title: Long-term locoregional vascular morbidity after isolated limb perfusion and external-beam radiotherapy for soft tissue sarcoma of the extremity.
abstract: BACKGROUND
  Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-alpha) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated.
  
  
  METHODS
  Thirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up.
  
  
  RESULTS
  Five patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17-159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50-1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median, 10.95; range, 8.0-32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011).
  
  
  CONCLUSIONS
  ILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity.
authors: Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.
authors: Miriam L
authors: ML
authors: Hoven-Gondrie
authors: Katja M J
authors: KM
authors: Thijssens
authors: Jan J A M
authors: JJ
authors: Van den Dungen
authors: Jan
authors: J
authors: Loonstra
authors: Robert J
authors: RJ
authors: van Ginkel
authors: Harald J
authors: HJ
authors: Hoekstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects*; D005121:Extremities / Q000098:blood supply; D005260:Female; D006801:Humans; D007511:Ischemia / Q000209:etiology / Q000601:surgery; D023821:Limb Salvage / Q000379:methods; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D012509:Sarcoma / Q000601:surgery / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000601:surgery / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D014652:Vascular Diseases / Q000209:etiology* / Q000601:surgery
chemical_list: D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan