Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases - results of a preliminary study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.     

cⅠA期非小细胞肺癌纵隔淋巴结切除方式的临床研究

目的 探讨不同淋巴结切除方式在病理诊断为T1的cⅠA期非小细胞肺癌治疗中的作用.方法 根据淋巴结切除方式的不同,将1998年1月至2002年5月115例病理诊断为T1的cⅠA期非小细胞肺癌患者分为系统性纵隔淋巴结清扫组(清扫组)和纵隔淋巴结采样组(采样组),回顾性分析两组的并发症、N分期及预后之间的差异,评价各临床病理因素与预后的关系.结果 清扫组平均每例切除淋巴结(15.98±3.05)个,采样组平均每例切除淋巴结6.48±2.16个,两组差异有统计学意义(P＜0.01),但清扫组的手术时间、术后胸腔引流量及并发症发生率均多于采样组.两组在淋巴结分期的改变、总生存率与无病生存率等方面差异无统计学意义;进一步分析发现,当肿瘤直径＞2 cm时,清扫组与采样组的5年总生存率分别为78.2%和54.5%,无病生存率分别为75.1%和51.3%,清扫组均高于采样组(P＜0.05);当肿瘤直径≤2 cm时,两组的5年总生存率与无病生存率无明显差别.病理类型方面,大细胞癌和腺鳞癌5年总生存率低于腺癌和鳞状细胞癌(P＜0.05),有淋巴结转移的5年总生存率与无病生存率明显低于无淋巴结转移者(P均＜0.01).结论 对于术中确定为T1的cⅠA期非小细胞肺癌,当肿瘤直径≤2 cm时,选择纵隔淋巴结采样术可以相对减小创伤;当肿瘤直径＞2 cm时,选择系统性纵隔淋巴结清扫术可能更有助于长期生存.     

Improved staging using intraoperative ultrasound for mediastinal lymphadenectomy in non-small lung cancer surgery

BackgroundExtent of lymph node involvement in patients with non-small cell lung cancer (NSCLC) is the cornerstone of staging and influences both multimodality treatment and final outcome. The aim of this study was to investigate accuracy and characteristics of intraoperative ultrasound guided systematic mediastinal nodal dissection in patients with resected NSCLC.MethodsFrom January 2008 to June 2013, 244 patients undergoing intraoperative surgical staging after radical surgery for NSCLC were included in prospective study. The patients were divided in two groups according to systematic mediastinal nodal dissection: 124 patients in intraoperative ultrasound nodal dissection guided group and 120 in standard nodal dissection group. The lymph nodes were mapped by their number and station and histopathologic evaluation was performed.ResultsOperating time was prolonged for 10 min in patients with ultrasound guided mediastinal nodal dissection, but number and stations of evaluated lymph nodes were significantly higher (p < 0.001) in the same group. Skip nodal metastases were found in 24% of patients without N1 nodal involvement. Twelve (10%) patients were upstaged using US guided mediastinal lymphadenectomy. In US guided group 5-year survival rate was 59% and in the group of standard systematic mediastinal lymphadenectomy 43% (p = 0.001) Standard staging system seemed to be improved in ultrasound guided mediastinal lymphadenectomy patients. Complication rate showed no difference between analyzed groups.ConclusionHigher number and location of analyzed mediastinal nodal stations in patients with resected NSCLC using ultrasound is suggested to be of great oncological significance. Our results indicate that intraoperative ultrasound may have important staging implications.     

Oncological issues in staging mediastinal lymph node metastasis for left lung cancer

ObjectiveWe aimed to discuss the underlying oncological issues in staging of mediastinal lymph node metastasis in patients with left lung cancer who underwent extended radical lymphadenectomy (ERL).MethodsThis multi-institutional retrospective study analyzed 116 patients with left non-small-cell lung cancer who underwent bilateral paratracheal lymph node dissection (ERL) via median sternotomy. The clinicopathological records of patients with mediastinal lymph node metastasis were examined for prognostic factors, including age, sex, histology, tumor size, cN number, preoperative data, metastatic stations (number and distribution), pT, and adjuvant chemotherapy.ResultsMediastinal lymph node metastases were found in 43 patients, and right paratracheal lymph node metastases (pN3) were found in 13 patients. The 5-year overall survival rate was 25.2% in patients with pN3 tumors (n = 13) and 23.1% in patients with pN2 tumors (n = 30). The prognosis did not differ between patients with pN3 and pN2. Univariate analyses showed that histology, cN, and adjuvant chemotherapy were significant prognostic factors in patients with mediastinal lymph node metastasis. In these 43 patients, cN and adjuvant chemotherapy were significant independent prognostic factors in multivariate analysis.ConclusionsThe prognostic factors for left lung cancer with mediastinal lymph node metastasis were cN status and adjuvant chemotherapy, and not pN status (pN2 or pN3). We hope that the study results, which suggest that there may be no difference in prognosis between pN2 and pN3, would broaden the discussion of oncological issues in the staging of mediastinal lymph node metastasis of left lung cancer.     

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.     

Lymph node-positive bladder cancer treated with radical cystectomy and lymphadenectomy: effect of the level of node positivity

Background

The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear.

Objective

Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND).

Design, setting, and participants

A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo.

Intervention

RC with mapping PLND.

Measurements

We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression.

Results and limitations

Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04–3.46], p = 0.036; versus HR: 4.3 [95% CI, 2.25–8.34], p < 0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10–42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22–54] and 35% [95% CI, 11–60], respectively). This study is limited by the lack of prospective randomization and a control group.

Conclusions

The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.     

New Endoscopic Ultrasound (EUS) Applications in Lung Cancer: Evaluation of Patients With Negative Mediastinal CT and Re-Staging After Neoadjuvant Treatment

The main purpose of staging in non-small cell lung cancer (NSCLC) is to assess mediastinal lymph node involvement, with thoracic CT being the main non-invasive test for this. However, given that up to 15% of patients who show no mediastinal lymph node involvement in the CT has lymph node metastasis during surgery, other examinations are required. Endoscopic ultrasonography guided fine-needle aspiration (EUS-FNA) was shown to be able to detect advanced disease (metastatic mediastinal lymph nodes, adrenal metastasis, mediastinal invasion by the tumor) in approximately 25% of patients with a CT that suggested a non-advanced disease.Another situation in which CT has a very limited value is in the evaluation of the response to induction therapy, with its most limiting factor being its intrinsic inability to distinguish between a tumor and necrosis. In this context, EUS-FNA was shown to have a good performance, with a sensitivity, negative predictive value and precision of 75%, 67%, and 83%, respectively.In conclusion, EUS-FNA may be considered a good alternative in the pre-operative staging of patients with NSCLC, with and without diseased mediastinal lymph nodes in CT, and could play an important role in the mediastinal re-staging of these patients by identifying a patient sub-group who might benefit from additional surgical treatment.     

Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography

BACKGROUND: Computed tomography (CT) is the most common method of staging lung cancer. We have previously shown endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) to be highly accurate in staging patients with nonsmall cell lung cancer (NSCLC) who have enlarged mediastinal lymph nodes on CT scan. In this study we report the accuracy and yield of EUS-FNA in staging patients without enlarged mediastinal lymph nodes by CT. METHODS: Patients with NSCLC and CT scan showing no enlarged mediastinal lymph nodes (> 1 cm for all nodes except > 1.2 cm for subcarinal) in the mediastinum underwent EUS. Fine needle aspiration was performed on at least one lymph node, if present, in the upper mediastinum, aortopulmonary window, subcarinal, and periesophagus regions. Each specimen was evaluated with on-site cytopathology and confirmed with complete cytopathologic examination. RESULTS: Sixty-nine patients without enlarged mediastinal lymph nodes were evaluated. Endoscopic ultrasound detected malignant mediastinal lymph nodes in 14 of 69 patients as well as other advanced (American Joint Committee on Cancer [AJCC] stage III/IV) in 3 others (1 left adrenal, and 2 with mediastinal invasion of tumor) for a total of 17 of 69 (25%, 95% confidence interval: 16% to 34%) patients. Eleven additional patients were found to have advanced disease by bronchoscopy (2), mediastinoscopy (2), and thoracotomy with mediastinal lymph node dissection (7). The sensitivity of EUS for advanced mediastinal disease was 61% (49% to 75%), and the specificity was 98% (95% to 100%). CONCLUSIONS: Endoscopic ultrasound guided fine needle aspiration can detect advanced mediastinal disease and avoid unnecessary surgical exploration in almost one of four patients who have no evidence of mediastinal disease on CT scan. In addition to previously reported results in patients with enlarged lymph nodes on CT, these data suggest that all potentially operable patients with nonmetastatic NSCLC may benefit from EUS staging.     

Complete mediastinal lymphadenectomy: the core component of the multidisciplinary therapy in resectable non-small cell lung cancer.

There is a great deal of concern about metastasis of lung cancer to regional lymph nodes, due partly to the work of groups of thoracic surgeons in Japan and North America beginning in the 1970s. The classification of regional lymph node stations for lung cancer staging published by Mountain and Dresler has been widely adopted for more than ten years. Anatomic landmarks for 14 levels of intrapulmonary, hilar, and mediastinal lymph nodes stations are designated. Skip transfer and occult lymph node metastasis, confirmed by studies regarding the mode of spread of intrathoracic lymphatic metastasis, are two theoretical bases for complete mediastinal lymphadenectomy of lung cancer. However, whether or not the degree of the dissection influences prognosis, the role of systematic nodal dissection (SND) vs mediastinal lymph node sampling (MLD) in resectable non-small cell lung cancer (NSCLC) remains controversial. A systematic literature search was performed to identify relevant reports, making full use of the 'Cited by,' 'Related Records,' 'References,' and 'Author Index' functions in the PubMed and ISI Web of Science databases. This paper presents a review of the role of mediastinal lymph node distribution and methods of determining suitability for hilar and mediastinal lymphadenectomy based on the four subsets of stage IIIA-N2, balancing the cost vs effect of mediastinal lymph node dissection in resectable NSCLC, focusing on the stage migration bias in clinical trials comparing SND and MLS, recommending a reasonable node dissection sequence, improving the prospects for the perioperative anti-tumor therapy based on mediastinal lymphadenectomy, and evaluating the various preoperative staging techniques. Finally, we believe that, besides the role of complete resection and accurate staging, the complete mediastinal lymphadenectomy is the core component of the lung cancer multidisciplinary therapy, and suggest that the values of lymphadenectomy should be further assessed using decision-tree analysis based on large-scale prospective randomized trials and pooled analysis to evaluate the costs vs effects.     

A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines

OBJECTIVE: To prospectively assess the outcome of patients treated according to the European Association of Urology (EAU) guidelines on the management of penile cancer, a system originally based on retrospective series. PATIENTS AND METHODS: Between 2002 and 2005, 100 consecutive patients (median age 62 years) with penile cancer were treated at one institution; all were categorized and treated according to EAU guidelines. Data were analysed using the z-test, with significance defined as P < 0.05. RESULTS: Survival curves were limited to those with >12 months of follow-up (mean 29); the survival of the whole group was 92%. Of men with palpable nodes, 72% had lymph node involvement, whereas 18% of those with impalpable nodes who had lymphadenectomy according to the guidelines had lymph node disease. The grade of the primary tumour was more predictive than T stage for lymph node involvement and survival. The 3-year disease-specific survival for N0, N1 and N2 disease was 100%, 100% and 73%, respectively, and survival at 12 months for N3 disease was 67%. The median survival for those with metastases was 3 months. CONCLUSION: The overall survival of men with penile cancer is high, with a clear benefit for early lymphadenectomy in men with positive nodal disease. However, the current EAU guidelines are limited in predicting those patients with micrometastatic disease, with the result that 82% of patients undergo unnecessary prophylactic lymphadenectomy. There is a need to identify more accurate molecular markers for predicting lymph node disease, or the role of novel staging techniques must be assessed.     

Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials

BACKGROUND: Surgery is considered the treatment of choice for patients with resectable stage I and II (and some patients with stage IIIA) non-small cell lung cancer (NSCLC), but there have been no previously published systematic reviews. METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted to determine whether surgical resection improves disease specific mortality in patients with stages I-IIIA NSCLC compared with non-surgical treatment, and to compare the efficacy of different surgical approaches. RESULTS: Eleven trials were included. No studies had untreated control groups. In a pooled analysis of three trials, 4 year survival was superior in patients undergoing resection with stage I-IIIA NSCLC who had complete mediastinal lymph node dissection compared with lymph node sampling (hazard ratio estimated at 0.78 (95% CI 0.65 to 0.93)). Another trial reported an increased rate of local recurrence in patients with stage I NSCLC treated with limited resection compared with lobectomy. One small study reported a survival advantage among patients with stage IIIA NSCLC treated with chemotherapy followed by surgery compared with chemotherapy followed by radiotherapy. No other trials reported significant improvements in survival after surgery compared with non-surgical treatment. CONCLUSION: It is difficult to draw conclusions about the efficacy of surgery for locoregional NSCLC because of the small number of participants studied and methodological weaknesses of the trials. However, current evidence suggests that complete mediastinal lymph node dissection is associated with improved survival compared with node sampling in patients with stage I-IIIA NSCLC undergoing resection.     

Mediastinal lymph nodes: Ignore? Sample? Dissect? The role of mediastinal node dissection in the surgical management of primary lung cancer

The role of mediastinal lymph node dissection (MLND) during the resection of non-small-cell lung cancer is still unclear although most surgeons agree that a minimum of hilar and mediastinal nodes must be examined for appropriate pathological staging. Current surgical practices vary from visual inspection of the mediastinum with biopsy of only abnormal looking nodes to systematic mediastinal node sampling which is to the biopsy of lymph nodes from multiple levels whether they appear abnormal or not to MLND which involves the systematic removal of all lymph node bearing tissue from multiple sites unilaterally or bilaterally within the mediastinum. This review article looks at the evidence and arguments in favour of lymphadenectomy, including improved pathological staging, better locoregional control, and ultimately longer disease-free survival and those against which are longer operating time, increased operative morbidity, and lack of evidence for survival benefit.     

Detection of Micrometastatic Tumor Cells in pN0 Lymph Nodes of Patients With Completely Resected Nonsmall Cell Lung Cancer: Impact on Recurrence and Survival

OBJECTIVE: To detect occult micrometastatic tumor cells in pN0 lymph nodes of nonsmall cell lung cancer (NSCLC) by a combination of cytokeratin and p53 immunohistochemistry staining, and to evaluate the relation between the micrometastasis in pN0 lymph nodes and the prognosis of patients with completely resected stage 1 NSCLC. SUMMARY BACKGROUND DATA: The average 5-year survival rate for patients with completely resected stage 1 NSCLC is only about 70%; thus, about 30% of these patients have recurrent disease. This suggests that occult micrometastasis may exist at the time of surgery; the rate is clearly underestimated by current clinical staging examinations and conventional histopathologic methods. METHODS: A total of 474 hilar and mediastinal lymph nodes were removed during surgery from 49 patients with completely resected stage 1 NSCLC. The lymph nodes analyzed for micrometastasis using immunohistochemical staining with the biclonal anticytokeratin antibody, AE1/AE3. Of these 474 lymph nodes from 49 patients, 263 lymph nodes from 25 patients, whose primary tumors were positive for the p53 protein, were subjected to immunohistochemical staining with the monoclonal anti-p53 protein antibody DO-1. RESULTS: Cells positive for cytokeratin and p53 protein were found in 35 (7.4%) of 474 and 20 (7.6%) of 263 lymph nodes, respectively; 17 (34.7%) of 49 patients had cytokeratin-positive cells and 10 (40.0%) of 25 patients had p53-positive cells in their pN0 lymph nodes. By a combination of cytokeratin and p53 protein immunohistochemical staining, micrometastatic tumor cells were identified in pN0 lymph nodes in 22 (44.9%) of 49 patients. The patients with lymph node micrometastasis identified by a combination of cytokeratin and p53 protein immunohistochemical staining had a poorer prognosis than those without micrometastasis on both univariate and multivariate analyses (overall survival, P =.0003 and 0.013, respectively). CONCLUSIONS: The detection of lymph nodal micrometastasis by cytokeratin and p53 protein immunohistochemical staining will be helpful to predict the recurrence and prognosis of patients with completely resected stage 1 NSCLC.     

Accuracy of staging node-negative pancreas cancer: a potential quality measure

OBJECTIVE: To determine the optimal number of lymph nodes to examine for accurate staging of node-negative pancreatic adenocarcinoma after pancreaticoduodenectomy. DESIGN, SETTING, AND PATIENTS: Data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program (1988-2002) were used to identify 3505 patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreas, including 1150 patients who were pathologically node negative (pN0) and 584 patients with a single positive node (pN1a). Perioperative deaths were excluded. Univariate and multivariate survival analyses were performed. MAIN OUTCOME MEASURE: Examination of 15 lymph nodes appears to be optimal for accurate staging of node-negative adenocarcinoma of the pancreas after pancreaticoduodenectomy. RESULTS: The number of nodes examined ranged from 1 to 54 (median, 7 examined nodes). Univariate survival analysis demonstrated that dichotomizing the pN0 cohort on 15 or more examined lymph nodes resulted in the most statistically significant survival difference (log-rank chi(2) = 14.49). Kaplan-Meier survival curves demonstrated a median survival difference of 8 months (P < .001) in favor of the patients who had 15 or more examined nodes compared with patients with fewer than 15 examined nodes. Multivariate analysis validated that having 15 or more examined nodes was a statistically significant predictor of survival (hazard ratio, 0.63; 95% confidence interval, 0.49-0.80; P < .0001). Furthermore, a multivariate model based on the survival benefit of each additional node evaluated in the pN0 cohort demonstrated only a marginal survival benefit for analysis of more than 15 nodes. Approximately 90% of the pN1a cohort was identified with examination of 15 nodes. CONCLUSIONS: Examination of 15 lymph nodes appears to be optimal to accurately stage node-negative adenocarcinoma of the pancreas after pancreaticoduodenectomy. Furthermore, evaluation of at least 15 lymph nodes of a pancreaticoduodenectomy specimen may serve as a quality measure in the treatment of pancreatic adenocarcinoma.     

Video-assisted mediastinoscopic lymphadenectomy (VAMLA)--a method for systematic mediastinal lymphnode dissection.

OBJECTIVE: Video-assisted mediastinal lymphadenectomy (VAMLA) increases quality of mediastinal lymph node staging in bronchial carcinoma. The video-mediastinoscope allows systematic lymphadenectomy by bimanual preparation. Complete bilateral resection of lymph nodes in stations 1, 2, 3, 4 and 7 (Naruke) can safely be done after visualization of limiting structures (trachea, main bronchi, oesophagus, pericardium, pulmonary artery, aorta, upper vena cava and azygos vein). In this initial study, we compared histopathological findings from VAMLA with final lymph node staging from subsequent thoracotomy. METHODS: Between January 2001 and December 2001, 25 patients were operated by VAMLA (among 162 mediastinoscopies), two patients for diagnostic purposes and 23 for staging of bronchial carcinoma. Eighteen patients underwent subsequent thoracotomy for tumor resection and systematic lymphadenectomy. Pathological findings were reviewed. RESULTS: In VAMLA, lymph node dissection of station 2R, 2L and 4R was achieved in 96, 28 and 92%, respectively, whereas resection of lymph nodes in station 7 and 4L was performed in 100%. Other locations were dissected in 44%. A mean of 8.6 lymph nodes were removed in each patient. No residual lymph node tissue was found in the subcarinal compartment at open surgery. When comparing histopathological staging from VAMLA with final pathology, there were no false negative results. Seventeen patients who had N0 disease at VAMLA proved to be N0 or N1 at thoracotomy, one patient diagnosed as N2 at mediastinoscopy had N2 disease at final pathology. The only complication observed in VAMLA was a blood loss of >100 ml in 12% of patients without need for transfusion or surgical intervention. CONCLUSION: Mediastinal lymph node staging is improved by VAMLA. A systematic lymphadenectomy is performed bimanually through the video mediastinoscope. The number of lymph nodes removed is doubled compared to standard mediastinoscopy. There were no false negative results at final pathology. This new technique presents the basis for video-assisted thoracic surgery (VATS) lobectomy because complete resection of the mediastinal lymph nodes can be achieved by VAMLA. Potential complications of VAMLA such as injury of major mediastinal vessels, airways, pneumothorax or recurrent laryngeal nerve injury indicate the need for a full thoracic surgical infrastructure.     

Pathologic N0 status in pulmonary adenocarcinoma is predictable by combining serum carcinoembryonic antigen level and computed tomographic findings

OBJECTIVES: It is not clear whether lymphadenectomy has therapeutic benefit in non-small cell lung cancer management. To avoid unnecessary lymphadenectomy, we attempted to identify clinical or radiologic predictors of pathologic N0 disease in patients with peripheral adenocarcinoma. METHODS: From August 1992 through April 1997, 269 consecutive patients with peripheral adenocarcinoma who underwent major lung resection and systematic lymph node dissection were enrolled in this study. We reviewed their contrast-enhancement computed tomographic scans and recorded the maximum dimension of tumors both on pulmonary (pDmax) and on mediastinal (mDmax) window setting images, the largest dimension perpendicular to the maximum axis on both pulmonary (pDperp) and mediastinal (mDperp) window setting images, and the size of all detectable hilar-mediastinal lymph nodes. We defined a new radiologic parameter, tumor shadow disappearance rate (TDR), which is calculated with the following formula: TDR = 1 - (mDmax x mDperp)/(pDmax x pDperp). RESULTS: In multivariable analysis a lower serum carcinoembryonic antigen level and a higher tumor shadow disappearance rate were significant predictors of pathologic N0 disease. Lymph node size on computed tomographic scanning was not a significant predictor. Among 59 patients with a normal preoperative carcinoembryonic antigen level and a tumor shadow disappearance rate of 0.8 or more, 58 (98%) patients had pathologic N0 disease, and the other patient had pathologic N1 disease. CONCLUSIONS: Mediastinal lymph node involvement was not found in patients with a normal preoperative serum carcinoembryonic antigen level and a tumor shadow disappearance rate 0.8 or more. The patients who meet these criteria may be successfully managed with major lung resection without systematic mediastinal lymphadenectomy.     

Elective lymph node dissection in patients with melanoma: systematic review and meta-analysis of randomized controlled trials

HYPOTHESIS: Elective lymph node dissection does not improve survival in patients with melanoma without clinically detectable lymph node metastases. OBJECTIVE: To determine whether elective lymph node dissection in patients with melanoma without clinically detectable regional metastases decreases overall mortality. DESIGN: Systematic review and meta-analysis of randomized controlled trials comparing elective lymph node dissection with delayed lymphadenectomy at the time of clinical recurrence. SETTING: Randomized controlled trials available by February 2001. SUBJECTS: The included trials comprised 1533 participants. INTERVENTION: Elective lymph node dissection compared with delayed lymphadenectomy or no lymphadenectomy in patients with melanoma without clinically detectable regional metastases. MAIN OUTCOME MEASURE: Overall mortality in treatment groups as compared with control groups at the end of a 5-year follow-up period. RESULTS: Three randomized controlled trials met the inclusion criteria. The pooled odds ratio for overall mortality for the 3 trials was 0.86 (95% confidence interval, 0.68-1.09). Results are statistically nonsignificant, but they have potential clinical significance. CONCLUSIONS: This systematic review of randomized controlled trials comparing elective lymph node dissection with surgery delayed until the time of clinical recurrence shows no significant overall survival benefit for patients undergoing elective lymph node dissection. Trials included in this review, however, contain significant bias. The question is not answered for all patients, and the results do not exclude the possibility that some subgroups may benefit from elective lymph node dissection. Further research is required.     

Surgical treatment of N2 involved non-small cell lung cancer--the systematic extended lymph node dissection based on the regional lymphatic drainage]

From the study on regional lymphtic drainage, we have decided the extent of lymphadenectomy as follows; a) For the left lung cancer and the right upper lobe primary, systematic bilateral mediastinal dissection (R3 alpha) through a median sternotomy, b) For the cases with the highest mediastinal node involvement, lower half of radical neck dissection (R3 gamma) through a cervical collar incision in addition to a). The cN diagnosis by CT interpretation and pN diagnosis were compared. The under estimated rates of N were 32% of 137 patients with the left lung primary. 46 patients with pN2(+) included 14 patients (31%) with pN3 disease. As for the right upper lobe primary, 17 patients with pN2(+) included 13 patients (76%) with pN3 disease. Postoperative survival rates calculated with Kaplan-Meiermethod; 1) The five-year survival rates were 43% of 46 patients with pT1-3 N2-3 of the left lung primary. 2) As for the right upper lobe primary, the two-year survival rates were 51% of 17 patients with pT1-4 N2-3. 3) The three-year survival rates of 26 patients with pN3 gamma diagnosed as cN0-3 alpha preoperatively were 41%. These systematic extended dissection (R3 alpha, R3 gamma) would bring better prognosis in the patients with pN2-3 disease.     

Surgical strategy for clinical stage I non-small cell lung cancer in octogenarians.

OBJECTIVE: The purpose of this study was to determine whether lobectomy without radical systematic mediastinal lymphadenectomy (LA) is a satisfactory alternative surgical treatment for octogenarians with clinical stage I non-small cell lung cancer (NSCLC). METHODS: From April 1985 through December 2001, 49 patients aged 80 years and older who underwent surgical treatment for clinical stage I NSCLC were reviewed. Lobectomy without radical systematic mediastinal LA was performed for 27 patients (LA0 group) and lobectomy with radical systematic mediastinal LA was performed for 22 patients (LA group). RESULTS: The mortality rate was 0% in the LA0 group and 4.5% in the LA group. Five-year survival rate according to the type of surgery was 44.8% in the LA0 group and 55.5% in the LA group, a difference that was not significant (P=0.88). Although there was no significant statistical difference, postoperative pulmonary complication was more frequent in the LA group than in the LA0 group (32% in the LA group versus 11% in the LA0 group P=0.07). Five-year survival rates according to serum carcinoembryonic antigen (CEA) levels were 0% for patients with elevated CEA levels (n=9) and 56.5% for patients with normal CEA levels (n=40) (P<0.01). CONCLUSION: Lobectomy without radical systematic mediastinal LA appears to be a satisfactory surgical procedure for octogenarians with clinical stage I NSCLC. However, mediastinoscopy is necessary in such octogenarians if their serum CEA level is elevated so that the precise clinical stage can be determined and an accurate prognosis can be given.