Essential thrombocythemia and pregnancy

Essential thrombocythaemia (ET) is an acquired myeloproliferative neoplasm, characterised by persistent thrombocytosis and a tendency for either thrombosis or haemorrhage. Among myeloproliferative neoplasms, ET is the most prevalent in young women, which constitute a special group due to their childbearing potential. An increased risk of fetal and maternal complications has been demonstrated in patients with ET. The most common pregnancy-related complication is spontaneous abortion during the first trimester. Recurrent abortion, fetal growth restriction, stillbirth and placental abruption are less frequent. Maternal complications are relatively rare and essentially represented by thromboembolic and bleeding events. Here we summarize the literature describing pregnancy and its outcome in patients with ET and discuss some recommendations for the management of pregnancy.     

Diversity of class 1 integron gene cassette Pc promoter variants in clinical Escherichia coli strains and description of a new P2 promoter variant

Gene cassettes of class 1 integrons may be differently expressed depending on the Pc promoter variant as well as occasionally from a second promoter located downstream of Pc, named P2. So far, the distribution of the variants has only been described in an in silico study. In this study, the prevalence of these variants in vivo was analysed in a population of 85 Escherichia coli strains from a variety of phylogenetic groups isolated from healthy subjects and clinical samples in Spain and France from 2004 to 2007. The weakest variants (PcW and PcH1) prevailed (variants associated with the integrase having the most efficient excision activity), whilst the two strongest variants, PcW_TGN-10 and PcS, were less frequent. Furthermore, a new variant of P2 associated with PcW was characterised in one integron (harbouring the gene cassette bla_OXA-1–aadA1) from a French strain of a healthy subject. This variant was hereafter named P2m3 and shows a G → A substitution in its −10 element (TACAGT to TACAAT), a mutation that doubled the strength of P2 and approached the level of expression of the strong PcW_TGN-10 variant. When the correlation between the Pc variants and the origin of the strains was analysed, no significant difference (P < 0.05) was observed in the Pc variant distribution according to the geographic origin or clinical setting.     

Concomitant chemo-radiotherapy and local dose of radiation as risk factors for second malignant neoplasms after solid cancer in childhood: a case-control study

Radiotherapy and chemotherapy are associated with an increased risk of a second malignant neoplasm (SMN) after a cancer during childhood. This study specified the dose-effect relationship between radiotherapy, chemotherapy and the risk of a SMN, and investigated the effect of chemo-radiotherapy on the risk of SMN. A case-control study nested in a European cohort of 4,581 patients treated for a solid cancer during childhood was conducted. One hundred and fifty three cases with a SMN and 442 controls were matched according to sex, age at first cancer, calendar year, type of first cancer and follow-up. The local radiation dose was estimated at the site of the SMN, for each case and at the same site, for the matched controls. The local dose of radiation significantly increased the risk of a SMN. The best model was linear with an excess relative risk per Gray equal to 0.13 (95% CI, 0.06; 0.26). Any chemotherapy significantly increased the risk of a SMN, odd ratio(adjusted) (OR(adjusted)) = 2.4 (95% confidence interval (95% CI), 1.4-4.1), but no dose-effect relationship was observed between any drug category and the risk of a SMN. Patients who had received concomitant chemo-radiotherapy were significantly more at risk of developing a SMN than patients who had been treated with sequential chemo-radiotherapy, even after adjustment for the local dose of radiation and the 6 most frequently administered drugs, OR(adjusted) = 2.3 (95%CI, 1.1-4.8). Radiation was found to be the foremost treatment-related risk factor for the occurrence of a SMN. Compared to sequential treatment, concomitant chemo-radiotherapy may lead to a higher risk of a SMN.     

Sedation with 50% nitrous oxide/oxygen for outpatient dental treatment in individuals with intellectual disability

Persons with intellectual disability have difficulty in cooperating with outpatient care, and many are referred for general anaesthesia. Intellectual disability has traditionally been a contraindication for conscious sedation. We evaluated the behavioural impact, effectiveness, and tolerance of sedation in this population using a fixed 50% nitrous oxide/oxygen mixture as a single agent. We used dental treatment as a model of outpatient care; 349 patients (192 males, 157 females; mean age 22y [SD 14]; range 3-81y) were recruited over a 12-month period at seven centres. Sedation was deemed successful if planned dental treatment was completed. Behaviour was scored with the modified Venham scale. Out of 605 sessions, 91.4% were successful. No serious adverse effects occurred. Minor adverse events (such as nausea) occurred in 10.1% of sessions. We conclude that the use of safe and effective conscious sedation may reduce the indications for general anaesthesia.     

Three-dimensional sonographic measurement of contralateral lung volume in fetuses with isolated congenital diaphragmatic hernia

PURPOSE: To use 3-dimensional sonography (3DUS) to measure contralateral lung volume and evaluate the potential of this measurement to predict neonatal outcome in isolated congenital diaphragmatic hernia (CDH). METHODS: Between January 2002 and December 2004, the contralateral lung volumes of 39 fetuses with isolated CDH were measured via 3DUS using rotational multiplanar imaging. The observed/expected contralateral fetal lung volume ratios (o/e-ContFLVR) were compared with the lung/head ratio (LHR), observed/expected total fetal lung volume ratio (o/e-TotFLVR), and postnatal outcome. RESULTS: Contralateral lung volumes are less reduced than total lung volumes in CDH. The bias and precision of 3DUS in estimating contralateral lung volumes were 0.99 cm(3) and 1.11 cm(3), respectively, with absolute limits of agreement ranging from -1.19 cm(3) to +3.17 cm(3). The o/e-ContFLVR was significantly lower in neonatal death cases (median, 0.49 cm(3); range, 0.22-0.99 cm(3)) than in survival cases (median, 0.58 cm(3); range, 0.42-0.92 cm(3) [p < 0.01]). Overall accuracy of the o/e-ContFLVR, o/e-TotFLVR, and LHR in predicting neonatal death were 67.7% (21/31), 80.7% (25/31), and 77.4% (24/31), respectively. CONCLUSION: Although o/e-ContFLVR can be precisely measured with 3DUS and can be used to predict neonatal death in CDH, it is less accurate than LHR and o/e-TotFLVR for that purpose.     

Type II topoisomerase mutations in clinical isolates of Enterobacter cloacae and other enterobacterial species harbouring the qnrA gene

The qnr genes are transferable genes that confer low-level quinolone resistance by protection of topoisomerase. The occurrence of mutations in DNA gyrase (gyrA, gyrB) and topoisomerase IV (parC, parE) genes in strains harbouring qnr was investigated in 28 qnrA-positive clinical isolates, among which 7 strains also harboured qnrS. Topoisomerase mutations were found in 25 (89%) of the 28 strains, with at least two mutations (gyrA and parC) in 13 strains and one mutation in 12 strains. Isolates of the Enterobacter cloacae complex were compared with reference strains of the new Enterobacter species. gyrA mutations were found at position 83 (Ser or Thr for Ile, Tyr, Leu or Phe depending on the species), and new gyrB mutations were described (S463A, S464F). qnrA had an additive effect of a 10-fold increase in the minimum inhibitory concentration (MIC) whatever the number of topoisomerase mutations, and qnrS was additive to qnrA with a further 2- to 10-fold increase in the MIC. Comparison of MICs with susceptibility breakpoints showed that strains combining qnrA and topoisomerase mutations were resistant to fluoroquinolones, but the three strains lacking a topoisomerase mutation were susceptible using ciprofloxacin and levofloxacin but not using nalidixic acid or moxifloxacin testing.     

Unsuspected FDG–PET findings in the follow-up of patients with lymphoma

18F-Fluorodeoxyglucose–positron emission tomography (FDG–PET) plays an increasing role in the management of patients with lymphoma, for which it is successfully used for staging and treatment monitoring. We report seven patients with a history of lymphoma who presented a positive FDG–PET suggestive of lymphoma relapse and for which FDG–PET oriented biopsies revealed alternative diagnoses. Early in lymphoma follow-up, persistence of focal increased FDG activity corresponded to inflammatory or infectious lesions in two patients: one aspergillosis and one sarcoidosis. Later in the follow-up, five cases of secondary malignancies were identified (three lung cancers, one epidermoid carcinoma, and one villous tumor) in this particularly exposed population. The routine use of FDG PET to evaluate lymphoma significantly increases the probability of detecting unexpected diseases. These cases illustrate the potential pitfalls in PET follow-up. Because FDG is not lymphoma-specific, a relapse suspected only on FDG–PET imaging requires biopsy, as alternative diagnoses—infectious or malignant—are possible. Our data draws clinician’s attention to potential false–positive FDG–PET findings, which may lead to therapeutic mistakes. Our data also suggests that FDG–PET might be a new imaging modality for long-term monitoring of late effects, especially second cancer occurrence.     

Combining a new CO2 laser wave guide with transoral robotic surgery: a feasibility study on four patients with malignant tumors

We present a series of patients treated by transoral robotic surgery (TORS) using a new CO₂ laser wave guide (CO₂ LWG) (Lumenis, Santa Clara, CA). Patients older than 18?years, with malignant pharyngo-laryngeal tumors were enrolled in this prospective study after signing an informed consent. Four patients were enrolled in the study. The mean age was 56?years. One patient had a T1 base of tongue tumor, two patients had supraglottic tumors (T1, T2), and one had a T1 palatine tonsil tumor. All the procedures could be performed using a Maryland forceps, a 0° endoscope and a CO₂ LWG introduced via the robotic arm introducer. The laser parameters were: superpulse or continuous mode, 7–15?W, continuous delivery. The average set-up time was 30?min. The average surgical time was 94?min. No complications were noted due to the intraoperative use of the robot or the CO₂ LWG. One laser fiber was used for each of the surgeries. The mean coagulation depth was 200?μm (range 100–300). The mean hospital stay was 6?days. The CO₂ LWG is a reliable tool for TORS. It allowed more than 1?h of work without any trouble.     

Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Société Fran?aise d'Oncologie Pédiatrique.

PURPOSE: To estimate the risk of secondary leukemia as a function of the dose of epipodophyllotoxins and anthracyclines. METHODS: We conducted a case-control study of the risk of secondary leukemia or myelodysplasia after a solid tumor in childhood within the Société Fran?aise d'Oncologie Pédiatrique, including 61 patients with leukemia matched with 196 controls. The characteristics of the first cancer, the patient's family history of cancer, and the treatment (type, cumulative dose of chemotherapy, schedule of etoposide administration, and radiation dose delivered to active bone marrow) were compared in the two groups. RESULTS: Only two factors were found to increase the risk of leukemia in multivariate analysis, namely, the type of the first tumor, with an excess risk in patients with Hodgkin's disease (relative risk 6.4; 95% confidence interval [CI], 1.6 to 24) or osteosarcoma (relative risk 5; 95% CI, 1.3 to 19), and exposure to epipodophyllotoxins and anthracyclines. The risk of leukemia increased regularly with the cumulative dose of etoposide. In summary, patients who received between 1.2 and 6 g/m(2) of epipodophyllotoxins or more than 170 mg/m(2) of anthracyclines had a seven-fold higher risk (95% CI, 2.6 to 19) compared with patients who received lower doses or none of these drugs. The risk of leukemia in patients who received more than 6 g/m(2) of epipodophyllotoxins was multiplied by 197 (95% CI, 19 to 2,058). The risk of leukemia was not increased by exposure to alkylating agents or radiotherapy. CONCLUSION: Both epipodophyllotoxins and anthracyclines increase the risk of secondary leukemia. The current challenge is to minimize the mutagenic effects of these drugs by diminishing cumulative doses without losing the therapeutic benefits.