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Prospective Multicenter Study On the Incidence of Neoplastic Progression in Barrett Esophagus Patients
231 Prospective Multicenter Study On the Incidence of Neoplastic Progression in Barrett Esophagus Patients Marjolein Sikkema, Marjon Kerkhof, E.W. Steyerberg, Herman Van Dekken, Anneke Van Vuuren, Willem a. Bode, Hans Van Der Valk, Dirk Jan Bac, Raimond Giard, Wilco Lesterhuis, Robert Heinhuis, Elly C. Klinkenberg, Gerrit a. Meijer, Frank T. Borg, Jan-Willem Arends, Jeroen J. Kolkman, Joop Van Baarlen, Richard a. De Vries, Andries H. Mulder, Antonie J. Van Tilburg, Johan Offerhaus, Fiebo J. Ten Kate, Johannes G. Kusters, E.J. Kuipers, Peter D. Siersema Background and aim: Barrett esophagus (BE) is a premalignant disorder, predisposing to esophageal adenocarcinoma (EAC). The latter is assumed to develop through the cascade of intestinal metaplasia (IM), low-grade dysplasia (LGD) and high-grade dysplasia (HGD). For that reason, regular endoscopic and histologic follow-up is recommended in BE patients. It has been reported that the incidence of EAC and of BE is increasing over the last decades in Western countries, however these reported incidences show considerable variation. We evaluated the incidence of progression from no dysplasia (ND) towards LGD and from ND or LGD towards HGD and EAC in a Dutch BE cohort. Methods: In this prospective, multicenter cohort study, 783 BE patients were included with ND (n Z 664) or LGD (n Z 119) at baseline and a BE segment (with a histologic diagnosis of IM) of 2 cm or more. Endoscopic and histologic surveillance was performed according to the ACG guidelines (2002). The annual risk of progression towards LGD, HGD and EAC was analyzed with incidence densities. Results: After 2 years of follow-up, 80 (10%) patients were lost-to-follow-up. Of these, 15 patients had died from other causes than EAC and 65 patients refused further participation. The mean age ( SD) at baseline (n Z 703) was 60.3 11.1 years with 73% males. Five hundred-sixty-one of the remaining 703 (80%) BE patients were known with BE prior to this study with a median follow-up of 4.0 years (interquartile range 2.0 to 8.0). Mean ( SD) followup time in this study was 2.0 0.4 years with a total of 1192 patient-years of followup for patients with only baseline ND and a total of 1383 patient-years of follow-up for patients with ND and LGD. Thirty-two of 604 BE patients with baseline ND developed LGD during 1192 patient-years of follow-up, which equals one LGD case per 37 patient-years. HGD developed in 11/703 BE patients, and EAC in 11/703 BE patients during 1383 patient-years of follow-up, which corresponds to one HGD case per 125 patient-years and one EAC case per 125 patient-years. This equals 22/ 703 BE patients with neoplastic progression during follow-up, yielding an incidence of one case HGD or EAC per 63 patient-years. Conclusion: In BE patients with a columnar BE-segment of two cm or more and ND or LGD at baseline, the annual risk of progression towards HGD or EAC is 1.6%. BE patients with baseline ND had an annual risk of developing LGD of 2.7%. Longer follow-up is however needed to accurately establish the natural history of BE.
232 A Randomized Prospective Trial Comparing the Cap-Technique and Multi-Band Mucosectomy Technique for Piecemeal Endoscopic Resection in Barrett’s Esophagus Roos E. Pouw, Joep J. Gondrie, Lorenza Alvarez Herrero, Frederike G. Van Vilsteren, Femke Peters, Wilda Rosmolen, Fiebo J. Ten Kate, Kausilia K. Krishnadath, Paul Fockens, Bas L. Weusten, Jacques J. Bergman Background: Endoscopic resection (ER) is an important treatment modality for patients with Barrett’s esophagus (BE) containing high-grade dysplasia (HGD) or intramucosal cancer (IMC). The most widely used ER technique, the cap-technique (Cap), requires submucosal lifting and prelooping of a snare in the cap, making it technically demanding and laborious when used for piecemeal resections. In addition, a new snare is needed for every resection. The newer multi-band mucosectomy (MBM) technique uses a modified variceal band ligator and requires no submucosal lifting or prelooping of a snare, and multiple resections can be performed with the same snare. Aim of this study was to prospectively compare Cap and MBM for piecemeal ER in BE. Methods: In an ongoing randomized trial, patients with BE-HGD/IMC scheduled for piecemeal ER were included. After delineation of the area to be resected, patients were randomized to Cap or MBM. Assessment criteria were: number of resections/procedure, procedure time, time/ resected specimen, complications, maximum diameter of specimens, and costs of disposables. Results: 45 pts (35 men, median age 70 yrs, median Prague C3M5) were randomized; 22 to Cap, 23 to MBM. Results are shown in table 1. Procedure time (29 vs. 50 min, p Z 0.04) and costs (V240 vs. V322, p Z 0.01) were significantly less with MBM compared to Cap. MBM resulted in smaller resection specimens than Cap (18 vs. 21 mm, p ! 0.001). There were two severe complications: two Cap resections were complicated by a perforation that healed after endoscopic treatment with clips (n Z 1) or stenting (n Z 1). Conclusion: Data of this ongoing randomized study show that piecemeal ER with MBM is faster and cheaper than with the Cap, and may be associated with fewer complications. MBM, however, results in significantly smaller sized and possibly less deep resections and may, therefore, be more suited for resection of flat lesions with a low risk of submucosal invasion, whereas the Cap technique may be preferred for ER of elevated and nodular lesions.
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Table 1. Patient characteristics and assessment criteria ()presented as: median (IQR))
Male : Female Age (yrs)) BE length acc. to Prague classification) No. of pts with HGIN:IMC in ER-specimen (all clear vertical margins) Number of resections/procedure) Total procedure time, min.) Time/resected specimen, min.) No. of ERs with complications: severe (perforation) mild (bleeding) Max. diameter of specimens, mm) Costs disposables/procedure, euro’s)
Cap (n Z 22)
MBM (n Z 23)
17 : 5 71 (63-75) C3 (1-8) M5 (4-9)
18 : 5 68 (62-75) C4 (1-6) M5 (3-7)
10 : 7 4 (2-8) 50 (29-65) 10 (8-14)
3 : 15 5 (3-9) 29 (16-52) 6 (4-7)
p-value
ns 0.04 0.00
2 12 09 ns ns 21 (19-25) 18 (15-20) 0.00 322 (275-474) 240 (240-480) 0.01
233 Study of Preoperative and Postoperative Pathology in High Grade Barrett’s Dysplasia John Y. Nasr, Luketich James, Robert E. Schoen Introduction: High grade dysplasia in the setting of Barrett’s disease is often managed with surgical resection, because of the risk of concomitant adenocarcinoma. However, improvements in endoscopic diagnosis may have reduced the risk of undetected cancer. We investigated the association of adenocarcinoma with high grade dysplasia at surgical resection in relation to date of procedure. Methods: Using the electronic medical record, we identified patients who underwent esophagectomy for high grade dysplasia, at the University of Pittsburgh Medical Center, between 1993 and 2007. Preoperative diagnosis was confirmed by reviewing pathology reports and postoperative pathology reports were reviewed and compared to the preoperative diagnosis. Results: 68 patients (12 females and 56 males) with a preoperative diagnosis of high grade dysplasia were evaluated. The mean age was 64 years (range 36 to 86 years). 12 of 68 (17.6 %) had adenocarcinoma, 2 were downgraded to low grade dysplasia and 54 were confirmed as HGD. Subgroup analysis was performed based on the date of operation. When analyzed by date of operation, 3/20 (15%) had adenocarcinoma between 1993 - 2000 versus 9/48 (18.8%) between 2001 - 2007 (p Z 0.770). Among the most recent cases, 8/40 (20%) had adenocarcinoma from 1993 - 2003, versus 4/ 28 (14%) between 2004 - 2007 (p Z 0.379). Conclusion: The rate of adenocarcinoma in association with HGD and Barrett’s in this series was 18%, and remained at a similar rate, even in the last few years of clinical practice. Advanced endoscopic techniques to identify adenocarcinoma in the setting of HGD/Barrett’s remain a clinical priority.
234 Are Patients with ‘‘Low Risk’’ Submucosal Invasion of Early Barrett’s Carcinoma Eligible for Curative Endoscopic Therapy? Outcomes of Endoscopic Therapy and Surgery in 80 Patients with Suspected Or Definite Diagnosis of Submucosal Barrett’s Cancer Hendrik Manner, Andrea May, Oliver Pech, Liebwin Gossner, Thomas Rabenstein, Michael Vieth, Christian Ell Background: Recently published surgical series have shown that even in case of incipient submucosal invasion of Barrett’s cancer (BC), the risk for lymph node (LN) metastasis appears to be very low. Recently presented results of our group have shown that endoscopic resection (ER) might be associated with favourable outcomes even in these patients. Study aims: To show selection of patients with submucosal (sm) BC for different treatment approaches; to analyse lymph node (LN) status of patients referred to surgery; to evaluate long-term results after ER in ‘‘low risk’’ sm BC. Methods: From 09/96 to 09/03, the endosonographic suspicion or definite diagnosis of sm BC by ER or surgery was made in 80 pt referred to our department. 28 pt were referred to surgery after initial ER (n Z 22) or because of the tumor’s macroscopic or endosonographic appearance (n Z 6). 30 pt were treated endoscopically with palliative intent, and one pt by photodynamic therapy and ER. 21 pt fulfilled the definition of ‘‘low risk’’ sm cancer: Invasion of the upper sm third (sm1), absence of infiltration into lymphatic (nor blood) vessels, histological grade G1/2, and gross type I/II. In these pt, ETwas carried out using ER with the suck-andcut technique. Results: In 8/28 pt primarily referred to surgery, LN status was positive. One of the 21 pt fulfilling our low-risk criteria was referred to surgery directly after detection of sm1 invasion at the beginning of the study. One pt died (not tumourrelated) before completion of ET. Using definitive ET, complete remission (CR) was achieved in 18/19 pt (95%) after a mean of 5.3 months (range 1-18) and a mean of 2.9 resections (range 1-9). Only one minor complication (bleeding without drop of haemoglobin O 2 g/dl) occurred (5% of pt). During a mean follow-up (FU) of 69 months (range 48-103), recurrent or metachronous carcinomas were found in 5 pt (28%). Repeat ETwas carried out successfully using ER (4 pt) and APC (1 pt). In one of
Volume 67, No. 5 : 2008 GASTROINTESTINAL ENDOSCOPY AB75
232 A Randomized Prospective Trial Comparing the Cap-Technique and Multi-Band Mucosectomy Technique for Piecemeal Endoscopic Resection in Barrett’s Esophagus Roos E. Pouw, Joep J. Gondrie, Lorenza Alvarez Herrero, Frederike G. Van Vilsteren, Femke Peters, Wilda Rosmolen, Fiebo J. Ten Kate, Kausilia K. Krishnadath, Paul Fockens, Bas L. Weusten, Jacques J. Bergman Background: Endoscopic resection (ER) is an important treatment modality for patients with Barrett’s esophagus (BE) containing high-grade dysplasia (HGD) or intramucosal cancer (IMC). The most widely used ER technique, the cap-technique (Cap), requires submucosal lifting and prelooping of a snare in the cap, making it technically demanding and laborious when used for piecemeal resections. In addition, a new snare is needed for every resection. The newer multi-band mucosectomy (MBM) technique uses a modified variceal band ligator and requires no submucosal lifting or prelooping of a snare, and multiple resections can be performed with the same snare. Aim of this study was to prospectively compare Cap and MBM for piecemeal ER in BE. Methods: In an ongoing randomized trial, patients with BE-HGD/IMC scheduled for piecemeal ER were included. After delineation of the area to be resected, patients were randomized to Cap or MBM. Assessment criteria were: number of resections/procedure, procedure time, time/ resected specimen, complications, maximum diameter of specimens, and costs of disposables. Results: 45 pts (35 men, median age 70 yrs, median Prague C3M5) were randomized; 22 to Cap, 23 to MBM. Results are shown in table 1. Procedure time (29 vs. 50 min, p Z 0.04) and costs (V240 vs. V322, p Z 0.01) were significantly less with MBM compared to Cap. MBM resulted in smaller resection specimens than Cap (18 vs. 21 mm, p ! 0.001). There were two severe complications: two Cap resections were complicated by a perforation that healed after endoscopic treatment with clips (n Z 1) or stenting (n Z 1). Conclusion: Data of this ongoing randomized study show that piecemeal ER with MBM is faster and cheaper than with the Cap, and may be associated with fewer complications. MBM, however, results in significantly smaller sized and possibly less deep resections and may, therefore, be more suited for resection of flat lesions with a low risk of submucosal invasion, whereas the Cap technique may be preferred for ER of elevated and nodular lesions.
www.giejournal.org
Table 1. Patient characteristics and assessment criteria ()presented as: median (IQR))
Male : Female Age (yrs)) BE length acc. to Prague classification) No. of pts with HGIN:IMC in ER-specimen (all clear vertical margins) Number of resections/procedure) Total procedure time, min.) Time/resected specimen, min.) No. of ERs with complications: severe (perforation) mild (bleeding) Max. diameter of specimens, mm) Costs disposables/procedure, euro’s)
Cap (n Z 22)
MBM (n Z 23)
17 : 5 71 (63-75) C3 (1-8) M5 (4-9)
18 : 5 68 (62-75) C4 (1-6) M5 (3-7)
10 : 7 4 (2-8) 50 (29-65) 10 (8-14)
3 : 15 5 (3-9) 29 (16-52) 6 (4-7)
p-value
ns 0.04 0.00
2 12 09 ns ns 21 (19-25) 18 (15-20) 0.00 322 (275-474) 240 (240-480) 0.01
233 Study of Preoperative and Postoperative Pathology in High Grade Barrett’s Dysplasia John Y. Nasr, Luketich James, Robert E. Schoen Introduction: High grade dysplasia in the setting of Barrett’s disease is often managed with surgical resection, because of the risk of concomitant adenocarcinoma. However, improvements in endoscopic diagnosis may have reduced the risk of undetected cancer. We investigated the association of adenocarcinoma with high grade dysplasia at surgical resection in relation to date of procedure. Methods: Using the electronic medical record, we identified patients who underwent esophagectomy for high grade dysplasia, at the University of Pittsburgh Medical Center, between 1993 and 2007. Preoperative diagnosis was confirmed by reviewing pathology reports and postoperative pathology reports were reviewed and compared to the preoperative diagnosis. Results: 68 patients (12 females and 56 males) with a preoperative diagnosis of high grade dysplasia were evaluated. The mean age was 64 years (range 36 to 86 years). 12 of 68 (17.6 %) had adenocarcinoma, 2 were downgraded to low grade dysplasia and 54 were confirmed as HGD. Subgroup analysis was performed based on the date of operation. When analyzed by date of operation, 3/20 (15%) had adenocarcinoma between 1993 - 2000 versus 9/48 (18.8%) between 2001 - 2007 (p Z 0.770). Among the most recent cases, 8/40 (20%) had adenocarcinoma from 1993 - 2003, versus 4/ 28 (14%) between 2004 - 2007 (p Z 0.379). Conclusion: The rate of adenocarcinoma in association with HGD and Barrett’s in this series was 18%, and remained at a similar rate, even in the last few years of clinical practice. Advanced endoscopic techniques to identify adenocarcinoma in the setting of HGD/Barrett’s remain a clinical priority.
234 Are Patients with ‘‘Low Risk’’ Submucosal Invasion of Early Barrett’s Carcinoma Eligible for Curative Endoscopic Therapy? Outcomes of Endoscopic Therapy and Surgery in 80 Patients with Suspected Or Definite Diagnosis of Submucosal Barrett’s Cancer Hendrik Manner, Andrea May, Oliver Pech, Liebwin Gossner, Thomas Rabenstein, Michael Vieth, Christian Ell Background: Recently published surgical series have shown that even in case of incipient submucosal invasion of Barrett’s cancer (BC), the risk for lymph node (LN) metastasis appears to be very low. Recently presented results of our group have shown that endoscopic resection (ER) might be associated with favourable outcomes even in these patients. Study aims: To show selection of patients with submucosal (sm) BC for different treatment approaches; to analyse lymph node (LN) status of patients referred to surgery; to evaluate long-term results after ER in ‘‘low risk’’ sm BC. Methods: From 09/96 to 09/03, the endosonographic suspicion or definite diagnosis of sm BC by ER or surgery was made in 80 pt referred to our department. 28 pt were referred to surgery after initial ER (n Z 22) or because of the tumor’s macroscopic or endosonographic appearance (n Z 6). 30 pt were treated endoscopically with palliative intent, and one pt by photodynamic therapy and ER. 21 pt fulfilled the definition of ‘‘low risk’’ sm cancer: Invasion of the upper sm third (sm1), absence of infiltration into lymphatic (nor blood) vessels, histological grade G1/2, and gross type I/II. In these pt, ETwas carried out using ER with the suck-andcut technique. Results: In 8/28 pt primarily referred to surgery, LN status was positive. One of the 21 pt fulfilling our low-risk criteria was referred to surgery directly after detection of sm1 invasion at the beginning of the study. One pt died (not tumourrelated) before completion of ET. Using definitive ET, complete remission (CR) was achieved in 18/19 pt (95%) after a mean of 5.3 months (range 1-18) and a mean of 2.9 resections (range 1-9). Only one minor complication (bleeding without drop of haemoglobin O 2 g/dl) occurred (5% of pt). During a mean follow-up (FU) of 69 months (range 48-103), recurrent or metachronous carcinomas were found in 5 pt (28%). Repeat ETwas carried out successfully using ER (4 pt) and APC (1 pt). In one of
Volume 67, No. 5 : 2008 GASTROINTESTINAL ENDOSCOPY AB75