Löning Martin, Diddens Heyke, Küpker Wolfgang, Diedrich Klaus, Hüttmann Gereon
Department of Obstetrics and Gynecology, University of Lübeck, Lübeck, Germany.
Cancer. 2004 Apr 15;100(8):1650-6. doi: 10.1002/cncr.20155.
The aim of the current clinical study was to evaluate the in vivo fluorescence detection of ovarian carcinoma metastases in a second-look laparoscopic procedure after intraperitoneally applied 5-aminolevulinic acid (ALA).
Five hours before laparoscopic surgery, ALA was applied intraperitoneally via short infusion in a concentration of 30 mg/kg bodyweight in a sterile, 1% solution. Application of ALA resulted in the endogenous production of the fluorescent photosensitizer, protoporphyrin IX (PP IX). The Combilight PDD 5133 system served as a light source, permitting the switch from white light mode to blue light mode to excite the PP IX accumulated in the ovarian tissue specimens. By means of blue light illumination, intraperitoneally located red fluorescent lesions, which were suspected to be metastases, underwent a biopsy. In addition, several biopsy specimens were taken from nonfluorescent areas of the peritoneal cavity.
In 13 of 29 patients, ovarian carcinoma was confirmed histologically or cytologically. In 12 of these patients, metastases were visible by red fluorescence. In total, 123 biopsies were performed. Comparison of histologic assessment of the biopsy specimens with the fluorescence detection showed that strong red fluorescence had a sensitivity of 92% for detecting tumor tissue on specimens. In only 2% of all biopsy specimens was endometriosis observed in benign tissue specimens using fluorescence. In four of 13 patients with ovarian carcinoma, lesions were detected under fluorescence, which were not observed under white light illumination.
Laparoscopic fluorescence detection of endogenous PP IX after intraperitoneal application of ALA may provide a higher sensitivity of finding peritoneal metastases of epithelian ovarian carcinoma compared with conventional laparoscopy. Direct visualization of in vivo fluorescence after ALA application may improve the early detection of intraperitoneal ovarian carcinoma micrometastases. The high tissue selectivity of PP IX accumulation in tumor tissue specimens also offers the opportunity for therapeutic approaches using photodynamic therapy in the future.
当前临床研究的目的是评估在腹腔内应用5-氨基酮戊酸（ALA）后的二次腹腔镜检查中对卵巢癌转移灶进行体内荧光检测的效果。
在腹腔镜手术前5小时，将浓度为30mg/kg体重的ALA以无菌1%溶液通过短时间输注腹腔内给药。ALA的应用导致内源性产生荧光光敏剂原卟啉IX（PP IX）。Combilight PDD 5133系统用作光源，可从白光模式切换到蓝光模式以激发积聚在卵巢组织标本中的PP IX。通过蓝光照明，对腹腔内疑似转移的红色荧光病变进行活检。此外，还从腹腔的非荧光区域采集了多个活检标本。
29例患者中有13例经组织学或细胞学确诊为卵巢癌。其中12例患者的转移灶可通过红色荧光观察到。总共进行了123次活检。将活检标本的组织学评估与荧光检测结果进行比较，结果显示强红色荧光检测标本中肿瘤组织的灵敏度为92%。在所有活检标本中，仅2%的良性组织标本通过荧光观察到子宫内膜异位症。在13例卵巢癌患者中的4例中，在荧光下检测到了白光照明下未观察到的病变。
腹腔内应用ALA后进行腹腔镜荧光检测内源性PP IX，与传统腹腔镜检查相比，可能在发现上皮性卵巢癌腹膜转移方面具有更高的灵敏度。ALA应用后体内荧光的直接可视化可能会改善腹腔内卵巢癌微转移灶的早期检测。PP IX在肿瘤组织标本中积累的高组织选择性也为未来使用光动力疗法的治疗方法提供了机会。
