Complete Node Research Articles

Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy

BackgroundMeta-analysis of randomized trials has shown that postoperative radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients with resected N1 non–small cell lung cancer (NSCLC). Conversely, the locoregional recurrence (LR) rate is reported to be high without adjuvant PORT in these patients. We have evaluated the pattern of failure, actuarial risk and risk factors for LR in order to identify the subset of N1 NSCLC patients with the highest risk of LR. These patients could potentially benefit from PORT.MethodsWe conducted a retrospective study on 199 patients with pathologically confirmed T1–3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical margins or received preoperative therapy or PORT. The median follow-up was 53.8 months. Complete mediastinal lymph node (MLN) dissection and examination was defined as ≥3 dissected and examined MLN stations; incomplete MLN dissection or examination (IMD) was defined as <3 dissected or examined MLN stations. The primary end point of this study was freedom from LR (FFLR). Differences between patient groups were compared and risk factors for LR were identified by univariate and multivariate analyses.ResultsLR was identified in 41 (20.6%) patients, distant metastasis (DM) was identified in 79 (39.7%) patients and concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses identified that nonsmokers, ≤23 dissected lymph nodes, visceral pleural invasion and lymph node ratio >10% were significantly associated with lower FFLR rates (P < 0.05). Multivariate analyses further confirmed positive lymph nodes at station 10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in patients with both these risk factors (48%).ConclusionsThe incidence of LR in patients with surgically resected T1–3N1M0 NSCLC is high. Patients with IMD and positive lymph nodes at station 10 have the highest risk of LR, and may therefore benefit from adjuvant PORT. Further investigations of PORT in this subset of patients are warranted.

Validity of using lobe-specific regional lymph node stations to assist navigation during lymph node dissection in early stage non-small cell lung cancer patients

The validity of our proposed lobe-specific regional lymph node stations (LSRLNS) was evaluated as a method for navigation during lymphadenectomy in patients with early stage non-small cell lung cancer (NSCLC). A total of 725 NSCLC patients with c-T2N1M0 or less extensive disease who had undergone a curative operation with complete mediastinal lymph node dissection (MLND) were studied. The LSRLNS were #2, #3, #4 and #10 for the right upper lobe, #11i, #11s, #7 and #8 for the right lower lobe, #4, #5 and #6 for the left superior division, #11, #5 and #7 for the left lingular division and #11, #7 and #8 for the left lower lobe. If the LSRLNS were used for pathological examinations during surgery, 599 p-N0 and 39 p-N1 patients diagnosed with no metastasis would have been subjected to a selective MLND, while 20 p-N1 and 65 p-N2 patients who had a diagnosis of metastasis would have been navigated to a complete MLND. Two p-N2 patients with a diagnosis of no metastasis would have inappropriately undergone a selective MLND, resulting in the false negative rate at 0.3 %. Intra-operative pathological examination using our LSRLNS may accurately reveal the status of metastasis, and appropriately lead to a selective or complete MLND in patients with c-T2N1M0 or less extensive disease.

Radical pancreaticoduodenectomy via mesenteric approach

Radical pancreaticoduodenectomy is the only effective method for the treatment of malignancies in the pancreatic head and the periampulary region.Early determination of the involvement of the superior mesenteric artery (SMA)is important for the selection of the surgical procedure and judgment of the prognosis.The operation should follow the principle of tumor-free and adequate resection range,safe resection margin and complete lymph node resection.For this purpose,we performed the radical pancreaticoduodenectomy via mesenteric approach.The SMA was dissected first,and then the tumor was en-bloc resected.From December 2011 to December 2012,24 patients with tumors in the pancreatic head or the periampullary region received radical pancreaticoduodenectomy via the mesenteric approach at the Second Affiliated Hospital of Harbin Medical University,and the short-term outcome was satisfactory. Key words: Pancreatic head neoplasms; Neoplasms in the periampulary region; Pancreaticoduodenectomy; Mesenteric approach; R0 resection

Applicability of two different validated models to predict axillary non-sentinel lymph node status by sentinel node biopsy in a single Italian center

The necessity of complete axillary lymph node dissection (CALND) after sentinel lymph node biopsy (SLNB) for women with sentinel lymph node metastases is a matter of debate because non-sentinel lymph nodes after CALND contain no further metastases in about 50 % of cases. Our study aims to determine the applicability in our setting of two different validated nomograms to predict axillary lymph node status after SLNB. We collected data about all women who underwent SLNB in our Department of Surgery from 2007 to 2010, focusing on tumor, patient, and breast characteristics. Data was analyzed by R (version 2.15.2); p < 0.05 was considered significant. Among 511 women who underwent SLNB, 126 received CALND due to sentinel lymph node metastasis, and 73.0 % of these had no further metastatic non-sentinel lymph node. The area under the receiver operating characteristic (ROC) curves for the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Tenon score were 78.5 % (95 % CI 70.1-86.8 %) and 77.0 % (95 % CI 67.9-86.0 %) (p = 0.678), respectively. Both the MSKCC nomogram and the Tenon score were predictive for the axillary non-sentinel lymph node status by SLNB. The MSKCC nomogram was the more accurate of the two and the Tenon score was the easier one to apply.

Investigation of the diagnostic precision and utility of sentinel lymph node biopsy in the treatment of patients with Merkel cell carcinoma (MCC).

9042 Background: Merkel cell carcinoma (MCC) is a relatively uncommon and aggressive cutaneous neuroendocrine neoplasm with a high incidence of local recurrence and regional and distant metastasis. The management and identification of prognostic factors remains of value in the treatment of these patients. Although the optimal multidisciplinary treatment of MCC has yet to be determined, the purpose of this study was to investigate whether sentinel lymph node biopsy confers a lower risk of recurrent disease in patients with Merkel cell carcinoma at our institution. Methods: After obtaining institutional review board approvals, all patients with a diagnosis of MCC from 2002-2012 were obtained from our tumor registries. Clinical features, pathologic characteristics, management modalities, and patient outcomes were retrospectively reviewed. Results: Of 20 patients with MCC, nine patients underwent sentinel lymph node biopsy, another four received therapeutic lymph node dissections, and seven patients did not have lymph node evaluation at the initial operation. The most common nodal basins involved were cervical and axillary. Recurrent disease was observed in seven patients (35%). Three patients underwent complete regional lymph node dissection after developing clinically positive nodal disease subsequent to only wide local excision at the index operation (15%). Three patients developed locoregional recurrence and the seventh patient developed metastatic disease to the liver. Of these seven patients with recurrent disease, only two (28.57%) had initial lymph node evaluation. Twelve patients (60%) received adjuvant therapy with chemotherapy (carboplatin/etoposide) and/ or radiation therapy. Conclusions: Merkel cell carcinoma continues to demonstrate its propensity for high rates of recurrence and metastatic disease. Of the seven patients with recurrent locoregional and/or nodal disease in our study, only two patients had initial lymph node evaluation, which was statistically significant with a p value of 0.01175. Further analysis focusing on additional prognostic factors is necessary to optimize our management algorithms and patient outcomes.

Prevalence of and factors contributing to missing lymph tissue in uterine cancer staging surgery

ObjectiveWe wished to investigate the prevalence of missing lymph nodes (MLN), factors contributing to MLN, and the effect of MLN on progression free survival (PFS). MethodsPatients with uterine cancer undergoing abdominal hysterectomy and lymphadenectomy were recruited. All surgeries adhered to the Gynecologic Oncology Group protocol in collecting all the lymph node tissues in paraaortic, common iliac, obturator fossa, and external and internal iliac bilaterally. Data regarding race, age, body mass index (BMI), lymph node counts, staging, location of missing lymph nodes, length of surgery, and estimated blood loss were collected and analyzed in reference to missing lymph nodes. The definition of missing lymph node was an incomplete nodal specimen obtained without actual lymph node tissue. ResultsBetween April 2003 and January 2010, 235 consecutive patients were enrolled prospectively; 108 patients had missing lymph nodes post-operatively (46%), and 127 patients had complete lymph nodes. We found no correlation between MLN relative to race (P=0.97), age (P=0.25), BMI (P=0.09), estimated blood loss (P=0.38), American Society of Anaesthesiologist physical status classification system (P=0.18), surgery time (P=0.22), hospital stay (P=0.05), nodes without cancer (P=0.12), nodes with cancer (P=0.99), stage (P=0.90), grade (P=0.17), or PFS (P=0.29). ConclusionIn our study, although prevalence of missing lymph nodes seems relatively high, none of the perioperative variables studied appeared to contribute to missing lymph nodes. Finally, missing lymph nodes did not affect progression free survival.

Video-assisted thoracoscopic pneumonectomy: a minimally invasive approach for a rare inidication

Minimally invasive video-assisted thoracoscopic surgery (VATS) is considered as an alternative to thoracotomy for early stage lung cancer. Since 2009, we use a VATS approach for all early stage lung tumors as well as benign indications for lung lobectomy. As experience with the technique is growing, indications are expanded. Here, we report our first minimally invasive pneumonectomies of two patients with non-small cell lung cancer (NSCLC). Case 1: A 60-year-old man was diagnosed with a centrally located tumor of the right lung invading all three lobes without any obvious lymph node metastasis in the preoperative work-up. The patient was scheduled for a right-sided VATS pneumonectomy. Case 2: A 62-year-old woman was diagnosed with a centrally located tumor of the left lung with an ipsilateral positron emission tomography (PET) positive lymph node (aortopulmonary window). After neoadjuvant treatment, the patient was scheduled for a left-sided pneumonectomy. Written informed consent was given in both cases. The procedures were completed using three incisions. A complete mediastinal lymph node dissection was performed. The postoperative courses were uneventful. VATS pneumonectomy is feasible in highly selected cases. It offers all advantages known from minimally invasive lung lobectomy with less pain and faster rehabilitation, which might facilitate the delivery of adjuvant treatment.

Abstract P1-01-29: Intraoperative molecular analysis of sentinel lymph node as a new predictor of axillary status in early breast cancer patients.

Abstract The one-step nucleic acid amplification (OSNA) assay (Sysmex Corporation, Kobe, Japan) is a new diagnostic device that uses molecular biological techniques to analyze sentinel lymph node (SLN). Intraoperative SLN assessed by OSNA has been validated as an accurate method for detection of SLN metastasis compared to conventional histological examination. Although recent reports have shown that breast cancer patients with &amp;lt;2 positive SLNs can be spared of a complete axillary lymph node dissection (cALND), there are still a number of patients for whom prediction of non SLN metastasis may be helpful for cALND decision making. The aim of the present study is to assess the intraoperative positive SLN total tumor load (TTL, defined as the amount of CK19 mRNA copies [copies/μL] in all positive SLNs) obtained by OSNA and to determine whether it is predictive of non-SLNs metastasis independently of the number of affected SLN and the type of surgery. Data were collected during the month of June 2012 from medical records and include age, tumor size and grade, estrogen and progesterone receptor status, HER2 status, Ki67, presence of lymphovascular invasion (LVI), total number of SLN and non-SLN, number of positive and negative non-SLN, size of SLN and non-SLN metastasis, and TTL in each SLN. A total number of 701 patients were recruited, of which 697 (99,4%) met the study selection criteria. Univariate logistic regression showed that, in addition to TTL (p &amp;lt; 0,001), the number of affected SLNs (p &amp;lt; 0,001), tumor size (p &amp;lt; 0,001), HER2 status (p = 0,007), and LVI (p &amp;lt; 0,001) were predictive of ALND status. The multivariate logistic regression analysis showed that TTL is an independent predictor of metastatic non-SLNs, after adjusting for the tumor size, HER2 status, LVI and, in particular, the number of affected SLNs. Moreover, the ROC curve analysis showed that, as compared to the number of affected SLN, TTL has a better ROC curve, as measured by the AUC: LogTTL 0.709 (95% CI, 0.667–0.760); number of affected SLN 0.610 (95% CI, 0.570–0.652), p &amp;lt; 0.001. Furthermore, in patients possessing a TTL&amp;lt;15000, the frequency of non-SLN metastasis was 14,7% (NPV = 85,3%, PPV = 41,1%, Sensitivity = 76,7%, Specificity = 55,2%). Taking this value as a cutpoint, 85 patients with mastectomy may have spared a cALND considering the predictive results of the TTL. In seven patients with &amp;gt; 3 positive SLN the TTL was &amp;lt; 15000 so this group, even with 3 positive SLNs, have 14.7% of having additional non SLN metastasis. In conclusion, TTL by OSNA is a newly standardized, automated, and reproducible tool that predicts axillary node status better and independently of the number of affected SLNs and the type of surgery. This value can then help clinicians to personalize surgical treatment. Prospective studies will be carried out to determine the clinical impact of this variable in the management of patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-29.

Whole sentinel lymph node analysis by a molecular assay predicts axillary node status in breast cancer

Background:The one-step nucleic acid amplification (OSNA) assay is a rapid procedure for the detection of lymph node (LN) metastases using molecular biological techniques. The aim of this study was to assess the reliability of the whole sentinel lymph node (SLN) analysis by the OSNA assay as a predictor of non-SLN metastases.Methods:Consecutive 742 patients with breast cancer were enroled in the study. The association of non-SLN or ⩾4 LN metastases with clinicopathological variables was investigated using multivariate logistic analysis.Results:In total, 130 patients with a positive SLN who underwent complete axillary LN dissection were investigated. The frequency of non-SLN metastases in patients who were OSNA+ and ++ was 19.3% and 53.4%, respectively, and that in patients with ⩾4 LN metastases who were OSNA+ and ++ was 7.0% and 27.4%, respectively. The cytokeratin 19 (CK19) mRNA copy number (⩾5.0 × 103; OSNA++) in the SLN was the most significant predictors of non-SLN metastases (P=0.003). The CK19 mRNA copy number (⩾1.0 × 105) in the SLN was the only independent predictor of ⩾4 LN metastases (P=0.014).Conclusion:Whole SLN analysis using the OSNA assay could become a valuable method for predicting non-SLN and ⩾4 LN metastases.

EComment. Mucoepidermoid carcinoma: common findings and surgical treatment

We read with interest the paper by Papiashvilli and co-authors, reporting on an interesting case of mucoepidermoid carcinoma of the lower trachea in a 9-year old boy [1]. Mucoepidermoid carcinomas are rare neoplasms [2] of the bronchial tree arising from mucous and serous glands of the epithelium. They are rare and represent about 1% to 5% of bronchial adenomas, including also adenoid cystic carcinomas (cylindromas), mucous gland adenomas and carcinoids. The term “bronchial adenomas” is not correct because it refers to a benign process, and experience has demonstrated that these tumours have a broad spectrum of biologic activity and can sometimes have malignant behaviour. The term “bronchial adenomas” has therefore been recently replaced by “bronchial gland tumours”. These slow-growing tumours usually manifest with irritation and obstruction of the tracheobronchial tree and symptoms are related to their site [3]. When these masses are located in the trachea, as with the case presented by Papiashvilli et al, they produce upper respiratory tract occlusion with cough, wheezing and dyspnea. In this young patient, respiratory distress was interpreted as asthma until a CT scan showed the tracheal obstruction. Tracheal obstruction must always be suspected in intractable asthma, also in young patients. In cases of localization in the proximal or segmental bronchi, symptoms are usually related to progressive occlusion of a bronchus and therefore are characterized by relapsing pneumonia. Complete surgical resection is the treatment of choice for mucoepidermoid carcinoma. Endoscopic resection has been attempted, but the incidence of local relapse is high. It has a role only as a temporary option in order to plan and facilitate surgery. The principles of surgery are a clear margin at frozen section, complete locoregional lymph nodes removal and maximum sparing of lung parenchyma with tracheobronchial resection and reconstruction techniques. In the case reported by Papiashvilli and co-workers they performed an excellent and successful operation through a sternotomy, which is an unusual access to the lower trachea. As reported by the authors, the choice was based on “difficulty ventilating the child” and “the existence of immediate cardiopulmonary by-pass facilities”. Being general thoracic surgeons, we would have made the same operation through a right thoracotomy, and would have been ready to use a partial by-pass with peripheral cannulation, if required. We appreciate the report of such an unusual case successfully treated in a young boy. Conflict of Interest: None declared

Prediction of the non-sentinel node metastasis in patients without clinically axillary lymph node metastasis, with implication of breast cancer subtypes.

e13060 Background: The accuracy of the nomogram about non-sentinel lymph node metastasis (NSLNM ) in breast cancer patients is still controversial to avoid axillary dissection particularly sentinel lymph node biopsy was positive. The aim of this study was to evaluate the necessity of adding breast cancer subtypes to the NSLNM nomgram variables. Methods: Between 2009 and 2011, consecutive breast cancer patients without clinically axillary lymph node metastasis (n=140) who received sentinel lymph node biopsy at Higashiosaka General Hospital were studied retrospectively. Twenty-two patients were turned out that breast cancer already spread to the sentinel nodes and all of 22 patients received complete axillary lymph node dissection. Results: Twelve patients had only sentinel lymph node metastases(Group S), 10 patients had non-SLN metastases (Group A). Patient characteristics and average probability of spread to additional lymph node developed by Memorial Sloan-Kettering Cancer Center (MSKCC) Nomogram were almost the same results in both groups. However, subtypes of Group S consisted of 8 HER2 positive , 2 triple negative, and 2 luminal A cases, subtypes of Group A consisted of 4 luminal A and 6 luminal B cases. Conclusions: Our data suggested that luminal type breast cancer tends to spread to non-sentinel lymph node metastasis and adding HER2, Ki-67, and intrinsic biological subtypes may improve predictivity of MSKCC nomogram.

Clinical experience with atypical spitzoid tumors in patients younger than age 18: Does fluorescence in situ hybridization predict lymph node metastasis?

8586 Background: Determining the malignant potential of atypical spitzoid melanocytic proliferations can be diagnostically challenging, and many patients are therefore managed as if they had melanoma. However, few studies focus specifically on atypical spitzoid tumors (AST). Further, cytogenetic analysis using fluorescence in situ hybridization (FISH) has been used to determine malignant potential. We reviewed our institutional experience to determine staging and clinical outcomes, and the correlation between FISH findings and regional nodal positivity in patients with AST. Methods: With IRB approval, we retrospectively reviewed all patients aged &lt;18 years treated for AST from 1981-2011 to determine staging variables, outcome, and the results of 4-probe FISH assay. A total of 44 patients with a median age of 11.5 years were identified. All pathology was re-reviewed by a single dermatopathologist. Staging was based on 2010 AJCC criteria. Correlations were determined using either the Pearson or Spearman correlation coefficient. Results: Median lesion thickness was 2.8 mm (range: 0.55-12) and eight (18%) lesions met spitzoid melanoma criteria. Median followup was 4.1 years for all patients (5.5 years for spitzoid melanomas). Thirty-nine patients (89%) underwent sentinel lymph node biopsies (SLNB) and 15 (38%) were positive. Lymph node (LN) positivity correlated with tumor thickness (p=0.002), stage (p=0.001), and mitotic rate (p=0.05). FISH was available for 17/39 patients who had SLNB; sensitivity and specificity for LN metastases were 50% and 54%, respectively. Of 15 patients with a positive SLNB, 12 underwent completion LN dissection, three of which were positive for 1, 2, and 3 additional nodes, respectively. There were no recurrences or disease-related deaths. Conclusions: Traditional indicators of thickness and stage predicted nodal involvement in pediatric patients with AST. However, FISH results did not predict nodal status and should not be used to guide management. With 100% disease specific survival and no recurrences, AST should be considered a separate entity from melanoma and complete excision may be sufficient therapy.

Metastatic sentinel node and axillary lymphadenectomy revisited.

Complete axillary lymph node dissection (ALND) is an integral part of the surgical treatment for breast carcinoma in spite of carrying a high morbidity and frequent secondary side effects.

Complete versus Selective Axillary Lymph Node Dissection in Treatment of Early Breast Carcinoma

Axillary lymph node dissection for staging the axilla in breast carcinoma patients is associated with considerable morbidity, such as edema of the arm, pain, sensory disturbances, impairment of arm mobility, and shoulder stiffness. Selective lymph node biopsy electively removes the palpable lymph node, which gets the drainage from the tumor and should therefore be associated with nearly zero morbidity. Postoperative morbidity (increase in arm circumference, subjective lymphedema, pain, numbness, effect on arm strength and mobility, and stiffness) of the operated arm was prospectively compared in 20 breast carcinoma patients after axillary lymph node dissection (ALND) and 20 patients following Selective lymph node (SLN) biopsy. Patient characteristics were comparable between the two groups. Postoperative follow-up was 15.4 months (range, 4-24 months) in the SLN group and 17.0 months (range, 4-24 months) in the ALND group. Following axillary dissection, patients showed a significant increase in upper and forearm circumference of the operated arm compared with the SLN patients, as well as a significantly higher rate of subjective lymphedema, pain, numbness, and motion restriction. Neither difference between groups regarding arm stiffness or arm strength, nor did the type of surgery affect daily living.

P3-14-18: Primary Tumor Response to Neoadjuvant Chemotherapy Is Significantly Associated with Nodal Pathological Complete Response in Breast Cancer Patients with Cytologically Proven Axillary Node Metastasis.

Abstract Background: Axillary node status is the most significant factor for the prediction of outcome in breast cancer patients whether they received neoadjuvant chemotherapy or not. However, a reliable method to predict nodal response to neoadjuvant chemotherapy is not established yet. The aim of this study was to identify the predictive factors of axillary pathological complete response (pCR) after neoadjuvant chemotherapy in breast cancer patients with cytologically proven axillary lymph node metastases. Patients and methods: A total of 123 patients with axillary metastases confirmed by ultrasound-guided fine-needle aspiration biopsy were subsequently treated with four cycles of anthracycline (60mg/m2) plus cyclophosphamide (600mg/m2) followed by doxetaxel (75-100mg/m2) between August 2008 and March 2011. After neoadjuvant chemotherapy, all patients underwent a definite breast surgery with complete axillary lymph node dissection. Clinicopathological parameters were evaluated using a chi-square test and logistic regression model in association with node pCR. Results: The mean age at diagnosis was 47.9 years in all patients. Eighty-one (65.9%) patients were preoperative clinical T2 stage, 74 (60.2%) showed estrogen receptor (ER)-positivity, and 36 (29.3%) demonstrated HER2−positivity. A pCR of the axilla and breast was determined in 56 (46%) and 40 (31.7%) patients, respectively. Breast Pcr rate is significantly associated with age≤50 at diagnosis, ER(−),PR(−) and higher Ki-67 proliferation. Axillary pCR rate is significantly associated with age at diagnosis of 50 or less, smaller primary tumor size at diagnosis, tumor responsiveness to neoadjuvant chemotherapy, estrogen hormone receptors-negativity, higher Ki-67 proliferative index at diagnosis, and subtypes of HER2−enriched or triple negative breast cancer. When these factors entered logistic regression model, tumor response( SD+PD vs CR+PR: OR 8.603, P=0.007), Ki67((−) vs (+): OR 7.157, p=0.009), ER status((+) vs (−) : OR 4.943, P=0.036), pre-operation tumor size(&amp;gt;2cm vs ≤2cm: OR 5.116, p=0.044), HER2 status( (−) vs (+): OR 5.029,p=0.046) remained to be significant for the prediction of axillary pCR, favorable nodal response. Conclusion: Our study suggests that primary tumor response to neoadjuvant chemotherapy is significantly associated with favorable nodal response. The factors of tumor and nodal response were similar. There are many issues remained to be determined yet. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-18.

Tumor Necrosis as a Prognostic Factor for Stage IA Non-Small Cell Lung Cancer

In stage IA non-small cell lung cancer (NSCLC), lobectomy and mediastinal lymph node dissection is considered the standard treatment. However, 20% to 30% of patients have cancer recurrences. The purpose of this study was to determine the patterns and risk factors for recurrence in patients with stage IA NSCLC. We retrospectively reviewed the medical records of 201 patients who had confirmed stage IA NSCLC by lobectomy and complete lymph node dissection. There were 131 male patients with a mean age of 60.68±9.26 years. The median follow-up period was 41.4 months. Recurrences were reported in 16 patients. One hundred fourteen and 87 patients were T1a (≤2 cm) and T1b (>2 cm to ≤3 cm), respectively. The pathologic results were as follows: adenocarcinomas and bronchioloalveolar carcinomas (n=134); squamous cell carcinomas (n=57); and other diagnoses (n=10). Tumor necrosis and lymphatic invasion were significant adverse risk factors for recurrence based on univariate analysis. Multivariate analysis showed that tumor necrosis was the only significant risk factor to predict cancer recurrence (hazard ratio, 4.336; p=0.032). The 5-year overall survival was 94.8% for necrosis-negative patients and 86.2% for necrosis-positive patients (p=0.04). The 5-year disease-free survival was 92.1% for necrosis-negative patients and 78.9% for necrosis-positive patients (p=0.016). Tumor necrosis was shown to be an adverse risk factor for survival and recurrence in patients with stage IA NSCLC. Thus, close observation and individualized adjuvant therapy might be helpful for patients with stage IA NSCLC with tumor necrosis.

Lymph Node Ratio: A Proposed Refinement of Current Axillary Staging in Breast Cancer Patients

The optimal method for classifying lymph node (LN) status in breast cancer patients is unknown. We sought to determine if LN ratio (LNR) improves axillary staging. Kentucky Cancer Registry data (1996 to 2007) were used to compare LN categorization schemas. Overall survival (OS) was evaluated using the Kaplan-Meier method and log rank tests. Schemas included: LN positive (+) vs negative (-) disease, current American Joint Committee on Cancer (AJCC) staging (0 vs 1 to 3 vs 4 to 9 vs ≥10 LN+), and LNR 0 vs 0.01 to 0.20 vs 0.21 to 0.65 vs >0.65 (LN- vs low, intermediate, and high risk LN+ groups). There were 1,436 patients who had complete LN evaluation data: 880 (61.3%) were LN- and 556 (39.6%) were LN+; 309 (21.5%) had 1 to 3 positive LNs, 138 (9.6%) had 4 to 9 positive LNs, and 109 (7.6%) had 10 or more positive LNs. For LN+ patients, the median number of positive LNs was 3; median LNR was 0.23. The median follow-up was 65 months. LN status was associated with 5-year OS (91.3% and 73.3% for LN- and LN+ groups, respectively, p < 0.001). Increasing AJCC pN stage was associated with worse OS (5-year OS 80.5%, 75.3%, and 49.8% for pN1 to N3, respectively, p < 0.001). LNR was also associated with OS (5-year OS of 83.1%, 72.7%, and 52.7% for the low, intermediate, and high risk LN+ groups, respectively, p < 0.001). In subgroup analyses of patients in the 1 to 3 and 4 to 9 LN+ groups, OS was statistically associated with LNR (p = 0.021 and p = 0.016, respectively). On multivariable survival analysis, LNR was associated with OS, independent of AJCC categorization, p = 0.003. LNR was associated with OS, regardless of AJCC LN categories.

Breast Axillary Lymph Node Metastasis

The surgical management of breast cancer has evolved over the years from extensive radical mastectomy to breast conservation surgery. Until the introduction of the sentinel lymph node biopsy (SLNB), all patients with invasive breast cancer would undergo complete axillary lymph node dissection (ALND) and thus be at risk of suffering from its associated high morbidity. SLNB has become the standard of care and represented significant progress toward reducing the invasive procedures for the management of the axilla. The most recent clinical trials (NSABP-B32 and ACOSOG Z0011) performed in patients that underwent SLNB support this procedure as an accurate predictor of the risk of further axillary node involvement and of breast cancer recurrence. Additionally, the ACOSOG Z0011 trial challenged the standard of practice in the management of the axilla, in which ALND is mandated for all the patients with a positive sentinel node. A similar outcome was demonstrated for a selected group of patients (treated with breast conserving surgery and radiotherapy) with positive SLNB then followed by ALND or SLNB only. In light of these results, the role of ALND in the current management of breast cancer is being reevaluated for specific patient subpopulations. In this special issue, this timely subject is provocatively reviewed in addition to other relevant topics, such as the controversial meaning of the presence of micrometastasis and isolated tumor cells in the SLN in relation to local recurrence and overall survival and the feasibility of performing SLNB after neoadjuvant treatment and transaxillary breast augmentation. Despite the advances in the lymphatic mapping and in the intraoperative methods for SLN analysis, the accurate identification of tumor cells in this node continues to be a challenge in clinical practice, and significant false-negative results in SLNB are still observed. In a research study published in this issue, a preferential cellular distribution of the malignant cells in the SLN is reported, suggesting that the pathological analysis directed to this area may contribute to a more precise identification of nodal metastasis. Additional progress in this direction involves the development of molecular markers, which would tackle not only the misdiagnosed SLN-negative patients but also the ones with low risk of recurrence that are unnecessarily submitted to SLNB. In this sense, the Bayesian-based nomogram developed by Westover et al. is proposed to be particularly useful, especially in cases where the SLNB assessment is predicted to be less sensitive. This nomogram would also lead to the identification of high-risk individuals for recurrence, based on the calculation of residual axillary disease risk, despite a negative SLNB. Several new reports, mostly based on gene expression profiling, have suggested that the different rates of recurrence can be due to the distinct molecular types of breast cancer. The development of a genomic signature that effectively discriminates patients by lymph node status, as the one proposed by Ellsworth et al., could stratify patients based on their need of surgical evaluation of the lymph nodes, sparing the ones in which disease will probably be limited to its primary site. The assessment of specific tumor markers in the lymph nodes is also discussed in this special issue, including a review of the prognostic and/or predictive implications of lymph node metastasis in tumors with elevated levels of CXCR4 (a protein chemokine receptor) and VEGF-C (a vascular endothelial cellular growth factor). From the Halsted radical mastectomy to the commercial gene expression profiling tests, axillary lymph node management and recurrence prediction are still evolving topics for patients with breast cancer. The continued improvement of molecular tumor profiling and bioinformatics from larger and better defined patient cohorts will certainly provide answers to many challenging questions regarding the axillary metastatic process. The clarification of this complex molecular mechanism and the identification of novel and integrative molecular markers that can reliably predict lymph node involvement that will affect risk of recurrence and survival will continue to form the basis of the contemporary approach for breast cancer management, where an early prediction of axillary metastasis and a personalized cancer treatment can be achieved. Luciane R. Cavalli Rachel E. Ellsworth Christoph Klein Giuseppe Viale

Renal cell carcinoma in children and adolescents

Although rare in children and adolescents, renal cell carcinomas (RCCs) raise important questions concerning the best treatment approach and accurate pathologic classification. The differences emerging between childhood and adulthood RCC probably prevent any direct generalized application of therapies to children that are validated for adults. The translocation type of RCC, which forms a distinct category characterized by translocations involving Xp11.2 or, less frequently, 6p21, has recently emerged as the predominant type of RCC in children and adolescents, whereas it is rarely diagnosed in adults. This new finding emphasizes how important it is to prospectively classify RCCs in children with standardized ‘modern’ diagnoses. The standard cornerstone of therapy for RCC in children and adolescents remains radical nephrectomy. Nephron-sparing surgery is currently recommended in adults for selected small-volume tumors, but additional data are needed before this experience can be extensively transferred to the pediatric population. The therapeutic value of complete retroperitoneal lymph node dissection is still controversial, especially in patients without suspected nodal involvement, be they adults or children. The backbone of systemic therapies for adult RCC has recently been changed by the introduction of drugs designed to target tumor-related angiogenesis and signal transduction. It is worth noting that the largest clinical efficacy trials on targeted molecules have been conducted on clear-cell RCC. While targeted drugs have become the standard of care for adult metastatic RCC, there are currently no published reports on their role in children, and their use should be considered for patients with unresectable metastatic or advanced-stage RCC. On the other hand, the utility of targeted therapies in the adjuvant setting remains to be seen for both adults and children.

Wächterlymphknotenbiopsie beim Mammakarzinom

Complete axillary lymph node dissection has been the traditional operation to determine whether cancer has spread beyond the breast. In the large majority of patients with breast cancer, lymphatic mapping and γ-probe-guided and/or blue dye sentinel node biopsy can be used to locate the first node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel node biopsy routinely. Thus, they may be spared complete axillary dissection if the sentinel node is negative. Decreased arm swelling and pain are associated with sentinel lymph node biopsy compared with axillary lymph node dissection.