260 Grasic Kuhar C et al. / Digital ischemic events related to gemcitabine Blaise et al.9 reported two cases of digital ischemia. First was a female treated with gemcit- abine as the second line for lymph-node metastatic squamous cell carcinoma of unknown origin. The second patient was treated for bladder carcinoma with gemcitabine and carboplatine. Both resolved after the interruption of gemcitabine and addition- al medical treatment. Another case attributed to vascular toxicity of gemcitabine is reported by Holstein et al.10 treat- ed with platinum plus gemcitabine for advanced urothelial carcinoma. After the second cycle of chemotherapy the patient presented with dig- ital ischemia. Digital amputation was avoided by sympathicolysis by bilateral blockade of brachial plexus and application of iloprost, heparin, corti- costeroids and acetylsalicylic acid. Patients with scleroderma are at high risk for de- veloping digital infarction because of their under- lying vascular disease and associated Raynaud’s phenomenon. Clowse et al.11 presented a patient with scleroderma who developed multiple ischem- ic digits after receiving combination chemotherapy of carboplatin plus gemcitabine for lung cancer. D’Allesandro et al.12 reported a case with Raynaud type phenomenon, intermittent fever, digital necrosis and a fingertip gangrene after receiving two applications of gemcitabine for bladder can- cer. The authors suggested caution in using such chemotherapy in subjects with autoimmune disor- ders (scleroderma, positive HEP-2 and cryoglobu- lin).11,13 Digital ischemic changes resolved in most cases after stopping the application of chemotherapy and the treatment with prostacyclin antagonists (iloprost or buflomedil). A more sophisticated treatment with sympathicolysis by bilateral tho- racic block was reported to be efficient in digital ischemic event in scleroderma patient, where gan- grenous ulcers occurred due to vaso-occlusive disease, which is a combination of occlusive vas- culitis and symphatically-mediated vasospasm.6 Sympathectomy and iloprost infusion were report- ed to be successful in the treatment of severe acral ischemia and necrotic lesions of several fingertips after receiving palliative chemotherapy with gem- citabine for inoperable squamous cell carcinoma of the tonsil.14 In our Case 1 the first signs of the impaired dig- ital circulation (swollen and painful cold blue fin- gers) occurred after three weekly doses of gemcit- abine therapy and worsened after the next weekly application of the same drug, therefore the causal relationship between gemcitabine and digital arte- Radiol Oncol 2010; 44(4): 257-261. rial ischemia seems very probable. The patient had no history or symptoms of preexsisting PAOD or connective tissue disease. The Raynaud’s phenom- enon can be a paraneoplastic manifestation in dis- seminated pancreatic cancer, but would already be present at presentation of disease and would prob- ably improve with the effective anticancer therapy. The occurrence of digital ischemia was probably related to vascular toxicity of gemcitabine, as in- dicated by resolving microcirculation in 4 of 5 af- fected digits after the discontinuation of gemcitab- ine and the intervention with vasodilating agent iloprost. In Case 2 after the cumulative dose of gemcit- abine of 4000 mg/m2 and cisplatin 300 mg/m2 ar- terial ischemic necrosis on two digits of the right foot occurred. After a detailed investigation of the patient, severe preexisting PAOD of both legs with the very good collateral circulation was diagnosed. Gemcitabine may also be capable to cause endothe- lial damage and thrombocytosis.1,2 The latter could also attribute to impaired microcirculation in our case (platelet count at 3rd cycle of chemotherapy 1211 x 109/L). At that time the patient was on frac- tionated heparin in prophylactic dosing. Instead of heparin, the antiagregation therapy with acetylsal- icylic acid would be more appropriate in prevent- ing digital arterial thrombosis. After the dilatation of the occluded segment of the main leg arterial vessel and vasodilatation effect of iloprost infu- sion both macro and microcirculation improved, respectively. Digital ischemic necroses resolved without durable consequences. In both cases painful cold trophic skin changes were clinically suspicious of compromised arte- rial microcirculation, confirmed by absent plethys- mographic signals. In Case 1 Doppler ultrasound showed good macrocirculation, which was se- verely impaired in Case 2, as already suggestive of PAOD by patient’s long smoking history. Clinically absent pedal pulses and angiologic examination with arteriography could place angioplastic inter- vention before the initiation of chemotherapy with gemcitabine and cisplatin. A noninvasive evalu- ation of the leg arterial perfusion could be done by MRI enhanced angiography15 and an invasive angiography being applied only in cases where an invasive procedure is indicated. The antiagre- gation therapy (acetylsalicylic acid 100 mg a day) in case of severe reactive thrombocytosis in cancer patients as well as in patients with cardiovascular factors is indicated and could prevent the develop- ment of digital ischemia in Case 2. Discontinuation of cisplatin plus gemcitabine and the intervention