18F-FDG-PET-TC en sarcomas de partes blandas: ¿cuándo? / 18F-FDG-PET-CT in soft tissue sarcomas: when to image?

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Phase I trial of sorafenib in combination with ifosfamide in patients with advanced sarcoma: a Spanish group for research on sarcomas (GEIS) study.

BACKGROUND: This phase I trial assessed safety, pharmacokinetics (PK), dose limiting toxicity (DLT), maximum tolerated dose and recommended dose (RD) of the combination of sorafenib plus ifosfamide in patients with advanced sarcoma. METHODS: Twelve sarcoma patients (9 soft-tissue, 3 bone sarcoma) were treated with sorafenib plus ifosfamide (starting doses 200 mg bid and 6 g/m(2) respectively). A 3 + 3 dose escalation design with cohorts of 3-6 patients was used. A study to assess the in vitro efficacy of the combination was also conducted. RESULTS: Three DLTs were observed: fatigue grade 4 with sorafenib 400 mg bid plus ifosfamide 6 g/m(2) and encephalopathy and emesis grade 3 with sorafenib 400 mg bid plus ifosfamide 7.5 g/m(2). Other toxicities included diarrhea, hand-foot syndrome, mucositis, neutropenia, skin rash and thrombocytopenia. There were no relevant effects on PK of sorafenib but an increase in ifosfamide active metabolite 4-hydroxy-ifosfamide was observed. Eight patients achieved stable disease lasting more than 12 weeks. An additive effect was observed in vitro. CONCLUSIONS: RD was sorafenib 400 mg bid plus ifosfamide 6 g/m(2), allowing administration of active doses of both agents. Limited preliminary antitumor activity was also observed. A phase II study is currently ongoing.

SEOM guidelines on thrombosis in cancer patients

The association between cancer and thrombosis is well established. Venous thromboembolism (VTE) is considered a main cause of mortality and morbidity in cancer patients and is commonly underestimated by oncologists. In recent years the incidence rates of VTE have notably increased. Several studies have clearly shown that cancer patients who are diagnosed with VTE present a poorer prognosis. The Spanish Society of Medical Oncology (SEOM) presents the guidelines for thrombosis and cancer in order to improve the prevention and management of VTE (AU)

Value of FDG-PET for monitoring treatment response in patients with advanced GIST refractory to high-dose imatinib. A multicenter GEIS study.

AIM: The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in monitoring response in refractory GIST. METHODS: This multicenter study prospectively evaluated 21 patients with locally advanced and/or metastatic GIST refractory to with high-dose imatinib (800 mg/day) treated with doxorubicin 15-20 mg/m2/weekly for 4 cycles, followed by imatinib maintenance (400 mg/day). CT and FDG-PET were performed at baseline and after completion of therapy. RESULTS: Mean baseline tumor size on CT was 5.9 cm. Median progression-free survival (PFS) was 219 days (range 62-1108). Three out of 21 patients (14%) had partial responses (PR) under RECIST criteria, 12 patients (57%) remained stable (SD) and 6 showed progression (PD) of the disease during treatment (29%). Six patients had PR by FDG-PET, 15 showed SD (n=9) or PD (n=6) based on EORTC criteria. Patients with a PFS <6 mo showed a significantly higher ∑SUVmax at baseline (26.04±13.4) than those with PFS≥6 mo (9.82±5.0) (P<0.05). A correlation was found between PET response and PFS: PR 14±6.1 mo, SD 5.5±0.8 mo and PD 3.5±4.1 mo (P<0.05). A residual SUVmax <5 after treatment correlated with improved PFS (314±315 days vs 131±91 days) (P<0.01). Survival curves showed a significant association between PET response and PFS (P<0.05). Patients with wild-type genotype KIT (KIT-WT) showed a significantly lower baseline SUVmax (5.36±1.4) than non-WT KIT (8.40±3.6) (P<0.05). CONCLUSION: FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT. Baseline ∑SUVmax can predict response to treatment in this series.

Tratamiento del osteosarcoma. Revisión / Treatment of osteosarcoma. A review

Se presenta una actualización del traamiento del osteosarcoma convencional, con exclusión de las formas secundarias por malignización de otras patologías, así como las formas de osteosarcoma parostal-yuxtacortical. La supervivencia global es del 73%, aunque el protocolo sigue abierto y se evalúa la toxicidad y se plantean cambios en la forma de administrar las drogas para disminuir los efectos secundarios a corto y largo plazo (AU)

An update on the conventional treatment of osteosarcoma, excluding secondary forms due to malignancies by other diseases, as well as the parosteal-juxtacortical forms. The overall survival is 73%, although the protocol is still open. The toxicity and changes established in the forms of administering the drugs to decrease the secondary effects in the short and long term are assessed (AU)

Hemoperitoneo en GIST metastásico / No disponible

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Cancer antigen 125 associated with multiple benign and malignant pathologies.

BACKGROUND: Cancer antigen (CA) 125 tumor-associated antigen is a high molecular glycoprotein used for follow-up of epithelial ovarian cancer. The test is often requested as a differential diagnosis in patients with pleural or peritoneal fluid. This study analyzes the prevalence of CA-125 increases in a population of patients attending a general hospital and discusses the possible clinical implications of increased levels. METHODS: On 4 different days, 380 CA-125 assays were performed in randomly selected patients attending our hospital. Serum CA-125 was measured with a commercial enzyme immunoassay, and clinical records were reviewed for assessment of clinical parameters. RESULTS: Sixty-one patients (16%) had increased CA-125. The pathologies of these patients were heart failure in 9 (14.7%), lung disease 11 (18%), hepatic cirrhosis in 7 (11.4%), malignant tumors in 9 (14.7%), intra-abdominal nonhepatic disease in 6 (10%), previous surgery in 17 (27.8%), and miscellaneous in 2 (3%). Effusions were seen in 34 patients (55.7%). CONCLUSIONS: Our data confirm the variety of benign and malignant pathologies coursing with increased CA-125. Cardiovascular and chronic liver disease were the most frequent diagnoses in patients with increased CA-125; this supports the opinion that CA-125 lacks utility as a marker for malignancy. CA-125 could have a role in the follow-up of cardiovascular, hepatic, and tumoral diseases with serosal involvement.

Loss of heterozygosity in the region including the BRCA1 gene on 17q in colon cancer.

Colon cancer has been proved to be an excellent model to identify and to study the different genetic alterations taking part in its development. BRCA1, a susceptibility gene for breast cancer, has been identified. Evidence of a significant risk for colon cancer in BRCA1-linked families has been reported. We undertook the present study to investigate the possible relation of BRCA1 and other genes on chromosome 17q21 to colon cancer. Eighty-five tumors were examined for loss of heterozygosity at seven microsatellite loci spanning the 17q21 region. Loss of heterozygosity was present in 39 (49%) of the 79 informative cases, with at least one marker. Two loci, D17S855 and D17S579, showed higher rates of allelic loss (16% and 22%, respectively) than the remaining markers. Tumors on the right side of the colon exhibited allelic loss more frequently than those on the left side. Our data suggest that BRCA1 and other genes in the 17q21 region may play an important role in the development of colon cancer.

Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient.

UNLABELLED: Previous studies have compared sedation profiles with midazolam (Mz) and propofol (Pf), particularly in heterogeneous populations of patients. Decreases in blood pressure and heart rate have been reported after the administration of propofol. These side effects are potentially deleterious in severe trauma patients, particularly in patients with head trauma. To assess the safety and efficacy of Mz and Pf, alone or in combination, in the prolonged sedation of severe trauma patients, we designed a prospective, controlled, randomized, study. One hundred consecutively admitted trauma patients requiring mechanical ventilation and sedation for more than 48 h were studied. Patients were sedated according to three different protocols based on the continuous i.v. administration of Mz alone, Pf alone, and Mz in combination with Pf. All patients received morphine chloride. Safety and efficacy were assessed during the sedation and wake-up periods according to clinical and laboratory variables. Cerebral hemodynamics were also studied in patients with head trauma. Patients were sedated for 6.3 +/- 4.0 days (mean +/- SD). All three sedation regimens were equally efficacious in achieving the desired sedation goal. The incidence of adverse events during the sedation period was also similar. In head trauma patients with intracranial pressure (ICP) monitoring, we did not find differences in ICP, cerebral perfusion pressure, or jugular venous oxygen saturation among the three groups. The serum triglyceride concentration was significantly higher in the Pf group. Wake-up time was significantly shorter in the Pf group. We conclude that both Mz and Pf are safe and efficacious in the sedation of severe trauma patients. The use of Pf in these patients is associated with a high incidence of hypertriglyceridemia and a shorter wake-up time. IMPLICATIONS: In a prospective, controlled, randomized study, we confirmed the safety and efficacy of midazolam and propofol, alone or in combination, in the prolonged sedation of a homogeneous group of severe trauma patients, particularly in patients with head trauma. The propofol group had shorter wake-up times and higher triglyceride levels.

[Current treatment of candidemia in non-neutropenic patients. Amphotericin B or fluconazole? A retrospective study of 62 consecutive patients]. / Tratamiento actual de la candidemia en pacientes no neutropénicos. Anfotericina B o fluconazol? Estudio retrospectivo de 62 casos consecutivos.

BACKGROUND: To analyze the epidemiologic characteristics of non-neutropenic patients with candidemia in a general hospital and the advantages and disadvantages of treatment with amphotericin B or fluconazole. PATIENTS AND METHODS: A total of 62 adult non-neutropenic patients with candidemia and treated with amphotericin B (n = 35) or fluconazole (n = 27) were studied. All episodes were considered to be associated with infection in a vein catheter. The demographic characteristics, risk factors for the development of candidemia, Candida species recovered from blood culture, underlying diseases, and clinical manifestations in both groups were compared. The evolution regarding secondary effects developed with both drugs, therapy failures, long term complications, and overall mortality rate associated with candidemia were analyzed. RESULTS: Both groups were comparable with the exception of the percentage of patients infected with species different from Candida albicans, which was higher in the group of patients who received amphotericin B (57%) than in the fluconazole group (26%) (p = 0.02), and in that patients with severe renal failure or AIDS had received preferentially fluconazole. There were no statistically significant differences regarding the evolution of patients treated with amphotericin B or fluconazole with the following factors: therapy failure (27% versus 19%; p = 0.7), overall mortality rate (40% versus 44%; p = 0.6), and mortality directly related to candidemia (33% versus 30%). Mortality was significantly higher among patients who had not their vein catheters removed early (78%) compared with those who had their vein catheters removed early (34%) (p = 0.01). Sixty-six percent of patients treated with amphotericin developed some severe secondary effect, whereas no patient in the fluconazole group developed such effects. CONCLUSIONS: Both amphotericin B and fluconazole seem to be effective drugs for the treatment of vein catheter related candidemia in the non-neutropenic patient, although fluconazole is far less toxic. The early removal of the vein catheter plays a prognostic role with at least the same relevance than the type of antifungal therapy chosen.

Neuroleptic malignant syndrome in a patient with head injury.

Neuroleptic malignant syndrome is an idiosyncratic reaction associated with the use of neuroleptic drugs. We report a case of this rare syndrome in a head injury patient associated with some unusual features: rhabdomyolysis with a high level of creatine kinase, the development of acute renal failure, the early use of continuous venovenous haemofiltration in treatment and rigidity that was refractory to conventional treatment with dantrolene and bromocriptine. The diagnosis in patients with multiple injuries must be based on a high index of suspicion.