Results of surgical intervention for p-stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe

OBJECTIVES: Non-small cell lung cancer with mediastinal lymph node involvement is a heterogeneous entity different from single mediastinal lymph node metastasis to multiple nodes or extranodal disease. The objective of this study was to identify the subpopulation of patients with N2 disease who can benefit from surgical intervention. METHODS: We reviewed 219 consecutive patients with N2 non-small cell lung cancer treated with a thoracotomy between November 1980 and June 2002 and retrospectively analyzed 154 of those who had p-stage IIIA disease and underwent a complete resection. Age, sex, side (right or left), histology, location (upper or middle-lower lobe), tumor size, c-N factor, and N2 level (single or multiple) were used as prognostic variables. RESULTS: The 3- and 5-year survivals were 45.3% and 28.1%, respectively, in patients with p-stage IIIA (N2) disease. Survival for those with single N2 non-small cell lung cancer was significantly better than in those with multiple N2 disease (P =.0001), and patients with a tumor in the upper lobe showed a significantly longer survival than those with middle-lower lobe involvement (P =.0467). The 3- and 5-year survivals for patients with single N2 disease with a primary tumor in the upper lobe were 74.9% and 53.5%, respectively. A multivariate analysis with Cox regression identified 5 predictors of better prognosis: younger age, squamous cell carcinoma as determined by histology, primary tumor location in the upper lobe, c-N0 status, and a single station of mediastinal node metastasis. CONCLUSION: Our results suggest that of the heterogeneity of N2 diseases, patients with single N2 disease with non-small cell lung cancer in the upper lobe are good candidates for pulmonary resection.     

ⅢA-N2期非小细胞肺癌纵隔淋巴结跳跃式转移的临床和预后分析

目的 探讨ⅢA-N2期非小细胞肺癌(NSCLC)纵隔淋巴结跳跃式转移的临床病理特征和分布规律,并分析跳跃转移对生存期的影响.方法 回顾性分析2000年1月至2004年12月478例行手术并经病理证实的ⅢA-N2期非小细胞肺癌患者的临床资料,分为跳跃转移组和非跳跃转移组,分析两组的临床病理特征,N2分布情况以及对生存期的影响并进行统计学分析.结果 全组N2跳跃转移的发生率为40.6%,与性别和吸烟情况有关(χ2=5.340,p=0.021和χ2=7.143,P=0.008),且鳞状细胞癌易发生跳跃转移(χ2=7.602,P=0.022),上叶较下叶更易发生跳跃转移(χ2=5.097,P=0.024),上纵隔淋巴结区为跳跃转移好发区(χ2=7.046,P=0.030).跳跃转移时,右上肺癌易转移至2、3、4组淋巴结,右中和右下肺癌则易转移至7组淋巴结;左上肺癌时,71.7%的转移N2淋巴结位于5、6组淋巴结,而左下肺癌则较易转移至7、9组淋巴结.跳跃转移组5年生存率优于非跳跃转移组(22.1%比13.6%,P=0.001),生存分析显示,跳跃转移是影响N2患者生存期的独立因素.结论 在N2期NSCLC中,跳跃转移易发生于肺上叶以及上纵隔区.跳跃转移可作为ⅢA-N2期NSCLC的一个亚群,具有更高的生存率.     

Mediastinal lymph node infiltration in non-small cell lung cancer and its role in curative surgery.

Despite the importance of lymph node infiltration for the classification and prognosis of non-small cell lung cancer (NSCLC), there are no accepted standards for quality of mediastinal lymphadenectomy. In 270 consecutive patients undergoing potentially curative surgery for NSCLC, including complete ipsilateral lymph node dissection, we investigated the possibility of a correlation between tumour location and lymph node infiltration. The tumours were classified as UICC stage I (n = 115), II (n = 42) or IIIa (n = 113). Patients with N2-disease (n = 68) showed up to 81% skip metastasis. Because of the observed dissemination of lymph node metastasis, tumour location could not predict nodal infiltration. The variability of nodal involvement and the frequent occurrence of skip metastasis thus make complete ipsilateral lymphadenectomy mandatory for curative management of NSCLC.     

肺癌跳跃式纵隔淋巴结转移的临床病理探讨

目的　探索肺癌跳跃式纵隔淋巴结转移的病理特点 ,为合理施行淋巴结清除术提供可靠的理论依据。方法　 1992年 10月至 1998年 6月 ,为 398例肺癌病人施行了根治性肺切除、规范淋巴结清除术 ,对其中 4 7例 ( 2 9 4 % )跳跃式纵隔转移淋巴结病例进行病理学研究。结果　各型或各叶肺癌中 ,跳跃式转移淋巴结分布最密集的部位依次是第 7、4、3、5组淋巴结 ,分别占 2 9 8%、2 4 5 %、14 9%与10 6 % ;就鳞癌与腺癌而言 ,肿瘤长径在 1cm以内者均无跳跃式淋巴结转移 ,跳跃式淋巴结转移率随长径增加而增加 ;低分化腺癌淋巴结转移率明显高于高分化者 (P <0 0 1) ;发生跳跃式淋巴结转移的肿瘤平均长径鳞癌与腺癌分别为 15 3mm与 9 1mm。结论　对肺癌淋巴结的廓清 ,切勿仅凭手触摸或靠肉眼观察淋巴结大小而盲目判定其是否转移或清除。除T1 中肿瘤长径 <1cm的鳞癌外 ,淋巴结的规范清除应重视其跳跃性 ,原则上必须包括同侧胸腔的肺门及上、下纵隔各组淋巴结 ,尤其要重视跳跃式淋巴结转移分布较密集区域 ,即右侧的第 3、4、7组与左侧的第 4、5、7组淋巴结     

Verteilungsmuster und Befall regionärer Lymphknoten bei nicht-kleinzelligem Bronchialcarcinom

Despite the important role of lymph node infiltration for the classification and prognosis of non-small-cell lung cancer (NSCLC), no standards exist to evaluate the quality of mediastinal lymphadenectomy. Researches at several centers are not convinced that complete ipsilateral lymphadenectomy is necessary. We investigated 270 consecutive patients undergoing a potential curative operation for NSCLC including complete ipsilateral lymph node dissection in order to ascertain whether or not there is a correlation between tumor localization and lymph node infiltration. Patients were classified into the UICC (1987) stages I (n = 115), II (n = 42), and IIIa (n = 113). In patients with N1-positive lymph nodes (n = 61) we found higher 5-year survival for patients with only intrapulmonary lymph node infiltration (39%) than for patients with hilar infiltration (21%). Patients with N2 disease showed skip metastases in up to 81% of cases. We found that no tumor location predicted the lymph node infiltration. Due to the variability of lymph node infiltration and the frequently occurring skip metastases, complete ipsilateral lymphadenectomy should be the standard for curative operations for NSCLC.     

Skip metastases: analysis of their clinical significance and prognosis in the IIIA stage of non-small cell lung cancer.

OBJECTIVE: To determine the clinical significance of skip metastases (pN2/S) in patients with resected pIIIA/N2 NSCLC. The incidence of pN2/S after mediastinal lymph node dissection (MLD) and sampling (MLS) were compared. METHOD: From 1997 to 2000, 580 lung resections for NSCLC performed at our department. The 151 patients (26.5%) at stage IIIA/N2 (pN2+) were grouped according to their skip metastases status. Group A included the ordinary pN2 (pN2/O) cases (71%) and group B the pN2/S (29%). Age, gender, type of resection, right or left lesion, histology, tumor lobe predilection, MLD or MLS pathologic results, the level and the number of node stations involved and survival were analyzed. RESULTS: In 44 patients (29%) pN2/S disease was present. Statistical analysis revealed significant difference between pN2/O and pN2/S for the following: (1) pN2/S was more common for right-sided lesions (P=0.007); (2) Squamous carcinoma was the main type of pN2/S (P=0.007) and (3) pN2/S was more frequently detected after MLD than after MLS (P=0.001). Although pN2/S involved more often upper mediastinal lymph nodes (Nos. 2, 3) and one station level (pN2/S: 41 vs. pN2/O: 19.6%, P=0.228) was not found statistically significant. pN2/O was more common after right upper lobectomy and pN2/S after right lower lobectomy. The 3-year survival was more favorable for the pN2/S group (A: 24 vs. B: 36%, P=0.07). CONCLUSION: (1) MLD was found to be more reliable for pN2/S detection than MLS. (2) The presence of pN2/S proved to be a less aggressive form of lymphatic spread that should be taken into account in the future. (3) Strong correlation between right lower lobe tumors and pN2/S was demonstrated. (4) Different routes of cancer lymphatic spread between pN2/S and pN2/O are suggested.     

Systemic mediastinal lymph node dissection of right lung cancer: surgical quality control and analysis of mediastinal lymph node metastatic patterns

Standardization of systemic mediastinal lymph node dissection (SMLD) of lung cancer requires further investigation. A consecutive 124 right lung cancer patients were recruited for pulmonary resection plus SMLD. Three mediastinal lymph node compartments, (i) the upper compartment (station 1-4), (ii) the middle compartment (station 7-8) and (iii) the lower compartment (station 9), were en bloc collected to achieve surgical quality control and to analyze mediastinal lymph node metastatic patterns. The number of total harvested lymph nodes, N1 nodes and N2 nodes were 21.9+/-8.7, 9.2+/-4.7 and 12.8+/-6.7, respectively. Tumor location (peripheral or central) (P=0.023) and status of blood vessel invasion (P=0.002) were identified as risk factors for nodal involvement. Right upper lobe (RUL) cancer with N2 disease primarily metastasized to the upper compartment (27.3%) (P=0.001). For right lower lobe (RLL) cancer, lymph node metastasis most commonly detected in the middle compartment (48.8%) (P=0.001). Single mediastinal compartment metastasis occurred in 64.7% (11/17) of adenocarcinomas from RUL and RML, whereas multiple compartments metastasis occurred in all adenocarcinoma cases (12/12) from RLL (P=0.001). SMLD needs to standardize the extent of lymphadenectomy and number of removed lymph nodes for surgical quality control. Simplifying mediastinal lymph node stations to three compartments may benefit surgical excision.     

Lymph node dissection in lung cancer]

The standard surgical treatment for stage I, II, and IIIa non-small cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection. In our series of 214 patients with N2 disease the 5-year survival rate was 23%. Systematic mediastinal lymph node dissection provides further prognostic information on the N factor. Among NSCLC patients with a pathological diagnosis of N2, there are significant differences in the 5-year survival rate based the 3 factors of clinical N factor, N1 station metastasis, and N2 station metastasis.     

Significant Prognostic Factors for Completely Resected pN2 Non-small Cell Lung Cancer without Neoadjuvant Therapy

Purpose: To identify prognostic factors for pathologic N2 (pN2) non-small cell lung cancer (NSCLC) treated by surgical resection.Methods: Between 1990 and 2009, 287 patients with pN2 NSCLC underwent curative resection at the Cancer Institute Hospital without preoperative treatment.Results: The 5-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) rates were 46%, 55% and 24%, respectively. The median follow-up time was 80 months. Multivariate analysis identified four independent predictors for poor OS: multiple-zone mediastinal lymph node metastasis (hazard ratio [HR], 1.616; p = 0.003); ipsilateral intrapulmonary metastasis (HR, 1.042; p = 0.002); tumor size >30 mm (HR, 1.013; p = 0.002); and clinical stage N1 or N2 (HR, 1.051; p = 0.030). Multivariate analysis identified three independent predictors for poor RFS: multiple-zone mediastinal lymph node metastasis (HR, 1.457; p = 0.011); ipsilateral intrapulmonary metastasis (HR, 1.040; p = 0.002); and tumor size >30 mm (HR, 1.008; p = 0.032).Conclusion: Multiple-zone mediastinal lymph node metastasis, ipsilateral intrapulmonary metastasis, and tumor size >30 mm were common independent prognostic factors of OS, CSS, and RFS in pN2 NSCLC.     

非小细胞肺癌淋巴结清扫方式临床研究

目的 比较非小细胞肺癌不同纵隔淋巴结清扫方式间的差异,为规范化开展肺癌淋巴结清扫临床研究提供依据.方法 在202例Ⅰa-Ⅲa期肺癌中进行前瞻性临床对照试验,比较常规清扫(RMLD)和全纵隔骨骼化清扫(SCLD)两种术式,分析手术经过和术后病理分期情况.结果 RMLD 107例,SCLD 95例.两组术前一般情况、临床分期及肺切除方式无明显差异,SCLD组平均扫除淋巴结组数显著高于RMLD组(8.9组对6.2组,P＜0.001),术后总体并发症(14.7%对14.0%,P=0.884)和病死率(2.1%对1.9%,P=0.904)无差异,但SCLD组分别有3例(3.2%)右侧乳糜胸和左侧喉返神经损伤发生.术后病理证实两组组织学类型及分期无明显差异,RNLD和SCLD组pN2分别占27.1%和24.2%(P=0.888),跳跃性纵隔转移率(RMLD 9.3%对SCLD 7.4%,P=0.613)以及纵隔多组转移率(RMLD 15.0%对SCLD 16.8%,P=0.714)亦无明显差异.分析纵隔各组淋巴结转移率发现上叶肺癌下纵隔转移率＜5%,而中、下叶肺癌上、下纵隔转移率均＞10%;cT1病例以及低度恶性肿瘤无一发生纵隔转移.结论 对非小细胞肺癌行常规纵隔清扫可达到与全纵隔骨骼化清扫同样的分期效果,后者手术风险并不高于常规清扫,但应避免右侧乳糜胸和左侧喉返神经损伤的发生;上叶肺癌仅需扫除上纵隔淋巴结而无需常规清扫下纵隔;早早期肺癌以及低度恶性肿瘤没有必要进行常规纵隔清扫.     

Border between N1 and N2 stations in lung carcinoma: lessons from lymph node metastatic patterns of lower lobe tumors

OBJECTIVE: Distinction of lymph node stations is one of the most crucial topics still not entirely resolved by many lung cancer surgeons. The nodes around the junction of the hilum and mediastinum are key points at issue. We examined the spread pattern of lymph node metastases, investigated the prognosis according to the level of the involved nodes, and conclusively analyzed the border between N1 and N2 stations. METHODS: We reviewed the records of 604 consecutive patients who underwent complete resection for non-small cell lung carcinoma of the lower lobe. RESULTS: There were 390 patients (64.6%) with N0 disease, 127 (21.0%) with N1, and 87 (14.4%) with N2. Whereas 11.3% of patients with right N2 disease had skip metastases limited to the subcarinal nodes, 32.6% of patients with left N2 disease had skip metastases, of which 64.2% had involvement of N2 station nodes, except the subcarinal ones. The overall 5-year survivals of patients with N0, N1, and N2 disease were 71.0%, 50.8%, and 16.7%, respectively (N0 vs N1 P = .0001, N1 vs N2, P < .0001). Although there were no significant differences in survival according to the side of the tumor among patients with N0 or N1 disease, patients with a left N2 tumor had a worse prognosis than those with a right N2 tumor (P = .0387). The overall 5-year survivals of patients with N0, intralobar N1, hilar N1, lower mediastinal N2, and upper mediastinal N2 disease were 71.0%, 60.1%, 38.8%, 24.8%, and 0%, respectively. Significant differences were observed between intralobar N1 and hilar N1 disease ( P = .0489), hilar N1 and lower mediastinal N2 disease (P = .0158), and lower and upper mediastinal N2 disease (P = .0446). Also, the 5-year survivals of patients with involvement up to station 11, up to station 10, and up to station 7 were 41.4%, 37.9% and 37.7%, respectively (difference not significant). CONCLUSIONS: N1 and N2 diseases appeared as a combination of subgroups: intralobar N1 disease, hilar N1 disease, lower mediastinal N2 disease, and upper mediastinal N2 disease. Interestingly, the survivals of patients with involvement up to interlobar nodes (station 11), main bronchus nodes (station 10), and subcarinal nodes (station 7) were identical. These data constitute the basis for a larger investigation to develop a lymph node map in lung cancer.     

Metastases to the mediastinal lymph nodes in a series of two-hundred-consecutive operations for primary lung cancer

We examined the characteristics of lymph nodes metastases to the mediastinum on cases of two-hundred-consecutive operations for primary lung cancer from October of 1987 to May of 1990, comparing the intraoperative macroscopic diagnosis of lymph nodes to the histologic reports. The purpose of this study is to know how important the mediastinal dissection is and how many cases resulting in vain are hidden behind it. Thirty three cases were excluded because of limited operation or other reasons. Remaining a hundred sixty seven cases were divided on the basis of lymph node metastasis into following 5 groups. Forty three cases (26%), of which N2 disease was correctly diagnosed macroscopically, true positive for N2, were classified into group A. Sixteen cases (10%), group B, in which we failed to detect N2 positive from dissected specimens during operation, was considered to be false negative for N2, thirty one cases of N1 disease (18%), were classified into group C and thirteen cases of N0 disease (8%) into group D with false positive of lymph node prediction for metastasis. Sixty four cases of N0 disease (40%) were classified into group E, true negative for N0 prediction, which were correctly detected by macroscopic appearance of lymph nodes. Nine cases had only mediastinal lymph nodes metastases without hilar and lobar lymph node. Almost of them with this skip phenomenon occurred in the patients with adenocarcinoma in the upper lobe. It could be concluded that we dissected the mediastinal lymph nodes in this series, salvaging one N2 disease of ten cases and wasting our efforts four cases of those cases, in vain.     

ⅢA-N2期非小细胞肺癌切除术后影响预后的因素分析

目的 分析ⅢA-N2期非小细胞肺癌患者的临床情况和影响预后的相关因素,探讨手术及辅助治疗对预后的影响.方法 回顾性分析2000年1月至2005年12月经手术治疗的657例ⅢA-N2期非小细胞肺癌患者的临床资料,应用Kaplan-Meier法进行生存分析.单因素分析各变量与预后的关系采用Log-rank检验,多因素分析采用Cox模型.结果 术后全组患者的l、3和5年累计生存率分别为64.4%、26.0%和17.9%,中位生存期18个月.单因素分析中,影响生存期的不利因素为:肿瘤最大径>3 cm,高T分期,N2淋巴结无跳跃转移,纵隔淋巴结阳性数>4个,隆突下淋巴结阳性,治疗方式(单纯手术预后差,患者术后联合放化疗优于术后单纯化疗),术后未放疗、化疗,化疗周期小于4个.多因素分析显示,肿瘤直径(P=0.001),隆突下淋巴结阳性(P=0.019),纵隔淋巴结转移个数(P=0.006),术后化疗周期(P=0.007),术后放疗(P=0.055)和术后放化疗(P=0.026)对预后有明显影响.结论 ⅢA-N2期非小细胞肺癌患者5年生存率低,肿瘤直径、隆突下淋巴结阳性、纵隔淋巴结转移个数、术后化疗周期、术后联合放化疗是影响预后的独立因素.术后单站和多站纵隔淋巴结转移的预后相似,影响预后的主要是纵隔淋巴结的阳性个数,术后联合放化疗优于术后单纯化疗.     

Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography.

OBJECTIVE: We sought to assess the incidence, pattern and predictors of occult mediastinal lymph node involvement (N2) in non-small cell lung cancer patients with negative mediastinal uptake of 2-deoxy-2-[(18)F]-fluoro-d-glucose ((18)FDG) on integrated positron emission tomography-computerised tomography (PET-CT). METHODS: All patients who underwent surgical resection in our unit over a 30-month period were reviewed (n=215). All patients had preoperative PET-CT prior to lung resection as an adjunct to a dedicated chest CT. Diabetic patients, patients who received neoadjuvant chemotherapy and those with positive mediastinal nodes on PET-CT (N2/N3) were excluded from this study. The population of interest was 153 non-small cell cancer patients (NSCLC), all of which had no FDG uptake in the mediastinum. No preoperative mediastinoscopy was carried out in this group and all underwent curative intent surgical resection. The pathological results were retrospectively reviewed and correlated with CT and integrated PET-CT findings. RESULTS: The incidence of occult N2 disease in NSCLC patients with negative mediastinal uptake of (18)FDG on PET-CT was 16% (25 of 153). The highest incidence of occult N2 involvement was in American thoracic society (ATS) 7 (16 of 25 patients, 64%) followed by ATS 4 (seven patients of 25, 28%). In univariate analysis, the following were significant predictors of occult N2 disease: centrally located tumours (P=0.049), right upper lobe tumours (P=0.04), enlarged lymph nodes (>1cm) on CT (P=0.048) and PET positive uptake in N1 nodes (P=0.006). In multivariate analysis, the following were independent predictors of occult N2 disease: centrally located tumours, right upper lobe tumours and PET positive uptake in N1 nodes (P<0.05). CONCLUSIONS: In NSCLC patients who are clinically staged as N2/N3 negative in the mediastinum by integrated PET-CT, 16% will have occult N2 disease following resection. Patients with the following: centrally located tumours, right upper lobe tumours and positive N1 nodes on PET should have preoperative cervical mediastinoscopy to rule out N2 nodal involvement, especially in ATS stations 7 and 4 as the incidence of occult nodal metastasis in these nodes is high. This study has potential implications in decision-making and planning best treatment approach.     

非小细胞肺癌跳跃性纵隔淋巴结转移及其廓清的临床探讨

目的：探讨非小细胞肺癌（NSCLC）跳跃性纵隔淋巴结转移（跳跃性N2）的特点及转移方式，为制定合理的纵隔淋巴结廓清范围提供依据。方法：回顾性总结121例（广州军区总医院1996－1999年101例和北京大学深圳医院1999－2000年20例）经系统性淋巴结廓清后病理证实为N2的NSCLC患者的临床资料，将跳跃性N2与非跳跃性N2的数据进行比较。结果：发现跳跃性N2 23例（19．0％，其中腺癌18例（78．3％）。跳跃性N2患者中平均每例纵隔淋巴结转移组为1．1组，明显低于非跳跃性N2的3．1组。肺上叶肿瘤跳跃性N2多位于第4或第5组淋巴结，肺下叶肿瘤跳跃性N2多位于第7和第8组淋巴结。结论：跳跃性N2是NSCLC纵隔淋巴结转移的一个独特亚群。在行肺上叶癌根治术时，应常规清扫第4和第5组淋巴结；在行肺下叶癌根治术时，应常规清扫第7和第8组淋巴结。     

直径≤3cm的周围型非小细胞肺癌纵隔淋巴结转移规律的初步研究

目的探讨直径≤3cm的周围型非小细胞肺癌(non-small cell lung cancer,NSCLC)纵隔淋巴结转移的情况,分析早期周围型NSCLC纵隔淋巴结转移的规律。方法 2000年1月1日～2008年12月31日治疗直径≤3cm的周围型NSCLC161例,男89例,女72例,年龄(63.4±10.7)岁,行肺叶切除或肺局限性切除加系统性纵隔淋巴结清扫术,分析其临床特征、病理特点及纵隔淋巴结转移规律。结果全组手术顺利,无死亡及严重并发症发生。肺叶切除153例,肺楔形切除7例,肺段切除1例。全组共清扫淋巴结2456枚,平均每例4.5±1.6组、13.1±7.3枚。术后病理:腺癌99例,鳞癌30例,肺泡细胞癌19例,其他类型肺癌13例。术后TNM分期:ⅠA期50例,ⅠB期62例,ⅡA期6例,ⅡB期10例,ⅢA期33例。N1组淋巴结转移率为23.6%(38/161),N2组转移率为20.5%(33/161),其中隆突下淋巴结转移率为8.1%(13/161),跳跃式纵隔转移率为6.8%(11/161),全组未发现下纵隔淋巴结转移。肺泡细胞癌及直径≤2cm的鳞癌、直径≤1cm的腺癌均无pN2转移。上肺癌发生pN2转移时上纵隔100%(19/19)受累,其中21.1%(4/19)同时伴有隆突下淋巴结转移;下肺癌则除主要转移至隆突下外(64.3%,9/14),还常直接单独转移至上纵隔(35.7%,5/14)。转移的纵隔淋巴结左肺癌主要分布在第5、6、7组,右肺癌主要分布在第3、4、7组。结论对于直径≤3cm的周围型NSCLC,肿瘤直径越大,其纵隔淋巴结转移率越高,肺泡细胞癌、直径≤2cm的鳞癌和≤1cm的腺癌其纵隔淋巴结转移率相对较低;上肺癌主要转移在上纵隔,下肺癌则隆突下及上纵隔均可转移;第5、6、7组淋巴结是左肺癌主要转移的位置,第3、4、7组是右肺癌主要转移的位置,术中应重点清扫。     

Current status of induction treatment for N2-Stage III non-small cell lung cancer

Locally advanced non-small cell lung cancer (NSCLC), particularly clinical Stage IIIA NSCLC with mediastinal lymph node metastasis, is known to be quite heterogeneous, comprising approximately one-fourth of cases of NSCLC. In this subset, patients with a minor tumor load in the mediastinal lymph nodes, such as microscopically or pathologically proven N2 in the resected specimens, are treated with surgery followed by adjuvant chemotherapy. Meanwhile, the current standard of care for patients with bulky or infiltrative N2 disease is concurrent chemoradiotherapy. The potential role of surgery in multi-modality treatment for clinical N2-Stage IIIA remains controversial. Several prospective clinical trials of this subset have been conducted; however, the heterogeneity of the N2 status and differences in chemotherapy regimens and/or radiation modalities between clinical trials make the results difficult to compare. No optimal chemotherapy regimen has been established to control possible micrometastasis, and radiotherapy is often used to achieve maximum local disease control and minimize post-surgical complications. This review summarizes the findings of prospective clinical trials that assessed the role of surgery in treating clinical N2-Stage IIIA patients within the last two decades and discusses the present status of induction treatment followed by surgery for clinical N2-Stage IIIA NSCLC.     

Skip metastases in thyroid cancer leaping the central lymph node compartment

HYPOTHESIS: Discontinuous nodal metastasis, or skip metastasis, in thyroid cancer may display clinicopathologic features different from those seen in continuous nodal metastasis and thus may have a different prognosis. DESIGN: Retrospective analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS: Two hundred fifteen consecutive patients who underwent systematic central lymph node dissection for papillary, follicular, or medullary thyroid cancer and who on histopathologic analysis exhibited nodal metastases in at least 1 lateral or mediastinal lymph node compartment. MAIN OUTCOME MEASURES: Various clinicopathologic variables that were stratified for tumor entity and type of nodal metastasis (discontinuous vs continuous). RESULTS: Skip metastases (negative central and positive lateral or mediastinal compartments) were found in 13 (19.7%) of 66 papillary, 0 of 8 follicular, and 30 (21.3%) of 141 medullary thyroid cancers. After adjustment for multiple testing, skip metastasis was only associated with significantly fewer positive lymph nodes: 3.7 vs 12.9 nodes (r = -0.43, P<.001) in papillary thyroid cancer and 6.0 vs 17.1 nodes (r = -0.40, P<.001) in medullary thyroid cancer. No other significant correlation was identified with any other clinicopathologic variable. CONCLUSIONS: Skip metastasis is an epiphenomenon of low-intensity nodal metastasis in thyroid cancer and entails a moderate risk of local recurrence. Consequently, clearing the central lymph node compartment should be considered when lateral or mediastinal lymph node compartments are involved.     

The spread of metastatic lymph nodes to the mediastinum from left upper lobe cancer: results of superior mediastinal nodal dissection through a median sternotomy.

BACKGROUND: This study endeavored to clarify the location, frequency, and prognostic value of metastatic lymph nodes in the mediastinum among patients with left upper lung cancer who underwent complete dissection of the superior mediastinal lymph node through a median sternotomy. METHODS: Forty-four patients with left upper lobe cancer underwent extended radical mediastinal nodal dissection (ERD), all of whom were analyzed in this retrospective study. The group comprised 12 females and 32 males, with ages ranging from 28 to 70 years (median age, 60 years). Mediastinal nodal status was assessed according to the systems of Mountain/Dresler 7 and Naruke 8. The clinicopathological records of each patient were examined for prognostic factors, including age, sex, histology, tumor size, c-N number, preoperative serum CEA level, metastatic stations and distribution of metastatic nodes according to Naruke's system 8. The superior mediastinal lymph nodes which cannot be dissected through a left thoracotomy (bilateral #1 and #2, #3, right #3a, and right #4 according to Naruke's map 8 were defined as extra-superior mediastinal nodes for left lung cancer (ESMD). RESULTS: Fourteen patients had one or more metastases to mediastinal lymph nodes, among whom the most common metastatic station was the aortic nodes: 71.4% had metastasis to #5 or #6 (57.1% to #5 and 50% to #6). The next most common metastatic station was the left tracheobronchial nodes (42.8%). Metastasis to the ESMD occurred in 7 of the 44 study subjects (16%), representing a 50% rate of occurrence (7/14) among those with mediastinal nodal involvement. Univariate analysis found that CN factor and aortic nodal involvement (#5, #6) were significant predictive factors for ESMD metastasis. Multivariate analysis determined that only aortic nodal involvement was significant (p = 0.008). Furthermore, ESMD metastasis was rare (5.8%) in the absence of aortic node metastasis. The overall survival rate at 5 years was 50% among the patients without ESMD metastasis. However, the survival rate was 32% at 3 years and 0% at 5 years among the seven patients with ESMD metastasis. CONCLUSIONS: The aortic lymph node is the most common site of metastasis from left upper lobe cancer. Multivariate analysis demonstrated that aortic nodal involvement was a significant predictive factor for ESMD metastasis. Based upon the rates of metastasis and the post-operative prognosis in our study patients, dissection of aortic nodes and left tracheobronchial nodes may be important for patients with left upper lobe cancer. Whether ESMD dissection has a beneficial effect on prognosis remains controversial.     

选择性颈胸腹三野淋巴结清扫治疗胸段食管鳞癌

目的 研究胸段食管鳞癌的淋巴结转移规律，探讨合适的淋巴结清扫范围。方法 87例接受食管次全切除术的胸段食管鳞癌患者，根据术前食管腔内超声和颈部超声检查结果，选择性进行胸腹二野或颈胸腹三野淋巴结清扫。结果 超声发现颈部淋巴结肿大并行三野清扫35例（40．2％，三野清扫组），其中原发肿瘤位于胸上段食管者的比例（16／24例，66．7％）显著高于中、下段肿瘤者（19／63例，30．2％）（P=0．002）。三野清扫术扫除淋巴结13．7组／例，显著多于二野清扫组（52例，59．8％）的10．5组／例（P〈0．001）。术后病理检测三野清扫组转移淋巴结1．5组／例，也显著多于二野清扫组的0．8组／例（P〈0．01）。颈淋巴结转移（pM1-LN）17例（占全组19．5％，占三野清扫组48．6％），有区域淋巴结转移者的颈淋巴结转移比例（15／48例，31．3％）显著高于无区域淋巴结转移者（2／39例，5．1％）（P〈0．01）。上、中、下纵隔及上腹部的淋巴结转移率分别为25．3％、23．O％、5．7％和24．1％，颈淋巴结转移与上纵隔（P〈0．01）及中纵隔（P〈0．01）淋巴结转移显著相关，但与下纵隔及上腹部淋巴结转移无关。三野清扫组术后并发症发生率（60．0％）显著高于二野清扫组（34．6％，P=0．020）。喉返神经损伤发生率两组差异无统计学意义（P〉0．05）；但喉返神经损伤者吻合口瘘发生率（7／13例，53．8％）显著高于无喉返神经损伤者（10／74例，13．5％，P=0．001）。术后死亡率两组差异无统计学意义（P〉0．05）。结论 应对肿瘤位于胸上段食管、或上纵隔及中纵隔淋巴结已发生转移的食管癌患者在超声指导下进行选择性颈胸腹三野淋巴结清扫术，以降低手术风险、提高手术根治效果。