John H. Stone, Arezou Khosroshahi, Vikram Deshpande, John K. C. Chan, J. Godfrey Heathcote, Rob Aalberse, Atsushi Azumi, Donald B. Bloch, William R. Brugge, Mollie N. Carruthers, Wah Cheuk, Lynn Cornell, Carlos Fernandez-Del Castillo, Judith A. Ferry, David Forcione, Gunter Kloppel, Daniel L. Hamilos, Terumi Kamisawa, Satomi Kasashima, Shigeyuki Kawa, Mitsuhiro Kawano, Yasufumi Masaki, Kenji Notohara, Kazuichi Okazaki, Ji Kon Ryu, Takako Saeki, Dushyant Sahani, Yasuharu Sato, Thomas Smyrk, James R. Stone, Masayuki Takahira, Hisanori Umehara, George Webster, Motohisa Yamamoto, Eunhee Yi, Tadashi Yoshino, Giuseppe Zamboni, Yoh Zen, and Suresh Chari

/pdf/recommendations-for-the-nomenclature-of-igg4-related-disease-xdmno9q2yi.pdf

Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations

Objective. Patients with IgG4-related systemic disease (IgG4-RSD) frequently show an incomplete response to treatment with glucocorticoids and traditional disease-modifying antirheumatic drugs (DMARDs). B lymphocyte depletion is a therapeutic strategy known to be effective for pemphigus vulgaris, an autoimmune condition mediated by IgG4 autoantibodies. This study was performed to assess the clinical and serologic responses to B lymphocyte depletion therapy with rituximab in patients with IgG4-RSD. Methods. Four patients with IgG4-RSD were treated with 2 intravenous doses (1 gram each) of rituximab. Clinical improvement was assessed by monitoring the tapering/discontinuation of prednisone and DMARDs, and by measuring the serum concentrations of B lymphocytes, immunoglobulins, and IgG subclasses before and after therapy. Results. Clinical features of IgG4-RSD in these 4 patients included autoimmune pancreatitis, sclerosing cholangitis, lymphoplasmacytic aortitis, salivary gland involvement, orbital pseudotumor, and lacrimal gland enlargement. The 3 patients with elevated serum IgG and IgG4 levels at baseline had a mean IgG concentration of 2,003 mg/dl (normal range 600–1,500 mg/dl) and a mean IgG4 concentration of 2,160 mg/dl (normal range 8–140 mg/dl). Among these patients, the serum IgG4 concentrations declined by a mean of 65% within 2 months of rituximab administration. All 4 patients demonstrated striking clinical improvement within 1 month of the initiation of rituximab therapy, and tapering or discontinuation of their treatment with prednisone and DMARDs was achieved in all 4 patients. A decrease in IgG concentration was observed for the IgG4 subclass only. Conclusion. Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4-RSD, and is a viable treatment option for this condition. The decline in serum IgG4 concentrations was substantially steeper than that of the autoantibody concentrations in immune-mediated conditions in which rituximab is effective, such as in rheumatoid arthritis. In addition, the reduction in IgG-subclass levels appeared to be specific for IgG4. The swift improvement of IgG4-RSD suggests that rituximab achieves its effects in IgG4-RSD by depleting the pool of B lymphocytes that replenish short-lived IgG4-secreting plasma cells.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.27435

Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease.

Purpose of reviewTo summarize the existing knowledge of various clinical presentations of IgG4-related systemic disease (IgG4-RSD) and to review the evolving list of organs affected by IgG4-RSD.Recent findingsThe term IgG4-RSD encompasses a variety of clinical entities once regarded as being entirel

A clinical overview of IgG4-related systemic disease.

Background: Synchronous occurrence of intraductal papillary mucinous neoplasm (IPMN) and ductal carcinoma of the pancreas has been reported. Branch duct IPMNs with lower likelihood of malignancy are not submitted to resection but are followed-up, so ductal carcinoma may develop during the follow-up. The development of ductal carcinoma of the pancreas during follow-up of branch duct IPMNs was investigated. Methods: 60 patients with branch duct IPMN who had an intraductal tumour of Results: Ductal carcinoma of the pancreas distinct from IPMN developed in 5 of 60 (8%) branch duct IPMNs during follow-up. The 5-year rate of development of ductal carcinoma was 6.9% (95% CI 0.4% to 13.4%), the incidence of ductal carcinoma was 1.1% (95% CI 0.1% to 2.2%) per year and the standardised incidence ratio of development of ductal carcinoma was 26 (95% CI 3 to 48). Patients >70 years old developed ductal carcinoma significantly more frequently than those under 69. Four of five ductal carcinomas identified during follow-up were resectable. Cancer developed in IPMN in 2 of 60 (3%) branch duct IPMNs during follow-up. Conclusions: During follow-up of branch duct IPMNs, ductal carcinoma of the pancreas not infrequently developed distinct from IPMN. In the follow-up of IPMN, special attention should be paid to the development of ductal carcinoma of the pancreas.

https://gut.bmj.com/content/gutjnl/57/11/1561.full.pdf

Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas

https://www.advancessurgery.com/article/S0065-3411(10)00012-6/pdf

Update on Familial Pancreatic Cancer

AIM: As intraductal papillary mucinous neoplasm (IPMN)has a favorable prognosis, associated malignancies have potential significance in these patients. We examined the incidence and characteristics of pre-existing, coexisting and subsequent malignancies in patients with IPMN. METHODS: Seventy-nine cases of IPMN were diagnosed by detection of mucous in the pancreatic duct during endoscopic retrograde pancreatography. Histological diagnosis was confirmed in 30 cases (adenoma (n = 19)and adenocarcinoma (n = 11). Other primary malignancies associated with IPMN, occurring in the prediagnostic or postdiagnostic period, were investigated. Postdiagnostic follow-up period was 3.3±0.5 years (range, 0.2-20 years).RESULTS: Other 40 malignancies occurred in 28 patients (35%). They were found before (n = 15), at (n = 19) and after (n = 6) the diagnosis of IPMT. Major associated malignancies were gastric cancer (n = 12), colonic cancer (n = 7), esophageal cancer (n = 4), pulmonary cancer (n = 4), and independent pancreatic cancer (n = 3).Pancreatic cancer was synchronous with IPMN in two patients and metachronous in one (3 years after diagnosis of IPMN). Thirty-one lesions were treated surgically or endoscopically. Fourteen patients died of associated cancers. Development of other malignancies was related to age (71.9±8.2 vs66.8±9.3, P＜0.05), but not to gender or site of the tumor.CONCLUSION: IPMN is associated with a high incidence of other malignancies, particularly gastric and colonic cancers. Common genetic mechanisms between IPMN and other associated malignancies might be present. Clinicians should pay attention to the possibility of associated malignancies in preoperative screening and follow-up of patients with IPMN.

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas

瞄准：检验组织学并且免疫从自体免疫的胰腺炎(AIP ) 的主要十二指肠的乳头状的小突起拿的活体检视标本的组织化学的调查结果病人们。方法：在有 AIP 的 3 个病人并且 5 个控制病人的 resected 胰的主要十二指肠的乳头状的小突起[胰腺的癌(n = 3 ) 并且长期的含酒精的胰腺炎(n = 2 )] 免疫用 anti-CD4-T 房间， CD8-T 房间和 IgG4 抗体被染色。与怀疑的视神经乳头炎与 AIP 和 5 个控制病人从 2 个病人的主要十二指肠的乳头状的小突起拿的钳活体检视标本有希望地在组织化学地检验的十二指肠镜检查和免疫期间被拿。结果：包括许多 CD4 积极或 CD8 积极的 T 淋巴细胞和 IgG4 积极的血浆房间(>or=10/HPF ) 的中等或严重的 lymphoplasmacytic 渗入，与 AIP 在所有 3 个病人的主要十二指肠的乳头状的小突起被观察。一样的调查结果也在与 AIP 从 2 个病人的主要十二指肠的乳头状的小突起拿的活体检视标本，但是在控制被检测，仅仅有一些(<or=3/HPF ) 渗入主要十二指肠的乳头状的小突起的 IgG4 积极的血浆房间。结论：IgG4 积极的血浆房间的丰富的渗入明确地与 AIP 在病人的主要十二指肠的乳头状的小突起被检测。尽管这是初步的研究，从主要十二指肠的乳头状的小突起拿的活体检视标本的 IgG4-immunostaining 可以支持 AIP 的诊断。

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis： A prospective study using IgG4-immunostaining

基于组织学并且免疫有自体免疫的胰腺炎(AIP ) 的病人的各种各样的机关的组织化学的检查， IgG4 相关的致硬化的疾病的一个新奇 clinicopathological 实体被建议了。这是被广泛的 IgG4 积极的血浆细胞和各种各样的器官的 T 淋巴细胞渗入描绘的系统病。临床的表明在胰，胆汁管，胆囊，唾液的腺，制动火箭腹膜，肾，肺，和前列腺，在纸巾，有 obliterative 静脉炎的纤维变性病理地被导致是明显的。AIP 不简单地是胰腺炎，但是事实上，是 IgG4 相关的致硬化的疾病的一口胰腺的疾病陈述语气。这疾病包括 AIP，致硬化的胆管炎，胆汁，硅铝带淋巴腺炎，制动火箭腹纤维变性， tubulointerstitial 肾炎，间质性肺炎，前列腺炎，煽动性的假肿瘤和淋巴结病，全 IgG4 相关。没有胰腺的参与的 IgG4 相关的致硬化的疾病被发现了与 AIP 被联系的大多数，而且那些被报导了。在一些情况中，，仅仅一或二个机关临床上涉及其它，三或四个机关被影响。疾病在老人主要发生并且对类固醇治疗作出回应很好。与 anti-IgG4 抗体染色的浆液 IgG4 层次和免疫在做诊断是有用的。因为恶性瘤经常在起始的表示上被怀疑， IgG4 相关的致硬化的疾病应该在鉴别诊断被考虑避免不必要的外科。

Okamoto

Papers

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas

Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis： A prospective study using IgG4-immunostaining

IgG4-related sclerosing disease