食管癌内镜分期与治疗原则NCCN指南2016v1

食管癌NCCN指南2016v1

PRINCIPLES OF ENDOSCOPIC STAGING AND THERAPY 内镜分期与治疗原则

Endoscopy has become an important tool in the diagnosis, staging, treatment, and surveillance of patients with esophageal and esophagogastric junction (EGJ) cancers. Although some endoscopy procedures can be performed without anesthesia, most are performed with the aid of conscious sedation administered by the endoscopist or assisting nurse or deeper anesthesia (monitored anesthesia care) provided by the endoscopist, nurse, a nurse anesthetist, or an anesthesiologist. Some patients who are at risk of aspiration during endoscopy may require general anesthesia. 内镜已经成为食管与食管胃接合处(EGJ)恶性肿瘤患者诊断、分期、治疗及监测的一个重要手段。尽管一些内镜检查实施不用麻醉，但是大多需由内镜医师或护理助理实施清醒性镇静或由内镜医师、护士、麻醉护士或麻醉医师实施较深的麻醉(监护麻醉管理)。某些有吸入风险的患者在内镜检查过程中可能需要全身麻醉。山东省肿瘤医院呼吸肿瘤内科张品良

DIAGNOSIS 诊断

* Diagnostic and surveillance endoscopies are performed with the goal of determining the presence and location of esophageal neoplasia and to biopsy any suspicious lesions. Thus, an adequate endoscopic exam addresses both of these components.
*实施内镜诊断与监测的目的是确定食管肿瘤形成的存在与部位并对任何可疑病变进行活检。因此，这两部分都需要适当的内窥镜检查。

* The location of the tumor relative to the teeth and EGJ, the length of the tumor, the extent of circumferential involvement, and the degree of obstruction should be carefully recorded to assist with treatment planning. If present, the location, length and circumferential extent of Barrett’s esophagus should be characterized in accordance with the Prague criteria, and mucosal nodules should be carefully documented.
*肿瘤相对于粗糙和食管胃接合处的位置、肿瘤长度、环周累及范围以及阻塞程度均应该仔细记录以帮助制定治疗计划。如果存在巴雷特食管，应该根据布拉格标准描写部位、长度和环周范围，并且应该仔细记录黏膜结节。

* High-resolution endoscopic imaging and narrow-band imaging are presently available and may enhance visualization during endoscopy, with improved detection of lesions in Barrett’s and non-Barrett’s esophagus and stomach.
*目前可以利用的高分辨率内窥镜成像与窄带成像技术可以增强内镜检查过程中的可视化，增加巴雷特与非巴雷特食管和胃病灶的检出。

* Multiple biopsies, six to eight, using standard size endoscopy forceps should be performed to provide sufficient material for histologic interpretation. Larger forceps are recommended during surveillance endoscopy of Barrett’s esophagus for the detection of dysplasia.
*使用标准规格内镜钳应该进行6-8处多点活检以提供足够的材料用于组织学判读。在巴雷特食管内镜监测期间为了检出异型增生推荐更大的钳子。

* Endoscopic resection (ER) of focal nodules should be performed in the setting of early-stage disease to provide accurate depth of invasion, degree of differentiation, and the presence of vascular and/or lymphatic invasion. ER should be considered in the evaluation of areas of Barrett’s esophagus associated with high-grade dysplasia (HGD) and also patches of squamous cell dysplasia, specifically focusing on areas of nodularity or ulceration. Pathologists should be asked to provide an assessment of the depth of tumor infiltration into the lamina propria, muscularis mucosa and submucosa, invasion of vascular structures, and nerves and the presence of tumor or dysplastic cells at the lateral and deep margins. ER may be fully therapeutic when a lesion less than or equal to 2 cm in diameter is fully removed and histopathologic assessment demonstrates well or moderate differentiation, invasion no deeper than the superficial submucosa, no lymphovascular invasion (LVI), and clear lateral and deep margins.
*在早期疾病中应该进行局灶性结节的内镜切除术(ER)以提供准确的侵犯深度、分化程度以及是否存在血管和/或淋巴管侵犯。为了评价具有高级别异型增生(HGD)还有鳞状细胞异型增生斑片的巴雷特食管的范围应该考虑内镜黏膜切除术，特别关注结节或溃疡范围。病理学家应该提供评估肿瘤浸润入固有层、黏膜肌层与黏膜下层的深度、侵犯血管结构及神经以及在横向及纵向边缘是否存在肿瘤或不典型增生细胞。当彻底切除的病变直径≤2厘米并且组织病理学显示高或中分化、侵犯深度未超出浅表黏膜下层、无脉管侵犯(LVI)且横向与纵向边缘干净时，内镜黏膜切除术可能是根治性治疗。

* Cytologic brushings or washings are rarely adequate in the initial diagnosis.
*在初次诊断中细胞刷或冲洗很难胜任。

STAGING 分期

* Endoscopic ultrasound (EUS) performed prior to any treatment is important in the initial clinical staging of neoplastic disease. Careful attention to ultrasound images provides evidence of depth of tumor invasion (T designation), presence of abnormal or enlarged lymph nodes likely to harbor cancer (N designation), and occasionally signs of distant spread, such as lesions in surrounding organs (M designation).
*在肿瘤疾病的最初临床分期中，在任何治疗前完成内镜超声(EUS)是重要的。关注超声图像提供的肿瘤侵犯深度(指定T)、存在可能隐藏恶性肿瘤的异常或增大的淋巴结(指定N)以及偶尔出现的远处扩散迹象如器官周围的病变(指定M)证据。

* Hypoechoic (dark) expansion of the esophageal wall layers identifies the location of tumor, with gradual loss of the layered pattern of the normal esophageal wall corresponding with greater depths of tumor penetration, correlating with higher T-categories. A dark expansion of layers 1–3 correspond with infiltration of the superficial and deep mucosa plus the submucosal, T1 disease. Isolated thickening of the mucosal layer alone may be difficult to appreciate resulting in loss of sensitivity of EUS for superficial disease. Similarly, standard EUS scopes, with 7.5 to 12 MHz frequency transducers, may lack the resolution to accurately distinguish the penetration of the tumor through the muscularis mucosa, or superficial from deep penetration of the submucosa. A dark expansion of layers 1–4 correlates with penetration into the muscularis propria, T2 disease, and expansion beyond the smooth outer border of the muscularis propria correlates with invasion of the adventitia, T3 disease. Loss of a bright tissue plane between the area of tumor and surrounding structures such as the pleura, diaphragm, and pericardium correlates with T4a disease, while invasion of surrounding structures such as the trachea, aorta, lungs, heart, liver, or pancreas correlates with T4b disease.

*食管壁层低回声(暗)扩张视为肿瘤部位，正常的食管壁分层模式逐渐丧失相应具有更深的肿瘤穿透深度，与T分类较高相关。1-3层暗扩张符合黏膜浅层与黏膜深层加黏膜下层浸润，T1病变。对于浅表性病变只有黏膜层孤立性肥厚可能难以评价造成超声内镜的敏感性丧失。同样，标准的超声内镜示波器，具有7.5-12MHz频率换能器，精度可能不足以准确鉴别肿瘤穿透黏膜肌层或浅表的黏膜下层的深层穿透。1-4层的暗扩张与穿入固有肌层相关，T2病变，而在固有肌层的光滑外缘以外扩张与外膜侵犯相关，T3病变。在肿瘤部位和周围结构如胸膜、膈肌和心包之间鲜明的组织平面消失与T4a病变相关，而周围结构如气管、主动脉、肺、心脏、肝脏或胰腺侵犯与T4b病变相关。

* For small, nodular lesions less than or equal to 2 cm, ER is encouraged as it provides a more accurate depth of invasion than the results of EUS. A decision to proceed to further therapy such as resection, ablation, or to consider the ER completely therapeutic would depend on the final pathologic assessment of the resection specimen.
*对于≤50px的小结节灶，鼓励内镜黏膜切除术，因为其比超声内镜提供更准确的侵犯深度。决定进行进一步治疗如切除、消融或考虑根治性内镜黏膜切除术应取决于最后切除标本的病理学评估。

* Mediastinal and perigastric lymph nodes are readily seen by EUS, and the identification of enlarged, hypoechoic (dark), homogeneous, well-circumscribed, rounded structures in these areas correlates with the presence of malignant or inflammatory lymph nodes. The accuracy of this diagnosis is significantly increased with the combination of features, but is also confirmed with the use of fine-needle aspiration (FNA) biopsy for cytology assessment. FNA of suspicious lymph nodes should be performed if it can be performed without traversing an area of primary tumor or major blood vessels, and if it will impact on treatment decisions. The pre-procedure review of CT and PET scans, when available, prior to esophagogastroduodenoscopy (EGD)/EUS, to become fully familiar with the nodal distribution for possible FNA is recommended.
*超声内镜容易看到纵隔和胃周淋巴结，在这些区域中发现增大的、低回声(暗区)、均匀的、非常局限的圆形结构与存在恶性或炎性淋巴结相关。综合这些特征显著提高了诊断准确性，通过使用细针穿刺抽吸(FNA)活检细胞学评估也证实了这点。如果不用穿越原发肿瘤区域或较大的血管就可以完成可疑淋巴结的细针穿刺，并且如果其将影响治疗决策，应该进行细针穿刺。操作前复习CT和PET扫描，当可以得到时；推荐在食管胃十二指肠镜(EGD)/超声内镜检查前，为了可能进行的细针穿刺应充分熟悉淋巴结分布。

* Obstructing tumors may increase the risk of perforation while performing staging EUS exams. The use of wire-guided EUS probes, or miniprobes, may permit EUS staging with a lower risk. In certain cases, dilating the malignant stricture to allow completion of staging may be appropriate but there is increased risk of perforation after dilation.
*当施行超声内镜分期检查时肿瘤阻挡可能增加穿孔的风险。使用线引导的超声内镜探针或微型探头，可允许使用具有较低风险的超声内镜分期。在某些情况下，扩张恶性狭窄以允许完成分期可能是恰当的，但在扩张后有增加穿孔风险。

PRIMARY TREATMENT 初始治疗

* The goal of endoscopic therapy [by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and/or ablation] is the complete removal or eradication of early-stage disease (pTis, pT1a, selected superficial pT1b without LVI) and pre-neoplastic tissue (Barrett’s esophagus).
*内镜治疗【内镜黏膜切除术（EMR）、内镜黏膜下剥离术（ESD）和/或消融】的目标是完全清除或根除早期疾病（pTis、pT1a、部分无脉管侵犯的浅表pT1b）与癌前组织（巴雷特食管）。

* Early-stage disease, Tis, also known as HGD, needs to be fully characterized, including evaluating presence of nodularity, lateral spread and ruling out multifocal disease, as well as ruling out lymph node metastases by EUS in select higher risk cases. This is important to permit decisions on endoscopic therapy with ablative methods such as radiofrequency ablation (RFA), cryoablation, photodynamic therapy (PDT), and/or ER. Areas of nodularity or ulceration should be resected rather than ablated. Completely lat, small lesions (≤2 cm) of squamous cell HGD/Tis (carcinoma in situ) and Barrett’s esophagus associated with flat HGD should be treated by ER as it provides more accurate histologic assessment of the lesion. Larger flat lesions (>2 cm) can be treated effectively by ER, but this is associated with greater risk of complications. Such lesions can be effectively treated by ablation alone, but there are very limited data on treating squamous cell HGD by ablation alone.
*早期疾病，Tis，亦称高级别异型增生，需要充分描述特征，包括评估存在的结节状态、横向播散并排除多灶性疾病，以及在部分更高危病例中通过超声内镜排除淋巴结转移。内镜消融治疗如射频消融（RFA）、冷冻消融术、光动力疗法（PDT）和/或内镜黏膜切除术的许可证决策是重要的。结节或溃疡区域应该切除而不是摘除。十分平坦、鳞状细胞高级别异型增生的小病灶(≤2厘米)/Tis(原位癌)以及有平坦高级别异型增生的巴雷特食管应该通过内镜黏膜切除术治疗，因为其提供更准确的病变组织学评估。更大的平坦病灶(>2厘米)可以通过内镜黏膜切除术有效治疗，但是这与更大的并发症风险有关。这种病灶可经单独消融有效治疗，但是有关单独通过消融治疗鳞状细胞高级别异型增生的数据十分有限。

* Lesions that are found to be pathologically limited to the lamina propria or muscularis mucosae (pT1a), or the superficial submucosa (pT1b), in the absence of evidence of lymph node metastases, LVI, or poor differentiation grade can be treated with full ER. However, a thorough and detailed discussion regarding comparative risk of esophagectomy versus potential for concurrent nodal disease should be undertaken, preferably between patient and surgeon, especially in cases with larger tumors, or deeper invasion. Ablative therapy of residual Barrett’s esophagus should be performed following ER. Complete eradication of Barrett’s esophagus can also be performed with more aggressive application of EMR (widefield EMR) or ESD at the initial intervention, if necessary to completely resect an area of superficial tumor or mucosal nodularity less than or equal to 2 cm in maximal dimension.
*病理发现病灶限于固有层或黏膜肌层(pT1a)或浅表黏膜下层(pT1b)，在没有淋巴结转移、脉管侵犯或低分化证据的情况下可用充分的内镜黏膜切除术治疗。但是，对于可能同时存在淋巴结病变者需要进行全面细致的有关食管切除术相对危险性的讨论，最好为患者与外科医生间，特别是在肿瘤更大或侵犯更深的病例中。在内镜黏膜切除术后应该进行残余巴雷特食管的消融治疗。在最初干预时也可以实施更具侵袭性的黏膜下切除(广泛的黏膜下切除)或内镜黏膜下剥离术以彻底根治巴雷特食管，如有必要完全切除浅表肿瘤区域或最大尺寸≤50px黏膜结节。

* The level of evidence for ablation of squamous cell carcinoma (SCC) after ER is low. However, additional ablation may be needed if there is multifocal HGD/carcinoma in situ elsewhere in the esophagus. Ablation may not be needed for lesions that are completely excised.
*在内镜黏膜切除术后鳞癌(SCC)消融的证据等级低。但是，在食管的其他地方如果有多灶性高级别异型增生/原位癌可能需要追加消融。消融可能不需要完全切除病变。

* Endoscopic therapy is considered “preferred” for patients with limited early-stage disease (Tis and T1a, less than or equal to 2 cm, and well or moderately differentiated carcinoma), because the risk of harboring lymph node metastases, local or distant recurrence, and death from esophageal cancer is low following endoscopic therapy.
*对于局限性早期疾病(Tis和T1a、≤50px及高或中分化癌)患者内窥镜治疗认为是“首选的”，因为在内镜治疗后淋巴结转移、局部或远处复发以及死于食管癌的风险低。

TREATMENT OF SYMPTOMS 症状的处理

* Esophageal dilation can be performed with the use of dilating balloons or bougies to temporarily relieve obstruction from tumors, or treatment-related strictures. Caution should be exercised to avoid overdilation, to minimize the risk of perforation.
*可以借助扩张气囊或探条实施食管扩张以暂时减轻肿瘤阻塞或治疗相关的狭窄。告诫应该训练避免过度扩张，以避免穿孔风险。

* Long-term palliation of dysphagia can be achieved with endoscopic tumor ablation by Nd:YAG Laser, PDT and cryoablation, or endoscopic and radiographic-assisted insertion of expandable metal or plastic stents.
*用钕∶钇铝石榴石激光光动力疗法和冷冻消融术内镜肿瘤消融或内镜与放射影像辅助插入可膨式金属或塑料支架可获得吞咽困难的长期缓解。

* Long-term palliation of anorexia, dysphagia, or malnutrition may be achieved with endoscopic or radiographic-assisted placement of feeding gastrostomy or jejunostomy. The placement of a gastrostomy in the preoperative setting may compromise the gastric vasculature, thereby interfering with the creation of the gastric conduit in the reconstruction during esophagectomy and should be avoided.
*用内镜或放射影像辅助放置进餐用胃造口或空肠造口可能实现厌食、吞咽困难或营养不良的长期缓解。在术前情况下安排胃造口术可能损害胃脉管系统，从而在食管切除重建中妨碍胃管的创建因此应该避免。

POST-TREATMENT SURVEILLANCE 治疗后监测

* Consider deferring assessment endoscopy with biopsy to 6 weeks or later after completion of preoperative therapy in patients whom avoidance of surgery is being considered.
*在认为可避免手术的患者中，在完成术前治疗后考虑推迟至6周或以后进行内镜活检评估。

* EUS exams performed after chemotherapy or radiation therapy have a reduced ability to accurately determine the present stage of disease. Similarly, biopsies performed after chemotherapy or radiation therapy may not accurately diagnose the presence of residual disease.
*在化疗或放疗后实施超声内镜检查降低准确确定目前疾病分期的能力。同样，在化疗或放疗后实施活检也许不能准确诊断残留病变的存在。

* Endoscopic surveillance following definitive treatment of esophageal cancer requires careful attention to detail for mucosal surface changes, and multiple biopsies of any visualized abnormalities. Strictures should be biopsied to rule out neoplastic cause. EUS-guided FNA should be performed if suspicious lymph nodes or areas of wall thickening are seen on cross-sectional imaging.
*在食管癌根治性治疗之后内镜监测需要详细关注黏膜表面改变，并对所有直视的异常进行多点活检。狭窄应该进行活检以排除肿瘤原因。如果断面成像见到可疑淋巴结或壁增厚的区域应该进行超声内镜引导的细针穿刺。

* Endoscopic surveillance after ablative therapy or ER of early-stage esophageal cancer should continue after completion of treatment. Biopsies should be taken of the neosquamous mucosa even in the absence of mucosal abnormalities as dysplasia may occasionally be present beneath the squamous mucosa.
*早期食管癌在消融治疗或内镜黏膜切除术后，内镜监测应该在治疗结束以后继续进行。新生的鳞状上皮黏膜应该获取活检，即使在没有黏膜异常的情况下，因为异型增生可能偶尔出现在鳞状上皮黏膜下面。

* Endoscopic surveillance should also include a search for the presence of Barrett's esophagus and four-quadrant biopsies to detect residual or recurrent dysplasia. The ablation of residual or recurrent high-grade and low-grade dysplasia using RFA or cryoablation should be considered. Ablation of non-dysplastic Barrett's esophagus is not recommended.
*内镜监测应该也包括寻找巴雷特食管的存在，并且四象限活检以检出残留或复发的异型增生。残留或复发性高分级和低分级异型增生的消融应该考虑使用射频或冷冻消融。不建议非异型性巴雷特食管的消融。

* Patients who have received therapeutic ER should have endoscopic surveillance and mucosal ablation where appropriate every 3 months for the first year. Follow up as clinically indicated after two years. Follow-up for Barrett’s esophagus alone may be required.
*已接受治疗性内镜切除术的患者应该在第1年每3个月1次进行内镜监测和黏膜消融是合理的。两年后根据临床需要随访。对单纯性巴雷特食管随访可能是必需的。