Complications of CE are one of the most common causes of mortality in CE patients, with size, location, and number of cysts, and the 'watch and wait' treatment strategy being the main factors associated with mortality.

Gemcitabine and haemolyticuraemic syndromeGemcitabine is a pyrimidine antimetabolite with a broad spectrum of activity, and is used in pancreatic carcinoma.The main dose-limiting side-effects are myelosuppression, vomiting, flu-like symptoms, and in rare cases, haemolyticuraemic syndrome (HUS). We report a patient who developed HUS related to the administration of gemcitabine therapy.A 54-year-old man underwent a duodenopancreatectomy after a carcinoma of the pancreas was detected. The tumour and the two involved lymph nodes were removed.Fifteen months later, local relapse and multiple pulmonary metastases were detected; subsequently, chemotherapy with intravenous gemcitabine (1000 mg/m 2 on days 1, 8 and 15) and tegafur orally (400 mg every 12 h for 21 days), both every 4 weeks, was initiated.After the fourth course, the patient was dyspnoeic and hypertensive, and suffered from daily chest pain, which suggested the existence of angina pectoris. Laboratory analyses revealed a haemolytic anaemia (haemoglobin 6.9 g/dl; indirect bilirubin and LDH elevated; decreased haptoglobin; increased reticulocyte count; negative direct Coombs; fragmentocytes on peripheral blood smear), deteriorating renal function and thrombocytopenia.Because of these clinical and analytical findings, we diagnosed haemolytic-uraemic syndrome; therapy with corticosteroids was begun and we considered plasmapheresis. This was not possible because the patient underwent a new episode of angina pectoris and, later, a myocardial infarct.In the light of the serious situation and poor prognosis, it was decided not to adopt aggressive measures and to apply a symptomatic treatment; the patient died in the following hours.HUS is a thrombotic microangiopathy characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure.HUS is caused by several factors such as infectious diseases, malignancy, autoimmunity, pregnancy and drugs. Numerous drugs are implicated, including chemotherapeutic drugs such as mitomycin C, and more rarely, gemcitabine (incidence of 0.008 -0.078%) [1].Casper et al. [2] were the first to report the association of gemcitabine therapy and HUS. The mechanism is unknown, although endothelial activation may be involved. Erythrocyte fragmentation and renal failure are caused by the occlusion of arteries and arterioles by platelets and fibrinoid thrombi. The renal biopsy shows a thrombotic microangiopathy, with prominent thickening of the glomerular capillary wall [3].The patient's clinical history and the laboratory findings were compatible with HUS, which occurred in conjunction with gemcitabine administration. Haemolytic-uraemic syndrome appears to be more frequent among males aged 50 -69, but this may be more representative of the natural disease prevalence (lung or pancreatic carcinoma) rather than of any gender or age sensitivity to this event [4].Although a dose -response relation is well documented for mitomycin C-induced HUS, a dose or duration effect has been difficult to establish with gemcitabine. Our pati...

The individualization of EFV dosage guided by genotyping 516G>T CYP2B6 and therapeutic drug monitoring could increase the efficiency of EFV use in antiretroviral treatment.

Summary:Relatively few cases of the 20 ring chromosome [r(20)] syndrome have been reported. Epileptic seizures, behavioral problems, mental retardation, and absence of definite dysmorphic features characterize this syndrome. We present a patient with the classic genetic and phenotypic findings. A 42-month-old boy with mild dysmorphic features and psychomotor retardation has had generalized tonic-clonic seizures, resistant to antiepileptic drug therapy since he was 26 months old. Electroencephalography (EEG) was performed on several occasions, as were brainstem auditory evoked potentials (BAEPs), magnetic resonance imaging (MRI), and cytogenetic studies. The EEG showed slow waves in anterior regions intermingled with spikes in temporal areas. The BAEPs were abnormal, and neuroimaging studies were normal. The chromosome r(20) appeared in 100 metaphases studied. Parental chromosomes were of normal karyotype. The genetic and EEG finding from this patient strongly suggest that epilepsy associated with 20 ring chromosome syndrome is a distinct new entity, although the clinical manifestations may be broader than previously recognized.

ObjectiveDuring clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca.MethodsA panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab.ResultsThe subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training.ConclusionsThis expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

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Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 mg twice daily. The trough plasma concentrations for LPV were fourfold above that recommended for PI-pretreated patients and toxicity associated with LPV/r and PI regimens was observed. These high concentrations continued after delivery in spite of a dosage reduction. The pharmacogenetic analysis revealed a genetic polymorphism in the CYP3A4 gene that encodes a non-functional protein. The pharmacokinetic study could indicate the occurrence of a phenomenon of non-linear pharmacokinetics which would justify why dosage reduction after pregnancy did not proportionally affect the patient's degree of exposure to the drug. In addition, an increment in CYP3A activity during pregnancy could explain lower LPV/r exposure during this period compared to postpartum, despite the impaired activity of CYP3A4 caused by the polymorphism.

A 48-year-old Caucasian male patient presented with severe adverse drug events (ADEs) while being treated with a standard dose (600 mg/day) of efavirenz. The patient's clinical course was favourable; however, he also described intense nightmares, cramps in his legs and anxiety disturbances that made him highly irritable. Measurement of the patient's efavirenz plasma concentrations revealed a mean minimum steady-state concentration during a dosage interval (C(min,ss)) of 12.7 mg/L, which was much higher than that recommended for this drug (therapeutic range 1-4 mg/L). Consequently, the dose of efavirenz was reduced to 400 mg/day, which resulted in a decrease in the frequency of ADEs. Subsequent genotype testing showed that the patient was homozygous for both the CYP2B6-G516T (T/T) and CYP2B6-A785G (G/G) alleles; these polymorphisms are associated with reduced enzymatic activity and elevated efavirenz plasma concentrations. Because of this and the fact that the patient's mean efavirenz C(min,ss) was still high (4.6 mg/L), a second dosage reduction was undertaken, to 200 mg/day. This also resulted in a reduction in ADEs. At present, the patient's CD4+ levels remain stable, his viral load continues to be undetectable and the mean efavirenz C(min,ss) is within the therapeutic range (2.7 mg/L).