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Endoscopic therapy in patients with Barrett's esophagus and portal hypertension
CASE STUDIES
Endoscopic therapy in patients with Barrett’s esophagus and portal hypertension Ganapathy A. Prasad, MD, Kenneth K. Wang, MD, Ann M. Joyce, MD, Michael L. Kochman, MD, Lori S. Lutzke, Lynn S. Borkenhagen Rochester, Minnesota, Philadelphia, Pennsylvania, USA
Background: Endoscopic mucosal resection has been used to stage and treat early neoplasia in Barrett’s esophagus. The ability to do this in the setting of portal hypertension has not been reported. Objective: Our purpose was to describe the feasibility and efficacy of endoscopic mucosal resection in patients with portal hypertension and Barrett’s esophagus. Design: Retrospective case series. Setting: Two tertiary referral centers. Patients: Patients with Barrett’s esophagus and high-grade dysplasia or adenocarcinoma in the setting of portal hypertension. Intervention: Endoscopic mucosal resection of endoscopically visible lesions. Main Outcome Measurements: Complete resection of neoplastic lesion, lack of variceal bleeding. Results: Four patients were treated with endoscopic mucosal resection a total of 5 times. Endoscopic mucosal resection was successfully performed without significant GI bleeding. Limitations: This preliminary case series describes feasibility of the procedure. Whether this can be generalized remains to be determined, although it may be an option in poor surgical candidates. Conclusions: Endoscopic mucosal resection appears to be relatively safe in selected patients with portal hypertension and Barrett’s esophagus. Further studies are needed to confirm these findings.
Endoscopic therapy is increasingly being used in the management of esophageal neoplasia arising in a background of Barrett’s esophagus.1-4 Management of highgrade dysplasia (HGD) in Barrett’s esophagus and mucosal adenocarcinoma with endoscopic mucosal resection (EMR) in combination with other ablative techniques has been shown in preliminary studies to have results comparable to those of esophagectomy.5 Endoscopic therapy of HGD is associated with lower morbidity and mortality rates compared with esophagectomy. Currently, patients with Barrett’s esophagus and HGD, who are poor operative candidates, are often referred for endoscopic therapy. There is currently little information in the literature concerning the feasibility and safety of endoscopic therapy in patients with neoplasia arising in Barrett’s esophagus
who have chronic liver disease and portal hypertension. We report the combined experience of 2 tertiary care referral centers with EMR of neoplastic lesions arising in Barrett’s esophagus in 4 consecutive patients with cirrhosis, portal hypertension, and esophageal varices.
CASE 1
Copyright ª 2007 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2006.11.024
An 82-year-old man with nonalcoholic steatohepatitis (NASH)–related cirrhosis (Child Pugh classification B, MELD (model end-stage liver disease) score 15, international normalized ratio [INR] 1.3, platelets 90,000/mL [normal 150,000-450,000/mL]) and varices had Barrett’s esophagus and HGD on outside mucosal biopsy specimens. Endoscopy showed a 2-cm segment of Barrett’s esophagus, with a 3-mm nodule and F1 (small straight) esophageal varices (Fig. 1). At the initial endoscopy, endoscopic variceal ligation (EVL) of 3 variceal trunks proximal
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Figure 1. Evidence of portal hypertension (F1, small straight esophageal varices) before endoscopic mucosal resection.
and distal to the nodule was performed with use of a Duette multiband ligator device (Wilson Cook, WinstonSalem, NC). Mucosal biopsy specimens showed HGD. The patient returned 1 week later, at which time endoscopy revealed clean-based ulceration at the banding sites without evidence of residual varices. The nodule at the gastroesophageal junction was removed by 3 mucosal resections with an Olympus EMR cap (EMR-001, Olympus, Melville, NY) according to a previously described standard technique4 (Fig. 2). Two EMR specimens revealed HGD with negative margins and the third revealed low-grade disease (LGD). The patient did well after the EMR without any complications. Four months later, hepatocellular carcinoma developed, which was treated with radiofrequency ablation.
CASE 2 A 58-year-old man with NASH-related cirrhosis (Child Pugh classification B, MELD score 10, INR 0.9, platelet count 85,000/mL) had Barrett’s esophagus and HGD detected on routine endoscopy. He also had a history of variceal hemorrhage and transjugular intrahepatic portosystemic shunt (TIPS) placement, followed by hepatic encephalopathy (controlled with lactulose and rifaximin). Initial endoscopy revealed a 5-cm segment of Barrett’s esophagus with a polypoid lesion and F2 (tortuous varices occupying less than a third of the esophageal lumen) esophageal varices. EUS confirmed the presence of intraesophageal and periesophageal varices. Three bands were placed in the distal and proximal esophagus with a Duette multiband ligator device. He returned 1 month later, at which time endoscopy revealed no varices in the proximal Barrett’s esophagus segment. EMR was performed by using the Duette multiband mucosectomy device. Histopathologic examination revealed HGD with negative margins. Mucosal biopsy specimens revealed HGD. The patient did well without any complications. He underwent photo528 GASTROINTESTINAL ENDOSCOPY Volume 65, No. 3 : 2007
Figure 2. Site after mucosal resection of early adenocarcinoma. Three mucosal resections were performed.
dynamic therapy 6 weeks later to treat the remaining dysplastic mucosa without complications.
CASE 3 A 78-year old man with alcoholic cirrhosis (Child Pugh classification A, MELD score 9, platelet count 150,000/mL, and INR 0.9) had Barrett’s esophagus and HGD detected on routine endoscopy. Endoscopy revealed a 2-cm segment of Barrett’s esophagus at the gastroesophageal junction. Small, straight varices (F1) were seen in the lower esophagus. EUS examination did not reveal any evidence of submucosal varices or mucosal lesions. Two mucosal resections were performed with the Duette multiband mucosectomy device (Fig. 3). Minimal oozing was seen at the site of the second EMR, which was controlled with the application of a single hemoclip (Boston Scientific, Natick, Mass) (Fig. 4). The patient was observed overnight in the hospital. Twenty-four hours after endoscopy, the hemoglobin remained stable and he was discharged. Histopathologic examination revealed intramucosal carcinoma in the EMR specimen with involvement of one lateral margin. Endoscopy performed a month later revealed an elevated area of erythematous mucosa adjacent to the prior EMR site, which was resected with the Duette device. After the resection, a Quickclip (Olympus) was placed prophylactically to secure good hemostasis. Histologic examination revealed HGD with negative margins. The patient returned for endoscopic surveillance 3 months later, at which time EMR and biopsy specimens revealed nondysplastic Barrett’s esophagus at the gastroesophageal junction.
CASE 4 A 60-year-old man with alcoholic cirrhosis (Child Pugh classification A, MELD score 10, platelet count 87,000/mL, www.giejournal.org
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Endoscopic therapy in Barrett’s esophagus and portal hypertension
Figure 3. Banding of an early adenocarcinoma with placement of the snare above the band for endoscopic resection.
Figure 4. Placement of hemoclip after mucosal resection of early adenocarcinoma. The ligation band is still seen in place over the site of resection.
INR 1.2) and chronic gastroesophageal reflux underwent endoscopy, which revealed a 4-cm segment of Barrett’s esophagus with LGD and a 2-cm pedunculated polyp at the gastroesophageal junction. Endoscopy done 18 months later revealed a 1.5-cm nodule with HGD and no esophageal varices. EUS revealed a mucosally based lesion, small collateral periesophageal vessels, and no suspicious lymphadenopathy. Twenty milliliters of normal saline solution was injected into the submucosa to lift the lesion for EMR. After the third application of a needle, oozing of blood was noted. A band was then placed on the lesion (SpeedView 7, Boston Scientific) and proximal and distal to the lesion. The lesion was then snare resected with electrocautery. Persistent oozing was seen after resection and the patient was admitted for overnight observation. The patient’s hematocrit remained stable and he was discharged the next morning. Histopathologic examination of the resected specimen showed polypoid LGD. A follow-up endoscopy in 3 months with biopsies revealed LGD. Although the patient was then referred for photodynamic therapy, he did not wish to undergo ablative therapy and has also refused further endoscopic surveillance.
During the past decade, EMR has been gaining acceptance in Europe and the United States as an alternative modality for the treatment of neoplastic lesions arising in the background of Barrett’s esophagus.1-3,6-9 The primary advantage of EMR is that it can remove large portions of mucosa and submucosa, which allows histologic staging and diagnosis of lesions in Barrett’s esophagus.10 EMR may also be curative for smaller lesions.4 EMR is a relatively safe procedure, but it can lead to complications: bleeding (reported in 4%-10% of patients),11 perforation (0.1%-5%), and stricture formation, especially after
circumferential EMR8 and when used in combination with PDT.1 Barrett’s esophagus has been reported in 2% to 3% of patients undergoing endoscopy as part of a liver transplant evaluation.12,13 Patients with cirrhosis may also have risk factors for Barrett’s esophagus, such as obesity (associated with NASH and gastroesophageal reflux). The association of alcohol with esophageal neoplasia and gastroesophageal reflux remains debatable, with studies reporting contradictory findings.14-16 Patients with cirrhosis and portal hypertension have been reported in some studies to have delayed gastric emptying/GI transit,17,18 which may potentiate gastroesophageal reflux. With the increasing acceptance of EMR in the management of neoplasia arising in Barrett’s esophagus, patients with comorbidities and high operative risk are often referred for endoscopic therapy. Patients with cirrhosis and portal hypertension are well known to have greater operative mortality because of the risk for hepatic decompensation after surgery and the presence of vascular collaterals, which could cause severe hemorrhage with mucosal resection.19 Varices can increase the risk of bleeding after EMR. This is the first report from the United States on EMR performed for Barrett’s esophagus in patients with HGD in a background of portal hypertension after the eradication of varices by EVL. Iwase et al20 reported the resection of early stage squamous esophageal cancer in a patient with alcoholic cirrhosis and esophageal varices. This lesion was confirmed to be mucosally confined by EUS examination. The authors first used esophageal sclerotherapy (EST) by using 2% sodium tetradecyl sulfate to obliterate varices in 2 sessions. After visual confirmation of eradication of varices, they performed EMR of the neoplastic lesion, without immediate or delayed bleeding. The patient did not have recurrence of the cancer or varices at endoscopy performed 1 year after the resection. Other authors have also
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reported endoscopic management of patients with squamous esophageal cancer with EMR21 and with PDT and radiation.22 Endlicher et al23 have also recently reported the use of variceal ligation for eradication of varices before endoscopic treatment of mucosally confined squamous esophageal cancer with EMR in a 71-year-old patient with alcoholic cirrhosis and esophageal varices. This was done in 1 session without significant complications but needed a follow-up EMR in 3 months because of recurrence. After 18 months of follow-up, the patient had no evidence of macroscopic recurrence, although LGD was still found on biopsy specimens. Patients with Barrett’s esophagus and HGD are at significant risk for either coexistent carcinoma24,25 or progression to carcinoma,26-30 with rates as high as 57% over 2 years being reported. One study31 reported lower rates (17% over 7 years) of progression, although this study used a single pathologist and excluded prevalent cancers (cancers arising within 1 year of diagnosis of HGD: 4/34 patients). Patients with cirrhosis have a shortened life expectancy, and an argument could be made that endoscopic surveillance alone (with the increased risk of bleeding from underlying varices) may be an acceptable strategy in these patients. We have previously reported that EMR is superior to biopsy and EUS alone in staging patients with HGD with visible nodules, with the diagnosis changing in as many as 40% of patients after EMR.10 In patients with low MELD scores who have a relatively longer life expectancy, identification and potential treatment of an early cancer with EMR would be reasonable. This, however, highlights the need to closely weigh the risks and benefits of performing EMR on patients with portal hypertension and esophageal varices. We would also like to emphasize that 3 of 4 patients treated in this case series had small esophageal varices that were obliterated by EVL before EMR was attempted and had well-compensated cirrhosis with low MELD scores and no evidence of coagulopathy. Patients with higher MELD scores and coagulopathy may not be suitable candidates. EMR is an invasive procedure with a well-documented bleeding risk. Patients are routinely discharged after EMRs at our institutions. Two patients in this case series were hospitalized after the procedure: case 3 was admitted to the hospital for observation because a hemoclip was applied for achieving hemostasis, and case 4 was admitted to the hospital because the EMR site had persistent oozing. Neither patient, however, had a significant decline in blood pressure or hemoglobin and neither needed a blood transfusion. However, this demonstrates the potential for life-threatening complications after EMR in this high-risk population and the need for securing hemostasis and for close postprocedure monitoring. Scarring induced by prior EVL may result in failure of the lesions to lift after saline solution injection performed during EMR, potentially precluding safe performance of EMR; this was not observed in our patients. Resection of
lesions situated on top of varices may be challenging; however, if the varix is decompressed by the application of bands distally, resection of the lesion after confirmation of adequate variceal decompression (with EUS) could be considered. EMR in this case series was used as a diagnostic/staging tool. Patients with residual dysplastic mucosa were treated either with sequential EMRs (as in case 3, with continued demonstration of adequate variceal decompression), surveillance (as opted for by case 4), or with photodynamic therapy (as in case 2). Long-term follow-up results would be crucial in determining the role of EMR in patients with dysplasia arising in Barrett’s esophagus when they have underlying portal hypertension. In this preliminary report, EMR of esophageal lesions in a background of portal hypertension, when performed in centers with expertise on carefully selected patients after obliteration of varices, appears to be feasible and can be effective in removing neoplastic lesions. EUS may allow confirmation of variceal eradication or absence, allowing either the confirmation of adequate therapy or the performance of EMR without variceal ligation. Aggressive hemostasis and close monitoring for bleeding after EMR in such patients would be prudent.
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DISCLOSURE The authors have no conflicts of interest.
REFERENCES 1. Buttar NS, Wang KK, Lutzke LS, et al. Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett’s esophagus. Gastrointest Endosc 2001;54:682-8. 2. Ell C, May A, Gossner L, et al. Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett’s esophagus. Gastroenterology 2000;118:670-7. 3. May A, Gossner L, Pech O, et al. Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett’s oesophagus: acute-phase and intermediate results of a new treatment approach [see comment]. Eur J Gastroenterol Hepatol 2002;14: 1085-91. 4. Prasad GA, Wang KK, Lutzke LS. Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett’s esophagus. Clin Gastroenterol Hepatol 2006;4:173-8. 5. Pacifico RJ, Wang KK, Wongkeesong LM. Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett’s esophagus. Clin Gastroenterol Hepatol 2003;1:252-7. 6. May A, Gossner L, Behrens A, et al. A prospective randomized trial of two different endoscopic resection techniques for early stage cancer of the esophagus [see comment]. Gastrointest Endosc 2003;58:167-75. 7. Nijhawan PK, Wang KK. Endoscopic mucosal resection for lesions with endoscopic features suggestive of malignancy and high-grade dysplasia within Barrett’s esophagus [see comment]. Gastroint Endosc 2000;52:328-32. 8. Seewald S, Akaraviputh T, Seitz U, et al. Circumferential EMR and complete removal of Barrett’s epithelium: a new approach to management
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9.
10. 11.
12.
13. 14.
15.
16. 17.
18. 19. 20.
21.
22.
of Barrett’s esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma. Gastrointest Endosc 2003;57:854-9. Larghi A, Lightdale CJ, Memeo L, et al. EUS followed by EMR for staging of high-grade dysplasia and early cancer in Barrett’s esophagus. Gastrointest Endosc 2005;62:16-23. Prasad GA, Wang KK, Buttar NS, et al. Evaluation of Barrett’s esophagus with EUS and EMR [abstract]. Am J Gastroenterol 2004;99:AB82. May A, Gossner L, Pech O, et al. Local endoscopic therapy for intraepithelial high-grade neoplasia and early adenocarcinoma in Barrett’s oesophagus: acute-phase and intermediate results of a new treatment approach. Eur J Gastroenterol Hepatol 2002;14:1085-91. Zaman A, Hapke R, Flora K, et al. Prevalence of upper and lower gastrointestinal tract findings in liver transplant candidates undergoing screening endoscopic evaluation. Am J Gastroenterol 1999;94:895-9. Weller DA, DeGuide JJ, Riegler JL. Utility of endoscopic evaluations in liver transplant candidates. Am J Gastroenterol 1998;93:1346-50. Lindblad M, Rodriguez LA, Lagergren J. Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study. Cancer Causes Control 2005;16:285-94. Lewis SJ, Smith GD. Alcohol, ALDH2, and esophageal cancer: a metaanalysis which illustrates the potentials and limitations of a mendelian randomization approach. Cancer Epidemiol Biomarkers Prev 2005;14: 1967-71. Kato I, Nomura AM. Alcohol in the aetiology of upper aerodigestive tract cancer. Eur J Cancer B Oral Oncol 1994;30B:75-81. Galati JS, Holdeman KP, Dalrymple GV, et al. Delayed gastric emptying of both the liquid and solid components of a meal in chronic liver disease. Am J Gastroenterol 1994;89:708-11. Ishizu H, Shiomi S, Kawamura E, et al. Gastric emptying in patients with chronic liver diseases. Ann Nucl Med 2002;16:177-82. Keegan MT, Plevak DJ. Preoperative assessment of the patient with liver disease. Am J Gastroenterol 2005;100:2116-27. Iwase H, Kusugami K, Suzuki M, et al. Endoscopic resection of earlystage esophageal cancer accompanied by esophageal varices. Gastrointest Endosc 2000;51:749-52. Inoue H, Endo M, Takeshita K, et al. Endoscopic resection of carcinoma in situ of the esophagus accompanied by esophageal varices. Surg Endosc 1991;5:182-4. Ido K, Yamamoto H, Kawamoto C, et al. Esophageal varices obliterated by photodynamic therapy for coexisting early esophageal carcinoma. Gastrointest Endosc 1997;45:420-3.
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Endoscopic therapy in Barrett’s esophagus and portal hypertension 23. Endlicher E, Gelbmann C, Schlottmann K, et al. Endoscopic mucosal resection for early esophageal cancer with esophageal varices [in German]. Z Gastroenterol 2004;42:609-13. 24. Rice TW, Falk GW, Achkar E, et al. Surgical management of high-grade dysplasia in Barrett’s esophagus. Am J Gastroenterol 1993;88:1832-6. 25. Heitmiller RF, Redmond M, Hamilton SR. Barrett’s esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy. Ann Surg 1996;224:66-71. 26. Reid BJ, Prevo LJ, Galipeau PC, et al. Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol 2001;96:2839-48. 27. Rabinovitch PS, Longton G, Blount PL, et al. Predictors of progression in Barrett’s esophagus III: baseline flow cytometric variables. Am J Gastroenterol 2001;96:3071-83. 28. Reid BJ, Levine DS, Longton G, et al. Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 2000;95:1669-76. 29. Reid BJ. p53 and neoplastic progression in Barrett’s esophagus. Am J Gastroenterol 2001;96:1321-3. 30. Reid BJ, Blount PL, Rabinovitch PS. Biomarkers in Barrett’s esophagus. Gastrointest Endosc Clin North Am 2003;13:369-97. 31. Schnell TG, Sontag SJ, Chejfec G, et al. Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology 2001;120:1607-19.
Received June 30, 2006. Accepted November 14, 2006. Current affiliations: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA (G. P., K. K. W., L. S. L., L. S. B.) and Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA (A. M. J., M. L. K.). Supported by National Institutes of Health grants No. CA85992-01 and CA097048-01. Reprint requests: Kenneth K. Wang, MD, Barrett’s Esophagus Unit, GI Diagnostic Unit, Alfred Main, St. Mary’s Hospital, 200 1st St SW, Rochester, MN 55905.
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Endoscopic therapy in patients with Barrett’s esophagus and portal hypertension Ganapathy A. Prasad, MD, Kenneth K. Wang, MD, Ann M. Joyce, MD, Michael L. Kochman, MD, Lori S. Lutzke, Lynn S. Borkenhagen Rochester, Minnesota, Philadelphia, Pennsylvania, USA
Background: Endoscopic mucosal resection has been used to stage and treat early neoplasia in Barrett’s esophagus. The ability to do this in the setting of portal hypertension has not been reported. Objective: Our purpose was to describe the feasibility and efficacy of endoscopic mucosal resection in patients with portal hypertension and Barrett’s esophagus. Design: Retrospective case series. Setting: Two tertiary referral centers. Patients: Patients with Barrett’s esophagus and high-grade dysplasia or adenocarcinoma in the setting of portal hypertension. Intervention: Endoscopic mucosal resection of endoscopically visible lesions. Main Outcome Measurements: Complete resection of neoplastic lesion, lack of variceal bleeding. Results: Four patients were treated with endoscopic mucosal resection a total of 5 times. Endoscopic mucosal resection was successfully performed without significant GI bleeding. Limitations: This preliminary case series describes feasibility of the procedure. Whether this can be generalized remains to be determined, although it may be an option in poor surgical candidates. Conclusions: Endoscopic mucosal resection appears to be relatively safe in selected patients with portal hypertension and Barrett’s esophagus. Further studies are needed to confirm these findings.
Endoscopic therapy is increasingly being used in the management of esophageal neoplasia arising in a background of Barrett’s esophagus.1-4 Management of highgrade dysplasia (HGD) in Barrett’s esophagus and mucosal adenocarcinoma with endoscopic mucosal resection (EMR) in combination with other ablative techniques has been shown in preliminary studies to have results comparable to those of esophagectomy.5 Endoscopic therapy of HGD is associated with lower morbidity and mortality rates compared with esophagectomy. Currently, patients with Barrett’s esophagus and HGD, who are poor operative candidates, are often referred for endoscopic therapy. There is currently little information in the literature concerning the feasibility and safety of endoscopic therapy in patients with neoplasia arising in Barrett’s esophagus
who have chronic liver disease and portal hypertension. We report the combined experience of 2 tertiary care referral centers with EMR of neoplastic lesions arising in Barrett’s esophagus in 4 consecutive patients with cirrhosis, portal hypertension, and esophageal varices.
CASE 1
Copyright ª 2007 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2006.11.024
An 82-year-old man with nonalcoholic steatohepatitis (NASH)–related cirrhosis (Child Pugh classification B, MELD (model end-stage liver disease) score 15, international normalized ratio [INR] 1.3, platelets 90,000/mL [normal 150,000-450,000/mL]) and varices had Barrett’s esophagus and HGD on outside mucosal biopsy specimens. Endoscopy showed a 2-cm segment of Barrett’s esophagus, with a 3-mm nodule and F1 (small straight) esophageal varices (Fig. 1). At the initial endoscopy, endoscopic variceal ligation (EVL) of 3 variceal trunks proximal
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Figure 1. Evidence of portal hypertension (F1, small straight esophageal varices) before endoscopic mucosal resection.
and distal to the nodule was performed with use of a Duette multiband ligator device (Wilson Cook, WinstonSalem, NC). Mucosal biopsy specimens showed HGD. The patient returned 1 week later, at which time endoscopy revealed clean-based ulceration at the banding sites without evidence of residual varices. The nodule at the gastroesophageal junction was removed by 3 mucosal resections with an Olympus EMR cap (EMR-001, Olympus, Melville, NY) according to a previously described standard technique4 (Fig. 2). Two EMR specimens revealed HGD with negative margins and the third revealed low-grade disease (LGD). The patient did well after the EMR without any complications. Four months later, hepatocellular carcinoma developed, which was treated with radiofrequency ablation.
CASE 2 A 58-year-old man with NASH-related cirrhosis (Child Pugh classification B, MELD score 10, INR 0.9, platelet count 85,000/mL) had Barrett’s esophagus and HGD detected on routine endoscopy. He also had a history of variceal hemorrhage and transjugular intrahepatic portosystemic shunt (TIPS) placement, followed by hepatic encephalopathy (controlled with lactulose and rifaximin). Initial endoscopy revealed a 5-cm segment of Barrett’s esophagus with a polypoid lesion and F2 (tortuous varices occupying less than a third of the esophageal lumen) esophageal varices. EUS confirmed the presence of intraesophageal and periesophageal varices. Three bands were placed in the distal and proximal esophagus with a Duette multiband ligator device. He returned 1 month later, at which time endoscopy revealed no varices in the proximal Barrett’s esophagus segment. EMR was performed by using the Duette multiband mucosectomy device. Histopathologic examination revealed HGD with negative margins. Mucosal biopsy specimens revealed HGD. The patient did well without any complications. He underwent photo528 GASTROINTESTINAL ENDOSCOPY Volume 65, No. 3 : 2007
Figure 2. Site after mucosal resection of early adenocarcinoma. Three mucosal resections were performed.
dynamic therapy 6 weeks later to treat the remaining dysplastic mucosa without complications.
CASE 3 A 78-year old man with alcoholic cirrhosis (Child Pugh classification A, MELD score 9, platelet count 150,000/mL, and INR 0.9) had Barrett’s esophagus and HGD detected on routine endoscopy. Endoscopy revealed a 2-cm segment of Barrett’s esophagus at the gastroesophageal junction. Small, straight varices (F1) were seen in the lower esophagus. EUS examination did not reveal any evidence of submucosal varices or mucosal lesions. Two mucosal resections were performed with the Duette multiband mucosectomy device (Fig. 3). Minimal oozing was seen at the site of the second EMR, which was controlled with the application of a single hemoclip (Boston Scientific, Natick, Mass) (Fig. 4). The patient was observed overnight in the hospital. Twenty-four hours after endoscopy, the hemoglobin remained stable and he was discharged. Histopathologic examination revealed intramucosal carcinoma in the EMR specimen with involvement of one lateral margin. Endoscopy performed a month later revealed an elevated area of erythematous mucosa adjacent to the prior EMR site, which was resected with the Duette device. After the resection, a Quickclip (Olympus) was placed prophylactically to secure good hemostasis. Histologic examination revealed HGD with negative margins. The patient returned for endoscopic surveillance 3 months later, at which time EMR and biopsy specimens revealed nondysplastic Barrett’s esophagus at the gastroesophageal junction.
CASE 4 A 60-year-old man with alcoholic cirrhosis (Child Pugh classification A, MELD score 10, platelet count 87,000/mL, www.giejournal.org
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Endoscopic therapy in Barrett’s esophagus and portal hypertension
Figure 3. Banding of an early adenocarcinoma with placement of the snare above the band for endoscopic resection.
Figure 4. Placement of hemoclip after mucosal resection of early adenocarcinoma. The ligation band is still seen in place over the site of resection.
INR 1.2) and chronic gastroesophageal reflux underwent endoscopy, which revealed a 4-cm segment of Barrett’s esophagus with LGD and a 2-cm pedunculated polyp at the gastroesophageal junction. Endoscopy done 18 months later revealed a 1.5-cm nodule with HGD and no esophageal varices. EUS revealed a mucosally based lesion, small collateral periesophageal vessels, and no suspicious lymphadenopathy. Twenty milliliters of normal saline solution was injected into the submucosa to lift the lesion for EMR. After the third application of a needle, oozing of blood was noted. A band was then placed on the lesion (SpeedView 7, Boston Scientific) and proximal and distal to the lesion. The lesion was then snare resected with electrocautery. Persistent oozing was seen after resection and the patient was admitted for overnight observation. The patient’s hematocrit remained stable and he was discharged the next morning. Histopathologic examination of the resected specimen showed polypoid LGD. A follow-up endoscopy in 3 months with biopsies revealed LGD. Although the patient was then referred for photodynamic therapy, he did not wish to undergo ablative therapy and has also refused further endoscopic surveillance.
During the past decade, EMR has been gaining acceptance in Europe and the United States as an alternative modality for the treatment of neoplastic lesions arising in the background of Barrett’s esophagus.1-3,6-9 The primary advantage of EMR is that it can remove large portions of mucosa and submucosa, which allows histologic staging and diagnosis of lesions in Barrett’s esophagus.10 EMR may also be curative for smaller lesions.4 EMR is a relatively safe procedure, but it can lead to complications: bleeding (reported in 4%-10% of patients),11 perforation (0.1%-5%), and stricture formation, especially after
circumferential EMR8 and when used in combination with PDT.1 Barrett’s esophagus has been reported in 2% to 3% of patients undergoing endoscopy as part of a liver transplant evaluation.12,13 Patients with cirrhosis may also have risk factors for Barrett’s esophagus, such as obesity (associated with NASH and gastroesophageal reflux). The association of alcohol with esophageal neoplasia and gastroesophageal reflux remains debatable, with studies reporting contradictory findings.14-16 Patients with cirrhosis and portal hypertension have been reported in some studies to have delayed gastric emptying/GI transit,17,18 which may potentiate gastroesophageal reflux. With the increasing acceptance of EMR in the management of neoplasia arising in Barrett’s esophagus, patients with comorbidities and high operative risk are often referred for endoscopic therapy. Patients with cirrhosis and portal hypertension are well known to have greater operative mortality because of the risk for hepatic decompensation after surgery and the presence of vascular collaterals, which could cause severe hemorrhage with mucosal resection.19 Varices can increase the risk of bleeding after EMR. This is the first report from the United States on EMR performed for Barrett’s esophagus in patients with HGD in a background of portal hypertension after the eradication of varices by EVL. Iwase et al20 reported the resection of early stage squamous esophageal cancer in a patient with alcoholic cirrhosis and esophageal varices. This lesion was confirmed to be mucosally confined by EUS examination. The authors first used esophageal sclerotherapy (EST) by using 2% sodium tetradecyl sulfate to obliterate varices in 2 sessions. After visual confirmation of eradication of varices, they performed EMR of the neoplastic lesion, without immediate or delayed bleeding. The patient did not have recurrence of the cancer or varices at endoscopy performed 1 year after the resection. Other authors have also
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reported endoscopic management of patients with squamous esophageal cancer with EMR21 and with PDT and radiation.22 Endlicher et al23 have also recently reported the use of variceal ligation for eradication of varices before endoscopic treatment of mucosally confined squamous esophageal cancer with EMR in a 71-year-old patient with alcoholic cirrhosis and esophageal varices. This was done in 1 session without significant complications but needed a follow-up EMR in 3 months because of recurrence. After 18 months of follow-up, the patient had no evidence of macroscopic recurrence, although LGD was still found on biopsy specimens. Patients with Barrett’s esophagus and HGD are at significant risk for either coexistent carcinoma24,25 or progression to carcinoma,26-30 with rates as high as 57% over 2 years being reported. One study31 reported lower rates (17% over 7 years) of progression, although this study used a single pathologist and excluded prevalent cancers (cancers arising within 1 year of diagnosis of HGD: 4/34 patients). Patients with cirrhosis have a shortened life expectancy, and an argument could be made that endoscopic surveillance alone (with the increased risk of bleeding from underlying varices) may be an acceptable strategy in these patients. We have previously reported that EMR is superior to biopsy and EUS alone in staging patients with HGD with visible nodules, with the diagnosis changing in as many as 40% of patients after EMR.10 In patients with low MELD scores who have a relatively longer life expectancy, identification and potential treatment of an early cancer with EMR would be reasonable. This, however, highlights the need to closely weigh the risks and benefits of performing EMR on patients with portal hypertension and esophageal varices. We would also like to emphasize that 3 of 4 patients treated in this case series had small esophageal varices that were obliterated by EVL before EMR was attempted and had well-compensated cirrhosis with low MELD scores and no evidence of coagulopathy. Patients with higher MELD scores and coagulopathy may not be suitable candidates. EMR is an invasive procedure with a well-documented bleeding risk. Patients are routinely discharged after EMRs at our institutions. Two patients in this case series were hospitalized after the procedure: case 3 was admitted to the hospital for observation because a hemoclip was applied for achieving hemostasis, and case 4 was admitted to the hospital because the EMR site had persistent oozing. Neither patient, however, had a significant decline in blood pressure or hemoglobin and neither needed a blood transfusion. However, this demonstrates the potential for life-threatening complications after EMR in this high-risk population and the need for securing hemostasis and for close postprocedure monitoring. Scarring induced by prior EVL may result in failure of the lesions to lift after saline solution injection performed during EMR, potentially precluding safe performance of EMR; this was not observed in our patients. Resection of
lesions situated on top of varices may be challenging; however, if the varix is decompressed by the application of bands distally, resection of the lesion after confirmation of adequate variceal decompression (with EUS) could be considered. EMR in this case series was used as a diagnostic/staging tool. Patients with residual dysplastic mucosa were treated either with sequential EMRs (as in case 3, with continued demonstration of adequate variceal decompression), surveillance (as opted for by case 4), or with photodynamic therapy (as in case 2). Long-term follow-up results would be crucial in determining the role of EMR in patients with dysplasia arising in Barrett’s esophagus when they have underlying portal hypertension. In this preliminary report, EMR of esophageal lesions in a background of portal hypertension, when performed in centers with expertise on carefully selected patients after obliteration of varices, appears to be feasible and can be effective in removing neoplastic lesions. EUS may allow confirmation of variceal eradication or absence, allowing either the confirmation of adequate therapy or the performance of EMR without variceal ligation. Aggressive hemostasis and close monitoring for bleeding after EMR in such patients would be prudent.
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DISCLOSURE The authors have no conflicts of interest.
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Endoscopic therapy in Barrett’s esophagus and portal hypertension 23. Endlicher E, Gelbmann C, Schlottmann K, et al. Endoscopic mucosal resection for early esophageal cancer with esophageal varices [in German]. Z Gastroenterol 2004;42:609-13. 24. Rice TW, Falk GW, Achkar E, et al. Surgical management of high-grade dysplasia in Barrett’s esophagus. Am J Gastroenterol 1993;88:1832-6. 25. Heitmiller RF, Redmond M, Hamilton SR. Barrett’s esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy. Ann Surg 1996;224:66-71. 26. Reid BJ, Prevo LJ, Galipeau PC, et al. Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol 2001;96:2839-48. 27. Rabinovitch PS, Longton G, Blount PL, et al. Predictors of progression in Barrett’s esophagus III: baseline flow cytometric variables. Am J Gastroenterol 2001;96:3071-83. 28. Reid BJ, Levine DS, Longton G, et al. Predictors of progression to cancer in Barrett’s esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets. Am J Gastroenterol 2000;95:1669-76. 29. Reid BJ. p53 and neoplastic progression in Barrett’s esophagus. Am J Gastroenterol 2001;96:1321-3. 30. Reid BJ, Blount PL, Rabinovitch PS. Biomarkers in Barrett’s esophagus. Gastrointest Endosc Clin North Am 2003;13:369-97. 31. Schnell TG, Sontag SJ, Chejfec G, et al. Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology 2001;120:1607-19.
Received June 30, 2006. Accepted November 14, 2006. Current affiliations: Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA (G. P., K. K. W., L. S. L., L. S. B.) and Gastroenterology Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA (A. M. J., M. L. K.). Supported by National Institutes of Health grants No. CA85992-01 and CA097048-01. Reprint requests: Kenneth K. Wang, MD, Barrett’s Esophagus Unit, GI Diagnostic Unit, Alfred Main, St. Mary’s Hospital, 200 1st St SW, Rochester, MN 55905.
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