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 and management of autoimmune pancreatitis： Experience from China

AIM： To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis （AIP）. METHODS： In this retrospective study, the data of patients with diagnosed chronic pancreatitis （CP） between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria： （1） diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; （2） characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, y-globulin levels or presence of autoantibodies; （3） response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS： Twenty-five （22 male, 3 female; mean age 54 years, 36-76 years） out of 510 CP patients were diagnosed as AIP, which accounted for 49% （21/43） of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases （72%）, abdominal pain in 11 （44%）, weight loss in 10 （40%）, and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas （18 cases）, strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, theremaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION： AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. T     

慢性胰腺炎研究进展

慢性胰腺炎以胰腺慢性纤维化、钙化、胰管慢性炎症和胰管结石为主要病理改变,其发病率在国内外有逐年升高的趋势.虽然内镜治疗技术的飞速发展、胰酶替代药物的广泛应用、影像学和实验室技术的发展使慢性胰腺炎的内科诊断和治疗措施有了较大的进展。但确切的病因和发病机制尚不清楚,其诊断和治疗也尚未达成共识.因此,迫切需要开展慢性胰腺炎的流行病学、病因学、诊断学和治疗学等相关基础与,临床研究,为慢性胰腺炎的诊治提供理论和实践依据,并尽快制定出科学、客观的慢性胰腺炎诊治规范,指导其诊断和治疗.     

Autoimmune pancreatitis： Functional and morphological recovery after steroid therapy

Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in Japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test (OGTT) indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography (US) and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancrea-tography (ERCP) an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily. After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis. However, in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.     

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.     

自身免疫性胰腺炎临床特征分析

目的 探讨自身免疫性胰腺炎(autoimmune pancreatitis,AIP)的临床特点,提高对AIP的认识,降低误诊率.方法 分析2006-2009年期间在解放军总医院诊治的AIP患者的临床表现、影像及病理学特征和诊疗经过,并与1995-2005年期间的本院资料进行对比.结果 2006-2009年期间诊治8例AIP患者(男6例,女2例),年龄35～69(52.4±9.4)岁.主要临床表现为黄疸6例(6/8),腹痛5例(5/8),伴有其他免疫疾病4例(4/8).影像学见胰腺局部肿大3例(3/8),弥漫性肿大5例(5/8),其胰周均可见"香蕉皮样"囊状环,胰管不规则狭窄.病理检查见胰腺组织、胆管、涎腺及肝内可见大量淋巴细胞和浆细胞浸润及实质纤维化.7例(7/8)口服泼尼松治疗后临床表现、实验室及影像学表现均明显好转.我院1995-2005年期间资料显示,95.7%(22/23)误诊为胆道或胰腺癌,91.3%(21/23)行开腹手术,自2006年以后无一例出现误诊(0/8).结论 AIP是全身免疫系统异常体现在胰腺的一种损伤,常伴发其他免疫性疾病,综合免疫指标检测、影像学、病理学检查及试验性糖皮质激素治疗等可获确诊.     

Pancreatic cancer in patients with autoimmune pancreatitis: A scoping review

BackgroundChronic pancreatitis is a known risk factor of pancreatic cancer (PDAC). A similar association has been suggested but not demonstrated for autoimmune pancreatitis (AIP).ObjectiveThe aim of our study was to identify and analyse all published cases of AIP and PDAC co-occurrence, focusing on the interval between the diagnoses and the cancer site within the pancreas.MethodsRelevant studies were identified through automatic searches of the MEDLINE, EMBASE, Scopus, and Web of Science databases, and supplemented by manual checks of reference lists in all retrieved articles. Missing/unpublished data were obtained from the authors of relevant publications in the form of pre-prepared questionnaires.ResultsA total of 45 cases of PDAC in AIP patients were identified, of which 12 were excluded from the analysis due to suspicions of duplicity or lack of sufficient data. Thirty-one patients (94%) had type 1 AIP. Synchronous occurrence of PDAC and AIP was reported in 11 patients (33%), metachronous in 22 patients (67%). In the metachronous group, the median period between diagnoses was 66.5 months (2–186) and a majority of cancers (86%) occurred more than two years after AIP diagnosis. In most patients (70%), the cancer originated in the part of the pancreas affected by AIP.ConclusionsIn the literature, there are reports on numerous cases of PDAC in AIP patients. PDAC is more frequent in AIP type 1 patients, typically metachronous in character, and generally found in the part of the pancreas affected by AIP.     

Risk factors for development of endocrine insufficiency in chronic pancreatitis

Endocrine insufficiency is a common and frequent complication of chronic pancreatitis. Identifying the role of pancreatic damage in the development of diabetes is important for early identification and appropriate management.MethodsAll consecutive CP patients between January 2019 and May 2020 were retrospectively studied. Relevant statistical tests were performed. A two sided p value < 0.05 was considered statistically significant.ResultsTotal 587 chronic pancreatitis patients were included of which 118 (20.1%) patients developed diabetes with duration of 12 (IQR 4–48) months. Older age (OR 1.079; 95% CI 1.045–1.113; p < 0.001), presence of pancreatic parenchymal (OR 2.284; 95% CI 1.036–5.038; p = 0.041) and ductal (OR 2.351; 95% CI 1.062–5.207; p = 0.035) calcifications, exocrine insufficiency (OR 6.287; 95% CI 2.258–17.504; p < 0.001), and pancreatic duct stricture (OR 3.358; 95% CI 1.138–9.912; p = 0.028) were independently associated with development of diabetes mellitus in chronic pancreatitis patients. On cox-regression analysis, smoking (HR 2.370; 95% CI 1.290–4.354; p = 0.005) and pancreatic ductal calcification (HR 2.033; 95% CI 1.286–3.212; p = 0.002) were independently associated with earlier onset of diabetes mellitus in patients with chronic pancreatitis.ConclusionPancreatic calcification, pancreatic duct stricture and pancreatic exocrine insufficiency are associated with development of diabetes mellitus in chronic pancreatitis indicating disease progression. Smoking is the modifiable risk factors associated with early onset of diabetes mellitus in CP patients.     

Strategy to differentiate autoimmune pancreatitis from pancreas cancer

Autoimmune pancreatitis (AIP) is a newly described entity of pancreatitis in which the pathogenesis appears to involve autoimmune mechanisms. Based on histological and immunohistochemical examinations of various organs of AIP patients, AIP appears to be a pancreatic lesion reflecting a systemic "IgG4-related sclerosing disease". Clinically, AIP patients and patients with pancreatic cancer share many features, such as preponderance of elderly males, frequent initial symptom of painless jaundice, development of new-onset diabetes mellitus, and elevated levels of serum tumor markers. It is of uppermost importance not to misdiagnose AIP as pancreatic cancer. Since there is currently no diagnostic serological marker for AIP, and approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological, and histopathological features. Findings suggesting AIP rather than pancreatic cancer include: fluctuating obstructive jaundice; elevated serum IgG4 levels; diffuse enlargement of the pancreas; delayed enhancement of the enlarged pancreas and presence of a capsule-like rim on dynamic computed tomography; low apparent diffusion coefficient values on diffusion-weighted magnetic resonance image; irregular narrowing of the main pancreatic duct on endoscopic retrograde cholangiopancreatography; less upstream dilatation of the main pancreatic duct on magnetic resonance cholangiopancreatography, presence of other organ involvement such as bilateral salivary gland swelling, retroperitoneal fibrosis and hilar or intrahepatic sclerosing cholangitis; negative work-up for malignancy including endoscopic ultrasound-guided fine needle aspiration; and steroid responsiveness. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection.     

Natural course of chronic pancreatitis and predictors of its progression

BackgroundThe natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP.MethodsThis study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model.ResultsA total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5–7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4–2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34–0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66–1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03–1.7); p = 0.028] and diabetes[HR:2.7(2.2–3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7–31.2); p < 0.001], smoking-history[HR:6.5(2.2–19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05–0.4); p < 0.001].ConclusionACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.     

胰管内支架治疗慢性胰腺炎

目的 探讨胰管内支架引流术治疗慢性胰腺炎的临床疗效。方法 对１４例临床及影像学检查确诊的慢性胰腺炎伴胰管狭窄患者在内镜下进行了胰管内支架引流术,并对术后腹痛缓解率、胃纳、脂肪泻、体重变化及并发症发生率作了近期及远期了随访观察。结果 １４例患者均在内镜下内支架一次性置入成功,支架规格为５～１０Ｆ,术后随访２８～５２０ｄ,平均２１０ｄ,１４例患者术后近期（〈３个月）腹痛缓解率为９２．９％（１３／１４）     

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.     

Pharmacological management of pain in chronic pancreatitis

Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.     

Concomitant autoimmune and genetic pancreatitis leads to severe inflammatory conditions

Chronic pancreatitis characterized by an early onset should be extensively investigated including the search for a mutation of the PRSS1, SPINK-1 or CFTR genes and potential features of autoimmune pancreatitis. We here describe a case of chronic pancreatitis with an onset at a very young age in which a mutation of the PRSS1 and several features of autoimmune pancreatitis were identified.     

Determination of steroid response by abdominal ultrasound in cases with autoimmune pancreatitis

Background

Abdominal ultrasound is the most convenient modality for examining the morphology of the pancreas without physical stress. Steroid response is one of the key features of autoimmune pancreatitis; however, visualizing this response has not been evaluated using ultrasonography.

Methods

Thirty-three consecutive autoimmune pancreatitis cases were retrospectively investigated for pancreatic and extrapancreatic lesions by ultrasonography before steroid therapy (n = 33) and at two weeks (n = 28) and one month (n = 19) after starting oral steroid treatment.

Results

Steroid treatment resulted in obvious shrinkage of the pancreatic lesion in 86% of the cases at two weeks and in 97% until one month. The maximum thickness of the pancreatic lesion was reduced from 28 to 22 mm in two weeks (P < 0.0001), and pancreatic echographic findings improved in one month. Swelling of the peripancreatic lymph node was recognized in 48% and the aortic wall thickness in 12%, mostly reduced in two weeks (P = 0.005). One case of definitive autoimmune pancreatitis revealed a steroid response only by following endoscopic retrograde cholangiopancreatography but not by ultrasonography or computed tomography.

Conclusions

Abdominal ultrasound revealed a steroid response in most cases of autoimmune pancreatitis within two weeks. Ultrasonography is suitable for initial confirmation of a steroid response; however, atypical cases showing insufficient response or not fulfilling criteria should undergo further examination.