Is Complete Lymph Node Dissection After a Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma Always Necessary

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Review

Is complete lymph node dissection after a positive sentinel lymph node biopsy forcutaneous melanoma always necessary? A meta-analysis

V. Nagaraja, G.D. Eslick*

The Whiteley-Martin Research Centre, Discipline of Surgery, The University of Sydney, Nepean Hospital, Penrith, New South Wales, Australia

Accepted 20 February 2013

Available online---

Abstract

Background: The current recommendation for patients with cutaneous melanoma and a positive sentinel lymph node (SLN) biopsy is a com-plete lymph node dissection (CLND). However, metastatic melanoma is not present in approximately 80% of CLND specimens. A meta-

analysis was performed to identify the clinicopathological variables most predictive of non-sentinel node (NSN) metastases when the sen-

tinel node is positive in patients with melanoma.

Methods: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google

scholar, Science Direct, and Web of Science. The search identified 54 relevant articles reporting the frequency of NSN metastases in mel-

anoma. Original data was abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI).

Findings: The pooled estimates that were found to be significantly associated with the high likelihood of NSN metastases were: ulceration

(OR: 1.88, 95% CI: 1.53e2.31), satellitosis (OR: 3.25, 95% CI: 1.86e5.66), neurotropism (OR: 2.51, 95% CI: 1.39e4.53), >1 positive

SLN (OR: 1.77, 95% CI: 1.2e2.62), Starz 3 (old) (OR: 1.83, 95% CI: 0.89e3.76), Angiolymphatic invasion (OR: 2.46, 95% CI:

1.34e4.54), extensive location (OR: 2.22, 95% CI: 1.74e2.81), macrometastases >2 mm (OR: 1.95, 95% CI: 1.61e2.35), extranodal ex-

tension (OR: 3.38, 95% CI: 1.79e6.40) and capsular involvement (OR: 3.16, 95% CI: 1.37e7.27). There were 3 characteristics not asso-

ciated with NSN metastases: subcapsular location (OR: 0.51, 95% CI: 0.38e0.67), Rotterdam Criteria


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numerous studies have been published trying to challenge

the standard approach of performing the CLND. Most of

these attempts are based on retrospective studies of pro-

spective databases.11e21 Sentinel node (SN) tumor burden

is the most important prognostic factor for patients with

early stage melanoma.22 Important morphometric classifi-

cations are based on the depth of tumor invasion measuredfrom the capsule in the SLN (Starz Classification),23 the

microanatomic location (Dewar criteria)24 and the maxi-

mum diameter of the largest tumor lesion (Rotterdam

criteria).20

We sought to determine which of the clinicopathologic

prognostic factors could be used to predict the presence

of positive non-SLNs. We hypothesized that patients with

greater microscopic SLN tumor burden would be at in-

creased risk for non-SLN disease in their CLND specimen,

to assess which classification best predicts additional lymph

node involvement and that a subset of patients could be

identified in whom the risk of positive non-SLNs is suffi-

ciently low that patients may be spared the morbidity asso-ciated with lymphadenectomy,25e28 thus helping to identify

patients who would most likely benefit from CLND.

Methods

Study protocol

We followed the Preferred Reporting Items for System-

atic reviews and Meta-Analyses PRISMA guidelines in per-

forming our systematic review.29

We performeda systematic search through MEDLINE (from 1950),

PubMed (from 1946), EMBASE (from 1949), Current Con-

tents Connect (from 1998), Cochrane library, Google

scholar, Science Direct, and Web of Science to March 27,

2013. The search terms included Melanoma AND Sen-

tinel Lymph Node Biopsy AND Lymphatic Metastasis

AND Predictive OR complete lymph node dissection in

Melanoma OR positive non-sentinel lymph nodes in Mela-

noma, which were searched as text word and as exploded

medical subject headings where possible. No language re-

strictions were used in either the search or study selection.

The reference lists of relevant articles were also searched

for appropriate studies.

Study selection

We included studies that met the following inclusion

criteria:

1. Studies identifying the population of patients with

a positive sentinel lymph node who underwent com-

pletion lymph node dissection; and

2. Original data (or odds ratios) reporting on the number

of SLN positive patients who had positive NSNs

stratified by various patient/tumor characteristics.

A summary of the search strategy is provided in Fig. 1.

Chu et al.30 and Van der pleog et al.31 were excluded

as the former did not differentiate between NSN positivity

clearly and in the later not all patients with sentinel

lymph positive underwent CLND. There was no extract-

able data in 12 papers6,32e42 and hence they were

excluded.

Data extraction

We performed the data extraction using a standardized

data extraction form, collecting information on the publica-

tion year, study design, number of cases, total sample size,

population type, country, continent, mean age, clinical data

(age, sex, Breslow thickness, SLN tumor burden, ulcera-

tion, satellitosis, regression, neurotropism, histology, angio-

lymphatic invasion, primary site, sentinel lymph node (sln)

location, SLN tumor characteristic, number of tumor posi-

tive slns, extranodal extension, capsular involvement). Pre-

dominantly 4 SLN tumor burden classifications were used

in these studies namely Dewar classification24 [Subcapsu-

lar: metastasis confined to subcapsular sinus, Combined:

subcapsular and parenchymal metastases, Parenchymal:

Potentially relevant studies

identified and screened for

retrieval (n=507)

Studies excluded, did not meet

the inclusion criteria (n=438)

Studies retrieved for more

detailed evaluation (n=69)

Potentially appropriate studies

to be incl uded in the meta-

analysis (n=57)

Studies included in meta-

analysis (n=54)

Studies with usable

information, by

outcome (n=54)

Studies excluded, no extractable

data (n=12)

Study excluded, with reasons

(n=3)

Studies withdrawn by outcome

with reasons (n=0)

Figure 1. Flowchart of included studies.

2 V. Nagaraja, G.D. Eslick / EJSO xx (2013) 1e12

Please cite this article in press as: Nagaraja V, Eslick GD, Is complete lymph node dissection after a positive sentinel lymph node biopsy for cutaneous

melanoma always necessary? A meta-analysis, Eur J Surg Oncol (2013), http://dx.doi.org/10.1016/j.ejso.2013.02.022


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metastasis entirely within paracortical area of parenchyma,

Multifocal: Multiple discrete deposits (must include some

parenchymal deposits) Extensive: any metastasis larger

than 5 mm, any node with extracapsular spread], old Starz

classification43 [consisted of three categories; S1, S2 andS3 and these categories were based on the number of pos-

itive sections (n) and the maximum distance from the inte-

rior margin to the capsule of the SN ( d). The criteria for

these respective categories was n < 1 and d< 1 mm for

S1, n > 2 and d > 1 mm for S2 and n > 2 and

d > 1 mm for S3], new Starz classification23

(d< 0.3 mm for SI, d> 0.3 mm and 1 mm for SIII) and Rotterdam criteria20 [The size of

the SN tumor burden was also recorded, three different tu-

mor burden size groups were defined, sub-micrometastases

(clusters of more than 10 cells, but

1 mm]. The odds ratioand confidence intervals for the above mentioned parame-

ters were calculated (Figs. 2e8).

Statistical analysis

Pooled odds ratios and 95% confidence intervals were

calculated for the Factors Predicting Positive Nonsentinel

Lymph Nodes using a random effects model.43 We testedheterogeneity using the I2 statistic, which represents the

percentage of the total variability across studies which is

due to heterogeneity. I2 values of 25, 50 and 75% corre-

sponded to low, moderate and high degrees of heterogene-

ity respectively.44 We quantified publication bias using the

Eggers regression model45 with the effect of bias assessed

using the fail-safe number method.46 All analyses were per-

formed with Comprehensive Meta-analysis (version 2.0).

Results

Fifty-four studies were included in the analysis (Table 1).The total number of patients was 8388. The reported preva-

lence of NSN metastases ranges from 8% to 38%.

Figure 2. Extensive location.

Figure 3. Macrometastases >2 mm.

3V. Nagaraja, G.D. Eslick / EJSO xx (2013) 1e12




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Risk factors for NSN metastases

Factors identified with nonsentinel node metastases were

ulceration (OR: 1.88, 95% CI: 1.53e2.31), satellitosis (OR:

3.25, 95% CI: 1.86e5.66), neurotropism (OR: 2.51, 95% CI:

1.39e4.53), >1 positive SLN (OR: 1.77, 95% CI:

1.2e2.62), Starz 3 (old) [n > 2 and d> 1 mm n (the number

of 1-mm-thin sentinel lymph node slices with [immuno-]

histologicallydetectable tumor cells) and d(themaximum dis-

tance of tumor cells to the interior margin of the lymph node

capsule). (OR: 1.83, 95% CI: 0.89e3.76), Angiolymphatic in-

vasion (OR: 2.46, 95% CI: 1.34e4.54), extensive location

(OR: 2.22, 95% CI: 1.74e2.81), macrometastases >2 mm

(OR: 1.95, 95% CI: 1.61e2.35), extranodal extension (OR:

3.38, 95% CI: 1.79e6.40) and capsular involvement (OR:

3.16, 95% CI: 1.37e7.27) as depicted in Table 2. Three char-

acteristics were associated with low risk of NSN metastases:

subcapsular location (OR: 0.51, 95% CI: 0.38e0.67), Rotter-

dam Criteria


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Discussion

As we try to extend the limits of minimally invasive pro-

cedures, efforts must be made to identify the subset of pa-

tients with a positive SLN who would be spared from the

burden CLND. During the past several years, clinicopatho-logical variables in 54 well-described studieshave been iden-

tified in an attempt to select those patients most likely to

benefit from CLND when the SLN is positive. This meta-

analysis is the first to indicate that clinical and pathologic

features of primary melanoma and SLN tumor predict

NSN positivity. Features like ulceration, satellitosis, neuro-

tropism, >1 positive sln, starz 3 (old), extensive location

(Dewar classification), macrometastases>2 mm, extranodal

extension, and capsular involvement were found to be signif-

icantly associated with the high likelihood of NSN metasta-

ses. Three characteristics: subcapsular location, rotterdam

criteria2 mm. In their study, no patient with an S/U

score of 0 had a positive NSLN. In addition, patients with

an S/U score of 2 were twice as likely for positive NSLNs

than patients with an S/U score of 1. Roka61 et al. patients

with sentinel node metastasis had a significantly lower S/U

Table 1

Characteristics of the 54 studies included in the systematic review and meta-analysis.

Author Year Country %Female No. of CLND NSLN positivity%

Younan et al.15 2010 Canada 46.30% 81 12.34%

Fink et al.17 2011 Austria 44.60% 121 24.19%

Fink et al.16 2005 Austria e 26 15.36%

Franco et al.18 2010 Italy 40.42% 47 23.40%

Namikawa et al.19 2012 Japane

149 38.26%Van akkooi et al.91 2008 EORTC Melanoma

Group (MG)

47.00% 388 25.55%

Van der Pleog et al.12 2009 Netherlands e 116 12.93%

Pearlman et al.21 2006 USA e 80 21.25%

Page et al.90 2007 USA e 70 24.30%

Guggenheim et al.89 2008 Switzerland 42.05% 100 22.00%

Glumac et al.88 2008 Slovenia 51.35% 74 21.62%

Denis et al.87 2007 France e 35 14.28%

Francischetto et al.48 2010 Brazil 55.30% 103 25.24%

Scheri et al.60 2007 USA e 52 11.53%

Wiener et al.57 2010 Australia 38.70% 323 16.52%

Ghaferi et al.86 2009 USA 42.00% 429 16.55%

Elias et al.85 2004 USA e 80 15.00%

Debarbieux et al.50 2007 France 42.85% 98 22.20%

Cochran et al.55 2004 USAe

80 21.11%

Ariyan et al.84 2009 USA 34.20% 222 16.66%

Santinami et al.83 2009 Greece e 150 24.00%

Gershenwald et al.47 2008 USA 39.70% 359 14.00%

Frankel et al.82 2008 USA 34.60% 136 21.20%

Cascinelli et al.10 2006 Italy e 176 18.75%

Cadili et al.62 2010 Canada e 111 15.31%

Cadili et al.63 2009 Canada 47.00% 68 18.00%

Cadili et al.81 2010 Australia e 606 23.50%

Quaglino et al.80 2011 Italy e 100 31.00%

Murali et al.11 2011 Australia 38.80% 309 17.20%

Carlson et al.79 2003 USA e 104 15.38%

Van der ploeg et al.13 2011 EORTC Melanoma

Group (MG)

56.50% 1009 21.00%

Lee et al.9 2003 USA e 191 24.00%

Sabel et al.56 2005 USA e 221 15.00%

Van Akkooi et al.20 2006 Netherlands 44.78% 67 14.92%

Govindarajan et al.54 2006 Canada e 127 15.74%

Roka et al.61 2007 Austria 38.82% 85 21.17%

Rossi et al.14 2007 Italy 51.04% 96 20.83%

Satzger et al.49 2008 Germany 40.55% 180 15.55%

Scolyer et al.52 2004 Australia e 140 17.14%

Starz et al.78 2001 Germany e 53 20.75%

Starz et al.23 2004 Germany e 45 26.67%

Dewar et al.24 2004 United Kingdom 44.8% 146 16.43%

Vuylsteke et al.53 2005 Netherlands 48% 71 26.76%

Reeves et al.51 2003 USA 39% 98 16.32%

Pu et al.77 2003 USA e 23 8.69%

Nowecki et al.76 2003 Poland 21.13% 145 26.89%

McMaster et al.75 2002 USA 40.87% 282 15.95%

Kunte et al.74 2010 Germany 36.93% 176 14.77%

Joseph et al.73 1998 USA e 64 7.81%

Wagner et al.72 1999 USA 44.9% 147 17.00%

Wagner et al.93 2000 USA 37.03% 57 26.31%

Wagner et al.92 2003 USA e 90 20.00%

Wagner et al.94 2000 USA 16.67% 12 33.30%

Bogenrieder et al.71 2011 Netherlands 45.7% 70 25.71%





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score as compared to patients with positive NSLN (median

0 vs. 1; p < 0.04), but still 5 of 42 (12%) of patients with

a S/U score of zero tested positive for additional lymph

node metastasis upon CLND. Ulceration was a significant

predictor of NSLN with an OR 1.88 of (95% CI

1.53e2.31) in our study.

Risk Score was by proposed The University of Alberta

Hospital.62,63 The score was calculated for each patient ac-

cording to the following criteria: one point for patient age

>55 years, one point for total SLN metastasis size

>5 mm; accordingly, each patient was awarded a score

of 0, 1, or 2. The total score was found to be highly pre-

dictive of CLND positivity with metastasis (p value


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development of a new model based on these 9 predictors

that is generally applicable among different populations.

Patients with a predicted low risk of further node involve-

ment could then be spared a CLND even if the SLN is

metastatic. Although this model allows stratification of

the risk of NSN involvement and therefore provides useful

prognostic information to aid in management decisions,a recommendation not to perform CLND should be

made with great caution in patients with positive SNs

and should be based on clinical factors and patient prefer-

ences on a case-by-case basis.

Many retrospective studies (for e.g. Morton et al.,64

Kretschmer et al.,65 van Akkooi AC et al.,66 Nowecki et al.,67

Faries et al.68 etc), 1 randomized controlled trial and 1 meta-

analysis (Pasquali et al.69) have assessed whether differences

in survival and regional disease control exist between patients

having SNB-guided CLND and TLND for clinically evident

lymph node disease. Morton et al.22 depicts that SNB-guided

CLND is associated with a significantly better outcome com-

pared with TLND for clinically evident lymph node diseaseand strongly suggest that patients with SN-positive melanoma

who underwent immediate CLND had a survival advantage

over those who underwent CLND only when regional lymph

node metastases became clinically apparent.

The considerable variation in reported predictors of NSN

positivity is due to differences in sample size, populations

studied, protocols for pathologic processing and examination

of primary tumors and SNs, and methods of data analysis, as

well asthe effects of interobserver variation in pathologic in-

terpretation.70 Obviously, all retrospective studies have the

disadvantage that can be overcome only by a prospective,

randomized controlled trial. Several prospective trials arecurrently under way to further investigate the possibility of

reducing the 80% of unnecessary CLND operations.

Whether CLND may be safely avoided in patients at low

risk of NSN positivity (as stratified by N-SNORE, Hannover

Scoring System, Rotterdam system, Dewar Classification,

Starz Classification, Size ulceration score and RD Criteria)

will require investigation in a prospective randomized clini-

cal trial. The MSLT-II and EORTC MINITUB studies, cur-

rently in progress, are comparing CLND with close clinical

and ultrasound follow-up in patients with SN-positive dis-

ease, and the results may be helpful in determining which pa-

tients may be safely spared a CLND.

We suggest the development of a new model based on

these 12 predictors that is generally applicable among dif-

ferent populations. Patients with a predicted low risk of fur-

ther node involvement could then be spared a CLND even

if the SLN is metastatic. However, it is unclear how mini-

mal residual disease left in the axilla would affect the local

recurrence rate and ultimate prognosis in patients predicted

to have only SLN metastases if the SLNs are involved.

Acknowledgments

None.

Contributors

Vinayak Nagaraja conceived and designed the study. Vi-

nayak Nagaraja provided study materials and identified

studies. Vinayak Nagaraja and Guy D. Eslick collected

and assembled data. Guy D. Eslick analyzed and inter-

preted the data. Vinayak Nagaraja drafted the manuscript.Guy D. Eslick edited the manuscript.

Funding

Nil.

Conflicts of interest

We declare that we have no conflicts of interest.

References

1. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the Ameri-

can Joint Committee on Cancer staging system for cutaneous mela-

noma. J Clin Oncol 2001;19(16):363548.

2. Morton DL, Wen DR, Wong JH, et al. Technical details of intraoper-

ative lymphatic mapping for early stage melanoma. Arch Surg 1992;

127(4):3929.

3. Thompson JF. The Sydney Melanoma Unit experience of sentinel

lymphadenectomy for melanoma. Ann Surg Oncol 2001;8(9

Suppl.):44S7S.

4. Thompson JF, Stretch JR, Uren RF, Ka VS, Scolyer RA. Sentinel

node biopsy for melanoma: where have we been and where are we

going? Ann Surg Oncol 2004;11(3 Suppl.):147S51S.

5. Morton DL, Thompson JF, Essner R, et al. Validation of the ac-

curacy of intraoperative lymphatic mapping and sentinel lympha-denectomy for early-stage melanoma: a multicenter trial.

Multicenter Selective Lymphadenectomy Trial Group. Ann Surg

1999;230(4):45363.

6. Testori A, De Salvo GL, Montesco MC, et al. Clinical considerations

on sentinel node biopsy in melanoma from an Italian multicentric

study on 1,313 patients (SOLISM-IMI). Ann Surg Oncol 2009;

16(7):201827.

7. Balch CM. Prognostic factors analysis of 17,600 melanoma patients:

validation of the American Joint Committee on Cancer melanoma

staging system. J Clin Oncol 2001;19(16):362234.

8. Balch CM,MortonDL, GershenwaldJE, et al. Sentinel node biopsyand

standard of carefor melanoma.J Am Acad Dermatol 2009;60(5):8725.

9. Lee JH, Essner R, Torisu-Itakura H, Wanek L, Wang H, Morton DL.

Factors predictive of tumor-positive nonsentinel lymph nodes after

tumor-positive sentinel lymph node dissection for melanoma.J Clin Oncol 2004;22(18):367784.

10. Cascinelli N, Bombardieri E, Bufalino R, et al. Sentinel and nonsen-

tinel node status in stage IB and II melanoma patients: two-step prog-

nostic indicators of survival. J Clin Oncol 2006;24(27):446471.

11. Murali R, DesilvaC, ThompsonJF,ScolyerRA. Non-Sentinel Node Risk

Score (N-SNORE): a scoring system for accurately stratifying risk of

non-sentinel node positivity in patients with cutaneous melanoma with

positive sentinel lymph nodes. J Clin Oncol 2010;28(29):44419.

12. van der Ploeg IM, Kroon BB, Antonini N, Valdes Olmos RA,

Nieweg OE. Comparison of three micromorphometric pathology

classifications of melanoma metastases in the sentinel node. Ann

Surg 2009;250(2):3014.

13. van der Ploeg AP, van Akkooi AC, Rutkowski P, et al. Prognosis in

patients with sentinel node-positive melanoma is accurately defined





10/12

by the combined Rotterdam tumor load and Dewar topography crite-

ria. J Clin Oncol 2011;29(16):220614.

14. Rossi CR, De Salvo GL, Bonandini E, et al. Factors predictive of

nonsentinel lymph node involvement and clinical outcome in mela-

noma patients with metastatic sentinel lymph node. Ann Surg Oncol

2008;15(4):120210.

15. Younan R, Bougrine A, Watters K, et al. Validation study of the s

classification for melanoma patients with positive sentinel nodes:

the Montreal experience. Ann Surg Oncol 2010;17(5):141421.

16. Fink AM, Weihsengruber F, Spangl B, et al. S-classification of sen-

tinel lymph node biopsy predicts the results of complete regional

lymph node dissection. Melanoma Res 2005;15(4):26771.

17. Fink AM, Weihsengruber F, Duschek N, et al. Value of micromor-

phometric criteria of sentinel lymph node metastases in predicting

further nonsentinel lymph node metastases in patients with mela-

noma. Melanoma Res 2011;21(2):13943.

18. Franco R, Cantile M, Scala S, et al. Histomorphologic parameters

and CXCR4 mRNA and protein expression in sentinel node mela-

noma metastasis are correlated to clinical outcome. Cancer Biol

Ther 2010;9(6):4239.

19. Namikawa K, Yamazaki N, Nakai Y, et al. Prediction of additional

lymph node positivity and clinical outcome of micrometastases in

sentinel lymph nodes in cutaneous melanoma: a multi-institutional

study of 450 patients in Japan. J Dermatol 2012;39(2):1307.

20. van Akkooi AC, de Wilt JH, Verhoef C, et al. Clinical relevance of

melanoma micrometastases (


11/12

associated with status of the completion lymphadenectomy and rate

of subsequent relapse. Ann Surg Oncol 2007;14(2):90612.

55. Cochran AJ, Wen DR, Huang RR, Wang HJ, Elashoff R, Morton DL.

Prediction of metastatic melanoma in nonsentinel nodes and clinical

outcome based on the primary melanoma and the sentinel node. Mod

Pathol 2004;17(7):74755.

56. Sabel MS, Griffith K, Sondak VK, et al. Predictors of nonsentinel

lymph node positivity in patients with a positive sentinel node for

melanoma. J Am Coll Surg 2005;201(1):3747.

57. Wiener M, Acland KM, Shaw HM, et al. Sentinel node positive mel-

anoma patients: prediction and prognostic significance of nonsentinel

node metastases and development of a survival tree model. Ann Surg

Oncol 2010;17(8):19952005.

58. Meier A, Satzger I, Volker B, Kapp A, Gutzmer R. Comparisonof clas-

sification systems in melanoma sentinel lymph nodese an analysis of

697 patients from a single center. Cancer2010;116(13):317888.

59. Satzger I, Volker B, Al Ghazal M, Meier A, Kapp A, Gutzmer R.

Prognostic significance of histopathological parameters in sentinel

nodes of melanoma patients. Histopathology 2007;50(6):76472.

60. Scheri RP, Essner R, Turner RR, Ye X, Morton DL. Isolated tumor

cells in the sentinel node affect long-term prognosis of patients

with melanoma. Ann Surg Oncol 2007;14(10):28616.

61. Roka F, Mastan P, Binder M, et al. Prediction of non-sentinel node

status and outcome in sentinel node-positive melanoma patients.

Eur J Surg Oncol 2008;34(1):828.

62. Cadili A, McKinnon G, Wright F, et al. Validation of a scoring sys-

tem to predict non-sentinel lymph node metastasis in melanoma.

J Surg Oncol 2010;101(3):1914.

63. Cadili A, Smylie M, Danyluk J, Dabbs K. Prediction of nonsentinel

lymph node metastasis in malignant melanoma. J Surg Res 2009;

154(2):3249.

64. Morton DL, Hoon DS, Cochran AJ, et al. Lymphatic mapping and

sentinel lymphadenectomy for early-stage melanoma: therapeutic

utility and implications of nodal microanatomy and molecular stag-

ing for improving the accuracy of detection of nodal micrometasta-

ses. Ann Surg 2003;238(4):53849.

65. Kretschmer L, Hilgers R, Mohrle M, et al. Patients with lymphatic

metastasis of cutaneous malignant melanoma benefit from sentinellymphonodectomy and early excision of their nodal disease. Eur J

Cancer 2004;40(2):2128.

66. van Akkooi AC, Bouwhuis MG, de Wilt JH, Kliffen M, Schmitz PI,

Eggermont AM. Multivariable analysis comparing outcome after

sentinel node biopsy or therapeutic lymph node dissection in patients

with melanoma. Br J Surg 2007;94(10):12939.

67. Nowecki ZI, Rutkowski P, Michej W. The survival benefit to patients

with positive sentinel node melanoma after completion lymph node

dissection may be limited to the subgroup with a primary lesion Bre-

slow thickness greater than 1.0 and less than or equal to 4 mm (pT2-

pT3). Ann Surg Oncol 2008;15(8):222334.

68. Faries MB, Thompson JF, Cochran A, et al. The impact on morbidity

and length of stay of early versus delayed complete lymphadenec-

tomy in melanoma: results of the Multicenter Selective Lymphade-

nectomy Trial (I). Ann Surg Oncol 2010;17(12):33249.69. Pasquali S, Mocellin S, Campana LG, et al. Early (sentinel lymph

node biopsy-guided) versus delayed lymphadenectomy in melanoma

patients with lymph node metastases: personal experience and liter-

ature meta-analysis. Cancer 2010;116(5):12019.

70. Murali R, Cochran AJ, Cook MG, et al. Interobserver reproducibility

of histologic parameters of melanoma deposits in sentinel lymph no-

des: implications for management of patients with melanoma. Can-

cer 2009;115(21):502637.

71. Bogenrieder T, vanDijk MR,Blokx WA, et al. No non-sentinel node in-

volvement in melanoma patients with limited Breslow thickness and

low sentinel node tumour load. Histopathology 2011;59(2):31826.

72. Wagner JD, Davidson D, Coleman 3rd JJ, et al. Lymph node tumor

volumes in patients undergoing sentinel lymph node biopsy for cuta-

neous melanoma. Ann Surg Oncol 1999;6(4):398404.

73. Joseph E, Brobeil A, Glass F, et al. Results of complete lymph node

dissection in 83 melanoma patients with positive sentinel nodes. Ann

Surg Oncol 1998;5(2):11925.

74. Kunte C, Geimer T, Baumert J, et al. Analysis of predictive factors

for the outcome of complete lymph node dissection in melanoma pa-

tients with metastatic sentinel lymph nodes. J Am Acad Dermatol

2011;64(4):65562.

75. McMasters KM, Wong SL, Edwards MJ, et al. Frequency of nonsen-

tinel lymph node metastasis in melanoma. Ann Surg Oncol 2002;

9(2):13741.

76. Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A, Ruka W. Sen-

tinel lymph node biopsy in melanoma patients with clinically nega-

tive regional lymph nodes e one institutions experience.

Melanoma Res 2003;13(1):3543.

77. Pu LL, Wells KE, Cruse CW, Shons AR, Reintgen DS. Prevalence of

additional positive lymph nodes in complete lymphadenectomy spec-

imens after positive sentinel lymphadenectomy findings for early-

stage melanoma of the head and neck. Plast Reconstr Surg 2003;

112(1):439.

78. Starz H, Balda BR, Kramer KU, Buchels H, Wang H.

A micromorphometry-based concept for routine classification of sen-

tinel lymph node metastases and its clinical relevance for patients

with melanoma. Cancer 2001;91(11):211021.

79. Carlson GW, Murray DR, Lyles RH, Staley CA, Hestley A, Cohen C.

The amount of metastatic melanoma in a sentinel lymph node: does it

have prognostic significance? Ann Surg Oncol 2003;10(5):57581.

80. Quaglino P, Ribero S, Osella-Abate S, et al. Clinico-pathologic fea-

tures of primary melanoma and sentinel lymph node predictive for

non-sentinel lymph node involvement and overall survival in mela-

noma patients: a single centre observational cohort study. Surg Oncol

2011;20(4):25964.

81. Cadili A, Scolyer RA, Brown PT, Dabbs K, Thompson JF. Total sen-

tinel lymph node tumor size predicts nonsentinel node metastasis and

survival in patients with melanoma. Ann Surg Oncol 2010;17(11):

301520.

82. Frankel TL,GriffithKA, Lowe L, et al. Do micromorphometric features

of metastatic deposits within sentinel nodes predict nonsentinel lymph

node involvement in melanoma?Ann Surg Oncol 2008;15(9):240311.83. Santinami M, Carbone A, Crippa F, et al. Radical dissection after

positive groin sentinel biopsy in melanoma patients: rate of further

positive nodes. Melanoma Res 2009;19(2):1128.

84. Ariyan C, Brady MS, Gonen M, Busam K, Coit D. Positive nonsen-

tinel node status predicts mortality in patients with cutaneous mela-

noma. Ann Surg Oncol 2009;16(1):18690.

85. Elias N, Tanabe KK, Sober AJ, et al. Is completion lymphadenec-

tomy after a positive sentinel lymph node biopsy for cutaneous mel-

anoma always necessary? Arch Surg 2004;139(4):4004.

86. Ghaferi AA, Wong SL, Johnson TM, et al. Prognostic significance of

a positive nonsentinel lymph node in cutaneous melanoma. Ann Surg

Oncol 2009;16(11):297884.

87. Denis MH, Dudrap E, Courville P, Auquit-Auckbur I, Joly P,

Milliez PY. Influence of the size and the localization of metastases

in melanoma sentinel lymph nodes on the results of lymphadenec-tomy. Ann Chir Plast Esthet 2007;52(1):2834.

88. Glumac N, Hocevar M, Zadnik V, Snoj M. Sentinel lymph node mi-

crometastasis may predict non-sentinel involvement in cutaneous

melanoma patients. J Surg Oncol 2008;98(1):468.

89. Guggenheim MM, Hug U, Jung FJ, et al. Morbidity and recurrence

after completion lymph node dissection following sentinel lymph

node biopsy in cutaneous malignant melanoma. Ann Surg 2008;

247(4):68793.

90. Page AJ, Carlson GW, Delman KA, Murray D, Hestley A, Cohen C.

Prediction of nonsentinel lymph node involvement in patients with

a positive sentinel lymph node in malignant melanoma. Am Surg

2007;73(7):6748.

91. van Akkooi AC, Nowecki ZI, Voit C, et al. Sentinel node tumor bur-

den according to the Rotterdam criteria is the most important





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prognostic factor for survival in melanoma patients: a multicenter

study in 388 patients with positive sentinel nodes. Ann Surg 2008;

248(6):94955.

92. Wagner JD, Ranieri J, Evdokimow DZ, et al. Patterns of initial recur-

rence and prognosis after sentinel lymph node biopsy and selective

lymphadenectomy for melanoma. Plast Reconstr Surg 2003;112(2):

48697.

93. Wagner JD, Park HM, Coleman 3rd JJ, Love C, Hayes JT. Cervical

sentinel lymph node biopsy for melanomas of the head and neck

and upper thorax. Arch Otolaryngol Head Neck Surg 2000;126(3):

31321.

94. Wagner JD, Gordon MS, Chuang TY, et al. Predicting sentinel and

residual lymph node basin disease after sentinel lymph node biopsy

for melanoma. Cancer 2000;89(2):45362.

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melanoma always necessary? A meta-analysis Eur J Surg Oncol (2013) http://dx doi org/10 1016/j ejso 2013 02 022

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Is Complete Lymph Node Dissection After a Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma Always Necessary