Minimally Invasive Systematic Mediastinal Lymphadenectomy for Lung Cancer Surgery

Is Minimally Invasive Outpatient Pneumonectomy the Current Standard of Care for Lung Cancer?

Constituent part of radical lung resection for lung cancer is a dissection of mediastinal lymph nodes. Lymphadenectomy is a standard procedure in an assessment of clinical stage of the disease. The aim of the study was to map metastasizing of bronchogenic non-small cell lung carcinoma into homolateral mediastinal lymph nodes and to assess the importance of mediastinal lymphadenectomy for exact staging and survival. Study of 31patients with lung resection and systematic mediastinal lymphadenectomy operated from August 2004 to January 2007, with pre-operative stage Ia to IIb (TNM classification) - according to CT without mediastinal lymph nodes invasion and with positive histological finding after systematic mediastinal lymphadenectomy. Tumors in right upper lobe metastasized in 45.5 % into group 1 nodes (stages N1-N4) and group 3 nodes (stages N7) and in 9 % into group 4 nodes (stages N8-N9). Tumors of the right middle lobe metastasized in 100 % into group 3 nodes (stage N7).Tumors of the right lower lobe metastasized in 87.5 % into group 3 nodes (N7) and in 12.5 % into group 4 nodes (stages N8-N9). Tumors of the left upper lobe metastasized in 9.0 % in group 1 nodes (stages N1-N4), in 82 % into group 2 nodes (stages N5-N6) and in 9.0 % were found skip metastases into group 4 nodes (stages N8-N9). Tumors of the left lower lobe metastasized in 26.7 % in group 4 nodes, 46.6 % into group 3 nodes, in 20,0 % into group 2 nodes and in 6,7 % into group 1 nodes. Systematic mediastinal lymphadenectomy is crucial for determining the stage of the disease according to the TNM classification. Systematic lymphadenectomy is essential for the diagnosis of stage IIIa disease and setting of additional therapy that prolongs survival (Ref. 17).

To assess the influence of mediastinal lymphadenectomy on postoperative concentration of interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1 ra) in serum, sputum, and pleural fluid, in patients operated upon due to lung cancer and benign pulmonary diseases. Thirty-three patients undergoing uncomplicated resections, including 23 with lung cancer and 10 with benign diseases, were analyzed. In patients with right lung cancer we performed a systematic lymphadenectomy, while in patients with left lung cancer systematic sampling was performed. Serum IL-6 and IL-1 ra concentration was measured before and after surgery, and on postoperative days 1, 3, and 7, as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1, by ELISA test. In 23 patients with cancer, 19.0+/-11.43 mediastinal lymph nodes were removed (in 11 patients with right lung cancer 27.6+/-7.6 and in 12 patients with left lung cancer 11.1+/-8.1). No differences were found in serum and sputum concentration of IL-6 and IL-1 ra between patients after right and left thoracotomy due to cancer and between patients with cancer and patients with benign diseases. Patients with cancer had a lower concentration of IL-1 ra in pleural fluid (median 16950, range 16050-45470.05 pg/ml) than patients with benign diseases (76665.6 pg/ml (range 53618-89617.9); p=0.0008). In 23 cancer patients a negative correlation between concentration of cytokines in pleural fluid and a number of mediastinal lymph nodes resected was observed (Spearman correlation coefficient for IL-6: r=-0.44, p=0.04; for IL-1 ra: r=-0.57, p=0.01). Such correlation was not observed for a number of positive N2 lymph nodes. Systematic lymphadenectomy added to major lung resection does not increase postoperative humoral immune response in uncomplicated cases, as measured by levels of IL-6 and IL-1 ra in serum, pleural fluid, and sputum.

So far it has not clearly been demonstrated that systematic mediastinal lymphadenectomy improves survival in patients with non-small cell lung cancer. One explanation might be that in some patients an early spread of tumor cells has occurred which might not be curable by surgical means. To test this hypothesis lymph nodes of patients which were treated either by lymph node sampling or systematic lymphadenectomy were screened for micrometastatic spread of tumor cells and the influence of nodal micrometastases on the efficacy of lymphadenectomy was analyzed. Lymph nodes from patients (n=94) which were included in a randomized trial of lymph node sampling (LS, n=41) versus radical systematic lymphadenectomy (LA, n=53) were screened by immunohistochemistry for disseminated tumor cells using the antibody Ber-Ep4. The median observation time was longer than 5 years and follow-up data were available from all 94 patients. Kaplan-Meier curves were calculated and tested for statistical significance using the log-rank test. Standard histopathological analysis revealed no lymph node involvement (pN0) in 61 patients, pN1 disease in 13 patients and pN2 disease in 20 patients without significant differences between LA and LS with respect to T-stage, N-stage or age and sex of the patients. By immunohistochemistry a minimal nodal spread of tumor cells was detected in 21 out of 94 patients (LS, n=10 (24%); LA, n=11 (21%)). Similar to the entire group of patients also in the subset of patients with nodal micrometastases the type of lymphadenectomy did not significantly influence the long-term survival (P=0.27 and P=0.39, respectively). In contrast, in patients with a negative immunohistochemical analysis systematic lymphadenectomy resulted in an improved overall survival (P=0.044). Our data provide some evidence that systematic lymphadenectomy improves survival in patients without an early locoregional spread of cancer cells. As long as these patients can not be identified preoperatively all patients should undergo a systematic mediastinal lymphadenectomy.

Evaluation of the surgical fat-filling procedure in the treatment of refractory cough after systematic mediastinal lymphadenectomy in patients with right lung cancer

Number of Mediastinal Lymph Nodes in Non-Small Cell Lung Cancer: A Gaussian Curve, Not a Prognostic Factor

In this study, we evaluate the feasibility and safety of single-port video-assisted thoracoscopic surgery (VATS) sleeve lobectomy (SL) and systematic mediastinal lymphadenectomy and summarize our surgical experience. From October 2014 to December 2015, eight cases of single-port VATS SL [seven male patients and one female patient, median age 56.0 (range, 38-63) years] were performed by a single group of surgeons in Fujian Medical University Fujian Union Hospital. The median tumor size was 2.7 cm. Types of resection included four right upper, one right lower, and three left upper sleeve lobectomies. Systematic mediastinal lymphadenectomy was performed in all patients. A modified anastomosis technique developed by the author (Chen's technique) was applied for bronchial anastomosis. Postoperative outcome and short-term follow-up data were recorded and analyzed. All eight operations were completed uneventfully with no conversion to thoracotomy or reoperation required. No perioperative death was observed. Major results (medians or percentages) were as follows: operative duration, 234.5 [185-345] min; bronchial anastomosis duration, 38.0 [30-43] min; blood loss, 65.0 [50-200] mL; number of lymph node dissected, 22.5 [18-37]. The postoperative complication rate was 37.5% (three of eight cases, including two pulmonary infections and one atrial fibrillation). All patients recovered and were discharged uneventfully with symptomatic therapy. Pathology showed squamous cell carcinoma in seven patients and adenocarcinoma in one patient; two patients were in TNM stage IB, three in stage IIA, one in stage IIB, and two in stage IIIA. The mean follow-up was 7.5 [2-15] months. There were no tumor recurrences or bronchial anastomotic complications. Single-port VATS SL and mediastinal lymphadenectomy are safe and feasible. Improvements in operating procedures can help facilitate single-port VATS. The application of Chen's technique in bronchial anastomosis is easy and reliable and shows a satisfactory short-term clinical outcome.

The increasing age of the population has raised the importance of determining the minimally required surgical treatment for elderly lung cancer patients. Despite a number of previous studies, the therapeutic impact of a radical mediastinal lymphadenectomy (RLA) associated with a pulmonary resection for lung cancer remains controversial. Herein, we investigated the impact of lymph node dissection on the overall survival for elderly lung cancer patients and assessed whether the non-performance of an RLA could be justified in the surgical treatment for these elderly patients. We analysed the data for 160 patients aged 70 years and older (113 males, 47 females) who underwent curative-intent surgery for non-small-cell lung cancer. They were divided into two groups, according to the method used for the intra-operative mediastinal lymph node dissection, the radical systematic lymphadenectomy (RLA, n=76) and the non-radical lymphadenectomy (NLA, n=94) groups. A Cox proportional hazards model and the Kaplan-Meier method were used for the survival analyses. Propensity-based analyses were also used to reduce the effect of non-randomisation and possible bias in indication of treatment between the two groups. RLAs had no protective effect on mortality; the hazard ratio for the RLA group in comparison to the NLA group was 0.97 (95% confidence interval (CI): 0.32-2.89) in the multivariate analysis and 1.43 (95% CI: 0.42-4.91) in the propensity-based stratifying analysis. The 3-year survival probability was 81.3% (95% CI: 67.1-89.8) for the NLA group, which was marginally better than that of the RLA group (77.5% (95% CI: 63.3-86.8)). There was no significant difference in the overall survival between the two groups (p=0.26). The 3-year survival probability of the NLA group at each quartile of the propensity score also tended to be better than that of the RLA group, which did not show any significant difference. There was no survival benefit shown for RLA associated with pulmonary resections in the present cohort, even in the propensity-based analyses. Although some reports recommend a systematic mediastinal lymphadenectomy for proper staging and better survival, a pulmonary resection with non-performance of radical lymphadenectomy could be an acceptable surgical treatment for the increasing number of elderly lung cancer patients.

A best evidence topic was constructed according to a structured protocol. The question addressed was whether radical mediastinal lymphadenectomy should be performed during lung metastasectomy of renal cell carcinoma (RCC). Of the 13 papers found through a report search, seven represent the best evidence to answer this clinical question. The authors, journal, date, country of publication, study type, group studied, relevant outcomes and results of these papers are given. We conclude that on the whole, the seven-retrieved studies support the realization of systematic radical mediastinal lymphadenectomy. The published literature showed a prevalence of lymph node involvement (LNI) that approaches 30%. The majority of the studies conclude that LNI is a significant, independent prognostic of survival. Indeed, some authors did not report any 5-year survival in the case of LNI. On the contrary, however, a 5-year survival of ~50% was reported when no LNI was present. To date, the published data do not allow conclusions to be drawn regarding the prognosis of hilar vs mediastinal LNI: only one paper focused on the difference between hilar and mediastinal location and showed no difference. In addition, only one study has compared the survival of patients with or without lymphadenectomy, showing greater survival when mediastinal lymphadenectomy was performed. Despite the poor prognosis of patients with LNI, surgery seems to be the best treatment for potentially curative RCC with metastases. It is known that RCC metastases do not respond well to chemotherapy and radiotherapy. Indeed, reported 5-year survival rate ranged between 3 and 11% for non-operated patients. Consequently, resection must be as complete as possible and include a systematic total mediastinal lymphadenectomy, which will probably yield better loco-regional control and evaluation of prognostic factor. However, the published evidence remains quite limited and mainly based on retrospective studies on highly selected patients, with a low level of evidence. Indeed, most patients referred to surgery are younger, fitter, and have fewer metastases. Consequently, the survival gain could be biased, related more to the resectability and the good performance status rather to the resection itself. Consequently, although these preliminary results are interesting, they must be interpreted with caution.

Impact of histological components on selecting limited lymphadenectomy for lung adenocarcinoma ≤ 2 cm

This study was to explore the appropriate extent of mediastinal lymph node dissection for clinical stage T₁a N₀ M₀ non-small cell lung cancer (NSCLC) by comparison between two modes of mediastinal lymph node dissection. A total of 96 clinical stage T₁a N₀ M₀ NSCLC cases received radical surgery were randomly divided to lobe-specific mediastinal lymphadenectomy (LL) group and systematic mediastinal lymphadenectomy (SL) group from the year 2004 to 2008. The effects of SL and LL on morbidity, N staging, overall survival (OS) and disease-free survival (DFS) were investigated. Meanwhile, associations between clinicopathological parameters and metastasis of lymph nodes were analyzed. The mean operating time and blood loss in LL group were significantly less than that in the SL group (135.48 ± 25.44 min vs. 180.85 ± 39.36 min, 155.11 ± 25.17 ml vs. 161.32 ± 28.20 ml, P < 0.05), the mean numbers of dissected lymph nodes of the SL group was significantly greater than that in the LL group (17.1 ± 3.7 vs. 9.4 ± 2.1, P < 0.05). The post-operative overall morbidity rate was higher in the SL group than that in the LL group (P < 0.05). There were no significant difference in migration of N staging, OS and DFS between two groups. The post-operative N staging, the tumor cells differentiation and the ratio of ground glass opacity (GGO) in tumor were the independent factors influencing long-term survival. Moreover, the significant correlation was seen between the metastasis of lymph nodes and clinicopathological parameters including tumor location and the GGO ratio. The LL group had similar efficacy as the SL group in the clinical stage T₁a N₀ M₀ NSCLC and there was unnecessary to perform systematic lymphadenectomy in such patients with a high ratio of GGO.

Analysis of the T Descriptors and Other Prognosis Factors in Pathologic Stage I Non-small Cell Lung Cancer in China

BackgroundAccurate prediction of lymph node metastasis (LNM) is critical for selecting optimal surgical procedures in early‐stage lung adenocarcinoma (LUAD). This study aimed to develop nomograms for intraoperative prediction of LNM in clinical stage IA LUAD.MethodsA total of 1227 patients with clinical stage IA LUADs on computed tomography (CT) were enrolled to construct and validate nomograms for predicting LNM (LNM nomogram) and mediastinal LNM (LNM‐N2 nomogram). Recurrence‐free survival (RFS) and overall survival (OS) were compared between limited mediastinal lymphadenectomy (LML) and systematic mediastinal lymphadenectomy (SML) in the high‐ and low‐risk groups for LNM‐N2, respectively.ResultsThree variables were incorporated into the LNM nomogram and the LNM‐N2 nomogram, including preoperative serum carcinoembryonic antigen (CEA) level, CT appearance, and tumor size. The LNM nomogram showed good discriminatory performance, with C‐indexes of 0.879 (95% CI, 0.847–0.911) and 0.880 (95% CI, 0.834–0.926) in the development and validation cohorts, respectively. The C‐indexes of the LNM‐N2 nomogram were 0.812 (95% CI, 0.766–0.858) and 0.822 (95% CI, 0.762–0.882) in the development and validation cohorts, respectively. LML and SML had similar survival outcomes among patients with low risk of LNM‐N2 (5‐year RFS, 88.1% vs. 89.5%, Pp = 0.790; 5‐year OS, 96.0% vs. 93.0%, p = 0.370). However, for patients with high risk of LNM‐N2, LML was associated with worse survival (5‐year RFS, 64.0% vs. 77.4%, p = 0.036; 5‐year OS, 66.0% vs. 85.9%, p = 0.038).ConclusionsWe developed and validated nomograms to predict LNM and LNM‐N2 intraoperatively in patients with clinical stage IA LUAD on CT. These nomograms may help surgeons to select optimal surgical procedures.

To evaluate the evidence comparing systematic mediastinal lymphadenectomy (SML) and mediastinal lymph node sampling (MLS) in the treatment of pathological stage I NSCLC using meta-analytical techniques. A literature search was undertaken until January 2014 to identify the comparative studies evaluating 1-, 3-, and 5-year survival rates. The pooled odds ratios (OR) and the 95 % confidence intervals (95 % CI) were calculated with either the fixed or random effect models. One RCT study and four retrospective studies were included in our meta-analysis. These studies included a total of 711 patients: 317 treated with SML, and 394 treated with MLS. The SML and the MLS did not demonstrate a significant difference in the 1-year survival rate. There were significant statistical differences between the 3-year (P = 0.03) and 5-year survival rates (P = 0.004), which favored SML. This meta-analysis suggests that in pathological stage I NSCLC, the MLS can get the similar outcome to the SML in terms of 1-year survival rate. However, the SML is superior to MLS in terms of 3- and 5-year survival rates.

To evaluate the effectiveness of lymphadenectomy in the treatment of non-small cell lung cancer (NSCLC). The extent of lymphadenectomy in the treatment of NSCLC is still a matter of controversy. Although some centers perform mediastinal lymph node sampling (LS) with resection of only suspicious lymph nodes, others recommend a radical, systematic mediastinal lymphadenectomy (LA) to improve survival and to achieve a better staging. In a controlled, prospective, randomized clinical trial, the effects of LA on recurrence rates and survival were analyzed, comparing LS and LA in 169 patients with operable NSCLC. After a median follow-up of 47 months, LA did not improve survival in the overall group of patients (hazard ratio: 0.78; 95% confidence interval: 0.47-1.24). Although recurrences rates tended to be reduced among patients who underwent LA, these decreases were not statistically significant (hazard ratio: 0.82; 95% confidence interval: 0.54-1.27). However, analysis of subgroups of patients according to histopathologic lymph node staging revealed that LA appears to prolong relapse-free survival (p = 0.037) with a borderline effect on overall survival (p = 0.058) in patients with limited lymph node involvement (pN1 disease or pN2 disease with involvement of only one lymph node level); in patients with pN0 disease, no survival benefit was observed. Radical systematic mediastinal lymphadenectomy does not influence disease-free or overall survival in patients with NSCLC and without overt lymph node involvement. However, a small subgroup of patients with limited mediastinal lymph node metastases might benefit from a systematic lymphadenectomy.