Predictors of Malignancy in Patients With Indeterminate Biliary Strictures and Atypical Biliary Cytology: Results From Retrospective Cohort Study.

BACKGROUND: Atypical cellular features are commonly encountered in patients with indeterminate biliary strictures, which are nondiagnostic of malignancy yet cannot rule it out. This study aims to identify clinical features that could discriminate patients with indeterminate biliary strictures and atypical biliary cytology who may harbor underlying malignancy. METHODS: All patients with an indeterminate biliary stricture and an atypical brush cytology obtained during endoscopic brushings were identified in a large tertiary-care center. Demographical information, clinical data and the final pathological diagnosis were collected. The study cohort was divided based on the final diagnosis into benign and malignant groups. Descriptive and multivariable analyses were performed. RESULTS: A total of 151 patients were included in the analysis. Of these, 62.9% were males with mean age of 61.7 ± 16.4 years. Overall, there was an almost equal distribution of patients in the benign and malignant groups. Older age (≥65 years), jaundice, weight loss, intrahepatic biliary and pancreatic duct dilation, double-duct sign and presence of a mass were associated with malignancy in the univariate analysis. However, only older age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00 to 1.03), jaundice (OR 3.33, 95% CI 1.11 to 9.98) and presence of a mass (OR 12.10, 95% CI 4.94 to 29.67) were significantly associated with malignancy in the multivariate analysis. High CA19-9 was associated with malignancy only in patients with primary sclerosing cholangitis. CONCLUSION: In patients with indeterminate biliary stricture and atypical brush cytology, older age, jaundice and presence of a mass are significant predictors of malignancy. Patients with such characteristics need prompt evaluation to rule out underlying malignancy.

Clinical and pathological predictors of failure of endoscopic therapy for Barrett's related high-grade dysplasia and early esophageal adenocarcinoma.

BACKGROUND AND AIMS: Multimodal endoscopic treatment for Barrett's esophagus (BE) related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) is safe and effective. However, there is a paucity of data to predict the response to endoscopic treatment. This study aimed to identify predictors of failure to achieve complete eradication of neoplasia (CE-N) and complete eradication of intestinal metaplasia (CE-IM). METHODS: We performed a retrospective analysis of prospectively collected data of all HGD/EAC cases treated endoscopically at a tertiary referral center. Only patients with confirmed HGD/EAC from initial endoscopic mucosal resection (EMR) were included. Potential predictive variables including clinical characteristics, endoscopic features, and index histologic parameters of the EMR specimens were evaluated using multivariate Cox regression. RESULTS: A total of 457 patients were diagnosed with HGD/EAC by initial EMR from January 2008 to January 2019. Of these, 366 patients who underwent subsequent endoscopic treatment with or without RFA were included. Cumulative incidence rates at 3 years for CE-N and CE-IM were 91.4% (95% CI 87.8-94.2%) and 66.8% (95% CI 61.2-72.3%), respectively during a median follow-up period of 35 months. BE segment of 3-10 cm (HR 0.45; 95% CI 0.36-0.57) and > 10 cm (HR 0.25; 95% CI 0.15-0.40) were independent clinical predictors associated with failure to achieve CE-N. With respect to CE-IM, increasing age (HR 0.88; 95% CI 0.78-1.00) was another predictor along with BE segment of 3-10 cm (HR 0.37; 95% CI 0.28-0.49) and > 10 cm (HR 0.15; 95% CI 0.07-0.30). Lymphovascular invasion increased the risk of CE-N and CE-IM failure in EAC cases. CONCLUSION: Failure to achieve CE-N and CE-IM is associated with long-segment BE and other clinical variables. Patients with these predictors should be considered for a more intensive endoscopic treatment approach at expert centers.

Endoscopic Resection of Ampullary Tumours: Long-term Outcomes and Adverse Events.

BACKGROUND: The management of ampullary lesions has shifted from surgical approach to endoscopic resection. Previous reports were limited by small numbers of patients and short follow-up. The aim of this study is to describe short- and long-term outcomes in a large cohort of patients undergoing endoscopic ampullectomy. METHODS: Retrospective study of endoscopic ampullectomies performed at a tertiary center from January 1999 to October 2016. Information recorded includes patient demographics, clinical outcomes, lesion pathology, procedural events, adverse events and follow-up data. RESULTS: Overall, 103 patients underwent endoscopic resection of ampullary tumours (mean age 62.3 ± 14.3 years, 50.5% female, mean lesion size 20.9 mm; 94.9% adenomas, with a majority of lesions exhibiting low-grade dysplasia (72.7%). Complete endoscopic resection was achieved in 82.5% at initial procedure. Final complete endoscopic resection was achieved in all patients with benign pathology on follow-up procedures. Final pathology showed that 11% had previously undiagnosed invasive carcinoma. Delayed postprocedure bleeding occurred in 21.4%, all of which were managed successfully at endoscopy. Acute pancreatitis complicated 15.5% of procedures (mild in 93.8%). Perforation occurred in 5.8%, all treated conservatively except for one patient requiring surgery. Piecemeal resection was associated with significantly higher recurrence compared to en-bloc resection (54.3% versus 26.2%, respectively, P = 0.012). All recurrences were treated endoscopically. CONCLUSION: Endoscopic ampullectomy appears both safe and effective in managing patients with ampullary tumours in experienced hands. Most adverse events can be managed conservatively. Many patients develop recurrence during long-term follow-up but can be managed endoscopically. Recurrence rates may be reduced by performing initial en-bloc resection.

Long-term outcomes after temporary placement of a self-expanding fully covered metal stent for benign biliary strictures secondary to chronic pancreatitis.

BACKGROUND AND AIMS: Temporary single, fully covered self-expanding metal stent (FCSEMS) placement for benign biliary strictures (BBSs) associated with chronic pancreatitis (CP) may require fewer interventions than endotherapy with multiple plastic stents and may carry less morbidity than biliary diversion surgery. This study aimed to assess long-term outcomes in CP-associated BBSs after FCSEMS placement and removal. METHODS: In this open-label, multinational, prospective study, subjects with CP and a BBS treated with FCSEMS placement with scheduled removal at 10 to 12 months were followed for 5 years after FCSEMS indwell. Kaplan-Meier analyses assessed BBS resolution and cumulative probability of freedom from recurrent stent placement to 5 years after FCSEMS indwell. RESULTS: One hundred eighteen patients were eligible for FCSEMS removal. At a median of 58 months (interquartile range, 44-64) post-FCSEMS indwell, the probability of remaining stent-free was 61.6% (95% confidence interval [CI], 52.5%-70.7%). In 94 patients whose BBSs resolved at the end of FCSEMS indwell, the probability of remaining stent-free 5 years later was 77.4% (95% CI, 68.4%-86.4%). Serious stent-related adverse events occurred in 27 of 118 patients (22.9%); all resolved with medical therapy or repeated endoscopy. Multivariate analysis identified severe CP (hazard ratio, 2.4; 95% CI, 1.0-5.6; P = .046) and longer stricture length (hazard ratio, 1.2; 95% CI, 1.0-1.4; P = .022) as predictors of stricture recurrence. CONCLUSION: In patients with symptomatic BBSs secondary to CP, 5 years after placement of a single FCSEMS intended for 10 to 12 months indwell, more than 60% remained asymptomatic and stent-free with an acceptable safety profile. Temporary placement of a single FCSEMS may be considered as first-line treatment for patients with CP and BBSs. (Clinical trial registration number: NCT01014390.).

Treatment of post-cholecystectomy biliary strictures with fully-covered self-expanding metal stents - results after 5 years of follow-up.

BACKGROUND: Endoscopic treatment of post-cholecystectomy biliary strictures (PCBS) with multiple plastic biliary stents placed sequentially is a minimally invasive alternative to surgery but requires multiple interventions. Temporary placement of a single fully-covered self-expanding metal stent (FCSEMS) may offer safe and effective treatment with fewer re-interventions. Long-term effectiveness of treatment with FCSEMS to obtain PCBS resolution has not yet been studied. METHODS: In this prospective multi-national study in patients with symptomatic benign biliary strictures (N = 187) due to various etiologies received a FCSEMS with scheduled removal at 6-12 months and were followed for 5 years. We report here long-term outcomes of the subgroup of patients with PCBS (N = 18). Kaplan Meier analyses assessed long-term freedom from re-stenting. Adverse events were documented. RESULTS: Endoscopic removal of the FCSEMS was achieved in 83.3% (15/18) of patients after median indwell of 10.9 (range 0.9-13.8) months. In the remaining 3 patients (16.7%), the FCSEMS spontaneously migrated and passed without complications. At the end of FCSEMS indwell, 72% (13/18) of patients had stricture resolution. At 5 years after FCSEMS removal, 84.6% (95% CI 65.0-100.0%) of patients who had stricture resolution at FCSEMS removal remained stent-free. In addition, at 75 months after FCSEMS placement, the probability of remaining stent-free was 61.1% (95% CI 38.6-83.6%) for all patients. Stent or removal related serious adverse events occurred in 38.9% (7/18) all resolved without sequalae. CONCLUSIONS: In patients with symptomatic PCBS, temporary placement of a single FCSEMS intended for 10-12 months indwell is associated with long-term stricture resolution up to 5 years. Temporary placement of a single FCSEMS may be considered for patients with PCBS not involving the main hepatic confluence. TRIAL REGISTRATION NUMBERS: NCT01014390; CTRI/2012/12/003166; Registered 17 November 2009.

Clinical characteristics of young patients with early Barrett's neoplasia.

BACKGROUND: Esophageal adenocarcinoma (EAC) and high-grade dysplasia (HGD) may appear in young patients with Barrett's esophagus (BE). However, characteristics of Barrett's-related neoplasia in this younger population remain unknown. AIM: To identify clinical characteristics that differ between young and old patients with early-stage Barrett's-related neoplasia. METHODS: We conducted a retrospective analysis of a prospectively maintained database comprised of consecutive patients with early-stage EAC (pT1) and HGD at a tertiary-referral center between 2001 and 2017. Baseline characteristics, drug and risk factor exposures, clinicopathological staging of EAC/HGD and treatment outcomes [complete eradication of neoplasia (CE-N), complete eradication of intestinal metaplasia (CE-IM), recurrence of neoplasia and recurrence of intestinal metaplasia] were retrieved. Multivariate analyses were performed to identify factors that differed significantly between older and younger (≤ 50 years) patients. RESULTS: We identified 450 patients with T1 EAC and HGD (74% and 26%, respectively); 45 (10%) were ≤ 50 years. Compared to the older group, young patients were more likely to present with ongoing gastroesophageal reflux disease (GERD) symptoms (55% vs 38%, P = 0.04) and to be obese (body mass index > 30, 48% vs 32%, P = 0.04). Multivariate logistic regression analysis showed that young patients were significantly more likely to have ongoing GERD symptoms [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.04-3.85, P = 0.04] and to be obese (OR 2.06, 95%CI 1.07-3.98, P = 0.03) whereas the young group was less likely to have a smoking history (OR 0.39, 95%CI 0.20-0.75, P < 0.01) compared to the old group. However, there were no significant differences regarding tumor histology, CE-N, CE-IM, recurrence of neoplasia and recurrence of intestinal metaplasia (mean follow-up, 44.3 mo). CONCLUSION: While guidelines recommend BE screening in patients > 50 years of age, younger patients should be considered for screening endoscopy if they suffer from obesity and GERD symptoms.

Clinical characteristics may distinguish patients with esophageal adenocarcinoma arising from long- versus short-segment Barrett's esophagus.

BACKGROUND AND AIMS: Patients with long-segment Barrett's esophagus (LSBE; ≧3 cm) have higher risk of developing esophageal adenocarcinoma (EAC) than those with short-segment Barrett's esophagus (SSBE; <3 cm). However, it is unclear whether patients developing EAC from LSBE or SSBE differ significantly according to baseline clinical characteristics. METHODS: We conducted a retrospective analysis of a prospectively maintained database comprising consecutive patients with early EAC treated by endoscopic mucosal resection at a single, tertiary-referral center. Information regarding baseline clinical characteristics were determined. Univariate and multivariate logistic regression were performed to identify factors that differed significantly between patients with EAC arising from SSBE and LSBE. RESULTS: A total of 145 LSBE EAC and 179 SSBE EAC cases were identified. The LSBE EAC patients had a stronger association with having a hiatal hernia compared to the SSBE EAC patients. In contrast, inverse associations were observed in LSBE EAC patients with statin use and smoking pack-years relative to SSBE EAC patients. CONCLUSIONS: Patients who developed EAC on a background of LSBE were more likely to have a hiatus hernia compared to patients with SSBE EAC, who were more likely to have higher smoking pack-years and higher rates of statin use.

Hot avulsion may be effective as salvage treatment for focal Barrett's esophagus remaining after endoscopic therapy for dysplasia or early cancer: a preliminary study.

BACKGROUND AND STUDY AIM: Both endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) are used to treat Barrett's esophagus (BE) complicated by dysplasia and intramucosal cancer. However, focal areas of BE can remain after otherwise successful application of these techniques. We report the results of hot avulsion using a hot biopsy forceps to resect these residual focal areas. PATIENTS AND METHODS: This was a retrospective study from a prospective database in a tertiary reference center from August 2013 to May 2015. All included patients had undergone hot avulsion for eradication of residual focal areas of BE that were ≤ 1 cm and not suspicious for dysplasia, following at least one previous endoscopic treatment for dysplasia or intramucosal cancer. RESULTS: 35 patients harboring 124 residual areas of 1 - 7 mm were treated with hot avulsion. After a mean follow-up of 17.4 months, all patients achieved complete eradication of residual focal BE. One of the patients required a second hot avulsion treatment. Hot avulsion provided samples in all cases but limited the assessment of dysplasia (cautery artifact) in 20.2 % of them. The only complication was bleeding in two patients, which was easily stopped by soft coagulation. CONCLUSIONS: Hot avulsion appears to be effective and safe in removing focal BE ≤ 1 cm at its greatest length remaining after endoscopic treatment for dysplasia or early cancer. Further studies are required before this technique can be considered the standard of care.

Achalasia-Specific Quality of Life After Pneumatic Dilation or Laparoscopic Heller Myotomy With Partial Fundoplication: A Multicenter, Randomized Clinical Trial.

OBJECTIVES: Achalasia is a chronic, progressive, and incurable esophageal motility disease. There is clinical uncertainty about which treatment should be recommended as first-line therapy. Our objective was to evaluate the effectiveness of pneumatic dilation compared with laparoscopic Heller myotomy with partial fundoplication in improving achalasia-specific quality of life. METHODS: This was a prospective, multicenter, randomized trial at five academic hospitals in Canada. Fifty previously untreated adults with a clinical diagnosis of primary achalasia, confirmed by manometric testing, were enrolled between November 2005 and March 2010, and followed for 5 years after treatment. Randomization was stratified by site, in random blocks of size four and with balanced allocation. Patients were treated with pneumatic dilation or laparoscopic Heller myotomy with partial fundoplication. The primary outcome was the difference between the treatments in the mean improvement of the achalasia severity questionnaire (ASQ) score at 1 year from baseline. Prespecified secondary outcomes included general and gastrointestinal quality of life, symptoms, esophageal physiology measures (lower esophageal sphincter relaxation and pressure, esophageal emptying, abnormal esophageal acid exposure), complications, and incidence of retreatment. Functional and imaging studies were performed blinded and all outcome assessors were blinded. RESULTS: There were no significant differences between treatments in the improvement of ASQ score at 1 year from baseline (27.5 points in the Heller myotomy arm vs. 20.2 points in the pneumatic dilation arm; difference 7.3 points, 95% confidence interval -4.7 to 19.3; P=0.23). There were no differences between treatments in improvement of symptoms, general and gastrointestinal quality of life, or measures of esophageal physiology. Improvements in ASQ score diminished over time for both interventions. At 5 years, there were no differences between treatments in improvement of ASQ score, symptoms, and general or gastrointestinal quality of life. There were no serious adverse events. No patient who received Heller myotomy required retreatment, whereas five patients treated initially with pneumatic dilation required retreatment. CONCLUSIONS: Treatment with pneumatic dilation or laparoscopic Heller myotomy similarly improves achalasia-specific disease severity at 1 year. Either of the therapeutic approaches can be used as first-line therapy for previously untreated adults with achalasia.

Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium.

OBJECTIVES: Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data. METHODS: The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates. RESULTS: Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8-25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9-25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11-33). Two CRC and two SBC were detected during surveillance within 6-11 months and 9-16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed. CONCLUSIONS: The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3-5 and 8 years, respectively.

Pylephlebitis After Colonic Polypectomy Causing Fever and Abdominal Pain.

Pylephlebitis is a rare condition with a high mortality risk if not recognized and treated early. The most common symptoms include fever and abdominal pain, with the majority of cases manifesting with a polymicrobial bacteremia. We report an elderly woman with pylephlebitis presenting with fever, abdominal pain, diarrhea, and vomiting, likely secondary to a polypectomy 6 weeks prior. Abdominal CT revealed portal vein thrombus and blood cultures grew Streptococcus milleri and Haemophilus parainfluenza type V. Pylephlebitis should be considered when symptoms and signs of infection develop following endoscopic procedures, particularly in patients with an underlying hypercoaguable disease.

Wire-guided cannulation versus contrast-guided cannulation in pediatric endoscopic retrograde cholangiopancreatography.

BACKGROUND/AIM: Wire-guided cannulation (WGC) of the common bile duct may be associated with fewer complications and higher success rate compared with contrast-guided cannulation (CGC) in adults. Data in children are lacking. The aim of this study was to compare the successful cannulation and complication rate of WGC and CGC in pediatric endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: We report a retrospective cohort study comparing WGC to CGC in a pediatric cohort. We reviewed the medical records of 167 children who underwent ERCP over a 10-year time period (CGC, 1999-2003, WGC, 2003-2009). Indications, findings, and success were analyzed. RESULTS: A total of 93 patients (56%) underwent WGC and 74 (44%) CGC. Children in the WGC group were younger (9.5 ± 4.7 vs. 11.5 ± 4.6 years in CGC; P = 0.006) and underwent more therapeutic ERCP interventions (70% vs. 40% in CGC), whereas diagnostic ERCP was more common in the CGC group (60%; P < 0.005). The overall success (96%) and complication rate (8%) were identical in both groups but a trend toward a reduction in the complication rate over time was noted in the WGC group. Post-ERCP pancreatitis (PEP) was documented in one patient in the WGC group (1.1%) and three patients (4.2%) in the CGC group (P-NS). CONCLUSION: The success and complication rate in both CGC and WGC are comparable in children but considering the patient and procedure complexity and the trend toward lower PEP in the WGC group, WGC may be the preferable cannulation technique for ERCP in children.

Progression and Management of Duodenal Neoplasia in Familial Adenomatous Polyposis: A Cohort Study.

OBJECTIVE: To describe the natural history and outcomes of surveillance of duodenal neoplasia in familial adenomatous polyposis (FAP). BACKGROUND: Duodenal cancer is the most common cause of death in FAP. METHODS: Cohort study of patients prospectively enrolled in an upper endoscopic surveillance protocol from 1982 to 2012. The duodenum was assessed by side-viewing endoscopy and classified as stage 1 to 5 disease. Endoscopic and/or operative interventions were performed according to stage. RESULTS: There were 218 patients in the protocol (98 with advanced stage). They had a median of 9 endoscopies (range: 2-25) over a median of 11 years (range: 1-26). Median age at diagnosis of stage 3 disease (adenoma: 2.1-10 mm) was 41 years and stage 4 disease (adenoma >10 mm) was 45 years. Median time from first esophagogastroduodenoscopy to stage 4 disease was 22.4 years. The risk of stage 4 disease was 34.3% [95% confidence interval (CI) 23.8-43.4] at 15 years. In multivariate analysis, sex, type of colorectal surgery, years since colorectal surgery, and stage were significantly associated with risk of progression to stage 4 disease. Five of 218 (2.3%) patients developed duodenal cancer at median age of 58 years (range: 51-65). The risk of developing duodenal cancer was 2.1% (95% CI: 0-5.2) at 15 years. CONCLUSIONS: Patients with advanced duodenal polyposis progress in the severity of disease (size and degree of dysplasia); however, the rate of progression to carcinoma is slow. Aggressive endoscopic and surgical intervention, especially in the presence of large polyps and high-grade dysplasia, appears to be effective in preventing cancer deaths in FAP.

Imatinib-induced gastric antral vascular ectasia in a patient with chronic myeloid leukemia.

KEY CLINICAL MESSAGE: Gastric antral vascular ectasia (GAVE) has been reported very rarely in imatinib-treated gastrointestinal stromal tumor (GIST) and scleroderma/pulmonary hypertension patients. We present the first report of a case of GAVE in a chronic myeloid leukemia (CML) patient after treatment with imatinib. This diagnosis should be considered in CML patients with upper gastrointestinal symptoms and anemia.

Successful management of benign biliary strictures with fully covered self-expanding metal stents.

BACKGROUND & AIMS: Fully covered self-expanding metal stents (FCSEMS) are gaining acceptance for the treatment of benign biliary strictures. We performed a large prospective multinational study to study the ability to remove these stents after extended indwell and the frequency and durability of stricture resolution. METHODS: In a nonrandomized study at 13 centers in 11 countries, 187 patients with benign biliary strictures received FCSEMS. Removal was scheduled at 10-12 months for patients with chronic pancreatitis or cholecystectomy and at 4-6 months for patients who received liver transplants. The primary outcome measure was removal success, defined as either scheduled endoscopic removal of the stent with no removal-related serious adverse events or spontaneous stent passage without the need for immediate restenting. RESULTS: Endoscopic removal of FCSEMS was not performed for 10 patients because of death (from unrelated causes), withdrawal of consent, or switch to palliative treatment. For the remaining 177 patients, removal success was accomplished in 74.6% (95% confidence interval [CI], 67.5%-80.8%). Removal success was more frequent in the chronic pancreatitis group (80.5%) than in the liver transplantation (63.4%) or cholecystectomy (61.1%) groups (P = .017). FCSEMS were removed by endoscopy from all patients in whom this procedure was attempted. Stricture resolution without restenting upon FCSEMS removal occurred in 76.3% of patients (95% CI, 69.3%-82.3%). The rate of resolution was lower in patients with FCSEMS migration (odds ratio, 0.22; 95% CI, 0.11-0.46). Over a median follow-up period of 20.3 months (interquartile range, 12.9-24.3 mo), the rate of stricture recurrence was 14.8% (95% CI, 8.2%-20.9%). Stent- or removal-related serious adverse events, most often cholangitis, occurred in 27.3% of patients. There was no stent- or removal-related mortality. CONCLUSIONS: In a large prospective multinational study, removal success of FCSEMS after extended indwell and stricture resolution were achieved for approximately 75% of patients. ClincialTrials.gov number, NCT01014390.

Does integration of various ion channel measurements improve diagnostic performance in cystic fibrosis?

RATIONALE: The diagnosis of cystic fibrosis (CF) may remain inconclusive despite comprehensive evaluation. OBJECTIVES: Determine whether combined ion channel measurements (C-ICMs) obtained from different end-organ epithelia can help diagnose CF. METHODS: Prospective enrollment of (1) a training sample of 156 non-CF subjects and 107 patients with CF, and (2) a validation cohort of 202 patients with single-organ CF-like phenotypes. All subjects had genotyping, sweat test, and nasal potential difference (NPD). Principal components analysis was applied to derive various candidate C-ICMs by combining sweat chloride plus every one or two combination(s) of four NPD parameters (maximal potential difference [MaxPD], change in potential difference in response to perfusion with amiloride [ΔAmil], change after chloride-free and isoproterenol perfusion [ΔCl-free+Iso], and total change in potential difference [ΔAmil+Cl-free+Iso]). MEASUREMENTS AND MAIN RESULTS: The best of the 10 candidate C-ICMs, which combined sweat chloride and two NPD parameters (ΔCl-free+Iso and ΔAmil+Cl-free+Iso), diagnosed CF in the training sample with 100% sensitivity and specificity (CF cutoff > 0). In the validation cohort, C-ICM was normal in all subjects with normal sweat test and normal/borderline NPD, with the exception of one subject. C-ICM was abnormal in all subjects when the sweat test was abnormal and the NPD was abnormal/borderline, and when the sweat test was borderline and the NPD was abnormal. C-ICM was abnormal in 75 and 85.7% of subjects with normal sweat chloride plus abnormal NPD, and those with abnormal sweat test plus normal NPD, respectively. In borderline sweat test cases, 23.5, 90, and 100% of subjects had abnormal C-ICM with normal, borderline, and abnormal NPD, respectively. CONCLUSIONS: The concept of combining different measures of cystic fibrosis transmembrane conductance regulator function into a single composite score is feasible. The C-ICM may be useful for diagnostic determination of patients with questionable CF.

Does extensive genotyping and nasal potential difference testing clarify the diagnosis of cystic fibrosis among patients with single-organ manifestations of cystic fibrosis?

BACKGROUND: The phenotypic spectrum of cystic fibrosis (CF) has expanded to include patients affected by single-organ diseases. Extensive genotyping and nasal potential difference (NPD) testing have been proposed to assist in the diagnosis of CF when sweat testing is inconclusive. However, the diagnostic yield of extensive genotyping and NPD and the concordance between NPD and the sweat test have not been carefully evaluated. METHODS: We evaluated the diagnostic outcomes of genotyping (with 122 mutations included as disease causing), sweat testing and NPD in a prospectively ascertained cohort of undiagnosed patients who presented with chronic sino-pulmonary disease (RESP), chronic/recurrent pancreatitis (PANC) or obstructive azoospermia (AZOOSP). RESULTS: 202 patients (68 RESP, 42 PANC and 92 AZOOSP) were evaluated; 17.3%, 22.8% and 59.9% had abnormal, borderline and normal sweat chloride results, respectively. Only 17 (8.4%) patients were diagnosable as having CF by genotyping. Compared to sweat testing, NPD identified more patients as having CF (33.2%) with fewer borderline results (18.8%). The level of agreement according to kappa statistics (and the observed percentage of agreement) between sweat chloride and NPD in RESP, PANC and AZOOSP subjects was 'moderate' (65% observed agreement), 'poor' (33% observed agreement) and 'fair' (28% observed agreement), respectively. The degree of agreement only improved marginally when subjects with borderline sweat chloride results were excluded from the analysis. CONCLUSIONS: The diagnosis of CF or its exclusion is not always straightforward and may remain elusive even with comprehensive evaluation, particularly among individuals who present at an older age with single-organ manifestations suggestive of CF.

IgG4 related disease - a retrospective descriptive study highlighting Canadian experiences in diagnosis and management.

BACKGROUND: Appreciating the utility of published diagnostic criteria for autoimmune pancreatitis, when compared to the characteristics of patients clinically managed as having disease, informs and refines ongoing clinical practice. METHODS: Comparative retrospective descriptive evaluation of patients with autoimmune pancreatitis including dedicated radiology review. RESULTS: 66 subjects with radiographic OR clinical features of autoimmune pancreatitis were initially identifiable (Male: n = 50), with 55 confirmed for evaluation. The most common presentation included pain (67%), weight loss (65%), and jaundice (62%). Diffuse enlargement of the pancreas was evident in 38%, whilst multifocal, focal, or atrophic changes were seen in 7%, 33% and 9% respectively. 13% had no pancreatic parenchymal involvement. Peripheral rim enhancement was seen in 23 patients (42%). Where discernible, disease was a) Sclerosing pancreatitis and cholangitis, n = 21; b) Sclerosing cholangitis, n = 9; c) Sclerosing pancreatitis, n = 4; d) Sclerosing pancreatitis and cholangitis with pancreatic pseudotumour, n = 7; e) Sclerosing cholangitis with hepatic pseudotumour, n = 3; f) Sclerosing pancreatitis with pancreatic pseudotumour, n = 1. 56% of the patients had systemic manifestations and the median serum IgG4 at diagnosis was 5.12 g/L. The Korean criteria identified most patients (82%) compared to HISORt (55%) or the Japan Pancreas Society (56%). The majority (HISORt 60%; Japan Pancreas Society 55%; Korean 58%) met diagnostic criterion by radiological findings and elevated serum IgG4. Treatment and response did not differ when stratified by diagnostic criteria. CONCLUSION: Our descriptive and retrospective dataset confirms that in non-expert practice settings, autoimmune pancreatitis scoring systems with a focus on radiology and serology capture most patients who are clinically felt to have disease.