恶性嗜铬细胞瘤的治疗

1、恶性嗜铬细胞瘤的治疗第1页，共35页，2022年，5月20日，11点32分，星期三9/18/20221Introduction rule of 10s for pheochromocytoma (PCC) 10% bilateral 10% extra-adrenal 10% extra-abdomen 10% malignant 10% familial 10% children 10% normal blood pressure第2页，共35页，2022年，5月20日，11点32分，星期三9/18/20222IntroductionThe most frequent site of met

2、astases is the skeletonAdditional sites are liver, retroperitoneum with lymph nodes, CNS, pleura, and kidney第3页，共35页，2022年，5月20日，11点32分，星期三9/18/20223Malignant vs. BenignCurrently, there is no effective cure for malignant pheochromocytoma.There are also no reliable histopathological methods for disti

3、nguishing benign from malignant tumors.Malignancy requires evidence of metastases at non-chromaffin sites distant from that of the primary tumor.第4页，共35页，2022年，5月20日，11点32分，星期三9/18/20224Metastatic disease in pheochromocytoma may be present at the time of initial diagnosis or may only became evident

4、after surgical removal of the primary tumor, usually within 5 years, but sometimes 16 or more years later.第5页，共35页，2022年，5月20日，11点32分，星期三9/18/20225Due to the rarity of the tumor, clinical studies about pheochromocytoma suffer from a fragmented nature and usually involve too small a number of cases t

5、o reach conclusive results.第6页，共35页，2022年，5月20日，11点32分，星期三9/18/20226Because there is currently no effective cure for malignant pheochromocytoma, most treatment are palliative, but in some cases may reduce tumor burden and prolong survival.Without treatment, the 5-year survival is generally less than

6、 50%.The course, however, can be highly variable with occasional patients living more than 20 years after diagnosis.第7页，共35页，2022年，5月20日，11点32分，星期三9/18/20227Once malignancy is diagnosed, therapy is generally directed at controlling blood pressure, but may also include tumor debulking.第8页，共35页，2022年，

7、5月20日，11点32分，星期三9/18/20228Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization第9页，共35页，2022年，5月20日，11点32分，星期三9/18/20229Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization第10页，共35页，2022年，5月20日，11点32分，星期三9/1

8、8/202210Primary surgical resection is the treatment of choice whenever possibleLimited disease: curative intentionExtended disease: still to be considered in the first place for debulking and as palliative treatment(Mundschenk et al. 1998)第11页，共35页，2022年，5月20日，11点32分，星期三9/18/202211ProblemWhen signs

9、of regional involvement or distant disease are absent, there is currently no reliable preoperative diagnostic test that can differentiate between malignant and benign pheochromocytomas Should pheochromocytoma size influence surgical approach? 第12页，共35页，2022年，5月20日，11点32分，星期三9/18/202212A comparison o

10、f 90 malignant and 60 benign pheochromocytomas (Wen T. Shen et al.2004)Comparison of tumor size for benign pheochromocytomas and malignant pheochromocytomas with local disease only Size does not reliably predict malignancy in pheochromocytomas with local disease only 第13页，共35页，2022年，5月20日，11点32分，星期三

11、9/18/202213Malignant (n=29)Benign (n=55)Tumor size (mean SD)6.1 3.1 cm5.3 2.3 cm2 cm012.0-3.9 cm9104.0-5.9 cm6256.0-7.9 cm5138.0-9.9 cm5310 cm43第14页，共35页，2022年，5月20日，11点32分，星期三9/18/202214Malignant PCCs presenting with only local disease cannot be discriminated from benign PCCs by size alone. When PC

12、Cs do not have evidence of invasion or distant metastases and the surgeon acquires an appropriate level of experience, the majority of these tumors can be safely resected laparoscopically. 第15页，共35页，2022年，5月20日，11点32分，星期三9/18/202215Laparoscopic adrenalectomy for pheochromocytoma should be converted

13、to open adrenalectomy for difficult dissection, invasion, adhesions, or surgeon inexperience 第16页，共35页，2022年，5月20日，11点32分，星期三9/18/202216Surgical approachTransabdominal approach is necessaryminimally invasive proceduresretroperitoneal approaches should be abandonedto definitely preserve the tumor cap

14、sule and perform total lymphadecectomy(Orchard et al. 1993)第17页，共35页，2022年，5月20日，11点32分，星期三9/18/202217Secondary TumorsNo experience with adjuvant pre and postoperative radiation existsGenerally are multipleRadical surgical resection is often impossibleOther treatment modalities have to be considered

15、第18页，共35页，2022年，5月20日，11点32分，星期三9/18/202218Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization第19页，共35页，2022年，5月20日，11点32分，星期三9/18/202219第20页，共35页，2022年，5月20日，11点32分，星期三9/18/202220131I-MIBG is the treatment of choice for all unresectable, MIBG positive

16、 tumors58 cases of malignant PCC treated by 131I-MIBGtherapeutic results and adverse events(ZHU Ruisen et al. 1999)第21页，共35页，2022年，5月20日，11点32分，星期三9/18/202221Patients were classified into 3 groups according to their tumor size 20 cm3 (26 cases) In group 1, the mean absorption dose per gram of tumor

17、was above 1 000 cGy. After treatment ,tumors disappeared or shrinked in all patients 第22页，共35页，2022年，5月20日，11点32分，星期三9/18/202222In group 2 , the absorption dose was similar to that of group 1, but the mean absorption dose per gram was 717.6 cGy , and tumor mass regression was 36 % ;76 % reduced urin

18、ary catecholamine In group 3 , the absorption dose per gram tumor tissue was 277 cGy , and 30 % tumor enlargement , 20 % died ; the remaining 50 % symptomatic improvement without any change in tumor size第23页，共35页，2022年，5月20日，11点32分，星期三9/18/202223131 I-MIBG is of certain therapeutic effectiveness of

19、symptomatic improvementComplete tumor mass disappearance has only been found in small tumorsTreatment with 131 I-MIBG should be instituted immediately after surgical resection to eradicate the residual tumor cells and to prevent recurrencesBone marrow suppression is temporary and not dosage related第

20、24页，共35页，2022年，5月20日，11点32分，星期三9/18/202224In 1997, Loh et al. published a review of the worldwide experience involving 116 patients treated with 131I-MIBG for malignant pheochromocytoma. Overall, there was a symptomatic response in 76%, a hormonal response in 45%, and tumor regression in 30%. The ac

21、tivity of 131I-MIBG per single dose was 96300 mCi, and the mean cumulative activity was 490350 mCi.Only five CRs to 131I-MIBG were reported.第25页，共35页，2022年，5月20日，11点32分，星期三9/18/202225LimitationsNot all patients with multiple metastases of malignant pheochromocytomas have sufficient uptake of MIBG to

22、 allow MIBG therapyMIBG negative lesions coexist with MIBG postive lesions, requiring combined treatment第26页，共35页，2022年，5月20日，11点32分，星期三9/18/202226As a single agent,131I-MIBG has limited efficacy in treating malignant pheochromocytoma. Its use in combination with other cytotoxic agents, as is curren

23、tly being studied in patients with neuroblastoma, may result in additional benefit(Sisson et al. 1999)第27页，共35页，2022年，5月20日，11点32分，星期三9/18/202227Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization第28页，共35页，2022年，5月20日，11点32分，星期三9/18/202228Only sparse d

24、ata on chemotherapeutic regimens are available, most of them in reports of few casesThe most well-established regimen is CVD (Averbuch et al. 1988)CTX 750mg/m2 d1, VCR 1.4mg/m2 d1, Dacarbazine 600mg/m2 d1,2Cycle 21 days第29页，共35页，2022年，5月20日，11点32分，星期三9/18/202229The CVD regimen was based on the treat

25、ment for advanced neuroblastoma.This regimen has been reported to produce good responses in malignant pheochromocytoma, but the median duration of remission is 21 monthsComplete long-term disease remissions with chemotherapy have not been reported.第30页，共35页，2022年，5月20日，11点32分，星期三9/18/202230Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyTrans