More about: irinotecan-related cholinergic syndrome induced by coadministration of oxaliplatin.

JNCI Journal of the National Cancer Institute (Impact Factor: 14.34). 02/1999; 91(1):91-2. DOI: 10.1093/jnci/91.1.91a
Source: PubMed
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    ABSTRACT: Camptothecins represent an established class of effective agents that selectively target topoisomerase I by trapping the catalytic intermediate of the topoisomerase I-DNA reaction, the cleavage complex. The water-soluble salt camptothecin-sodium - introduced in early trials in the 1960s - was highly toxic in animals, whereas the semisynthetic derivatives irinotecan and topotecan did not cause haemorrhagic cystitis because of their higher physicochemical stability and solubility at lower pH values. Myelosuppression, neutropenia and, to a lesser extent, thrombocytopenia are dose-limiting toxic effects of topotecan. In contrast to the structurally-related topotecan, irinotecan is a prodrug which has to be converted to SN-38, its active form. SN-38 is inactivated by conjugation, thus patients with Gilbert's syndrome and other forms of genetic glucuronidation deficiency are at an increased risk of irinotecan-induced adverse effects, such as neutropenia and diarrhoea. The cytotoxic mechanism of podophyllotoxin is the inhibition of topoisomerase II. Common adverse effects of etoposide include dose-limiting myelosuppression. Hypersensitivity reactions are more common with etoposide and teniposide than with etoposide phosphate because the formulations of the former contain sensitising solubilisers. Leukopenia and thrombocytopenia occur in 65% and 80%, respectively, of patients after administration of conventional doses of teniposide. Anorexia, vomiting and diarrhoea are generally of mild severity after administration of conventional doses of topoisomerase II inhibitors. Clinical pharmacokinetic studies have revealed substantial interindividual variabilities regarding the area under the concentration-time curve values and steady-state concentrations for all drugs reviewed in this article. Irinotecan, etoposide and teniposide are degraded via complex metabolic pathways. In contrast, topotecan primarily undergoes renal excretion. Regarding etoposide and teniposide, the extent of catechol formation over time during drug metabolism may be associated with a higher risk for secondary malignancies.
    Drug Safety 02/2006; 29(3):209-30. · 2.62 Impact Factor
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    ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare idiopathic benign disease characterized by proliferation of Langerhans cells, most commonly in the skull. In extremely rare cases, the tumor can occur in the sternum. A 4-year-old girl presented to our institution with a firm, nontender mass in her anterior chest that had indolently enlarged to approximately 2 cm in diameter over the previous several months. Computed tomography, magnetic resonance imaging, and F18-flurodeoxy-glucose positron emission tomography computed tomography were performed for preoperative diagnosis, but the findings were inconclusive. Therefore, we performed surgical excision under general anesthesia, followed by microscopic and immunohistochemical analysis of the excised specimen. The mass was eventually diagnosed as a LCH arising from the sternum. No postoperative oncological treatment was given, and follow-up has continued for 1 year until the time of writing without any tumor recurrence. To our knowledge, only 10 cases of LCH arising from the sternum have been reported in the medical literature. Among them, surgical approaches including curettage and partial sternotomy were performed in only 6 cases. Without exception, all patients experienced excellent clinical outcomes. Therefore, additional clinical experiences are required. No standard treatment of choice for this disease currently exists. In our experience, curettage of the involved soft tissue mass and bone followed by appropriate reconstruction of the defect is considered a good option for the treatment of solitary LCH of the sternum. In addition, LCH should be considered in the differential diagnoses when a sharp delineated osteolytic mass is detected in the sternum.
    Journal of Pediatric Surgery 01/2012; 47(1):e9-12. · 1.38 Impact Factor
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    ABSTRACT: Portal vein thrombosis (PVT) or stenosis (PVS) often requires challenging techniques for reconstruction in living donor liver transplantation (LDLT). A total of 57 LDLTs were performed between October 1996 and December 2010. There were 16 cases (28%) with PVT/PVS that underwent modified portal vein anastomosis (m-PVa). The m-PVa techniques were classified into 3 groups: patch graft (Type-1), interposition graft (Type-2), and using huge shunt vessels (Type-3). The reconstruction patterns were evaluated with regard to age, graft vessels, PV flow, and complication rate. The m-PVas were Type-1 in 10 cases, Type-2 in 3 cases, and Type-3 in 3 cases. The vessel graft in Type-1 was the inferior mesenteric vein (IMV) in 8 and the jugular vein in 2 cases, whereas the vessel graft in Type-2 was IMV in 2 and the saphenous vein in 1 case; in Type-3, the vessel grafts were renoportal, gonadal-portal, and coronary-portal anastomoses, respectively. The postoperative PV flow was sufficient in all types and slightly higher in Type-3. The postoperative complications occurred in 20% of the patients who underwent Type-1, in 33% who underwent Type-2, and in 0% who underwent Type-3. The m-PVa was effective to overcome the surgical difficulty during transplantation. Pretransplant planning for the selection of the type of reconstruction is important for recipients with PVT/PVS.
    Journal of Pediatric Surgery 12/2011; 46(12):2291-5. · 1.38 Impact Factor


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