Sean T. McCarthy

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (nu200a=u200a6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94u200a%, 82u200a%, and 89u200a%, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κu200a=u200a0.67, 95u200a%CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κu200a=u200a0.78u200a±u200a0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κu200a=u200a0.63; IOR κu200a=u200a0.76u200a±u200a0.11), bright particles on a dark background of pseudocysts (IOA κu200a=u200a0.71; IOR κu200a=u200a0.78u200a±u200a0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κu200a=u200a0.62; IOR κu200a=u200a0.68u200a±u200a0.20). Three (6.1u200a% of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. Study registration: NCT02516488

Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos)

BACKGROUND AND AIMSnEUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis.nnnMETHODSnSix endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (nxa0= 23) or clinical (nxa0= 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used.nnnRESULTSnA total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κxa0= 0.81 (almost perfect); 95% CI, 0.71-0.90; and κxa0= 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κxa0= 0.83 (almost perfect); 95% CI, 0.73-0.92; and κxa0= 0.85 ± 0.11 (almost perfect), respectively.nnnCONCLUSIONSnEUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).

An Unusual Finding During Evaluation for Dysphagia

Question: A 27-year-old man with a past medical history notable for asthma, food allergies, and congenital pectus excavatum presented with worsening dysphagia. He reported a 5-year history of intermittent solid food dysphagia but denied any history of food impaction. A computed tomography scan of the chest showed an elongated mediastinal mass with associated mass effect on the left atrium and esophageal lumen and esophageal wall thickening without mediastinal lymphadenopathy. On upper endoscopy, a large fistulous opening in the lower third of the esophagus was found corresponding to the ‘mass’ seen on computed tomography (Figure A). Proximal esophageal biopsies showed mildly increased intraepithelial eosinophils (up to 10 per high-power field [HPF]). An esophagram showed the large opening without extravasation of contrast or communication with the thoracic cavity (Figure B). The patient was managed expectantly and started on twice a day proton pump inhibitor. Follow-up endoscopy in 8 weeks showed a dramatic improvement in the size of the defect (Figure C, D). Repeat esophageal biopsies showed increased intraepithelial eosinophils, up to 25 per HPF in the distal esophagus and up to 30 per HPF in the proximal esophagus (Figure E). What is the most likely explanation for this patient’s endoscopic findings? Look on page 703 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Pan-Esophageal Pressurization in Achalasia: Is 30 mmHg the Best Discriminator for Predicting Good Treatment Outcome?

Background: Achalasia is classically defined by absent peristalsis and impaired EGJ relaxation. Recent data from esophageal pressure topography (EPT) studies suggest that additional features defining esophageal pressurization patterns may define clinically relevant subtypes. In particular, pan-esophageal pressurization (PEP) >30 mmHg has been shown to be a predictor of good treatment outcome. However, the 30 mmHg threshold for defining PEP was arbitrary and there is concern that this threshold value may be too high. The aim of this study was to evaluate the relationship between PEP values 30 mmHg). Impaired EGJ relaxation was defined as an Integrated Relaxation Pressure (IRP) >15 mmHg relative to gastric pressure. The level of PEP, spanning from the UES to the EGJ, was measured with the isobaric contour tool (ManoViewTM) as the pressure (relative to atmospheric) first showing a 1cm break. The average of the two highest PEP measurements was used to classify patients into two groups for comparison: A) ≤ 15 mmHg and B) >15 mmHg but ≤ 30 mmHg. Treatment outcome after therapy was determined by chart review. Failure of therapy was defined as continued symptoms prompting further intervention, continued weight loss, or related hospitalization. Results: Of the 3600 patients, 33 patients (20M/13F, mean age 54) were found to have an abnormal IRP and no evidence of contractile activity or PEP > 30 mmHg in at least 2 swallows. The mean PEP in this group was 14.1 (± 6.5) mmHg. Patients with PEP 15 mmHg, approaching statistical significance with a p value of 0.076. A comparison between the two groups of PEP is presented in the table. Conclusion: Pan-esophageal pressurization measurements are an important predictor of outcome in Type I achalasia. Although statistical significance was not achieved, our data confirm a trend towards better outcome in the group with higher values of PEP. We hypothesize that the ability of the esophagus to pressurize to a level above 15 mmHg likely provides sufficient driving pressure for flow across the EGJ after achalasia therapy. Thus, the threshold PEP for defining Type II achalasia may be lower than the previously described threshold of 30 mmHg. Results Table

62 Use of the Hospital Odynophagia Dysphagia Questionnaire as a Measure of Patient Reported Outcome in a Comparative Analysis of Achalasia Treatments

Introduction: Although achalasia is the best defined esophageal motor disorder, no standardized patient reported outcome measure currently exists for intervention trials. Furthermore, treatment outcome from a patients perspective can be quite different from the goals and assessment of the treating physician. This may reflect different levels of expectation and also a lack of a threshold definition of success. Our goal was to compare patient reported outcomes assessed with the Hospital Odynophagia Dysphagia Questionnaire (HODQ) to the clinical impression of the treating physician. Methods: 40 non-spastic achalasia patients (15F, ages 24-82) undergoing either pneumatic dilation (PD) or Heller myotomy (HM) were contacted by phone to assess clinical outcome using the HODQ. The HODQ is comprised of 10 questions related to post-procedure frequency of symptoms, severity of symptoms, and food impaction events (scores ranging 0-5 per question, max score of 50). A HODQ score ≤6 is the upper limit of normal. Post-treatment HODQ scores between HM and PD were compared. In addition, we compared the HODQ score with the clinical impression of the treating physician. A good outcome was defined as the physicians impression that the patient had a symptomatic improvement, no weight loss, and no need for further treatment. A poor response was defined as minimal to no improvement requiring further intervention. Results: Of the 40 patients, 15 had HM (3F, ages 24-65) and 25 had PD (12F, ages 22-82). The meanHODQ score after follow-up of 3-30monthswas 7.85 (SD, 8.2). Patients that underwent HM had a lower mean HODQ score compared with PD (HM, 5.7 SD (5.9); PD, 9.2, SD (9.2)), but this was not statistically significant (p=0.15). Thirty-two patients (80%) had a good clinical outcome based on the treating physician assessment, while 5 had a poor outcome and another 3 had insufficient documentation to define physician assessed outcome. Fourteen (44%) of the 32 patients deemed to have a good outcome by their physician had an abnormal HODQ score (mean 12.4, range, 7-25). Conclusion: There is substantial discepancy in physician-reported versus patient-reported outcome in achalasia treatment. Although 80% of the patients were assessed as treatment successes by their physician, 44% had a HODQ score suggesting significant persistent dysphagia. Future studies of achalasia teatment should recognize the distinction between the expectations of the patients in terms of symptom relief and the goals of reducing complications such asmalnutrition and aspiration. In addition, achalasia patients shoiuld be counseled that some dysphagia will likely persist despite successful therapy.