External validation of blue light imaging (BLI) criteria for the optical characterization of colorectal polyps by endoscopy experts.

BACKGROUND AND AIM: Recently, the BLI Adenoma Serrated International Classification (BASIC) system was developed by European experts to differentiate colorectal polyps. Our aim was to validate the BASIC classification system among the US-based endoscopy experts. METHODS: Participants utilized a web-based interactive learning system where the group was asked to characterize polyps using the BASIC criteria: polyp surface (presence of mucus, regular/irregular and [pseudo]depressed), pit appearance (featureless, round/non-round with/without dark spots; homogeneous/heterogeneous distribution with/without focal loss), and vessels (present/absent, lacy, peri-cryptal, irregular). The final testing consisted of reviewing BLI images/videos to determine whether the criteria accurately predicted the histology results. Confidence in adenoma identification (rated "1" to "5") and agreement in polyp (adenoma vs non-adenoma) identification and characterization per BASIC criteria were derived. Strength of interobserver agreement with kappa (k) value was reported for adenoma identification. RESULTS: Ten endoscopy experts from the United States identified conventional adenoma (vs non-adenoma) with 94.4% accuracy, 95.0% sensitivity, 93.8% specificity, 93.8% positive predictive value, and 94.9% negative predictive value using BASIC criteria. Overall strength of interobserver agreement was high: kappa 0.89 (0.82-0.96). Agreement for the individual criteria was as follows: surface mucus (93.8%), regularity (65.6%), type of pit (40.6%), pit visibility (66.9%), pit distribution (57%), vessel visibility (73%), and being lacy (46%) and peri-cryptal (61%). The confidence in diagnosis was rated at high ≥4 in 67% of the cases. CONCLUSIONS: A group of US-based endoscopy experts have validated a simple and easily reproducible BLI classification system to characterize colorectal polyps with >90% accuracy and a high level of interobserver agreement.

Qualitative and Quantitative Contrast-enhanced Endoscopic Ultrasound Improves Evaluation of Focal Pancreatic Lesions.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) is a sensitive method to evaluate the pancreas but its diagnostic capability for several diseases is limited. We compared the diagnostic yield of unenhanced EUS with that of contrast-enhanced EUS for focal pancreas lesions and identified and tested quantitative parameters of contrast enhancement. METHODS: We performed a prospective tandem-controlled trial in which 101 patients with focal pancreas lesions (48 with masses, 28 with cysts, and 25 with pancreatitis) underwent conventional EUS followed by contrast EUS using intravenous perflutren microspheres. The diagnosis at each stage was scored and compared with a standard (findings from surgical pathology analysis, cytologic, and/or 6-month clinical follow-up evaluations). Quantitative parameters were generated by time-intensity curve analysis. Solid lesions were divided into derivation and testing cohorts for a crossover validation analysis of the quantitative parameters. The primary outcome was diagnostic yield of unenhanced vs contrast EUS in analysis of focal pancreas lesions. RESULTS: Contrast increased the diagnostic yield of EUS from 64% (65/101 lesions accurately assessed) to 91% (92/101 lesions accurately assessed); the odds ratio [OR] was 7.8 (95% CI, 2.7-30.2) for accurate analysis of lesions by contrast-enhanced EUS relative to unenhanced EUS. The contrast increased accuracy of analysis of pancreas masses (OR, 6.0; 95% CI, 1.8-31.8), improving assessment of neuroendocrine and other (non-carcinoma) tumors. Contrast increased the diagnostic yield for pancreas cysts to 96% (27/28) compared with 71.4% (20/28) for unenhanced EUS (P = .02), due to improved differentiation of mural nodules vs debris. Time-intensity curve analysis revealed distinct patterns of relative peak enhancement (rPE) and in-slope (rIS) for different lesions following contrast injection: for adenocarcinomas, values were low rPE and low rIS; for neuroendocrine masses, values were high rPE and normal IS; and for chronic pancreatitis foci, values were normal rPE and low rIS. In the validation cohort, these parameters correctly characterized 91% of lesions and improved yield relative to unenhanced EUS (OR, 10; 95% CI, 1.4-34.0). CONCLUSIONS: Contrast-enhanced EUS improves the accuracy of analysis of focal pancreas lesions, compared with unenhanced EUS. Integration of practical quantitative parameters, specifically relative peak enhancement and in-slope, might increase the diagnostic accuracy of contrast EUS. ClinicalTrials.gov no: 02863770.

Dynamic liver test patterns do not predict bile duct stones.

BACKGROUND: Numerous models have been developed to predict choledocholithiasis. Recent work has shown that these algorithms perform suboptimally. Identification of clinical predictors with high positive and negative predictive value would minimize adverse events associated with unnecessary diagnostic endoscopic retrograde cholangiopancreatography (ERCP) while limiting the use of expensive tests including magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for indeterminate cases. METHODS: Consecutive unique inpatients who received their first ERCP at Los Angeles County Medical Center between January 2010 and November 2016 for suspected bile duct stones were reviewed. The primary outcome was the proportion of patients with specific combinations of liver enzyme patterns, transabdominal ultrasound, and clinical features who had stones confirmed on ERCP. As a secondary outcome, we assessed the performance of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification algorithm in our population. RESULTS: Of the 604 included patients, bile duct stones were confirmed in 410 (67.9%). Detailed assessment of liver enzyme patterns alone and in combination with clinical features and imaging findings yielded no highly predictive algorithms. Additionally, the ASGE high-risk criterion had a positive predictive value of only 68% for stones. For the 236 patients for whom MRCP was performed, this imaging modality was shown to have highest predictive value for the presence of stones on ERCP. CONCLUSION: Exhaustive exploration of various threshold values and dynamic patterns of liver enzymes combined with clinical features and basic imaging findings did not reveal an algorithm to accurately predict the presence of stones on ERCP. The ASGE risk stratification criteria were also insensitive in our population. Though desirable, there may be no "perfect" combination of clinical features that correlate with persistent bile duct stones. MRCP or EUS may be considered to avoid unnecessary ERCP and associated complications.

A Raman-based endoscopic strategy for multiplexed molecular imaging.

Endoscopic imaging is an invaluable diagnostic tool allowing minimally invasive access to tissues deep within the body. It has played a key role in screening colon cancer and is credited with preventing deaths through the detection and removal of precancerous polyps. However, conventional white-light endoscopy offers physicians structural information without the biochemical information that would be advantageous for early detection and is essential for molecular typing. To address this unmet need, we have developed a unique accessory, noncontact, fiber optic-based Raman spectroscopy device that has the potential to provide real-time, multiplexed functional information during routine endoscopy. This device is ideally suited for detection of functionalized surface-enhanced Raman scattering (SERS) nanoparticles as molecular imaging contrast agents. This device was designed for insertion through a clinical endoscope and has the potential to detect and quantify the presence of a multiplexed panel of tumor-targeting SERS nanoparticles. Characterization of the Raman instrument was performed with SERS particles on excised human tissue samples, and it has shown unsurpassed sensitivity and multiplexing capabilities, detecting 326-fM concentrations of SERS nanoparticles and unmixing 10 variations of colocalized SERS nanoparticles. Another unique feature of our noncontact Raman endoscope is that it has been designed for efficient use over a wide range of working distances from 1 to 10 mm. This is necessary to accommodate for imperfect centering during endoscopy and the nonuniform surface topology of human tissue. Using this endoscope as a key part of a multiplexed detection approach could allow endoscopists to distinguish between normal and precancerous tissues rapidly and to identify flat lesions that are otherwise missed.

Massive pancreatic pseudocyst with portal vein fistula: case report and proposed treatment algorithm.

Pancreatic pseudocyst is a relatively common occurrence resulting from acute or chronic pancreatitis. However, a rare subset of these patients present with a pseudocyst fistulizing into the portal vein. We present the case of a 58 year-old woman with a rapidly expanding pancreatic pseudocyst with portal venous fistulization causing portal vein thrombosis, in addition to biliary and duodenal obstruction. The patient underwent surgical decompression with a cyst-gastrostomy and was well until one week post-operatively when she experienced massive gastrointestinal hemorrhage leading to her death. A review of the literature is presented and a treatment algorithm to manage patients with pancreatic pseudocyst to portal vein fistula is proposed.

Prevention and management of post-ERCP pancreatitis.

Pancreatitis remains as one of the most frequent and serious complications of ERCP. Research has identified several patient-related and procedural risk factors, which help guide the endoscopist in prophylaxis and management of pancreatitis. Recent studies have had a major impact on both procedural techniques and pharmacological methods for prophylaxis of post-ERCP pancreatitis. The purpose of this article is to review the relevant literature and describe the most recent and effective approaches in prevention and management of post-ERCP pancreatitis.

Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts.

BACKGROUND: Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts. METHODS: A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed. RESULTS: Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%). CONCLUSION: Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

A prospective study of total gastrectomy for CDH1-positive hereditary diffuse gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome. Up to 30% of families with HDGC have mutations in the E-cadherin gene, CDH1. The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively. METHODS: Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. Proportions were compared by Fisher's exact test, and survival by the Breslow modification of the Wilcoxon rank-sum test. RESULTS: Each patient underwent total gastrectomy (TG), and 17 (94%) were found to have signet ring cell adenocarcinoma. Twelve of 13 asymptomatic patients had T1, N0 cancer, and only 2/12 (16%) had it diagnosed preoperatively despite state-of-the-art screening methods. Each asymptomatic patient did well postoperatively, and no patient has recurred. For five symptomatic patients, each (100%) was found to have signet ring cell adenocarcinoma (P = 0.002 versus asymptomatic) by preoperative endoscopy; three (60%) had lymph node involvement and two (40%) had distant metastases at time of operation. Two-year survival was 100% for asymptomatic and 40% for symptomatic patients (P < 0.01). CONCLUSION: The data show that asymptomatic patients with family history of HDGC and CDH1 mutation have high probability of having signet ring cell adenocarcinoma of the stomach that is not able to be diagnosed on endoscopy; when symptoms arise, the diagnosis can be made by endoscopy, but they have metastases and decreased survival. Surveillance endoscopy is of limited value, and prophylactic gastrectomy (PG) is recommended for patients with family history of HDGC and CDH1 mutations.

Determining scope position during colonoscopy without use of ionizing radiation or magnetic imaging: the enhanced mapping ability of the NeoGuide Endoscopy System.

BACKGROUND: Knowledge of the position and shape of the endoscope could overcome many challenges of performing colonoscopy, e.g., loop formation. A novel computer-assisted colonoscope (NeoGuide Endoscopy System) delivers a real-time, three-dimensional map of the tip position and insertion tube shape in addition to the video image of the colon lumen. The aim of this study is to evaluate the mapping capabilities of the NeoGuide Endoscopy System in terms of colonic looping, insertion depth, tip position, and tip angle formation. METHODS: Ten endoscopists with various levels of experience were each shown 70 map images generated by the NeoGuide endoscopy system in a benchtop anatomical colon model. First endoscopists were asked to determine the tip angle based on the map image and the system's corresponding tip positioning aid (20 images). In the second part they had to identify the scope-tip position in the colon model (40 images). In the third part ten images were presented for identification of colonic loops. RESULTS: The tip angle was correctly identified in 99% (198/200) of images. Using only the map images the scope position was accurately determined in 87.5% (350/400). Identification of colonic looping of the scope was appropriate in 99% (99/100). Overall accuracy was 92.4%, and overall positive predictive value was 94.9%. CONCLUSION: Three-dimensional map images generated by the NeoGuide endoscopy system provide accurate information regarding tip position, insertion tube position, and colonic looping.

EUS-guided gold fiducial insertion for image-guided radiation therapy of pancreatic cancer: 50 successful cases without fluoroscopy.

BACKGROUND: Image-guided radiation therapy (IGRT) accurately delivers a high dose of potentially tumoricidal radiation to its target while sparing adjacent healthy tissue. Application of IGRT to unresectable pancreatic cancer requires the use of fiducials to track the precise location of the tumor. Fiducial markers have been successfully placed endoscopically. OBJECTIVE: To determine the feasibility of EUS-guided gold fiducial placement for IGRT. DESIGN: Prospective case series. SETTING: Tertiary medical center. PATIENTS: Consecutively referred patients with locally advanced unresectable pancreatic adenocarcinoma for EUS-guided insertion of gold fiducials from December 2006 to February 2009. INTERVENTIONS: Under only EUS guidance, fiducial markers were deployed into or near the tumor by using a 19-gauge needle. In most cases, a sterile water injection technique was used to insert the fiducials. Fluoroscopy was not used in any case. MAIN OUTCOME MEASUREMENTS: Successful placement of an adequate number of fiducials to proceed with IGRT as determined by CT. RESULTS: Fifty-seven consecutive patients were included. Fifty cases (88%) were successful. Of the cases in which fiducial placement was attempted and follow-up was adequate, 94% (50 of 53) of cases were successful. LIMITATIONS: Single-center, nonrandomized study. CONCLUSIONS: EUS-guided fine-needle insertion was safe and effective in delivering gold fiducial markers for image-guided radiation therapy. Fluoroscopy was not required for successful fiducial placement.

Endoscopy is accurate, safe, and effective in the assessment and management of complications following gastric bypass surgery.

OBJECTIVES: Roux-en-Y gastric bypass (RYGB) is a common intervention for morbid obesity. Upper gastrointestinal (UGI) symptoms are frequent and difficult to interpret following RYGB. The aim of our study was to examine the role of endoscopy in evaluating UGI symptoms after RYGB and to assess the safety and efficacy of endoscopic therapy. METHODS: Between 1998 and 2005, a total of 1,079 patients underwent RYGB for clinically severe obesity and were followed prospectively. Patients with UGI symptoms after RYGB who were referred for endoscopy were studied. RESULTS: Of 1,079 patients, 76 (7%) who underwent RYGB were referred for endoscopy to evaluate UGI symptoms. Endoscopic findings included normal surgical anatomy (n=24, 31.6%), anastomotic stricture (n=40, 52.6%), marginal ulcer (n=12, 15.8%), unraveled nonabsorbable sutures causing functional obstruction (n=3, 4%) and gastrogastric fistula (n=2, 2.6%). Patients with abnormal findings on endoscopy presented with UGI symptoms at a mean of 110.7 days from their RYGB, which was significantly shorter than the time of 347.5 days for patients with normal endoscopy (P<0.001). A total of 40 patients with anastomotic strictures underwent 86 endoscopic balloon dilations before complete symptomatic relief. In one patient, a needle knife was used to open a completely obstructed anastomotic stricture. Unraveled, nonabsorbable suture material was successfully removed using endoscopic scissors in three patients. CONCLUSIONS: Patients presenting with UGI symptoms less than 3 months after surgery are more likely to have an abnormal finding on endoscopy. Endoscopic balloon dilation is safe and effective in managing anastomotic strictures. Endoscopic scissors are safe and effective in removing unraveled, nonabsorbable sutures contributing to obstruction.

Use of flexible endoscopic scissors to cut obstructing suture material in gastric bypass patients.

With the epidemic increase in obesity in the USA and consequent increased demand for bariatric surgery, new complications of the surgery are being described. The most common surgery practiced is the Roux-en-Y gastric bypass (RYGBP). Unraveling of suture material at the gastrojejunal anastomosis may occur, which may be troublesome if nonabsorbable suture is employed. We describe, for the first time, two patients who developed obstructive symptoms as a consequence of food matter/bezoars entrapped within a mesh of unraveled nonabsorbable suture material at their anastomoses. One of these patients also developed ulceration, presumably as a result of pressure necrosis from the entrapped bezoar. We describe a third patient where the placement of nonabsorbable sutures led to obstructive symptoms by limiting distensibility at an otherwise satisfactory anastomosis. We also describe for the first time, the use of a new endoscopic scissors in cutting luminal suture material with subsequent resolution of the clinical problem.

Preoperative endoscopic screening for laparoscopic Roux-en-Y gastric bypass has a low yield for anatomic findings.

BACKGROUND: Patients undergoing laparoscopic Roux-en-Y bariatric surgery undergo screening esophagoduodenoscopy (EGD) during preoperative evaluation. The hypothesis is to examine the utility of this examination. The purpose of this study was to evaluate the prevalence of clinically significant upper gastrointestinal (UGI) tract findings at screening EGD in patients undergoing laparoscopic Roux-en-Y bariatric surgery. A secondary aim was to determine whether preprocedure symptoms could predict findings at EGD. METHODS: We evaluated records of patients undergoing EGD prior to bariatric surgery between 2000 and 2005 at the Stanford University Medical Center. Clinical, endoscopic, and pathological data were analyzed. The prevalence of endoscopic findings of clinical significance was determined. RESULTS: Two hundred seventy two complete patient records were identified and included in the study. Of these, 237 (87%) were female and 197 (72%) were Caucasian. The mean age was 43 +/- 9.68 years and mean body mass index was 48 +/- 7.95 kg/m(2). Of the 272 patients, 33 (12%) had EGD findings of clinical significance including erosive esophagitis (3.7%), Barrett's esophagus (3.7%), gastric ulcers (2.9%), erosive gastritis (1.8%), duodenal ulcers (0.7%), and gastric carcinoid (0.3%). No patients had malignancy. Of these 33 patients, 22 (67%) had UGI symptoms. CONCLUSIONS: Significant findings at screening EGD were found in 12% of patients. While EGD may be low-yield, the findings could be useful in guiding clinical decision making.

Endoscopic ultrasound-guided intratumoural therapy for pancreatic cancer.

Pancreatic cancer is the second most frequent gastrointestinal malignancy and carries a dismal prognosis. The current standard of care includes resection, if possible, as well as systemic chemoradiation therapy. Endoscopic ultrasound (EUS) is an established technique for the diagnosis and staging of pancreatic adenocarcinoma. Interventional EUS via fine needle injection (FNI) for the treatment of pancreatic cancer is a rapidly expanding field. The present article reviews the up-to-date developments in EUS FNI for intratumoural pancreatic cancer therapy, including antitumoural agents, immunotherapy, ablative techniques and new delivery systems. The therapeutic modalities discussed are currently under development and will hopefully reach clinical practice if benefit is demonstrated through clinical trials. EUS FNI may be an exciting new technique for the delivery of desperately needed novel therapies for pancreatic cancer.

Diagnosis of pancreatic gastrointestinal stromal tumor by EUS guided FNA.

CONTEXT: Gastrointestinal stromal tumors of the pancreas are very rare. Only two case reports have been published, both with diagnoses made on surgical pathology. We present the first case of pancreatic stromal tumor diagnosed by endoscopic ultrasound guided fine needle aspiration. CASE REPORT: A 47-year-old male presented with self limited nausea and vomiting. A CT scan revealed a subtle, hypervascular mass in the uncinate process of the pancreas. Endoscopic ultrasound confirmed the pancreatic mass and fine needle aspiration was performed giving a bloody sample. Cytology showed spindle cell proliferation with CD117 positive immunohistochemistry, confirming a pancreatic gastrointestinal stromal tumor. CONCLUSION: We present a case of pancreatic stromal tumor diagnosed by endoscopic ultrasound guided fine needle aspiration. Although very rare in the pancreas, gastrointestinal stromal tumors should be considered in the differential diagnosis of solid pancreatic masses and blood aspirates.

NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes.

During the development of neoplasia, epithelial tissues undergo biochemical and structural changes that can manifest in tissue fluorescence. There have been several reports on different in vivo fluorescence characteristics between normal and precancerous (dysplastic) tissues. However, it has been difficult to identify and quantify the origins of these changes, mainly because of distortions introduced in measured tissue fluorescence spectra by tissue scattering and absorption. Such distortions can be removed by combining information in simultaneously measured fluorescence and reflectance spectra. Thus, we can recover the intrinsic (undistorted) tissue fluorescence. In this report, we show that extraction of the intrinsic fluorescence allows us: (a) to determine the fluorescence spectra of NAD(P)H and collagen in an in vivo environment, and (b) to use these NAD(P)H and collagen spectra to describe, quantitatively, diagnostically significant biochemical changes between normal and dysplastic tissues. Specifically, by analyzing intrinsic fluorescence of human epithelial tissue as it becomes deoxygenated in vivo, we can resolve the fluorescence spectra of NAD(P)H and collagen, two of the major tissue fluorophores. This is important because fluorescence depends on the local environment of the chromophore. Then, we extract the intrinsic fluorescence spectra of sites from 35 patients with suspected cervical lesions and 7 patients with Barrett's esophagus and describe them accurately as a linear combination of NAD(P)H and collagen contributions. In both tissue cases, we find that low collagen and high NAD(P)H fluorescence characterizes the high-grade dysplastic lesions when compared with nondysplastic tissues. These data present evidence for the presence of detectable levels of NAD(P)H fluorescence in human epithelial tissues in an in vivo setting and demonstrate that NAD(P)H and collagen may be used as quantitative fluorescence biomarkers for in vivo detection of dysplasia in the cervix and the esophagus.

Computed tomography, endoscopic, laparoscopic, and intra-operative sonography for assessing resectability of pancreatic cancer.

Pancreas cancer is the fourth leading cancer killer in adults. Cure of pancreas cancer is dependent on the complete surgical removal of localized tumor. A complete surgical resection is dependent on accurate preoperative and intra-operative imaging of tumor and its relationship to vital structures. Imaging of pancreatic tumors preoperatively and intra-operatively is achieved by pancreatic protocol computed tomography (CT), endoscopic ultrasound (EUS), laparoscopic ultrasound (LUS), and intra-operative ultrasound (IOUS). Multi-detector CT with three-dimensional (3-D) reconstruction of images is the most useful preoperative modality to assess resectability. It has a sensitivity and specificity of 90 and 99%, respectively. It is not observer dependent. The images predict operative findings. EUS and LUS have sensitivities of 77 and 78%, respectively. They both have a very high specificity. Further, EUS has the ability to biopsy tumor and obtain a definitive tissue diagnosis. IOUS is a very sensitive (93%) method to assess tumor resectability during surgery. It adds little time and no morbidity to the operation. It greatly facilitates the intra-operative decision-making. In reality, each of these methods adds some information to help in determining the extent of tumor and the surgeon's ability to remove it. We rely on pancreatic protocol CT with 3-D reconstruction and either EUS or IOUS depending on the tumor location and operability of the tumor and patient. With these modern imaging modalities, it is now possible to avoid major operations that only determine an inoperable tumor. With proper preoperative selection, surgery is able to remove tumor in the majority of patients.