Nirav Thosani

Role of EUS-FNA-Based Cytology in the Diagnosis of Mucinous Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis

BackgroundPreoperative diagnosis of malignancy in pancreatic cystic lesions (PCLs) remains challenging. Most non-mucinous cystic lesions (NMCLs) are benign, but mucinous cystic lesions (MCLs) are more likely to be premalignant or malignant.AimThe aim of this study was to assess the sensitivity, specificity, and positive and negative likelihood ratios (LRs) of EUS-FNA-based cytology in differentiating MCLs from non-mucinous PCLs.MethodsWe conducted a comprehensive search of MEDLINE, SCOPUS, Cochrane, and “CINAHL Plus” databases to identify studies, in which the results of EUS-FNA-based cytology of PCLs were compared with those of surgical biopsy or surgical excision histopathology. A DerSimonian-Laird random effect model was used to estimate the pooled sensitivity, specificity, and LRs, and a summary receiver-operating characteristic (SROC) curve was constructed.ResultsWe included 376 patients from 11 distinct studies who underwent EUS-FNA-based cytology and also had histopathological diagnosis. The pooled sensitivity and specificity in diagnosing MCLs were 0.63 (95% CI, 0.56–0.70) and 0.88 (95% CI, 0.83–0.93), respectively. The positive and negative LRs in diagnosing MCLs were 4.46 (95% CI, 1.21–16.43) and 0.46 (95% CI, 0.25–0.86), respectively. The area under the curve (AUC) was 0.89.ConclusionsEUS-FNA-based cytology has overall low sensitivity but good specificity in differentiating MCLs from NMCLs. Further research is required to improve the overall sensitivity of EUS-FNA-based cytology to diagnose MCLs while evaluating PCL.

Diagnostic accuracy of EUS in differentiating mucosal versus submucosal invasion of superficial esophageal cancers: a systematic review and meta-analysis

BACKGROUND The prognosis of esophageal cancer (EC) depends on the depth of tumor invasion and lymph node metastasis. EC limited to the mucosa (T1a) can be treated effectively with minimally invasive endoscopic therapy, whereas submucosal (T1b) EC carries relatively high risk of lymph node metastasis and requires surgical resection. OBJECTIVE To determine the diagnostic accuracy of EUS in differentiating T1a EC from T1b EC. DESIGN We performed a comprehensive search of MEDLINE, SCOPUS, Cochrane, and CINAHL Plus databases to identify studies in which results of EUS-based staging of EC were compared with the results of histopathology of EMR or surgically resected esophageal lesions. DerSimonian-Laird random-effects model was used to estimate the pooled sensitivity, specificity, and likelihood ratio, and a summary receiver operating characteristic (SROC) curve was created. SETTING Meta-analysis of 19 international studies. PATIENTS Total of 1019 patients with superficial EC (SEC). INTERVENTIONS EUS and EMR or surgical resection of SEC. MAIN OUTCOME MEASUREMENTS Sensitivity and specificity of EUS in accurately staging SEC. RESULTS The pooled sensitivity, specificity, and positive and negative likelihood ratio of EUS for T1a staging were 0.85 (95% CI, 0.82-0.88), 0.87 (95% CI, 0.84-0.90), 6.62 (95% CI, 3.61-12.12), and 0.20 (95% CI, 0.14-0.30), respectively. For T1b staging, these results were 0.86 (95% CI, 0.82-0.89), 0.86 (95% CI, 0.83-0.89), 5.13 (95% CI, 3.36-7.82), and 0.17 (95% CI, 0.09-0.30), respectively. The area under the curve was at least 0.93 for both mucosal and submucosal lesions. LIMITATIONS Heterogeneity was present among the studies. CONCLUSION Overall EUS has good accuracy (area under the curve ≥0.93) in staging SECs. Heterogeneity among the included studies suggests that multiple factors including the location and type of lesion, method and frequency of EUS probe, and the experience of the endosonographer can affect the diagnostic accuracy of EUS.

Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes in both adults and children. NAFLD has a histologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. It is imperative to distinguish simple steatosis from NASH since the latter has a progressive disease course and can lead to end-stage liver disease. Liver biopsy has been considered as the gold standard for the diagnosis of NASH. However, liver biopsy is invasive, costly, and can rarely cause significant morbidity (risk of morbidity, 0.06-0.35%; risk of mortality, 0.1-0.01%). Imaging studies such as ultrasonography, computed tomography, and magnetic resonance imaging have limited sensitivity in detecting steatosis and cannot distinguish steatosis from NASH. Alanine aminotransferase (ALT) has been used as a surrogate marker for liver injuries. However, ALT is not an ideal marker for either diagnosis of NAFLD or distinguishing steatosis from NASH. Better noninvasive biomarkers or panels of biomarkers that are cheaper, reliable, and reproducible are urgently needed for patients with NASH to assist in establishing diagnosis, providing risk information, and monitoring disease progression and treatment response. In this article, we plan to concisely review the current advances in the use of biomarkers for the diagnosis of NASH.

ASGE Technology Committee systematic review and meta-analysis assessing the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for adopting real-time imaging–assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett’s esophagus

BACKGROUND AND AIMS Endoscopic real-time imaging of Barretts esophagus (BE) with advanced imaging technologies enables targeted biopsies and may eliminate the need for random biopsies to detect dysplasia during endoscopic surveillance of BE. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. METHODS We conducted meta-analyses calculating the pooled sensitivity, negative predictive value (NPV), and specificity for chromoendoscopy by using acetic acid and methylene blue, electronic chromoendoscopy by using narrow-band imaging, and confocal laser endomicroscopy (CLE) for the detection of dysplasia. Random effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. RESULTS The pooled sensitivity, NPV, and specificity for acetic acid chromoendoscopy were 96.6% (95% confidence interval [CI], 95-98), 98.3% (95% CI, 94.8-99.4), and 84.6% (95% CI, 68.5-93.2), respectively. The pooled sensitivity, NPV, and specificity for electronic chromoendoscopy by using narrow-band imaging were 94.2% (95% CI, 82.6-98.2), 97.5% (95% CI, 95.1-98.7), and 94.4% (95% CI, 80.5-98.6), respectively. The pooled sensitivity, NPV, and specificity for endoscope-based CLE were 90.4% (95% CI, 71.9-97.2), 98.3% (95% CI, 94.2-99.5), and 92.7% (95% CI, 87-96), respectively. CONCLUSIONS Our meta-analysis indicates that targeted biopsies with acetic acid chromoendoscopy, electronic chromoendoscopy by using narrow-band imaging, and endoscope-based CLE meet the thresholds set by the ASGE PIVI, at least when performed by endoscopists with expertise in advanced imaging techniques. The ASGE Technology Committee therefore endorses using these advanced imaging modalities to guide targeted biopsies for the detection of dysplasia during surveillance of patients with previously nondysplastic BE, thereby replacing the currently used random biopsy protocols.

Photodynamic therapy vs radiofrequency ablation for Barrett’s dysplasia: Efficacy,safety and cost-comparison

AIM To compare effectiveness, safety, and cost of photodynamic therapy (PDT) and radiofrequency ablation (RFA) in treatment of Barretts dysplasia (BD). METHODS Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared. Thirty-three patients with high-grade dysplasia (HGD) had treatment with porfimer sodium photosensitzer and 630 nm laser (130 J/cm), with maximum of 3 treatment sessions. Fifty-three patients with BD (47 with low-grade dysplasia -LGD, 6 with HGD) had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions. Both groups received proton pump inhibitors twice daily. Endoscopic biopsies were acquired at 2 and 12 mo after enrollment, with 4-quadrant biopsies every 1 cm of the original BE extent. A complete histological resolution response of BD (CR-D) was defined as all biopsies at the last endoscopy session negative for BD. Fishers exact test was used to assess differences between the two study groups for primary outcomes. For all outcomes, a two-sided P value of less than 0.05 was considered to indicate statistical significance. RESULTS Thirty (91%) PDT patients and 39 (74%) RFA were men (P = 0.05). The mean age was 70.7 ± 12.2 and 65.4 ± 12.7 (P = 0.10) year and mean length of BE was 5.4 ± 3.2 cm and 5.7 ± 3.2 cm (P = 0.53) for PDT and RFA patients, respectively. The CR-D was (18/33) 54.5% with PDT vs (47/53) 88.7% with RFA (P = 0.001). One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA. PDT was five times more costly than RFA at our institution. The two groups were not randomized and had different BD grading are the limitations of the study. CONCLUSION In our experience, RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Radiation exposure to patients during ERCP is significantly higher with low-volume endoscopists

BACKGROUND Patients are exposed to radiation during ERCP, and this may increase their lifetime risk of the development of cancer and other deleterious radiation effects. OBJECTIVE To evaluate the association between the endoscopists ERCP volume and the patient radiation dose during ERCP. DESIGN Single-center, retrospective study. SETTING Tertiary referral center. PATIENTS AND INTERVENTIONS A total of 197 patients undergoing 331 ERCPs. MAIN OUTCOME MEASUREMENTS Patient radiation exposure parameters including fluoroscopy time, total radiation dose, dose area product, and effective dose for all ERCPs performed at our academic medical center by 2 high-volume endoscopists (HVEs) (≥200 ERCPs/year) and 7 low-volume endoscopists (LVEs). Radiation exposure for each ERCP was adjusted against a validated procedure complexity scale and the Stanford Fluoroscopy Complexity Score, which was created based on the numbers of interventions that would mandate additional radiation exposure. RESULTS ERCPs performed by LVEs were associated with a significantly higher median total radiation dose (98.30 mGy vs 74.13 mGy), dose area product (13.98 Gy-cm(2) vs 8.8 Gy-cm(2)), and effective dose (3.63 mSv vs 2.28 mSv), despite lower median Stanford Fluoroscopy Complexity Scores (3.0 vs 6.0) compared with HVEs. No significant difference was noted in median fluoroscopy time (4.0 minutes vs 3.30 minutes) between LVEs and HVEs. LIMITATIONS Retrospective, single-center study at a tertiary referral center. CONCLUSION ERCPs performed by LVEs are associated with significantly higher radiation exposure to patients compared with those performed by HVEs despite the fact that procedures performed by HVEs are of greater complexity.

Underwater endoscopic mucosal resection for recurrences after previous piecemeal resection of colorectal polyps (with video)

BACKGROUND Conventional endoscopic treatment of a recurrent adenoma after piecemeal EMR (PEMR) of a colorectal laterally spreading tumor (LST) is technically difficult with low en bloc resection rates because of the inability to snare fibrotic residual. OBJECTIVE To assess the feasibility of salvage underwater EMR (UEMR) for the treatment of recurrent adenoma after PEMR of a colorectal LST. DESIGN Retrospective, cross-sectional study. SETTING Single, tertiary-care referral center. PATIENTS Patients who have recurrent adenoma after PEMR of colorectal LST (≥2 cm). INTERVENTIONS UEMR versus EMR. MAIN OUTCOME MEASUREMENT En bloc resection rate, endoscopic complete removal rate, recurrence rate on follow-up colonoscopy, adjunctive ablation rate with argon plasma coagulation (APC) during salvage procedure, and independent predictive factors for successful en bloc resection and endoscopic complete removal. RESULTS Eighty salvage procedures (36 UEMRs vs 44 EMRs) were analyzed. En bloc resection rate (47.2% vs 15.9%, P = .002) and endoscopic complete removal rate (88.9% vs 31.8%, P < .001) were higher in the UEMR group than in the EMR group. APC ablation of visible residual during salvage procedure was lower in UEMR group than EMR group (11.1% vs 65.9%, P < .001). Recurrence rate on follow-up colonoscopy was significantly lower in the UEMR group than the EMR group (10% vs 39.4%, P = .02). UEMR was an independent predictor of successful en bloc resection and endoscopic complete removal. LIMITATIONS Retrospective, single-center study. CONCLUSIONS UEMR can be a useful and feasible technique as a salvage procedure for recurrent colorectal adenoma after PEMR.

Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: A meta-analysis

AIM To conduct a systematic review and meta-analysis of published population-based randomized controlled trials (RCTs). METHODS RCTs evaluating the difference in mortality and incidence of colorectal cancer (CRC) between a screening flexible sigmoidoscopy (FS) group and control group (not assigned to screening FS) with a minimum 5 years median follow-up were identified by a search of MEDLINE and EMBASE databases and the Cochrane Central Register for Controlled Trials through August 2013. Random effects model was used for meta-analysis. RESULTS Four RCTs with a total of 165659 patients in the FS group and 249707 patients in the control group were included in meta-analysis. Intention-to-treat analysis showed that there was a 22% risk reduction in total incidence of CRC (RR = 0.78, 95%CI: 0.74-0.83), 31% in distal CRC incidence (RR = 0.69, 95%CI: 0.63-0.75), and 9% in proximal CRC incidence (RR = 0.91, 95%CI: 0.83-0.99). Those who underwent screening FS were 18% less likely to be diagnosed with advanced CRC (OR = 0.82, 95%CI: 0.71-0.94). There was a 28% risk reduction in overall CRC mortality (RR = 0.72, 95%CI: 0.65-0.80) and 43% in distal CRC mortality (RR = 0.57, 95%CI: 0.45-0.72). CONCLUSION This meta-analysis suggests that screening FS can reduce the incidence of proximal and distal CRC and mortality from distal CRC along with reduction in diagnosis of advanced CRC.

Diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs: A systematic review and meta-analysis

OBJECTIVES Differential diagnosis of malignant and benign intraductal papillary mucinous neoplasms (IPMNs) is essential to determine the optimal treatment. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently used to diagnose pancreatic cystic lesions worldwide, but few studies have focused on the diagnostic yield to distinguish malignant and benign IPMNs. Therefore, we aim to systematically review the diagnostic yield of EUS-FNA-based cytology to distinguish malignant and benign IPMNs. METHODS Relevant studies with a reference standard of definitive surgical histology which published between 2002 and 2012 were identified via MEDLINE and SCOPUS. Malignant IPMNs included invasive adenocarcinoma, carcinoma in situ, and high-grade dysplasia. RESULTS Four studies with 96 patients were included in this meta-analysis. For diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs, the pooled sensitivity and specificity were 64.8% (95% CI, 0.44-0.82) and 90.6% (95% CI, 0.81-0.96), respectively. Similarly, the positive likelihood ratio and negative likelihood ratio were 6.35 (95% CI, 2.95-13.68) and 0.43 (95% CI, 0.14-1.34), respectively. Malignant IPMNs were observed in 20.8% (20/96) of patients in EUS-FNA studies. CONCLUSIONS EUS-FNA-based cytology has good specificity but poor sensitivity in differentiating benign from malignant IPMNs. Newer techniques or markers are needed to improve diagnostic yield.

Diagnostic yield of endoscopic retrograde cholangiopancreatography‐based cytology for distinguishing malignant and benign intraductal papillary mucinous neoplasm: Systematic review and meta‐analysis

Published studies have revealed the diagnostic yield of cytology obtained from endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing malignant and benign intraductal papillary mucinous neoplasm (IPMN). However as a result of small sample sizes, the overall magnitude of benefit is unknown. Additionally, the optimal endoscopic procedure for cytology acquisition is also unclear. The aim of the present study was to evaluate the diagnostic yield of ERCP‐based cytology in patients with IPMN and clarify the optimal sampling technique.