淺表食管癌診斷性內(nèi)鏡切除的技術(shù)可行性和腫瘤學(xué)安全性GIE201811.ppt

Technical feasibility and oncologic safety of diagnostic endoscopic resection for superficial esophageal cancer 淺表食管癌診斷性內(nèi)鏡切除的技術(shù)可行性和腫瘤學(xué)安全性,Abstract,Background and Aims: Active use of endoscopic resection (ER) for cM3-SM2 esophageal cancer may enable sufficient extent of esophageal resection and help determine the need for lymph node dissection based on histopathologic findings. However, ER preceding esophagectomy may have an adverse impact on outcomes. This study was designed to determine the technical feasibility and oncologic safety of diagnostic ER. 背景和目的：積極使用內(nèi)鏡切除(ER)治療cM3-SM2型食管癌，可使食管切除的范圍足夠，并可根據(jù)組織病理學(xué)結(jié)果確定是否需要淋巴結(jié)清掃。然而，食管切除術(shù)前ER可能對預(yù)后有不良影響。本研究旨在探討診斷性ER的技術(shù)可行性及腫瘤學(xué)安全性。,回顧食管癌TNM分期,第八版 TNM 分類,T 分期分為 Tis：高度不典型增生；T1：癌癥侵犯黏膜固有層，粘膜肌層或粘膜下層，并被分為 T1a（癌癥侵犯黏膜固有層或粘膜肌層）和 T1b（癌侵犯粘膜下層）；T2：癌侵犯固有肌層；T3：癌癥侵犯外膜；T4：癌侵入局部結(jié)構(gòu)并且被分類為 T4a：癌侵入相鄰結(jié)構(gòu)例如胸膜，心包膜，奇靜脈，膈肌或腹膜，T4b：癌侵入主要相鄰結(jié)構(gòu)，例如主動脈，椎體或氣管。 N 分類為 N0：無區(qū)域淋巴結(jié)轉(zhuǎn)移; N1：涉及 12 個區(qū)域淋巴結(jié)轉(zhuǎn)移; N2：涉及 3-6 個區(qū)域淋巴結(jié)轉(zhuǎn)移；N3：涉及 7 個或以上區(qū)域淋巴結(jié)轉(zhuǎn)移。M 分類為 M0：無遠(yuǎn)處轉(zhuǎn)移；M1：遠(yuǎn)處轉(zhuǎn)移,Methods: A single-institution retrospective cohort study was performed between July 2008 and June 2014. During this period, 135 consecutive patients with clinical T1a-M3N0M0, T1b-SM1N0M0, and T1b-SM2N0M0 primary esophageal cancer were referred to our division. Eight patients who underwent chemoradiotherapy as primary treatment were excluded because of inadequate pathologic findings. Based on oncologic and physical factors, we categorized the remaining 127 patients into 2 groups: primary esophagectomy (n = 54) and primary ER (n = 73). 方法:在2008年7月至2014年6月間進(jìn)行單機(jī)構(gòu)回顧性隊列研究。在此期間，共有135例臨床T1a-M3N0M0、T1b-SM1N0M0、T1b-SM2N0M0原發(fā)性食管癌患者轉(zhuǎn)入我科。8例以放化療為主治療的患者因病理表現(xiàn)不佳被排除在外。根據(jù)腫瘤和物理因素，我們將其余127例患者分為兩組:直接手術(shù)食管切除術(shù)(54例)和先行內(nèi)鏡下切除(73例)。,Results: In all 127 patients, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 95.7% and 87.6%, respectively. No adverse event requiring surgical intervention was observed after ER. Diagnostic ER had no negative impact on surgical outcomes, DFS, and OS after esophagectomy. Fourteen patients (19.2%) of those who received primary ER underwent curative resection, whereas 11 (20.4%) who had pT1a disease, no lymphovascular invasion, and no pathologic lymph node metastasis underwent primary esophagectomy. 結(jié)果:127例患者的3年總生存率(OS)和無病生存率(DFS)分別為95.7%和87.6%。ER術(shù)后無不良事件需要手術(shù)治療。診斷性ER對食管切除術(shù)后的手術(shù)結(jié)局、DFS、OS無不良影響。先行ER患者中有14例(19.2%)行根治性切除，而11例pT1aN0M0患者 (20.4%) 行直接食管切除術(shù)。,Conclusions: Diagnostic ER for cM3-SM2 esophageal cancer with or without subsequent esophagectomy was feasible and safe, not only from a surgical perspective but also an oncologic perspective. Approximately 20% of cM3-SM2N0M0 patients can potentially avoid undergoing additional treatment including esophagectomy using diagnostic ER. 結(jié)論:cM3-SM2食管癌無論有無后續(xù)食管切除術(shù)，無論是從手術(shù)角度還是從腫瘤學(xué)角度，診斷性ER都是可行和安全的。大約20%的cM3-SM2N0M0患者使用診斷性ER可以避免接受包括食管切除術(shù)在內(nèi)的額外治療。,Introduction,Although esophagectomy with 3-field lymph node dissection is the standard therapy for clinical T1a/T1b (cM3-cSM2)N0M0 esophageal cancer, it has high risk of postoperative mortality and morbidity because of its complexity. The procedure is associated with other long-term postoperative problems, such as aspiration pneumonia caused by dysphagia and malnutrition. 雖然T1a/T1b (cM3-cSM2)N0M0食管癌的標(biāo)準(zhǔn)治療方法是食管切除術(shù)加3野淋巴結(jié)清掃，但其復(fù)雜性使其術(shù)后死亡率和發(fā)病率較高。該手術(shù)與其他長期的術(shù)后問題有關(guān)，如吞咽困難引起的吸入性肺炎和營養(yǎng)不良。,Endoscopic resection (ER) is the standard treatment for clinical T1a-M1/M2 N0M0 disease with cancerous involvement of no more than three fourths of the esophageal circumference; it is a safe, less-invasive procedure that preserves esophageal function. ER for pathologic T1a-M1 and T1a-M2 is sufficiently radical because pathologic lymph node metastasis is rarely observed. According to the Japanese Esophageal Society guidelines, ER may be indicated in patients with pathologic T1a-M3 and T1b-SM1 lesions not accompanied by clinical evidence of lymph node metastasis. 內(nèi)鏡切除(ER)是臨床T1a-M1/M2 N0M0疾病的標(biāo)準(zhǔn)治療方法，其癌變累及食管周長不超過四分之三;這是一種安全、低侵入性的保留食管功能的手術(shù)。 ER對于病理性T1a-M1和T1a-M2的病變具有足夠的根治性，因為很少觀察到病理性淋巴結(jié)轉(zhuǎn)移。根據(jù)日本食管學(xué)會的指南，ER可能適用于病理T1a-M3和T1b-SM1不伴有淋巴結(jié)轉(zhuǎn)移的臨床征象的患者中。,However, performing unnecessary esophagectomy in patients with cT1a-M3/cT1b-SM1/cT1bSM2 disease is possible because tumor depth assessment accuracy is limited even after using magnifying endoscopy with narrow-band imaging (M-NBI), EUS, and esophagography. Moreover, because of technical advances, ER can be safely applied for cT1a-M3/cT1b-SM1/cT1b-SM2 disease and for involvement of more than three-fourths of the esophageal circumference. 然而，對于cT1a-M3/cT1b-SM1/cT1bSM2疾病患者進(jìn)行不必要的食管切除術(shù)是可能的，因為即使使用放大內(nèi)鏡和窄帶成像(M-NBI)、EUS和食管造影后，腫瘤深度評估的準(zhǔn)確性也有限。此外，由于技術(shù)的進(jìn)步，ER可安全地應(yīng)用于cT1a-M3/cT1b-SM1/cT1b-SM2疾病，并可用于累及食管周長的四分之三以上的病變。,Therefore, active use of ER and its subsequent pathologic findings (also referred to as diagnostic ER) can help determine the appropriate esophageal resection extent when necessary, combined with radical lymph node dissection, provided that ER preceding esophagectomy does not have any negative impact on outcomes. This study was designed to determine technical feasibility and oncologic safety of diagnostic ER for clinical T1a-M3, T1b-SM1, and T1b-SM2 esophageal cancer. 因此，如果在食管切除術(shù)前先行ER對預(yù)后沒有任何負(fù)面影響的話，積極使用ER及其后續(xù)病理發(fā)現(xiàn)(也稱為診斷ER)可以在必要時幫助確定適當(dāng)?shù)氖彻芮谐秶Y(jié)合根治性淋巴結(jié)清掃。本研究旨在確定臨床T1a-M3、T1b-SM1、T1b-SM2食管癌診斷性ER的技術(shù)可行性及腫瘤學(xué)安全性。,2018.07-2014.06 單中心,Among patients who underwent CRT/radiotherapy or those who received no additional treatment after ER, relapse in regional lymph nodes within 1 year after ER was considered as indicative of pre-existing lymph node metastasis. 在接受CRT/放療或ER后未接受額外治療的患者中，ER后1年內(nèi)局部淋巴結(jié)復(fù)發(fā)被認(rèn)為是原有淋巴結(jié)轉(zhuǎn)移的指示。 Disease-free survival (DFS) and overall survival (OS) were also calculated from the primary treatment date. The presence of residual tumors was classified as R0, no residual tumor; R1, microscopic; and R2, macroscopic residual tumor. 無病生存(DFS)和總生存(OS)也從最初的治療日期開始計算。殘余瘤的存在分為R0，無殘余瘤;R1,微觀;R2，肉眼可見的殘余腫瘤。,Methods,Pretreatment patient workup included laboratory investigations, upper GI endoscopy, esophagography, thoracoabdominal contrast-enhanced CT, and positron emission tomography. Esophageal cancer was diagnosed based on histopathologic examination of endoscopic biopsy specimens. Clinical cancer stage was determined according to International Union Against Cancer, seventh edition. 治療前的檢查包括實驗室檢查、胃腸道內(nèi)鏡檢查、食管造影、胸腹造影增強(qiáng)CT和正電子發(fā)射斷層掃描。通過內(nèi)鏡活檢標(biāo)本的病理組織學(xué)檢查診斷食管癌。臨床癌癥分期根據(jù)國際抗癌聯(lián)盟第七版確定。 Tumor invasion depth was determined by 6 experienced endoscopists based on both macroscopic findings and advanced imaging, including M-NBI according to the Japanese Esophageal Society classification, which is based on degree of microvascular irregularity observed by M-NBI. 腫瘤浸潤深度由6名經(jīng)驗豐富的內(nèi)鏡醫(yī)師根據(jù)宏觀表現(xiàn)和高級影像確定，其中M-NBI根據(jù)日本食管學(xué)會分類，根據(jù)M-NBI觀察到的微血管不規(guī)則程度。,On identifying type B1, B2, and B3 vessels in the tumor, the histologic tumor invasion depth was predicted as T1a-M1/M2, T1a-M3/T1b-SM1, and T1b-SM2 or greater, respectively.7,8 B1 is defined as type B vessels with a loop-like formation, B2 is defined as type B vessels without a loop-like formation that have a stretched and markedly elongated transformation, and B3 is defined as highly widened abnormal vessels.7 The avascular area was also defined as a low or no vascularity area surrounded by stretched irregular vessels. Large avascular areas were those 3 mm and were suggestive of T1b-SM2 or greater. 在鑒別腫瘤中B1、B2、B3型血管時，分別預(yù)測腫瘤的組織學(xué)侵襲深度為T1a-M1/M2、T1a-M3/T1b-SM1、T1b-SM2或以上。b1定義為B型血管有環(huán)狀結(jié)構(gòu)，B2定義為B型血管無環(huán)狀結(jié)構(gòu)，具有明顯的伸長變形，B3定義為高度加寬的異常血管。無血管區(qū)也被定義為被不規(guī)則血管包圍的低血管區(qū)或無血管區(qū)。大的無血管區(qū)域為3毫米，提示T1b-SM2或更高。,Kumagai等3基于手術(shù)切除標(biāo)本的實體顯微鏡和組織病理對比研究，提出乳頭內(nèi)毛細(xì)血管環(huán)(intrapapillary capillary loops，IPCL )的形態(tài)變化對區(qū)分正常、異常黏膜以及判斷食管癌的浸潤深度有重要的意義。IPCL是由黏膜下引流靜脈分出的樹狀血管所發(fā)出，正常為環(huán)形。IPCL常見的形態(tài)改變有交織、擴(kuò)張、直徑不規(guī)則和IPCL多形性等4種改變。根據(jù)IPCL形態(tài)改變的程度和局部黏膜碘染色的情況，可分為5級：（1）正常黏膜為碘染色陽性，ICPL形態(tài)正常；（2）炎癥浸潤為碘染色陽性，IPCL有擴(kuò)張和/或延長；（3）輕度不典型增生則碘染色陰性，IPCL形態(tài)無明顯改變或改變輕微；（4）重度不典型增生為碘染色陰性，IPCL在交織、擴(kuò)張、直徑不規(guī)則及多形性的4種形態(tài)改變中占2-3種以上；（5） 食管癌為碘染色陰性，IPCL可同時出現(xiàn)以上4種形態(tài)改變。Kumagai同時發(fā)現(xiàn)，m1期癌常只有IPCL的擴(kuò)張，m2期癌的IPCL既有擴(kuò)張又有延長，m3期癌多表現(xiàn)為IPCL變形和粗大腫瘤血管的混雜，sm期癌則只見到粗大的腫瘤血管，放大胃鏡的這種分期與組織病理學(xué)的符合率達(dá)83.3%（60/72）。,Moreover, we also used chromoendoscopy in combination with M-NBI. The presence of pink-color sign in the Lugol-voiding lesions evaluated a few minutes after spraying with a Lugol dye solution was regarded as diagnosis of esophageal cancer.9 EUS was also used according to the endoscopists preference. Tumor depth was determined using EUS as follows: the second, third, fourth, and fifth layers in a 9-layered image corresponded to the superficial epithelium plus the interface echo, deep epithelium, lamina propria plus interface echo, muscularis mucosae minus interface echo, and submucosa, respectively. Initial endoscopic diagnosis regarding invasion depth was confirmed based on the agreement by expert endoscopists at the medical conference before therapy. 此外，我們還將染色體內(nèi)鏡與M-NBI結(jié)合使用。在Lugol染色液噴灑幾分鐘后，在Lugol-voiding病灶中發(fā)現(xiàn)粉紅色標(biāo)記，被認(rèn)為是食道癌的診斷。也根據(jù)內(nèi)窺鏡醫(yī)師的喜好使用EUS。采用EUS方法確定腫瘤深度:9層圖像的第二層、第三層、第四層和第五層分別對應(yīng)于淺表上皮+界面回聲、深層上皮、固有層+界面回聲、肌層粘膜減去界面回聲和粘膜下層。在治療前的醫(yī)學(xué)會議上，經(jīng)內(nèi)鏡專家同意，初步確定了侵入深度的內(nèi)鏡診斷。,In our hospital, combined thoracoscopiclaparoscopic esophagectomy with 3-field lymphadenectomy was primarily performed.15 Only 8 patients underwent thoracic procedures through a right thoracotomy because of their request or the presence of pleural adhesions. Five patients who underwent primary esophagectomy and had lymph node metastasis or pathologic T2 disease underwent postoperative chemotherapy or CRT. In addition, 3 patients who had positive resection margin after esophagectomy also underwent CRT. 在我院，以胸腔鏡-腹腔鏡聯(lián)合食管切除術(shù)和三段式淋巴結(jié)切除術(shù)為主。僅8例患者因需要或存在胸膜粘連而行右側(cè)胸廓切開術(shù)。5例食管切除術(shù)后出現(xiàn)淋巴結(jié)轉(zhuǎn)移或病理T2疾病的患者術(shù)后接受化療或CRT治療。此外，3例食管切除術(shù)后切緣陽性的患者也行CRT治療。,Oncologic follow-up,The discharged patients visited our outpatient clinic at least after 1 month, 3 months, and every 6 months until 5 years after treatment. In the outpatient clinic, routine physical examination and routine laboratory investigations for squamous cell carcinoma antigen, carcinoembryonic antigen, and carbohydrate antigen 19-9 were performed. Upper GI endoscopy was performed once a year after ER to detect local recurrence and metachronous multicentric or multiple cancers. In addition, thoracoabdominal CT was performed every 6 months to detect local recurrence and systemic metastasis at least for 5 years after esophagectomy. 出院患者至少在治療后1個月、3個月、每6個月到門診就診一次，直到5年。門診對鱗狀細(xì)胞癌抗原、癌胚抗原、CA19-9進(jìn)行常規(guī)體檢及實驗室檢查。內(nèi)鏡檢查一年一次，檢查局部復(fù)發(fā)和異時多中心或多重癌癥。此外，每6個月進(jìn)行一次胸腹CT檢查，以發(fā)現(xiàn)食管切除術(shù)后至少5年的局部復(fù)發(fā)和全身轉(zhuǎn)移。,Diagnostic accuracy of preoperative staging of tumor depth,We evaluated positive predictive value (PPV) as an indicator of diagnostic accuracy of preoperatively estimated tumor depth. PPV for pathologic T1a-M3, T1b-SM1, and T1b-SM2 in patients with clinical findings of cT1a-M3, cT1b-SM1, and cT1b-SM2 was 70.9% (90/127 patients). PPV for pathologic T1a-M3 and T1b-SM1 was 55.2% (48/87 patients) and for pathologic T1b-SM2 was 42.5% (17/40 patients). PPV for pathologic T1b-SM2 or deeper in patients with a clinical diagnosis of T1b-SM2was 67.5% (27/40 patients). Fourteen patients (19.2%) of those who received primary ER underwent curative resection (defined as pT1a, no lymphovascular invasion, and complete resection), whereas 11 (20.4%) who had pT1a disease, no lymphovascular invasion, and no pathologic lymph node metastasis underwent primary esophagectomy. 我們評估陽性預(yù)測值(PPV)作為術(shù)前評估腫瘤深度診斷準(zhǔn)確性的指標(biāo)。cT1a-M3、cT1b-SM1、cT1b-SM2病理為T1a-M3、T1b-SM1、cT1b-SM2的患者，其診斷的PPV為70.9%(90/127例)。T1a-M3和T1b-SM1的PPV為55.2%(48/87例)，T1b-SM2為42.5%(17/40例)。T1b-SM2或以上患者的病理診斷為T1b-SM2的PPV為67.5%(27/40)。14例(19.2%)ER患者行根治性切除(定義為pT1a，無淋巴血管浸潤，完全切除)，11例(20.4%)患者有pT1a疾病，無淋巴血管浸潤，無病理淋巴結(jié)轉(zhuǎn)移行食管切除術(shù)。,Risk factor for regional lymph node metastasis and recurrence Twenty patients experienced regional lymph node metastasis (n Z 17) or recurrence at regional lymph nodes (n Z 3). Risk factors were determined by using univariate and multivariate analyses. Only lymphatic invasion was found to be a risk factor (P Z .001; hazard ratio HR, 13.54; 95% confidence interval CI, 2.69-68.22). Tumor length was not a statistically significant risk factor (P Z .053; HR, 1.02; 95% CI, .99-1.05); however, the probability of regional lymph node metastasis and recurrence was increased for tumors approximately 5.0 cm in size by using a partial dependency plot (Fig. 3). 區(qū)域淋巴結(jié)轉(zhuǎn)移和復(fù)發(fā)的危險因素: 20例患者經(jīng)歷區(qū)域淋巴結(jié)轉(zhuǎn)移(n=17)或區(qū)域淋巴結(jié)復(fù)發(fā)(n=3)，采用單因素和多因素分析確定危險因素。只有淋巴管侵犯被發(fā)現(xiàn)是一個危險因素(pz.001;危害比HR， 13.54;95%置信區(qū)間CI， 2.69-68.22)。腫瘤長度不是統(tǒng)計學(xué)上顯著的危險因素。然而，使用部分趨勢圖，腫瘤大小約5.0 cm，區(qū)域淋巴結(jié)轉(zhuǎn)移和復(fù)發(fā)的概率增加(圖3)。,According to univariate analyses, noncurative treatment was not a risk factor for death and recurrence; however, several factors, including ASA, performance status, Charlson comorbidity index score 3, lymphatic invasion, vessel invasion, pathologic lymph node metastasis, and tumor invasion depth greater than pT1b-SM2, were identified as significant risk factors. On multivariate analysis using a Cox regression model that included these factors, only vascular invasion and Charlson comorbidity index score 3 were identified as predictors of death. Moreover, ASA , Charlson comorbidity index score 3, and vascular invasion were also identified as predictors of recurrence. 根據(jù)單因素分析，非治愈治療不是死亡和復(fù)發(fā)的危險因素;但ASA、體能狀態(tài)、Charlson共病指數(shù)評分3、淋巴管浸潤、血管浸潤、病理淋巴結(jié)轉(zhuǎn)移、腫瘤浸潤深度大于pT1b-SM2等因素均為顯著危險因素。在多因素Cox回歸模型中，只有血管性侵犯和Charlson共病指數(shù)評分3是死亡的預(yù)測因子。此外，ASA、Charlson共病指數(shù)3、血管浸潤也是復(fù)發(fā)的預(yù)測指標(biāo)。,Discussion,The present study demonstrated the technical feasibility and oncologic safety of diagnostic ER for clinical T1a-M3, T1b-SM1, and T1b-SM2 esophageal cancer. To our knowledge, this is the first report demonstrating the potential advantages of diagnostic ER over primary esophagectomy for cM3-SM2 esophageal cancer. Few studies have investigated the use of diagnostic ER for minimizing invasive treatment. Fujiya et al. reported that diagnostic endoscopic submucosal dissection should be considered as a primary treatment for limited subset of patients with cT1b gastric cancer. 本研究論證了臨床T1a-M3、T1b-SM1、T1b-SM2食管癌診斷性ER的技術(shù)可行性及腫瘤學(xué)安全性。據(jù)我們所知，這是第一個證明ER診斷對于臨床M3-SM2食管癌比原來食管切除術(shù)有潛在優(yōu)勢的報道。很少有研究調(diào)查使用診斷性ER來減少侵入性的治療。Fujiya等人報道，診斷性內(nèi)鏡下粘膜剝離術(shù)應(yīng)該被認(rèn)為是cT1b胃癌患者的一個主要治療方法。,The Japan Clinical Oncology Group has conducted a phase II trial (JCOG0508) to evaluate the efficacy and safety of diagnostic ER + selective CRT for patients with cT1b-SM1 and cT1b-SM2 esophageal cancer. This is a representative study in Japan; however, patients with cT1aM3 tumor were not included in the study. Patients with cT1a-M3 disease and lymph vascular invasion are also at a risk of lymph node metastasis. Therefore, esophageal cancer prognosis must be investigated in these patients, as performed in the present study. This study has 3 major findings. 日本臨床腫瘤學(xué)組進(jìn)行了II期試驗(JCOG0508)，以評估診斷性ER +選擇性CRT對cT1b-SM1和cT1b-SM2食管癌患者的療效和安全性。 這是日本的一個代表性研究;然而，cT1aM3腫瘤患者并未納入研究。cT1a-M3疾病和淋巴管浸潤患者也有淋巴結(jié)轉(zhuǎn)移的危險。因此，這些患者的食管癌預(yù)后必須進(jìn)行調(diào)查，正如本研究所做的。這項研究有三個主要發(fā)現(xiàn)。,First, our findings clearly suggested no adverse impact of diagnostic ER on short-term outcomes (including hospital stay, operative time, and adverse events) or long-term outcomes compared with those of primary esophagectomy. To our knowledge, no study has investigated the short- and long-term outcomes associated with the use of diagnostic ER to date. Diagnostic ER has potential negative impacts on short- and long-term outcomes, including the possibility of adverse events directly attributable to ER, risk of adverse events after esophagectomy after ER, the possible time lag of additional treatment when patients should undergo additional treatment based on the pathologic findings after ER, and potential increase in recurrence risk because of ER-induced changes in lymphatic flow. 首先，我們的發(fā)現(xiàn)明確表明，與原發(fā)性食管切除術(shù)相比，診斷性ER對短期預(yù)后(包括住院時間、手術(shù)時間、不良事件)或長期預(yù)后沒有不良影響。據(jù)我們所知，目前還沒有研究調(diào)查與使用診斷性ER相關(guān)的短期和長期結(jié)果。診斷性ER對短期和長期的結(jié)果有潛在的負(fù)面影響,包括直接歸因于ER的可能的不良事件,ER之后食管切除術(shù)后不良事件的風(fēng)險，ER病理結(jié)果提示患者需要其他治療時造成的延誤治療，和因為ER誘發(fā)的淋巴流動的變化所致潛在的復(fù)發(fā)風(fēng)險增加 。,However, in this study, ER was conducted with sufficiently low morbidity and seemed to not be inferior to the outcomes of a previous study. The incidence of postoperative adverse events of esophagectomy in this study was comparable with those in other studies irrespective of performance of diagnostic ER. There was no significant delay of treatment even if the patients underwent primary ER followed by additional treatment. No negative impact was observed on OS and DFS. 然而，在本研究中，ER的發(fā)病率很低，似乎并不比之前的研究差。本研究中食管切除術(shù)后不良事件的發(fā)生率與其他研究中不論有無診斷性ER的病例相當(dāng)。即使患者進(jìn)行了ER再進(jìn)行額外治療，治療也沒有明顯延遲。沒有觀察到對OS和DFS的負(fù)面影響。,Second, this study showed that curative resection was achieved in approximately 20% of the patients with cT1a-M3, T1b-SM1, and T1b-SM2 by ER alone. It is not necessarily easy to precisely predict the invasion depth of esophageal cancer. EUS is the criterion standard for T-staging in the United States and other Western countries. The reported PPVs of mucosal and advanced cancers have previously been found to be 75.0% and 100.0%, respectively, but the true diagnostic accuracy may not be that high because many studies have analyzed only images with good quality and EUS was not superior because of the image quality. Moreover, EUS for esophageal lesion has a risk of aspiration during the procedure. Therefore, M-NBI is more commonly used than EUS in Japan. 其次，本研究表明，約20%的cT1a-M3、T1b-SM1、T1b-SM2患者僅通過ER就達(dá)到了治療性切除。準(zhǔn)確預(yù)測食管癌侵襲深度并非易事。EUS是美國等西方國家T分期的主要標(biāo)準(zhǔn)。黏膜和晚期癌癥的陽性預(yù)測者以前分別被發(fā)現(xiàn)為75.0%和100.0%，但真正的診斷準(zhǔn)確率可能沒有那么高，因為很多研究都有只分析高質(zhì)量的圖像，而EUS的圖像質(zhì)量并不優(yōu)越。此外，食管病變的EUS術(shù)中有誤吸風(fēng)險。因此，在日本，M-NBI比EUS更常用。,Recently, some studies have reported promising diagnostic accuracy for prediction of invasion depth. In contrast to these studies, the PPVs for cT1a-M3 or cT1b-SM1 and cT1b-SM2 or deeper were 55.2% and 67.5%, respectively, in this study, even when using M-NBI. Our results seem to be inferior to these previous studies. A possible explanation for this discrepancy is the difference in study populations. We only included patients with estimated invasion depths deeper than the muscularis mucosae (MM), whereas most patients in previous studies showed invasion of the epithelium/lamina propria mucosae (EP/LPM). The present study suggests that diagnostic ER should have clinical significance for lesions with esti