胸段食管鳞癌淋巴结转移规律及淋巴结清扫方式探讨

目的探讨胸段食管鳞癌淋巴结转移规律及术中淋巴结清扫方式。方法 480例行根治术的胸段食管鳞癌患者,标记各部位清扫淋巴结分别送检,进行临床病理资料分析。结果本组386例患者有淋巴结转移。全组清扫淋巴结5 424枚,平均每例清扫11.3枚,689枚淋巴结有转移。22例患者出现跳跃性淋巴结转移,其中胸上段3例、中段9例、下段1例。胸上段食管鳞癌颈部淋巴结转移率47.6%,高于胸中段（10.5%）和胸下段（1.3%）,P均〈0.05。胸下段食管鳞癌向腹腔淋巴结转移率为33.1%,高于胸中段（19.4%）和胸上段（3.8%）,P均〈0.05。胸中段食管鳞癌有上纵隔淋巴结（23.5%）及下纵隔淋巴结（29%）和腹腔淋巴结（19.4%）的双向转移趋势,隆突下淋巴结转移多见,转移率54.2%。结论 胸上段食管癌淋巴结转移以颈段食管旁、锁骨上、上中纵隔转移多见,胸中段食管癌淋巴结转移具有明显的上下双向转移和跳跃性转移特点,胸下段食管癌淋巴结转移以腹部、中下纵隔转移多见。胸上段食管癌行颈、胸、腹三野淋巴结清扫,重点清扫颈段食管旁及锁骨上、下界包括隆突下淋巴结;胸下段食管癌可行胸、腹两野淋巴结清扫,重点清扫隆突下、下胸段食管旁、胃左动脉旁淋巴结;胸中段食管癌淋巴结清扫方式应根据具体情况设定。     

Two-step three-field lymph node dissection is beneficial for thoracic esophageal carcinoma

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome.     

Salvage lymphadenectomy for cervical lymph node recurrence after esophagectomy for squamous cell carcinoma of the thoracic esophagus

Prognosis of patients with recurrent esophageal cancer is usually unsatisfactory. We have successfully treated five patients with cervical node recurrence after esophagectomy with multimodal treatment including salvage lymphadenectomy. In order to clarify the efficacy of salvage surgery for cervical node recurrence, we have reviewed the clinical course and prognosis of these patients. From August 2004 to December 2007, 30 patients with 33 recurrent sites were treated in the Department of Surgery, Iizuka Hospital. Among these patients, there were five patients with recurrence limited within the cervical nodes. Salvage cervical lymphadenectomy was performed for all five patients. Curative resection was achieved in four patients and reduction surgery followed by planned chemoradiotherapy was performed in another patient. All stations including the suspicious node were dissected and a partial sternotomy was added for one patient whose recurrent tumor was located in the right recurrent nerve node. There was no mortality and one minor complication (subcutaneous hemorrhage) was observed. Median duration of hospital stay was 7 days. Adjuvant chemotherapy was performed for all patients. Median follow‐up period was 54 months and all patients are alive without relapse of the disease. Salvage cervical lymphadenectomy is a safe and effective treatment for patients with cervical node recurrence after esophagectomy.     

Prognosis of patients who develop cervical lymph node recurrence following curative resection for thoracic esophageal cancer

Patients with esophageal cancer often display relapse at cervical nodes after surgery, but their prognosis and a suitable therapy remains unknown. We retrospectively reviewed the records for 35 patients who underwent esophagectomy with lymphadenectomy who then displayed relapse at the cervical lymph nodes alone between 1985 and 2003 in order to observe the prognostic factors for such patients. Median survival time from the date of recurrence for all 35 patients was 12 months with 1-year, 2-year, 3-year and 5-year survival rate of 47.2%, 26.5%, 17.7% and 8.8%, respectively. With regard to the initial treatment against cervical node recurrence, 15 patients were treated by radiotherapy alone, eight by chemoradiotherapy, 11 by surgery and one by chemotherapy alone. Univariate analysis revealed that cervical node dissection at the prior esophagectomy (yes/no, P = 0.0178), time to recurrence (> 9 months or < 9 months, P = 0.0497) and the number of relapsed nodes (solitary/multiple, P = 0.0029) were significant prognostic factors. Among these factors, the number of relapsed nodes (solitary/multiple) was found to be the only significant prognostic factor with an odds ratio of 2.409 and 95% confidence interval of 1.033-5.619 by multivariate analysis. In conclusion, cervical node metastasis is generally considered to be distant organ metastasis. However, if it is a solitary node recurrence, substantial survival can be attained by appropriate loco-regional therapy.     

Preoperative chemotherapy for clinically node-positive patients with squamous cell carcinoma of the esophagus

Lymph node metastasis is one of the strongest prognostic factors for patients with esophageal cancer. Whether neoadjuvant chemotherapy is effective for metastatic nodes and improves the prognosis of clinically node-positive patients is unknown. Seventy-seven patients with clinically node-positive esophageal cancer, who were given preoperative chemotherapy (5-fluorouracil, cisplatin and adriamycin) followed by surgery, were retrospectively analysed. The histological effectiveness of the chemotherapy against the main tumor in the resected specimen was correlated with nodal status and prognosis. Of the 77 patients, the histological effects in the main tumors were grade 3 in one patient (1.3%), grade 2 in 10 (13.0%), grade 1b in seven (9.1%), grade 1a in 50 (64.9%) and grade 0 in nine (11.7%). Eleven patients (14.3%) were found to be pathologically node-negative. The pathological stages were significantly earlier in responders (grades 3-1b) than in non-responders (grades 1a-0) (P = 0.0001). The responders showed a significantly lesser degree of lymph node metastasis (P = 0.0005), fewer metastatic nodes (2.2 +/- 3.1 vs. 12.0 +/- 20.5, P = 0.0482) and better survival (P = 0.002) than the non-responders. The most common failure pattern for the non-responders was lymphatic recurrence, with an incidence of 47.5% (28/59), while that for the responders was 16.7%. Responders to neoadjuvant chemotherapy show fewer metastatic nodes and better prognosis than non-responders. Neoadjuvant chemotherapy may offer clinical benefit to responders.     

Pattern of lymph node metastases of esophageal squamous cell carcinoma based on the anatomical lymphatic drainage system

The recent anatomical studies of the esophagus showed that submucosal longitudinal lymphatic vessels connect to the superior mediastinal and the paracardial lymphatics and lymphatic routes to periesophageal nodes originate from the muscle layer. Using clinical data for lymph node metastasis, we verify these anatomical bases to clarify the rational areas of lymph node dissection in esophageal cancer surgery. Analysis was performed on 356 consecutive patients who underwent esophagectomy with three‐field dissection. Patients were divided into those with tumor limited within the submucosal layer and those with tumor invading or penetrating the muscle layer. Frequency of node metastasis was compared according to supraclavicular, upper mediastinum, mid‐mediastinum, lower mediastinum, perigastric and celiac areas. In patients with tumor limited to the submucosal layer, node metastasis was more frequent in the upper mediastinum and perigastric area than the mid‐ or lower mediastinum. Even in patients with tumor located in the lower esophagus, node metastasis was more frequent in the upper mediastinum than the mid‐mediastinum or lower mediastinum. In patients with tumor located in the mid‐esophagus, node metastasis was more frequent in the supraclavicular area than the mid‐mediastinum or lower mediastinum. In patients with tumor invading or penetrating the muscle layer, node metastasis in the mid‐ and lower mediastinum increased dramatically, but was still less frequent than those in the upper mediastinum or the perigastric area. Postoperative survival curves did not differ among the involved areas. The most predictive factor associated with lymph node metastasis for postoperative survival was not the area of involved nodes, but the number of involved nodes by multivariate analyses. These clinical results verify recent anatomical observations. The lack of difference in survival rates among the involved areas suggests that these areas should be staged equivalently. For adequate nodal staging, the upper mediastinum should be dissected for the lower esophageal tumor and supraclavicular areas should be dissected for the mid‐esophageal tumor even in patients with tumor limited to within the submucosal layer.     

Extent of prophylactic postoperative radiotherapy after radical surgery of thoracic esophageal squamous cell carcinoma

SUMMARY. The aim of this study was to assess if the entire mediastinum (M), the bilateral supraclavicular area (S), and the left gastric area (L) should be all included in the irradiation volume. The clinical data of 204 patients with thoracic esophageal squamous cell carcinoma who had undergone prophylactic postoperative radiotherapy after radical surgery were retrospectively reviewed. They were classified into four groups: group A, 26 patients with irradiated M alone; group B, 139 patients with irradiated M + S; group C, 10 patients with irradiated M + L; and group D, 29 patients whith irradiated M + S + L. The 5‐year disease‐free survival rates were 36% in group A, 31% in group B, 40% in group C and 44% in group D (χ2=3.05, P =0.39), respectively. Multivariate analysis revealed that the irradiated extent was not a significant influential factor (hazard ratio=0.84, 95% confidence interval, 0.69–1.03, P =0.10). None of 43 patients without the L irradiated and with disease in the upper and middle upper thirds (defined in middle third but with upper third invaded), and one of 83 patients without the L irradiated and with disease in the middle third only thoracic esophagus were shown to have abdominal lymph node metastasis. Supraclavicular lymph node metastasis in patients in the lower and middle lower thirds (defined in middle third but with lower third invaded) were, respectively, 1/43 and 1/18 whether the S was irradiated or not. It seems unnecessary that the L be irradiated when the primary site is in the upper, middle, and middle upper thirds of the thoracic esophagus after radical surgery. Similarly, S may be unnecessarily irradiated in the lower and middle lower thirds.     

Individualization of lymphadenectomy in superficial esophageal squamous cell cancer

Background As the result of the development of imaging means, the incidence of discovery of superficial esophageal squamous cell cancer (ESCC) has recently increased. Various treatment methods such as endoscopic mucosal resection and reduction of lymphadenectomy have been performed to preserve the quality of life. Because lymph node metastasis occurs even in the early stage of esophageal cancer, we should carefully select the treatment method, including lymphadenectomy. Methods We analyzed the distribution of solitary lymph metastasis of 27 superficial esophageal cancers. To analyze the distribution of micrometastasis, a total of 1542 lymph nodes obtained from 46 patients with pN0 submucosal cancer were immunohistochemically examined by cytokeratin antibody. Sentinel node mapping was performed in 23 patients with clinical T1 tumors. Results The location of lymph node metastasis in the 22 patients with solitary lymph metastasis in superficial cancer was limited to recurrent nerve nodes in the upper thoracic esophagus, recurrent nerve nodes, paraesophageal nodes, or perigastric nodes in the middle or lower thoracic esophagus. For eight patients with lymph node micrometastasis in pN0 patients with superficial esophageal cancer, the locations of micrometastasis were similar to those of solitary metastasis. In sentinel node mapping, all nodal metastasis was included in sentinel nodes with a single exception. Conclusions Individual lymphadenectomy in superficial ESCC will be established using methods such as analysis of past data, clinical diagnosis of lymph node metastasis by imaging, and sentinel node navigation surgery, including the diagnosis of micrometastasis.     

Radiofrequency ablation for pulmonary metastases from esophageal squamous cell carcinoma

Radiofrequency ablation (RFA) is increasingly being used for the treatment of intrathoracic malignancies. Although RFA has been found to be promising in the treatment of lung metastases from some types of neoplasms, little is known concerning its clinical significance in the treatment of pulmonary metastasis from esophageal squamous cell carcinoma (ESCC). This retrospective study evaluated the feasibility, safety, and effectiveness of computed tomography‐guided RFA for pulmonary metastasis from ESCC. A series of 10 ESCC patients with 17 pulmonary tumors were included. Correct placement of the ablation device into the target tumor proved to be feasible in all tumors (100%). The mean visual analog scale score, with values that ranged from 0 (no pain) to 10 (worst pain possible), was 1. This suggested that this procedure was well tolerated. No procedure‐related deaths occurred. A pneumothorax needing drainage was a major complication in two patients. Local control of ablated tumor lasting for at least 1 year was achieved in 10 (83%) of 12 assessable tumors. Although locoregional recurrences developed in two tumors, these lesions could be recontrolled by repeat treatment with RFA. Three patients died of recurrent disease. The predicted 1‐ and 2‐year overall survival rates after lung RFA were 77.8% and 62.2%, respectively. Percutaneous computed tomography‐guided RFA yielded relatively high levels of local control in patients with pulmonary metastases from ESCC and was associated with an acceptable level of complications. It was concluded that a prospective study will be necessary to evaluate the effectiveness of a combination of systemic therapy and RFA for ESCC lung metastases.     

Effect of bilateral supraclavicular postoperative radiotherapy in middle and lower thoracic esophageal carcinoma

AIM: To evaluate whether postoperative radiotherapy is an alternative to neck lymph node surgery and if it provides a survival benefit for those receiving two-field, chest and abdomen, lymphadenectomy.METHODS: A total of 530 cases with middle and lower thoracic esophageal carcinoma in our hospital from January 2008 to April 2009 were selected and analyzed, of which 219 cases received right chest, upper abdominal incision Ivor-Lewis surgery and simultaneously underwent mediastinal and abdominal two-field lymphadenectomy. If regional lymph node metastasis occurred within the recurrent laryngeal nerve, the patients would receive bilateral supraclavicular radiotherapy (DT = 5000cGy) to be adopted at postoperative 4-5 wk (Group A) or cervical lymphadenectomy at postoperative 3-4 wk (Group B). If there were no regional lymph node metastases within the recurrent laryngeal nerve, the patients only underwent two-field, chest and abdomen, lymphadenectomy (Group C).RESULTS: In 219 cases who underwent two-field lymphadenectomy, 91 cases were diagnosed with regional lymph node metastasis within the recurrent laryngeal nerve. Of them, 48 cases received cervical radiotherapy, and 43 cases underwent staging lymphadenectomy; 128 patients were not given the follow-up treatment of cervical radiotherapy because there was no regional lymph node metastasis within the recurrent laryngeal nerve. Five-year survival rates in group A and B were 47% and 50%, respectively, with no statistical difference between them, and the rate in group C was 58%.CONCLUSION: For patients with middle and lower thoracic esophageal carcinoma combined with lymph node metastasis within the recurrent laryngeal nerve, cervical radiotherapy can be a substitute for surgery and provide benefit.     

Prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery

The aim of this study was to retrospectively analyze and assess the outcomes and prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. One hundred twenty-six patients with node-positive thoracic esophageal squamous cell carcinoma who had undergone adjuvant therapy (postoperative radiotherapy alone or postoperative sequential chemoradiotherapy without receiving postoperative concurrent chemoradiotherapy) after radical surgery, were retrospectively reviewed from January 1996 to December 2003. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves were estimated using the Kaplan-Meier method. The 1-, 3- and 5-year overall survival rates of all 126 patients were 71.4, 39.1, and 22.0%, and disease-free survival rates were 64.3, 36.4, and 21.5%, respectively. Lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of lymph nodes removed, LNR) ≥0.2 ( P = 0.006), pT3 + pT4 ( P = 0.06) and sequential chemoradiotherapy ( P = 0.08) were associated with a poorer survival by univariate analysis. In multivariate analysis, LNR ( P = 0.01, hazard ratio = 0.57, 95% confidence interval, 0.37–0.87) and tumor depth of invasion ( P = 0.03, hazard ratio = 0.62, 95% confidence interval, 0.41–0.96) were the independent predictors of survival. Sequential chemoradiotherapy receded survival tendency without significant difference ( P = 0.09, hazard ratio = 0.64, 95% confidence interval, 0.37–1.08). Therefore, LNR and tumor depth of invasion were the independent prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. The addition of chemotherapy does not seem to confer a survival benefit.     

内皮抑素在食管鳞癌中的表达及其意义

目的研究内皮抑素在食管鳞癌中的表达及其意义。方法采用免疫组化SP法检测内皮抑素在62例食管鳞癌中的表达。结果食管鳞癌组织内皮抑素阳性表达率高于切缘组织和食管良性病组织（P〈0．01）,食管鳞癌内皮抑素表达水平与原发肿瘤的浸润深度、远处转移情况、细胞分化程度、临床TNM分期均有密切关系（P均〈0．05）,而与原发肿瘤部位、区域淋巴结转移状况以及食管鳞癌患者的年龄、性别、饮食习惯、家族史等均无明显关系（均P〉0．05）。结论内皮抑素可能在抑制食管鳞癌侵袭和转移过程中发挥重要作用,可以作为判断其预后的指标之一。     

Celiac lymph nodes: distant or regional for thoracic esophageal carcinoma?

Involvement of celiac nodes is defined as distant metastasis in the TNM classification for thoracic esophageal carcinoma. Some textbooks, however, describe dissection of these nodes as a standard technique. The present study was, therefore, undertaken to clarify which celiac nodes are regional for thoracic esophageal carcinoma and whether or not celiac node dissection would provide a survival benefit. Eight hundred and five patients who underwent R0 resection (no residual tumor) with systematic lymphadenectomy including the celiac axis area for thoracic esophageal carcinoma were retrospectively investigated. The frequency of metastasis and the therapeutic value of dissecting celiac nodes were compared to those associated with the left gastric artery area. The frequencies of left gastric and celiac nodal involvement were 15.4% and 9.6%, respectively, for thoracic esophageal carcinoma. As for tumor location, the incidences of metastasis around left gastric artery and celiac axis from the upper, middle and lower portion were 6.7% and 1.0%; 12.3% and 7.7%; and 25.7% and 17.4%, respectively. The 5‐year survivals of patients with celiac but not left gastric metastasis were 36.3% and 41.8% for the middle and lower portions, respectively, while the corresponding values with left gastric involvement but no celiac metastasis were 24.1% and 27.9%. These differences were not significant. The frequency of celiac node involvement was not low. And, their dissection has equivalent therapeutic value to that of left gastric nodes. Revision of the TNM classification to account for celiac node involvement in thoracic esophageal carcinoma, especially of the middle and lower portions, is needed.     

Risk factors of postoperative stricture after endoscopic submucosal dissection for superficial esophageal neoplasms: A meta-analysis

Background:As larger-sized superficial esophageal neoplasms became candidates for endoscopic submucosal dissection (ESD), post-ESD esophageal stricture has inevitably developed into a significant complication during long-term follow-up.Method:The PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, as well as China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Biomedical Literature Database, were searched to identify all the appropriate studies published from January 2000 through October 2019. For risk factor assessment between postoperative stricture and control groups, pooled odds ratios (OR) and weighted mean differences (WMD) estimation was done. All meta-analytical procedures were conducted by using Stata version 15.1 software.Results:The results showed that 11 studies with 2248 patients (284 structure cases and 1964 controls) were eligible for this meta-analysis. Statistical results indicated 6 substantial risk factors: lesion characteristics involving the upper third of the esophagus (OR 1.51, [1.02–2.25]), macroscopic type of IIa/IIc (OR 2.76, [1.55–4.92]), tumor depth of invasion above m1 (OR 7.47, [3.31–16.86]), and m2 (OR 12.67, [4.00–40.10]), longitudinal length (WMD 13.75 mm, [7.76–19.74]), circumferential diameter (WMD 10.87 mm, [8.13–13.60]), and circumferential range >3/4 (OR 38.17, [9.94–146.52]). Each additional 10% of the circumferential range increased the risk of stricture by 149% (OR 9282.46, [978.14–88089.35]).Conclusions:Six risk factors were assessed to have a key role in the elevated risk levels of post-ESD esophageal stricture. The results can help doctors identify patients with increased risk and thus can guide management of the adequate period of surveillance after ESD and take available approaches of stricture prevention.     

Doxorubicin,cisplatin, and fluorouracil combination therapy for metastatic esophageal squamous cell carcinoma

The chemotherapy regimen currently used for treating esophageal and gastric carcinoma has been either epirubicin, cisplatin, and fluorouracil (5‐FU) or docetaxel, cisplatin, and 5‐FU. Here, we report the efficacy and toxicity of doxorubicin, cisplatin, and 5‐FU for only esophageal squamous cell carcinoma (ESCC). Between January 2000 and October 2008, a total of 41 ESCC patients with a distant metastasis were enrolled. The most common sites of metastasis were liver (26, 63.4%), lung (9, 22.0%), and bone (8, 19.5%). Doxorubicin was administered on day 1 at 30 mg/m², cisplatin on days 1–5 at 14 mg/m²/day, and 5‐FU on days 1–5 at 700 mg/m²/day. The median number of cycles was 2.0 (range 1‐8). The dose intensities of doxorubicin, cisplatin, and 5‐FU were 92.9, 92.4, and 92.5%, respectively. The overall response rate was 43.9%; one showed complete response, 17 showed partial response, 13 showed a stable disease, and 10 showed progressive disease (PD). The median survival time was 306 days (95% CI = 74–935) and the 1‐year survival rate was 37.6%. Grade 3 neutropenia was seen in seven patients and grade 4 in one patient. Grade 3 fatigue, anorexia, mucositis, and diarrhea were observed in three, two, two, and one patient, respectively. This regimen is effective as a first‐line therapy for ESCC with distant metastasis.     

Two-field lymph-node dissection may be enough to treat patients with submucosal squamous cell carcinoma of the thoracic esophagus

Significance of extended radical surgical treatment including three-field lymph node dissection for squamous cell carcinoma (SCC) of the esophagus remains debatable. The aim of the current study was to reconsider the merits and demerits obtained by three-field lymph node dissection for esophageal carcinoma and also to attempt to elucidate an appropriate surgical strategy for submucosal SCC of the thoracic esophagus. Thirty-one patients with SCC of the thoracic esophagus who had been treated with esophagectomy and two-field (thoracic and abdominal) lymph node dissection without preoperative therapies were enrolled. Five-year survival rate was 75.0% and the incidence proportion of postoperative complication was 9.7%. These data regarding postoperative outcome of patients were by no means inferior to those in the previous reports referring the prognosis of patients with esophageal carcinoma who had been treated with three-field lymph node dissection. Authors would like to mention that two-field lymph node dissection associated with reduced incidence of postoperative complications might be enough to treat the submucosal SCC of the thoracic esophagus.     

Curative ESD for intraepithelial esophageal carcinoma with leiomyoma mimicking submucosal invasive carcinoma

This case report presents a 65-year-old man who developed early esophageal cancer with leiomyoma treated by endoscopic submucosal dissection (ESD). There have been several reports of co-existing superficial esophageal cancer and leiomyoma treated by endoscopic mucosal resection. However, there is no previous report describing the co-existing lesion treated by ESD. In order to determine treatment strategies for esophageal cancer, accurate endoscopic evaluation of the cancerous depth is essential. In the present case, the combination of endoscopic ultrasonography and narrow-band imaging system with magnifying endoscopy was extremely useful to evaluate the superficial esophageal cancer with leiomyoma, which lead to the appropriate treatment, ESD.