1、2022-11-11Therapy of Malignant Pheochromocytoma恶性嗜铬细胞瘤的治疗Literature Report.2022-11-12Introduction rule of 10s for pheochromocytoma(PCC)10%bilateral 10%extra-adrenal 10%extra-abdomen 10%malignant 10%familial 10%children 10%normal blood pressure.2022-11-13IntroductionThe most frequent site of metastas
2、es is the skeletonAdditional sites are liver,retroperitoneum with lymph nodes,CNS,pleura,and kidney.2022-11-14Malignant vs.BenignCurrently,there is no effective cure for malignant pheochromocytoma.There are also no reliable histopathological methods for distinguishing benign from malignant tumors.Ma
3、lignancy requires evidence of metastases at non-chromaffin sites distant from that of the primary tumor.2022-11-15Metastatic disease in pheochromocytoma may be present at the time of initial diagnosis or may only became evident after surgical removal of the primary tumor,usually within 5 years,but s
4、ometimes 16 or more years later.2022-11-16Due to the rarity of the tumor,clinical studies about pheochromocytoma suffer from a fragmented nature and usually involve too small a number of cases to reach conclusive results.2022-11-17Because there is currently no effective cure for malignant pheochromo
5、cytoma,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 50%.The course,however,can be highly variable with occasional patients living more than 20 years after diagnosis.2022-11-18Once malignancy
6、is diagnosed,therapy is generally directed at controlling blood pressure,but may also include tumor debulking.2022-11-19Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization.2022-11-110Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined Che
7、motherapyArterial Embolization.2022-11-111Primary 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).2022-11-112ProblemWhen signs
8、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?.2022-11-113A comparison of 90 malignant and 60 benign pheo
9、chromocytomas (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.2022-11-114Malignant(n=29)Benign(n=55)Tumor size(mean SD)6.1 3.1 c
10、m5.3 2.3 cm2 cm012.0-3.9 cm9104.0-5.9 cm6256.0-7.9 cm5138.0-9.9 cm5310 cm43.2022-11-115Malignant PCCs presenting with only local disease cannot be discriminated from benign PCCs by size alone.When PCCs do not have evidence of invasion or distant metastases and the surgeon acquires an appropriate lev
11、el of experience,the majority of these tumors can be safely resected laparoscopically.2022-11-116Laparoscopic adrenalectomy for pheochromocytoma should be converted to open adrenalectomy for difficult dissection,invasion,adhesions,or surgeon inexperience.2022-11-117Surgical approachTransabdominal ap
12、proach is necessaryminimally invasive proceduresretroperitoneal approaches should be abandonedto definitely preserve the tumor capsule and perform total lymphadecectomy(Orchard et al.1993).2022-11-118Secondary TumorsNo experience with adjuvant pre and postoperative radiation existsGenerally are mult
13、ipleRadical surgical resection is often impossibleOther treatment modalities have to be considered.2022-11-119Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization.2022-11-120.2022-11-121131I-MIBG is the treatment of choice for all unresectable,MIBG posi
14、tive tumors58 cases of malignant PCC treated by 131I-MIBGtherapeutic results and adverse events(ZHU Ruisen et al.1999).2022-11-122Patients 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 was above 1 000 cGy.After treat
15、ment,tumors disappeared or shrinked in all patients.2022-11-123In 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 urinary catecholamine In group 3,the absorption dose per gram tumor tissue was
16、 277 cGy,and 30%tumor enlargement,20%died;the remaining 50%symptomatic improvement without any change in tumor size.2022-11-124131 I-MIBG is of certain therapeutic effectiveness of symptomatic improvementComplete tumor mass disappearance has only been found in small tumorsTreatment with 131 I-MIBG s
17、hould be instituted immediately after surgical resection to eradicate the residual tumor cells and to prevent recurrencesBone marrow suppression is temporary and not dosage related.2022-11-125In 1997,Loh et al.published a review of the worldwide experience involving 116 patients treated with 131I-MI
18、BG for malignant pheochromocytoma.Overall,there was a symptomatic response in 76%,a hormonal response in 45%,and tumor regression in 30%.The activity 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.2022-11-126Limitat
19、ionsNot all patients with multiple metastases of malignant pheochromocytomas have sufficient uptake of MIBG to allow MIBG therapyMIBG negative lesions coexist with MIBG postive lesions,requiring combined treatment.2022-11-127As a single agent,131I-MIBG has limited efficacy in treating malignant pheo
20、chromocytoma.Its use in combination with other cytotoxic agents,as is currently being studied in patients with neuroblastoma,may result in additional benefit(Sisson et al.1999).2022-11-128Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined ChemotherapyArterial Embolization.2022-11-129O
21、nly sparse data 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.2022-11-130The CVD regimen was based on the treatment for advanced neurob
22、lastoma.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.2022-11-131Alternative of Current TherapySurgeryRadiopharmaceuticalsCombined
23、ChemotherapyTranscatheter Arterial Embolization.2022-11-132TAE has been successfully performed in the treatment of malignant PCC with liver metastasesThe therapeutic effects of TAE have been demonstrated to be enhanced by the combination therapy with anticancer chemotherapy.2022-11-133Mitomycin C ha
24、s been successfully used in TAE for liver metastasis in several cases of malignant PCC.2022-11-134.2022-11-135Malignant pheochromocytoma:past,present and futurePast Present FutureAdrenergic blockers,-methyl-paratyrosine&use of other drugs for symptomatic reliefSurgical debulking;131I-MIBG radiotherapy;Chemotherapy;ChemoembolizationMolecular targeting,cancer vaccines,gene therapy.
