术前皮下埋植式化疗泵动脉介入化疗四肢软组织肉瘤与癌性溃疡的疗效观察

Effects observation of subcutaneous intra-arterial chemotherapy with subcutaneously implanted pump for extremity soft tissues sarcoma and cancerous ulcer

目的观察四肢软组织肉瘤及癌性溃疡术前皮下埋植式化疗泵动脉介入化疗的疗效。方法回顾性分析2003年7月至2011年11月,我科收治的肉瘤及癌性溃疡31例,其中男15例,女16例,年龄14～83岁,平均49岁。癌性溃疡主要症状为疼痛、感染和出血。术前经化疗泵给予表阿霉素（90 mg/m2）和顺铂（120 mg/m2）,鳞癌加用博莱霉素（15 mg）,恶性黑色瘤加用氮烯咪胺（600 mg/m2）,介入化疗至少3周期;化疗后根据肿瘤边界和血液供应情况,决定是否手术或保守治疗。观察患者治疗前疼痛情况及治疗后疼痛缓解情况;参照WHO抗肿瘤药物客观疗效判定标准对实体肿瘤行疗效评价。结果本组平均随访时间67个月。（1）本组疼痛患者治疗前,中度疼痛18例,重度疼痛13例。化疗后1个周期均可达到疼痛缓解,其中完全缓解（complete remission,CR）19例,部分缓解（partial remission,PR）8例,轻度缓解（mild remission,MR）4例,疼痛缓解总有效率（total remission rate,RR）为87%;化疗3次后,仅有4例仍有轻度疼痛。（2）溃疡引起患者抵抗力明显下降。肿瘤溃疡经化疗后CR 7例,PR 15例,无效（no curative effect,NC）9例,溃疡愈合RR为71%。肿瘤溃疡明显散发腥臭味者12例,治疗后均渗出减少、腥臭味减低。以破溃出血为主要症状6例经3～4次化疗后完全止血。合并淋巴结转移的11例,化疗后淋巴结转移灶消失8例,明显缩小3例。（3）除患肢皮肤营养较健侧稍差外,未见其它不良反应。（4）本组化疗后肿瘤缩小后,行手术的19例（保肢16例、截肢3例）,其余12例保守治疗。保肢的16例中3例术后局部复发,局部复发率19%。术后出现病理轻度化疗反应者5例,中度化疗反应者10例,重度化疗反应者4例。结论术前皮下埋植式化疗泵动脉介入化疗四肢软组织肉瘤及癌性溃疡,能有效控制肿瘤破溃所产生的疼痛、感染及出血症状;为再手术创造了局部低血供及清晰的外科边界,减少复发率。

Objective To observe the efficiency of subcutaneous intra-arterial chemotherapy with subcutaneously implanted pump for extremity soft tissues sarcoma and cancerous ulcer. Methods Thirty-one patients with ulcerative skin squamous cell carcinoma or soft tissues sarcoma of extremities received treatment from July 2003 to November 2011, including 15 males and 16 females. The average age was 49 years old （ range： 14-83 years ）. Ten patients had sarcoma in upper extremities and 21 patients in lower extremities. The pathological types of studied cases included 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage. All the studied patients were administrated with cisplatin （ 120 mg / m^2 ） and doxorubicin （ 90 mg / m^2 ） by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin （ 15 mg ） and patients with malignant melanoma were applied with dacarbazine （ 600 mg / m^2 ）. The chemotherapy efficiency was observed after at 2-3 cycles of intra-arterial chemotherapy. Surgical or conservative treatment was chosen according to tumor boundary and blood supply after chemotherapy. Pain and pain relief were observed in patients pre-treatment and post-treatment. Effects on solid tumors were evaluated according to WHO （ World Hearth Organization ） criteria. Results The mean follow-up was 67 months in this group. （ 1 ） Before the treatment, moderate pain was in 18 cases, severe pain in 13 cases. Pain relief was achieved after one cycle of chemotherapy, including complete remission （ CR ） 19 cases, partial remission （ PR ） 8 cases, mild remission （ MR ） 4 cases. The total remission rate of pain （ RR ） was 87%. There were only four cases of mild pain after three times of chemotherapy. （ 2 ） Immunity was decreased due to the ulcers in patients. Tumor ulcer patients after chemotherapy： CR 7 cases, PR 15 cases, NC （ no curative effect ） NC 9 cases. Total remission rate of ulcer cicatrization （ RR ） was 71%. Stench from tumor ulceration occurred in 12 cases, all oozing and stench reduced post-treatment. Featured with ulceration and hemorrhage, hemostasis in 6 cases was achieved after 3-4 times of chemotherapy. In 11 cases of patients with lymph node metastasis, lymph node metastases disappeared in 8cases and reduced in size in 3 cases significantly after chemotherapy. （ 3 ） Except for malnourished skin comparing with the healthy side, no other adverse side effects existed. After tumor shrinking in chemotherapy, surgeries were performed in 19 cases （ 16 cases of limb salvage, 3 cases of amputation ）, and the remaining 12 cases were treated conservatively. Three out of 16 patients had local recurrence （ 19% ）. Postoperative pathologic response to chemotherapy occurred in 5 patients （ mild ）, 10 patients （ moderate ） and 4 cases （ severe ）. Conclusions The subcutaneous intra-arterial targeting chemotherapy can be applied to treat extremities sarcoma and cancerous ulcer to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms including pain, infection and bleeding, which will help to make a decreased blood supplied and well defined tumor boundary to finally decrease the recurrence rate.