Veno-occlusive disease in pediatric patients affected by Wilms tumor.

BACKGROUND: Hepatic veno-occlusive disease (VOD) is a rare and potentially severe complication of chemotherapy. We describe five patients who developed VOD after chemotherapy for Wilms tumor (WT) and evaluate the role of plasminogen activator inhibitor-1 (PAI-1) and defibrotide for diagnosis and therapy of VOD, respectively. PATIENTS AND METHODS: Thirty-five patients treated from 2002 to 2009 for WT were eligible. Diagnosis of VOD was according McDonald's criteria that required two of the following: jaundice, hepatomegaly and/or right upper quadrant pain, weight gain with or without ascites. RESULTS: VOD occurred in 5 of 35 patients (14%) after 21-105 days from starting chemotherapy. Two patients developed multiorgan failure (MOF). PAI-1 was high in four patients who were tested. Three patients were treated with defibrotide and no side effects were reported while two patients received supportive measures only. Four patients recovered and three of them received defibrotide. They are all alive and well after a median follow-up of 35 months. One of two patients not treated with defibrotide died of MOF. CONCLUSIONS: PAI-1 levels were abnormal in WT-VOD. Defibrotide was a safe, well-tolerated, and potentially efficacious therapy in this group of patients. Further prospective study is needed in WT-VOD to confirm these data.

Safety and efficacy of a caspofungin-based combination therapy for treatment of proven or probable aspergillosis in pediatric hematological patients.

BACKGROUND: Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect. METHODS: We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005. RESULTS: Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04. CONCLUSION: This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studies.

A simplified method of antibiotic lock therapy for Broviac-Hickman catheters using a CLC 2000 connector device.

INTRODUCTION: We report a simplified method of performing antibiotic lock therapy (ALT) based on a disposable central venous catheter (CVC) hub device, CLC 2000, enabling an open-ended CVC to be flushed with normal saline solution without heparin. METHODS: ALT was administered through a CLC 2000 connector for recurrent CVC-bloodstream infections (BSI) by the same organism in four patients and for CVC colonization in five patients. RESULTS: The antibiotic concentration obtained in the lumen of the CVC with ALT was 2,500-fold higher than the minimum inhibiting concentration of targeted bacteria for patients treated with vancomycin, 2,500-80,000-fold higher for patients treated with teicoplanin, and 10,000-fold higher for the patient treated with amikacin. All CVC-BSIs treated with ALT resulted in complete clinical and microbiological responses. No case of malfunction in withdrawing or flushing the CVC and no precipitation during the administration of the antibiotic solution was observed. No recurrence of CVC-BSI or CVC colonization by the same organism was diagnosed during subsequent follow-up, despite the fact that all patients had further periods of severe neutropenia. At the last follow-up, three CVCs had been removed for other infections (fever of unknown origin in two; fungemia in one), four CVCs had been removed at the end of therapy, and one CVC is still in situ 20 months after ALT. CONCLUSIONS: In conclusion, a course of ALT is feasible in cancer patients with infected but much-needed CVCs before resorting to removal. The use of the CLC 2000 connector device simplifies the procedure for preparation and administration of ALT without compromising its efficacy.

SECONDARY LEIOMYOSARCOMAS: A Report of 4 Cases.

Survivors of childhood cancer risk developing second malignant neoplasms (SMN). a small proportion of SMNs is represented by soft tissue sarcoma (STS), including leiomyosarcoma. The files of the STS Italian Cooperative Group (ICG) were reviewed and 4 patients with secondary leiomyosarcoma were identified, only two of them still alive. In 3 cases, the leiomyosarcoma occurred in the radiation field. The authors found no clear differences between primary and secondary leiomyosarcomas, but leiomyosarcoma proved to be the most frequent SMN registered by the ICG, confirming the need for further studies to identify any distinctive features or syndromes.

A case of vinblastine overdose managed with plasma exchange.

Severe, life-threatening toxicity may be caused by errors in chemotherapy administration. To contribute with some useful information on drug-induced toxic effects and salvage therapy, we report a case of vinblastine (VBL) overdose (25 mg/m(2)) in a 12-year-old child affected by an end-stage metastatic primitive neuroectodermal tumor. Early signs of toxicity were acute, severe musculoskeletal pain and fever. This was followed by intestinal hypotonia, severe esophagitis, and peripheral neuropathy. Two consecutive plasma exchange procedures were performed at 4 and 18 hr after the administration of the overdose of VBL. The overall toxicity this child experienced was much less severe than expected; this finding, in combination with the known pharmacokinectis data of VBL in children, made us hypothesize that plasma exchange might have had a role in lowering the side effects of drug over dosage.

Effect of tartaric acid and dietary fibre from sun-dried raisins on colonic function and on bile acid and volatile fatty acid excretion in healthy adults.

Sun-dried raisins are a source of dietary fibre and tartaric acid. The effects of tartaric acid on colon function have not been the focus of extensive research. The purpose of the present study was to evaluate the effects of dietary fibre and tartaric acid from sun-dried raisins on colon function and on faecal bile acid and short-chain fatty acid (SCFA) excretion in healthy adults. Thirteen healthy subjects were fed 120 g sun-dried raisins/d or 5 g cream of tartar (equivalent to the tartaric acid in 120 g sun-dried raisins)/d for 9 weeks, divided into 3-week cycles. The experimental diets were fed in a crossover design after an initial control period. Faeces were collected for the last 4 d of each cycle for analysis of SCFA and bile acids. Intestinal transit time decreased from 42 h on the baseline diet to 31 h on cream of tartar (P<0.1) and to 28 h on sun-dried raisins (P<0.05). Faeces were softer on both sun-dried raisins and cream of tartar, but sun-dried raisins increased faecal wet weight (P<0.05), while cream of tartar did not. Sun-dried raisins caused significant reductions from baseline values in total bile acid concentration (from 1.42 (SD 1.03) to 1.09 (SD 0.76) mg/g, P<0.05), whereas cream of tartar did not (1.40 (SD 1.06) mg/g). Sun-dried raisins also significantly reduced the lithocholic (LC):deoxylithocholic acid (DC) ratio (from 1.63 (SD 0.85) to 1.09 (SD 0.50), P<0.02), whereas cream of tartar reduced the ratio, but to a lesser extent (1.29 (SD 0.79), NS). Both faecal bile acids and the LC:DC ratio are indicators of reduced risk for colon cancer. Sun-dried raisins increased total SCFA excretion (from 5.6 (SD 3.4) to 7.6 (SD 3.0) g/4 d, P<0.05), which remained unchanged with cream of tartar (5.6 (SD 3.0) g/4 d). Both sun-dried raisins and cream of tartar appear to be good stool softeners and to shorten intestinal transit time, although the fibre in sun-dried raisins has the added benefit of increasing faecal weight. Both sun-dried raisins and cream of tartar modulate the composition of faecal bile acids and SCFA in a way that has potential health benefits.

Effect of sun-dried raisins on bile acid excretion, intestinal transit time, and fecal weight: a dose-response study.

The effect of increasing doses of sun-dried raisins (SDR) on intestinal transit time (TT), fecal weight (FW), and fecal bile acids (FBA) was investigated in 16 healthy adults (6 men and 10 women). In three cycles of 2 weeks each, subjects consumed 84, 126, or 168 g/day of SDR. Four-day fecal collections were performed during the second week of each cycle, and TT, FW, and FBA were measured. FW (mean +/- SEM), increased from 168 +/- 14 g/day without raisins (cycle 1), with a TT of 54 +/- 6 hours, to 200 +/- 24 g/day with 168 g/day raisins (cycle 4), with a TT of 42 +/- 6 hours. Intermediate increases in FW and decreases in TT were observed for cycles 2 and 3. A physiologically meaningful decrease in TT (less than 2 days), to 44 +/- 6 hours, was reached at cycle 2 (not statistically significant). FBA, a possible indicator of colon cancer risk, showed a significant decrease, from 1.00 +/- 0.18 mg/g wet feces at baseline to 0.38 +/- 0.07 mg/g in cycle 2 (P <.005), and remained low in cycles 3 and 4. Major decreases were observed in cycle 2 for fecal lithocholic (P <.02), deoxycholic (P <.002), chenodeoxycholic, and cholic acids, and their concentrations remained low in cycles 3 and 4. Two servings of raisins per day (84 g/day), a relatively small change in diet, can cause beneficial changes in colon function and may decrease the risk for colon cancer.