Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is a multisystem disorder that often has extrapancreatic manifestations such as immunoglobulin G4-associated cholangitis (IAC). Patients respond rapidly to steroids but can relapse after therapy. We assessed the clinical management of relapse in a group of patients with AIP/IAC. METHODS: We performed a prospective study of patients diagnosed with AIP from 2004-2007 who received steroids. Treatment outcome was defined clinically, radiologically, and biochemically as response to steroids, remission after steroids, failure to wean steroids, and relapse. Steroids +/- azathioprine (AZA) were used to treat patients who failed, relapsed, or could not be weaned from steroids. RESULTS: Twenty-eight patients with AIP were studied; 23 (82%) had IAC. All patients responded within 6 weeks to prednisolone therapy. Twenty-three patients achieved remission after a median of 5 months of treatment (range, 1.5-17 months), whereas 5 patients (18%) could not be weaned because of a disease flare. Of the patients who achieved remission, 8 of 23 (35%) subsequently relapsed. Overall, 13 of 23 patients (57%) with AIP/IAC relapsed, compared with 0 of the 5 with isolated AIP (P = .04, Fisher exact test). Steroids were increased/restarted in all patients who relapsed; 10 also received AZA. Remission was achieved and maintained in 7 patients; they remain on AZA monotherapy at a median of 14 months (range, 1-27 months). CONCLUSIONS: Relapse or failure to wean steroids occurred in 46% of patients with AIP. Patients with IAC are at particularly high risk of relapse. AZA appears to be effective in patients with post-treatment relapse or who cannot be weaned from steroids. To view this article's video abstract, go to the AGA's YouTube Channel.

Complications and diagnostic difficulties arising from biliary self-expanding metal stent insertion before definitive histological diagnosis.

BACKGROUND: Self-expanding metal bile duct stents provide good palliation for inoperable malignant disease. However, problems may arise if metal stents are inserted before definitive histological diagnosis. The aim of this study was to evaluate the outcome of such patients. METHODS: A retrospective case note review was conducted of patients referred to a tertiary pancreaticobiliary center between 1992 and 2004 in whom a metal bile duct stent was inserted for presumed unresectable malignant disease before definitive histological diagnosis. RESULTS: There were 21 patients identified. Final diagnoses were: group 1, benign disease (n = 3); group 2, resectable malignancy (n = 2); group 3, unresectable malignancy (n = 12); and group 4, diagnosis remains uncertain (n = 4). During a follow-up of 22, 38 and 111 months, the patients in group 1 had one, eight and five episodes of stent occlusion. In group 2, both patients underwent pancreaticoduodenectomy for ampullary carcinoma, 2 and 6 months after presentation. In group 3, the median time to a confirmed malignant diagnosis was 2 months (range 1-27 months). In group 4, a median of two biopsies (range 1-4) were negative for malignancy, during a median follow up of 13 months (range 3-46). Overall in eight patients, the metal stents caused artifacts on computed tomography and/or were associated with tissue in-growth making the differentiation between benign and malignant disease difficult. CONCLUSION: These cases indicate that metal bile duct stent insertion before definitive histological diagnosis can be problematic. A proportion of cases will have benign strictures and in others the confirmation of malignancy may be made more difficult.

Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series.

OBJECTIVE: Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression. METHODS: Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted. RESULTS: Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 mumol/L to 11 mumol/L (P= 0.001), and ALT from 97 IU/L to 39 IU/L (P= 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well. CONCLUSIONS: Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.

The use of immunoglobulin g4 immunostaining in diagnosing pancreatic and extrapancreatic involvement in autoimmune pancreatitis.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is recognized increasingly as a multisystem disorder. We evaluated the use of immunoglobulin (Ig)G4 immunostaining of pancreatic and extrapancreatic biopsy specimens to make a definitive diagnosis of AIP. METHODS: Seventeen biopsy specimens and 3 gallbladder resections were assessed from 11 patients with clinical and radiologic features of AIP. Biopsy specimens from pancreas, liver, colon, stomach, duodenum, bone marrow, salivary gland, and kidney were analyzed morphologically, immunostained for IgG4-positive plasma cells, and compared with controls. RESULTS: Positive IgG4 immunostaining enabled a definitive diagnosis in 10 of 11 (91%) AIP patients. In both pancreatic and extrapancreatic tissues, high levels of IgG4 immunostaining (>10 IgG4-positive plasma cells/high-power field) were found in 17 of 20 (85%) specimens from AIP patients compared with 1 of 175 (0.6%) specimens from controls (P < .05). Positive extrapancreatic IgG4 immunostaining was found in 8 of 11 (73%) patients, including all those with diagnostic features in the pancreas. Increased tissue IgG4 was found irrespective of serum IgG4 level. CONCLUSIONS: The finding of IgG4 immunostaining within a range of clinically involved tissues supports the hypothesis that AIP is a multisystem disease. Positive IgG4 immunostaining in extrapancreatic tissues may allow a definitive diagnosis of AIP to be made in those with evidence of pancreatic disease, without the necessity of pancreatic biopsy or surgical exploration. Immunostaining of involved tissue for IgG4 may be particularly useful when AIP is suspected clinically but the serum IgG4 level is normal.

Photodynamic therapy of malignant biliary strictures using meso-tetrahydroxyphenylchlorin.

OBJECTIVES: The palliation of patients with malignant bile duct obstruction using metal or plastic biliary stents may be limited by stent occlusion. The aim of this study was to determine the safety and efficacy of endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy in the treatment of irresectable malignant biliary strictures and recurrent stent occlusion. METHODS: Thirteen patients with malignant biliary obstruction owing to carcinoma of the biliary tract (n=9), pancreas (n=3) or stomach (n=1), were studied. All had been initially palliated with metal (n=10) or polyethylene (n=3) biliary stents, but presented with recurrent obstructive jaundice because of local tumour progression. Patients received meso-tetrahydroxyphenyl chlorin 0.15 mg/kg intravenously 72 h before endoluminal light activation with an endoscopically placed optical fibre, followed by polyethylene stent insertion. RESULTS: Before photodynamic therapy, patients had a median of three (range 0-5) stent occlusions in the preceding 11 (2-22) months, with a median patency of plastic stents placed inside metal bile duct stents for recurrent stent occlusion of 3.5 (0.5-13) months. After photodynamic treatment, tumour necrosis and/or metal stent recanalization was seen in all patients, with a median of 0 (0-3) stent occlusions during 7 (1-43) months follow-up. The median patency of plastic stents placed inside metal stents after photodynamic therapy was 5 (1-43) months. The median survival after diagnosis and photodynamic therapy administration was 21 (10-56) and 8 (1-43) months, respectively. Photodynamic therapy was generally well tolerated but two patients developed cholangitis within the first week, complicated in one by a fatal liver abscess and two developed haemobilia within 4 weeks of treatment, one of whom died with a gall bladder empyema. CONCLUSION: In patients with malignant biliary obstruction, endoscopically delivered meso-tetrahydroxyphenyl chlorin photodynamic therapy causes efficient tumour necrosis and recanalization of blocked metal stents, but there is a significant risk of complications.

Prospective comparison of secretin-stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III.

BACKGROUND: In sphincter of Oddi dysfunction (SOD), sphincter of Oddi manometry (SOM) predicts the response to sphincterotomy, but is invasive and associated with complications. AIM: To evaluate the role of secretin-stimulated magnetic resonance cholangiopancreatography (ss-MRCP) in predicting the results of SOM in patients with suspected type II or III SOD. METHODS: MRCP was performed at baseline and at 1, 3, 5 and 7 min after intravenous secretin. SOD was diagnosed when the mean basal sphincter pressure at SOM was >40 mm Hg. Long-term outcome after SOM, with or without endoscopic sphincterotomy, was assessed using an 11-point (0-10) Likert scale. RESULTS: Of 47 patients (male/female 9/38; mean age 46 years; range 27-69 years) referred for SOM, 27 (57%) had SOD and underwent biliary and/or pancreatic sphincterotomy. ss-MRCP was abnormal in 10/16 (63%) type II and 0/11 type III SOD cases. The diagnostic accuracy of ss-MRCP for SOD types II and III was 73% and 46%, respectively. During a mean follow-up of 31.6 (range 17-44) months, patients with normal SOM and SOD type II experienced a significant reduction in symptoms (mean Likert score 8 vs 4; p = 0.03, and 9 vs 1.6; p = 0.0002, respectively), whereas in patients with SOD type III, there was no improvement in pain scores. All patients with SOD and an abnormal ss-MRCP (n = 12) reported long-term symptom improvement (mean Likert score 9.2 v 1.2, p<0.001). CONCLUSIONS: ss-MRCP is insensitive in predicting abnormal manometry in patients with suspected type III SOD, but is useful in selecting patients with suspected SOD II who are most likely to benefit from endotherapy.