258 Grasic Kuhar C et al. / Digital ischemic events related to gemcitabine FIGURE 1. Ischemic necrosis on digits I and II of right foot after 4 cycles of chemo- therapy with cisplatin and gemcitabine (Case 2). reversible posterior leukoencephalopathy are re- ported.1 Digital ischemic events are rare in cancer pa- tients. They are most frequently related to vascular disease due to hypercholesterolemia, arterial hy- pertension, diabetes or exposure to tobacco. They may also occur as a complication of connective tissue diseases, i.e. vasculitis with digital ischemic events. In the present article we report two cases of dig- ital ischemic events during the therapy with gem- citabine alone and in combination with cisplatin and review data in the literature regarding this rare side effect. Case 1 A 65-year-old male was presented in March 2009 with primary metastatic adenocarcinoma of pan- creas (metastases in retroperitoneal and cervical nodes). He had a history of nephrolythiasis ten years ago and 5 months lasting history of hydrone- phrosis of the left kidney of grade III, caused by enlarged retroperitoneal lymph nodes. At presenta- tion he was overweight with grade I renal impair- ment (creatinine 129 μmol/L). He complained of pain in the upper abdomen. Tumour marker CA 19-9 was elevated (> 12 000 IU); platelet count was 376 x 109/L. In March 16 2009 he started the treatment with gemcitabine monotherapy in a weekly dose 1000 Radiol Oncol 2010; 44(4): 257-261. mg/m2. After 3 weekly doses he had less pain in the abdomen and tumour marker CA 19-9 halved (6163 IU). Platelet count was elevated (570 x 109/L). He complained of painful swelling in three digits of right hand and acrocyanosis. After the 4th dose of gemcitabine pain in digits increased and the pa- tient was admitted to the local hospital. Raynaud’s syndrome was suspected. Criteria for paraneoplas- tic microthrombosis, which was suspected, were not met. At the beginning the patient was treated with acetylsalicylic acid. No improvement was re- corded. On the control visit in our institution (May 05 2009) the patient complained of severe pain in five digits of both hands. The examination showed dry fingertips necrosis. Radial and ulnar pulses were normal. The Doppler ultrasound of both arms showed normal macrocirculation. Digital ple- thismography showed an absent signal on digits I, II and IV of the right and digits III and V of the left hand. Gemcitabine induced vasculitis causing ischemia was suspected and gemcitabine treat- ment was stopped. The patient was treated with the prolonged infusion of a prostacycline analogue iloprost trometamol (20 mg/day for three weeks) and analgesic therapy with NSARD and opioids. Digital changes in all but one of affected digits re- solved at the next visit in June 24 2009. Ischemic changes of distal phalange of digit V of the left hand required the amputation. The patient died in August 2009 due to the progressive disease. Case 2 A 77- year-old male presented in May 06 2009 with a diagnosis of locally advanced bladder cancer (T4aN2M0). He was heavy a smoker in the past and had a history of gastric perforation due to peptic ulcer ten years ago. In February 2009 he was tempo- rary on amiodarone medication due to paroxysm of atrial fibrillation. Otherwise he was in good physi- cal condition. In April 2009 he underwent an at- tempt of radical cistoprostatectomy. Due to the lo- cal extension of the tumour only Bricker neovesica and biopsy of pelvic lymphnodes was performed. In May 2009 he was presented for induction chemo- therapy and definitive radiotherapy afterwards. From May to August 2009 he received four cycles of chemotherapy with cisplatin and gemcitabine (cisplatin 75 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 every three weeks). None of the planned gemcitabine doses on day 8 was applied due to the infection. In August 8 2009 the patient presented with painful black spots on digits I and