On-site Cytopathology EUS-FNA

Pancreatic Cancer Clinical Trial

Official title:

The Clinical Impact of Immediate On-site Cytopathology Evaluation During Endoscopic Ultrasound-Guided Fine Needle Aspiration of Pancreatic Mass: A Multicenter, Prospective Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01386931
• Other study ID #: 11-0919
• Secondary ID: 11-0919
• Status: Completed
• Start date: June 2011
• Est. completion date: June 16, 2017

Study information

• Verified date: May 2018
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is a multicenter prospective randomized controlled trial. Potential participants in this study include patients referred for Endoscopic Ultrasound-guided fine needle aspiration (EUS-FNA) of a solid pancreatic lesion at one of the participating centers. If the patient meets inclusion criteria and signs the informed consent, they will be randomized into one of the two study arms in a 1:1 ratio. Patients will either undergo EUS-FNA with or without an on-site cytopathologist present during EUS-FNA. Patients assigned to the on-site cytopathologist arm will have the cytopathologist dictate the number of fine needle aspiration (FNA) passes performed by the endosonographer. This number will be based on the adequacy of specimen and the ability to provide a preliminary diagnosis. In the other arm, in the absence of an on-site cytopathologist, the endosonographer will perform a predetermined number of 7 passes (standard of care in the absence of an on-site cytopathologist). The technique of performing EUS-FNA (needle type, use of stylet, suction) will be standardized among all endosonographers in order to rule out confounding factors. After EUS-FNA is performed all slides will be sent to the pathology department. The slides will be sent for review regardless of which arm the patient is randomized into, and they will be reviewed by experienced cytopathologists for the purpose of determining the final diagnoses.

Future clinical intervention will be monitored for the purpose of reporting the impact EUS-FNA has on the patient's clinical course and determining diagnostic accuracy. Patients will be followed prospectively for at least one year, and the gold-standard for final diagnosis of pancreatic malignancy will be defined by the presence of malignant cytology or histologic evidence (if the patient undergoes surgery) or with clinical and/or imaging follow-up consistent with pancreatic cancer (death or clinical progression). A detailed account of medical equipment used during each procedure, procedure time, clinic visits/hospitalizations due to procedure related complications, and number of repeat procedures will be recorded systematically.

The investigators hypothesize that an on-site cytopathologist during EUS-FNA for pancreatic masses improves diagnostic yield, accuracy, and lowers the duration, complications and the need for repeat procedures.

Description:

Endoscopic Ultrasound (EUS) plays an integral role in the diagnosis of suspected pancreatic cancer, and the EUS findings are crucial for determining the course of future management and potential treatment options for these patients. EUS is the most sensitive imaging modality for the detection of pancreatic masses, and has a sensitivity of greater than or equal to 90%. Furthermore, EUS-guided fine needle aspiration (EUS-FNA) plays an important role in accurate staging of pancreatic cancer with a sensitivity of 85% and specificity close to 100%. EUS-FNA is considered to be cost-effective by virtue of its impact on therapeutic management. In particular, real-time tissue sampling by EUS-FNA is possible when a cytopathologist (pathologist skilled in evaluating fine needle aspiration specimens) is able to be present at the time of FNA in order to review the biopsy slides and make a preliminary diagnosis. The availability of an on-site cytopathologist has the potential to provide quick diagnostic and predictive information to confirm the presence and staging of suspected malignancy. The rationale for an on-site cytopathologist includes increasing the adequacy and yield of biopsy tissue/aspirate which can decrease the need for additional passes to obtain a diagnostic yield of tissue. This hypothesis, however, has not been formally examined.

In this proposed randomized controlled multicenter trial, the investigators hypothesize that an on-site cytopathologist during EUS-FNA for pancreatic masses improves diagnostic yield, accuracy, and lowers the duration, complications and the need for repeat procedures. This hypothesis will be explored in the context of the following specific aims.

Specific aim #1: To compare the diagnostic yield of malignancy and proportion of inadequate specimens between the two groups.

Specific aim #2: To compare the sensitivity, specificity and accuracy of EUS-FNA between the two groups using histologic diagnosis or cytologic diagnosis in conjunction with clinical and/or imaging follow-up as the gold standard.

Specific aim #3: To compare the duration, rate of complications and repeat procedures between the two groups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: June 16, 2017
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients age: greater than or equal to 18 years

• Presence of a solid pancreatic mass lesion confirmed by at least a single investigational modality such as computerized axial tomography (CT) scan, magnetic resonance imaging (MRI) or Endoscopic Ultrasound (EUS)

• Ability to provide written informed consent

Exclusion Criteria:

• Severe coagulopathy [International Normalized Ratio (INR) > 1.8] or thrombocytopenia (platelet count <50,000)

• Pure cystic lesions of the pancreas

• Inability to sample lesion due to the presence of intervening blood vessels

• Results of EUS-FNA would not impact patient management

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Procedure:
• EUS-guided FNA performed with on-site Cytopathologist
Patients assigned to the on-site cytopathologist arm will have the cytopathologist dictate the number of FNA passes performed by the endosonographer. This number will be based on the adequacy of specimen and the ability to provide a preliminary diagnosis.
• EUS-guided FNA performed without on-site Cytopathologist
In the absence of an on-site cytopathologist, the endosonographer will perform a predetermined number of 7 passes (standard of care in the absence of an on-site cytopathologist).

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	Kansas City Veteran Affairs Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (27)

Agarwal B, Abu-Hamda E, Molke KL, Correa AM, Ho L. Endoscopic ultrasound-guided fine needle aspiration and multidetector spiral CT in the diagnosis of pancreatic cancer. Am J Gastroenterol. 2004 May;99(5):844-50. — View Citation

Chang KJ, Katz KD, Durbin TE, Erickson RA, Butler JA, Lin F, Wuerker RB. Endoscopic ultrasound-guided fine-needle aspiration. Gastrointest Endosc. 1994 Nov-Dec;40(6):694-9. — View Citation

Cherian PT, Mohan P, Douiri A, Taniere P, Hejmadi RK, Mahon BS. Role of endoscopic ultrasound-guided fine-needle aspiration in the diagnosis of solid pancreatic and peripancreatic lesions: is onsite cytopathology necessary? HPB (Oxford). 2010 Aug;12(6):389-95. doi: 10.1111/j.1477-2574.2010.00180.x. — View Citation

DeWitt J, Devereaux B, Chriswell M, McGreevy K, Howard T, Imperiale TF, Ciaccia D, Lane KA, Maglinte D, Kopecky K, LeBlanc J, McHenry L, Madura J, Aisen A, Cramer H, Cummings O, Sherman S. Comparison of endoscopic ultrasonography and multidetector computed tomography for detecting and staging pancreatic cancer. Ann Intern Med. 2004 Nov 16;141(10):753-63. — View Citation

Eloubeidi MA, Chen VK, Eltoum IA, Jhala D, Chhieng DC, Jhala N, Vickers SM, Wilcox CM. Endoscopic ultrasound-guided fine needle aspiration biopsy of patients with suspected pancreatic cancer: diagnostic accuracy and acute and 30-day complications. Am J Gastroenterol. 2003 Dec;98(12):2663-8. — View Citation

Erickson RA, Sayage-Rabie L, Beissner RS. Factors predicting the number of EUS-guided fine-needle passes for diagnosis of pancreatic malignancies. Gastrointest Endosc. 2000 Feb;51(2):184-90. — View Citation

Faigel DO, Ginsberg GG, Bentz JS, Gupta PK, Smith DB, Kochman ML. Endoscopic ultrasound-guided real-time fine-needle aspiration biopsy of the pancreas in cancer patients with pancreatic lesions. J Clin Oncol. 1997 Apr;15(4):1439-43. — View Citation

Harewood GC, Wiersema LM, Halling AC, Keeney GL, Salamao DR, Wiersema MJ. Influence of EUS training and pathology interpretation on accuracy of EUS-guided fine needle aspiration of pancreatic masses. Gastrointest Endosc. 2002 May;55(6):669-73. — View Citation

Hunt GC, Faigel DO. Assessment of EUS for diagnosing, staging, and determining resectability of pancreatic cancer: a review. Gastrointest Endosc. 2002 Feb;55(2):232-7. Review. — View Citation

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. doi: 10.3322/caac.20073. Epub 2010 Jul 7. Erratum in: CA Cancer J Clin. 2011 Mar-Apr;61(2):133-4. — View Citation

Klapman JB, Logrono R, Dye CE, Waxman I. Clinical impact of on-site cytopathology interpretation on endoscopic ultrasound-guided fine needle aspiration. Am J Gastroenterol. 2003 Jun;98(6):1289-94. — View Citation

LeBlanc JK, Ciaccia D, Al-Assi MT, McGrath K, Imperiale T, Tao LC, Vallery S, DeWitt J, Sherman S, Collins E. Optimal number of EUS-guided fine needle passes needed to obtain a correct diagnosis. Gastrointest Endosc. 2004 Apr;59(4):475-81. — View Citation

Lee JH, Stewart J, Ross WA, Anandasabapathy S, Xiao L, Staerkel G. Blinded prospective comparison of the performance of 22-gauge and 25-gauge needles in endoscopic ultrasound-guided fine needle aspiration of the pancreas and peri-pancreatic lesions. Dig Dis Sci. 2009 Oct;54(10):2274-81. doi: 10.1007/s10620-009-0906-1. Epub 2009 Aug 11. — View Citation

Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc. 2000 Sep;52(3):367-71. — View Citation

Ngamruengphong S, Li F, Zhou Y, Chak A, Cooper GS, Das A. EUS and survival in patients with pancreatic cancer: a population-based study. Gastrointest Endosc. 2010 Jul;72(1):78-83, 83.e1-2. doi: 10.1016/j.gie.2010.01.072. — View Citation

Puli SR, Singh S, Hagedorn CH, Reddy J, Olyaee M. Diagnostic accuracy of EUS for vascular invasion in pancreatic and periampullary cancers: a meta-analysis and systematic review. Gastrointest Endosc. 2007 May;65(6):788-97. Epub 2007 Mar 9. Review. — View Citation

Rastogi A, Wani S, Gupta N, Singh V, Gaddam S, Reddymasu S, Ulusarac O, Fan F, Romanas M, Dennis KL, Sharma P, Bansal A, Oropeza-Vail M, Olyaee M. A prospective, single-blind, randomized, controlled trial of EUS-guided FNA with and without a stylet. Gastrointest Endosc. 2011 Jul;74(1):58-64. doi: 10.1016/j.gie.2011.02.015. Epub 2011 Apr 23. — View Citation

Savides TJ, Donohue M, Hunt G, Al-Haddad M, Aslanian H, Ben-Menachem T, Chen VK, Coyle W, Deutsch J, DeWitt J, Dhawan M, Eckardt A, Eloubeidi M, Esker A, Gordon SR, Gress F, Ikenberry S, Joyce AM, Klapman J, Lo S, Maluf-Filho F, Nickl N, Singh V, Wills J, Behling C. EUS-guided FNA diagnostic yield of malignancy in solid pancreatic masses: a benchmark for quality performance measurement. Gastrointest Endosc. 2007 Aug;66(2):277-82. — View Citation

Siddiqui UD, Rossi F, Rosenthal LS, Padda MS, Murali-Dharan V, Aslanian HR. EUS-guided FNA of solid pancreatic masses: a prospective, randomized trial comparing 22-gauge and 25-gauge needles. Gastrointest Endosc. 2009 Dec;70(6):1093-7. doi: 10.1016/j.gie.2009.05.037. Epub 2009 Jul 28. — View Citation

Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, Coleman J, Hruban RH, Lillemoe KD. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000 Nov-Dec;4(6):567-79. — View Citation

Tadic M, Kujundzic M, Stoos-Veic T, Kaic G, Vukelic-Markovic M. Role of repeated endoscopic ultrasound-guided fine needle aspiration in small solid pancreatic masses with previous indeterminate and negative cytological findings. Dig Dis. 2008;26(4):377-82. doi: 10.1159/000177025. Epub 2009 Jan 30. — View Citation

Turner BG, Cizginer S, Agarwal D, Yang J, Pitman MB, Brugge WR. Diagnosis of pancreatic neoplasia with EUS and FNA: a report of accuracy. Gastrointest Endosc. 2010 Jan;71(1):91-8. doi: 10.1016/j.gie.2009.06.017. — View Citation

Vilmann P, Saftoiu A. Endoscopic ultrasound-guided fine needle aspiration biopsy: equipment and technique. J Gastroenterol Hepatol. 2006 Nov;21(11):1646-55. Review. — View Citation

Wallace MB, Kennedy T, Durkalski V, Eloubeidi MA, Etamad R, Matsuda K, Lewin D, Van Velse A, Hennesey W, Hawes RH, Hoffman BJ. Randomized controlled trial of EUS-guided fine needle aspiration techniques for the detection of malignant lymphadenopathy. Gastrointest Endosc. 2001 Oct;54(4):441-7. — View Citation

Wani S, Gupta N, Gaddam S, Singh V, Ulusarac O, Romanas M, Bansal A, Sharma P, Olyaee MS, Rastogi A. A comparative study of endoscopic ultrasound guided fine needle aspiration with and without a stylet. Dig Dis Sci. 2011 Aug;56(8):2409-14. doi: 10.1007/s10620-011-1608-z. Epub 2011 Feb 17. — View Citation

Williams DB, Sahai AV, Aabakken L, Penman ID, van Velse A, Webb J, Wilson M, Hoffman BJ, Hawes RH. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut. 1999 May;44(5):720-6. — View Citation

Ylagan LR, Edmundowicz S, Kasal K, Walsh D, Lu DW. Endoscopic ultrasound guided fine-needle aspiration cytology of pancreatic carcinoma: a 3-year experience and review of the literature. Cancer. 2002 Dec 25;96(6):362-9. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compare the percent of patients with a positive diagnosis of malignancy in each of the two groups.	The Investigators would like to look at each of the two groups to assess whether or not having an onsite cytopathologist during EUS-FNA increases the diagnostic accuracy of pancreatic malignancies. To do this, the Investigators will compare the percent of patients in each group who were accurately diagnosed with a malignancy during EUS-FNA to see if the on-site cytopathologist group yields a higher percent of positively diagnosed malignancies.	1 year from the time of patient enrollment
Primary	Compare the percent of patients with inadequate samples (defined by an absence of cellular elements to account for a mass/lesion) between the two groups	Final slides will be reviewed by three experienced cytopathologists blinded to the patient's randomization group. The slides for each pass will be assessed for: cellularity, adequacy of specimen, contamination, amount of blood, and diagnosis. Using the cytopathologists' assessment of the FNA specimens, the Investigators will compare the percent of patients with inadequate samples in each group to see if the absence of an on-site cytopathologist corresponds with a higher percent of inadequate FNA samples.	1-2 weeks from patient enrollment/EUS-FNA
Secondary	Compare the sensitivity, specificity and accuracy of EUS-FNA between the two groups	Sensitivity, specificity and accuracy of EUS-FNA will be evaluated using histologic diagnosis or cytologic diagnosis in conjunction with clinical and/or imaging follow-up as the gold standard.	1 year from patient enrollment
Secondary	Compare the mean number of passes in the two groups	Once all patients have been enrolled and have undergone EUS-FNA with or without an on-site cytopathologist, the Investigators will be able to compare the mean number of fine needle aspiration passes taken during EUS for patients in each group.	1 year (length of time it takes to enroll all patients)
Secondary	Compare the complication rate in the two groups	The complication rates from the two groups of subjects will be evaluated when all subjects have been enrolled.	1 year (length of time it takes to enroll all patients)
Secondary	Compare the EUS procedure duration in each group	The EUS procedure duration from the two groups of subjects will be evaluated when all subjects have been enrolled.	1 year
Secondary	Compare the percent of patients requiring repeat procedures between the groups	The investigators will follow patients for one year after enrollment to see if they have had any repeat procedures for the purpose of diagnosing their pancreatic mass.	1 year after the time of patient enrollment