Susumu Iwasaki

Organ Correlation in IgG4-Related Diseases

IgG4-related disease (IgG4-RD) is a potentially multiorgan disorder. In this study, clinical and serological features from 132 IgG4-RD patients were compared about organ correlations. Underlying pathologies comprised autoimmune pancreatitis (AIP) in 85 cases, IgG4-related sclerosing cholangitis (IgG4-SC) in 12, IgG4-related sialadenitis (IgG4-SIA) in 56, IgG4-related dacryoadenitis (IgG4-DAC) in 38, IgG4-related lymphadenopathy (IgG4-LYM) in 20, IgG4-related retroperitoneal fibrosis (IgG4-RF) in 19, IgG4-related kidney disease (IgG4-KD) in 6, IgG4-related pseudotumor (IgG4-PT) in 3. Sixty-five patients (49%) had multiple IgG4-RD (two affected organs in 36 patients, three in 19, four in 8, five in 1, and six in 1). Serum IgG4 levels were significantly higher with multiple lesions than with a single lesion (P<0.001). The proportion of association with other IgG4-RD was 42% in AIP, the lowest of all IgG4-RDs. Serum IgG4 level was lower in AIP than in other IgG4-RDs. Frequently associated IgG4-RDs were SIA (25%) and DAC (12%) for AIP; AIP (75%) for IgG4-SC; DAC (57%), AIP (38%) and LYM (27%) for IgG4-SIA; AIP (26%) and LYM (26%) for IgG4-DAC; SIA (75%), DAC (50%) and AIP (45%) for IgG4-LYM; SIA (58%), AIP (42%) and LYM (32%) for IgG4-RF; AIP (100%) and SIA (67%) for IgG4-KID; and DAC (67%) and SIA (67%) for IgG4-PT. Most associated IgG4-RD lesions were diagnosed simultaneously, but IgG4-SIA and IgG4-DAC were sometimes identified before other lesions. About half of IgG4-RD patients had multiple IgG4-RD lesions, and some associations were seen between specific organs. Graphical Abstract

Assessment in steroid trial for IgG4-related sclerosing cholangitis

PURPOSE Response to steroids is included in the diagnostic criteria for IgG4-related sclerosing cholangitis (IgG4-SC). To assess how to appropriately conduct steroid trials for IgG4-related SC, we examined the clinical pictures of steroid responsiveness in IgG4-SC patients. MATERIAL AND METHODS A total of 29 patients with IgG4-SC (lower bile duct involvement, n=29; hilar/intrahepatic bile duct involvement, n=6) initially treated with steroids were enrolled in this study. Blood biochemistry was examined at about 5, 10 and 15 days after commencing steroid therapy. Endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiopancreatography (MRCP) were performed after steroid administration in 18 and 25 patients, respectively. RESULTS In 19 patients without biliary drainage, elevated serum levels of total bilirubin, alanine aminotransferase, and alkaline phosphatase were halved in 50%, 25%, and 44% of patients at about 5 days after starting steroids, and in 17%, 38%, and 44% at about 10 days. Responsiveness to steroids could be evaluated at 1-2 weeks on ERC or MRCP, but response was lower in the hilar/intrahepatic bile duct than in the lower bile duct. CONCLUSIONS Steroid responsiveness of IgG4-SC is recommended to be assessed by blood biochemistry at 5 and 10 days and on MRCP and/or ERC at 1-2 weeks after starting steroid.

Preoperative detection and handling of aberrant right posterior sectoral hepatic duct during laparoscopic cholecystectomy

An aberrant right posterior sectoral hepatic duct (PHD) draining into extrahepatic bile duct, gallbladder or cystic duct directly is a common and critical anomaly during cholecystectomy. This study aimed to investigate the frequency of aberrant PHD and describe why PHD is critical.

Major and minor duodenal papillae in autoimmune pancreatitis.

Objective The objective of this study was to evaluate picture of the major and minor duodenal papillae in patients with autoimmune pancreatitis (AIP). Methods Endoscopic features of the major and minor papillae were examined in 59 and 13 patients with AIP. After steroid therapy, changes of the major and minor papillae were observed in 5 and 6 patients. The major and minor papillae were observed with narrow band imaging in 24 and 6 patients. Biopsy specimens from the major (n = 50) and minor (n = 13) papillae were immunostained using an anti-IgG4 antibody. Results Endoscopic features of the major and minor papillae were abnormal in 26 patients (44%; swelling [n = 20] and redness [n = 14]) and 5 patients (38%; swelling [n = 5]). Swelling of the pancreatic head, irregular narrowing of the main pancreatic duct of the pancreatic head, stenosis of the lower bile duct, and abundant infiltration of IgG4-positive plasma cells were more frequent in the patients with an abnormal major papilla compared with those with a normal major papilla. On narrow band imaging, dilated vessels were observed in abnormal papillae. After therapy, swelling of the major and minor papillae improved in all 4 and 2 patients. Conclusions Endoscopic features of the major and minor papillae were abnormal in 44% and 38% of the patients with AIP.

Characteristic findings of endoscopic retrograde cholangiopancreatography in autoimmune pancreatitis.

Background/Aims Diffuse or segmental irregular narrowing of the main pancreatic duct (MPD), as observed by endoscopic retrograde cholangiopancreatography (ERCP), is a characteristic feature of autoimmune pancreatitis (AIP). Methods ERCP findings were retrospectively examined in 40 patients with AIP in whom irregular narrowing of the MPD was detected near the orifice. The MPD opening sign was defined as the MPD within 1.5 cm from the orifice being maintained. The distal common bile duct (CBD) sign was defined as the distal CBD within 1.5 cm from the orifice being maintained. Endoscopic findings of a swollen major papilla and histological findings of specimens obtained from the major papilla were examined in 26 and 21 patients, respectively. Results The MPD opening sign was detected in 26 of the 40 patients (65%). The distal CBD sign was detected in 25 of the 32 patients (78%), which showed stenosis of the lower bile duct. The patients who showed the MPD opening sign frequently showed the distal CBD sign (p=0.018). Lymphoplasmacytic infiltration, but not dense fibrosis, was histologically detected in biopsy specimens obtained from the major papilla. Conclusions On ERCP, the MPD and CBD adjacent to the major papilla are frequently maintained in patients with AIP involving the pancreatic head. These signs are useful for diagnosing AIP on ERCP.

Endoscopic Lithotomy and ESWL for Pancreatic Stones

The indication for the treatment of pancreatic stones is stone location in the main pancreatic duct (MPD) or Santorini duct and the presence of abdominal symptoms. If the diameter of the stone is >5 mm, the initial therapy is extracorporeal shock wave lithotripsy (ESWL), which is safe and minimally invasive. ESWL achieves adequate fragmentation and improves abdominal symptoms. Before ESWL, we usually perform endoscopic pancreatic sphincterotomy (EPST) because it prevents the impaction of crushed stones, acute pancreatitis, and acute cholangitis. However, if the stone is large or multiple stones are present, the success rate of ESWL alone is low, and endoscopic lithotomy is needed. If the size of the stone becomes ˂4 mm after ESWL, endoscopic lithotomy can be performed safely using basket forceps and a balloon catheter. We perform electrohydraulic lithotripsy (EHL) under peroral pancreatoscopy if ESWL fails to fragment the stone. If the stenosis of the MPD is present on the duodenum side of the stone, we perform endoscopic dilation using a dilation catheter and balloon followed by endoscopic pancreatic stenting. Endoscopic treatment is safer if these techniques are used.

Tips for Using SpyGlass Peroral Pancreatoscopy and X-Ray-Guided Electrohydraulic Lithotripsy for Refractory Pancreatic Stones

Objective: Extracorporeal shock wave lithotripsy (ESWL) and endoscopic stone lithotomy (EL) are minimally invasive procedures that are useful for treating pancreatic stones. However, large-diameter and impacted stones can be refractory to these treatments. We retrospectively evaluated the efficacy of peroral pancreatoscopy (POPS) and X-ray-guided electrohydraulic lithotripsy (EHL) in treating refractory pancreatic stones. Methods: From May 2005 to April 2014, 159 chronic pancreatitis and pancreatic lithiasis patients were treated with ESWL and EL. EHL was performed as a second attempt for unsuccessful ESWL and EL cases. For refractory cases, we used the 10 Fr SpyGlass Direct Visualization System for POPS-guided EHL. X-ray-guided EHL (using a 7 Fr biliary dilator as an outer sheath) was performed when a 10 Fr SpyGlass system was difficult to insert into the main pancreatic duct. Results: A total of 18 patients were included in this study. The mean stone diameter was 12.3 ± 4.5 mm, with 7 patients having a single stone and 11 patients having multiple stones. POPS-guided EHL was performed in nine cases and X-ray-guided EHL was performed in nine cases. Fragmentation was successful in nine (50%) patients: four treated with POPS-guided EHL and five treated with X-ray-guided EHL. Two patients developed mild post-ERCP pancreatitis following X-ray-guided EHL. Conclusions: POPS-guided and X-ray-guided EHL may be an alternative treatment for refractory stones. Because EHL can cause severe complications, adequate precautions are necessary for these treatments.

10 Fr S-Type Plastic Pancreatic Stents in Chronic Pancreatitis Are Effective for the Treatment of Pancreatic Duct Strictures and Pancreatic Stones

Aim Endoscopic pancreatic stenting for refractory pancreatic duct strictures associated with impacted pancreatic stones in chronic pancreatitis cases has yielded conflicting results. We retrospectively evaluated the efficacy of endoscopic treatment in chronic pancreatitis patients with pancreatic duct strictures. Methods Pancreatic sphincterotomy, dilatation procedures, pancreatic brush cytology, and pancreatic juice cytology were routinely performed, and malignant diseases were excluded. After gradual dilatation, a 10 Fr plastic pancreatic stent was inserted. The stents were replaced every 3 months and removed after the strictures were dilated. Statistical analyses were performed to determine the risk of main pancreatic duct restenosis. Results Endoscopic pancreatic stents were successfully placed in 41 of a total of 59 patients (69.5%). The median duration of pancreatic stenting was 276 days. Pain relief was obtained in 37 of 41 patients (90.2%). Seventeen patients (41.5%) had recurrence of main pancreatic duct stricture, and restenting was performed in 16 patients (average placement period 260 days). During the follow-up period, pancreatic cancer developed in three patients (5.1%). Multivariate analysis revealed that the presence of remnant stones after stenting treatment was significantly associated with a higher rate of main pancreatic duct restenosis (p = 0.03). Conclusion The use of 10 Fr S-type plastic pancreatic stents with routine exchange was effective for both short-term and long-term outcomes in chronic pancreatitis patients with benign pancreatic duct strictures and impacted pancreatic stones.