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Endoscopic ultrasound (EUS) in restaging of esophageal cancer after adjuvant chemoradiation
ENDOSCOPIC ULTRASOUND t597
599
INTEROBSERVER AGREEMENT AMONG ENDOSONOGRA]PEgERS FOR STAGING OF PANCREATIC CANCER BY ENDOSCOPIC ULTRASOUND. F. Gross, D. Ciaeeia, C. Schmitt, M. Catalano, J. Affrenfi, K. Binmceller, P. Stevens, T. Savides, M. Bhutani, L. RJcobein,N. Niekl, D. Faigel, J, Birk, C. Lightdale. Indiana Univemity Medical Center, University of TennesseeChattanooga Unit, St. Luke's Medical Center, University of Florida, University Hospital Hamburg, Columbia Presbyterian Medical Center, University of California at San Diego, Wright State University,University of Kentucky, Portland VAMC, Winthrop University HoepitaYSUNYStonyBrook. Endoscopic Ultrasound (EUS) has been reported to be an accurate modality for staging panerentic cancer (CA). However, there is limited data regarding the effects of intembserver variation on the overall accuracy and clinical utility of EUS for staging pancreatic CA. AIM OF STUDY: To determine interobserver reliability for EUS staging of pancreatic tumors. METHODS: Twelve patients with previously diagnosed pancreatic duetal adenecarcinoma undenvent staging with EUS. Surgical correlation was obtained in aJl pafica'Rs.A blinded observer developed a study videotape of real-time EUS for each case. The videotape was then distributedto ten endosonograpbers with at least one year of previous experience who independently reviewed the tape and recorded their interpretation of the EUS tumor stage for eada case based upon previously reported EUS criteria for staging pancreatic CA. A multiple observer kappa (k) statistic was calculated for eneh staging category (T, N, and T+N), vascalar invasion and overall k. Kappa accounts for agreement due to chance alone and standardized ranges are available. The Light (G) statistie was utilized to allow for the presence of the gold standard. Accuracy was assessed using a simple matrix format. RESULTS: Overall agreement was highly statistically significant for T stage: k=0.22 ( G=5.52, Z=2.35, p<0.0l).Observers were more likely to agree with T3 stage tumors (94%) than "1"2(40%) or T1 (33%) lesions. The Overall agreement for N stage was highly statistically significant: k=0.23 (G----4.44,Z=4.90, p<0.01). Agreement for absence of nodal involvement (63%) was better than that for the presence of nodal involvement (56%). For overall staging if+N): k=0.18 (G-=9.19, Z=4.98, p<.01). For vascular invasion: k------~.26(G=-3.90, z=3.33, p<.01). The agreement for T and N stage improved as stage increased (p<0.01) and in the presence of vascular invasion (p<0.01). CONCLUSION: Interobserver agreement is good for staging pancreatic tumors by EUS. However, it appears to be better for some tumor stages than others. Experience may play a role in the successful use of this medality to evaluate pancreatic rumors.
EUS-GUIDED INJECTION OF BOTULINUM TOXIN (BOTOX) FOR ACHALASIA: FINAL REPORT OF AN OPEN STUDY. BJ Hoffinan, W Knapplo, MS Bhutani, L Aahakkon, GN Verne RH Hawes. Digestive Disease Center. Medical University of South Carolina. Charleston, SC Purpose: We have previously reported that EUS-guided injection of Botox for treatment of aehalasia may have an improved long-term success rate compared to blind injection. The following is an update with incm.asedpatient numbers and longer follow up. Methods: 26 patients with manometrieally documented idiopathic achalasia answered a questionnaire regarding symptoms of regurgitation, chest pain, and dysphagia before treatment and every 3 months after. They were scored based upon the following scale: 0, none; 1, occasionally; 2, daily; 3, with every meal~ The maximum possible score was nine; failure of treatment was considered a score of 3 or more. EUS was performed using the Pontax FG32UA linear array eehoendoscopa. A 4 cm long, 23 gauge needle was passed through the echoendoscope and advanced into the museularis propria at the level of the LES under renl-time EUS guidance. Four injectious of 1 ec Botox (20 u/co) were made into the LES in different quadrants. Results: 25 patients ages 20-84 (52) were studied. 9 of thuse patients had prior therapy with either myotomy, dilatation, or blind injection. Response duration ranged from 0-24 mo (9.7). 3 (12%) of patients failed treatment and went to myotomy. 3(12%) of patients initially responded but required repeat therapy within 18 months. All of the patients who required repeat injection responded. There was no ago difference between respondars and nonrespondars. All of the patients who failed treatment had prior therapy. 2/3 of the patients who required repeat injection had prior therapy. Complications included mild chest pain in 8% and GERD in 4%. Canelusious: Patients treated with EUS-guided Botox injection for idiopathic achalasia demonstrate a longer improvement in their symptoms over published reports of endoscopic blind injection. Further investigation is needed to determine which patients optimally respond to Botox. A randomized trial comparing blind to EUS-guided injection has been initiated.
t598
t600
IS PANCREATITIS A COMPLICATION OF ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION OF THE PANCREAS? F. Crress~ S. Ikenberry, D. Ciaccia, J. Kid, G. Lchman; Division of Gastroenterology, Indiana University Medical Center, Indianapolis, IN. and Winthrop-University Hospital, SUNY StonyBrook School of Medicine Introduction: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of the pancreas is increasingly being utilized to diagnose pancreatic masses. We have previously reported 2 cases of clinical panereatitis following EUS guided FNA of the pancreas. Aim of Study: To determine the frequency of chemical and clinical panereatitis following EUS guided FNA of the pancreas. Methods: All patients having EUS guided FNA biopsy of the pancreas were eligible. Exclusion criteria included: All patients with acute p a n c r e n ~ or having ERCP within 48 hours of the EUS FNA. Serum amylase and lipase levels were measured immediately prior to and 2 hours post EUS FNA. Patients were called 24-72 hours after FNA to follow up for increased pain, nausea, or vomiting suggesting clinical pancreatitis. RasuRs: Data was prospeotively collected on 36 patients. Pro- and post-FNA amylase and lipase levels were available for all patients. Ten patients bad a past history of panereatitis prior to the EUS FNA. Pro and Post EUS Guided FNA Serum Enzyme Levels Amylase MeanPre [ Mean Post ] Mean Change [ CI PValue [ 70.0 75.0 5.0 - 31.4~ 20:2 .47 Lipase 315.0 547.6 232.0 - 45819, ~6.05 .044 CI = Confidence Interval As a group, there was a mean increase in serum amylase and lipase levels. When matched pair analysis was performed, the differences were not statistically significant for amylase levels but were for lipase (p<0.05) suggesting that lipase may be a more sensitive marker. There were no episodes of clinical panereatitis. The lipase levels were elevated the most in 60% (6/10) of patients with a past history of pancreatitis. Conclusion: This prospective study found no evidence of clinical pancrentitis. Patients with a prior history of pancreatitis had higher amylase and lipase levels than those who did not suggesting this as a possible risk factorl Based on this prospective study, further investigations are warranted to evaluate the true risk of pancreatitis from this procedure.
ENDOSCOPIC ULTRASOUND(EUS) IN RESTAGING OF ESOPHAGEALCANCERAFTER ADJUVANT CHEMORADIATION G isenhern. A Chek, M Canto, N Levitan, J Clayman, B Pollack, M V Sivak, Jr. UniversityHospitalsof Cleveland,Case Western ReserveUniversity, Cleveland,OH. Background Endoscopic ultrasound {EUS) is established as the most accurate method currently available for determining the depth of primary cancer invasion (T stage). Standard EUS criteria may not be accuratein assessingdepth of cancerinvasionand nodal status after patients have received chemotherapy or radiotherapy due to residual fibrosis and inflammation. Methods We conducted a prospective study to determine if EUS estimation of tumor size could be used to assess responseto preoperativeadjuvant chemoradiation. Using EUS,TNM stage was assessedon 31 patients {22 men: 9 women; mean age - 62 yrs) with cancerof esophagus or cerdia (19 adenocarcinoma, 12 squamous cell cancer) prior to initiation of combined radiation and 5-FUIcisplatin (and/or carboplatinum) chemotherapy. The crosssectional area (MAX) of the tumor in the transverseplane at the location where the tumor had maximal thickness was calculated to estimate tumor size. EUS staging and measurementof MAX were repeated at completion of adjuvant therapy just prior to surgery. Responseto preoperativeadjuvant chemoradiationwas definedas 50% reduction in MAX. Surgicalstaging was comparedbetweenrespendersand nonresponders. Results Eight patients who did not undergo surgery were excluded from analysis. EUS T stage in the remaining23 patients prior to therapy was as follows: 3 T2, 16 T3, and 4 T4. Followingchemoradiation,EUST staging was changedin 6 pts {3 T4 downstsoedto T3, 2 T3 downstaged to T2, and 1 T3 downstagedto T1). At surgical pathology, 3 pts had no residual tumor in the esophagus(TO), 5 had TI, 3 had T2, 10 had T3, and 2 had T4 tumors. EUS T staging accuracy following adjuvant therapy was only 43%. MAX decreasedfrom a mean of 5.5 +/- 2.4 sq cm to 1.6 +1. 0.9 sq cm in responders, whereas MAX went from 7.0 +/- 3.0 sq cm to 5.4 +/- 2.2 sq cm in nonresponders(p-O.009 using Wilcoxon rank-sum statistics). 10/13 patients with at least a 50% reduction in MAX (responders)had TO, T1, or T2 tumors at surgery whereas 9/10 nonresponders had T3 or T4 tumors at surgery {p=0.001 using likelihood chi-squarestatistics). There was no difference in T stage between respondersand nnnrespondersprior to chemoradiation. Conclusions [1] standard EUS staging criteria are not accurate after adjuvant chemoradistien,[2] reductionin maximal cross.sectionalarea (MAX) of tumor appearsto be a more useful measure for assessing responseof esophageal cancer to preoperativeadjuvant chemoradiation, and [3] responders (patients with a > 50% reduction of MAX) have an increasedlikelihoodof downstaging at surgerythan nonresponders.
AB174
GASTROINTESTINAL ENDOSCOPY
VOLUME 45, NO. 4, 1997
599
INTEROBSERVER AGREEMENT AMONG ENDOSONOGRA]PEgERS FOR STAGING OF PANCREATIC CANCER BY ENDOSCOPIC ULTRASOUND. F. Gross, D. Ciaeeia, C. Schmitt, M. Catalano, J. Affrenfi, K. Binmceller, P. Stevens, T. Savides, M. Bhutani, L. RJcobein,N. Niekl, D. Faigel, J, Birk, C. Lightdale. Indiana Univemity Medical Center, University of TennesseeChattanooga Unit, St. Luke's Medical Center, University of Florida, University Hospital Hamburg, Columbia Presbyterian Medical Center, University of California at San Diego, Wright State University,University of Kentucky, Portland VAMC, Winthrop University HoepitaYSUNYStonyBrook. Endoscopic Ultrasound (EUS) has been reported to be an accurate modality for staging panerentic cancer (CA). However, there is limited data regarding the effects of intembserver variation on the overall accuracy and clinical utility of EUS for staging pancreatic CA. AIM OF STUDY: To determine interobserver reliability for EUS staging of pancreatic tumors. METHODS: Twelve patients with previously diagnosed pancreatic duetal adenecarcinoma undenvent staging with EUS. Surgical correlation was obtained in aJl pafica'Rs.A blinded observer developed a study videotape of real-time EUS for each case. The videotape was then distributedto ten endosonograpbers with at least one year of previous experience who independently reviewed the tape and recorded their interpretation of the EUS tumor stage for eada case based upon previously reported EUS criteria for staging pancreatic CA. A multiple observer kappa (k) statistic was calculated for eneh staging category (T, N, and T+N), vascalar invasion and overall k. Kappa accounts for agreement due to chance alone and standardized ranges are available. The Light (G) statistie was utilized to allow for the presence of the gold standard. Accuracy was assessed using a simple matrix format. RESULTS: Overall agreement was highly statistically significant for T stage: k=0.22 ( G=5.52, Z=2.35, p<0.0l).Observers were more likely to agree with T3 stage tumors (94%) than "1"2(40%) or T1 (33%) lesions. The Overall agreement for N stage was highly statistically significant: k=0.23 (G----4.44,Z=4.90, p<0.01). Agreement for absence of nodal involvement (63%) was better than that for the presence of nodal involvement (56%). For overall staging if+N): k=0.18 (G-=9.19, Z=4.98, p<.01). For vascular invasion: k------~.26(G=-3.90, z=3.33, p<.01). The agreement for T and N stage improved as stage increased (p<0.01) and in the presence of vascular invasion (p<0.01). CONCLUSION: Interobserver agreement is good for staging pancreatic tumors by EUS. However, it appears to be better for some tumor stages than others. Experience may play a role in the successful use of this medality to evaluate pancreatic rumors.
EUS-GUIDED INJECTION OF BOTULINUM TOXIN (BOTOX) FOR ACHALASIA: FINAL REPORT OF AN OPEN STUDY. BJ Hoffinan, W Knapplo, MS Bhutani, L Aahakkon, GN Verne RH Hawes. Digestive Disease Center. Medical University of South Carolina. Charleston, SC Purpose: We have previously reported that EUS-guided injection of Botox for treatment of aehalasia may have an improved long-term success rate compared to blind injection. The following is an update with incm.asedpatient numbers and longer follow up. Methods: 26 patients with manometrieally documented idiopathic achalasia answered a questionnaire regarding symptoms of regurgitation, chest pain, and dysphagia before treatment and every 3 months after. They were scored based upon the following scale: 0, none; 1, occasionally; 2, daily; 3, with every meal~ The maximum possible score was nine; failure of treatment was considered a score of 3 or more. EUS was performed using the Pontax FG32UA linear array eehoendoscopa. A 4 cm long, 23 gauge needle was passed through the echoendoscope and advanced into the museularis propria at the level of the LES under renl-time EUS guidance. Four injectious of 1 ec Botox (20 u/co) were made into the LES in different quadrants. Results: 25 patients ages 20-84 (52) were studied. 9 of thuse patients had prior therapy with either myotomy, dilatation, or blind injection. Response duration ranged from 0-24 mo (9.7). 3 (12%) of patients failed treatment and went to myotomy. 3(12%) of patients initially responded but required repeat therapy within 18 months. All of the patients who required repeat injection responded. There was no ago difference between respondars and nonrespondars. All of the patients who failed treatment had prior therapy. 2/3 of the patients who required repeat injection had prior therapy. Complications included mild chest pain in 8% and GERD in 4%. Canelusious: Patients treated with EUS-guided Botox injection for idiopathic achalasia demonstrate a longer improvement in their symptoms over published reports of endoscopic blind injection. Further investigation is needed to determine which patients optimally respond to Botox. A randomized trial comparing blind to EUS-guided injection has been initiated.
t598
t600
IS PANCREATITIS A COMPLICATION OF ENDOSCOPIC ULTRASOUND GUIDED FINE NEEDLE ASPIRATION OF THE PANCREAS? F. Crress~ S. Ikenberry, D. Ciaccia, J. Kid, G. Lchman; Division of Gastroenterology, Indiana University Medical Center, Indianapolis, IN. and Winthrop-University Hospital, SUNY StonyBrook School of Medicine Introduction: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of the pancreas is increasingly being utilized to diagnose pancreatic masses. We have previously reported 2 cases of clinical panereatitis following EUS guided FNA of the pancreas. Aim of Study: To determine the frequency of chemical and clinical panereatitis following EUS guided FNA of the pancreas. Methods: All patients having EUS guided FNA biopsy of the pancreas were eligible. Exclusion criteria included: All patients with acute p a n c r e n ~ or having ERCP within 48 hours of the EUS FNA. Serum amylase and lipase levels were measured immediately prior to and 2 hours post EUS FNA. Patients were called 24-72 hours after FNA to follow up for increased pain, nausea, or vomiting suggesting clinical pancreatitis. RasuRs: Data was prospeotively collected on 36 patients. Pro- and post-FNA amylase and lipase levels were available for all patients. Ten patients bad a past history of panereatitis prior to the EUS FNA. Pro and Post EUS Guided FNA Serum Enzyme Levels Amylase MeanPre [ Mean Post ] Mean Change [ CI PValue [ 70.0 75.0 5.0 - 31.4~ 20:2 .47 Lipase 315.0 547.6 232.0 - 45819, ~6.05 .044 CI = Confidence Interval As a group, there was a mean increase in serum amylase and lipase levels. When matched pair analysis was performed, the differences were not statistically significant for amylase levels but were for lipase (p<0.05) suggesting that lipase may be a more sensitive marker. There were no episodes of clinical panereatitis. The lipase levels were elevated the most in 60% (6/10) of patients with a past history of pancreatitis. Conclusion: This prospective study found no evidence of clinical pancrentitis. Patients with a prior history of pancreatitis had higher amylase and lipase levels than those who did not suggesting this as a possible risk factorl Based on this prospective study, further investigations are warranted to evaluate the true risk of pancreatitis from this procedure.
ENDOSCOPIC ULTRASOUND(EUS) IN RESTAGING OF ESOPHAGEALCANCERAFTER ADJUVANT CHEMORADIATION G isenhern. A Chek, M Canto, N Levitan, J Clayman, B Pollack, M V Sivak, Jr. UniversityHospitalsof Cleveland,Case Western ReserveUniversity, Cleveland,OH. Background Endoscopic ultrasound {EUS) is established as the most accurate method currently available for determining the depth of primary cancer invasion (T stage). Standard EUS criteria may not be accuratein assessingdepth of cancerinvasionand nodal status after patients have received chemotherapy or radiotherapy due to residual fibrosis and inflammation. Methods We conducted a prospective study to determine if EUS estimation of tumor size could be used to assess responseto preoperativeadjuvant chemoradiation. Using EUS,TNM stage was assessedon 31 patients {22 men: 9 women; mean age - 62 yrs) with cancerof esophagus or cerdia (19 adenocarcinoma, 12 squamous cell cancer) prior to initiation of combined radiation and 5-FUIcisplatin (and/or carboplatinum) chemotherapy. The crosssectional area (MAX) of the tumor in the transverseplane at the location where the tumor had maximal thickness was calculated to estimate tumor size. EUS staging and measurementof MAX were repeated at completion of adjuvant therapy just prior to surgery. Responseto preoperativeadjuvant chemoradiationwas definedas 50% reduction in MAX. Surgicalstaging was comparedbetweenrespendersand nonresponders. Results Eight patients who did not undergo surgery were excluded from analysis. EUS T stage in the remaining23 patients prior to therapy was as follows: 3 T2, 16 T3, and 4 T4. Followingchemoradiation,EUST staging was changedin 6 pts {3 T4 downstsoedto T3, 2 T3 downstaged to T2, and 1 T3 downstagedto T1). At surgical pathology, 3 pts had no residual tumor in the esophagus(TO), 5 had TI, 3 had T2, 10 had T3, and 2 had T4 tumors. EUS T staging accuracy following adjuvant therapy was only 43%. MAX decreasedfrom a mean of 5.5 +/- 2.4 sq cm to 1.6 +1. 0.9 sq cm in responders, whereas MAX went from 7.0 +/- 3.0 sq cm to 5.4 +/- 2.2 sq cm in nonresponders(p-O.009 using Wilcoxon rank-sum statistics). 10/13 patients with at least a 50% reduction in MAX (responders)had TO, T1, or T2 tumors at surgery whereas 9/10 nonresponders had T3 or T4 tumors at surgery {p=0.001 using likelihood chi-squarestatistics). There was no difference in T stage between respondersand nnnrespondersprior to chemoradiation. Conclusions [1] standard EUS staging criteria are not accurate after adjuvant chemoradistien,[2] reductionin maximal cross.sectionalarea (MAX) of tumor appearsto be a more useful measure for assessing responseof esophageal cancer to preoperativeadjuvant chemoradiation, and [3] responders (patients with a > 50% reduction of MAX) have an increasedlikelihoodof downstaging at surgerythan nonresponders.
AB174
GASTROINTESTINAL ENDOSCOPY
VOLUME 45, NO. 4, 1997