Kataoka 2016.
| Study characteristics | |||
| Patient Sampling | Country: Japan Study design: a prospective cohort study of patients with histologically‐diagnosed endometrial cancer clinical stage IA‐II scheduled for surgery, between April 2009 and December 2012. Patients received either Tc99 labelled phytate (Tc99) method), or Tc99 + indocyanine green (ICG) (Tc99+ICG). Inclusion criteria: patients with endometrial cancer verified by pathological diagnosis scheduled to receive hysterectomy with retroperitoneal lymphadenectomy, clinical stage IA–II (FIGO2009) and confined to uterus by MRI and CT imaging, over 20 years old at the time of signature of informed consent. Exclusion criteria: patients with grade 1 endometrioid adenocarcinoma without muscular invasion at preoperative evaluation with MRI; obvious extrauterine spread at their preoperative evaluation with MRI and CT; other malignancy within previous 5 years; perioperative findings of bulky lymph nodes or extrauterine dissemination; concomitant cancer elsewhere. |
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| Patient characteristics and setting | Number of patients: 55 (Tc99+ICG 32; ICG alone 23) Median age years (range):Tc99 + ICG = 54 (30‐77); ICG alone = 54 (27‐76) Mean/median BMI: not reported Histopathological cell type: Tc99+ICG: endometrioid = 27 (84.3%); serous = 2 (6.3%); mixed = 3 (9.4%) ICG alone: endometrioid = 22 (95.7%); serous = 0 (0%); mixed = 1 (4.3%) FIGO stage: Tc99+ICG: IA = 15 (46.9%), IB = 2 (6.3%), II = 3 (9.4%), IIIA = 3 (9.4%), IIIB = 1 (3.1%), IIIC1 = 1 (3.1%), IIIC2 = 7 (21.9%) ICG alone: IA = 14 (60.9%), IB = 3 (13.0%), II = 1 (4.3%), IIIA = 0 (0%), IIIB = 0 (0%), IIIC1 = 2 (8.7%), IIIC2 = 3 (13.0%) Grade on hysterectomy specimen: Tc99 + ICG: grade 1 = 4 (12.5%), grade 2 = 20 (62.5%) , grade 3 = 8 (25%) ICG alone: grade 1 = 7 (30.5%), grade 2 = 13 (56.5%), grade 3 = 3 (13%) Lymphovascular space involvement: Tc99+ICG: present = 18 (56.3), absent = 14 (43.7%) ICG alone: present = 10 (43.5%), absent = 13 (56.5%) Setting: single centre in Japan, namely Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinjuku‐ku, Tokyo, Japan. |
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| Index tests | Type of endometrial sampling: not reported Experience of operator: not reported Tracer used and amount: ICG: Indocyanine green (ICG) (volume not specified) Tc99+ICG: As above + 99m‐Technetium (99mTc)‐labelled phytate (0.2 mL at 5 points, total 2 mCi). Method and timing of application: ICG: Intraoperatively, ICG was injected sub‐serosally at 5 points of the uterine corpus, and dye uptake was detected by macroscopic observation (observation by the naked eye). Six minutes after injection, retroperitoneal spaces were then opened and retroperitoneal sentinel dye‐containing nodes were detected macroscopically. When identified, these nodes were marked with ligation approximately within 30 minutes after the injection. Tc99+ICG: As above, as well as: 16 hours preoperatively, 99m‐Technetium (99mTc)‐labelled phytate was injected into the sub‐endometrium at 5 points (0.2 mL × 5, total 2 mCi) just around the tumour using hysteroscopy of a 6.5 mm operative hysteroscope after cervical dilation under anaesthesia. Preoperative lymphoscintigraphy was obtained 15 hours after the tracer injection. Intraoperative radio‐labelled SN sampling was performed using a handheld gamma probe Method of detection (histopathological assessment, including ultrastaging): intraoperative frozen section diagnosis of the SNs was performed in every case. Pathologic ultrastaging was performed, with multiple serial sectioning of the entire sentinel lymph node at 200 μm to 300 μm, with 3 consecutive HE levels with one slide for immunostaining per level. Immunostaining for cytokeratin (clone AE1/AE3, Milipore Inc., dilution 1:150) was performed in SNs after HE routine histological examination. Non‐SNs were processed using entire node examination with HE staining. Macrometastases were considered as tumour foci larger than 2 mm, whereas micrometastases were considered as tumour foci between 0.2 mm and 2 mm. Isolated tumour cells (ITC) were defined as deposits less than 0.2 mm. |
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| Target condition and reference standard(s) | Type: 55 patients with a preoperative histological diagnosis of grade I, II, or III endometrial cancer, all of whom received pelvic +/‐ para‐aortic (38.2%) lymphadenectomy. All surgeries were carried out by laparotomy. Lymph node number and site: SN detection rate 100%. Mean SNs removed per patient: Tc99+ICG: 6.0 (range 1‐10) ICG: 4.1 (range 1‐9). Anatomical sites: Tc99+ICG: pelvic 3.7 (range 1‐7), para‐aortic 2.3 (range 0‐4) ICG: pelvic 2.9 (range 0‐5), para‐aortic 1.1 (range 0‐5) |
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| Flow and timing | All patients received the index and reference standard within 1 month. The patients did not all receive the same reference standard. Only 21/55 (38%) patients received pelvic and para‐aortic lymphadenectomy. The remaining 62% received pelvic lymphadenectomy alone. All patients were included in the analysis. | ||
| Comparative | |||
| Notes | Study results: the sentinel node detection rate was 100% for both RI + Dye and Dye alone methods. Based on the final diagnosis with cytokeratin staining: Tc99+ICG: sensitivity 100% (8/8), negative predictive value (NPV) 100% (24/24), ICG alone (includes patients in Tc99 + ICG group): sensitivity 83.3% (10/12), negative predictive value (NPV) 95.3% (10/12). Tc99 + ICG TP = 8; FP = 0; FN = 0; TN = 24; failed = 0. FIGO stage IA = 15; Stage Ib+ = 17; Type 1 and 2 tumours. Subserosal injection; bilateral detection rate not given. ICG only (includes patients in Tc99+ICG group) TP = 10; FP = 0; FN = 2; TN = 43; failed = 0. FIGO stage IA = 29 (including 15 from Tc99+ICG group); FIGO IB+ = 26 (including 17 fro Tc99+ICG group); Type 1 and 2 tumours. Subserosal injection; bilateral detection rate not given. Operating time: not given Intraoperative complications: no allergic reactions. Nothing else specified. Postoperative complications: nothing specified. There appear to be 13 patients with positive nodes in table 4, although only 12 accounted for in description of FP/FN rates. The additional patient is in the IGC only group. |
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| 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? | Yes | ||
| 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? | No | ||
| Were all patients included in the analysis? | Yes | ||
| Could the patient flow have introduced bias? | Unclear risk | ||