Critical limb ischaemia associated with chemotherapy for breast cancer

Abstract

The chemotherapeutic agents used for cancer have a wide range of reported side-effects but these have so far not included critical limb ischaemia. We have seen three cases in women being treated for ductal carcinoma of the breast. CASE HISTORIES Case 1A woman of 56 was seen after her left foot had been cold and painful for 24 hours. In addition she said that for two months her fingers had been intermittently cold and blue. Her only risk factor for peripheral vascular disease was cigarette smoking, about ten a day. Recently an invasive ductal cancer of the breast had been treated with wide local excision and axillary clearance. One out of fifteen lymph nodes contained tumour but she was not thought to have metastatic disease elsewhere. She had undergone five cycles of cyclophosphamide, methotrexate and 5-fluorouracil (5-FU) chemotherapy (CMF) and was taking tamoxifen. The 5-FU was administered as an intravenous bolus of 987.5 mg at alternating one-week and three-week intervals. The last infusion had been 3 days earlier. On direct questioning, it was clear that the patient had first developed transient pain in her left foot after her first cycle of chemotherapy. When the pain recurred after the second cycle, deep venous thrombosis had been excluded by duplex scanning.On examination her left foot was cold and pulseless and the third and fourth toes were dusky blue. A doppler signal was just audible over the posterior tibial artery but anklebrachial pressure indices were not recordable. An arteriogram revealed a normal aorta and iliac vessels but the left superficial femoral artery was attenuated with occlusion of the popliteal just above the joint line (Figure 1).The chemotherapy was stopped and she was treated with an intravenous bolus of 5000 units of unfractionated heparin followed by an intravenous heparin infusion of 24 000 units over 24 hours. Three successive intravenous infusions of Iloprost (a prostacyclin analogue) 50 mg, in 250 mL 5% glucose, were given without improvement. Two days later a left chemical sympathectomy was performed and the foot became warmer though still painful. Aspirin 150 mg daily was then started. Over the coming weeks she improved clinically and the fourth toe returned to normal. However, the pain remained troublesome. Further duplex scanning revealed no distal popliteal or trifurcation vessels but the posterior tibial vessel was seen to re-form just above the medial malleolus as a reasonable sized vessel with very damped flow. She underwent a reverse autologous long saphenous vein left popliteo-posterior tibial bypass and the third toe was amputated. Postoperatively she was heparinized and subsequently warfarinized. The graft remains patent at one year. Case 2A woman aged 46 was seen when three months of increasing pain in the fingers and toes, with occasional discoloration, culminated in a long episode of pain and redness in the right foot. She was undergoing cyclical intravenous CMF chemotherapy for invasive ductal 444

Mesozoic to Cenozoic tectono‐metamorphic history of the South Pamir–Hindu Kush (Chitral, NW Pakistan): Insights from phase equilibria modelling, and garnet–monazite petrochronology

“…An improved understanding of the thermal and structural history of the Mesozoic Eurasian plate margin will allow better insight into the initial boundary conditions (e.g. crustal thickness, structure and thermo-mechanical properties) for the development of the large and hot Tibetan-Himalaya orogen, and, therefore, also into the associated crustal deformation processes, such as the interpreted channel flow in the Miocene or eastward escape beneath the Tibetan plateau at present day (Beaumont, Jamieson, Nguyen, & Medvedev, 2004;Carosi, Montomoli, Iaccarino, & Visonà, 2018;Cottle, Larson, & Kellett, 2015;Godin, Grujic, Law, & Searle, 2006;Parsons et al, 2016;Searle, Law, & Jessup, 2006).…”