Torne 2013.

Study characteristics
Patient Sampling	Country: Spain Study design: a prospective study of 293 women with endometrial cancer attending Department of Obstetrics and Gynecology of the Hospital Clinic of Barcelona March 2006 to March 2011 Inclusion criteria: unfavourable histology (serous papillary, clear cell or FIGO grade III endometrioid adenocarcinomas) or suspicion of deep myometrial invasion (> 50%) on magnetic resonance imaging (MRI) or involvement of the cervical stroma suspected by MRI or confirmed by hysteroscopically‐directed biopsy. Exclusion criteria: contraindication for surgical treatment or suspicion of metastatic disease in the preoperative staging evaluation or presence of pathological pelvic or paraaortic lymph nodes in the CT scan or MRI or previous history surgery or radiotherapy in the pelvic or paraaortic node regions or impossibility to perform a transvaginal ultrasound exam;BMI > 45.
Patient characteristics and setting	Number of patients:74 Mean/median age (SD, IQR, range): Not reported Mean/median BMI: not reported Histopathological cell type: endometrioid 53 (71%), clear cell 5 (6.8%), serious papillary 12 (16.2%), carcinosarcoma 3 (4%), other 1 (1.4%) FIGO stage: IA ‐ 30 (40.5%), IB ‐ 19 (25.6%), II ‐ 16 (21.6%), IIIA ‐ 1 (1.4%) IIIB ‐ 0 (0%), IIIC1 ‐ 6 (8.1%), IIIC2 ‐ 1 (1.4%), IVA ‐ 0 (0%), [IVB 1 (1.4%) – isolated peritoneal implant identified in surgery] Grade on hysterectomy specimen:1 ‐ 17 (23.0%), 2 ‐ 25 (33.8%), 3 ‐ 32 (43.2%) Lympho‐vascular space involvement:not reported Setting: single Centre in Barcelona, Department of Obstetrics and Gynecology of the Hospital Clinic of Barcelona, University of Barcelona Faculty of Medicine, Spain
Index tests	Type of endometrial sampling suction device, curettage or direct biopsy: curettage or hysteroscopic direct biopsy Experience of operator: not reported Tracer used and amount: during the pilot phase of the study, 9 patients received 4ml of Tch99, however the SLN visualisation rate was only 44.4% with this volume and these cases were therefore excluded from further analysis. For the next 8 cases, 8 mL of Tch99 was used, and this was then deemed adequate volume to be used in the study based on SLN visualisation rates achieved (NB: 148 MBq in all cases regardless of volume). Method and timing of application: ultrasound‐guided injections (TUMIR method) within anterior and posterior myometrial wall. (4 mL in each) with a 20‐G needle Method of detection: SLN detection: Preoperative, at 30 minutes and 2 to 4 hours, after injection with gamma probe, followed by PET CT. Intraoperative, at 18 to 20 hours post injection with a laparoscopic gamma probe and removed. SLN dissection: complete pelvic and para‐aortic laparoscopic lymph node dissection in all patients. Ultrastaging: 2 mm thick sections in shortest LN diameter. 4 mm thick sections H&E stained, if negative 2 new sections at 400 mm interval, one stained with H&E and one for cytokeratin 7.
Target condition and reference standard(s)	Type: all patients underwent laparoscopic surgery, included pelvic and para‐aortic lymph node dissection to the level of the left renal vein. Lymph node number and site: Area of SLN drainage (n = 55); pelvic (exclusive) 30 (54.5%), paraaortic (exclusive) 7 (12.8%) Pelvic and paraaortic 18 (32.7%) Side of pelvic node detection (n = 48): ‐ Left pelvic 21 (43.7%) ‐ Right pelvic 13 (27.1%) ‐ Bilateral 14 (29.2%) Site of paraaortic node detection (n = 25): ‐ Supramesenteric 4 (16.0%) ‐ Inframesenteric 15 (60.0%) ‐ Supramesenteric ‐ Inframesenteric 6 (24.0%).
Flow and timing	All patients received the index and reference standard within 1 month. All patients received the same reference standard and index tests. The initial 9 patients in the pilot received a different amount of tracer and were not included in the analysis; this initial subgroup served to evaluate the volume of radiotracer required for adequate SLN visualisation. All patients that were not part of this pilot were subsequently included in the analysis.
Comparative
Notes	Prospective study of 74 patients with high‐risk endometrial cancer recruited between March 2006 and March 2011 at a single centre in Barcelona. All patients received myometrial injection of Tch‐99. SLN detection rate was 74.3%. Sensitivity 92.3%. NPV 97.7%. Study results: Bilateral detection: 14 (29%) (NB unclear Unilateral detection: 34 (70.8%) (NB unclear) Isolated para‐aortic: 7 (1.2%) (NB unclear) Sensitivity: 92.3% (95% C.I. 22.9–100) NPV: 97.7% (95% C.I. 82.0–100), TP = 12; FP = 0; FN = 1; TN = 42; failed = 19. FIGO stage IA = 30; Stage IB+ = 44; type 1 and 2 tumours. Subserosal uterine injection (transvaginal USS guidance); bilateral detection = 14 patients. Adverse reaction from index or reference test: none Operating time: not reported Other intraoperative complications: not reported. Other postoperative complications: not reported.
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	Yes
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Could the selection of patients have introduced bias?		Unclear risk
Are there concerns that the included patients and setting do not match the review question?			Low concern
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	No
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
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
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
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
Could the patient flow have introduced bias?		Low risk