Hepatopancreatobiliary manifestations of inflammatory bowel disease

Inflammatory bowel disease (IBD) is frequently associated with extraintestinal manifestations such as hepatopancreatobiliary manifestations (HPBMs), which include primary sclerosing cholangitis (PSC), pancreatitis, and cholelithiasis. PSC is correlated with IBD, particularly ulcerative colitis (UC); 70–80% of PSC patients in Western countries and 20–30% in Japan have comorbid UC. Therefore, patients diagnosed with PSC should be screened for UC by total colonoscopy. While symptoms of PSC-associated UC are usually milder than PSC-negative UC, these patients have a higher risk of colorectal cancer, particularly in the proximal colon. Therefore, regular colonoscopy surveillance is required regardless of UC symptoms. Administration of 5-aminosalicylic acid or ursodeoxycholic acid may prevent colorectal cancer and cholangiocarcinoma. While PSC is diagnosed by diffuse multifocal strictures on cholangiography, it must be carefully differentiated from immunoglobulin G4 (IgG4)-associated cholangitis, which shows a similar cholangiogram but requires different treatment. When PSC is suspected despite a normal cholangiogram, the patient may have small-duct PSC, which requires a liver biopsy. IBD patients have a high incidence of acute and chronic pancreatitis. Most cases are induced by cholelithiasis or medication, although some patients may have autoimmune pancreatitis (AIP), most commonly type 2 without elevation of serum IgG4. AIP should be accurately identified based on characteristic image findings, because AIP responds well to corticosteroids. Crohn’s disease is frequently associated with gallstones, and several risk factors are indicated. HPBMs may influence the management of IBD, therefore, accurate diagnosis and an appropriate therapeutic strategy are important, as treatment depends upon the type of HPBM.     

Ansa pancreatica as a predisposing factor for recurrent acute pancreatitis

AIM To determine the non-biased prevalence and clinical significance of ansa pancreatica in patients with acute pancreatitis using magnetic resonance imaging(MRI).METHODS Our institutional review board approved this crosssectional study, which consisted of a community-based cohort of 587 consecutive participants in a whole-body health-check program, and 73 subjects with episode of acute pancreatitis(55 patients with a single episode of acute pancreatitis, and 18 patients with recurrent acute pancreatitis). All of the subjects underwent abdominal MRI including magnetic resonance cholangiopancreatography, medical examinations, and blood tests. Two board-certified, diagnostic, abdominal radiologists evaluated the images, and ansa pancreatica was diagnosed based on its characteristic anatomy on MRI.RESULTS Compared with the community group [5/587(0.85%)], patients with recurrent acute pancreatitis had a significantly higher frequency of ansa pancreatica [2/18(11.1%)](P = 0.016; OR = 14.3; 95%CI: 1.27-96.1), but not compared with patients with single-episode acute pancreatitis [1/55(1.8%)](P = 0.42; OR = 2.1; 95%CI: 0.44-19.7). Multiple logistic regression analysis using age, alcohol intake, presence of ansa pancreatica, and presence of autoimmune disease as independent covariates, revealed a significant relationship between the presence of ansa pancreatica and recurrent acute pancreatitis. The presence of autoimmune disease was also significantly associated with the onset of recurrent acute pancreatitis. On the other hand, neither age nor alcohol intake were significantly related to the onset of recurrent acute pancreatitis.CONCLUSION The present study is the first to provide robust evidence that the presence of ansa pancreatica is significantly associated with recurrent acute pancreatitis.     

Ulcerative Colitis and Immunoglobulin G4

Background/Aims

Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4.

Methods

Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients.

Results

UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05).

Conclusions

UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity.     

内镜下胰管括约肌切开术后早期并发症的前瞻性研究

目的评价内镜下胰管括约肌切开术后早期并发症的发生率及相关危险因素。方法前瞻性观察2006年5月至2007年4月行ERCP的住院患者,将ERCP下行胰管括约肌切开术的患者纳入研究。在ERCP术前及术中分别将患者和操作相关情况记录在统一的观察表上;术后随访并发症的发生情况直至出院;有关数据进行统计学分析。结果在纳入观察的165例行胰管括约肌切开术的患者中,25例发生并发症（15．2％）,其中急性胰腺炎22例（13．3％,轻度15例、中度6例、重度1例）,出血1例（0．6％）,急性胆管炎2例（1．2％）,无穿孔或操作相关的死亡发生。多变量分析提示术后急性胰腺炎危险因素是：女性（OR=3．8,95％CI1．4～10．8）、复发性胰腺炎（OR=3．1,95％CI1．0-9．9）、副乳头切开术（OR=5．9,95％CI1．2—28．8）。结论与常规ERCP操作比较,内镜下胰管括约肌切开术后急性胰腺炎的发生率较高。特别是女性、复发性胰腺炎、行副乳头切开术的患者,术后更易发生急性胰腺炎。     

经皮胆道支架植入术后高淀粉酶血症和胰腺炎的发生率及危险因素分析

目的分析经皮肝穿刺胆道支架植入(PTBS)术后高淀粉酶血症和急性胰腺炎的临床特征,探讨其相关危险因素。方法回顾性收集2016年3月—2020年2月于南京医科大学第一附属医院介入放射科收治且接受PTBS治疗的249例恶性胆道梗阻患者的临床资料。根据术后患者有无高淀粉酶血症或急性胰腺炎,将所有患者分为高淀粉酶血症和胰腺炎组(n=55)、无高淀粉酶血症和胰腺炎组(n=194),并分析其发生率、严重程度及相关危险因素。计量资料两组间比较采用t检验或Mann-Whitney U检验。计数资料两组间比较采用χ²检验。将上述单因素分析中P<0.1的因素纳入多因素logistic回归分析,探究PTBS术后高淀粉酶血症和急性胰腺炎的独立危险因素。结果PTBS术后,共55例(22.1%)发生血清淀粉酶异常升高,其中26例(10.4%)诊断为高淀粉酶血症,29例(11.7%)诊断为急性胰腺炎。所有胰腺炎均表现为轻度。多因素logistic回归分析发现,年龄(≤60岁)(OR=2.2,95%CI:1.07~4.52,P=0.033)、碘-125粒子条植入(OR=2.8,95%CI:1.21~6.45,P=0.016)、胆道支架跨乳头释放(OR=6.3,95%CI:2.85~14.05,P<0.001)及术中胰管显影(OR=13.9,95%CI:5.64~34.03,P<0.001)是PTBS术后高淀粉酶血症和急性胰腺炎的危险因素。结论高淀粉酶血症和急性胰腺炎是PTBS术后相对常见的并发症。年龄≤60岁、同期碘粒子条植入、胆道支架跨乳头释放及术中胰管显影是PTBS术后发生高淀粉酶血症和胰腺炎的独立风险因素。     

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.     

Colectomy is a risk factor for venous thromboembolism in ulcerative colitis

AIM: To compare venous thromboembolism(VTE) in hospitalized ulcerative colitis(UC) patients who respond to medical management to patients requiring colectomy. METHODS: Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by:(1) responsive to inpatient medical therapy(n = 382);(2) medically refractory requiring emergent colectomy(n = 309); and(3) elective colectomy(n = 329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course(i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications(i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios(OR) with 95%CI.RESULTS: The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparinprophylaxis. In contrast, VTE was higher among patients who underwent an emergent(8.7%) and elective(4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal(45.8%) followed by lower extremity(19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective(adjusted OR = 3.69; 95%CI: 1.30-10.44) and emergent colectomy(adjusted OR = 5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time(adjusted OR = 1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. CONCLUSION: VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif,number 13 in inflammatory bowel diseases

AIM To evaluate the levels of von Willebrand factor(VWF) and metalloproteinase with thrombospondin type-1 motif, number 13(ADAMTS13) in inflammatory bowel disease(IBD) and correlate them with the disease activity.METHODS Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis(UC), 38 with Crohn's disease(CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level(VWF:Ag), VWF ristocetin cofactor activity(VWF:RCo), VWF collagen-binding activity(VWF:CB), and ADAMTS13 antigen level(ADAMTS13:Ag) and activity(ADAMTS13act) were measured. The following ratios were assessed: V W F : R C o/V W F : A g, V W F : C B/V W F : A g, V W F : A g/ADAMTS13 act, and ADAMTS13act/ADAMTS13:Ag. RESULTS Compared to controls, the odds ratio(OR) of an elevated VWF: Ag 150% was 8.7(95%CI: 2.7-28.1) in the UC group and 16.2(95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo(+38%). The ORs of VWF:CB/VWF:Ag 0.7(a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9(95%CI: 4.4-32.4) and 13.3(95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag(-23%) and ADAMTS13act(-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13 act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag(r =-0.76) and ADAMTS13act(r =-0.81). CONCLUSION Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.     

A new clinicopathological entity of IgG4-related autoimmune disease

Background Autoimmune pancreatitis (AIP) is occasionally associated with other autoimmune diseases.Methods To investigate the pathophysiology of AIP, we immunohistochemically examined the pancreas and other organs in eight patients with AIP, and in controls, using anti-CD4-T and CD8-T cell subsets, as well as IgG4 antibodies.Results In AIP patients, severe or moderate infiltration of IgG4-positive plasma cells associated with CD4- or CD8-positive T lymphocytes was detected in the peripancreatic tissue (6/6), bile duct (8/8), gallbladder (8/8), portal area of the liver (3/3), gastric mucosa (5/7), colonic mucosa (2/2), salivary glands (1/2), lymph nodes (6/6), and bone marrow (2/2), as well as in the pancreas (8/8). There were few IgG4-positive plasma cells at the same sites in controls.Conclusions These results suggest that AIP is not simply pancreatitis but that it is a pancreatic lesion involved in IgG4-related systemic disease with extensive organ involvement. We propose a new clinicopathological entity, of a systemic IgG4-related autoimmune disease in which AIP and its associated diseases might be involved.     

Autoimmune pancreatitis: current diagnostic criteria are suboptimal

Background and Aims: The preoperative diagnosis of autoimmune pancreatitis (AIP) is difficult, given its similar clinical presentation to pancreatic cancer. The aims of the study are to describe our center's experience with AIP and apply the Japanese AIP diagnostic criteria to a cohort of patients with histologically‐proven AIP in order to assess their performance characteristics. Methods: A prospective pathology database was queried for AIP patients who were evaluated and/or treated at Johns Hopkins Hospital from 2002 to 2009. AIP histology was defined by the presence of lymphoplasmacytic infiltration, periductal inflammation, fibrosis, and periphlebitis. Imaging, clinical, and biochemical data were analyzed. Results: Thirty patients had pancreatic resection with pathological confirmation of AIP. Imaging revealed pancreatic mass (45%), focal prominence without mass lesion (24%), diffuse enlargement (17%), and normal pancreas (14%). Twenty‐four patients underwent an endoscopic retrograde cholangiopancreatography and/or magnetic resonance cholangiopancreatography, and 4/24 (17%) had pancreatic ductal narrowing or irregularity. Extrapancreaticobiliary organ involvement was found in 6% (n = 2) of patients. Biliary strictures were present in 87% of patients. Of 16 patients who underwent preoperative tissue biopsy, 10 had non‐diagnostic pathology, five had cellular atypia, and one had AIP. Serum immunoglobulin G4 (IgG4) levels were elevated in 12 of 29 (41%) patients. Three (10%) patients had evidence of extrapancreatic manifestations of AIP. When applying the Japanese criteria to the 27 patients who had serum IgG4 measurement, preoperative biopsy, and cross‐sectional abdominal imaging, only 44% of the patients would have been diagnosed accurately. Conclusions: When applied to a highly‐selected single‐center referral population in the USA, current Japanese guidelines for the diagnosis of AIP are found to have suboptimal sensitivity.     

Autoimmune pancreatitis type-1 associated with intraduct papillary mucinous neoplasm: Report of two cases

Chronic pancreatitis lesions usually embrace both intraduct papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC). Patients at genetically-determined high risk of PDAC often harbor IPMN and/or chronic pancreatitis, suggesting IPMN, chronic pancreatitis and PDAC may share pathogenetic mechanisms. Chronic autoimmune pancreatitis (AIP) may also herald PDAC. Concurrent IPMN and AIP have been reported in few patients. Here we describe two patients with IPMN who developed type-1 AIP fulfilling the Honolulu and Boston diagnostic criteria. AIP diffusively affected the whole pancreas, as well as peripancreatic lymph nodes and the gallbladder. Previous pancreatic resection of focal IPMN did not show features of AIP. One of the patients carried a CFTR class-I mutation. Of notice, serum IgG4 levels gradually decreased to normal values after IPMN excision. Common risk factors to IPMN and AIP may facilitate its coincidental generation.     

A case of autoimmune pancreatitis associated with ulcerative colitis

A 31-year-old man was admitted to our hospital because of upper abdominal pain. He had been diagnosed with ulcerative colitis (UC) at age 28, but the disease has been in remission since then. On admission, he had slight fever, abdominal pain, and bloody stools six times a day, and the serum levels of pancreatic enzyme and IgG4 were elevated. Diffuse enlargement of the pancreas was detected by abdominal computed tomography; furthermore, narrowing of the main pancreatic duct was revealed using endoscopic retrograde cholangiopancreatography. Based on these findings, he was given a diagnosis of autoimmune pancreatitis (AIP) associated with UC. Both diseases improved without using steroids. After discharge, he has not had any recurrence of AIP or UC despite not being on steroid treatment, although the serum IgG4 level has shown a slight tendency to elevate.     

自身免疫性胰腺炎误诊误治17例临床分析

目的 总结自身免疫性胰腺炎(AIP)误诊误治的原因.方法 回顾性分析2005年5月至2010年7月间我院收治的17例有误诊误治经历的AIP患者的临床资料.结果 AIP的主要临床症状包括腹部轻度疼痛13例、进行性黄疸12例、发热6例、体重减轻9例.15例伴随一种或一种以上胰腺外脏器的自身免疫性疾病,包括过敏性鼻炎、颌下淋巴结肿大、颌下腺肿大、过敏性哮喘、类风湿性关节炎、干燥综合征、糖尿病、原发性硬化性胆管炎和自身免疫性肝炎.实验室检查方面,血清球蛋白增高11例、IgG增高14例、γ球蛋白增高13例、抗核抗体阳性13例、抗胰岛素IgG抗体阳性2例.影像学检查方面,胰腺弥漫性肿大15例,伴主胰管弥漫性狭窄或节段性狭窄、胰腺段胆总管狭窄、近端胆管扩张、胆囊增大;胰头、钩突局灶性肿大2例.17例中有13例误诊为胰腺癌,其中4例行胰十二指肠切除术,7例行胆肠吻合术,2例被认为肿瘤晚期失去治疗机会;4例被误诊为普通慢性胰腺炎.确诊AIP后,17例患者均接受糖皮质激素治疗,效果显著.随访6～45个月(平均15个月),4例复发,再次子糖皮质激素治疗效果好.随访期间未发现胰腺癌.结论 AIP 临床特点与胰腺癌相似,加之我国现阶段对AIP认识不足、重视不够,是导致误诊和误治的主要原因.

Abstract：

Objective To summarize the reasons of mis-diagnosis and mis-treatment of autoimmune pancreatitis (AIP). Methods Clinical data of 17 patients with AIP,who were admitted to the hospital from May 2005 to July 2010 and experienced mis-diagnosis and mis-treatment, were retrospectively analyzed. Results The main clinical manifestations included epigastric pain (13 cases),progressive obstructive jaundice (12 cases), fever (6 cases) and weight loss (9 cases). Fifteen patients had extrapancreatic organ involvemnet, including allergic rhinitis, swelling of lymphoglandulae submaxillares, swelling of submaxillary gland, allergic asthma, rheumatoid arthritis, Sjogren syndrome, diabetes mellitus, primary sclerosing cholangitis and autoimmune hepatitis. Of these 17 cases, 11 cases presented with high serum globulin, 14 cases with high serum IgG, 13 cases with high serum γ-globulin, 13 cases with positive anti-nuclear antibody and 2 cases with positive anti-insulin IgG antibody. The abdominal imaging demonstrated that 15 patients had diffuse enlargement of the pancreas with diffuse or segmental narrowing of main pancreatic duct, narrowing of the intrapancreatic common bile duct, dilation of the proximal biliary duct and gallbladder enlargement. Focal enlargement of the pancreas was found in 2 cases. Thirteen cases were misdiagnosed as pancreatic carcinoma. Among them, 4 cases underwent pancreaticoduodenectomy and 7 cases underwent choledochojejunostomy. Two cases were misdiagnosed as end stage of cancer that lost therapeutic chance. Another 4 cases were misdiagnosed as chronic pancreatitis. Steroid therapy was administered in all patients with satisfactory response. All patients were followed-up for 15 months (ranged from 6 months to 45 months), and recurrence was found in 4 cases. Satisfactory response was found in patients treated with steroid for the second time. No pancreatic cancer was found in these patients in the follow up period. Conclusion The main causes of mis-diagnosis and mis-treatment of AIP may be contributed by difficulty in differentiating AIP from pancreatic carcinoma based on clinical manifestations and inadequate knowledge of AIP as well as insufficient attention to AIP in China.     

Epidemiology,clinical presentation,diagnosis and treatment of autoimmune pancreatitis: A retrospective analysis of 53 patients

BackgroundMost of the data about epidemiology, clinical presentation and treatment of autoimmune pancreatitis (AIP) is based on case series or small study groups. We therefore analyzed all cases of AIP treated at our clinic retrospectively.MethodsWe searched our clinical database for the diagnosis pancreatitis between January 2007 and June 2014, selected patients with AIP and entered all relevant information in a database for statistical analysis.ResultsIn total 53 patients with AIP were treated at our institution, 62% with type 1 and 23% with type 2 AIP. Gender distribution was male/female 3.1:1 for type 1 and 1:1.2 for type 2 AIP. The median age was 63.0 and 32.5 years for type 1 and type 2 AIP, respectively. The most common symptom is abdominal pain particular in patients with type 2 AIP whereas jaundice was only apparent in patients with type 1 AIP. The international diagnostic criteria seem to facilitate diagnosis of AIP as unnecessary pancreatic surgery in patients with AIP decreases. In 62.6% of the patients therapy was indicated and 84.8% showed a response to initial therapy with steroids. Recurring disease occurred in 28.3% of the cases but only 3.8% suffered a second relapse. Permanent maintenance therapy with steroids or additional therapy with immunomodulatory drugs is successful in recurring disease.ConclusionOur data further corroborate previous findings on epidemiology, clinical presentation and treatment of AIP. AIP is a well manageable autoimmune disease in most patients. Better biopsy techniques and simplified diagnostic criteria might further alleviate diagnosis of AIP.     

Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer

OBJECTIVES: To determine the sensitivity and specificity of elevated serum IgG4 level for the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer, its main differential diagnosis. METHODS: We measured serum IgG4 levels (normal 8-140 mg/dL) in 510 patients including 45 with AIP, 135 with pancreatic cancer, 62 with no pancreatic disease, and 268 with other pancreatic diseases. RESULTS: Sensitivity, specificity, and positive predictive values for elevated serum IgG4 (>140 mg/dL) for diagnosis of AIP were 76%, 93%, and 36%, respectively, and 53%, 99%, and 75%, respectively, for IgG4 of >280 mg/dL. Among subjects with elevated IgG4, non-AIP subjects (N = 32) differed from AIP subjects (N = 34) in that they were more likely to be female (45%vs 9%, P < 0.001), less likely to have serum IgG4 >280 mg/dL (13%vs 71%, P < 0.001), or elevation of total IgG (16%vs 56%, P < 0.001). Serum IgG4 levels were elevated in 13/135 (10%) pancreatic cancer patients; however, only 1% had IgG4 levels >280 mg/dL compared with 53% of AIP. Compared with AIP, pancreatic cancer patients were more likely to have CA19-9 levels of >100 U/mL (71%vs 9%, P < 0.001). CONCLUSION: Elevated serum IgG4 levels are characteristic of AIP. However, mild (<2-fold) elevations in serum IgG4 are seen in up to 10% of subjects without AIP including pancreatic cancer and cannot be used alone to distinguish AIP from pancreatic cancer. Because AIP is uncommon, IgG4 elevations in patients with low pretest probability of having AIP are likely to represent false positives.     

Acute Pancreatitis in Patients with Ulcerative Colitis

Twenty-two patients (13 men and 9 women; median age, 34 years; range, 15–64 years) with ulcerative colitis (UC) were evaluated to determine the incidence of acute pancreatitis with UC at the First Department of Internal Medicine, Mie University School of Medicine, during 1989–2001. Among these, three patients (14%) were diagnosed as having had episodes of acute pancreatitis during the mean follow-up period of 6 years. One patient presented with acute pancreatitis and UC simultaneously. Two patients had drug-induced pancreatitis (one due to azathioprine and the other due to 5-ASA). In conclusion, acute pancreatitis is not a frequent, but an occasional extraintestinal manifestation of UC.     

Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience.

BACKGROUND & AIMS: The Japan Pancreas Society criteria for diagnosis of autoimmune pancreatitis (AIP) mandate presence of characteristic imaging (diffuse pancreatic enlargement with diffusely irregular, narrow pancreatic duct). AIP has unique histologic features associated with infiltration of tissues of affected organs with abundant IgG4-positive cells. We propose expanded diagnostic criteria for AIP with a cohort of histologically confirmed AIP. METHODS: We reviewed the pancreatic imaging findings on computed tomography scans, serum IgG4 levels, other organ involvement, and response to steroids in 29 consecutive patients who met histologic criteria for AIP. RESULTS: Computed tomography scans (n = 22) showed diffuse pancreatic enlargement in 6 (27%) patients; the rest had focal enlargement, distinct mass, normal pancreas, or focal acute pancreatitis. Serum IgG4 level was elevated in 15 of 21 (71%) patients, and other organ involvement (eg, intrahepatic biliary strictures) was noted in 11 of 29 (38%) patients. All 17 patients treated with steroids exhibited resolution/marked improvement of pancreatic/extrapancreatic manifestation. On the basis of this experience we propose that diagnosis of AIP can be made in patients with > or =1 of these criteria: (1) diagnostic histology, (2) characteristic imaging on computed tomography and pancreatography with elevated serum IgG4 level, or (3) response to steroid therapy of pancreatic/extrapancreatic manifestations of AIP. Twenty additional patients met expanded diagnostic criteria for AIP, and their demographic and clinical profile was similar to that of the 29 patients meeting histologic criteria. CONCLUSIONS: AIP defined by histological criteria shows a wide spectrum of radiologic features, with characteristic imaging seen only in a minority. Incorporation of additional features into current diagnostic criteria can identify the full spectrum of clinical presentations of AIP.     

Autoimmunpankreatitis

Autoimmune pancreatitis (AIP) has been established for more than 15?years as a disease entity of chronic pancreatitis. Although the autoimmune etiology is well established AIP is still an enigmatic disease. Morphological hallmarks of the disease are narrowing of the pancreatic duct system and frequently even narrowing of the bile duct by periductal lymphoplasmocytic inflammation. In cases of more localized inflammation obstructive jaundice due to a mass-forming lesion in the pancreatic head may mimic pancreatic ductal adenocarcinoma. Therefore, even in tertiary referral center, AIP patients underwent pancreatic surgery for suspected pancreatic cancer due to misclassification. Histopathologically, the disease can be differentiated into lymphoplasmacytic sclerosing pancreatitis (LPSP) with IgG4-positive cells or idiopathic ductocentral chronic pancreatitis (IDCP) with granulocyte epithelial lesions and eosinophils. Recently, LPSP has been coined AIP type 1 and IDCP as AIP type 2 following a recent consensus conference. Serologically, patients may present with elevated serum IgG and IgG4 levels. Additionally, autoantibodies have been described targeting ductal and acinar antigens. Association with other autoimmune manifestations in a wide range of organs is relatively frequent. In most cases, autoimmune pancreatitis responds to steroid treatment very quickly, which is of specific importance when considering the differential diagnosis of pancreatic cancer.     

Relapse rate and predictors of relapse in a large single center cohort of type 1 autoimmune pancreatitis: long-term follow-up results after steroid therapy with short-duration maintenance treatment

Background

Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation of IgG4-related disease, shows a favorable prognosis in the short term. However, disease relapse is common in long-term follow-up, despite a successful initial treatment response. This study aimed to identify the predictors of relapse and long-term outcomes in patients with type 1 AIP.

Methods

Patients with more than 2 years of follow-up who met the International Consensus Diagnostic Criteria for type 1 AIP were included. Patients who had undergone pancreatic operations associated with AIP or who lacked sufficient clinical data were excluded.

Results

All 138 patients achieved clinical remission with initial steroid therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24–197) months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within 3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of the proximal bile duct, was a significant independent predictor of relapse (hazard ratio 2.65; 95% confidence interval 1.44–4.89; p = 0.002), according to multivariate analysis. During the follow-up period, 16 (11.6%) patients experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de novo pancreatic calcifications/stones. No pancreatic cancer occurred in any patients.

Conclusions

Type 1 AIP has common relapses, and patients with OOI, especially OOI of the proximal bile duct, appear to be at increased risk for relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic calcifications/stones, are common in patients with relapse. To reduce the relapse, longer maintenance treatment may be needed especially for patients at high risk for relapse.