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The article presents a case study of a 29-year-old woman who was diagnosed of having a desmoplastic small round cell tumor in the ovary. It states that the patient has used contraceptive pills for 14 years due to irregular menstrual cycles and has interrupted the assumption of the pill due to a desire for pregnancy. It adds that a laparoscopic right ovariectomy and an anatomical pathology have confirmed a right ovarian mass of 132 grams (g) in weight and an 8.5 centimeter (cm) in size.

Carmona-Rivera C, Hess RA, O'Brien K, Golas G, Tsilou E, White JG, Gahl WA, Huizing M. Novel mutations in the HPS1 gene among Puerto Rican patients. Hermansky-Pudlak syndrome (HPS) is a disorder of oculocutaneous albinism (OCA) and platelet storage pool deficiency. Eight different disease-causing genes have been identified, whose gene products are thought to be involved in the biogenesis of lysosome-related organelles. HPS type 1 (HPS-1) is the most common HPS subtype in Puerto Rico, with a frequency of 1:1800 in the northwest of the island due to a founder mutation, i.e. a 16-bp duplication in exon 15 of the HPS1 gene (c.1472_1487dup16; p.H497Q fsX90). We identified three Puerto Rican HPS-1 patients who carried compound heterozygous HPS1 mutations. One patient was heterozygous for c.937G>A, causing a missense mutation (p.G313S) at the 3′ splice junction of exon 10. This mutation resulted in activation of a cryptic intronic splice site causing an aberrantly spliced HPS1 mRNA that included 144-bp of intronic sequence, producing 11 novel amino acids followed by a stop codon. The other two patients were heterozygous for the previously reported c.972delC in HPS1, resulting in a frameshift and a premature stop codon (p.M325W fsX6). These findings indicate that, among Puerto Ricans, other HPS1 mutations apart from the 16-bp duplication should be considered in the analysis of this population. [ABSTRACT FROM AUTHOR]

Abstract: Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2–3years of tamoxifen, or as an extended treatment after 5years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available. [Copyright &y& Elsevier]

What is already known about this subject • There are few data about the safety of paclitaxel in patients with clinically significant liver impairment. A study by Venook and colleagues (J Clin Oncol 1998; 16: 1811–19) studied paclitaxel pharmacokinetics (PK) and pharmacodynamics (PD) in patients with liver impairment. The results were mainly descriptive, as detailed PK–PD data were available for only a subgroup of patients. • Another study by Wilson and colleagues found a correlation between tumour involvement of the liver, aspartate aminotransferase and total bilirubin concentrations and reduced paclitaxel clearance in 48 patients with advanced breast cancer in an early combined Phase I/II study (J Clin Oncol 1994; 12: 1621–9). • Finally, the study by Huizing and colleagues (Ann Oncol 1995; 6: 699–704) described two advanced breast cancer patients with liver impairment who experienced higher paclitaxel AUC concentrations and more severe neuropathywhen exposed to paclitaxel 250 mg m−2 as a 3-h infusion. • Liver impairment has been studied as a covariate within population models of paclitaxel in patients with normal or mildly impaired liver function (Henningsson et al. Eur JCancer 2003; 39: 1105–14; Joerger et al. Clin Cancer Res 2006; 12: 2150–7). Both studies found a negative correlation between total bilirubin concentrations and paclitaxel elimination. What this study adds • A direct relationship between liver impairment, paclitaxel elimination and susceptibility to neutropenia/thrombopenia. • As a result of PK–PD simulations, suggestions could be made for (further) dose adaptations for patients with more severe liver impairment. Aims To assess quantitatively the safety and pharmacology of paclitaxel in patients with moderate to severe hepatic impairment. Methods Solid tumour patients were enrolled into five liver function cohorts as defined by liver transaminase and total bilirubin concentrations. Paclitaxel was administered as a 3-h intravenous infusion at doses ranging from 110 to 175 mg m−2, depending on liver impairment. Covariate and semimechanistic pharmacokinetic–pharmacodynamic (PK–PD) population modelling was used to describe the impact of liver impairment on the pharmacology and safety of paclitaxel. Results Thirty-five patients were included in the study, and PK data were assessed for 59 treatment courses. Most patients had advanced breast cancer ( n = 22). Objective responses to paclitaxel were seen in four patients (11%). Patients in higher categories of liver impairment had a significantly lower paclitaxel elimination capacity ( R2 = −0.38, P = 0.05), and total bilirubin was a significant covariate to predict decreased elimination capacity with population modelling ( P = 0.002). Total bilirubin was also a significant predictor of increased haematological toxicity within the integrated population PK–PD model ( P < 10−4). Data simulations were used to calculate safe initial paclitaxel doses, which were lower than the administered doses for liver impairment cohorts III–V. Conclusions Total bilirubin is a good predictor of paclitaxel elimination capacity and of individual susceptibility to paclitaxel-related myelosuppression in cancer patients with moderate to severe liver impairment. The proposed, adapted paclitaxel doses need validation in prospective trials. [ABSTRACT FROM AUTHOR]

Holoprosencephaly (HPE) is the most common structural malformation of the developing forebrain. At birth, nearly 50% of children with HPE have cytogenetic anomalies. Approximately 20% of infants with normal chromosomes have sequence mutations in one of the four main HPE genes (SHH, ZIC2, SIX3, and TGIF). The other non-syndromic forms of HPE may be due to environmental factors or mutations in other genes, or potentially due to submicroscopic deletions of HPE genes. We used two complementary assays to test for HPE associated submicroscopic deletions. Firstly, we developed a multicolour fluorescent in situ hybridisation (FISH) assay using probes for the four major HPE genes and for two candidate genes (DISPI and FOXA2). We analysed lymphoblastoid cell lines (LCL) from 103 patients who had CNS findings of HPE, normal karyotypes, and no point mutations, and found seven microdeletions. We subsequently applied quantitative PCR to 424 HPE DNA samples, including the 103 samples studied by FISH: 339 with CNS findings of HPE, and 85 with normal CNS and characteristic HPE facial findings. Microdeletions for either SHH, ZIC2, SIX3, or TGIF were found in 16 of the 339 severe HPE cases (that is, with CNS findings; 4.7%). In contrast, no microdeletion was found in the 85 patients at the mildest end of the HPE spectrum. Based on our data, microdeletion testing should be considered as part of an evaluation of holoprosencephaly, especially in severe HPE cases. [ABSTRACT FROM AUTHOR]