Abstract：
OBJECTIVE: To test the performance of ex vivo fluorescence confocal microscopy (FCM; Vivascope 2500M-G4), as compared to intra-operative frozen section (IFS) analysis, to evaluate surgical margins during robot-assisted radical prostatectomy (RARP), with final pathology as the reference standard.
METHODS: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter-observer agreement (Cohen\'s κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen\'s κ) was reported. For all analyses, four combinations of FCM results were evaluated.
RESULTS: At ex vivo FCM, the inter-observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results.
CONCLUSIONS: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub-par when compared to the established standard of care (IFS analysis).
METHODS: Overall, 54 margins in 45 patients treated with RARP were analysed with: (1) ex vivo FCM; (2) IFS analysis; and (3) final pathology. FCM margins were evaluated by two different pathologists (experienced [M.I.: 10 years] vs highly experienced [G.R.: >30 years]) as strongly negative, probably negative, doubtful, probably positive, or strongly positive. First, inter-observer agreement (Cohen\'s κ) between pathologists was tested. Second, we reported the sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) of ex vivo FCM. Finally, agreement between ex vivo FCM and IFS analysis (Cohen\'s κ) was reported. For all analyses, four combinations of FCM results were evaluated.
RESULTS: At ex vivo FCM, the inter-observer agreement between pathologists ranged from moderate (κ = 0.74) to almost perfect (κ = 0.90), according to the four categories of results. Indeed, at ex vivo FCM, the highly experienced pathologist reached the best balance between sensitivity (70.5%) specificity (91.8%), PPV (80.0%) and NPV (87.1%). Conversely, on IFS analysis, the sensitivity, specificity, PPV and NPV were, respectively, 88.2% vs 100% vs 100% vs 94.8%. The agreement between the ex vivo FCM and IFS analyses ranged from moderate (κ = 0.62) to strong (κ = 0.86), according to the four categories of results.
CONCLUSIONS: Evaluation of prostate margins at ex vivo FCM appears to be feasible and reliable. The agreement between readers encourages its widespread use in daily practice. Nevertheless, as of today, the performance of FCM seems to be sub-par when compared to the established standard of care (IFS analysis).
摘要：
目的：为了测试离体荧光共聚焦显微镜（FCM；Vivascope2500M-G4）的性能，与术中冰冻切片(IFS)分析相比，评估机器人辅助前列腺癌根治术（RARP）期间的手术切缘，以最终病理为参考标准。
方法：总的来说，用以下方法分析了45例接受RARP治疗的患者的54个切缘：（1）离体FCM；（2）IFS分析；（3）最终病理学。FCM边缘由两名不同的病理学家（经验丰富的[M.I.：10年]与经验丰富的[G.R.：>30年]）评估为强烈阴性，可能是负面的，令人怀疑,可能是积极的，或强烈的积极。首先,对病理学家之间的观察者间一致性(科恩κ)进行了测试。第二,我们报告了敏感性，特异性，离体FCM的阳性预测值(PPV)和阴性预测值(NPV)。最后,报道了离体FCM和IFS分析(科恩κ)的一致性。对于所有分析，评估了FCM结果的四种组合。
结果：在离体FCM，病理学家之间的观察者之间的一致性从中等(κ=0.74)到几乎完美(κ=0.90)，根据四类结果。的确,在体外FCM，经验丰富的病理学家在灵敏度（70.5%）特异性（91.8%）之间达到最佳平衡，PPV（80.0%）和NPV（87.1%）。相反，关于IFS分析，灵敏度,特异性，PPV和NPV分别为，分别,88.2%vs100%vs100%vs94.8%。离体FCM和IFS分析之间的一致性范围从中等（κ=0.62）到强（κ=0.86），根据四类结果。
结论：在离体FCM中评估前列腺边缘似乎是可行和可靠的。读者之间的协议鼓励其在日常实践中的广泛使用。然而，截至今天,与既定的护理标准(IFS分析)相比，FCM的表现似乎低于标准。
方法：总的来说，用以下方法分析了45例接受RARP治疗的患者的54个切缘：（1）离体FCM；（2）IFS分析；（3）最终病理学。FCM边缘由两名不同的病理学家（经验丰富的[M.I.：10年]与经验丰富的[G.R.：>30年]）评估为强烈阴性，可能是负面的，令人怀疑,可能是积极的，或强烈的积极。首先,对病理学家之间的观察者间一致性(科恩κ)进行了测试。第二,我们报告了敏感性，特异性，离体FCM的阳性预测值(PPV)和阴性预测值(NPV)。最后,报道了离体FCM和IFS分析(科恩κ)的一致性。对于所有分析，评估了FCM结果的四种组合。
结果：在离体FCM，病理学家之间的观察者之间的一致性从中等(κ=0.74)到几乎完美(κ=0.90)，根据四类结果。的确,在体外FCM，经验丰富的病理学家在灵敏度（70.5%）特异性（91.8%）之间达到最佳平衡，PPV（80.0%）和NPV（87.1%）。相反，关于IFS分析，灵敏度,特异性，PPV和NPV分别为，分别,88.2%vs100%vs100%vs94.8%。离体FCM和IFS分析之间的一致性范围从中等（κ=0.62）到强（κ=0.86），根据四类结果。
结论：在离体FCM中评估前列腺边缘似乎是可行和可靠的。读者之间的协议鼓励其在日常实践中的广泛使用。然而，截至今天,与既定的护理标准(IFS分析)相比，FCM的表现似乎低于标准。
