Kingsbury J S, Cecere W, Mang T S, Liebow C
Department of Oral and Maxillofacial Surgery, State University of New York at Buffalo, School of Dental Medicine 14214, USA.
J Oral Maxillofac Surg. 1997 Apr;55(4):376-81; discussion 381-2. doi: 10.1016/s0278-2391(97)90130-0.
Photodynamic therapy (PDT) involves the selective destruction of neoplastic cells through the activation of a photosensitizer by light. We have previously shown that the photosensitizer Photofrin (porfimer sodium) is selectively accumulated in transformed lesions destined to become malignant, but not yet definable histologically as precancers. The aim of this investigation was to determine if this premalignant tissue could be selectively destroyed by systemically administered Photofrin activated by 630 nm red light via an argon dye laser.
The carcinogenic model used was the DMBA (9, 10 dimethyl 1,2 benzanthracene)-treated hamster cheek pouch. The animals were treated with 0.5% DMBA in acetone thrice weekly for 6 weeks (experiment I, premalignant lesions), or 12 weeks (experiment II, malignant lesions). Ten animals were in experiment I; nine animals were in experiment II. These were divided into experimental and control subgroups. The 6-week experimental group received PDT and CO2 laser incision into the DMBA-treated area. The CO2 laser was used as a promoter of neoplasia in a field that had already undergone initiation from the DMBA treatment. The control groups received either CO2 laser incision alone into the DMBA-treated field or CO2 laser incision and argon pumped dye laser treatment (without Photofrin). The 12-week experimental group received PDT after CO2 laser excision of tumors. The controls received CO2 excision alone, or CO2 excision combined with postoperative hyperthermia.
One hundred percent (three of three) of cheeks in experiment I receiving PDT developed necrosis of the treated area within 24 to 48 hours, but 0% (0 of three) subsequently developed tumors. No necrosis was seen in control cheeks receiving Photofrin without irradiation (0 of four) or irradiation without Photofrin (0 of six), and 56% (five of nine) of cheeks exposed to identical carcinogenic stimulus, without PDT, developed tumors (n = 9). In experiment II, 0% (0 of six) of cheeks receiving postoperative PDT developed tumor recurrence. In experiment II controls, 50% (three of six) of cheeks that underwent excision and hyperthermia developed tumor recurrence. In cheeks treated only with CO2 laser excision of tumors, a recurrence rate of 67% (four of six) was noted. These results were found to be statistically significant by the Student t-test on the binomial distribution (P < .01). One animal was treated with DMBA for 6 weeks, administered Photofrin, and the right cheek was irradiated and the animal was left for 30 weeks. The irradiated cheek epithelium necrosed but no cancer developed, whereas the positive control cheek developed a large cancer.
These results suggest that photodynamic therapy possesses significant potential in elimination of premalignant tissue. This could be beneficial in treating potentially premalignant lesions such as oral leukoplakia, and useful as adjunctive therapy in removal of areas of field cancerization adjacent to surgical sites.
光动力疗法（PDT）通过光激活光敏剂来选择性破坏肿瘤细胞。我们之前已经表明，光敏剂卟吩姆钠（Photofrin）选择性地积聚在注定会恶变但在组织学上尚未可定义为癌前病变的转化性病变中。本研究的目的是确定这种癌前组织是否可以通过经氩离子染料激光激活的630nm红光全身给药的卟吩姆钠进行选择性破坏。
所使用的致癌模型是经9,10 - 二甲基 - 1,2 - 苯并蒽（DMBA）处理的仓鼠颊囊。动物每周三次用0.5% DMBA丙酮溶液处理6周（实验I，癌前病变）或12周（实验II，恶性病变）。实验I中有10只动物；实验II中有9只动物。这些动物被分为实验组和对照组。6周的实验组接受光动力疗法和对DMBA处理区域进行二氧化碳激光切开。二氧化碳激光被用作在已经经过DMBA处理引发肿瘤的区域促进肿瘤形成的因素。对照组要么仅对DMBA处理区域进行二氧化碳激光切开，要么进行二氧化碳激光切开并接受氩离子泵浦染料激光治疗（不使用卟吩姆钠）。12周的实验组在二氧化碳激光切除肿瘤后接受光动力疗法。对照组接受单纯二氧化碳切除，或二氧化碳切除并术后热疗。
实验I中接受光动力疗法的脸颊（3只中的3只）100%在24至48小时内出现治疗区域坏死，但随后0%（3只中的0只）发生肿瘤。未接受照射的卟吩姆钠处理的对照脸颊（4只中的0只）或未接受卟吩姆钠的照射的对照脸颊（6只中的0只）均未出现坏死，并且在未接受光动力疗法、暴露于相同致癌刺激的脸颊中，56%（9只中的5只）发生肿瘤（n = 9）。在实验II中，接受术后光动力疗法的脸颊0%（6只中的0只）出现肿瘤复发。在实验II对照组中，接受切除和热疗的脸颊50%（6只中的3只）出现肿瘤复发。在仅用二氧化碳激光切除肿瘤的脸颊中，观察到复发率为67%（6只中的4只）。通过对二项分布的学生t检验发现这些结果具有统计学意义（P < 0.01）。一只动物用DMBA处理6周，给予卟吩姆钠，右侧脸颊接受照射，并将动物留存30周。照射的脸颊上皮坏死但未发生癌症，而阳性对照脸颊出现了大的癌症。
这些结果表明光动力疗法在消除癌前组织方面具有显著潜力。这对于治疗潜在的癌前病变如口腔白斑可能有益，并且作为辅助疗法用于切除手术部位附近的场癌化区域也可能有用。
