Patients with sentinel lymph node positive melanoma: Who needs completion lymph node dissection?

Introduction

Completion lymph node dissection (CLND) for melanoma after positive sentinel lymph node biopsy (SLNB) was recently shown to improve regional but not overall survival, likely due to the majority of patients harboring no further nodal disease. We sought to determine predictors of non-sentinel node (NSN) positivity.

Extended lymph node dissection in robot-assisted radical prostatectomy： lymph node yield and distribution of metastases

In this study, we reported our experience performing robotic extended lymph node dissection （eLND） in patients with prostate cancer. A total of 147 patients with intermediate and high-risk prostate cancer who underwent robotic eLND from May 2008 to December 2011 were included in this analysis. The dissection template extended to the ureter crossing the iliac vessels. We assessed lymph node yield, lymph node positivity, and perioperative outcomes. Lymph node positivity was also evaluated according to the number of lymph nodes （LNs） removed （〈22 vs 〉22）. The median number of LNs removed was 22 （11-51）, and 97 positive LNs were found in 24 patients （16.3%）. While the obturator fossa was the most common site for LN metastases （42.3%, 41/97）, the internal iliac area was the most common area for a single positive LN packet （20.8%, 5/24）. Eight patients （33.3%, 8/24） had positive LNs at the common iliac area. The incidence of positive LNs did not differ according to the number of LNs removed. Complications associated with eLND occurred in 21 patients （14.3%） and symptomatic lymphocele was found in five patients （3.4%）. In conclusion, robotic eLND can be performed with minimal morbidity. Furthermore, LN yield and the node positive rate achieved using this robotic technique are comparable to those of open series. In addition, the extent of dissection is more important than the absolute number of LNs removed in eLND, and the robotic technique is not a prohibitive factor for performing eLND.     

Do all patients with sentinel node metastasis from breast carcinoma need complete axillary node dissection?

OBJECTIVE: To determine the likelihood of nonsentinel axillary metastasis in the presence of sentinel node metastasis from a primary breast carcinoma. SUMMARY BACKGROUND DATA: Sentinel lymphadenectomy is a highly accurate technique for identifying axillary metastasis from a primary breast carcinoma. Our group has shown that nonsentinel axillary lymph nodes are unlikely to contain tumor cells if the axillary sentinel node is tumor-free, but as yet no study has examined the risk of nonsentinel nodal involvement when the sentinel node contains tumor cells. METHODS: Between 1991 and 1997, axillary lymphadenectomy was performed in 157 women with a tumor-involved sentinel node. Fifty-three axillae (33.5%) had at least one tumor-involved nonsentinel node. The authors analyzed the incidence of nonsentinel node involvement according to clinical and tumor characteristics. RESULTS: Only two variables had a significant impact on the likelihood of nonsentinel node metastasis: the size of the sentinel node metastasis and the size of the primary tumor. The rate of nonsentinel node involvement was 7% when the sentinel node had a micrometastasis (< or =2 mm), compared with 55% when the sentinel node had a macrometastasis (>2 mm). In addition, the rate of nonsentinel node tumor involvement increased with the size of the primary tumor. CONCLUSIONS: If a primary breast tumor is small and if sentinel node involvement is micrometastatic, then tumor cells are unlikely to be found in other axillary lymph nodes. This suggests that axillary lymph node dissection may not be necessary in patients with sentinel node micrometastases from T1/T2 lesions, or in patients with sentinel node metastases from T1a lesions.     

Is axillary lymph node dissection always necessary in breast cancer patients with a positive sentinel node?

Axillary lymph node dissection (ALND) is recommended for patients with breast cancer metastasis to a sentinel lymph node (SLN). However in 40-70% of cases, the SLN may be the only area of metastasis in the dissected axillary contents. In patients with a positive SLN, independently predictive factors for non-SLN metastasis include size of the primary tumor, the size of the SLN metastases, extracapsular extension, and the proportion of positive SLN's among all identified SLNs. Some authors have developed scores and nomograms to estimate a patient's risk for non-SLN metastases. These scores and nomograms should be applied prospectively to a large numper of SLN positive patients who thereafter undergo completion ALND. It is necessary to verify the predictive validity of these scores before we recommend the abandonment of ALND in patients with a very low likelihood of non-SLN metastasis. In this article we review the various predictive factors of non-SLN involvement and the scores or nomograms which have been developed to predict the likelihood of a positive ALND after a positive SLN biopsy.     

Central mesenteric lymph node BER-Ep4+ cells in colorectal cancer: challenge to sentinel node concept?

BACKGROUND: The role of sentinel lymph nodes in colorectal cancer remains unclear. METHODS: Cryosections from central para-aortic mesenterial lymph nodes were stained using mAb BER-Ep4. Overall survival and distant recurrence were calculated using Kaplan-Meier plots. RESULTS: All patients (n = 48) were free of distant metastases and curatively resected (R0). 23 pN0, 13 pN1 and 12 pN2 stages were found. 21/48 patients (44%) showed BER-Ep4+ cells in their central lymph nodes (7/23 pN0, 8/13 pN1, 6/12 pN2). In 6/23 pN0 patients, BER-Ep4+ cells were also found in locoregional nodes (p = 0.03, Fisher's exact test). pN status predicted overall survival (p = 0.006, Kaplan-Meier curve, log-rank test). An impact was exerted by central mesenteric BER-Ep4+ cells on overall survival (p = 0.009 in pN0 patients, p = 0.07 for all pN) and distant recurrence-free survival (p = 0.001 in pN0 patients, p = 0.007 for all pN). Multivariate analysis showed an independent prognostic effect on overall survival in pN0 patients (p = 0.022). CONCLUSION: Central lymph nodes are sentinels of disease not amenable to extended lymphadenectomy and might identify patients at risk of distant organ recurrence.     

Ultrasound guided percutaneous axillary lymph node core biopsy: How often is the sentinel lymph node being biopsied?

Patients with breast cancer now frequently undergo axillary ultrasound and core biopsy (CB) in an attempt to reduce the number of unnecessary sentinel lymph node (SLN) biopsies. This study aimed to establish the frequency of successful targeting of the SLN by ultrasound guided biopsy. A total of 137 patients had axillary ultrasound of which 121 underwent CB. 73 (60%) patients proceeded to SLN after negative CB. All SLNs were examined for evidence of metastases and previous CB. Of the 73 patients, 51 had no evidence of malignancy in the SLN (true negative=70%). However nodal deposits were found in the remaining 22 patients, representing a false negative rate for CB of 30%. Overall histopathological evidence of previous CB was identified in 47 (64%) of 73 patients undergoing SLN biopsy. The reason for false negative findings in the 22 (30%) patients was failure to sample the sentinel lymph node in 10 (45%) and failure to sample the metastatic disease in the sentinel node in 11 (55%). This study suggests that both better methods of identifying the sentinel lymph node and more adequate sampling are required.     

Does failure to visualize a sentinel node on preoperative lymphoscintigraphy predict a greater likelihood of axillary lymph node positivity?

BACKGROUND: Sentinel lymph node (SLN) mapping has become the standard of care for axillary staging in women with early-stage breast cancer. The purpose of the study was to investigate the hypothesis that nonvisualization of SLN on lymphoscintigraphy (LSG) predicts a subset of patients at risk of having a substantial burden of axillary tumor as evidenced by higher rate of lymph node involvement. STUDY DESIGN: We retrospectively reviewed the records of 1,500 patients who underwent dual-tracer SLN mapping for breast cancer between 1999 and 2004. LSG were reported as negative or positive. RESULTS: Ninety-one percent had axillary SLN(s) identified on LSG imaging. In 133 of 134 (99.3%) patients with a negative LSG, SLN(s) was identified intraoperatively either by blue dye or hand-held gamma detection. SLN was positive in 28.4% of LSG nonvisualized group and was positive in 29.1% of LSG visualized group (p>0.05). A significantly higher percentage of women older than 50 years of age had nonvisualization of SLN (p<0.0001). Body mass index (calculated as kg/m2) was >30 in 42.5% of LSG nonvisualized group and in 26.3% in LSG visualized group (p<0.0001). CONCLUSIONS: Failure to demonstrate axillary uptake by LSG appears to be related to technical factors and patient-related factors, such as body mass index and older age, but does not adversely affect SLN identification. The equivalent rate of positive SLNs in patients with a positive or negative LSG supports the null hypothesis that "failure to visualize" on LSG does not identify a subset of patients at higher risk of being axillary lymph node positive.     

High body mass index predicts multiple prostate cancer lymph node metastases after radical prostatectomy and extended pelvic lymph node dissection

Our aim is to evaluate the association between body mass index(BMI)and preoperative total testosterone(TT)levels with the risk of single and multiple metastatic lymph node invasion(LNI)in prostate cancer patients undergoing radical prostatectomy and extended pelvic lymph node dissection.Preoperative BMI,basal levels of TT,and prostate-specific antigen(PSA)were evaluated in 361 consecutive patients undergoing radical prostatectomy with extended pelvic lymph node dissection between 2014 and 2017・Patients were grouped into either nonmetastatic,one,or more than one metastatic lymph node invasion groups.The association among clinical factors and LNI was evaluated.LNI was detected in 52(14.4%)patients:28(7.8%)cases had one metastatic node and 24(6.6%)had more than one metastatic node.In the overall study population,BMI correlated inversely with TT(r=-0.256;P<0.0001).In patients without metastases,BMI inversely correlated with TT(r=-0.282;P<0.0001).In patients with metastasis,this correlation was lost.In the overall study population,BMI(odds ratio[OR]=1.268;P=0.005)was the only in dependent clinical factor associated with the risk of multiple metastatic LNI compared to cases with one metastatic node.In the nonmetastatic group,TT was lower in patients with BMI>28 kg m^2(P<0.0001).In patients with any LNI,this association was lost(P=0.232).The median number of positive nodes was higher in patients with BMI>28 kg m^2(P-0.048).In our study,overweight and obese patients had a higher risk of harboring multiple prostate cancer lymph node metastases and lower TT levels when compared to patients with normal BMI.     

Sentinel node metastasectomy in thin ≤1-mm melanoma

Background and aims Sentinel lymph node biopsy (SLNB) has been widely accepted as a precise tool to stage melanoma. In thin T1 melanomas (1 mm), the indication of SLNB is controversial since the risk of nodal metastasis is low. The aim of this study was to assess if SLNB detects occult nodal metastases among patients with thin melanomas.Patients and methods SLNB was performed prospectively in 135 patients with invasive melanoma in any depth category, including 56 T1 melanomas.Results Nodal metastases were detected in 18% by SLNB, and there were three sentinel-positive thin melanomas, constituting 5% of the T1 cases. Histopathologically, there were no factors of the primary tumors that would have predicted these metastases.Conclusion SLNB is a precise method to detect clinically silent nodal metastases in thin invasive melanoma. Certain histopathologic features of a thin primary lesion may correlate with the predictive probability of the sentinel node status. We were unable to identify these predictors, but the conclusions from this study are limited by the small sample size. Advanced melanoma is a lethal disease, and accurate staging is essential also in the T1 group. For stage III patients with occult nodal metastases, metastasectomy is a better option for cure than observation.     

Lymph node clearance: is surgical practice homogenous?

AIM: The aim of our study was to make evident the huge variability in lymph node dissection practice. MATERIAL AND METHODS: Therefore a retrospective study was conducted on 330 patients assessed for cervical, axillary or groin dissections. In each case the authors collected the primary diagnosis and clinical stage indicating lymph node clearance, identity of the surgeon and the pathologist, surgical technique including skin incision and landmarks of tissue removal, size of the clearance, and number of lymph nodes removed. Correlations between diagnosis, surgeon's or pathologist's identity, size of the clearance and number of nodes were analyzed using non-parametric tests. RESULTS: Standardized procedures as axillary dissections occurred few differences between surgeons. In groin or cervical dissections statistical differences were made evident with great technical variability. There was a positive correlation between size of the piece of lymphadenectomy and number of lymph nodes removed. CONCLUSION: Standardized procedures as axillary dissections provide few variations. Cervical and especially groin dissections should be harmonized, published and taught harmoniously in schools of surgery. So the expression "regional lymph node clearance" would mean.     

Critical analysis of the 2010 TNM classification in patients with lymph node–positive bladder cancer: Influence of lymph node disease burden

ObjectivesIn 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.Methods and materialsA total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.ResultsThe presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39–0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively).ConclusionsThe N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.     

Adjuvant chemotherapy is associated with improved overall survival in pelvic node–positive penile cancer after lymph node dissection: A multi-institutional study

ObjectivesWe determined whether adjuvant chemotherapy (AC) would be associated with improved survival after lymph node dissection (LND) for patients with penile cancer (PeCa) who have positive pelvic lymph nodes (PPLNs).MethodsWe retrospectively identified patients across 4 centers with penile squamous cell carcinoma who underwent LND from 1978 to 2013 and were found to have PPLNs. Patients who received chemotherapy before surgery or in the presence of recurrent disease were excluded. Cox regression was used to evaluate the association of AC with overall survival (OS), which was estimated using the Kaplan-Meier method. Differences in OS were determined with the log-rank test.ResultsDuring the study period, 141 patients who underwent LND for PeCa had PPLNs, and 84 of them met inclusion criteria. Median number of PPLNs was 2 (interquartile range [IQR]: 4–7), with 10% of cases occurring bilaterally and 55% having pelvic extranodal extension. AC was used in 36 (43%) patients. Patients who received AC were younger (P = 0.014), had less-aggressive penile tumor pathology (P<0.01), were less likely to receive adjuvant radiation (P<0.01), had less bilateral inguinal disease (P = 0.019), and had more inguinal extranodal extension (P = 0.042). Median follow-up was 12.1 months. Estimated median OS was 21.7 months (IQR: 11.8–104) in patients who received AC vs. 10.1 (IQR: 5.6–48.1) in those who did not (P = 0.048). AC was independently associated with improved OS on multivariate analysis (hazard ratio: 0.40; 95% CI: 0.19–0.87; P = 0.021).ConclusionsAC is associated with improved OS in patients with PeCa who have PPLNs after LND. Prospective studies are needed to demonstrate causality.     

Does lymph node dissection during nephroureterectomy affect oncological outcomes in upper tract urothelial carcinoma patients without suspicious lymph node metastasis on preoperative imaging studies?

Purpose

This study aimed to investigate the effects of lymph node dissection (LND) on upper tract urothelial carcinoma (UTUC) without suspicious lymph node (LN) metastasis on preoperative imaging studies.

Methods

From 1998 to 2012, 418 UTUC patients without suspicious LN metastasis on preoperative imaging studies were included. Patients were divided into two groups according to the performance of LND. The effects of LND on oncological outcomes were assessed after adjusting other variables. The mean follow-up duration was 69 months.

Results

Among the 132 patients who underwent LND, LN metastasis was pathologically identified in 16 patients (12.1 %). The median number of resected LNs for patients who underwent LND was 7. On multivariate analysis, the number of resected LNs and pathologic T stage was significant predictors of LN metastasis. The 5-year recurrence-free survival was 76.4 % for patients without LND and 65.4 % for patients with LND (p = 0.126). In addition, there was no difference in 5-year overall survival between the 2 groups (without LND; 71.7 % vs. with LND; 72.1 %, p = 0.756). Multivariate analysis showed that pathologic T stage, tumor grade, and lymphovascular invasion were risk factors for recurrence. Age at surgery, tumor size, pathologic T stage, tumor grade, and lymphovascular invasion were significantly associated with overall survival. However, performance of LND was not associated with recurrence and survival.

Conclusions

LND could be selectively performed in patients with clinically LN-negative UTUC based on patient/tumor characteristics and operative findings although sufficient LNs should be removed if LND is to be performed.