2)センチネルリンパ節の同定,生検による微小転移の検索 : 確実なリンパ節郭清と治療の個別化(シンポジウム2「子宮体癌治療戦略の新展開」,第63回日本産科婦人科学会・学術講演会)

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<Study 1: Feasibility of sentinel lymph node detection in endometrial cancer> The purpose of this study was to examine the feasibility of sentinel lymph node (SLN) detection techniques (hysteroscopic injection versus cervical injection) in patients with endometrial cancer. Hysteroscopic injection: Fifty-five patients with endometrial cancer who were scheduled for total abdominal hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and paraaortic lymphadenectomy at Tohoku University School of Medicine underwent sentinel lymph node detection. On the day before surgery, preoperative lymphoscintigraphy was performed by injection of 99m-Technetium (Tc)-labelled phytate into the endometrium during hysteroscopy. At the time of surgery, a gammadetecting probe was used to identify radioactive lymph nodes. In 20 patients in whom SLNs were detected and lymph node metastases were not detected by routine histological examination, all surgically removed lymph nodes, including SLNs, were examined histopathologically by immunohistochemistry staining with an anti-cytokeratin antibody (AE1/AE3) combined with step-serial sectioning at 0.2mm intervals. At least one sentinel node was detected in 43 of the 55 patients (74%). The mean number of sentinel nodes was 3.5. Thirty one of 43 patients had radioactive nodes in the paraaortic area. The sensitivity and negative predictive value for detecting lymph node metastases were both 100%. Micrometastases or isolated tumor cells were detected in 5 cases. Four of these 5 cases were detected in SLNs. The sensitivity for detecting lymph node metastases was 70% and negative predictive value was 94%. Cervical injection: Thirty-one patients were enrolled in this study. On the day before surgery, preoperative lymphoscintigraphy was performed by injection of 99m-Technetium (^<99m>Tc)-labeled phytate into the uterine cervix. At least one sentinel node was detected in 29 of the 31 patients (94%) and bi-lateral SLNs were detected in 27 patients. Nine of 10 patients with invasion into the outer half the myometrium had detectable SLNs. The mean number of sentinel nodes was 4.0. The detection area of SLNs was limited to the pelvic area only: SLNs could not be identified around the para-aortic area. Comparison between different detection techniques: The same SLNs were detected in 8 of 9 patients by hysteroscopic injection of RI compared with direct injection of blue dye into the uterine body. The same SLNs were detected in 17 of 17 patients by cervical injection of blue dye compared with cervical injection of RI. The SLN detection area by cervical injection of RI included that detected by direct uterine body injection of blue dye in all 12 cases. <Study 2: Comparing methods for intraoperative detection of lymph node metastasis> The purpose of this study was to assess methods of intraoperative detection of lymph node metastasis. Comparison between step-serial sectioning at 2mm intervals and 0.1mm intervals: A fresh lymph node was divided at 2.0mm intervals and examined intraoperatively. In cases without lymph node metastasis, SLNs were re-examined histologically by immunohistochemical staining with an anti-cytokeratin antibody (AE1/AE3) combined with step-serial sectioning at 0.1mm intervals. Macrometastases were detected in 2 of 97 SLNs and micrometastasis was detected in 1 case. In 2 of 75 cases without lymph node metastasis, isolated tumor cells (ITCs) were detected. Comparison of metastases detected by step-serial sections with One-step nucleic Acid Amplification (OSNA): The excised SLN was sectioned at 2.0mm intervals and divided into 2 groups (step-serial sectioning at 0.1mm intervals and OSNA assay of CK19 mRNA) in an alternating sequence. Forty-three of 44 negative lymph node diagnosed by step-serial section at 0.1mm intervals were also diagnosed negative by OSNA assay of CK19 mRNA. On the other hand, 3 of the 5 positive nodes diagnosed by step-serial section were diagnosed positive by OSNA but CK19 mRNA expression could not be detected in the two ITCs cases. <Study 3: Significance of micrometastasis> The purpose of this study was to examine the immunological and clinical significance of micrometastasis. Dendritic cell (DC) expression: We investigated whether the infiltration of immature and mature DCs differs in SLNs or non-SLNs, with or without micrometastases and with or without macrometastases. Twenty-seven SLNs without metastasis, 7 SLNs with micrometastasis, and 10 SLNs with macrometastasis were analyzed by immunohistochemistry using CD1a and CD83 to determine the infiltration of dendritic cells. CD83 expression was decreased in pelvic tumor-free SLNs compared with nodes containing micro- or macrometastases. This suggests that some degree of immunosuppression was occurring in the latter. Clinical course of patients with micrometastases or isolated tumor cells: Six cases with micrometastases and 2 cases with isolated tumor cells were investigated with respect to histopathological and clinical information as well as outcome. Seven of 8 cases underwent chemotherapy and none had recurrence (median observation period: 78 months), even though 3 of the 8 cases had metastasis to the paraaortic area. Conclusion Both techniques (hysteroscopic injection and cervical injection) may be useful in identifying pelvic SLNs in endometrial cancer. Micrometastases may be able to be detected intraoperatively by step-serial sectioning at 2mm intervals or by OSNA assay with CK19 mRNA. Micrometastases may have the same prognostic significance as macrometastases, and systematic lymphadenectomy and adjuvant chemotherapy may be recommended to patients with micrometastases.
2011-12-01

2)センチネルリンパ節の同定,生検による微小転移の検索 : 確実なリンパ節郭清と治療の個別化(シンポジウム2「子宮体癌治療戦略の新展開」,第63回日本産科婦人科学会・学術講演会)

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