IgG4-related sclerosing disease

Based on histological and immunohistochemical exami- nation of various organs of patients with autoimmune pancreatitis （AIP）, a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prosrate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AlP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4- related sclerosing diseases. This disease includes AlP, sclerosing cholangitis, cholecystitis, sialadenitis, retro-peritoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AlP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunos-taining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.

MRCP and MRI findings in 9 patients with autoimmune pancreatitis

AIM： To evaluate magnetic resonance cholangiopancreatography （HRCP） findings in conjunction with magnetic resonance （MR） images in autoimmune pancreatitis （AIP） patients. METHODS： Nine patients with AIP underwent HRI, HRCP, endoscopic retrograde cholangiopancreatography （ERCP）, computed tomography, and ultrasonography. The HRCP and MR images taken before and after steroid therapy were reviewed and compared with other imaging modalities. The HRCP findings of the AIP cases were compared to those of 10 cases with carcinoma of the head of the pancreas.RESULTS： On MRCP, the narrowed portion of the main pancreatic duct noted on ERCP was not visualized, while the non-involved segments of the main pancreatic duct were visualized. The degree of upstream dilatation of the proximal main pancreatic duct was milder than that seen in cases of pancreatic carcinoma. Stenosis or obstruction of the lower bile duct was detected in 8 patients. MR images showed enlargement of the pancreas with decreased signal intensity on T1- weighted MR images, increased signal intensity on T2- weighted MR images, and, in 3 patients, a hypointense capsule-like rim. After steroid therapy, the previously not visualized portion of the main pancreatic duct was seen, along with improvement of the bile duct stenosis. Pancreatic enlargement decreased, and the abnormal signal intensity on both T1- and T2-weighted MR images became isointense.CONCLUSION： MRCP cannot differentiate irregular narrowing of the main pancreatic duct seen with AIP from stenosis of the main pancreatic duct seen with pancreatic carcinoma. However, MRCP findings in conjunction with MR imaging of pancreatic enlargement that shows abnormal signal intensity on T1- and T2- weighted MR images are useful in supporting a diagnosis of AIP.

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

AIM： TO examine the histological and immunohistochemical findings of biopsy specimens taken from the major duodenal papilla of autoimmune pancreatitis （AIP） patients. METHODS： The major duodenal papilla in the resected pancreas of 3 patients with AIP and of 5 control patients [pancreatic carcinoma （n = 3） and chronic alcoholic pancreatitis （17 = 2）] was immunostained using anti-CD4-T cell, CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major duodenal papilla of 2 patients with AIP and 5 control patients with suspected papillitis were prospectively taken during duodenoscopy and immunohistochemically examined. RESULTS： Moderate or severe Iymphoplasmacytic in- filtration including many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells （≥10/HPF）, was observed in the major duodenal papilla of all 3 patients with AIR The same findings were also detected in the biopsy specimens taken from the major duodenal papilla of 2 patients with/kiP, but in controls, there were only a few （≤3/HPF） IgG4-positive plasma cells infiltrating the major duodenal papilla. CONCLUSIONS： An abundant infiltration of IgG4-positive plasma cells is specifically detected in the major duodenal papilla of patients with A/P. Although this is a preliminary study, IgG4-immunostaining of biopsy specimens taken from the major duodenal papilla may support the diagnosis of AIR

Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas

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 v566.8±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. 2005 The WJG Press and Elsevier Inc. All rights reserved

Pancreatic cancer with a high serum IgG4 concentration

Differentiation between autoimmune pancreatitis and pancreatic cancer is sometimes difficult. It has been reported that serum IgG4 concentrations are significantly elevated and particularly high (>135 mg/dL) in autoimmune pancreatitis. Measurement of serum IgG4 has become a useful tool for differentiating between autoimmune pancreatitis and pancreatic cancer. However, we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL) who underwent pancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4 levels continued after the resection. On histology, adenocarcinoma of the pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the lower bile duct and duodenum, but there were no findings of autoimmune pancreatitis. Although a small metastasis was detected in one parapancreatic lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma cells infiltrated the cancerous areas of the pancreas, but only a few IgG4-positive plasma cells were detected in the noncancerous areas. Pancreatic cancer cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive plasma cells was detected in the swollen regional lymph nodes and in the duodenal mucosa. We believe that the serum IgG4 level was elevated in this patient with pancreatic cancer as the result of an IgG4-related systemic disease that had no clinical manifestations other than lymphadenopathy.

Thermo-chemo-radiotherapy for advanced bile duct carcinoma

AIM： Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis,with a life expectancy of about 6 mo to i year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy.METHODS： Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy （TCRT）. All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely.Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy.We administered heat to the patient for 40 rain after the tumor temperature had risen to 42℃. The chemotherapeutic agents employed were cis-platinum （CDDP,50 mg/m^2） in combination with 5-fluorouracil （5-FU,800 mg/m^2） or methotrexate （MTX, 30 mg/m^2） in combination with 5-FU （800 mg/m^2）. Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT.RESULTS： In respect to resolution of the bile duct, there were three complete regression （CR）, two partial regression （PR）, and three no change （NC）. Mean survival was 13.2＋10.8 mo （mean＋SD）. Four patients survived for more than 20 too. Percutaneous transhepatic biliary drainage （PTBD） tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed.CONCLUSION： Although the number of cases is rather small, TCRT in the treatment of locally advanced bile duct carcinoma is promising in raising local control and thus,long-term survival.

Sclerosing cholecystitis associated with autoimmune pancreatitis

AIM： TO evaluate the histopathological and radiological findings of the gallbladder in patients with autoimmune pancreatitis （AIP）. METHODS： The radiological findings of the gallbladder of 19 AIP patients were retrospectively reviewed. Resected gallbladders of 8 AIP patients were examined histologically and were immunostained with anti- IgG4 antibody. Controls consisted of gallbladders resected for symptomatic gallstones （n = 10） and those removed during pancreatoduodenectomy for pancreatic carcinoma （n = 10）, as well as extrahepatic bile ducts and pancreases removed by pancreatoduodenectomy for pancreatic carcinoma （n = 10）. RESULTS： Thickening of the gallbladder wall was detected by ultrasound and/or computed tomography in 10 patients with AIP （3 severe and 7 moderate）; in these patients severe stenosis of the extrahepatic bile duct was also noted. Histologically, thickening of the gallbladder was detected in 6 of 8 （75%） patients with AIP; 4 cases had transmural lymphoplasmacytic infiltration with fibrosis, and 2 cases had mucosal-based lymphoplasmacytic infiltration. Considerable transmural thickening of the extrahepatic bile duct wall with dense fibrosis and diffuse ly,mphoplasmacytic infiltration was detected in 7 patients. Immunohistochemically, severeor moderate infiltration of IgG4-positive plasma cells was detected in the gallbladder, bile duct, and pancreas of all 8 patients, but was not detected in controls. CONCLUSION： Gallbladder wall thickening with fibrosis and abundant infiltration of IgG4-positive plasma cells is frequently detected in patients with AIP. We propose the use of a new term, sclerosing cholecystitis, for these cases that are induced by the same mechanism as sclerosing pancreatitis or sclerosing cholangitis in AIP.