总结了关于 AIP 与胰腺癌的临床表现、血清学改变、影像学改变及激素反应四个方面的鉴别诊断要点。通过综合分析上述鉴别要点,胰腺占位患者的正确诊断可以得以明确,一些 AIP 患者也可以避免不必要的开腹手术。     

Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis

Background Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein. Methods In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated. Results Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction. Conclusions Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.     

Long-term outcome of autoimmune pancreatitis

Purpose  Autoimmune pancreatitis (AIP) is a unique form of pancreatitis and can be complicated with various extrapancreatic lesions. Little is known about the long-term clinical course of AIP. Here we aimed to document the clinical course of AIP. Methods  For this study, we recruited 21 patients, averaging 66.5 years in age (range, 19–84 years) and observed them at a mean interval of 40.8 months (range, 18–130 months). Three of the patients were also diagnosed with retroperitoneal fibrosis, 3 had sialoadenitis, 2 had chronic thyroiditis, 1 had interstitial nephritis, and 1 had interstitial pneumonia. Three of the patients underwent surgical therapy, 12 patients received methylprednisolone (PSL) treatment, and the 6 remaining patients received no treatment. Results  Enlargement of the pancreas was attenuated in all the PSL-treated patients. Seven of the 21 patients showed pancreatic atrophy, of whom 2 were non-PSL-treated patients. Three patients developed chronic pancreatitis. One patient was diagnosed with pancreatic cancer after 50 months of PSL therapy. Conclusions  As with chronic pancreatitis patients, AIP patients should be observed closely for abnormality in pancreatic function.     

Diagnosis of autoimmune pancreatitis using endoscopic ultrasonography

Background  Revised clinical criteria for autoimmune pancreatitis (AIP) have been proposed by the Research Committee of Intractable Disease of the Pancreas and the Japan Pancreas Society. These criteria require distinguishing AIP from neoplastic lesions. However, this can be difficult, and patients often undergo surgery on the basis of suspected pancreatic cancer (PC). Methods  AIP was diagnosed in 25 patients at the Aichi Cancer Center Hospital (ACCH) according to the revised AIP criteria. In each patient, endoscopic ultrasonography (EUS) was used to describe the conventional pancreatic parenchymal and ductal features of chronic pancreatitis (Sahai criteria), and other abnormal features, namely, diffuse hypoechoic areas (DHAs), diffuse enlargement (DE), focal hypoechoic areas (FHAs), focal enlargement, bile duct wall thickening (BWT), lymphadenopathy, and peripancreatic hypoechoic margins (PHMs). We compared these features between 25 patients with AIP and 30 patients with pancreatic cancer resected at ACCH. Results  Few conventional EUS features of chronic pancreatitis (CP) were seen in patients with AIP (mean, 2.0 features). Frequencies of DHA, DE, BWT, and PHM were significantly higher in AIP than in PC. DHAs, DE, and FHAs resolved after steroid treatment. Conclusions  Novel EUS features of AIP are useful in distinguishing AIP from PC and for following the effects of steroid therapy.     

Characteristics of pancreatic diabetes in patients with autoimmune pancreatitis

OBJECTIVE: Although patients with autoimmune pancreatitis (AIP) tend to have concurrent diverse disorders, very few studies have focused on diabetes mellitus (DM) coexisting with AIP. METHODS: In total 102 AIP patients with DM were divided into three groups. Those with DM before the onset of AIP were labeled group A (n = 35), those who developed DM and AIP simultaneously were labeled group B (n = 58) and those who developed DM after steroid therapy for AIP were labeled group C (n = 9). The characteristics of DM among the three groups were evaluated. RESULTS: No significant differences were noted in the age of DM onset among the three groups. However, the mean duration of DM was significantly longer in group A (8.7 years) than in groups B and C. AIP developed 6.8 years after DM onset in group A, whereas it developed 1.8 years after steroid therapy in group C. Group A had the highest rate (25.7%) of family members with a history of AIP. Levels of serum albumin, total cholesterol and triglyceride were significantly lower in group A. No correlations were found between glycated hemoglobin and benzoyl‐tyrosyl para‐aminobenzoic acid. Hypoglycemia was observed in 20% of patients under insulin therapy. Most of them were habitual drinkers and received no pancreatic enzymes. Group A showed a high prevalence of retinopathy, nephropathy and macrovascular disorders than group B. CONCLUSION: Aspects of AIP‐associated pancreatic diabetes were clarified. AIP‐associated DM must be controlled by a full assessment of the pancreatic endocrine and exocrine function.     

Relationship between autoimmune pancreatitis and pancreatic cancer: A single-center experience

ObjectivesOrdinary chronic pancreatitis (CP), such as alcoholic CP, is well established to have the increased risk for pancreatic cancer (PaC), nevertheless an association between autoimmune pancreatitis (AIP) and PaC is still unknown. The aims of this study are to examine the frequency of patients who developed PaC during follow-up after being diagnosed with type 1 AIP and to compare the incidence rate of PaC between patients with type 1 AIP and CP.MethodsSixty-three patients with type 1 AIP and 41 patients with CP were enrolled. We examined development of PaC during follow-up from their clinical records.ResultsThe mean follow-up period was 62.4 months in AIP group and 49.2 months in CP group. The occurrence of PaC was observed in 3 patients with AIP during the mean follow-up period of 94.7 months (range, 31–186), whereas a single CP patient developed PaC 38 months after CP diagnosis. The incident rate of PaC during follow-up was comparable between the 2 groups [4.8% (3/63) in type 1 AIP group vs. 2.4% (1/41) in CP group]. In all of 3 AIP patients who developed accompanying PaC, the clinical remission of AIP was achieved with maintenance steroid therapy, when tumors were discovered. In the histological examination of one surgical patient with PaC, lymphoplasmacytic infiltration in storiform fibrosis with abundant IgG4-positive cell infiltration was observed around the PaC area.ConclusionsSimilar to patients with ordinary CP, surveillance for development of PaC is needed at regular interval during follow-up in AIP patients.     

自身免疫性胰腺炎诊治进展

自身免疫性胰腺炎(AIP)是一种由自身免疫介导、以胰腺肿大及胰管不规则狭窄为特征的胰腺慢性炎症性疾病,病理以胰管纤维化伴有淋巴浆细胞浸润为特征,其治疗尚缺乏统一标准。本文就自身免疫性胰腺炎的流行病学、发病机制、临床特点、影像学检查、病理学特点、诊断标准、治疗及预后七个方面的相关研究进展进行综述,以加深对其认识及了解。     

自身免疫性胰腺炎的研究进展

自身免疫性胰腺炎是一种特殊类型的慢性胰腺炎,在较长时间的临床实践中没有认清其本质.近年来,随着研究的深入,发现自身免疫性胰腺炎与其他胰腺炎相比较有所不同,呈现多种临床特征,因此作为一个独立的临床疾病,受到越来越多的关注.现将近几年来关于自身免疫性胰腺炎的发病机制、临床表现、诊断和治疗进展作一综述.     

自身免疫性胰腺炎的内镜超声表现

目的 分析总结自身免疫性胰腺炎在内镜超声的特征表现.方法 回顾分析2004年8月至2007年9月确诊的11例原发性自身免疫性胰腺炎的临床资料,总结内镜超声的影像特点.结果 内镜超声下见胰腺实质回声极低,胰腺弥漫或局部增大,边缘呈波浪样改变;肝外胆管扩张,胆管壁明显增厚,呈均匀中低回声;可见胰腺周边淋巴结肿大.所有病例均未见明显胰管扩张或胰石、胰腺钙化和囊肿形成;未见周边血管受累.结论 自身免疫性胰腺炎在内镜超声下具有相对特征性的表现,有助于自身免疫性胰腺炎的临床诊断.     

Differences between diffuse and focal autoimmune pancreatitis

AIM: To investigate differences in clinical features between diffuse- and focal-type autoimmune pancreatitis (AIP).METHODS: Based on radiological findings by computed tomography and/or magnetic resonance imaging, we divided 67 AIP patients into diffuse type (D type) and focal type (F type). We further divided F type into head type (H type) and body and/or tail type (B/T type) according to the location of enlargement. Finally, we classified the 67 AIP patients into three groups: D type, H type and B/T type. We compared the three types of AIP in terms of clinical, laboratory, radiological, functional and histological findings and clinical course.RESULTS: There were 34 patients with D-type, 19 with H-type and 14 with B/T-type AIP. Although obstructive jaundice was frequently detected in D-type patients (88%) and H-type patients (68%), no B/T-type patients showed jaundice as an initial symptom (P < 0.001). There were no differences in frequency of abdominal pain, but acute pancreatitis was associated more frequently in B/T-type patients (36%) than in D-type patients (3%) (P = 0.017). Serum immunoglobulin G (IgG)4 levels were significantly higher in D-type patients (median 309 mg/dL) than in B/T-type patients (133.5 mg/dL) (P = 0.042). Serum amylase levels in B/T-type patients (median: 114 IU/L) were significantly greater than in H-type patients (72 IU/L) (P = 0.049). Lymphoplasmacytic sclerosing pancreatitis (LPSP) was histologically confirmed in 6 D-type, 7 H-type and 4 B/T-type patients; idiopathic duct-centric pancreatitis was observed in no patients. Marked fibrosis and abundant infiltration of CD20-positive B lymphocytes with few IgG4-positive plasma cells were detected in 2 B/T-type patients. Steroid therapy was effective in all 50 patients (31 D type, 13 H type and 6 B/T type). Although AIP relapsed during tapering or after stopping steroids in 3 D-type and 3 H-type patients, no patients relapsed in B/T type. During follow-up, radiological features of 6 B/T-type patients were not changed and 1 B/T-type patient improved naturally.CONCLUSION: Clinical features of H-type AIP were similar to those of D-type, but B/T-type differed from D and H types. B/T-type may involve diseases other than LPSP.     

Long-term outcomes of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) has been considered a favorable-prognosis disease; however,currently,there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation,exocrine insufficiency,and endocrine insufficiency are observed in 5%-41%,34%-82%,and 38%-57% of patients having the disease. Furthermore,the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term followup. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients,careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.     

Inflammatory pseudotumor of the liver and peripheral eosinophilia in autoimmune pancreatitis

AIM: Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, the etiology of which remains obscure. It is not associated with any particular diseases apart from phlebitis and Crohn's disease. METHODS: A middle-aged male with hepatic IPT and peripheral eosinophilia associated with autoimmune pancreatitis (AIP) was selected for this study and review of literature. RESULTS: A 59-year-old male was admitted with obstructive jaundice, marked eosinophilia (1 343/mm3) and hypergammaglobulinemia (4 145 mg/dL). Imaging techniques revealed dilatation of the intrahepatic bile duct, stenosis of the common bile duct with diffuse wall thickening, gallbladder wall thickening, irregular narrowing of the pancreatic duct, and swelling of the pancreatic parenchyma. Multiple liver masses were also demonstrated and diagnosed as IPT by biopsy specimens. Six months later, the abnormal features of the biliary tree remarkably improved by the oral administration of prednisolone, and the liver masses disappeared. The swelling of the pancreatic head also improved. The peripheral eosinophil count normalized. IPT associated with AIP, as we know, has not been reported in the literature. The clinical features of the present case mimicked those of pancreatic cancer with liver metastasis. This case deserves to be documented to prevent misdiagnosis of similar cases.     

自身免疫性胰腺炎与小胰腺癌的CT、MRCP征象分析

目的 分析自身免疫性胰腺炎(AIP)与小胰腺癌的CT、MRCP影像学征象的差异,提高对AIP的认识及诊断的准确率.方法 回顾性分析符合2008年AIP亚洲诊断标准的24例AIP及病理证实的25例小胰腺癌(≤2 cm)的影像学资料,从胰腺的形态改变、密度及强化方式、胰管及胰周、胰外表现等方面进行比较,采用×2检验或确切概率法行统计学处理.结果 在AIP和小胰腺癌组间,肿块部位、远端胰腺萎缩、肿块持续强化、胰管“截断征”、“鞘膜征”及肾脏受累征象差异具有统计学意义(x2 =9.010、10.506、15.288、8.688、6.292和4.966,P＜0.05),但是只有远端胰腺萎缩和肿块持续强化征象在局限性AIP与小胰腺癌组间差异具有统计学意义(P＜0.05).结论 弥漫性AIP的影像学改变具有特异性,与小胰腺癌容易鉴别诊断,但局灶性AIP与小胰腺癌鉴别诊断价值有限.     

Endoscopic ultrasound-guided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis

AIM: To investigate the usefulness of endoscopic ultra-sound-guided fine needle aspiration (EUS-FNA) in the differentiation of autoimmune pancreatitis (AIP).METHODS: We retrospectively reviewed 47 of 56 AIP patients who underwent EUS-FNA and met the Asian diagnostic criteria. On 47 EUS-FNA specimens, we evaluated the presence of adequate material and characteristic features of lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) mentioned in the International Consensus Diagnostic Criteria and examined if these findings make a contribution to the differential diagnosis of type 1 and type 2 AIP. A disposable 22-gauge needle was used for EUS-FNA.RESULTS: Adequate specimens including pancreatic tissue for differentiating AIP from cancer were obtained from 43 of 47 patients who underwent EUS-FNA. EUS-FNA was performed from the pancreatic head in 21 cases, which is known to be technically difficult when performed by core biopsy; there was no significant difference in the results compared with pancreatic body-tail. Nine of 47 patients met level 1 findings of LPSP and 5 patients met level 2 findings of LPSP. No one met level 1 findings of IDCP, but 3 patients met level 2 findings of IDCP. Of 10 seronegative cases, 2 cases were diagnosed with “definitive type 1 AIP”, and 3 cases were diagnosed with “probable type 2 AIP” when considering both the level 2 histological findings and response to steroids.CONCLUSION: EUS-FNA is useful in the differentiation of type 1 and type 2 AIP, particularly in seronegative cases.     

Corticosteroids prevent the progression of autoimmune pancreatitis to chronic pancreatitis

Background/objectivesPatients with autoimmune pancreatitis (AIP) sometimes progress to chronic pancreatitis (CP). We evaluated the ability of corticosteroids to prevent the progression to CP.MethodsWe defined patients with definitive findings of CP (stones in the main pancreatic duct [MPD] or multiple pancreatic calcifications) as having severe calcification (SC). A total of 145 AIP patients were enrolled. We measured the duration between AIP diagnosis and SC development and retrospectively compared the time to SC development between patients with and without steroids. Multivariate analysis for factors associated with SC were performed.ResultsNineteen (13%) patients progressed to SC. Since 95 patients had pancreatic head swelling and SC was found in these patients only, our analysis focused mainly on these at-risk populations. In Kaplan-Meier analysis limited to patients with pancreatic head swelling, the incidence of SC was significantly lower in patients with steroids than in those without (hazard ratio [HR] 0.18, 95% confidence interval [CI] 0.07–0.52; p < 0.001). Multivariate testing of patients with pancreatic head swelling confirmed that steroid therapy was significantly associated with a lower incidence of SC (HR 0.11, 95% CI 0.03–0.34; p < 0.001), while MPD dilation at AIP diagnosis was related to a higher incidence of SC (HR 4.02, 95% CI 1.43–11.7; p = 0.009).ConclusionsCorticosteroids appeared to prevent progression to CP in AIP patients, especially in those with pancreatic head swelling. Patients with both pancreatic head swelling and MPD dilation at diagnosis have a higher incidence of progression to CP. Steroid therapy is suggested for these high-risk cases.