Crosbie 2010.

Study characteristics
Patient sampling	Prospective study; sampling method not described; mean follow‐up was 5 years
Patient characteristics and setting	32 women with clinical stage I/II vulval SCC < 4 cm; depth > 1 mm; histologically confirmed; 17 midline and 15 lateralised tumours No nodal involvement evident clinically or radiologically Median age: 67 years (34 to 94) Setting: tertiary referral hospital in the UK; recruitment from 2002 to 2006
Index tests	Tc‐99m and blue dye Histological methods: ultrastaging with IHC staining was performed for SNs that were negative with standard section and H&E stains
Target condition and reference standard(s)	TC: groin lymph node involvement RS: complete IFL
Flow and timing	24 hours pre‐operatively Tc‐99m (40 MBq in a total volume of 0.2 ml) was injected as 4 intradermal peritumoural injections (or around scar) and LSG acquired immediately for 20 to 30 minutes, up to 1 to 2 hours if nodes were not visualised. SNs were marked on the skin. Pre‐operatively 3 ml blue dye was injected at the same perilesional locations Radioactivity was detected intra‐operatively by gamma probe and blue dye was detected by visual identification of blue stained node and draining lymphatics SND and IFL were performed during the same procedure
Comparative
Notes	'Midline' lesions were not defined Approximately half of the women in this cohort underwent excisional biopsy of the primary lesion prior to inclusion in the study. Significantly fewer SNs were detected in these women (2.6 versus 1.8; P value = 0.03). 2 women were excluded as they were unfit for surgery The only false negative case occurred without an obvious explanation/association, such as obesity, nodal enlargement or complete replacement of the node by tumour. The investigators postulated that excision of the primary lesion may compromise SN detection and predispose to false negatives. They advocate performing incisional biopsy only There were no groin recurrences or distant metastases in women with negative SNs during clinical follow‐up (mean 5 years, range 33 to 84 months)
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Unclear
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Yes
		Unclear	Low
DOMAIN 2: Index Test Test group
Had the test operator performed 10 or more procedures?	Unclear
		Unclear	Low
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
		Unclear	Low
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Yes
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Were other imaging tests performed prior to the index test to rule out groin lymph node metastases?	Unclear
		Unclear