Optimal Endoluminal Treatment of Barrett's Esophagus: Integrating Novel Strategies into Clinical Practice

Raf Bisschops

Expert Rev Gastroenterol Hepatol. 2010;4(3):319-333.

Abstract and Introduction

Abstract

Endoluminal therapy has become the first-choice treatment over the last 5 years for early Barrett's neoplasia limited to the mucosa. Long-term follow-up data on endoscopic resection have demonstrated the oncological safety of endoscopic resection in comparison to surgery. However, there is a high rate of recurrent disease, which can be avoided using additional ablation of the remaining Barrett. Radiofrequency ablation was recently introduced as an efficacious means to ablate Barrett's epithelium with a better safety profile than older ablation techniques. Recent studies show that endoscopic resection can be safely combined with radiofrequency ablation for treating dysplastic Barrett's after removal of visible lesions. This constitutes a completely new treatment paradigm that will be integrated in routine clinical practice in the forthcoming years.

Introduction

The incidence of esophageal adenocarcinoma and associated death has risen significantly over the last few decades in Western countries.^[1,2] The high rate of mortality associated with this disease results from both late detection, especially in patients who are not under surveillance, and from surgery-related mortality.^[3] Patients who are under surveillance are often diagnosed at an earlier disease stage^[4,5] and a subset of these patients are eligible for endoluminal treatment. Over the last 5 years a change in treatment paradigm has occurred for the management of these early lesions. Owing to relatively high mortality from surgery and excellent outcomes of endoscopic resection (ER), early Barrett's neoplasia is no longer considered to be a primary indication for subtotal esophagectomy. Endoluminal therapy includes different techniques for resection and ablation. ER can be performed by the lift and snare technique, cap-assisted endoscopic resection (Cap-ER), a multiband mucosectomy (MBM) device or endoscopic submucosal dissection (ESD). Ablation techniques include argon plasma coagulation (APC), photodynamic therapy (PDT), cryotherapy and radiofrequency ablation (RFA).

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Abstract and Introduction
Indications & Patient Selection for Endoluminal Therapy
Endoscopic Resection
Additional Ablation Techniques
Expert Commentary
Five-year View
References
Sidebar

Table 1. Results and complication of endoscopic resection for high-grade intraepithelial neoplasia and early carcinoma in Barrett's esophagus.
Author	n	Additional method	Remission (%)	FU (months)	Recurrence (%)	Perforation (%)	Minor bleeding (%)	Major bleeding (%)	Stenosis	Ref.
Behrens	44	+PDT	97.7	38	17.1		9.30			^[16]
Buttar	17	+PDT	94	13	0.0	0	6		30	^[15]
Chennat	49	Circumferential^†	100	22.9	0.0	0			36.70	^[24]
Conio	39		94	34.9	3.0		10.30			^[17]
Ell	64		83	12	14.0	0	12.50		0	^[13]
Ell	100		98	36.7	11.0	0	10		0	^[12]
Giovannini	21	Circumferential^†	86	18		11.0		19	2.6	^[20]
Larghi	24	Circumferential^†	100	28	8.3	0	4.5		12.50	^[23]
Lopes	41	Circumferential^†	90	31.6	36.5	5	19.0		2.40	^[21]
May	115	+PDT/APC	94	13	0.0		7.50		4.50	^[18]
Nijhawan	17	+PDT	100	14.6	0.0		0		0	^[14]
Pech	304	+PDT/APC	86	69.5	21.0	0	11.6	0.6	3.30	^[7]
Peters	33		79	19	19.0		46			^[11]
Peters	39	Circumferential^†	95	11	0.0	2.60	2.60	2.60	26	^[10]
Pouw	34	Circumferential^†	100	23	9.0	6	25.0		56.00	^[22]
Seewald	12	Circumferential^†	100	9	0.0		33	17		^[19]

^†Full eradication of Barrett's using circumferential endoscopic resection.
APC: Argon plasma coagulation; FU: Follow-up; PDT: Photodynamic therapy.

Table 2. Results of argon plasma coagulation for ablation of Barrett's esophagus.
Author	n	Indication	FU	Eradication of SIM (%)	Eradication of any neoplasia (%)	Eradication HGIN (%)	Number of sessions	Ref.
Attwood	29	HGIN	37	76	86	86	2	^[78]
Basu	50	ND	14	60	NA	NA	4	^[106]
Familiari	35	ND:13/LGIN:13	24	91	100	NA	2	^[107]
Ferraris	96	ND	36	82	NA	NA	3.2	^[108]
Kahaleh	39	ND:32/LGIN:7	36	38	71	NA	3	^[74]
Madisch	73	ND	51	80	NA	NA	2	^[109]
Manner	60	ND	14	62	NA	NA	2.7	^[77]
Morris	55	ND:37/LGIN:9/HGIN:9	38.5	NA	NA	NA	3	^[76]
Pagani	94	ND	12	72	NA	NA	3	^[110]

Studies with a follow-up of longer than 12 months and more than 29 patients are included.
FU: Follow-up; HGIN: High-grade intraepithelial neoplasia; LGIN: Low-grade intraepithelial neoplasia; NA: Not applicable; ND: Nondyplastic; SIM: Specialized intestinal metaplasia.

Table 3. Complications of argon plasma coagulation for ablation of Barrett's esophagus.
Author	Perforation (%)	Bleeding (%)	Stenosis (%)	Burried glands (%)	Ref.
Attwood	3.40	0	0	NA	^[78]
Basu	0	0	0	44	^[106]
Familiari	0	0	0	NA	^[107]
Ferraris	0	0	0	1	^[108]
Kahaleh	NA	NA	NA	NA	^[74]
Madisch	0	0	4	NA	^[109]
Manner	1.60	3	3	7	^[77]
Morris	3.60	0	0	30	^[76]
Pagani	0	0	1	NA	^[110]

Studies with a follow-up of longer than 12 months and more than 29 patients are included.
NA: Not applicable.

Table 4. Results of photodynamic therapy for ablation of Barrett's esophagus.
Author	n	Method	Indication	FU	Eradication of SIM (%)	Eradication of any neoplasia (%)	Eradication HGIN (%)	Number of sessions	Ref.
Ackroyd	40	5-ALA	LGIN	53	0	85	87	1	^[111]
Overholt	87	Porfimer sodium	LGIN:14/HGIN:73	19	45	79	90	1	^[112]
Overholt	94	Porfimer sodium plus Yag laser	HGIN:80/LGIN:14	50.7	56	80	77	1	^[113]
Overholt	138	Porfimer sodium	HGIN	24.4	52	75	75	1.9	^[81]
Pech	66	5-ALA	HGIN:35; EC:31	37	NA	98	98	1.3	^[83]
Wolfsen	34	Porfimer sodium plus APC	HGIN	18.5	56	100	100	1	^[89]
Wolfsen	69	Porfimer sodium	HGIN	19.2	56	NA	NA	1	^[90]

Studies with a follow-up of longer than 18 months and more than 30 patients are included.
5-ALA: 5-aminolevulinic acid; APC: Argon plasma coagulation; FU: Follow-up; HGIN: High-grade intraepithelial neoplasia; LGIN: Low-grade intraepithelial neoplasia; NA: Not applicable; SIM: Specialized intestinal metaplasia.

Table 5. Complications of photodynamic therapy for ablation of Barrett's esophagus.
Author	Mucosal laceration (%)	Perforation (%)	Bleeding (%)	Stenosis (%)	Burried glands (%)	Photoxicity (%)	Ref.
Ackroyd	0	0	0	0	2.50	2.50	^[111]
Overholt	0	0	0	34	4	4	^[112]
Overholt	NA	NA	NA	30	4	NA	^[113]
Overholt	0	0	0	36	NA	69	^[82]
Pech	0	0	0	0	0	0	^[83]
Wolfsen	0	2	0	23	NA	15	^[114]
Wolfsen	0	1	0	20	NA	18	^[115]

Studies with a follow-up >18 months and >30 patients are included.
NA: Not applicable.

Table 6. Results of radiofrequency ablation.
Author	n	Indication	Technique	P ER (n)	FU	Eradication of SIM (%)	Eradication of any neoplasia (%)	Eradication HGIN (%)	Number of sessions	Ref.
Fleischer	62	ND	360+90		30	98	NA	NA	3.4	^[90]
Ganz	92	HGIN	ER+360+90	24	12	54	80	90	1	^[98]
Gondrie	11	HGIN:9/LGIN:2	ER+360+90	6	14	100	100	100	4	^[92]
Gondrie	12	HGIN:11/LGIN:1	ER+360+90		14	100	100	100	3	^[91]
Hernandez	10	HGIN:2/LGIN:1/ND:7	ER+360+90	2	12	70	100	100	1.4	^[100]
Pouw	44	HGIN:32/LGIN:10/ND:2	ER+360+90	31	21	98	98	98	3.0	^[93]
Pouw	24	HGIN:10/LGIN: 11/ND:3	ER+360+90	23	22	88	95	95	2.0	^[94]
Roorda	13	HGIN:3/LGIN:4/ND:6	ER+360	1	12	46	71	71	1.4	^[97]
Shaheen	84	HGIN:42/LGIN:42/sham:42	ER+360+90	11	12	77	86	NA	2.6	^[80]
Sharma	10	LGIN	360+90		24	90	100	100	2.5	^[99]
Sharma	63	HGIN:24/LGIN:39	ER+360+90	2		79	89	NA	2.0	^[101]
Sharma	70	ND	360	NA	12	70	NA	NA	1.5	^[89]

ER: Endoscopic resection; FU: Follow-up; HGIN: High-grade intraepithelial neoplasia; LGIN: Low-grade intraepithelial neoplasia; NA: Not applicable; ND: Nondyplastic; P ER: Patients with endoscopic resection prior to radiofrequency ablation; SIM: Specialized intestinal metaplasia.

Table 7. Complications of radiofrequency ablation.
Author	Mucosal laceration (%)	Bleeding (%)	Stenosis (%)	Burried glands (%)	Ref.
Fleischer	1.5	1.5	0.0	0.0	^[90]
Ganz	0.0	0.0	0.7	0.0	^[98]
Gondrie	0.0	0.0	0.0	0.2	^[92]
Gondrie	0.0	0.0	0.0	0.0	^[91]
Hernandez	0.0	0.0	0.0	NA	^[100]
Pouw	6.8	0.0	9.0	0.1	^[93]
Pouw	0.0	4.0	4.0	0.0	^[94]
Roorda	0.0	0.0	0.0	NA	^[97]
Shaheen	0.0	1.0	6.0	5.1	^[80]
Sharma	0.0	0.0	0.0	0.0	^[99]
Sharma	0.0	0.0	1.5	0.0	^[101]
Sharma	1.5	1.5	0.0	0.0	^[89]

NA: Not applicable.

Box 1. Indications for curative endoscopic resection.
Lesion limited to the mucosa (T1a) No pathological lymph nodes Limited in size (2 cm) Well-to-moderately differentiated No lymphovascular infiltration in the endoscopic resection specimen

Box 2. Risk factors for recurrent disease after endoscopic resection without total eradication.
Piecemeal resection Long segment Barrett No ablative therapy of the remaining Barrett's after complete removal of high-grade intraepithelial neoplasia/mucosal carcinoma Multifocal disease Long interval of more than 10 months before complete remission is achieved

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