Publications by authors named "Virendra Joshi"

31 Publications

Probe-based confocal laser endomicroscopy in the evaluation of dominant strictures in patients with primary sclerosing cholangitis: results of a U.S. multicenter prospective trial.

Gastrointest Endosc 2021 09 30;94(3):569-576.e1. Epub 2021 Mar 30.

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Background And Aims: Patients with primary sclerosing cholangitis (PSC) and dominant biliary strictures carry increased risk for the development of cholangiocarcinoma. Although ERCP-based techniques including brush cytology and intraductal biopsy sampling represent first-line tissue sampling methods for dominant strictures, sensitivity is low. Probe-based confocal laser endomicroscopy (pCLE) offers microscopic-level imaging of subepithelial biliary mucosa. Because data regarding the use of pCLE in PSC are limited, we aimed to investigate its diagnostic performance in dominant strictures.

Methods: This was a multicenter prospective study involving PSC patients with dominant strictures. ERCP with pCLE was performed with use of the Miami classification (2+ criteria for malignant diagnosis) and Paris classification. Final malignant diagnoses required histopathologic confirmation, and benign diagnoses required a minimum of 1 year of follow-up without development of cancer.

Results: Fifty-nine patients (mean age, 49 years; 59% men) with 63 strictures were included in the study. Stricture locations included the common bile duct (31.7%), bifurcation (22.2%), and common hepatic duct (19%). Seven patients (11.9%) were found to have cholangiocarcinoma. The sensitivity and specificity of pCLE was 85.7% (95% confidence interval [CI], 42.1-99.6) and 73.1% (95% CI, 58.9-84.4), respectively. Within specific stricture locations, the highest sensitivity was seen at the bifurcation (100%; 95% CI, 2.5-100) and the right hepatic duct (100%; 95% CI, 29.2-100). The lowest sensitivities were seen at the common bile duct (25%; 95% CI, 5.5-57.2) and the left hepatic duct (28.6%; 95% CI, 3.7-70.9).

Conclusions: In this prospective multicenter study, pCLE had a high sensitivity in detecting cholangiocarcinoma, but technical aspects of the probe may limit evaluation in the common bile duct and left hepatic duct. Further evaluation is needed to elucidate the role of pCLE in the algorithm of excluding neoplasia in biliary strictures associated with PSC. (Clinical trial registration number: NCT02736708.).
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http://dx.doi.org/10.1016/j.gie.2021.03.027DOI Listing
September 2021

An international study of interobserver variability of "string sign" of pancreatic cysts among experienced endosonographers.

Endosc Ultrasound 2021 Jan-Feb;10(1):39-50

Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background And Objectives: No single optimal test reliably determines the pancreatic cyst subtype. Following EUS-FNA, the "string sign" test can differentiate mucinous from nonmucinous cysts. However, the interobserver variability of string sign results has not been studied.

Methods: An experienced endosonographer performed EUS-FNA of pancreatic cysts on different patients and was recorded on video performing the string sign test for each. The videos were shared internationally with 14 experienced endosonographers, with a survey for each video: "Is the string sign positive?" and "If the string sign is positive, what is the length of the formed string?" Also asked "What is the cutoff length for string sign to be considered positive?" Interobserver variability was assessed using the kappa statistic (κ).

Results: A total of 112 observations were collected from 14 endosonographers. Regarding string sign test positivity, κ was 0.6 among 14 observers indicating good interrater agreement (P < 0.001) while κ was 0.38 when observers were compared to the index endosonographer demonstrating marginal agreement (P < 0.001). Among observations of the length of the string in positive samples, 89.8% showed >5 mm of variability (P < 0.001), indicating marked variability. There was poor agreement on the cutoff length for a string to be considered positive.

Conclusion: String sign of pancreatic cysts has a good interobserver agreement regarding its positivity that can help in differentiating mucinous from nonmucinous pancreatic cysts. However, the agreement is poor on the measured length of the string and the cutoff length of the formed string to be considered a positive string sign.
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http://dx.doi.org/10.4103/eus.eus_73_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980687PMC
January 2021

Optical coherence tomography of the pancreatic and bile ducts: are we ready for prime time?

Endosc Int Open 2020 May 17;8(5):E644-E649. Epub 2020 Apr 17.

Ochsner, New Orleans, Louisiana, United States.

 First-generation optical coherence tomography (OCT) has been shown to increase diagnostic sensitivity for malignant biliary and pancreatic-duct strictures. A newer OCT imaging system, NVision Volumetric Laser Endomicroscopy (VLE), allows for in vivo cross-sectional imaging of the ductal wall at the microstructure level during endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to identify and evaluate characteristics on OCT that are predictive of benign and malignant strictures. Consecutive patients from six centers who underwent OCT between September 2016 and September 2017 were included in a dedicated registry. OCT images were analyzed, and nine recurring characteristics were further assessed. Final diagnosis was based on histology and/or surgical pathology. 86 patients were included (49 % male, mean age 64.7). OCT was performed in the bile duct in 79 patients and the pancreatic duct in seven. Nine OCT characteristics were identified: dilated hypo-reflective structures (n = 7), onion-skin layering (n = 8), intact layering (n = 17), layering effacement (n = 25), scalloping (n = 20), thickened epithelium (n = 42), hyper-glandular mucosa (n = 13), prominent blood vessels (n = 6), and a hyper-reflective surface (n = 20). Presence of hyper-glandular mucosa, hyper-reflective surface and scalloping significantly increased the odds of malignancy diagnosis by 6 times more (  = 0.0203; 95 % CI 1.3 to 26.5), 4.7 times more (  = 0.0255; 95 % CI 1.2 to 18.0) and 7.9 times more (  = 0.0035; 95 % CI 1.97 to 31.8) respectively. By providing in-vivo cross-sectional imaging of the pancreatic and biliary duct wall, OCT technology may improve sensitivity in diagnosing malignant strictures and provide standardizable criteria predictive of malignancy.
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http://dx.doi.org/10.1055/a-1119-6248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165011PMC
May 2020

Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal Adenocarcinoma and Surveillance of Barrett's Esophagus.

Mol Cell Proteomics 2018 12 10;17(12):2324-2334. Epub 2018 Aug 10.

QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia. Electronic address:

Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance of BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and the United States (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention (BE± low grade dysplasia) from those requiring intervention (BE with high grade dysplasia (BE-HGD) or EAC) with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed toward EAC, levels of serum C9 were significantly ( < 0.05) increased with disease progression in EPHA (erythroagglutinin from ) and NPL ( lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test.
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http://dx.doi.org/10.1074/mcp.RA118.000734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283291PMC
December 2018

Optical coherence tomography in gastroenterology: a review and future outlook.

J Biomed Opt 2017 Dec;22(12):1-17

NinePoint Medical, Inc., Bedford, Massachusetts, United States.

Optical coherence tomography (OCT) is an imaging technique optically analogous to ultrasound that can generate depth-resolved images with micrometer-scale resolution. Advances in fiber optics and miniaturized actuation technologies allow OCT imaging of the human body and further expand OCT utilization in applications including but not limited to cardiology and gastroenterology. This review article provides an overview of current OCT development and its clinical utility in the gastrointestinal tract, including disease detection/differentiation and endoscopic therapy guidance, as well as a discussion of its future applications.
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http://dx.doi.org/10.1117/1.JBO.22.12.121716DOI Listing
December 2017

Castleman Disease Presenting as an Abdominal Mass.

ACG Case Rep J 2017 24;4:e71. Epub 2017 May 24.

Department of Gastroenterology, Ochsner Clinic Foundation, Jefferson, LA.

Unicentric Castleman disease is a rare condition of lymphoid hyperplasia, of which only 15% of cases occur in the abdomen. We report a 66-year-old man who presented with complaints of abdominal pain. Computed tomography scans revealed nephrolithiasis and a homogeneous calcified mass between the pancreas and stomach and several para-pancreatic nodes. Direct visualization during exploratory laparotomy revealed a mass on the lesser curvature of the stomach. Pyloromyotomy and mass resection were performed. Biopsy showed reactive lymphoid hyperplasia consistent with the hyaline vascular variant of Castleman disease.
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http://dx.doi.org/10.14309/crj.2017.71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449581PMC
May 2017

Peripancreatic Mass of Unknown Origin.

Gastroenterology 2017 Jun 5;152(8):e7-e8. Epub 2017 May 5.

Department of Gastroenterology, Ochsner Clinic Foundation, New Orleans, Louisiana.

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http://dx.doi.org/10.1053/j.gastro.2016.10.051DOI Listing
June 2017

Improved classification of indeterminate biliary strictures by probe-based confocal laser endomicroscopy using the Paris Criteria following biliary stenting.

J Gastroenterol Hepatol 2017 Oct;32(10):1778-1783

Kaiser Permanente Health System, Sacramento, California, USA.

Background And Aims: Probe-based confocal laser endomicroscopy (pCLE) using the Miami Criteria has improved classification of indeterminate biliary strictures. However, previous biliary stenting may result in their misclassification as malignant strictures. Inflammatory criteria were added to form the Paris Classification to prevent this misclassification and reduce false positives. The aim of this study was to assess if the Paris Classification was more accurate than the Miami Classification in classifying indeterminate biliary strictures after biliary stenting.

Methods: This was a retrospective observational study involving 21 patients with indeterminate biliary strictures from whom 27 pCLE video sequences were obtained (20 benign and seven malignant). Patients with and without prior biliary stenting underwent pCLE. Two investigators classified the strictures as malignant or benign using the Miami and Paris Classifications. Diagnostic accuracy, sensitivity (Se), and specificity (Sp) of endoscopic retrograde-guided pCLE were compared with final histopathology.

Results: In those without biliary stenting, the Miami Criteria resulted in Se 88%, Sp 75%, positive predictive value (PPV) 64%, negative predictive value (NPV) 92%, and accuracy 79%, while the Paris Classification resulted in Se 63%, Sp 88%, PPV 71%, NPV 82%, and accuracy 79%. In those with prior biliary stenting, the Miami Criteria resulted in Se 88%, Sp 36%, PPV 23%, NPV 93%, and accuracy 45%, while the Paris Classification resulted in Se 63%, Sp 73%, PPV 31%, NPV 91%, and accuracy 71%. The kappa statistic was 0.56.

Conclusion: The Paris Classification improved specificity and accuracy of biliary stricture classification in those who had been previously stented and decreased the rate of misclassification of benign strictures as malignant.
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http://dx.doi.org/10.1111/jgh.13782DOI Listing
October 2017

Esophageal Granular Cell Tumor: A Benign Tumor or an Insidious Cause for Concern?

Ochsner J 2016 ;16(4):558-561

The University of Queensland School of Medicine, Ochsner Clinical School, New Orleans, LA ; Department of Gastroenterology, Ochsner Clinic Foundation, New Orleans, LA.

Background: Esophageal granular cell tumors (GCTs) are rare, often benign tumors of neurogenic origin. GCTs most frequently occur in the skin and subcutaneous tissues but are found in the gastrointestinal (GI) tract in 6%-10% of cases, with the distal two-thirds of the esophagus being the most common site. Owing to the insidious nature of GCTs, presentation is typically asymptomatic. In fact, GCTs are often discovered incidentally during investigation of other GI disturbances.

Case Report: We report the case of a 36-year-old white male who had a 2.3 × 2.0-cm submucosal mass of the midesophagus found during esophagogastroduodenoscopy (EGD) at an outside hospital for workup of chronic diarrhea. He was referred to us for further evaluation that led to a diagnosis of a large esophageal GCT.

Conclusion: Because of the rarity of GCTs in clinical practice and their poorly defined malignant classification, proper workup and management are essential to avoid the potential morbidity and mortality associated with large and/or malignant tumors. Although malignancy is uncommon, approximately 1%-2% of esophageal GCTs are malignant. Conservative management is tolerated for benign, asymptomatic lesions <10 mm in diameter, but endoscopic removal is recommended for large, symptomatic tumors or those with features suggestive of malignancy. Routine surveillance often includes EGD and/or esophageal ultrasonography to evaluate tumor size, location, and depth and to exclude malignancy or lymph node involvement.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5158167PMC
January 2016

Tumour-derived exosomes as a signature of pancreatic cancer - liquid biopsies as indicators of tumour progression.

Oncotarget 2017 Mar;8(10):17279-17291

Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane QLD 4029, Australia.

Pancreatic cancer is the fourth most common cause of death due to cancer in the world. It is known to have a poor prognosis, mostly because early stages of the disease are generally asymptomatic. Progress in pancreatic cancer research has been slow, leaving several fundamental questions pertaining to diagnosis and treatment unanswered. Recent studies highlight the putative utility of tissue-specific vesicles (i.e. extracellular vesicles) in the diagnosis of disease onset and treatment monitoring in pancreatic cancer. Extracellular vesicles are membrane-limited structures derived from the cell membrane. They contain specific molecules including proteins, mRNA, microRNAs and non-coding RNAs that are secreted in the extracellular space. Extracellular vesicles can be classified according to their size and/or origin into microvesicles (~150-1000 nm) and exosomes (~40-120 nm). Microvesicles are released by budding from the plasmatic membrane, whereas exosomes are released via the endocytic pathway by fusion of multivesicular bodies with the plasmatic membrane. This endosomal origin means that exosomes contain an abundance of cell-specific biomolecules which may act as a 'fingerprint' of the cell of origin. In this review, we discuss our current knowledge in the diagnosis and treatment of pancreatic cancer, particularly the potential role of EVs in these facets of disease management. In particular, we suggest that as exosomes contain cellular protein and RNA molecules in a cell type-specific manner, they may provide extensive information about the signature of the tumour and pancreatic cancer progression.
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http://dx.doi.org/10.18632/oncotarget.13973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370040PMC
March 2017

Glyco-centric lectin magnetic bead array (LeMBA) - proteomics dataset of human serum samples from healthy, Barrett׳s esophagus and esophageal adenocarcinoma individuals.

Data Brief 2016 Jun 1;7:1058-62. Epub 2016 Apr 1.

The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.

This data article describes serum glycoprotein biomarker discovery and qualification datasets generated using lectin magnetic bead array (LeMBA) - mass spectrometry techniques, "Serum glycoprotein biomarker discovery and qualification pipeline reveals novel diagnostic biomarker candidates for esophageal adenocarcinoma" [1]. Serum samples collected from healthy, metaplastic Barrett׳s esophagus (BE) and esophageal adenocarcinoma (EAC) individuals were profiled for glycoprotein subsets via differential lectin binding. The biomarker discovery proteomics dataset consisting of 20 individual lectin pull-downs for 29 serum samples with a spiked-in internal standard chicken ovalbumin protein has been deposited in the PRIDE partner repository of the ProteomeXchange Consortium with the data set identifier PRIDE: PXD002442. Annotated MS/MS spectra for the peptide identifications can be viewed using MS-Viewer (〈http://prospector2.ucsf.edu/prospector/cgi-bin/msform.cgi?form=msviewer〉) using search key "jn7qafftux". The qualification dataset contained 6-lectin pulldown-coupled multiple reaction monitoring-mass spectrometry (MRM-MS) data for 41 protein candidates, from 60 serum samples. This dataset is available as a supplemental files with the original publication [1].
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http://dx.doi.org/10.1016/j.dib.2016.03.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927955PMC
June 2016

Endoscopic Therapy With Lumen-apposing Metal Stents Is Safe and Effective for Patients With Pancreatic Walled-off Necrosis.

Clin Gastroenterol Hepatol 2016 12 14;14(12):1797-1803. Epub 2016 May 14.

Gastroenterology and Hepatology, Weill Cornell Medical Center, New York, New York.

Background & Aims: Endoscopic ultrasound-guided transmural drainage and necrosectomy have become the standard treatment for patients with pancreatic walled-off necrosis (WON). Lumen-apposing metal stents (LAMS) have shown success in the management of pancreatic fluid collections. However, there are few data on their specific roles in management of WON. We investigated the efficacy and safety of LAMS in treatment of WON.

Methods: We performed a retrospective multicenter case series of 124 patients with WON who underwent endoscopic transmural drainage by using LAMS at 17 tertiary care centers from January 2014 through May 2015. Patients underwent endoscopic ultrasound-guided cystogastrostomy or cystoenterostomy with placement of an LAMS into the WON collection. At the discretion of the endoscopist, we performed direct endoscopic necrosectomy, irrigation with hydrogen peroxide, and/or nasocystic drain placement. We performed endoscopic retrograde cholangiopancreatography with pancreatic duct stent placement when indicated. Concomitant therapies included direct endoscopic debridement (n = 78), pancreatic duct stent placement for leak (n = 19), hydrogen peroxide-assisted necrosectomy (n = 38), and nasocystic irrigation (n = 22). We collected data for a median time of 4 months (range, 1-34 months) after the LAMS placement. The primary outcomes were rates of technical success (successful placement of the LAMS), clinical success (resolution of WON, on the basis of image analysis, without need for further intervention via surgery or interventional radiology), and adverse events.

Results: The median size of the WON was 9.5 cm (range, 4-30 cm). Eight patients had 2 LAMS placed for multiport access, all with technical success (100%). Clinical success was achieved in 107 patients (86.3%) after 3 months of follow-up. Thirteen patients required a percutaneous drain, and 3 required a surgical intervention to manage their WON. The stents remained patent in 94% of patients (117 of 124) and migrated in 5.6% of patients (7 of 124). The median number of endoscopic interventions was 2 (range, 1-9 interventions).

Conclusions: On the basis of a retrospective analysis of 124 patients, endoscopic therapy of WON by using LAMS is safe and effective. Creation of a large and sustained cystogastrostomy or cystoenterostomy tract is effective in the drainage and treatment of WON.
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http://dx.doi.org/10.1016/j.cgh.2016.05.011DOI Listing
December 2016

Endoscopic Management of Necrotizing Pancreatitis: A Case Report and Review of the Literature.

J La State Med Soc 2015 Sep-Oct;167(5):210-2. Epub 2015 Oct 15.

Department of Gastroenterology at the LSU School of Medicine in New Orleans, LA.

Severe acute pancreatitis has two predominant phases. The first, "early" phase (1-2 weeks) is characterized by a severe pro-inflammatory state and is best ameliorated with conservative management. The second, "late" phase is a more complex immune-compromised state, during which pancreatic fluid collections become demarcated and walled-off. During this phase, patients are at an increased risk of infection and necrosis secondary to break in the gut barrier. Therefore, treatment becomes more complicated. Though open surgical necrosectomy has historically been the treatment of choice for infected pancreatic necrosis, it carries a mortality rate up to 40 percent, likely due to additional physiologic stress in an already pro-inflammatory state. A growing body of evidence suggests that primary minimally invasive approaches, including endoscopy, can be used with equivalent or increased efficacy and lower morbidity and mortality rates than the traditional methods.
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September 2017

EUS-Guided Needle-Based Confocal Laser Endomicroscopy: A Novel Technique With Emerging Applications.

Gastroenterol Hepatol (N Y) 2015 Apr;11(4):235-40

Dr Bhutani is a professor and Dr Koduru is a research intern in the Department of Gastroenterology, Hepatology, and Nutrition at the University of Texas MD Anderson Cancer Center in Houston, Texas. Dr Joshi is an associate professor in the Department of Gastroenterology at the Ochsner Clinic Foundation in New Orleans, Louisiana. Dr Karstensen is a research fellow, Dr Saftoiu is a visiting professor, and Dr Vilmann is a professor at the University of Copenhagen Herlev Hospital in Herlev, Denmark. Dr Saftoiu is also a professor at the Research Center of Gastroenterology and Hepatology at the University of Medicine and Pharmacy of Craiova in Craiova, Romania. Dr Giovannini is a professor at the Institut Paoli-Calmettes in Marseille, France.

Endoscopic ultrasound (EUS) has emerged as an excellent tool for imaging the gastrointestinal tract, as well as surrounding structures. EUS-guided fine-needle aspiration (EUS-FNA) has become the standard of care for the tissue sampling of a variety of masses and lymph nodes within and around the gut, providing further diagnostic and staging information. Confocal laser endomicroscopy (CLE) is a novel endoscopic method that enables imaging at a subcellular level of resolution during endoscopy, allowing up to 1000-fold magnification of tissue and providing an optical biopsy. A new procedure that has been developed in the past few years is needle-based confocal laser endomicroscopy (nCLE), which involves a mini-CLE probe that can be passed through a 1 9-gauge needle during EUS-FNA. This enables the real-time visualization of tissue at a microscopic level, with the potential to further improve the diagnostic accuracy of EUS-FNA. The device has been studied in animals as well as in humans, and the results so far have been promising. Recently, this method has also been used for the visualization of regulatory proteins and receptors in the pancreas, setting a cornerstone for nCLE in molecular imaging. The aim of this article is to review the role of EUS-guided nCLE in modern endoscopy and its implications in molecular imaging.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836594PMC
April 2015

The role of endoscopic ultrasound in pancreatic cancer screening.

Endosc Ultrasound 2016 Jan-Feb;5(1):8-16

Department of Gastroenterology, Hepatology and Nutrition, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.

Pancreatic cancer (PC) is a highly lethal cancer. Despite a significant advancement in cancer treatment, the mortality rate of PC is nearly identical to the incidence rates. Early detection of tumor or its precursor lesions with dysplasia may be the most effective approach to improve survival. Screening strategies should include identification of the population at high risk of developing PC, and an intense application of screening tools with adequate sensitivity to detect PC at an early curable stage. Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) seem to be the most promising modalities for PC screening based on the data so far. EUS had an additional advantage over MRI by being able to obtain tissue sample during the same examination. Several questions remain unanswered at this time regarding the age to begin screening, frequency of screening, management of asymptomatic pancreatic lesions detected on screening, timing of resection, and extent of surgery and impact of screening on survival. Novel techniques such as needle-based confocal laser endomicroscopy (nCLE), along with biomarkers, may be helpful to identify pancreatic lesions with more aggressive malignant potential. Further studies will hopefully lead to the development of strategies combining EUS with other technological/biological advancements that will be cost-effective and have an impact on survival.
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http://dx.doi.org/10.4103/2303-9027.175876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770628PMC
February 2016

Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

Mol Cell Proteomics 2015 Nov 24;14(11):3023-39. Epub 2015 Sep 24.

From the ‡The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia;

We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates were independently verified by lectin magnetic bead array-immunoblotting, confirming the validity of the relative quantitation approach. Thus, we have identified candidate biomarkers, which, following large-scale clinical evaluation, can be developed into diagnostic blood tests. A key feature of the pipeline is the potential for rapid translation of the candidate biomarkers to lectin-immunoassays.
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http://dx.doi.org/10.1074/mcp.M115.050922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638044PMC
November 2015

A 60-year-old man with chronic cough and green sputum.

Gastroenterology 2014 Sep 23;147(3):575-6. Epub 2014 Jul 23.

Ochsner Clinic Foundation, New Orleans, Louisiana.

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http://dx.doi.org/10.1053/j.gastro.2014.04.054DOI Listing
September 2014

Robotic-assisted laparoscopic wedge resection of a gastric leiomyoma with intraoperative ultrasound localization.

Minim Invasive Ther Allied Technol 2011 Dec 16;20(6):360-4. Epub 2011 Sep 16.

Department of Surgery, Department of Medicine, Tulane University School ofMedicine, New Orleans, LA, USA.

Gastric leiomyoma is a rare gastric neoplasm that traditionally has been resected for negative margins using an open approach. The laparoscopic approach may also treat various gastric tumors without opening the gastric cavity. Robotic surgery was developed in response to the limitations and drawbacks of laparoscopic surgery. Herein, we describe a case of robotic-assisted laparoscopic wedge resection of a gastric leiomyoma. A 63-year-old male complaining of abdominal pain was found to have an incidental 3 cm antral mass on an abdominal CT. Endoscopy with endoscopic ultrasound (EUS) confirmed a submucosal mass. Biopsy of the lesion was consistent with a leiomyoma. The DaVinci robotic system was used for partial gastrectomy and reconstruction, with the addition of intraoperative ultrasound to localize the lesion intraoperatively. Pathological examination of the resected mass confirmed a diagnosis of leiomyoma with negative margins. There were no intraoperative or postoperative complications. The patient was discharged home on the second postoperative day. Intraoperative endoscopic ultrasound is a safe technique that may improve the success rate of surgery by confirming the location of the lesion. Robotic assistance in gastric resection offers an easy minimally invasive approach to such tumors. This approach can achieve adequate surgical margins and lead to short hospital stays.
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http://dx.doi.org/10.3109/13645706.2010.549830DOI Listing
December 2011

A case report of intraoperative endoscopic ultrasound during robotic assisted Heller myotomy for severe esophageal achalasia.

J La State Med Soc 2011 May-Jun;163(3):134-8

Department of Surgery, Ochsner Medical Center, New Orleans, USA.

Esophageal achalasia is the best described primary esophageal motility disorder. Endoscopic ultrasound (EUS) is considered a useful adjunct for grading and establishing the prognosis of these patients. Recent experience using Da Vinci robotic assisted myotomy has demonstrated that this is a safe and effective approach of treatment. The benefit of magnification and three dimensional imaging helps prevent esophageal perforation and identify residual circular muscle fibers. This paper reports the relative efficacy and safety of intraoperative ultrasound during robotic assisted myotomy in a patient with severe achalasia. Intraoperative esophageal endoscopic ultrasound is a safe technique that may improve the success rate of surgery by confirming the adequacy of myotomy, thereby decreasing the likelihood of recurrent symptoms.
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September 2011

Biliary obstruction from a bile duct mass.

Gastroenterology 2011 Sep 28;141(3):812-3, 1129. Epub 2011 Jul 28.

Tulane University Medical School, New Orleans, Louisiana, USA.

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http://dx.doi.org/10.1053/j.gastro.2010.06.082DOI Listing
September 2011

Colo-renal fistula: An unusual cause of hematochezia.

World J Gastrointest Pathophysiol 2010 Aug;1(3):106-8

John D Wysocki, Virendra Joshi, Naveed Gil, Tulane University School of Medicine, LA 70112 , United States.

A 76 year old woman with bloody stools and symptomatic anemia presented to the Emergency Department approximately 2 wk after computed tomography (CT)-guided cryoablation to a 4.5 cm renal cell carcinoma on her left posterior kidney. The patient was initially prepped for a colonoscopy to view possible causes of lower gastrointestinal bleeding. However, the patient had a CT with PO contrast that revealed a variation of a renoalimentary fistula. The patient was subsequently brought to the operating room, and it was discovered that a colo-renal fistula had formed, with transmural perforation of the posterior descending colon. A left nephrectomy, left colectomy with colostomy and Hartmann's pouch was performed.
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http://dx.doi.org/10.4291/wjgp.v1.i3.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3097949PMC
August 2010

A simple and safe minimally invasive technique for laparoscopic gastrostomy.

JSLS 2010 Jan-Mar;14(1):62-5

Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana, USA.

Introduction: Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice in the nutritional management of patients requiring gastrostomies. However, PEG tubes are not always feasible. The aim of the present study was to determine the feasibility, complications, and adequacy of feeding support of a novel laparoscopic gastrostomy technique in adults where PEG tubes were neither feasible nor safe.

Methods: A retrospective chart review of patients who underwent a laparoscopic gastrostomy from August 2007 to July 2008 was performed. Demographic and outcome data were abstracted.

Results: Fourteen patients underwent laparoscopic gastrostomy. Nine had obstructing head/neck cancer, 2 had severe head trauma, and one was morbidly obese. Nine patients had previous abdominal surgery. The mean operative time was 29.8 minutes (+/-7.2). There were no conversions to open gastrostomy. Two ports (5mm and 10mm) were used in the majority of patients (78.5%). No major complications were observed. The mean follow-up was 3.1 months (range, 2 to 8).

Conclusion: This innovative 2-port laparoscopic technique for gastrostomy tube placement is safe and effective. It allows for the quick, accurate, and safe insertion of the feeding tube under direct visualization and avoids open techniques in patients where PEG tubes are not feasible.
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http://dx.doi.org/10.4293/108680810X12674612014626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021287PMC
July 2010

Natural orifice translumenal endoscopic surgery (NOTES) partial nephrectomy in a porcine model.

Surg Endosc 2010 Feb 8;24(2):485-9. Epub 2009 Jul 8.

Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA.

Background: This study aimed to evaluate the feasibility of natural orifice translumenal endoscopic surgery (NOTES) transgastric partial nephrectomy without hilar clamping in a porcine model.

Methods: A 45-kg male pig was placed in the supine position after endotracheal general anesthesia. A therapeutic gastroscope was introduced through the esophagus, and a 2-cm gastrotomy was performed using a diathermy electrocautery needle at the junction of the fundus and the proximal body. After incision of Gerota's fascia, the left kidney's upper pole was excised using the thulium laser without hilar dissection or clamping. An endoscopic wire loop was used to entrap and extract the specimen into the stomach. The gastroscope was subsequently withdrawn with the intact specimen. After hemostasis via reinsertion of the endoscope was ensured, metal clips were applied endoscopically to close the gastrotomy.

Results: The total operative time for the NOTES transgastric partial nephrectomy was 240 min. Use of the therapeutic double-channel gastroscope allowed for scarless NOTES. The available 3.7- and 2.8-mm gastroscope ports were used for gastrotomy, excision, removal of the specimen, and endoscopic clip application. The procedure was performed in a nonischemic fashion with application of the thulium laser, which provided adequate hemostasis. No further interventions such as suturing of the renal capsule or use of hemostatic agents were required. The final specimen was 3 cm in size, and the estimated blood loss was 200 ml. A major drawback of the thulium laser was excessive smoke produced by vaporization of the tissue, which was minimized with the use of external irrigation.

Conclusion: The findings show that NOTES transgastric partial nephrectomy with thulium laser is feasible. Further studies are needed to demonstrate long-term efficacy and provide additional data regarding practical applications of this novel approach and technique.
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http://dx.doi.org/10.1007/s00464-009-0610-4DOI Listing
February 2010

Peutz-Jeghers syndrome: a rare cause of gastric outlet obstruction.

Clin Gastroenterol Hepatol 2009 Nov 29;7(11):A20. Epub 2009 Jan 29.

Tulane School of Medicine, New Orleans, Louisiana, USA.

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http://dx.doi.org/10.1016/j.cgh.2009.01.006DOI Listing
November 2009

Crohn disease of the esophagus: a review of the literature.

South Med J 2008 Sep;101(9):927-30

Section of Gastroenterology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.

Esophageal Crohn disease is a difficult disease both to diagnose and treat. The diagnosis is made in patients with other extraintestinal manifestations of Crohn disease in whom other esophageal pathology has been ruled out. This often requires integration of clinical, endoscopic, radiographic, and histologic findings. Despite its relative rarity, it does cause severe symptoms that are difficult to treat. Treatment requires careful integration of medical, endoscopic, and surgical techniques. This review aims to discuss the significant literature regarding diagnosis and treatment of this important manifestation of inflammatory bowel disease. There is additional discussion of the literature regarding the efficacy of newer medical and endoscopic therapies, including biologic agents and removable polymer stents.
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http://dx.doi.org/10.1097/SMJ.0b013e31818047beDOI Listing
September 2008

HCV-hepatocellular carcinoma: new findings and hope for effective treatment.

Microsc Res Tech 2005 Nov;68(3-4):130-48

Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.

We present here a comprehensive review of the current literature plus our own findings about in vivo and in vitro analysis of hepatitis C virus (HCV) infection, viral pathogenesis, mechanisms of interferon action, interferon resistance, and development of new therapeutics. Chronic HCV infection is a major risk factor for the development of human hepatocellular carcinoma. Standard therapy for chronic HCV infection is the combination of interferon alpha and ribavirin. A significant number of chronic HCV patients who cannot get rid of the virus infection by interferon therapy experience long-term inflammation of the liver and scarring of liver tissue. Patients who develop cirrhosis usually have increased risk of developing liver cancer. The molecular details of why some patients do not respond to standard interferon therapy are not known. Availability of HCV cell culture model has increased our understanding on the antiviral action of interferon alpha and mechanisms of interferon resistance. Interferons alpha, beta, and gamma each inhibit replication of HCV, and the antiviral action of interferon is targeted to the highly conserved 5'UTR used by the virus to translate protein by internal ribosome entry site mechanism. Studies from different laboratories including ours suggest that HCV replication in selected clones of cells can escape interferon action. Both viral and host factors appear to be involved in the mechanisms of interferon resistance against HCV. Since interferon therapy is not effective in all chronic hepatitis C patients, alternative therapeutic strategies are needed to treat chronic hepatitis C patients not responding to interferon therapy. We also reviewed the recent development of new alternative therapeutic strategies for chronic hepatitis C, which may be available in clinical use within the next decade. There is hope that these new agents along with interferon will prevent the occurrence of hepatocellular carcinoma due to chronic persistent hepatitis C virus infection. This review is not inclusive of all important scientific publications due to space limitation.
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http://dx.doi.org/10.1002/jemt.20227DOI Listing
November 2005

Alpha interferon inhibits translation mediated by the internal ribosome entry site of six different hepatitis C virus genotypes.

J Gen Virol 2005 Nov;86(Pt 11):3047-3053

Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.

Certain genotypes of hepatitis C virus (HCV) respond less often than others to treatment with interferon (IFN). The mechanisms for this differential response are not known. In this report antiviral effects of IFN-alpha2b on translation were examined in a hepatic cell line using chimeric clones of internal ribosome entry site (IRES) sequences from six different HCV genotypes and the green fluorescence protein (GFP) gene. As a control, IFN action at the level of the IRES was examined in the presence of different cytokines. It was determined that IFN-alpha2b specifically inhibited the translation of GFP mediated by IRES sequences from six major HCV genotypes in a concentration-dependent manner. Other cytokines including tumour necrosis factor alpha, transforming growth factor beta 1, interleukin 1 and interleukin 6 have no inhibitory effect. The inhibition of translation in these experiments was not due to extensive intracellular degradation of IRES-GFP mRNA. These results suggest that the antiviral action of IFN-alpha2b blocks IRES-mediated translation and this effect is the same among HCVs of other genotypes.
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http://dx.doi.org/10.1099/vir.0.81132-0DOI Listing
November 2005

Interferons alpha, beta, gamma each inhibit hepatitis C virus replication at the level of internal ribosome entry site-mediated translation.

Liver Int 2005 Jun;25(3):580-94

Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.

Interferon (IFN)-alpha is the standard therapy for the treatment of chronic hepatitis C, but the mechanisms underlying its antiviral action are not well understood. In this report, we demonstrated that IFN-alpha, -beta and -gamma inhibit replication of the hepatitis C virus (HCV) in a cell culture model at concentrations between 10 and 100 IU/ml. We demonstrated that the antiviral actions each of each these IFNs are targeted to the highly conserved 5' untranslated region of the HCV genome, and that they directly inhibit translation from a chimeric clone between full-length HCV genome and green fluorescent protein (GFP). This effect is not limited to HCV internal ribosome entry site (IRES), since these IFNs also inhibit translation of the encephalomyocardititis virus (EMCV) chimeric mRNA in which GFP is expressed by IRES-dependent mechanisms (pCITE-GFP). These IFNs had minimal effects on the expression of mRNAs from clones in which translation is not IRES dependent. We conclude that IFN-alpha, -beta and -gamma inhibit replication of sub-genomic HCV RNA in a cell culture model by directly inhibiting two internal translation initiation sites of HCV- and EMCV-IRES sequences present in the dicistronic HCV sub-genomic RNA. Results of this in vitro study suggest that selective inhibition of IRES-mediated translation of viral polyprotein is a general mechanism by which IFNs inhibits HCV replication.
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http://dx.doi.org/10.1111/j.1478-3231.2005.01082.xDOI Listing
June 2005

Peptides identified through phage display direct immunogenic antigen to dendritic cells.

J Immunol 2004 Jun;172(12):7425-31

Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, USA.

Dendritic cells (DC) play a critical role in adaptive immunity by presenting Ag, thereby priming naive T cells. Specific DC-binding peptides were identified using a phage display peptide library. DC-peptides were fused to hepatitis C virus nonstructural protein 3 (NS3) while preserving DC targeting selectivity and Ag immunogenicity. The NS3-DC-peptide fusion protein was efficiently presented to CD4+ and CD8+ T cells derived from hepatitis C virus-positive blood cells, inducing their activation and proliferation. This immunogenic fusion protein was significantly more potent than NS3 control fusion protein or NS3 alone. In chimeric NOD-SCID mice transplanted with human cells, DC-targeted NS3 primed naive CD4+ and CD8+ T cells for potent NS3-specific proliferation and cytokine secretion. The capacity of peptides to specifically target immunogenic Ags to DC may establish a novel strategy for vaccine development.
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http://dx.doi.org/10.4049/jimmunol.172.12.7425DOI Listing
June 2004
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