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Pancreatic Neoplasms: HELP
Articles by Udayakumar Navaneethan
Based on 19 articles published since 2010
(Why 19 articles?)
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Between 2010 and 2020, Udayakumar Navaneethan wrote the following 19 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Biomarkers in bile-complementing advanced endoscopic imaging in the diagnosis of indeterminate biliary strictures. 2015

Lourdusamy, Vennisvasanth / Tharian, Benjamin / Navaneethan, Udayakumar. ·Vennisvasanth Lourdusamy, Benjamin Tharian, Udayakumar Navaneethan, Center for Interventional Endoscopy, Institute for Minimally Invasive Surgery, Florida Hospital, Orlando, FL 32803, United States. ·World J Gastrointest Endosc · Pubmed #25901209.

ABSTRACT: Biliary strictures present a diagnostic challenge and a conundrum, particularly when an initial work up including abdominal imaging and endoscopic retrograde cholangiopancreatography based sampling are non-diagnostic. Advances in endoscopic imaging have helped us diagnose these strictures better. However, even with modern technology, some strictures remain a diagnostic challenge. The proximity of bile fluid to the bile duct epithelia makes it an attractive option to investigate for bio-markers, which might be representative of the functions/abnormal changes taking place in the biliary system. A number of biomarkers in bile have been discovered recently in approaching biliary strictures with their potential future diagnostic utility, further supported by the immunohistochemical analysis of the resected tissue specimens. Novel biliary biomarkers especially carcinoembryonic cell adhesion molecule 6 and neutrophil gelatinase-associated lipocalin seem promising in differentiating malignant from benign biliary strictures. Recent developments in lipidomic profiling of bile are also very promising. Biliary biomarkers appear to complement endoscopic imaging in diagnosing malignant etiologies of biliary stricture. Future studies addressing these biomarkers need to be incorporated to the current endoscopic techniques to determine the best approach in determining the etiology of biliary strictures.

2 Review Comparative effectiveness of biliary brush cytology and intraductal biopsy for detection of malignant biliary strictures: a systematic review and meta-analysis. 2015

Navaneethan, Udayakumar / Njei, Basile / Lourdusamy, Vennisvasanth / Konjeti, Rajesh / Vargo, John J / Parsi, Mansour A. ·Digestive Disease Institute, The Cleveland Clinic, Cleveland, Ohio, USA; Center for Interventional Endoscopy, Orlando, Florida, USA. · Department of Gastroenterology, Yale University, New Haven, Connecticut, USA. · Digestive Disease Institute, The Cleveland Clinic, Cleveland, Ohio, USA. ·Gastrointest Endosc · Pubmed #25440678.

ABSTRACT: BACKGROUND: Evaluation of indeterminate biliary strictures typically involves collection and analysis of tissue or cells. Brush cytology and intraductal biopsies that are routinely performed during ERCP to assess malignant-appearing biliary strictures are limited by relatively low sensitivity. OBJECTIVE: To study the comparative effectiveness of brushings for cytology and intraductal biopsies in the etiology of biliary strictures. DESIGN: Meta-analysis. SETTING: Referral center. PATIENTS: PUBMED and Embase databases were reviewed for studies published to April 2014 where diagnostic correlation of histology was available. INTERVENTION: Database and review of study findings. MAIN OUTCOME MEASUREMENTS: Sensitivity and specificity. RESULTS: The pooled sensitivity and specificity of brushings for the diagnosis of malignant biliary strictures was 45% (95% confidence interval [CI], 40%-50%) and 99% (95% CI, 98%-100%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 33.43 (95% CI, 14.29-78.24). For intraductal biopsies, the pooled sensitivity and specificity were 48.1% (95% CI, 42.8%-53.4%) and 99.2% (95% CI, 97.6%-99.8%), respectively. The pooled diagnostic odds ratio to detect malignant biliary strictures was 43.18 (95% CI, 19.39-95.83). A combination of both modalities only modestly increased the sensitivity (59.4%; 95% CI, 53.7%-64.8%) with a specificity of 100% (95% CI, 98.8%-100.0%). The Begg-Mazumdar and Egger tests indicated a low potential for publication bias. LIMITATIONS: Inclusion of low-quality studies. CONCLUSION: Our study suggests that both brushings and biopsy are comparable and have limited sensitivity for the diagnosis of malignant biliary strictures. A combination of both only modestly increases the sensitivity.

3 Review Intraductal papillary mucinous neoplasm and acute pancreatitis. 2011

Venkatesh, Preethi G K / Navaneethan, Udayakumar / Vege, Santhi Swaroop. ·Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA. ·J Clin Gastroenterol · Pubmed #21602701.

ABSTRACT: Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic tumors that arise from the pancreatic ducts and are increasingly reported worldwide. Both benign and malignant tumors of the pancreas are thought to contribute to recurrent pancreatitis possibly by pancreatic duct obstruction, and IPMNs contribute to a major share of this burden. The rate of acute pancreatitis (AP) in IPMN patients in the largest published surgical series has varied from 12% to 67%. IPMN may be categorized into 3 forms on the basis of the areas of involvement: main pancreatic duct (MD-IPMN), side branch (SB-IPMN), or combined. Both MD-IPMN and SB-IPMN may be the cause of pancreatitis. The risk of AP seems to be similar with both main duct IPMN and SB-IPMN, although data are controversial. AP in IPMN patients is not severe and often recurs without treatment. The rate of AP does not seem to differ among benign and malignant IPMNs, and the correlation between the malignant potential and the occurrence of AP is ill defined. AP seems to occur more often in patients with IPMN that in those with usual pancreatic adenocarcinoma possibly because of obstruction of the main duct by thick, abundant mucus secretion. Although the Sendai guidelines recommend surgical resection in patients with SB-IPMN with AP, data are controversial. Moreover, in patients with an episode of pancreatitis, the finding of pancreatic cysts is often attributed to pseudocysts or fluid collections that make the diagnosis of IPMN less suspicious. Future longitudinal and prospective studies to understand the natural history of AP in patients with IPMN are required to better manage patients with recurrent AP in the setting of IPMN.

4 Article In memoriam: Fine-needle aspiration, birth: Fine-needle biopsy: The changing trend in endoscopic ultrasound-guided tissue acquisition. 2019

Bang, Ji Young / Kirtane, Sachin / Krall, Konrad / Navaneethan, Udayakumar / Hasan, Muhammad / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, USA. ·Dig Endosc · Pubmed #30256458.

ABSTRACT: BACKGROUND AND AIM: Fine-needle aspiration (FNA) cytology has been the preferred technique for procuring tissue at endoscopic ultrasound (EUS) procedures for the past 25 years. To overcome some of the limitations of FNA cytology, fine-needle biopsy (FNB) has been recently developed to yield histological tissue. Main objective was to compare the diagnostic yield of FNB compared to FNA for both onsite and offsite specimen assessment. METHODS: A retrospective study was conducted at a single tertiary referral center to evaluate the outcomes of FNA and FNB over a 4-year period. EUS-guided tissue sampling was carried out using 22- or 25-G FNA needles from 2014 to 2015, and 22-G FNB needle was used from 2016 to 2017. RESULTS: Of 3020 patients undergoing EUS-guided sampling of solid mass lesions (pancreatic masses 71.3%, other lesions 28.7%), FNA was carried out in 68.9% and FNB in 31.1%. Median number of passes required for diagnostic adequacy on rapid onsite evaluation was significantly lower for FNB compared to FNA (1 [IQR: 1-2] vs 2 [IQR 1-3], P < 0.001). Diagnostic yield on cell block was also significantly superior with FNB compared to FNA (92.3 vs 71.1%, P < 0.001). The superior performance of FNB over FNA was observed for both pancreatic (P < 0.001) and non-pancreatic lesions (P < 0.001). CONCLUSION: Given these promising findings, in the future, EUS-guided FNB will likely be the preferred technique for sampling of solid mass lesions.

5 Article Utility of rapid onsite evaluation of touch imprint cytology from endoscopic and cholangioscopic forceps biopsy sampling (with video). 2019

Ali, Saeed / Hawes, Robert H / Kadkhodayan, Kambiz / Rafiq, Ehsan / Navaneethan, Udayakumar / Bang, Ji Y / Varadarajulu, Shyam / Hasan, Muhammad K. ·Department of Internal Medicine, Florida Hospital, Orlando, Florida, USA. · Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA. ·Gastrointest Endosc · Pubmed #30193904.

ABSTRACT: BACKGROUND AND AIMS: Rapid onsite evaluation of touch imprint cytology (ROSE-TIC) is a simple and rapid method used for the diagnosis of benign and malignant lesions. We evaluated the diagnostic accuracy of ROSE-TIC for advanced intestinal luminal and indeterminate pancreatobiliary lesions during endoscopy. METHODS: This is a retrospective descriptive study of patients who underwent endoscopy or ERCP between January 1, 2014 and December 31, 2016. It included patients who were referred for the treatment of intestinal luminal lesions or evaluation of indeterminate pancreatobiliary lesions. The slides were prepared by gently touching the specimen onto a glass slide and were examined under the microscope. The main outcome measure was to determine the diagnostic accuracy of ROSE-TIC by comparing the onsite cytology findings with the corresponding off-site histologic diagnosis. RESULTS: All 222 patients (106 pancreatobiliary and 116 GI lesions) had a prior benign diagnosis of intestinal luminal lesions or indeterminate diagnosis of pancreatobiliary lesions. The overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ROSE-TIC were 97%, 85%, 83%, 97.2%, and 90%, respectively. The accuracy varied with the site of the biopsy sample. The accuracy was lowest for upper GI tract, where it was 85.2% but was 95% for lower GI tract lesions. CONCLUSIONS: By establishing a rapid onsite diagnosis, ROSE-TIC expedites decision-making on patient management. Prospective studies are needed to confirm these preliminary findings.

6 Article Stent placement by EUS or ERCP for primary biliary decompression in pancreatic cancer: a randomized trial (with videos). 2018

Bang, Ji Young / Navaneethan, Udayakumar / Hasan, Muhammad / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA. ·Gastrointest Endosc · Pubmed #29574126.

ABSTRACT: BACKGROUND AND AIMS: Studies on EUS-guided transmural biliary drainage (EUS-BD) have evaluated its efficacy as a rescue technique after failed ERCP. We performed a single-center, single-blind, randomized trial to compare EUS-BD and ERCP as primary treatment for distal biliary obstruction in pancreatic cancer. METHODS: Patients underwent EUS-BD (n = 33) or ERCP (n = 34). The primary endpoint was the rate of adverse events. Secondary endpoints were technical success, treatment success (defined as decline in serum bilirubin by 50% at a 2-week follow-up), reinterventions, and intraoperative technical outcome, when applicable. Follow-up was until death or a minimum of 6 months. RESULTS: The rates of adverse events were 21.2% (6.1% moderate severity; others mild severity) in the EUS-BD group and 14.7% (5.9% moderate severity; others mild severity) in the ERCP group (risk ratio, .69; 95% confidence interval, .24-1.97; P = .49). There were no procedure-related deaths. There was no significant difference in the rates of technical success (90.9% vs 94.1%, P = .67), treatment success (97% vs 91.2%, P = .61), or reinterventions (3.0% vs 2.9%, P = .99) between EUS-BD and ERCP cohorts, respectively. The endoscopic interventions did not impede subsequent pancreaticoduodenectomy that was performed in 5 of 33 patients (15.2%) in the EUS-BD and 5 of 34 patients (14.7%) in the ERCP group (P = .99). CONCLUSIONS: Given the similar rates of adverse events and treatment outcomes in this randomized trial, EUS-BD is a practical alternative to ERCP for primary biliary decompression in pancreatic cancer. (Clinical trial registration number: NCT03054987.).

7 Article Endoscopic Ultrasound-guided Specimen Collection and Evaluation Techniques Affect Diagnostic Accuracy. 2018

Bang, Ji Young / Navaneethan, Udayakumar / Hasan, Muhammad K / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida. · Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida. Electronic address: svaradarajulu@yahoo.com. ·Clin Gastroenterol Hepatol · Pubmed #29535060.

ABSTRACT: BACKGROUND & AIMS: Outcomes of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) evaluation vary with technique, needles, and methods of specimen evaluation. We performed a direct comparison of diagnostic yields of EUS-FNA samples collected using different gauge needles (22- vs 25-gauge), with or without suction. METHODS: We performed a randomized controlled study of 352 patients with suspected pancreatic masses, referred for EUS-FNA at a tertiary referral center. Patients were randomly assigned to 22-gauge needles with or without suction or 25-gauge needles with or without suction. Specimens were evaluated offsite by cell block and rapid onsite cytologic evaluation (ROSE). Final diagnoses were made based on histologic analyses or 12-month follow-up evaluations. The primary outcome was diagnostic adequacy of cell blocks. Secondary outcomes were operating characteristics of ROSE and EUS-FNA, number of passes required for accurate onsite diagnosis, and amount of blood in specimens. RESULTS: The final diagnoses were malignancy (81.5% of patients) and benign disease (17.0% of patients); 1.4% of patients were lost during follow up. Cell block, ROSE, and EUS-FNA led to diagnostic accuracies of 71.9%, 95.5%, and 96.6%, respectively. A 22-gauge needle with suction was associated with more passes for adequate onsite diagnosis (P = .003) and specimens contained more blood (P = .01). Diagnostic accuracy of specimens collected by transduodenal EUS-FNA was lower with 22-gauge needles with suction compared to other techniques (P = .004). CONCLUSION: In a randomized trial of patients undergoing EUS-FNA for pancreatic masses, samples collected with 22-gauge vs 25-gauge needles performed equally well for offsite specimen evaluation. Use of suction appears to increase number of passes needed and specimen bloodiness. Specimen collection techniques should be individualized based on method of evaluation. ClinicalTrials.gov no: NCT02424838.

8 Article Randomized trial comparing the Franseen and Fork-tip needles for EUS-guided fine-needle biopsy sampling of solid pancreatic mass lesions. 2018

Bang, Ji Young / Hebert-Magee, Shantel / Navaneethan, Udayakumar / Hasan, Muhammad K / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA. ·Gastrointest Endosc · Pubmed #29305893.

ABSTRACT: BACKGROUND AND AIMS: Recently, a 3-plane symmetric needle with Franseen geometry and a Fork-tip biopsy needle have been developed for histologic tissue procurement. We compared 22-gauge Franseen and 22-gauge Fork-tip needles in patients undergoing EUS-guided sampling of pancreatic masses. METHODS: Fifty patients underwent sampling using both 22-gauge Franseen and 22-gauge Fork-tip needles, with randomization of needle order. Two dedicated passes were performed using both needles for cell block. Subsequent passes were performed for rapid onsite evaluation (ROSE) using both needles alternately until diagnosis was established. The main outcome was to evaluate for histologic core tissue by comparing area of total tissue, tumor, desmoplastic fibrosis, and rate of retained tissue architecture between cohorts. Other outcomes were rates of diagnostic cell block and diagnostic adequacy at ROSE. RESULTS: Final diagnosis was pancreatic cancer in 44 patients, neuroendocrine tumor in 2, lymphoma in 1, and chronic pancreatitis in 3. There was no significant difference in area of total tissue (median 6.1 [interquartie range {IQR}, 3.5-10.5] vs 8.2 mm CONCLUSIONS: There was no significant difference between Franseen and Fork-tip needles in yielding histologic tissue. Given their ability to yield diagnostic cell block in greater than 90% of patients, the new-generation fine-needle biopsy needles may obviate the need for ROSE. (Clinical trial registration number: NCT02910960.).

9 Article EUS-guided fine needle biopsy of pancreatic masses can yield true histology. 2018

Bang, Ji Young / Hebert-Magee, Shantel / Navaneethan, Udayakumar / Hasan, Muhammad K / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA. ·Gut · Pubmed #28988195.

ABSTRACT: -- No abstract --

10 Article An Unusual Cause of Recurrent Gastrointestinal Bleeding After Whipple's Surgery. 2017

Ali, Saeed / Asad Ur Rahman, ? / Navaneethan, Udayakumar. ·Department of Internal Medicine, Florida Hospital, Orlando, Florida. · Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida. ·Gastroenterology · Pubmed #28672119.

ABSTRACT: -- No abstract --

11 Article Endoscopic ultrasonography-guided biopsy using a Franseen needle design: Initial assessment. 2017

Bang, Ji Young / Hebert-Magee, Shantel / Hasan, Muhammad K / Navaneethan, Udayakumar / Hawes, Robert / Varadarajulu, Shyam. ·Center for Interventional Endoscopy, Florida Hospital, Orlando, USA. ·Dig Endosc · Pubmed #27878861.

ABSTRACT: BACKGROUND AND AIM: Recently, a 22-gauge (G) needle with a Franseen tip design was developed for endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB). The present study evaluated the performance of the Franseen biopsy needle in EUS-guided tissue acquisition. METHODS: This is a retrospective study of patients who underwent EUS-FNB using the Franseen needle. Lesions were sampled using either the Franseen needle only or after failed diagnostic fine-needle aspiration (FNA). After rapid onsite evaluation (ROSE), two dedicated passes were carried out for histological assessment using the cell block technique. Main outcomes were: (i) rates of diagnostic adequacy for ROSE and histological diagnosis; and (ii) quality of histology as determined by total tissue area and tumor percentage in tissue. RESULTS: Thirty patients underwent EUS-FNB of pancreatic or other masses over a 3-month period. Twenty-four lesions were sampled using the Franseen needle only and six after failed diagnostic FNA. Final diagnosis was pancreatic cancer in 12, gastrointestinal stromal cell tumor in five, other tumors in four and benign disease in nine. Diagnostic adequacy for ROSE was 96.6% and histological diagnosis was established in 96.7% of patients. Median tissue area was 2.9 mm CONCLUSION: Preliminary data suggest that the Franseen needle yields diagnostic material for ROSE and histology in >95% of patients.

12 Article Intraprocedural increase in heart rate during EUS-guided celiac plexus neurolysis: Clinically relevant or just a physiologic change? 2016

Bang, Ji Young / Hasan, Muhammad K / Sutton, Bryce / Holt, Bronte A / Navaneethan, Udayakumar / Hawes, Robert / Varadarajulu, Shyam. ·Division of Gastroenterology-Hepatology, Indiana University, Indianapolis, Indiana, USA. · Center for Interventional Endoscopy, Florida Hospital, Orlando, Florida, USA. ·Gastrointest Endosc · Pubmed #27048974.

ABSTRACT: BACKGROUND AND AIMS: Although EUS-guided celiac plexus neurolysis (EUS-CPN) is performed frequently for palliation of pain in pancreatic cancer, response to treatment is variable. Although intraprocedural increases in heart rate during alcohol injection are observed frequently, their significance and relationship to treatment outcome are unknown. The objective of this study was to examine whether a correlation exists between an increase in heart rate and treatment outcomes in patients undergoing EUS-CPN for pain relief in pancreatic cancer. METHODS: This is a prospective observational study of patients with abdominal pain caused by inoperable pancreatic cancer who underwent EUS-CPN. Heart rate change was defined as an increase of ≥15 beats per minute (bpm) for ≥30 seconds during alcohol injection. Main outcome measures were to compare pain, quality of life, opioid use, and survival between heart rate change and no-change groups. RESULTS: Heart rate change was observed in 25 of 51 patients (49.0%) who underwent EUS-CPN over a 12-month period. Although the heart rate change cohort had significantly better adjusted scores for pain (60 vs 73; P = .042) and components of quality of life such as nausea and/or vomiting (65 vs 81; P = .004), financial difficulties (41 vs 57; P = .02), weight loss (45 vs 65; P = .007), and satisfaction with body image (52 vs 62; P = .035), there was no significant difference in postprocedural opioid use or survival between groups. CONCLUSIONS: Because patients with an increase in intraprocedural heart rate experienced significant improvement in pain and quality of life components, this observation must be further explored in order to improve the technique and outcomes of EUS-CPN.

13 Article Digital, single-operator cholangiopancreatoscopy in the diagnosis and management of pancreatobiliary disorders: a multicenter clinical experience (with video). 2016

Navaneethan, Udayakumar / Hasan, Muhammad K / Kommaraju, Kiran / Zhu, Xiang / Hebert-Magee, Shantel / Hawes, Robert H / Vargo, John J / Varadarajulu, Shyam / Parsi, Mansour A. ·Center for Interventional Endoscopy, Orlando, Florida, USA. · Center for Endoscopy and Pancreatobiliary Disorders, Cleveland Clinic, Cleveland, Ohio, USA. ·Gastrointest Endosc · Pubmed #26995690.

ABSTRACT: BACKGROUND AND AIMS: Digital cholangioscopes provide higher-resolution imaging of the pancreatobiliary tract compared with fiberoptic instruments. The role of a new, digital, single-operator cholangiopancreatoscopy (SOC) system for diagnosis and treatment of pancreatobiliary disorders in clinical practice is not known. METHODS: We performed a multicenter, observational study of 105 consecutive patients with suspected pancreatobiliary disorders. The main outcome measures were (1) sensitivity and specificity of SOC visual appearance and biopsies in the diagnosis of indeterminate biliary strictures and (2) achieving complete duct clearance in patients with biliary or pancreatic duct stones. RESULTS: A total of 98 cholangioscopy and 7 pancreatoscopy procedures were performed in 105 patients. Superior views of the ductal lumen and mucosa were obtained in all 44 patients with indeterminate biliary strictures. Among the 44 patients who underwent SOC-guided biopsies, the specimen was adequate for histologic evaluation in 43 patients (97.7%). The sensitivity and specificity of SOC visual impression for diagnosis of malignancy was 90% (95% confidence interval [CI], 69.9%-97.2%) and 95.8% (95% CI, 79.8%-99.3%), respectively. The sensitivity and specificity of SOC-guided biopsies for diagnosis of malignancy was 85% (95% CI, 64.0%-94.8%) and 100% (95% CI, 86.2%-100%). In patients with biliary or pancreatic duct stones (N = 36), complete duct clearance with stone removal in 1 session was accomplished in 86.1% of patients (31/36). Three patients (2.9%) experienced SOC-related adverse events that included cholangitis in 2 patients and postprocedure pancreatitis in 1 patient. CONCLUSIONS: SOC has become an integral part of the ERCP armamentarium and has high accuracy in the evaluation of indeterminate biliary strictures. Complete stone clearance was achieved in all but 1 patient with challenging biliary or pancreatic duct stones. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01815619.).

14 Article Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study. 2015

Navaneethan, Udayakumar / Parsi, Mansour A / Lourdusamy, Dennisdhilak / Grove, David / Sanaka, Madhusudhan R / Hammel, Jeffrey P / Vargo, John J / Dweik, Raed A. ·Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland, OH, USA, udhaykumar81@gmail.com. ·Dig Dis Sci · Pubmed #25708900.

ABSTRACT: BACKGROUND: The use of volatile organic compounds (VOCs) in bile was recently studied and appeared promising for diagnosis of malignancy. Noninvasive diagnosis of malignant biliary strictures by using VOCs in urine has not been studied. AIM: To identify potential VOCs in urine to diagnose malignant biliary strictures. METHODS: In this prospective cross-sectional study, urine was obtained immediately prior to ERCP from consecutive patients with biliary strictures. Selected-ion flow-tube mass spectrometry was used to analyze the concentration of VOCs in urine samples. RESULTS: Fifty-four patients with biliary strictures were enrolled. Fifteen patients had malignant stricture [six cholangiocarcinoma (CCA) and nine pancreatic cancer], and 39 patients had benign strictures [10 primary sclerosing cholangitis (PSC) and 29 with benign biliary conditions including chronic pancreatitis and papillary stenosis]. The concentration of several compounds (ethanol and 2-propanol) was significantly different in patients with malignant compared with benign biliary strictures (p < 0.05). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of malignant biliary strictures adjusted for age and gender based on VOC levels of 2-propranol, carbon disulfide, and trimethyl amine (TMA). The model [-2.4191 * log(2-propanol) + 1.1617 * log(TMA) - 1.2172 * log(carbon disulfide)] ≥ 7.73 identified the patients with malignant biliary stricture [area under the curve (AUC = 0.83)], with 93.3 % sensitivity and 61.5 % specificity (p = 0.009). Comparing patients with CCA and PSC, the model [38.864 * log(ethane) - 3.989 * log(1-octene)] ≤ 169.9 could identify CCA with 80 % sensitivity and 100 % specificity (AUC = 0.9). CONCLUSIONS: Measurement of VOCs in urine may diagnose malignant biliary strictures noninvasively.

15 Article Comparative effectiveness of pyruvate kinase M2 in bile, serum carbohydrate antigen 19-9, and biliary brushings in diagnosing malignant biliary strictures. 2015

Navaneethan, Udayakumar / Lourdusamy, Vennisvasanth / Poptic, Earl / Hammel, Jeffrey P / Sanaka, Madhusudhan R / Parsi, Mansour A. ·Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk Q3, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195, USA, udhaykumar81@gmail.com. ·Dig Dis Sci · Pubmed #25344422.

ABSTRACT: BACKGROUND: The role of M2-PK (pyruvate kinase) in bile has not been studied in comparison with brushings and carbohydrate antigen (CA) 19-9 in the diagnosis of malignant biliary strictures. AIM: To compare the diagnostic accuracy of biliary M2-PK with cytology and serum CA 19-9 METHODS: In this prospective cross-sectional study, bile was aspirated in 74 patients (discovery and validation cohort) undergoing endoscopic retrograde cholangiopancreatography. Levels of M2-PK were measured in bile and compared to brushings for cytology and CA 19-9. RESULTS: In the discovery cohort, the median bile M2-PK levels were significantly elevated in patients with malignant biliary strictures [187.9 U/l (interquartile range (IQR) 3.5, 3626.8)] compared to those with benign biliary conditions and primary sclerosing cholangitis [0 U/l (IQR 0, 15)] (P = 0.007). A M2-PK cutoff value of 109.1 U/l distinguished malignant from benign conditions with a sensitivity and specificity of 52.9 and 94.1 %, respectively, and area under curve (AUC) of 0.77. The sensitivity of CA 19-9 and brushings in diagnosing cancer was 52.9 % and 11.1 % and specificity 94.1 and 100 %, respectively. The presence of elevated M2-PK >109.1 U/l or CA 19-9 >33 U/ml or positive brushing was 88.2 % sensitive and 88.2 % specific, AUC of 0.89 in the diagnosis of malignancy. The diagnostic accuracy was confirmed in the validation cohort. CONCLUSIONS: As a stand-alone factor, none of the markers were able to distinguish benign from malignant biliary strictures with a high sensitivity. However, a combination was highly sensitive in diagnosing malignant biliary strictures.

16 Article Bile proteomics for differentiation of malignant from benign biliary strictures: a pilot study. 2015

Navaneethan, Udayakumar / Lourdusamy, Vennisvasanth / Gk Venkatesh, Preethi / Willard, Belinda / Sanaka, Madhusudhan R / Parsi, Mansour A. ·Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA udhaykumar81@gmail.com. · Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, OH, USA and Proteomics Core Laboratory, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. ·Gastroenterol Rep (Oxf) · Pubmed #25304323.

ABSTRACT: BACKGROUND: Determining the etiology of biliary strictures is challenging, and the sensitivities of the current tests to diagnose them are low. Protein biomarkers in bile, in combination with other tests, may improve sensitivity in diagnosing biliary strictures. OBJECTIVE: To analyse the differential abundance of proteins in benign and malignant biliary strictures through proteomic analysis of bile. METHODS: In this prospective, cross-sectional study, bile was aspirated in 24 patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) including six patients with primary sclerosing cholangitis (PSC), three with cholangiocarcinoma (CCA), ten with pancreatic cancer, and five with benign biliary conditions. Liquid chromatography/mass spectrometry was used to examine the bile for differential abundance of protein biomarkers. The relative abundance of various proteins was compared in the malignant vs. benign groups and in CCA vs. PSC. RESULTS: The majority of the proteins identified in bile were similar to those of the plasma (plasma proteins) and certain proteins were differentially expressed among the different groups (CCA, pancreatic cancer, PSC or benign). A total of 18 proteins were identified as being more abundant in the malignant group (CCA and pancreatic cancer) than in the benign strictures group, including myeloperoxidase, complement C3, inter-alpha-trypsin inhibitor heavy chain H4, apolipoprotein B-100, and kininogen-1 isoform 2. A total of 30 proteins were identified to be less abundant in the malignant group than in the benign group, including trefoil factor 2, superoxide dismutase [Cu-Zn], kallikrein-1, carboxypeptidase B and trefoil factor 1. CONCLUSIONS: Protein biomarkers in bile may differentiate malignant from benign biliary strictures. Larger studies are warranted to validate these observations.

17 Article Volatile organic compounds in bile can diagnose malignant biliary strictures in the setting of pancreatic cancer: a preliminary observation. 2014

Navaneethan, Udayakumar / Parsi, Mansour A / Gutierrez, Norma G / Bhatt, Amit / Venkatesh, Preethi G K / Lourdusamy, Dennisdhilak / Grove, David / Hammel, Jeffrey P / Jang, Sunguk / Sanaka, Madhusudhan R / Stevens, Tyler / Vargo, John J / Dweik, Raed A. ·Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland, Ohio, USA. · Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland Clinic, Cleveland, Ohio, USA. ·Gastrointest Endosc · Pubmed #24929484.

ABSTRACT: BACKGROUND: Ascertaining the nature of biliary strictures is challenging. The role of volatile organic compounds (VOCs) in bile in determining the cause of biliary strictures is not known. OBJECTIVE: To identify potential VOCs in the headspaces (gas above the sample) of bile in patients with malignant biliary strictures from pancreatic cancer. DESIGN: Prospective cross-sectional study. SETTING: Referral center. PATIENTS: Prospective study in which bile was aspirated in 96 patients undergoing ERCP for benign and malignant conditions. MAIN OUTCOME MEASUREMENTS: Selected ion flow tube mass spectrometry (VOICE200R SIFT-MS instrument; Syft Technologies Ltd, Christchurch, New Zealand) was used to analyze the headspace and to build a predictive model for pancreatic cancer. RESULTS: The headspaces from 96 bile samples were analyzed, including 24 from patients with pancreatic cancer and 72 from patients with benign biliary conditions. The concentrations of 6 compounds (acetaldehyde, acetone, benzene, carbon disulfide, pentane, and trimethylamine [TMA]) were increased in patients with pancreatic cancer compared with controls (P < .05). By using receiver-operating characteristic curve analysis, we developed a model for the diagnosis of pancreatic cancer based on the levels of TMA, acetone, isoprene, dimethyl sulfide, and acetaldehyde. The model [10.94 + 1.8229* log (acetaldehyde) + 0.7600* log (acetone) - 1.1746* log (dimethyl sulfide) + 1.0901* log (isoprene) - 2.1401 * log (trimethylamine) ≥ 10] identified the patients with pancreatic cancer (area under the curve = 0.85), with 83.3% sensitivity and 81.9% specificity. LIMITATIONS: Sample size. CONCLUSIONS: The measurement of biliary fluid VOCs may help to distinguish malignant from benign biliary strictures. Further studies are warranted to validate these observations. (Clinical Trial Registration Number NCT01565460.).

18 Article Predictors for detection of cancer in patients with indeterminate biliary stricture and atypical cells on endoscopic retrograde brush cytology. 2014

Navaneethan, Udayakumar / Singh, Tavankit / Gutierrez, Norma G / Jegadeesan, Ramprasad / Venkatesh, Preethi G / Brainard, Jennifer / Vargo, John J / Parsi, Mansour A. ·Department of Gastroenterology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. ·J Dig Dis · Pubmed #24612456.

ABSTRACT: OBJECTIVE: The management of atypical cells on endoscopic retrograde brush cytology (ERBC) in patients with indeterminate biliary stricture is unclear. This study aimed to investigate the detection of cancer (pancreatic and biliary carcinoma) in patients with atypical cells on ERBC and the factors predicting it. METHODS: From a prospectively maintained cytology database in a tertiary care center, patients with indeterminate biliary stricture and atypical cells on ERBC from 1996 to 2012 were studied. The date of the initial ERBC with atypical cells was identified as time zero. The primary outcome was to study the incidences and Kaplan-Meier estimates for detecting cancer. RESULTS: In all, 104 patients with 182.8 person-years of follow-up were identified. In 38 (36.5%) patients cancer was detected (19 cholangiocarcinoma, 15 pancreatic cancer, three ampullary cancer and one gallbladder carcinoma) over a mean follow-up of 4.4 months. On Cox regression analysis, the presence of clinical jaundice (hazard ratio [HR] 4.08, 95% CI 1.41-11.8), active alcohol consumption (HR 7.33, 95% CI 1.85-29.1) and elevated carbohydrate antigen 19-9 (CA19-9) level (>33 U/mL) (HR 8.42, 95% CI 1.75-40.6) at the time of ERBC were associated with increased risk for the detection of cancer. Detection of cancer was more common during the first 6 months of follow-up than at any time period thereafter. CONCLUSION: Elevated CA19-9 level, the presence of clinical jaundice and current alcohol consumption are associated with increased detection of cancer in patients with indeterminate biliary stricture and atypical cells on ERBC.

19 Article Vascular endothelial growth factor levels in bile distinguishes pancreatic cancer from other etiologies of biliary stricture: a pilot study. 2013

Navaneethan, Udayakumar / Gutierrez, Norma G / Jegadeesan, Ramprasad / Venkatesh, Preethi G K / Poptic, Earl / Liu, Xiuli / Sanaka, Madhusudhan R / Jang, Sunguk / Vargo, John J / Parsi, Mansour A. ·Section for Advanced Endoscopy and Pancreatobiliary Disorders, Department of Gastroenterology and Hepatology, Digestive Disease Institute, Desk A30, The Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH, 44195, USA, udhaykumar81@gmail.com. ·Dig Dis Sci · Pubmed #23828141.

ABSTRACT: BACKGROUND: Determining the benign or malignant nature of biliary strictures can be challenging. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. OBJECTIVE: The purpose of this study was to investigate whether VEGF levels in bile aspirated during endoscopic retrograde cholangiography (ERCP) can distinguish pancreatic cancer from other causes of biliary stricture. METHODS: Bile was directly aspirated in 53 consecutive patients from March 2012 to October 2012 during ERCP from the common bile duct including 15 with pancreatic cancer, 18 with primary sclerosing cholangitis (PSC), nine with cholangiocarcinoma (CCA), and 11 with benign biliary conditions (sphincter of Oddi and choledocholihiasis). Levels of VEGF in bile were measured. The diagnostic performance was then validated in a second, independent validation cohort of 18 patients (pancreatic cancer n = 10, benign n = 8). RESULTS: A total of 53 consecutive patients were recruited. The median bile VEGF levels were significantly elevated in patients with pancreatic cancer (1.9 ng/ml (interquartile range [IQR] 0.7, 2.2) compared to those with benign biliary conditions (0.3 ng/ml [IQR 0.2, 0.6]; p < 0.001), PSC (0.7 ng/ml [IQR 0.5, 0.9]; p = 0.02) or CCA (0.4 ng/ml [IQR 0.1, 0.5]; p < 0.001). A VEGF cut-off value of 0.5 ng/ml distinguished pancreatic cancer from CCA with a sensitivity and specificity of 93.3 and 88.9 %, respectively, and area under curve (AUC) of 0.93, and from benign conditions with a sensitivity and specificity of 93.3 and 72.7 %, respectively, with AUC of 0.89. The diagnostic accuracy of biliary VEGF was confirmed in the second independent validation cohort. CONCLUSIONS: This study suggests that measurement of biliary VEGF-1 levels distinguishes patients with pancreatic cancer from other etiologies of biliary stricture. This may be particularly relevant in approaching patients with indeterminate biliary stricture.