Lateral lymph node dissection in rectal cancer: State of the art review

Half of the local regional recurrences from rectal cancer are nowadays located in the lateral compartments, most likely due to lateral lymph node (LLN) metastases. There is evidence that a lateral lymph node dissection (LLND) can lower the lateral local recurrence rate. An LLND without neoadjuvant (chemo)radiotherapy in patients with or without suspected LLN metastases has been the standard of care in the East, while Western surgeons believed LLN metastases to be cured by neoadjuvant treatment and total mesorectal excision (TME) only. An LLND in patients without enlarged LLNs might result in overtreatment with low rates of pathological LLNs, but in patients with enlarged LLNs who are treated with (C)RT and TME only, the risk of a lateral local recurrence significantly increases to 20%. Certain Eastern and Western centers are increasingly performing a selective LLND after neoadjuvant treatment in the presence of suspicious LLNs due to new scientific insights, but (inter)national consensus on the indication and surgical approach of LLND is lacking. An LLND is an anatomically challenging procedure with intraoperative risks such as bleeding and postoperative morbidity. It is therefore essential to carefully select the patients who will benefit from this procedure and where possible to perform the LLND in a minimally invasive manner to limit these risks. This review gives an overview of the current evidence of the assessment of LLNs, the indications for LLND, the surgical technique, pitfalls in performing this procedure and the future studies are discussed, aiming to contribute to more (inter)national consensus.     

经“Ｈｏｌｙｐｌａｎｅ”间隙保留盆腔自主神经侧方淋巴结清扫术的临床观察

目的　探讨经“Ｈｏｌｙｐｌａｎｅ”间隙保留盆腔自主神经（ＨＰＡＮＰ）侧方淋巴结清扫术在男性直肠癌低位保肛术中的临床应用价值。方法　比较传统手术与ＨＰＡＮＰ侧方淋巴结清扫术在男性直肠癌低位保肛术中的应用情况,对各组患者的排尿功能、性功能、局部复发率和３年生存率等指标进行分析、评价。结果　ＨＰＡＮＰ侧方淋巴结清扫术组肿瘤下缘距肛门距离较传统手术组明显缩短（Ｐ＜０.０５）;术后排尿障碍、勃起障碍、射精障碍的发生率均低于传统手术组,组间比较差异有统计学意义（Ｐ＜０.０５）;ＨＰＡＮＰ手术术式分型与排尿障碍、勃起障碍、射精障碍分级之间呈正相关（Ｐ＜０.０５）;两组３年生存率无明显差异;局部复发率ＨＰＡＮＰ组明显低于传统手术组（Ｐ＜０.０５）。结论　ＨＰＡＮＰ侧方淋巴结清扫术对降低局部复发率、预防术后排尿障碍、勃起障碍、射精障碍等有较好的临床价值。     

低位直肠癌选择性侧方淋巴结清扫研究进展

盆腔侧方淋巴结(Lateral pelvic lymph node,LPLN)是低位直肠癌患者常见的局部转移部位,同时也是术后局部复发的主要部位,然而目前对于LPLN转移的治疗方案仍没有明确的定论.同时LPLN的转移应被看作是局部而不是全身,新辅助放化疗(Chemoradiotherapy,CRT)并不能替代手术清扫,...     

Controversy about treatment of colorectal cancer in view of surgeon--lymph node dissection for colorectal surgery (lateral lymph node dissection and TME)

Lateral lymph node dissection is technique for reducing local recurrence rate after resection of rectal cancer. In this study, we will report a decade experience for lateral lymph node dissection of rectal cancer in 491 cases. Lateral lymph node metastases occurred in 15.4% of rectal cancer which was below peritoneal reflection and through muscularis propria into non-peritoneal. It is a problem that it has never been well designed study of lateral lymph node dissection for rectal cancer. On the other hand, TME has also contributed reducing local recurrence rate. But, distant margin for resection of rectal cancer is controversial.     

对Ⅲ期低位直肠癌行择区扩大淋巴结清扫的临床意义

背景与目的：目前对于Ⅲ期低位直肠癌的淋巴结清扫范围存在争议：日本学者多主张行择区扩大清扫双侧髂总、髂内、髂外和闭孔淋巴结脂肪组织;欧美学者则多主张行全直肠系膜切除术,辅以新辅助治疗。本研究旨在探讨对Ⅲ期低位直肠癌行择区扩大淋巴结清扫的临床意义。方法：对31例Ⅲ期低位直肠癌的病例(术前影像学分期,术后经病理证实)行择区扩大淋巴结清扫,即顺序清扫双侧髂总、髂内、髂外和闭孔淋巴结脂肪组织,尽量保留盆腔自主神经,除非神经受到肿瘤浸润,并与35例行传统根治术的低位直肠癌的病例进行比较。结果：行择区扩大淋巴结清扫组内有5例侧方淋巴结阳性(低分化腺癌4例、黏液细胞癌1例,较高、中分化腺癌有明显差异)。行择区扩大淋巴结清扫组在性功能障碍、排尿困难发生率及手术时间上与行传统根治术组差异有统计学意义(P＜0.05),行择区扩大淋巴结清扫组在吻合口瘘和手术失血量上与行传统根治术组差异无统计学意义(P＞0.05),但择区扩大淋巴结清扫组在盆腔复发率及5年生存率上优于传统根治术组。结论：对Ⅲ期低位直肠癌行择区扩大淋巴结清扫对降低盆腔复发、提高生存率有临床意义。     

Predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis (clinical stage II/III): The analysis of data from the clinical trial (JCOG0212)

BackgroundMesorectal excision (ME) is the standard surgical procedure for lower rectal cancer. However, in Japan, total or tumor-specific ME with lateral pelvic lymph node dissection (LLND) is the standard surgical procedure for patients with clinical stages II or III lower rectal cancer, because lateral pelvic lymph node metastasis occasionally occurs in these patients. The aim of study was to elucidate the predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis.MethodsData form the clinical trial (JCOG0212) was analyzed. The JCOG0212 was a randomized controlled trial to confirm the non-inferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection for clinical stage II/III patients who don't have clinical lateral pelvic lymph node metastasis in terms of relapse free survival. This study was conducted at a multitude of institution33 major hospitals in Japan. Among the 351 patients who underwent lateral lymph node dissection in the JCOG0212 study, 328 patients were included in this study. Associations between pathological lateral pelvic lymph node metastasis and preoperative and postoperative factors were investigated. The preoperative factors were age, sex, clinical stage, tumor location, distance from anal verge, tumor size, and short-axis diameter of lateral pelvic lymph node on computed tomography and the postoperative factors were pathological T, pathological N, and histological grade.ResultsAmong the 328 patients, 24 (7.3%) had pathological lateral pelvic lymph node metastasis. In multivariable analysis of the preoperative factors, patient age (p = 0.067), tumor location (p = 0.025), and short-axis diameter of lateral pelvic lymph node (p = 0.002) were significantly associated with pathological lateral pelvic lymph node metastasis.ConclusionsPatient age, tumor location, and short-axis diameter of lateral pelvic lymph node were predictive factors of pathological lateral pelvic lymph node metastasis.     

Lateral lymph node dissection with radical surgery versus single radical surgery for rectal cancer: a meta-analysis

Objectives: To assess the value of lateral lymph node dissection( LLND) in the radical surgery of rectal cancer. Methods: The published Chinese and English literature was retrieved. A total of 15 papers fitted the selection criteria, including 4,858 patients. Among them 2,401 were in the LLND group and 2,457 in the non-LLND (NLLND) group. Evaluation parameters included 5-year survival rate recurrence rate, peri-operative outcomes, postoperative urinary and sexual functions. Results: The operating time was significantly shorter in the NLLND group than that in the LLND group (weighted mean difference (WMD)=109 min, 95 confidence interval(CI):90-129, P <0.001). Intra-operative blood loss was greater in the LLND group, but the difference was not significant (WMD=429 mL, 95 CI:325-854, P = 0.05).The frequency of peri-operative morbidity(OR, 1.57 95 CI:1.06-2.33, P = 0.02) was also significantly higher in the LLND group. There were no significant differences in 5-year survival rateand recurrence rate between the two groups. Data from individual studies(three)showed that the frequency of male urinary dysfunction (OR=5.12, 95CI 2.15-12.19, P=0.0002) and sexual dysfunction (P < 0.05) were greatly lower in the NLLND group. Conclusion: Meta analysis showed that LLND did not have specific advantage in decreasing postoperative recurrence and prolonging survival time. Furthermore it was associated with prolonged operation time, increased blood loss and elevated incidence of peri-operative complications and urinary and sexual dysfunction.     

Systematic review and meta-analysis of long-term oncological outcomes of lateral lymph node dissection for metastatic nodes after neoadjuvant chemoradiotherapy in rectal cancer

BackgroundStandard Western management of rectal cancers with pre-treatment metastatic lateral lymph nodes (LLNs) is neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). In recent years, there is growing interest in performing an additional lateral lymph node dissection (LLND). The aim of this systematic review and meta-analysis was to investigate long-term oncological outcomes of nCRT followed by TME with or without LLND in patients with pre-treatment metastatic LLNs.MethodsPubMed, Ovid MEDLINE, Embase, Cochrane Library and Clinicaltrials.gov were searched to identify comparative studies reporting long-term oncological outcomes in pre-treatment metastatic LLNs of nCRT followed by TME and LLND (LLND+) vs. nCRT followed by TME only (LLND-). Newcastle-Ottawa risk-of-bias scale was used. Outcomes of interest included local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Summary meta-analysis of aggregate outcomes was performed.ResultsSeven studies, including 946 patients, were analysed. One (1/7) study was of good-quality after risk-of-bias analysis. Five-year LR rates after LLND+ were reduced (range 3–15%) compared to LLND- (11–27%; RR = 0.40, 95%CI [0.25–0.62], p < 0.0001). Five-year DFS was not significantly different after LLND+ (range 61–78% vs. 46–79% for LLND-; RR = 0.72, 95%CI [0.51–1.02], p = 0.143), and neither was five-year OS (range 69–91% vs. 72–80%; RR = 0.72, 95%CI [0.45–1.14], p = 0.163).ConclusionIn rectal cancers with pre-treatment metastatic LLNs, nCRT followed by an additional LLND during TME reduces local recurrence risk, but does not impact disease-free or overall survival. Due to the low quality of current data, large prospective studies will be required to further determine the value of LLND.     

T1和T2期直肠癌淋巴结转移特点及预后

目的 探讨T1和T2期直肠癌淋巴结的转移特点及预后。方法 回顾性分析241例T1和T2期直肠癌的淋巴结转移特点,用X^2检验分析其相关因素,并对预后进行单因素及多因素分析。结果T1和T2期直肠癌行Mile＇s术132例,保肛术109例,淋巴结转移率为22．0％（53／241）,X^2。检验显示,肿瘤分化程度与淋巴结转移有关。5年生存率为91．5％。单因素分析显示,肿瘤组织学类型、浸润深度、分化程度、淋巴结转移、放疗与预后相关。多因素分析显示,肿瘤浸润深度为T1和T2期直肠癌患者预后的主要影响因素。结论 T1和T2期直肠癌均可发生淋巴结转移,肿瘤分化与淋巴结转移相关,根治性切除术预后较好,应作为首选的治疗方法。     

A case of lateral lymph node metastasis of submucosal rectal cancer

We report a case of lateral lymph node metastasis of submucosal rectal cancer. A 54-year-old man was pointed out with stool occult blood reaction positive. Screening colonoscopy revealed an 18 mm 0-Is rectal cancer in Rb 6 cm from anal verge. Endoscopic mucosal resection (EMR) was performed. Tumor appeared to be well treated, but pathological findings demonstrated the tumor invasion into submucosally (1,300 μm) with lymphovascular invasion ie ly (+) and v (+). Laparoscopic low anterior resection was then performed and no metastasis of lymph nodes (pSM, N0/stage I) was found. But he suddenly had an elevation of CEA (4 ng/mL to 26 ng/mL) after 14 months and following MRI and PET-CT revealed a recurrence in a right lateral lymph node (#283). Chemoradiation therapy (CRT) with CPT-11, UFT and LV was performed. After CRT, lateral lymph nodes and para aortic lymph nodes dissection were performed. Despite of the chemotherapy, he died after 13 months from a recurrence of lateral lymph node metastasis.     

Incidence and prognostic influence of lymph node micrometastases in rectal cancer.

AIMS: The aim of this study was to determine the rate of lymph node micrometastases and evaluate their prognostic significance in rectal cancer. METHODS: Patients with either Dukes A or B rectal carcinoma who had undergone curative resection by either low anterior resection or abdominal perineal resection between 1991 and 2000 were selected from a prospectively collated database. None of the patients had metastasis at the time of surgery and none received adjuvant or neoadjuvant therapy. A single section from each lymph node was stained with haematoxylin and eosin (H+E) and with CAM 5.2 by immunohistochemistry. Statistical analyses were performed with Chi-square test. RESULTS: A total of 774 lymph nodes with a median of 14 lymph nodes per patient were examined, from a cohort of 56 patients with a median age of 66 years. In the 56 patients in whom lymph node metastases were not detected by haematoxylin-eosin staining, cytokeratin staining was positive in 15 lymph nodes from 10 patients. Nine patients had disease recurrence at a median follow-up of 98 months. The presence of lymph node micrometastases by immunohistochemistry did not predict either disease-free (p=0.44) or overall survival (p=0.63). CONCLUSION: Immunohistochemical staining detects micrometastases in rectal cancer which are not observed with H+E staining. However, no significant relationship was observed between disease relapse and rectal micrometastases detected by immunohistochemistry.     

Extent of lymph node dissection in rectal carcinoma

Basing on 170 specimens of advanced rectal cancers radically resected, metastatic rule and extent of lymph node dissection were studied in order to guide future surgical treatment. In 170 cases, 77 had lymph node metastases. The lymph node metastatic rate was 45.3% and metastatic degree was 8.9% (527/5 912). Metastasis of the rectal cancer, according to the lymphatic anatomy, can be divided into upward, lateral and downward drain. Because the rectal cancer at any site can lead to the upward metastasis, the upward lymph node dissection, up to the base of inferior mesenteric artery (the third line of lymph nodes), must be done in all rectal cases, otherwise, 10% of patients would have residual cancer. In view of the lateral metastasis occurring only in rectal cancers under the peritoneal reflection, for which lateral lymph node dissection is necessary or one eighth of patients would have residual lesion. Generally, no lateral lymph node dissection is needed in cancers above the peritoneal reflection. Pathologic factor influencing the lymphatic metastasis is the form of tumor growth, such as poorly differentiated and mucoid adenocarcinomas aggressively growing deeply and extensively resulting in a higher lymph node metastatic rate, for which lymph node dissection must be performed.     

Pathologic features of superficial esophageal squamous cell carcinoma with lymph node and distal metastasis

BACKGROUND: Endoscopic mucosal resection (EMR) is a less invasive localized treatment for patients with esophageal carcinoma. However, indications for EMR use in cases of superficial esophageal carcinoma are controversial. The authors evaluated histopathologic risk factors for lymph node metastasis and recurrence. METHODS: In the specimens resected, the authors examined depth, the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. RESULTS: The authors found that the superficial area and the attached or infiltrated area reflected the depth of the tumor. However, there was a recurrence of esophageal carcinoma even in m3 cases attached only to the lamina muscularis mucosa. CONCLUSIONS: The authors concluded that ml and m2 esophageal carcinoma had almost no risk of lymph node metastasis and recurrence no matter how extensive the superficial area. In addition, sm2 and sm3 carcinoma have a high frequency of lymph node metastasis and recurrence. M3 and sm1 carcinoma run the risk of lymph node metastasis and recurrence however small the superficial area and the area attached to or infiltrating the lamina muscularis mucosa. Treatment strategies for patients with superficial esophageal carcinoma, including EMR, should take the above findings into account.     

局部治疗在直肠癌盆腔侧方淋巴结转移中的作用北大核心CSCD

盆腔侧方淋巴结(LPLN)转移是直肠癌预后不佳因素, 在低位、T3-T4期、直肠系膜淋巴结阳性情况下更常见, 但无准确预测转移的因素。高分辨率MRI是目前诊断LPLN转移的首选手段, 但阈值选择仍不明确。局部进展期直肠癌的侧方淋巴结转移治疗模式在全球存在分歧, 欧美国家主张放化疗联合直肠全系膜切除术, 而日本推荐直肠全系膜切除术联合LPLN清扫。放疗与手术联合可取得很好的局控, 利用放疗前、后MRI的侧方淋巴结信息, 可筛选出高危患者进行强化治疗, 如放化疗后行LPLN清扫或LPLN区放疗推量。目前各种手段在治疗LPLN转移方面的作用仍缺乏高质量证据, 尚需更多的研究来改善治疗策略。     

A case of small undifferentiated intramucosal gastric cancer with lymph node metastasis

Early gastric cancer (EGC) has a favorable prognosis after surgical gastrectomy. For intramucosal EGC with little risk of lymph node metastasis, endoscopic mucosal resection (EMR) is an accepted treatment method. Herein we document a noteworthy case of small undifferentiated gastric cancer with nodal metastasis. A 60-year-old Japanese woman underwent gastrectomy with D2 lymph node dissection for the treatment of EGC in the lower gastric body. Histological examination revealed that signet-ring cell carcinoma was located in approximately one-third of the superficial portion of the mucosal layer, with a tumor size of 13 mm. No lymphatic invasion, venous invasion, or fibrosis was observed in the submucosal layer. This case had nodal metastasis and was finally diagnosed as stage IB (T1N1M0) according to the Japanese Classification of Gastric Carcinoma (JCGC). The patient is alive without recurrence 6 years after treatment.     

直肠癌侧方淋巴结清扫的研究进展与相关争议

盆腔侧方淋巴结（lateral pelvic lymph node,LPLN）是中低位直肠癌常见的淋巴回流通路,有14%～30%的局部中晚期直肠癌患者同时合并LPLN转移。然而,术前诊断的遗漏和不规范的治疗是导致术后LPLN复发的常见原因,同时也是诊疗中的难点之一。目前,侧方淋巴结清扫术（lateral pelvic lymph node dissection,LPLND）的价值与意义,在国际上尚存争议。近些年来,新辅助放化疗（neoadjuvant chemoradiotherapy,nCRT）与LPLND相互替代的治疗模式趋于融合,逐渐形成了一套精确化、个体化的治疗策略。同时,随着外科器械设备的更新与淋巴结示踪剂技术的不断发展,使得以往制约LPLND的因素逐渐消失,可逐渐在临床推广开展。但针对直肠癌LPLN转移的治疗策略、nCRT后LPLND的适应证、预后价值、有效清扫范围、安全性仍存在诸多问题,需深入研究。      

食管癌淋巴结转移特点分析

目的:探讨食管癌淋巴结转移特点。方法:回顾性分析1 791例手术治疗的食管癌患者临床病理资料,分析淋巴结的转移规律及特点。结果:1 791例食管癌患者的淋巴结转移率为35.18%,淋巴结转移度为8.33%。基底细胞样鳞癌及腺鳞癌的淋巴结转移率及转移度与鳞癌无明显差异（均P>0.05）,而腺癌及神经内分泌癌的淋巴结转移率及淋巴结转移度明显高于鳞癌（均P<0.05）。肿瘤分化、病变长度、T分期及是否有脉管癌栓是淋巴结转移率的独立影响因素（均P<0.05）,并且肿瘤分化、T分期及是否有脉管癌栓是影响N分期的独立影响因素（均P<0.05）。上段食管癌的颈部淋巴结转移率要高于中、下段食管癌（P=0.002）,而纵隔及腹腔淋巴结转移率在不同部位之间无显著性差异（均P>0.05）。结论:肿瘤分化、T分期及是否有脉管癌栓是影响食管癌淋巴结转移率及N分期的重要因素;上段食管癌更容易发生颈部淋巴结转移;无论肿瘤位置都应加强对腹腔淋巴结的清扫。     

扩大淋巴结清扫范围对低位直肠癌预后的影响

目的：探讨扩大淋巴结清扫范围对低位直肠癌术后恢复、局部复发率、生存率和生存质量的影响。方法：回顾性分析我院３２７例低位直肠癌行根治性切除的病例资料,其中１７１例行全直肠系膜切除（ＴＭＥ）,１５６例全直肠系膜切除＋Ｃ区（侧方）淋巴结清扫（ＴＭＥ＋Ｃ）。结果：无手术死亡病例,两组在性别、年龄、肿瘤临床分期、组织学类型等方面差异无显著意义。ＴＭＥ组围手术期住院时间为（１０.９±１.８）天,低于ＴＭＥ＋Ｃ组（１４.０±２.０）天;住院费用ＴＥＭ组为（１.５２±０.１１）万元,低于ＴＭＥ＋Ｃ组（２.０１±０.１５）万元（p＜０.０５）;两组在总体局部复发率上无统计学差异,但Ｄｕｋｅｓ’Ｂ、Ｄｕｋｅｓ’Ｃ期ＴＭＥ＋Ｃ组局部复发率明显下降,两组差异有显著性（p＜０.０５）;总体５年生存率ＴＭＥ组为５３.２％,而ＴＭＥ＋Ｃ组为５７.１％,两组无显著差异（p＞０.０５）,亚组分析显示Ｄｕｋｅｓ’Ｂ期ＴＭＥ＋Ｃ组５年生存率高于ＴＭＥ组（p＜０.０５）;两组在生活质量方面无差异（p＞０.０５）。结论：Ｄｕｋｅｓ’Ａ和Ｄｕｋｅｓ’Ｃ期低位直肠癌行根治术且ＴＭＥ＋Ｃ术增加患者手术创伤,住院时间延长,但不提高５年生存率;Ｄｕｋｅｓ’Ｂ期直肠癌行根治术且ＴＭＥ＋Ｃ术虽然延长住院时间,但可改善患者５年生存率。     

影响N0期鼻咽癌放射治疗后颈淋巴结复发因素分析

目的分析颈淋巴结阴性(N0)鼻咽癌放射治疗后颈淋巴结复发的影响因素。方法采用Logistic回归方法回顾性分析接受放射治疗的N0期鼻咽癌211例复发因素。结果211例N0期鼻咽癌放射治疗后49例复发。采用面颈联合野放射治疗,上颈预防剂量>50 Gy比面颈分野上颈剂量50 Gy者颈淋巴结复发率低（t=12.93,P=0.000)。咽旁间隙受侵,T分期高,颈淋巴结复发率高（t=14.91,P=0.001及t=8.78,P=0.003)。全颈预防照射比单纯上颈预防照射的下颈复发率低（χ     

Frequency of noncontiguous lymph node involvement in patients with resectable nonsmall cell lung carcinoma.

BACKGROUND: This study was undertaken to investigate the patterns of lymph node spread and the frequency of involvement of noncontiguous lymph node stations in patients with nonsmall cell lung carcinoma who had complete surgical resection. METHODS: All patients who had surgical resection as their sole treatment for nonsmall cell lung carcinoma during the years 1987-1990 were reviewed. All patients were treated similarly. Generally, complete mediastinal lymph node dissection was performed after resection of the primary lesion and N1 lymph nodes. Patients were assessed for patterns of involvement of N1 and N2 lymph node stations. The frequency of noncontiguous involvement of lymph nodes (involvement of N2 lymph nodes without involvement of N1 lymph nodes) was determined. Patient and tumor characteristics were assessed to ascertain whether certain factors were likely to predict this noncontiguous pattern of lymph node spread. RESULTS: During the 4-year period of study, 336 patients with nonsmall cell lung carcinoma were managed with surgical resection alone. Of the 336, 100 had no involvement of lymph nodes, 108 had involvement of N1 lymph nodes only, 76 had involvement of N1 and N2 lymph nodes, and 52 had involvement of N2 lymph nodes only. Therefore, 52 of all 336 patients (15%) and 52 of 236 patients with lymph node involvement (22%) had noncontiguous lymph node spread. A review of the initial patient and tumor characteristics revealed that patients with a suggestion of enlarged mediastinal lymph nodes on preoperative computed tomography scans of the chest (compared with negative findings) and patients with T1 and T2 lesions (compared with T3 and T4) were more likely to have noncontiguous lymph node spread; the odds ratios (with 95% confidence intervals) were 2.18 (1.01-4.71) and 2.82 (1.36-5.84), respectively. CONCLUSIONS: Noncontiguous involvement of thoracic lymph nodes occurred in approximately 15% of patients who had complete surgical resection of nonsmall cell lung carcinoma. This factor suggests that lack of involvement of N1 lymph nodes does not rule out mediastinal involvement and provides important information for complete surgical staging.