N2 Metastasis Research Articles

Lung adenocarcinoma: Are skip N2 metastases different from non-skip?

ObjectiveThis study investigated the association between clinical pathologic features, especially adenocarcinoma subtypes and prognosis, and skip N2 metastasis in patients with lung adenocarcinoma. MethodsIn this study, 177 patients with lung adenocarcinoma and N2 metastasis were enrolled. Patients who had N2 lymph node metastases without N1 lymph node involvement were defined as skip N2 and otherwise as non-skip N2. We investigated the difference of clinicopathologic characteristics, recurrence-free survival, overall survival, and spectrum of well-identified molecular alterations in EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET genes in the 2 groups. ResultsSkip N2 metastasis was found in 45 patients, in whom a remarkably lower incidence of lymphovascular invasion was revealed (P = .01). Skip N2 metastasis was also associated with acinar subtype, good differentiation, and right lung cancer. The recurrence-free survival and overall survival were significantly better in the skip N2 group (5-year recurrence-free survival 37.4% vs 5.7%; log-rank P = .005; 5-year overall survival 60.7% vs 32.1%; log-rank P = .024). The predictive value of skip N2 was more significant in patients with lesions in the right lung (5-year recurrence-free survival 36.6% vs 0.0%; log-rank P = .002; 5-year overall survival 57.2% vs 27.9%; log-rank P = .016) and in patients whose tumor diameter was no more than 3 cm (5-year recurrence-free survival 43.1% vs 6.7%; log-rank P = .01; 5-year overall survival 74.6 vs 27.6%; log-rank P = .04). ConclusionsThere are distinct differences in clinicopathologic features and prognosis in patients with or without skip N2 metastasis. Considering the results of our study, subclassifications of mediastinal lymph node metastases could have clinical significance for patients with lung adenocarcinoma.

Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA-N2 Non–Small-Cell Lung Cancer After Curative Resection

IntroductionThere have been controversies regarding the prognostic relevance of the number of positive N2 nodes in pathologic stage IIIA-N2 non–small-cell lung cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2 with classifying the number of positive N2 nodes into subgroups. MethodsFrom January 1997 to December 2004, 250 patients were diagnosed with pathologic stage IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After excluding 44 patients with preoperative chemotherapy, incomplete resection, and postsurgical mortality, 206 patients were included in the analysis. Patients were classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83], N2b: 2-4 [n = 82], N2c: ≥ 5 [n = 41]), and its correlation with survival outcomes were investigated. ResultsWith a median follow-up of 96.3 months, 5-year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6-33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all patients. The number of metastatic N2 lymph nodes was associated with DFS (P < .001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were 38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%, respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes was an independent prognostic factor for DFS and OS. ConclusionStratification of patients according to the number of metastatic N2 lymph nodes may improve the accuracy of prognostic prediction among patients with curatively resected stage IIIA-N2 NSCLC.

Lectin microarray technology identifies specific lectins related to lymph node metastasis of advanced gastric cancer.

Although various molecular profiling technologies have the potential to predict specific tumor phenotypes, the comprehensive profiling of lectin-bound glycans in human cancer tissues has not yet been achieved. We examined 242 advanced gastric cancer (AGC) patients without or with lymph node metastasis-N0 (n = 62) or N+ (n = 180)-by lectin microarray, and identified the specific lectins highly associated with AGC phenotypes. In seven gastric cancer cell lines, in contrast to expressed-in-cancer lectins, not-expressed-in-cancer (NEC) lectins were tentatively designated by lectin microarray. Binding signals of the specific lectins were robustly reduced in AGC patients with N+ status as compared with those with N0 status. The receiver operating characteristic curve determined the optimal cutoff value to differentiate N0 status from N+ status, and subsequent profiling of NEC lectins identified Vicia villosa agglutinin (VVA) association with the significant other lectins involved in lymph node metastasis. VVA reaction was clearly found on cancer cells, suggesting that it may result from carcinoma-stroma interaction in primary AGC, because VVA is an NEC lectin. Most intriguingly, VVA reaction was remarkably attenuated in the tumor cells of the metastatic lymph nodes, even if it was recognized in primary AGC. In AGC, histological type was strongly associated with soybean agglutinin and Bauhinia purpurea lectin, whereas p53 mutation was the best correlated with Griffonia simplicifolia lectin II. Lectin microarrays can be used to very accurately quantify the reaction of glycans with tumor tissues, and such profiles may represent the specific phenotypes, including N+ status, histological type, or p53 mutation of AGC.

Risk factors for recurrence after complete resection of pathological stage N2 non-small cell lung cancer.

BackgroundTumor recurrence is the most common cause of treatment failure, especially after complete resection of pathological stage N2 non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological characteristics in order to identify independent risk factors for postoperative recurrence.MethodsBetween January 2001 and December 2013, 96 patients who underwent surgical resection for pathological N2 NSCLC were retrospectively reviewed. Recurrence-free survival (RFS) was calculated by the Kaplan-Meier method to explore risk factors, while the Cox proportional hazard model was used to assess independent predictors.ResultsThe median and five-year RFS rates were 15 months and 27.4%, respectively. Univariate analysis showed a significantly poorer prognosis for non-regional N2 metastasis, more than three metastatic N2 lymph nodes, multiple N2 station, and multiple N2 zone involvement. Multivariate analysis demonstrated that non-regional N2 metastasis (hazard ratio [HR] 1.857, 95% confidence interval [CI] 1.061–3.249, P = 0.030) and more than three metastatic N2 lymph nodes (HR 2.555, 95% CI 1.164–5.606, P = 0.019) were independent risk factors for RFS. Additionally, the incidence of non-regional N2 metastasis was higher in patients with a primary tumor in the left lower (57.1%) or right lower lobe (48.1%), followed by left upper (31.8%), right middle (14.3%) and right upper lobe (7.7%).ConclusionThe combination of the distribution and number of metastatic N2 lymph nodes provides a more accurate prediction for N2 NSCLC regarding recurrence. Non-regional N2 metastasis could occur with a primary tumor in any lobe, but occurs more frequently in the lower lobe.

Endobronchial Ultrasound versus Mediastinoscopy for Mediastinal Nodal Staging of Non–Small-Cell Lung Cancer

Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non-small-cell lung cancer (NSCLC). The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with that of mediastinoscopy in patients with NSCLC. A prospective trial was conducted in a tertiary referral center in Korea. Patients with histologically proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy. In total, 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%, 100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively. Significant differences in the sensitivity, accuracy, and NPV were evident between EBUS-TBNA and mediastinoscopy (p < 0.005). EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1-3 NSCLC. Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity, it should be the first-line procedure performed in patients with NSCLC.

Influence of visceral pleural invasion on survival in completely resected non-small-cell lung cancer.

Although the prognostic implications of visceral pleural invasion (VPI) are well established, it remains controversial whether the extent of VPI affects survival in patients with completely resected non-small-cell lung cancer (NSCLC). In addition, the impact of VPI according to nodal status is unclear. We evaluated the influence of the extent of pleural invasion on survival by analysing a multicentre retrospective database of patients who had undergone surgery for NSCLC. We retrospectively reviewed the clinicopathological characteristics and outcomes of 639 patients with NSCLC who underwent anatomic complete resection from 2005 to 2007 at nine hospitals affiliated with the Yokohama Consortium of Thoracic Surgeons. The median follow-up was 65.0 months. The extent of pleural invasion was PL0 in 462 patients, PL1 in 135 and PL2 in 42. The 5-year overall survival rate was significantly higher in patients with PL0 tumours (75.9%) than in those with PL1 (63.6%) or PL2 tumours (54.1%). On subgroup analysis according to nodal status, PL0 was associated with a higher survival rate than that of PL1 or PL2 tumours in patients with N0 or N1 metastasis, but not in those with N2 metastasis. There was no difference between PL1 and PL2 in any subgroup. Our results suggest that the presence of VPI, rather than the extent, has an impact on postoperative survival in patients with NSCLC who have N0 or N1 metastasis. Because very few previous studies have addressed the effects of VPI in patients with N1 disease, further re-evaluation of the prognostic impact of VPI is necessary in this subgroup of patients.

Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer.

Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing an optimal treatment strategy. This study aimed to determine the predictive risk factors for lymph node metastasis, including both N1 and N2 metastases, in clinical T1aN0 NSCLC patients. We retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no radiologic evidence of lymph node metastasis, and who had undergone surgical pulmonary resection with systematic mediastinal node dissection or sampling at the First Affiliated Hospital of Zhejiang University between January 2011 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for node metastasis. Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients. Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2 nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients had nodal skip metastasis. Variables of preoperative radiographic tumor size, non-upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and micropapillary predominant adenocarcinoma (AC) were identified as predictors for positive N1 or N2 node multivariate analysis. Pathologically positive lymph nodes were common in small size NSCLC patients with clinical negative lymph nodes. Therefore, preoperative staging should be performed more thoroughly to increase accuracy, especially for patients who have the larger size, non-upper lobe located, high CEA level or micropapillary predominant ACs.

Long-term oncologic results of laparoscopic D3 lymphadenectomy with complete mesocolic excision for right-sided colon cancer with clinically positive lymph nodes.

To assess surgical outcomes of patients undergoing D3 lymph node dissection and complete mesocolic excision for the treatment of right-sided colon cancer in the context that both procedures were performed laparoscopically. 244 consecutive patients with clinically staged III right-sided colon cancer were recruited to undergo the laparoscopic D3 lymph node dissection with complete mesocolic excision. Postoperatively, the patients were stratified as N0, N1, N2, and N3 groups according to the level of lymph node metastasis, prospectively followed up for more than 5 years, and compared. The 5-year cumulative recurrence rate and the estimated time-to-recurrence [mean (95 % confidence interval)] was 16.6 % (n = 7/42), 113.8 (101.4-126.2) months in N0 group; 21.3 % (n = 17/80), 108.9 (99.1-118.7) months in N1 group; 43.2 % (n = 32/74), 85.4 (73.0-97.8) months in N2 group; and 52.0 % (n = 25/48), 65.2 (49.0-81.4) months in N3 group. When N1 and N0 groups of patients were lumped together, and compared with patients with N2 or N3 metastasis, we found that the latter were with a significantly higher recurrence rate (p < 0.0001). D3 lymph node dissection with complete mesocolic excision could assure the harvest of sufficient number (n = 34.4 ± 8.4) of lymph nodes for precise pathologic cancer staging. Skip lymph node metastasis was detected in 19.8 % (n = 40/202) of patients, and such surgical procedures facilitated up-staging in 4.5 % (n = 11/244) of patients. The present study encourages the dissemination of such concepts to surgical oncologists dealing with colorectal cancer through didactic education, and international consensus meeting is therefore mandatory to optimize the surgery of colon cancer.

Characteristics and prognosis of mucinous gastric carcinoma.

Mucinous gastric carcinoma (MGC) is a rare histological subtype of undifferentiated gastric carcinoma, accounting for ~2.6-6.6% of all gastric cancer cases. The clinicopathological characteristics and prognosis of MGC are controversial. The present study aimed to determine the clinicopathological characteristics and prognosis of patients with MGC. We retrospectively compared the characteristics and postoperative survival of 70 patients with MGC and 2,492 non-MGC (NMGC) cases who underwent surgical resection between 1990 and 2010. MGC was characterised by larger tumor size, macroscopic Borrmann type 2 and 3, T4 invasion of the gastric wall, positive N2 and N3 lymph node metastasis, positive lymphatic vessel invasion, positive venous invasion, peritoneal metastasis and advanced tumor stage III and IV. The prognosis of MGC patients was worse compared to that of NMGC patients, as the former group consisted of more advanced-stage cases. When patients with similar disease stages were compared, the incidence of peritoneal metastasis was significantly higher among MGC patients. However, hepatic metastasis was found significantly more often in NMGC patients. Otherwise, the prognosis of MGC and NMGC patients with similar disease stages was not significantly different. Therefore, our findings indicated that, although MGC is more rare and mostly detected at an advanced stage, the diagnosis of the mucinous histological subtype was not an independent prognostic factor.

Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

BackgroundThe development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN) metastasis in NPC in the IMRT era.Material and MethodsWe retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492) of the patients with stage III or IV disease.ResultsThe incidence of RLN metastasis was 64.2% (481/749). Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001) and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001) rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively), but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively). Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020), and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively). In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994).ConclusionsIn the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN metastasis as N1a disease in future by a larger cohort study.

Prognostic value of metastatic N1 lymph node ratio and angiolymphatic invasion in patients with pathologic stage IIA non-small cell lung cancer.

With regard to pathologic stage IIA (pIIA) non-small cell lung cancer (NSCLC), there is a paucity of literature evaluating the risk factors for disease-free survival (DFS) and overall survival (OS). The aim of this study was to identify the prognostic factors of DFS and OS in patients with NSCLC pIIA.We performed a retrospective review of 98 stage II patients (7th edition of the American Joint Committee on Cancer) who underwent lung resection from January 2005 to February 2011. Of these, 23 patients were excluded for this study because of loss of follow-up or different substage, and 75 patients with pIIA were included for further univariate and multivariate analysis. Risk factors for DFS and OS were analyzed, including age, gender, smoking history, operation method, histology, differential grade, visceral pleural invasion, angiolymphatic invasion, and metastatic N1 lymph node ratio (LNR).Of the 75 patients with pIIA NSCLC who were examined, 29 were female and 46 were male, with a mean age of 61.8 years (range: 34–83 years). The average tumor size was 3.188 cm (range: 1.10–6.0 cm). Under univariate analysis, angiolymphatic invasion and metastatic N1 LNR were risk factors for DFS (P = 0.011, P = 0.007). Under multivariate analysis, angiolymphatic invasion and metastatic N1 LNR were all independent risk factors for DFS, while adjuvant chemotherapy and higher metastatic N1 LNR were independent prognostic factors for OS.For patients with pIIA, higher metastatic N1 LNR and angiolymphatic invasion were related to poor DFS. In addition to DFS, higher metastatic N1 LNR was also a poor prognostic factor for OS rates and adjuvant therapy effectiveness. Clinical physicians should devise different postsurgical follow-up programs depending on these factors, especially for patients with high risk.

Risk factors for N2 metastasis in patients with non-small-cell lung cancer

N staging is a key factor when considering the choice of treatment for non-small-lung cancer. It is possible that there is a correlation between N2 metastasis and some risk factors. The objective of the present study was to evaluate associations between several risk factors and N(2) metastasis using univariate and multivariate analyses, which may assist clinicians in therapeutic planning. The enrolled patients were divided into two groups on the basis of histopathological results after surgery: those with pN(2) disease (N(2) group) and those without (N(2) group). Sex, age, location, size, maximum standardized uptake value (SUV(max)) on fluorine-18 fluorodeoxyglucose PET, histopathological type, and tumor cell grade were compared between N(2) and N(2) groups. Correlations between each significant factor and groups were analyzed using univariate analyses. Independent risk factors were finally identified with multivariate analyses. A total of 258 patients met the inclusion criteria. Univariate analyses showed significant correlation between size, SUV(max), tumor cell grade, and N(2) status (P<0.05). Multivariate logistic regression showed that both SUV(max) and tumor cell grade were independent risk factors and had predictive value for N(2) disease (P<0.05). There were no N(2) node metastases when tumor SUV(max) was up to 2.5 and the tumor cell grade was low. However, the likelihood of metastasis increased to 0.29 and 0.28 when tumor SUV(max) was greater than 7.5 and when the tumor cell grade was high. SUV(max) and tumor cell grade are independent risk factors for N(2) metastasis.

Incidence of Occult N1 Disease in Patients With Clinical Stage I Non-Small Cell Lung Cancer: Implications for Patients Considered for Stereotactic Body Radiation Therapy

Most patients receiving stereotactic body radiation therapy (SBRT) for stage I non-small cell lung cancer (NSCLC) are staged clinically with PET/CT. While PET/CT is associated with a negative predictive value (NPV) of ∼90% for occult mediastinal (N2) disease, limited data exist for occult hilar/peribronchial (N1) disease. We hypothesize that PET/CT underestimates spread of cancer to N1 lymph nodes and that future SBRT patients may benefit from increased pathologic staging of these nodal stations. A retrospective study was performed of all patients with clinical stage I NSCLC (AJCC 7th edition) by PET/CT at a single institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Patients were excluded if PET/CT was performed more than 3 months prior to operation, or if lymph node involvement was “indeterminate” or “equivocal” on imaging. Findings on PET/CT were compared to pathologic nodal involvement to determine NPV. No patients were staged with endoscopic bronchial ultrasound (EBUS) prior to surgery. 105 patients were eligible for this study. Median age was 68 years [range: 43-87 years]. Only 4 patients (4%) had a previous lung cancer history but were determined to have a second primary cancer on pathologic review. Clinical T-stage distribution was as follows: T1a (43%), T1b (28.5%), and T2a (28.5%). Median time from PET/CT scan to operation was 4 weeks (range: 0.5-12 weeks). Median SUV max was 5.2 [range: 0.7-33.6]. Extent of resection included lobectomy (94%), bilobectomy (4%), and wedge (2%). The median number of N1 nodes sampled was 5 [range; 1-19] and the median number of N2 nodes sampled was 5 [range: 1-25]. Mean pathologic tumor size was 2.62 cm. Histologies included adenocarcinoma (52%), squamous cell carcinoma (33%), large cell carcinoma (10%), and adenosquamous (5%). A total of 8 of 105 patients (7.6%) were found to have occult N1 metastasis on pathologic review. The NPV of PET/CT for N1 disease among all stage I patients was 92.4%. Five of these 8 patients had T2 tumors. The NPV in patients with clinically-staged T1 and T2 tumors was 72/75 (96%) and 25/30 (83%), respectively (p = 0.027). No patients were found to have occult mediastinal nodes. Our results support pathologic assessment of N1 lymph nodes in stage I NSCLC patients being considered for SBRT, with greatest benefit in patients with T2 tumors. Diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of SBRT candidates.

Risk factors for N2 lymphatic metastasis in patients with non-small cell lung cancer

Objective To assess risk factors in NSCLC with N2 metastasis.Methods A total of 177 NSCLC patients (109 males,68 females; age:(60.1 ± 10.6) years) who underwent both 18F-FDG PET/CT scan and surgery were enrolled.They were divided into two groups.One was with N2 metastasis (N2+) and the other was without (non-N2+).The gender,age,location,size,primary tumor SUVmax,histopathologic type and differentiation grade between N2+ group and non-N2+ group were compared with x2 test and two-sample t test.After assignment of significant factors and groups,correlations between each factor and group were analyzed with uni-and multivariate analyses,and then the risk factors were identified finally with logistic regression analysis.Results Significant difference among factors of tumor size ((36.1±19.7) mm vs (49.3±24.4) mm),SUVmax(8.81±6.23 vs 11.21±4.43) and differentiation grades (high:3 vs 0; moderate:74 vs 11; poor:65 vs 24) were observed between non-N2+ group and N2+ group (t =-2.969,-2.633,x2 =6.143,all P＜0.05).Besides,the univariate analysis showed significant correlations between tumor size,SUVmax,differentiation grade and N2 status (r=0.201,0.245,0.185,all P＜0.05).However,multivariate logistic regression revealed that only SUVmax had a predictive value (β=0.546,P＜0.01).The incidence of N2 metastasis went up along with the increase of SUVmax.There was no N2 metastasis in the patients with SUVmax ≤2.5,and the incidence rate of metastasis increased to 0.29 in those with SUVmax＞7.5.Conclusion SUVmax may be an independent risk factor to predict N2 metastasis in NSCLC patients. Key words: Carcinoma, non-small cell lung; Neoplasm metastasis; Lymph nodes; Risk factors

8:18 AM Abstract No. 157 - Safety and feasibility of percutaneous microwave ablation (MVA) of lung tumors

Purpose: Percutaneous ablation of lung tumors is a minimally invasive therapy for patients with primary or metastatic cancer who are not surgical candidates or in whom standard therapy fails. We present our experience with percutaneous MWA of lung tumors. Materials and Methods: 14 consecutive patients (3 male, 11 female), aged 64-89, underwent 17 treatments of 17 target lesions. 9/17 tumors were primary non-small cell lung carcinomas and 8/17 were metastatic (Colon n1⁄42, Hepatobiliary n1⁄41, Neuroendocrine n1⁄41, Head and Neck n1⁄44). Clinical evaluation was performed at baseline, 2 weeks, 30 days and 6 months. Response was assessed using Modified Response Evaluation Criteria in Solid Tumors (n1⁄413) at 6 months and classified as: Complete Response (CR), Partial Response (PR), or Progressive Disease (PD). Complications were reported according to Society of Interventional Radiology Grading System [1,2]. Results: Baseline Eastern Cooperative Oncology Group performance status average was 0.9 (range 0-3). Mean tumor size for 2.4 cm (N1⁄417, 1.2 cm-5.8 cm); mean tumor size was 2.6 cm (Primary N1⁄49, 1.4 cm-4.5 cm) and 2.1cm (Metastatic n1⁄48, 1.2 cm-5.8 cm). 16/17 treatments were technically successful with one unsuccessful case secondary to inability to place the probe safely through the tumor. 30 day, 6 month and 1 year survival was: 100% (n1⁄414), 100% (n1⁄411) and 100%(n1⁄47). Response rates for primary and metastatic tumors were as follows: (Primary, n1⁄46) CR 83%, PR 17%, PD 0 %, (Metastatic, n1⁄47) CR 100%, PR 0.0%, PD 0%. One case of locally progressive disease was initially treated with palliative intent. Three major and 2 minor complications: pneumothorax requiring chest tube placement (3/17), pneumothorax without chest tube (1/17), self-resolved hemoptysis (1/17). Conclusion: Percutaneous microwave ablation is a feasible and potentially safe technique for lung tumor ablation with promising response rates.

Sialyl Lewis X as a predictor of skip N2 metastasis in clinical stage IA non-small cell lung cancer

BackgroundRadical segmentectomy has been performed for small-sized non-small cell lung cancer (NSCLC). However, underestimation of mediastinal lymph node metastasis in the absence of hilar or interlobar metastasis (skip N2) affects surgical strategy. Our aim was to investigate preoperative and intraoperative predictors of skip N2 in clinical stage (c-stage) IA NSCLC.MethodsFrom 1998 to 2011, 279 patients (155 men and 124 women) with c-stage IA NSCLC (230 pN0, 17 pN1, 12 skip N2, 20 non-skip N2) underwent systematic lobectomy (R0 resection) at our institute. We compared preoperative serum concentrations of carcinoembryonic antigen, cytokeratin 19 fragment, sialyl Lewis X (SLX), and pre- and intraoperative clinicopathological features of pN0 and skip N2 patients. Receiver operator characteristic (ROC) curve analysis was performed to distinguish between the two patient groups.ResultsThe 5-year survival rate of skip N2 patients was 78.6%, higher than that of non-skip N2 patients (44.9%), and not significantly different than that of pN0 (86.7%) or pN1 patients (82.4%). The mean serum SLX concentration in skip N2 patients (28.0 U/ml) was elevated compared to that in pN0 patients (22.9 U/ml). In ROC analysis of SLX, the area under the curve was 0.710, and the optimal cut-off value was 21.4 U/ml (sensitivity, 91.7%; specificity, 51.7%). In multivariate analysis, SLX was an independent predictor of skip N2 in patients with c-stage IA NSCLC (odds ratio, 9.43; p = 0.006).ConclusionsSkip N2 metastasis is common in patients with c-stage IA NSCLC with high serum SLX, and lobectomy with complete dissection of hilar and mediastinal lymph nodes should remain the standard surgical procedure for these cases.

Locally advanced gallbladder cancer: Which patients benefit from resection?

ObjectivesPatients with T3–4 gallbladder cancers (GBCs) often require extended surgical procedures, and up to 30% of patients have N2 metastases. This study investigated which patients with T3–4 GBC benefit from resection. MethodsConsecutive patients (n = 78) with T3–4 GBC who underwent resection between 1990 and 2011 were analysed (38 before 2003, 40 in 2003–2011). Forty patients required common bile duct (CBD) resection, 10 pancreatoduodenectomy, 4 right colectomy and 2 gastric resection. Fifty-two (67%) patients had LN metastases, including 22 with N2 metastases. ResultsThe in-hospital mortality rate was 8%, 11% before 2003 vs. 5% in 2003–2011. The morbidity rate (47%) remained stable during the study. Undergoing liver and pancreatic resection did not increase severe morbidity (0%) or mortality (10%). Sixty-seven (86%) patients had R0 resection. The 5-year survival rate was 17% (median follow-up, 65 months). Survival improved after 2002 (26% vs. 9%, p = 0.04). R1 patients had poor 3-year survival (0% vs. 32%, p = 0.001). N+ patients also had low survival (5-year survival, 10% vs. 32% in N0, p = 0.019), but N1 and N2 patients had similar outcomes. CBD resection and major hepatectomy did not worsen prognosis. Patients requiring pancreatoduodenectomy, gastric or colonic resection had 0% 3-year survival (p = 0.036 in multivariate analysis). ConclusionsResection of T3–4 GBC is worthwhile only if R0 surgery is achievable. Outcomes improved in most recent years. N2 metastases should not preclude surgery. Good results are possible even with CBD resection or major hepatectomy, while benefits from surgery are doubtful if pancreatoduodenectomy or other organ resection is needed.

Prognostic factors after complete resection of pN2 non–small cell lung cancer

This retrospective, multicenter study aimed to determine prognostic factors of completely resected pathologic N2 stage IIIA non-small cell cancer (NSCLC). From 25 participating hospitals, 496 patients (325 men and 171 women; median age, 65 years) who underwent complete resection without preoperative treatment for pT1-3 N2 M0, stage IIIA NSCLC between2000 and 2004 were enrolled. Lobectomy/bilobectomy was performed in 462 patients and pneumonectomy in 34. Some kind of adjuvant chemotherapy was administered to 296 patients. Survivals were calculated using the Kaplan-Meier method, and prognostic factors were determined using the Cox proportional hazards model. Five-year overall survival (OS) and disease-free survival (DFS) were 44.8% and 24.2%, respectively. pT classification (hazard ratio (HR), pT1/pT2/pT3=1/1.32/2.03), single or multiple N2 metastases (HR, single/multiple=1/1.36), and skip or nonskip N2 metastasis (HR, skip/nonskip=1/1.30) were found to be independent prognostic factors for DFS. Sex (HR, female/male=1/1.36), performance status (HR, PS-0/PS-1=1/1.37), tumor diameter (HR, 1.12 per 1-cm increase), pT-factor (HR, pT1/pT2/pT3=1/1.37/2.22), and extent of N2 metastasis (HR, localized/extended=1/1.39) were shown to be independent prognostic factors for OS. We found that pT classification was a significant prognostic indicator for OS and DFS whereas tumor diameter, performance status, and sex were ones for OS. Single N2 metastasis and skip N2 metastasis were demonstrated as favorable prognostic factors for DFS, limited N2 metastasis was one for OS, and these should be considered as stratification factors for trial on adjuvant therapy.

Differential diagnosis of solid pancreatic masses: Contrast-enhanced harmonic EUS (CEHEUS), quantitative EUS-elastography (QE-EUS) or both?

Background: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and quantitative-elastography endoscopic ultrasound (QE-EUS) are considered useful tools for the evaluation of solid pancreatic tumors (SPT). The aim of our study was to evaluate the diagnostic accuracy of CEH-EUS, QE-EUS, and the combination of both for the differential diagnosis of SPT. Methods: Sixty-two consecutive patients (mean age 64.3 years, range 32–89 years, 44 male) who underwent EUS for the evaluation of SPT were prospectively included. EUS was performed with a linear Pentax-EUS and a Hitachi-Preirus processor. The mass (area A) and a reference area B were selected during QE-EUS, and results expressed as B/A (strain ratio). A strain histogram of the mass was also evaluated. Microvascularization of the tumor was evaluated over 2 min during CEH-EUS after intravenous injection of 4.8 mL SonoVue. Final diagnosis was based on histopathology of surgical specimens or EUS-guided tissue acquisition and clinical follow-up in non-operated cases. Diagnostic accuracy of CEH-EUS, QE-EUS, and their combination was calculated. Results: Median size of the masses was 32 mm (range 12-111). Final diagnosis was pancreatic adenocarcinoma (n1⁄4 45), neuroendocrine tumor (n1⁄4 3), inflammatory mass (n1⁄4 10), pancreatic metastasis (n1⁄4 2), autoimmune pancreatitis (n1⁄4 1), and a mucinous cystadenocarcinoma (n1⁄4 1). Overall accuracies for determination of malignancy using QE-EUS, CEH-EUS, their combination, and EUS-guided tissue acquisition were 98.4% (95% confidence interval (CI): 91.4–99.7), 85.5% (95% CI: 74.7–92.2), 91.9% (95% CI: 82.5–96.5), and 91.5% (95% CI: 83.6–99.5), respectively. Conclusion: The combination of QE-EUS and CEH-EUS is a useful tool for the differential diagnosis of SPT, giving complementary information. However, this combination does not significantly increase the diagnostic accuracy of either of the techniques performed alone.

Heterogeneity of Clinical N1 Non-Small Cell Lung Cancer

There have been many reports of N1 node metastasis on computed tomography (CT) scan, but not on positron emission tomography (PET)-CT in nonsmall cell lung cancer. The aim of this study was to analyze the clinicopathologic correlation and survival of N1 disease on preoperative PET-CT. From January 2003 to December 2007, 1,748 curative lung resections were performed at a single institute. We enrolled 91 patients with clinical N1 on PET-CT. All the enrolled patients had undergone pulmonary resection with mediastinal lymph node dissection. According to the preoperative PET-CT, we classified the patients into two groups: those with single N1 metastasis (cN1a, n = 91) and those with multiple N1 metastases (cN1b, n = 8). Clinicopathologic N staging was compared and survival analysis was performed. Pathologic N2 was found in 19 (19%) patients and was more common in cN1b (4 of 8) than in cN1a group (15 of 91) (p = 0.042). Overall or disease-free survival rate was not different between cN1a and cN1b in the pathologic non-N2 (p = 0.723, 0.905) or in pathologic N2 (p = 0.954, 0.607) subgroups. Clinical N1 on PET-CT is heterogeneous in its pathologic staging and multiple clinical N1 is more related to pathologic N2 than single clinical N1. More cases are needed to show the prognostic significance of multiple clinical N1-pathologic N2.