Ann. N.Y. Acad. Sci. ISSN 0077-8923
A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Barrett’s Esophagus: The 10th OESO World Congress Proceedings
Barrett’s esophagus: treatments of adenocarcinomas I Srinadh Komanduri,1 Pierre H. Deprez,2 Ajlan Atasoy,3 Gunther Hofmann,4 Peter Pokieser,5,6 ¨ Ahmed Ba-Ssalamah,6 Jean-Marie Collard,7 Bas P. Wijnhoven,8 Roy J.J. Verhage,9 10 Bjorn Christoph Schuhmacher,11 Marcus Feith,12 and Hubert Stein13 ¨ Brucher, ¨ 1 Feinberg School of Medicine, Division of Gastroenterology/Hepatology, Northwestern University, Chicago, Illinois. 2 Cliniques Universitaires Saint-Luc, Universite´ Catholique de Louvain, Brussels, Belgium. 3 Division of Hematology Oncology, UPMC Cancer Pavillion, University of Pittsburgh, Pittsburgh, Pennsylvania. 4 Photo Dynamic Therapy LLC, Vienna, Austria. 5 Department of Medical Education, University of Vienna, Vienna, Austria. 6 Department of Radiology, Medical University of Vienna, Vienna, Austria. 7 Department Chirurgie de l’Appareil Digestif, Louvain Medical School, Brussels, Belgium. 8 Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. 9 University Medical Center Utrecht, Tubingen, Germany. Department of Surgery, Utrecht, the Netherlands. 10 Department of Surgery, University of Tubingen, ¨ ¨ 11 Chirurgischen Klinik and Poliklinik, Technical University of Munich, Munich, Germany. 12 Chirurgische Klinik und Poliklinik, Technische Universitat Munich, Germany. 13 Klinik fur ¨ Allgemein, Viszeral, und Thoraxchirurgie, Klinikum Nurnberg ¨ ¨ Munchen, ¨ Nord, Nurnberg, Germany ¨
The following on the treatments of adenocarcinomas in Barrett’s esophagus contains commentaries on endo mucosal resection; choice between other ablative therapies; the remaining genetic abnormalities following stepwise endoscopic mucosal resection and possible recurrences; the Fotelo–Fotesi PDT; the CT TNM classification of early stages of Barrett’s carcinoma; the indications of lymphadenectomy in intramucosal cancer; the differences in lymph node yield in transthoracic versus transhiatal dissection; video-assisted lymphadenectomy; and the importance of the length of proximal esophageal resectipon; and indications of sentinel node dissection. Keywords: endoscopic mucosal resection; Barrett’s esophagus; intramucosal cancer; high-grade dysplasia; EMR; ESD; submucosal dissection; stepwise radical endoscopic resection (SRER); esophageal adenocarcinoma; photonic therapy; surveillance; computer tomography; endosonography; PET multislice detector scanner; spiral CT; esophageal cancer; lymph nodes; transhiatal; transthoracic; minimally invasive esophagectomy; robot-assisted thoracolaparoscopic esophagectomy; lymphadenectomy; histological differentiation; squamous cell carcinoma; Will Rogers phenomenon; sentinel node concept; resection margin; sentinel lymph nodes
Concise summaries • The improvement of and high efficacy of ablative strategies and improved imaging modalities has led to the concept of a staging endoscopic mucosal resection (EMR) as a diagnostic strategy to ensure no evidence of invasive cancer that should be referred for esophagectomy. The overall recurrence rate of EMR for Barrett’s esophagus (BE)–associated mucosal advanced neoplasia appears to be extremely low. The addition of radiofrequency ablation appears to be even superior to EMR alone in recurrence risk. • Band ligation-EMR is the easiest method to use, but may induce bridging and may be complicated due to poor viewing and bleeding. The
most popular method therefore remains the cap-EMR, quite easy to learn and perform and allowing large specimens to be resected. Both techniques can be used to remove a superficial cancer occurring in Barrett’s mucosa or also to resect the full Barrett’s mucosa in a stepwise radical resection. For lesions larger than 15 mm, endoscopic submucosal dissection seems to be preferable, and may provide en bloc removal. • Stepwise radical endoscopic resection (ER) seems to be an effective approach to eradicate BE and early neoplasia with lower short-term recurrence rates compared to focal resection. • Ablation may have in some way eradicated the underlying genetic properties inherent to that doi: 10.1111/j.1749-6632.2011.06055.x
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mucosa and prevent recurrence of neoplasia. However, even if it appears that the neosquamous epithelium is free of genetic abnormalities, this is limited by the fact that we are unclear which markers are meaningful in prediction of neoplasia. The photonic tumor therapy system provides with its novel model a cost-effective modality, minimally invasive, repeatable if required without dose limitation, with no interaction with other treatment modalities. Multislice detector scanner, the current standard CT technique, serves as a basic staging tool for all stages of Barrett’s carcinoma, especially to detect distant metastasis and concomitant abnormalities. Its combination with FDG PET is still under investigation, but can be estimated as a future standard in the diagnostic work up of esophageal carcinoma. The clear diagnosis of a submucosal lesion is a formal indication of a three-field esophagectomy with radical lymph node dissection from the neck down to the abdomen.
1. What are the current results of EMR in lesions confined to the mucosa? Srinadh Komanduri
[email protected] EMR in the setting of BE-associated high-grade dysplasia (HGD) and intramucosal (IMC) cancer has been very effective.1,2 The treatment paradigm has been evolving with the improvement and high efficacy of ablative strategies such as RFA and improved imaging modalities. Integral to this strategy is identifying depth of penetration. This can be done with EUS before resection but, at times, can only be determined by surgical pathology with the resected specimen. This has led to the concept of a staging EMR as a diagnostic strategy to ensure no evidence of invasive cancer, which should be referred for esophagectomy. In superficial lesions, strategies of utilization of EMR include circumferential resection of all Barrett’s in the setting of HGD/IMC to resection visible
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• Lymphadenectomy is warranted for achievement of complete oncological clearance, and such extensive surgery can be facilitated by minimally invasive or video-assisted techniques in the hands of experienced endoscopic surgeons, taking into account the Will Rogers Phenomenon. • The incidence of tumor recurrence at the anastomotic site after esophagectomy varies with respect to the length of the resection margin, and a margin above three cm should be aimed for. • The increased morbidity of a transthoracic (TT) approach should be weighted against a less morbid transhiatal (TH) approach. Hopefully, more accurate staging techniques will be developed to better tailor the surgical treatment and lymph node dissection to the individual patient, enabling to perform the most radical operation with the lowest morbidity and mortality. • If the sentinel lymph node concept holds true, lymphadenectomy with its associated morbidity could be safely omitted in most patients with early adenocarcinoma without compromising the cure rates.
areas of nodularity, ulceration, or superficial mass lesions, then followed by ablation of the remainder of flat IM. More recently, data suggest EMR of all identifiable lesions under HD white light or NBI, followed by RFA, may be the optimal strategy, avoiding the higher stricture rates (>30%) associated with circumferential mucosal resection. In 2009, Chennat et al.3 published a series of 49 patients with HGD/IMC who underwent circumferential or complete EMR with 96.9% complete response to nearly two years. However they did have 37% symptomatic stricture rate. Recent data with the EURO-1 trial demonstrated EMR with RFA in the setting of HGD/IMC yielded 100% eradication of dysplasia and 96% CR-IM with no significant complications in 24 patients. Our center has experienced similar results without complications. Prasad et al. also compared patients treated with surgery or EMR (178 patients) and determined overall survival to be comparable and unrelated with very low recurrence rates.5
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What is the rate of recurrence in the mucosa remaining after ER? In the study by Chennat et al.,3 only 1 of 32 patients had any recurrence of disease to two years. In the EURO-1 trial with EMR followed by RFA no patients recurred after treatment. Finally, in the largest study by Prasad et al.,5 16 of 132 patients had endoscopic recurrence by two years. Fifteen out of sixteen patients had nodules resected with CR by EMR. The overall recurrence rate of EMR for BE-associated mucosal advanced neoplasia appears to be extremely low. The addition of RFA following EMR appears to be superior to EMR alone in lowering the risk of recurrence. 2. What are the criteria for a logical choice between EMR and other ablative techniques? Pierre H. Deprez
[email protected] Endoscopic treatment of superficial digestive tumors may be divided into resection and ablation techniques. Resection remains the gold standard management since it provides a pathological specimen that will allow adequate and optimal correct staging. EMR was developed in the 1990s for the resection of esophageal and gastric neoplasms and now includes a large variety of techniques either aimed at lifting or sucking a lesion before snaring it. The most popular EMR methods nowadays are the band-ligation EMR and the cap-assisted EMR.6 More recently, endoscopic submucosal dissection (ESD) has been developed by Japanese authors. The rationale for ESD is that there is no size limit for en bloc resection, while it is difficult to achieve en bloc resection of specimens larger than 15–20 mm with EMR, and that piecemeal resection by EMR leads to local recurrence rates of about 15%. Experience in the Western world, however, is still limited, and ESD is only performed in a few select centers, with low volumes of cases, no description of training programs, and few published reports.7 The criteria to choose between the different EMR techniques and ESD are the following: ease of use, efficacy in terms of R0 resection, safety, cost, indications, and previous endoscopic or surgical treatments.
Ease of use EMR or mucosectomy is, in fact, an inappropriate word, since all techniques involve resection of 250
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the muscularis mucosae and part of the submucosa. It is an easy method to apply in the esophagus, although Barrett’s mucosa may be “tricky” to remove due to thickening of mucosa consecutive to chronic inflammation, ulceration, and scarring. Band ligation-EMR is the easiest method to use, very similar to the technique applied for variceal banding. It provides effective piecemeal resection of the lesion and Barrett’s mucosa, but may induce bridging and may be complicated due to poor viewing and bleeding. The most popular method, therefore, remains the cap-EMR, quite easy to learn and perform and allowing for large specimens of more than 2 cm to be resected. Both techniques can be used to remove a superficial cancer occurring in Barrett’s mucosa or also to resect the full Barrett’s mucosa in a stepwise radical resection.8
Efficacy ER should match the surgical standards and aim at complete resection of the tumor (R0) with free deep and lateral margins. Piecemeal resection doesn’t provide adequate pathological analysis when considering not only the lateral margins, but also possibly deep margins, due to bridging and coagulation effects. The risk of recurrence after piecemeal ER has been shown in many other sites (esophageal squamous cell carcinoma, gastric adenocarcinoma, and colorectal lateral spreading tumors) to be mainly related to the size of the tumor and piecemeal rather than en bloc resection. En bloc and R0 resection should, therefore, be performed, and for lesions larger than 15 mm, this can only be accomplished by ESD removal. Table 1 summarizes the results of a prospective randomized trail comparing EMR and ESD in esophageal superficial cancer resection, showing higher R0 rates with ESD but with a procedure of longer duration and higher cost.9 Safety Safety should always remain a major concern for endoscopists. Several studies have shown that band ligation is safer than cap-assisted EMR and ESD. The main complications observed after EMR and ESD are early or delayed bleeding, perforation, and esophageal stricture. Risk of perforation is lower than 5% in most reports on esophageal EMR, but may reach 10% with ESD, especially in the Western world where training and expertise is still lacking. The immediate and delayed bleeding risk is below 10% and might even be lower with ESD than EMR
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Table 1. Prospective comparison of EMR-cap and ESD in the removal of superficial esophageal cancer
En bloc resection Surface resected (mm2 ) Procedure duration (min) Devices costs (€) R0 (free lat & deep margins) Follow-up (months) CR neoplasia CR intestinal metaplasia
EMR-Cap
ESD
P
None (1–11 pieces) 1,488 (185–3194) 61 (20–130) 264 (60–515) 24% 21.5 (7–42) 84% 52%
96% 2,453 (600–5400) 150 (64–334) 486 (247–1019) 64% 21 (6–41) 92% 68%