ORIGINAL ARTICLE
Radiofrequency Ablation of Treatment-refractory Gastric Antral Vascular Ectasia (GAVE) Naeem Raza, MD and David L. Diehl, MD, FACP, FASGE
Abstract: Gastric antral vascular ectasia (GAVE) is a rare but an important cause of gastrointestinal bleeding and anemia. Endoscopic ablation is usually successful, but treatment-refractory cases occur. We have used radiofrequency ablation (RFA) with the HALO90 device in these cases with positive results. Nine patients (5 female patients) with refractory GAVE were treated with RFA. Four had GAVE associated with cirrhosis, 4 had renal insufficiency, and 1 had both cirrhosis and renal insufficiency. Patients had received multiple endoscopic treatments before undergoing RFA over a period of up to 2 years (median 4; range, 2 to 15 y). A total of 2 to 6 (median 3) RFA sessions were performed until GAVE eradication. Endoscopic ablation was achievable in all patients. There were no complications of the treatments. Seven of the 9 patients had sustained response to RFA over a median follow-up of 11 months (range, 6 to 21 mo). Key Words: gastric antral vascular ectasia, GAVE, watermelon stomach, argon plasma coagulation, APC, endoscopic hemostasis, radiofrequency ablation, cirrhosis, gastrointestinal bleeding
(Surg Laparosc Endosc Percutan Tech 2015;25:79–82)
G
astric antral vascular ectasia (GAVE) is a well-described cause of gastrointestinal (GI) blood loss that may manifest as iron deficiency anemia or even overt GI hemorrhage. Histologically, the red streaks are composed of ectatic blood vessels in the superficial submucosal layer1 and may arise from disordered antral motility observed in some disorders.2 GAVE can occur in association with various autoimmune conditions and can also be seen with portal hypertension.3 Endoscopic ablation with Nd-YAG laser4 or argon plasma coagulation (APC)5,6 has been the standard treatment. More recently described endoscopic ablative techniques include radiofrequency (RF) ablation,7 cryoablation,8 and band ligation.9,10 Despite encouraging results of endoscopic ablation with the above modalities, occasional patients may be refractory to standard treatments. We have used the Barrett esophagus RF ablation probe (HALO90 system; BAˆRRX Medical Inc, Sunnyvale, Calif), as an alternative in 9 patients with GAVE refractory to standard ablation treatment with encouraging results.
Received for publication July 14, 2013; accepted October 22, 2013. From the Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, PA. The authors declare no conflicts of interest. Reprints: David L. Diehl, MD, FACP, FASGE, Department of Gastroenterology and Nutrition, Geisinger Medical Center, 100N. Academy Ave, 21-11, Danville, PA 17822 (e-mail: dldiehl@ geisinger.edu). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
Surg Laparosc Endosc Percutan Tech
METHODS AND DETAILS This study was approved by the institutional review board of the Geisinger Medical Center, Danville, PA. Data regarding the previous endoscopic procedures and prescribed treatment were collected. Between 2010 and 2012, we encountered 9 patients (5 female patients) with GAVE refractory to standard endoscopic ablation with APC. Refractory cases were defined as continued need for blood transfusion for bleeding from GAVE, despite at least 2 previous APC sessions. These patients were then treated with RF ablation therapy and are the basis for this case series. Diagnosis of the GAVE was confirmed by endoscopy and in 2 cases, EUS was required to rule out other vascular lesions because the GAVE was extensive and somewhat nodular and atypical in appearance. Hemoglobin (Hgb) levels and number of blood transfusion before and after RF therapy were determined. Details of the number of RF treatment sessions and number of pulses given per treatment were recorded. Clinical follow-up was continued, and need for further GAVE treatment, or endoscopy, for falling Hgb was noted (Table 1).
Technique Informed consent about this procedure was obtained from each patient. All patients were treated by a single physician (D.L.D.) accompanied by a gastroenterology fellow. The HALO90 RF ablation probe was attached to the tip of a standard diagnostic endoscope (Olympus GIF-180, 9.9 mm outer diameter). The default power setting of 12 J/cm2 was used. The paddle of the RF probe was oriented to the 6 o’clock or the 12 o’clock position as seen on the video screen, depending on the predominant location of the antral GAVE. No difficulty with or difference between passage of the probe-tipped endoscope was encountered related to either position of the probe. Mucosal irrigation with N-acetyl cysteine was not carried out, in contrast with RF ablation of Barrett esophagus. As per the method described by Gross et al,7 the RF ablation paddle is pressed against the mucosa by moving the up-down control of the endoscope and the gastric air is suctioned. Both of these increase surface contact with the treatment probe. Four pulses at a single location were applied in quick succession, resulting in a rectangular area of white coagulum. Thereafter, the probe was moved to an adjacent area and another 4 pulses were applied. This approach was continued until all of the visible areas of GAVE were ablated (Fig. 1). The HALO90 catheter can deliver a maximum of 80 pulses before automatic shut-off. In a single patient, 2 catheters were used to deliver 160 pulses for extensive GAVE that was present in the gastric fundus, body, and antrum. Patients were given twice daily oral proton-pump inhibitor postprocedure and asked to continue this until the follow-up examination, which was usually conducted 8 weeks later. At the follow-up endoscopy, residual areas of
Volume 25, Number 1, February 2015
www.surgical-laparoscopy.com |
79
Surg Laparosc Endosc Percutan Tech
Raza and Diehl
Volume 25, Number 1, February 2015
TABLE 1. Patient Characteristics
Total Required Transfusion Repeat Prior Baseline Before Treatment Chronic Therapy Ablation Hgb Hgb After Ablations Transfusions (Months Patient Age Liver Kidney (No. Treat- Sessions Levels Ablations (Units After After # (y) Sex Disease Disease Location ments) HALO90 (g/dL) (g/dL) PRBC) Ablations Eradication) 1
63
M
2 3 4
63 73 71
Yes (cirrhosis) F No M No M No
5
66
F
6 7
77 62
8 9
66 71
No
A
No Yes No
AC A A
No
Yes (on HD) F No No F Yes Yes (on (cirrhosis) HD) M Yes No F Yes Yes (cirrhosis)
APC (7)
2
6.1
10.3
19
1
No (21)
APC (4) APC (11) APC (5), cryotherapy (2) APC (15)
6 2 3
4.5 8.3 10.2
10.0 10.7 12.4
15 12 6
2 9 0
No (15) Yes (3) No (12)
6
6.4
10.5
4
1
Yes (11)
A AC
APC (2) APC (4)
2 2
7.9 8.6
11.8 9.1
2 17
0 6
No (34) No (10)
A A
APC (1) APC (4)
3 2
7.1 6.6
10.0 10.0
10 7
2 3
No (10) Yes (11)
A
A indicates antral location of GAVE; AC, antrum to cardia location of GAVE; APC, argon plasma coagulation; GAVE, gastric antral vascular ectasia; HD, hemodialysis; Hgb, hemoglobin; PRBC, packed red blood cells.
GAVE were again ablated. Follow-up endoscopies were performed until the GAVE was completely ablated; endoscopic ablation was achievable in all patients. After GAVE eradication, the patients were followed clinically with serial Hgb assessment. Repeat endoscopy was carried out if more bleeding requiring blood transfusion was encountered.
RESULTS Four of the 9 patients had GAVE in the setting of portal hypertension from cirrhosis. Four patients had renal insufficiency, 2 of which was hemodialysis (HD) dependent. One patient had both cirrhosis and renal insufficiency. Patients had received multiple [median 4; range, 2 to 15,
FIGURE 1. Examples of RF ablation of GAVE in 3 patients: pretreatment (A), during treatment (B and C), and after eradication (D). GAVE indicates gastric antral vascular ectasia; RF, radiofrequency ablation.
80 | www.surgical-laparoscopy.com
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Surg Laparosc Endosc Percutan Tech
Volume 25, Number 1, February 2015
interquartile range (IQR) 6.5] endoscopic treatments before RF ablation over a period of up to 2 years. A total of 2 to 6 (median 3, IQR 4) RF ablation sessions per patient were conducted until there was no visible ectasias on repeat endoscopy. Endoscopic ablation was achievable in all patients. There were no instances of difficulty introducing the endoscope-mounted ablation device through the esophagus. There were no complications of the treatments. One patient who had 160 pulses in a single session had minor abdominal discomfort that lasted a few days. Patients were followed up for a median of 11 months (range, 6 to 21; IQR 4) Six patients (67%) did not require repeat endoscopies for GAVE (Fig. 2); 3 of these had chronic renal insufficiency and one was cirrhotic. Two patients went 11 months without endoscopy or transfusion but then required transfusion and retreatment of recurrent GAVE. One patient required transfusion and repeat ablation 3 months after the initial round of treatment and had another recurrence requiring another ablation 3 months after the second. One patient (patient 7) with cirrhosis and on HD had longstanding eradication of GAVE proven by endoscopy but required transfusion for portosystemic gastropathy. The portosystemic gastropathy was present even before GAVE ablation.
DISCUSSION GAVE is a rare but significant cause of nonvariceal GI bleeding. The clinical presentation varies from overt GI bleeding to iron deficiency anemia. It was first reported by Rider et al11 in 1953. Characteristic histologic features include fibrinolysis, spindle cell proliferation, and fibrin thrombi.1 GAVE is typically located at the gastric antrum but has also been reported in the gastric cardia.12 GAVE can be associated with systemic sclerosis, cirrhosis, and chronic renal failure or may be “sporadic.” Clinical
Radiofrequency Ablation of Treatment-refractory GAVE
presentation and endoscopic findings in cirrhotic patients with GAVE can be difficult to differentiate from portal hypertensive gastropathy, but these conditions are different and require different treatments.13 Surgical resection has been carried out for GAVE, but complication rates are high given the typical comorbidities seen in these patients. Pharmacotherapy has been used with mixed results. Endoscopic ablation using thermal probes has given better results and is currently the standard treatment. Endoscopic ablation of GAVE was first described with Nd-YAG laser.4 This modality gave good results, with a good safety record. Concern about laser-induced perforation and lack of wide availability of this device led to use of other thermal treatments, such as APC. No randomized studies have been conducted to compare APC with Nd-YAG laser, but the good response to APC and wide availability of this device has led to this becoming the standard treatment for GAVE. Failure to respond to APC treatment is occasionally observed, and there is limited data on what to do in these cases. In a series of 12 GAVE patients treated with CO2 cryoablation,8 58% had previously failed APC treatment. Half had a complete response to the cryoablation after 3 treatments, and half had a partial response, as defined by need for more blood transfusions. Gross’ first reported study of RF ablation in 6 patients included 4 who had failed previous APC ablation. Limited follow-up of this cohort (mean 2 mo) makes firm conclusions on usefulness in APC-refractory cases difficult. Our study has longer follow-up and does seem to indicate that RFA is a reasonable alternative in APC-refractory GAVE. McGorisk et al14 described their experience with RFA for refractory GAVE and found a rise in the hemoglobin level in 18 of 21 (86%) patients. On a 6-month follow-up, the number of transfusion events also decreased. Our current study found 2 patients who had rebleeding 11 months after eradication; this indicates that longer treatment follow-up is
FIGURE 2. Graph showing units of packed red blood cells transfused before and after RF treatment. Darker lines indicate patients who required repeat RF treatment after eradication. RF indicates radiofrequency ablation.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.surgical-laparoscopy.com |
81
Raza and Diehl
Surg Laparosc Endosc Percutan Tech
necessary before complete transfusion independence can be declared. Band ligation is another treatment modality that can be considered for APC failures. Wells et al9 used ligation as primary treatment for 9 cases with bleeding cessation seen in 67% compared with 23% for thermal therapy (bipolar probe or APC). Banding also was found to be better in decreasing transfusion requirements, hospitalizations, and increased Hgb. No APC failures were included in this series, but the high efficacy of banding suggests that this modality may be a reasonable alternative. As can be seen in this series, comorbidities of liver or kidney insufficiency is often seen in treatment-refractory GAVE. In this series, all 3 of the patients without a complete response had renal insufficiency (one of which was HD dependent). One of these patients also had cirrhosis. Of the 4 cirrhotic patients in this series, 2 had long-term success with the RF ablation. Complete endoscopic ablation of all visible GAVE is a reasonable goal of treatment, but the endpoint of fewer or no transfusions is a more useful one to evaluate success of any endoscopic GAVE treatment. The factors that lead to development of the GAVE (eg, alterations in antral motility) are not eliminated and some degree of recurrence is likely. Impairment of coagulation, platelet function, or red cell generation such as that seen in liver, kidney, or bone marrow disease may lead to more gastric blood loss, even after “successful” GAVE eradication. Patients who can “keep up with” GI blood loss with bone marrow production of red blood cells (perhaps with the help of oral or intravenous iron) may not be transfusion-dependent after GAVE management. Thus, the natural history of GAVE after endoscopic ablation is highly dependent on patient comorbidities. The procedure is technically straightforward and well tolerated by the patients. The HALO90 catheter allows a uniform zone of coagulation, which may avoid “skip areas” that may be encountered with a smaller thermal probe such as APC or multipolar electrocoagulation. In addition, there is less treatment-induced oozing, which makes visualization during the procedure easier. Another reason that RF ablation may work better is that it delivers broad “coaptive coagulation.” The histology of GAVE shows that prominent submucosal vessels are present, and it is reasonable to think that coaptive coagulation is a better way of eliminating these. Coaptive coagulation is delivered with a focal probe such as bipolar electrocautery, but the contact area is small and “skip areas” are likely. In contrast, the HALO90 probe has a surface area of 2.6 cm2, allowing wide coaptive coverage. A newer RF probe (HALO90 Ultra) can potentially provide an area of ablation measuring 5.2 cm2. Nd-YAG and APC are not coaptive techniques and may not eliminate deeper submucosal vascular channels as effectively. It would be of interest to determine if primary treatment of nontreatment resistant GAVE with RF would be
82 | www.surgical-laparoscopy.com
Volume 25, Number 1, February 2015
more effective than APC in terms of needing fewer treatments. A randomized trial of APC versus RF would be necessary to answer this question. Such a study would likely have to be multicenter, given the relative infrequency with which GAVE is encountered. A randomized trial for treatment-resistant GAVE would be even harder to conduct, given the low numbers of these cases. However, RF ablation is technically easy to perform, is well tolerated, and as this case series shows, it is a valuable alternative treatment. Need for ongoing transfusions after treatment may be dependent on patient comorbidity, particularly with concomitant liver or kidney disease. REFERENCES 1. Selinger CP, Ang YS. Gastric antral vascular ectasia (GAVE) an update on clinical presentation, pathophysiology and treatment. Digestion. 2008;77:131–137. 2. Charneau J, Petit R, Cales P, et al. Antral motility in patient with cirrhosis with and without gastric antral vascular ectasia. Gut. 1995;37:488–492. 3. Burak WK, Lee SS, Beck PL. Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndrome. Gut. 2001;49:866–872. 4. Mathou NG, Lovat LB, Thorpe SM, et al. Nd:YAG laser induces long-term remission in transfusion-dependent patients with watermelon stomach. Laser Med Sci. 2004;18:213–218. 5. Kwan V, Bourke MJ, Williams SJ, et al. Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol. 2006;101:58–63. 6. Sebastian S, McLoughlin R, Qasim A, et al. Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia (watermelon stomach): long-term results. Dig Liver Dis. 2004;36:212–217. 7. Gross SA, Al-Haddad M, Gill KRS, et al. Endoscopic mucosal ablation for the treatment of gastric antral vascular ectasia with the HALO-90 system: a pilot study. Gastrointest Endosc. 2008;67:324–327. 8. Cho S, Zanati S, Yong E, et al. Endoscopic cryotherapy for the management of gastric antral vascular ectasia. Gastrointest Endosc. 2008;68:895–902. 9. Wells CD, Harrison ME, Gurudu SR, et al. Treatment of gastric antral vascular ectasia (watermelon stomach) with endoscopic band ligation. Gastrointest Endosc. 2008;68:231–236. 10. Sato T, Yamazaki K, Akaike J, et al. Endoscopic band ligation for refractory gastric antral vascular ectasia associated with liver cirrhosis. Clin J Gastro. 2011;4:108–111. 11. Rider JA, Klotz AP, Kirsner JB. Gastritis with veno-capillary ectasia as a source of massive gastric hemorrhage. Gastroenterol. 1953;24:118–123. 12. Stotzer PO, Willeri R, Kilander AF. Watermelon stomach: not only an antral disease. Gastrointest Endosc. 2002;55:897–900. 13. Payen JL, Cales P, Voigt JJ, et al. Severe portal hypertensive gastropathy and antral vascular ectasia are distinct entities in patients with cirrhosis. Gastroenterol. 1995;108:138–144. 14. McGorisk T, Krishnan K, Keefer L, et al. Radiofrequency ablation for refractory gastric antral vascular ectasia. Gastrointest Endosc. 2013;78:584–588.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Radiofrequency Ablation of Treatment-refractory Gastric Antral Vascular Ectasia (GAVE) Naeem Raza, MD and David L. Diehl, MD, FACP, FASGE
Abstract: Gastric antral vascular ectasia (GAVE) is a rare but an important cause of gastrointestinal bleeding and anemia. Endoscopic ablation is usually successful, but treatment-refractory cases occur. We have used radiofrequency ablation (RFA) with the HALO90 device in these cases with positive results. Nine patients (5 female patients) with refractory GAVE were treated with RFA. Four had GAVE associated with cirrhosis, 4 had renal insufficiency, and 1 had both cirrhosis and renal insufficiency. Patients had received multiple endoscopic treatments before undergoing RFA over a period of up to 2 years (median 4; range, 2 to 15 y). A total of 2 to 6 (median 3) RFA sessions were performed until GAVE eradication. Endoscopic ablation was achievable in all patients. There were no complications of the treatments. Seven of the 9 patients had sustained response to RFA over a median follow-up of 11 months (range, 6 to 21 mo). Key Words: gastric antral vascular ectasia, GAVE, watermelon stomach, argon plasma coagulation, APC, endoscopic hemostasis, radiofrequency ablation, cirrhosis, gastrointestinal bleeding
(Surg Laparosc Endosc Percutan Tech 2015;25:79–82)
G
astric antral vascular ectasia (GAVE) is a well-described cause of gastrointestinal (GI) blood loss that may manifest as iron deficiency anemia or even overt GI hemorrhage. Histologically, the red streaks are composed of ectatic blood vessels in the superficial submucosal layer1 and may arise from disordered antral motility observed in some disorders.2 GAVE can occur in association with various autoimmune conditions and can also be seen with portal hypertension.3 Endoscopic ablation with Nd-YAG laser4 or argon plasma coagulation (APC)5,6 has been the standard treatment. More recently described endoscopic ablative techniques include radiofrequency (RF) ablation,7 cryoablation,8 and band ligation.9,10 Despite encouraging results of endoscopic ablation with the above modalities, occasional patients may be refractory to standard treatments. We have used the Barrett esophagus RF ablation probe (HALO90 system; BAˆRRX Medical Inc, Sunnyvale, Calif), as an alternative in 9 patients with GAVE refractory to standard ablation treatment with encouraging results.
Received for publication July 14, 2013; accepted October 22, 2013. From the Department of Gastroenterology and Nutrition, Geisinger Medical Center, Danville, PA. The authors declare no conflicts of interest. Reprints: David L. Diehl, MD, FACP, FASGE, Department of Gastroenterology and Nutrition, Geisinger Medical Center, 100N. Academy Ave, 21-11, Danville, PA 17822 (e-mail: dldiehl@ geisinger.edu). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
Surg Laparosc Endosc Percutan Tech
METHODS AND DETAILS This study was approved by the institutional review board of the Geisinger Medical Center, Danville, PA. Data regarding the previous endoscopic procedures and prescribed treatment were collected. Between 2010 and 2012, we encountered 9 patients (5 female patients) with GAVE refractory to standard endoscopic ablation with APC. Refractory cases were defined as continued need for blood transfusion for bleeding from GAVE, despite at least 2 previous APC sessions. These patients were then treated with RF ablation therapy and are the basis for this case series. Diagnosis of the GAVE was confirmed by endoscopy and in 2 cases, EUS was required to rule out other vascular lesions because the GAVE was extensive and somewhat nodular and atypical in appearance. Hemoglobin (Hgb) levels and number of blood transfusion before and after RF therapy were determined. Details of the number of RF treatment sessions and number of pulses given per treatment were recorded. Clinical follow-up was continued, and need for further GAVE treatment, or endoscopy, for falling Hgb was noted (Table 1).
Technique Informed consent about this procedure was obtained from each patient. All patients were treated by a single physician (D.L.D.) accompanied by a gastroenterology fellow. The HALO90 RF ablation probe was attached to the tip of a standard diagnostic endoscope (Olympus GIF-180, 9.9 mm outer diameter). The default power setting of 12 J/cm2 was used. The paddle of the RF probe was oriented to the 6 o’clock or the 12 o’clock position as seen on the video screen, depending on the predominant location of the antral GAVE. No difficulty with or difference between passage of the probe-tipped endoscope was encountered related to either position of the probe. Mucosal irrigation with N-acetyl cysteine was not carried out, in contrast with RF ablation of Barrett esophagus. As per the method described by Gross et al,7 the RF ablation paddle is pressed against the mucosa by moving the up-down control of the endoscope and the gastric air is suctioned. Both of these increase surface contact with the treatment probe. Four pulses at a single location were applied in quick succession, resulting in a rectangular area of white coagulum. Thereafter, the probe was moved to an adjacent area and another 4 pulses were applied. This approach was continued until all of the visible areas of GAVE were ablated (Fig. 1). The HALO90 catheter can deliver a maximum of 80 pulses before automatic shut-off. In a single patient, 2 catheters were used to deliver 160 pulses for extensive GAVE that was present in the gastric fundus, body, and antrum. Patients were given twice daily oral proton-pump inhibitor postprocedure and asked to continue this until the follow-up examination, which was usually conducted 8 weeks later. At the follow-up endoscopy, residual areas of
Volume 25, Number 1, February 2015
www.surgical-laparoscopy.com |
79
Surg Laparosc Endosc Percutan Tech
Raza and Diehl
Volume 25, Number 1, February 2015
TABLE 1. Patient Characteristics
Total Required Transfusion Repeat Prior Baseline Before Treatment Chronic Therapy Ablation Hgb Hgb After Ablations Transfusions (Months Patient Age Liver Kidney (No. Treat- Sessions Levels Ablations (Units After After # (y) Sex Disease Disease Location ments) HALO90 (g/dL) (g/dL) PRBC) Ablations Eradication) 1
63
M
2 3 4
63 73 71
Yes (cirrhosis) F No M No M No
5
66
F
6 7
77 62
8 9
66 71
No
A
No Yes No
AC A A
No
Yes (on HD) F No No F Yes Yes (on (cirrhosis) HD) M Yes No F Yes Yes (cirrhosis)
APC (7)
2
6.1
10.3
19
1
No (21)
APC (4) APC (11) APC (5), cryotherapy (2) APC (15)
6 2 3
4.5 8.3 10.2
10.0 10.7 12.4
15 12 6
2 9 0
No (15) Yes (3) No (12)
6
6.4
10.5
4
1
Yes (11)
A AC
APC (2) APC (4)
2 2
7.9 8.6
11.8 9.1
2 17
0 6
No (34) No (10)
A A
APC (1) APC (4)
3 2
7.1 6.6
10.0 10.0
10 7
2 3
No (10) Yes (11)
A
A indicates antral location of GAVE; AC, antrum to cardia location of GAVE; APC, argon plasma coagulation; GAVE, gastric antral vascular ectasia; HD, hemodialysis; Hgb, hemoglobin; PRBC, packed red blood cells.
GAVE were again ablated. Follow-up endoscopies were performed until the GAVE was completely ablated; endoscopic ablation was achievable in all patients. After GAVE eradication, the patients were followed clinically with serial Hgb assessment. Repeat endoscopy was carried out if more bleeding requiring blood transfusion was encountered.
RESULTS Four of the 9 patients had GAVE in the setting of portal hypertension from cirrhosis. Four patients had renal insufficiency, 2 of which was hemodialysis (HD) dependent. One patient had both cirrhosis and renal insufficiency. Patients had received multiple [median 4; range, 2 to 15,
FIGURE 1. Examples of RF ablation of GAVE in 3 patients: pretreatment (A), during treatment (B and C), and after eradication (D). GAVE indicates gastric antral vascular ectasia; RF, radiofrequency ablation.
80 | www.surgical-laparoscopy.com
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Surg Laparosc Endosc Percutan Tech
Volume 25, Number 1, February 2015
interquartile range (IQR) 6.5] endoscopic treatments before RF ablation over a period of up to 2 years. A total of 2 to 6 (median 3, IQR 4) RF ablation sessions per patient were conducted until there was no visible ectasias on repeat endoscopy. Endoscopic ablation was achievable in all patients. There were no instances of difficulty introducing the endoscope-mounted ablation device through the esophagus. There were no complications of the treatments. One patient who had 160 pulses in a single session had minor abdominal discomfort that lasted a few days. Patients were followed up for a median of 11 months (range, 6 to 21; IQR 4) Six patients (67%) did not require repeat endoscopies for GAVE (Fig. 2); 3 of these had chronic renal insufficiency and one was cirrhotic. Two patients went 11 months without endoscopy or transfusion but then required transfusion and retreatment of recurrent GAVE. One patient required transfusion and repeat ablation 3 months after the initial round of treatment and had another recurrence requiring another ablation 3 months after the second. One patient (patient 7) with cirrhosis and on HD had longstanding eradication of GAVE proven by endoscopy but required transfusion for portosystemic gastropathy. The portosystemic gastropathy was present even before GAVE ablation.
DISCUSSION GAVE is a rare but significant cause of nonvariceal GI bleeding. The clinical presentation varies from overt GI bleeding to iron deficiency anemia. It was first reported by Rider et al11 in 1953. Characteristic histologic features include fibrinolysis, spindle cell proliferation, and fibrin thrombi.1 GAVE is typically located at the gastric antrum but has also been reported in the gastric cardia.12 GAVE can be associated with systemic sclerosis, cirrhosis, and chronic renal failure or may be “sporadic.” Clinical
Radiofrequency Ablation of Treatment-refractory GAVE
presentation and endoscopic findings in cirrhotic patients with GAVE can be difficult to differentiate from portal hypertensive gastropathy, but these conditions are different and require different treatments.13 Surgical resection has been carried out for GAVE, but complication rates are high given the typical comorbidities seen in these patients. Pharmacotherapy has been used with mixed results. Endoscopic ablation using thermal probes has given better results and is currently the standard treatment. Endoscopic ablation of GAVE was first described with Nd-YAG laser.4 This modality gave good results, with a good safety record. Concern about laser-induced perforation and lack of wide availability of this device led to use of other thermal treatments, such as APC. No randomized studies have been conducted to compare APC with Nd-YAG laser, but the good response to APC and wide availability of this device has led to this becoming the standard treatment for GAVE. Failure to respond to APC treatment is occasionally observed, and there is limited data on what to do in these cases. In a series of 12 GAVE patients treated with CO2 cryoablation,8 58% had previously failed APC treatment. Half had a complete response to the cryoablation after 3 treatments, and half had a partial response, as defined by need for more blood transfusions. Gross’ first reported study of RF ablation in 6 patients included 4 who had failed previous APC ablation. Limited follow-up of this cohort (mean 2 mo) makes firm conclusions on usefulness in APC-refractory cases difficult. Our study has longer follow-up and does seem to indicate that RFA is a reasonable alternative in APC-refractory GAVE. McGorisk et al14 described their experience with RFA for refractory GAVE and found a rise in the hemoglobin level in 18 of 21 (86%) patients. On a 6-month follow-up, the number of transfusion events also decreased. Our current study found 2 patients who had rebleeding 11 months after eradication; this indicates that longer treatment follow-up is
FIGURE 2. Graph showing units of packed red blood cells transfused before and after RF treatment. Darker lines indicate patients who required repeat RF treatment after eradication. RF indicates radiofrequency ablation.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
www.surgical-laparoscopy.com |
81
Raza and Diehl
Surg Laparosc Endosc Percutan Tech
necessary before complete transfusion independence can be declared. Band ligation is another treatment modality that can be considered for APC failures. Wells et al9 used ligation as primary treatment for 9 cases with bleeding cessation seen in 67% compared with 23% for thermal therapy (bipolar probe or APC). Banding also was found to be better in decreasing transfusion requirements, hospitalizations, and increased Hgb. No APC failures were included in this series, but the high efficacy of banding suggests that this modality may be a reasonable alternative. As can be seen in this series, comorbidities of liver or kidney insufficiency is often seen in treatment-refractory GAVE. In this series, all 3 of the patients without a complete response had renal insufficiency (one of which was HD dependent). One of these patients also had cirrhosis. Of the 4 cirrhotic patients in this series, 2 had long-term success with the RF ablation. Complete endoscopic ablation of all visible GAVE is a reasonable goal of treatment, but the endpoint of fewer or no transfusions is a more useful one to evaluate success of any endoscopic GAVE treatment. The factors that lead to development of the GAVE (eg, alterations in antral motility) are not eliminated and some degree of recurrence is likely. Impairment of coagulation, platelet function, or red cell generation such as that seen in liver, kidney, or bone marrow disease may lead to more gastric blood loss, even after “successful” GAVE eradication. Patients who can “keep up with” GI blood loss with bone marrow production of red blood cells (perhaps with the help of oral or intravenous iron) may not be transfusion-dependent after GAVE management. Thus, the natural history of GAVE after endoscopic ablation is highly dependent on patient comorbidities. The procedure is technically straightforward and well tolerated by the patients. The HALO90 catheter allows a uniform zone of coagulation, which may avoid “skip areas” that may be encountered with a smaller thermal probe such as APC or multipolar electrocoagulation. In addition, there is less treatment-induced oozing, which makes visualization during the procedure easier. Another reason that RF ablation may work better is that it delivers broad “coaptive coagulation.” The histology of GAVE shows that prominent submucosal vessels are present, and it is reasonable to think that coaptive coagulation is a better way of eliminating these. Coaptive coagulation is delivered with a focal probe such as bipolar electrocautery, but the contact area is small and “skip areas” are likely. In contrast, the HALO90 probe has a surface area of 2.6 cm2, allowing wide coaptive coverage. A newer RF probe (HALO90 Ultra) can potentially provide an area of ablation measuring 5.2 cm2. Nd-YAG and APC are not coaptive techniques and may not eliminate deeper submucosal vascular channels as effectively. It would be of interest to determine if primary treatment of nontreatment resistant GAVE with RF would be
82 | www.surgical-laparoscopy.com
Volume 25, Number 1, February 2015
more effective than APC in terms of needing fewer treatments. A randomized trial of APC versus RF would be necessary to answer this question. Such a study would likely have to be multicenter, given the relative infrequency with which GAVE is encountered. A randomized trial for treatment-resistant GAVE would be even harder to conduct, given the low numbers of these cases. However, RF ablation is technically easy to perform, is well tolerated, and as this case series shows, it is a valuable alternative treatment. Need for ongoing transfusions after treatment may be dependent on patient comorbidity, particularly with concomitant liver or kidney disease. REFERENCES 1. Selinger CP, Ang YS. Gastric antral vascular ectasia (GAVE) an update on clinical presentation, pathophysiology and treatment. Digestion. 2008;77:131–137. 2. Charneau J, Petit R, Cales P, et al. Antral motility in patient with cirrhosis with and without gastric antral vascular ectasia. Gut. 1995;37:488–492. 3. Burak WK, Lee SS, Beck PL. Portal hypertensive gastropathy and gastric antral vascular ectasia (GAVE) syndrome. Gut. 2001;49:866–872. 4. Mathou NG, Lovat LB, Thorpe SM, et al. Nd:YAG laser induces long-term remission in transfusion-dependent patients with watermelon stomach. Laser Med Sci. 2004;18:213–218. 5. Kwan V, Bourke MJ, Williams SJ, et al. Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol. 2006;101:58–63. 6. Sebastian S, McLoughlin R, Qasim A, et al. Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia (watermelon stomach): long-term results. Dig Liver Dis. 2004;36:212–217. 7. Gross SA, Al-Haddad M, Gill KRS, et al. Endoscopic mucosal ablation for the treatment of gastric antral vascular ectasia with the HALO-90 system: a pilot study. Gastrointest Endosc. 2008;67:324–327. 8. Cho S, Zanati S, Yong E, et al. Endoscopic cryotherapy for the management of gastric antral vascular ectasia. Gastrointest Endosc. 2008;68:895–902. 9. Wells CD, Harrison ME, Gurudu SR, et al. Treatment of gastric antral vascular ectasia (watermelon stomach) with endoscopic band ligation. Gastrointest Endosc. 2008;68:231–236. 10. Sato T, Yamazaki K, Akaike J, et al. Endoscopic band ligation for refractory gastric antral vascular ectasia associated with liver cirrhosis. Clin J Gastro. 2011;4:108–111. 11. Rider JA, Klotz AP, Kirsner JB. Gastritis with veno-capillary ectasia as a source of massive gastric hemorrhage. Gastroenterol. 1953;24:118–123. 12. Stotzer PO, Willeri R, Kilander AF. Watermelon stomach: not only an antral disease. Gastrointest Endosc. 2002;55:897–900. 13. Payen JL, Cales P, Voigt JJ, et al. Severe portal hypertensive gastropathy and antral vascular ectasia are distinct entities in patients with cirrhosis. Gastroenterol. 1995;108:138–144. 14. McGorisk T, Krishnan K, Keefer L, et al. Radiofrequency ablation for refractory gastric antral vascular ectasia. Gastrointest Endosc. 2013;78:584–588.
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