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Editorial
Early Esophageal Cancer. A Western Perspective
Carcinoma precoz de esófago. Una perspectiva occidental
Giovanni Zaninotto
Corresponding author
g.zaninotto@imperial.ac.uk

Corresponding author.
, Sheraz Markar
Departamento de Cáncer y Cirugía, Imperial College, London, United Kingdom
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In western countries the diagnosis of &#8220;early esophageal adenocarcinoma&#8221; &#40;EAC&#41; is exponentially increasing due mainly to Barrett&#39;s esophagus patients surveillance&#44; as recommended by most gastroenterological scientific societies&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> and to an improvement in diagnostic techniques that allow precise identification of small lesions that might have been previously missed&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> An accepted definition of &#8220;early cancer&#8221; is the presence of neoplastic cells confined to the mucosal and submucosal layer&#44; in the absence of nodal metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a> This correspond to the stage 0&#8211;1 of AJCC-UICC TNM classification and comprises Tis&#44; T1a and T1b lesions&#44; classified as stage 1&#44; provided that no nodes are involved &#40;N0&#41;&#46; Tumors confined to the mucosa layer &#40;Tis&#41; are also called high-grade dysplasia &#40;HGD&#41;&#46; With the diffusion of local endoscopic therapies that effectively resect only the neoplastic tissue&#44; it became necessary a further stratification of T1 tumors in T1a and T1b lesions&#44; according to their risk of nodal involvement&#46; T1a tumors are defined as tumors extending beyond the mucosa and invading the Lamina propria up to the muscolaris mucosa&#46; A further subdivision according to the Paris Classification<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">4</span></a> divided superficial lesions into m1 &#40;limited to the mucosa and corresponding to Tis-HGD&#41;&#44; and the proper T1a lesions in m2 &#40;limited to the <span class="elsevierStyleItalic">lamina propria</span>&#41; and m3 limited to the <span class="elsevierStyleItalic">muscolaris mucosae</span>&#46; T1b lesions &#8211; i&#46;e&#46; tumors invading the submucosa layer up to the <span class="elsevierStyleItalic">muscularis propria</span> &#8211; were classified in 3 subtypes&#58; sm1&#44; sm2&#44; and sm3 according to the depth of invasion&#44; using a conventional criteria of dividing the submucosa in 3 parts of 500<span class="elsevierStyleHsp" style=""></span>&#956;m each&#58; in this way the risk for nodal invasion is more accurately defined&#44; assuming that the more superficial lesions &#40;Tis&#44; T1a&#41; had no or minimal risk for nodal metastasis&#44; T1b sm1 has a low risk and T1b sm2&#47;3 has a consistent risk of nodal involvement&#46; According to Fotis et al&#46; the risk for nodal involvement is 29&#37; for sm1&#44; 71&#37; for sm2 and 42&#37; for sm3&#44; and the grade of tumor differentiation &#40;G&#41; also plays a modulating relevant role&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The major player in the diagnosis of EAC is the endoscopist&#58; narrow band imaging and magnified endoscopy allow the identification of any irregular areas&#59; chromoendoscopy with either Lugol and&#47;or methylene blue staining facilitates the identification of the squamous epithelium&#44; and enhances any area of intestinal metaplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> Biopsies should be aimed at any abnormal findings in addition to the random biopsy protocol according to Seattle&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">6</span></a> If pathology shows the presence of neoplastic tissue additional procedures must be aimed to obtain an accurate stage of the tumor&#46; The role of EUS is questionable if aimed to define the precise T of an early tumor&#44; since it has been proven unable to consistently accurately distinguish intramucosal from submucosal tumor invasion&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">7</span></a> but can accurately detect loco-regional nodes&#46; Suspected nodes may be further investigated with fine needle biopsy&#46; CT scan and PET can be used to detect distant metastases or nodes&#44; but they are not routinely recommended in EAC&#44; given the rarity of these findings&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> The biopsy specimen should be pinned and fixed for permanent rather than frozen section and&#44; a second opinion by a pathologist is strongly recommended&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Esophagectomy is one of the most demanding surgical procedures and is associated with a not negligible mortality&#44; between 2&#37; and 5&#37;&#44; a considerable morbidity &#40;50&#37;&#41;&#44; a substantial impact on quality of life&#44; especially in the first years after the operation&#46; It is therefore clear that an organ preserving treatment that could allow the removal of the cancer with reduced procedural associated risks and leaving the esophagus is appealing&#46; According to the USA national cancer database&#44; in the years from 2004 to 2010 endoscopic treatments for T1a tumors increased from 19&#37; to 53&#37; and from 6&#46;6&#37; to 23&#37; in T1b tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> The modalities of endoscopic therapies constantly evolve&#44; but simply&#44; they can be classified into ablative therapies and resective therapies that can be used alone or in combination&#46; Ablative therapies aims to destroy the epithelium by chemical means &#40;porphyrine&#41; or thermal means such as argon beam&#44; cryoablation and radiofrequency &#40;RFA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">11</span></a> This latter therapy is now the most popular&#44; both for ablating diffuse Tis &#40;HGD&#41; lesions&#44; where a &#8220;target&#8221; lesion is not evident and as a complement to endoscopic resection with the purpose to eliminate any remnant Barrett&#39;s epithelium&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a> Using this combined approach Phoa et al&#46; reported a 90&#37; remission rate at 5 years in a cohort of 54 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">13</span></a> The major drawbacks of &#8220;ablative&#8221; therapies is that there are no diagnosis of the extension in terms of tumor depth by the pathologist&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Isolated resection of esophageal tissue is usually performed by means of endoscopic mucosal resection &#40;EMR&#41; that remains the most popular method in western countries&#46; The target mucosal lesion is lifted by injecting saline and then is resected using a band ligation device and a snare&#46; Endoscopic submucosal dissection &#40;ESD&#41; is performed with a specific endoscopic knife&#58; the target lesion is marked circumferentially with a cautery&#44; progressively lifted with saline injection and resected along-with the submucosal tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a> Both therapies allow sampling of neoplastic tissue for adequate pathology examination and tumor staging&#46; Pech et al&#46; reported an excellent result &#40;93&#46;6&#37; of complete remission at long term follow-up of 56&#46;6 months&#41; in a cohort of 1061 patients with intramucosal carcinoma<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a> and 83&#46;6&#37; of complete remission in a select cohort of 61 patients with &#8220;low risk&#8221; T1b tumor at 47 months of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">16</span></a> According to the National Cancer Comprehensive Network &#40;NCCN&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">17</span></a> however&#44; any submucosal tumor &#40;T1b&#41; or deeper should have surgical resection&#44; given the high risk of nodal involvement&#46; A recent review on 7000 patients&#44; reported that nodal metastases were present in 27&#37;&#8211;54&#37; of T1b patients&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">18</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">To date there are no randomized controlled trial to directly compare the two options&#46; A large population based study of over 2000 patients with EAC &#40;Tis&#44; T1a&#44; T1b&#41; comparing surgery &#40;1586 pts&#46;&#41; and endoscopic therapies &#40;430 pts&#46;&#41; and 2 systematic reviews<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">19&#8211;21</span></a> failed to demonstrate any differences in survival between endoscopic and surgical therapies for EAC&#44; though patients with endoscopic therapies had a greater incidence of recurrence and a higher mortality due to non-neoplastic causes&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">19</span></a> Surgery had higher cost&#44; higher complication and higher mortality rate than the endoscopic approach&#44; however&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">21</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Few data exist on how manage &#8220;failure&#8221; after endoscopic local treatment&#46; In general&#44; the scenario of failures has the following patterns&#58; &#40;1&#41; Insufficient radicality&#44; as shown by margin involvement&#46; In this case&#44; if the lateral margin is involved&#44; further endoscopic retreatment is most commonly used&#46; If the deep margin is involved the risk for nodal invasion should prompt the referral of the patient for surgical resection&#46; &#40;2&#41; Persistence of neoplasia in other areas than those resected&#58; a new local resection can be attempted or&#44; if there are no visible lesions&#44; RFA can be used&#46; If the extent of BE is long and EAC is multifocal&#44; not amenable with limited therapies&#44; and the patient is fit&#44; surgical resection can be considered&#46; &#40;3&#41; Recurrence of the neoplasia during the follow up&#46; All patients with early esophageal cancer managed with endoscopic therapies should be kept under endoscopic surveillance with short intervals&#46; In case the tumor recurs it should be staged again and endoscopic therapy can be re-performed&#44; provided that the tumor is confined to T1a and there are no sign of metastasis to the local or distant nodes&#46; When the recurrent tumor extends deeper&#44; surgical resection&#177;neoadjuvant therapy&#44; or radio-chemotherapy or local radiotherapy&#44; depending on the patient fitness and tumor stage are employed&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Although an excellent survival of resected patients after failure of endoscopic treatment is reported from single high-volume center cohorts&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">22</span></a> some alarming data came from the Cologne group<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">23</span></a>&#58; they compared the outcome of 62 patients that had esophagectomy after endoscopic resection to a matched group of patients with early cancer who had surgery resection as first therapy&#46; The patients with previous endoscopic therapy had a significant reduction of 5-year survival rate compared to those who had primary surgery&#44; &#40;91&#37; vs 98&#37; <span class="elsevierStyleItalic">P</span>&#60;&#46;05&#41;&#46; Eleven percent of patients who had previous endoscopic therapies showed a T2&#47;T3 tumor at operation&#59; the interval between endoscopic therapy and surgery of more than 3 months and surgery within the first post-intervention year were associated with a worse outcome&#46; A reason for the worse outcome of esophagectomy after endoscopic resection lies probably in the diffusion of endoscopic management of EAC outside referral centers&#58; in the USA more than 20&#37; of esophageal endoscopic resections are performed in community hospitals&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> Endoscopic therapy of EAC certainly requires highly skilled endoscopists&#44; but differently from more complex cancer surgeries that require an assortment of expertise&#44; as anesthesiologists&#44; ICU specialists&#44; radiologists&#44; oncologists&#44; nutritionists&#44; pathologists&#44; it can be performed even in hospitals where only these endoscopic skills are available&#46; Moreover&#44; the reductive concept that endoscopic resection of EAC is an easy and un-consequential maneuver&#44; prompted many endoscopist to perform it as the first approach&#44; considering EMR-ESD as a &#8220;macro-biopsy&#8221; rather than a resection and starting the therapeutic process of an esophageal cancer patient before discussing the patient at the multi-disciplinary cancer-board and without a careful planning of the whole treatment&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion&#44; as EAC is becoming more frequent and local endoscopic therapies are more commonly employed&#44; a tendency to treat these patients without referring them to specialized centers is also increasingly adopted&#44; especially if the physician deems that only endoscopic procedures are needed&#46; Nevertheless&#44; though endoscopic therapy is far less dangerous than surgery&#44; the management of EAC patients is not less complex than that of more advanced cancer and requires adequate expertise and technologies&#46; A careful diagnostic approach and staging is mandatory before starting any therapeutic approach and these patients should be referred to specialized UGI cancer centers&#46;</p></span>"
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Article information
ISSN: 21735077
Original language: English
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es en pt

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