David G. Forcione

Consensus statement on the pathology of IgG4-related disease.

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.

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

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

A randomized trial comparing uncovered and partially covered self- expandable metal stents in the palliation of distal malignant biliary obstruction

BACKGROUND The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. OBJECTIVE To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. DESIGN Multicenter randomized trial. SETTING Four teaching hospitals. PATIENTS Adults with inoperable distal malignant biliary obstruction. INTERVENTIONS Uncovered or partially covered SEMS insertion. MAIN OUTCOME MEASURES Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. RESULTS From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively (P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups (P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively (P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated (P = .0061). LIMITATIONS Intended sample size was not reached. Allocation to treatment groups was unequal. CONCLUSIONS There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration.

Current trends in pancreatic cystic neoplasms.

OBJECTIVE To define how patients with pancreatic cysts are being diagnosed and treated. DESIGN Retrospective case series. SETTING University-affiliated tertiary care center. PATIENTS Four hundred one patients evaluated in the Department of Surgery between January 2004 and December 2007. MAIN OUTCOME MEASURES Clinical management, histological diagnosis, and results of surveillance. RESULTS Pancreatic cysts were incidentally discovered in 71% (284 of 401) of patients. There was no statistically significant difference in age (60.4 vs 63.1 years; P = .10), cyst size (31 vs 27 mm; P = .12), or histological diagnosis between symptomatic patients and patients with incidentally discovered cysts. Whereas the majority of symptomatic patients had their cystic neoplasms resected on diagnosis, 50% (142 of 284) of incidentally discovered cysts were initially managed nonoperatively. Of the patients who were managed with surveillance, 13 (8%) subsequently underwent resection after a median of 2.1 years because of an increase in cyst size, development of symptoms, increasing tumor markers, worrisome endoscopic ultrasonography findings, or patient anxiety. The most common diagnosis among resected lesions was either main-duct intraductal papillary mucinous neoplasm (25%) or branch-duct intraductal papillary mucinous neoplasm (23%). Invasive cancer was found in 29 of 256 (11%) resected cystic neoplasms, 9 of which were incidentally discovered, and in 7% (1 of 13) of patients who underwent watchful waiting prior to resection. CONCLUSIONS Incidentally discovered pancreatic cystic neoplasms composed 71% of our series, of which 50% were immediately resected. Subsequent morphologic changes or development of symptoms prompted an operation in 8% of patients after a period of surveillance. Invasive malignancy was present in 11% of all resected specimens but in 38% of main-duct intraductal papillary mucinous neoplasms.

Cytology Adds Value to Imaging Studies for Risk Assessment of Malignancy in Pancreatic Mucinous Cysts

Objective:Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. Background:The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main pancreatic duct (MPD) >6 mm, mural nodule (MN) and “positive” cytology as high risk stigmata for malignancy warranting surgical triage. Methods:We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [≥high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated. Results:Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (⩽30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%–44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features. Conclusions:Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.

Anti-Saccharomyces cerevisiae antibody (ASCA) positivity is associated with increased risk for early surgery in Crohn’s disease

Background: Anti-Saccharomyces cerevisiae antibodies (ASCA) are a specific but only moderately sensitive diagnostic marker for Crohn’s disease. We sought to explore the role of ASCA as a prognostic marker for aggressive disease phenotype in Crohn’s disease. Aims: To determine the role of ASCA status as a risk factor for early surgery in Crohn’s disease. Subjects: We performed a case control study in a cohort of patients, newly diagnosed with Crohn’s disease, between 1991 and 1999. All patients were followed for at least three years. Case subjects (n = 35) included those who had major surgery for Crohn’s disease within three years of diagnosis. Controls (n = 35) included patients matched to cases for age, sex, disease location, and smoking status, and who did not undergo major surgery for Crohn’s disease within three years of diagnosis. Methods: Blinded assays were performed on serum for ASCA (immunoglobulin (Ig)A and IgG). A paired analysis of cases-controls was performed to test for the association between ASCA status and risk of early surgery. Results: ASCA IgA was strongly associated with early surgery (odds ratio (OR) 8.5 (95% confidence interval (CI) 2.0–75.9); p = 0.0013). ASCA IgG+ and ASCA IgG+/IgA+ patients were also at increased risk for early surgery (OR 5.5 (95% CI 1.2–51.1), p = 0.0265; and OR 5.0 (95% CI 1.1–46.9), p = 0.0433, respectively). The association between ASCA and early surgery was evident in patients requiring surgery for ileal or ileocolonic disease. Conclusions: Patients with Crohn’s disease who are positive for ASCA IgA, IgG, or both, may define a subset of patients with Crohn’s disease at increased risk for early surgery.

The esophageal effects of cryoenergy during cryoablation for atrial fibrillation.

BACKGROUND Cryoenergy is being increasingly used for atrial fibrillation (AF) ablation, but the thermal effect of cryoenergy on the esophagus remains undefined. OBJECTIVE This study examines the esophageal effects of cryoenergy used during AF ablation. METHODS Catheter ablation was performed using a cryoballoon catheter in 67 AF patients (Cryoballoon group), and a spot cryocatheter to complete irrigated radiofrequency lesion sets at segments in close proximity to the esophagus in 7 AF patients (Cryo-Focal group). A temperature probe monitored the luminal esophageal temperature (LET) in all patients; LET changes did not guide therapy. Post-procedural endoscopy was performed on 35 of 67 (52%) Cryoballoon and all Cryo-Focal patients. RESULTS Significant LET decreases (>1 degrees C) occurred in 62 of 67 (93%) Cryoballoon patients. LET continued to decrease after termination of cryoablation before recovering to normal. Temperature decreases were more pronounced during ablation at the inferior (3.1 degrees C) than superior pulmonary veins (1.5 degrees C); the lowest observed temperature was 0 degrees C. Post-procedural endoscopy showed esophageal ulcerations in 6 of 35 (17%) patients. There were no atrial-esophageal fistulas, and all ulcers had healed on follow-up endoscopy. Patients with and without ulceration differed with respect to mean LET nadir, cumulative LET decrease, and number of LETs <30 degrees C. In the Cryo-Focal group, 6 +/- 2 spot cryolesions per patient resulted in 1.3 +/- 1 LET decreases per patient, and an absolute nadir of 32.5 degrees C. CONCLUSION Cryoballoon ablation can cause significant LET decreases, resulting in reversible esophageal ulcerations in 17% of patients. No ulcerations occurred with adjunctive spot cryoablation at regions near the esophagus during radiofrequency ablation procedures.

Accuracy of EUS in the evaluation of small gastric subepithelial lesions

BACKGROUND EUS combined with endoluminal resection techniques is increasingly used to provide a definitive diagnosis of small gastric subepithelial lesions seen on standard upper endoscopy. OBJECTIVE To evaluate the accuracy of EUS in diagnosing small gastric subepithelial lesions by using histology as the criterion standard. DESIGN A retrospective study. SETTING Academic tertiary care center. PATIENTS A total of 22 patients (15 women, mean age 62.2 years) with an endoscopically resected gastric subepithelial lesion were included in this 3-year retrospective study. MAIN OUTCOME MEASUREMENTS The size, echogenicity, the layer of origin, and presumptive diagnosis were determined by EUS. The diagnostic accuracy of EUS was determined by using histology as the criterion standard. RESULTS The mean size of the 22 lesions was 13.6 mm (range 8-20 mm). An endoscopic cap band mucosectomy device was used to resect 16 (72.7%) lesions, whereas 6 (27.3%) were resected with a saline solution-assisted and snare technique. Using histology as a criterion standard, we found that the accuracy of the EUS diagnosis was 10 of 22 (45.5%). EUS alone had an accuracy rate of 30.8% and 66.7%, respectively, in the diagnosis of neoplastic and non-neoplastic lesions. LIMITATIONS A single-center, retrospective analysis. CONCLUSION EUS imaging had a low accuracy rate in the diagnosis of gastric subepithelial lesions, and endoscopic submucosal resection should be performed to provide a histologic diagnosis. Resection of small subepithelial lesions of 20 mm or less can be accomplished en bloc with an endoscopic cap band mucosectomy device.

Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis

AIM To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs. METHODS Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendalls tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ² heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs.

Biliary Infections: Spectrum of Imaging Findings and Management

Infectious cholangitides encompass a wide spectrum of infectious processes affecting the biliary tree. They can have protean clinical and imaging appearances. Some manifest as an acute medical emergency with high mortality if not properly and emergently managed. Others are chronic processes that may predispose a patient to liver failure or cholangiocarcinoma. The clinical and imaging features and the subsequent therapy are dictated by the pathogens involved, the immune status of the host, and the degree and distribution of biliary obstruction. Bacteria cause most cases of infectious cholangitis in Western countries. In other parts of the world, parasites play an important role, either as causative agents or in predisposing the host to bacterial superinfection. Viral cholangitides primarily affect immunocompromised patients. The clinical and imaging features of cholangitis differ between immunocompetent and immunocompromised patients. Imaging plays a pivotal role in diagnosis of infectious cholangitis, helps identify predisposing causes, and demonstrates complications. Moreover, interventional radiology provides tools to treat acute life-threatening biliary infections, chronic entities, and complications.