Adjuvant bleomycin, vincristine and cisplatin (BOP) for high-risk stage I non-seminomatous germ cell tumours: a prospective trial (MRC TE17)

Adjuvant BEP (bleomycin, etoposide, cisplatin) is effective treatment for high-risk clinical stage I (HRCS1) non-seminomatous germ cell tumours (NSGCT), but the known toxicities of etoposide, and the expansion of the HR group to any patient with vascular invasion (50% of patients), led the Medical Research Council to pilot the BOP regimen. Patients received two courses of BOP 14 days apart: cisplatin 50 mg m−2 days 1 and 2, vincristine 1.4 mg m−2 (max. 2 mg) days 2 and 8, bleomycin 30 000 IU days 2 and 8. Primary outcome was relapse rate; quality of life, fertility, hearing and lung function were assessed pre- and post-treatment. In all, 100 patients were required. A total of 115 eligible patients were registered, all received two courses of chemotherapy. Median follow-up is 70 months; two relapses have occurred and the 5-year relapse-free rate is 98.3% (95% confidence interval (CI) 95.5%, 99.9%). As assessed by clinicians during treatment, complete (reversible) alopecia was present in 20% of patients; World Health Organization (WHO) grade 1/2 neurotoxicity was present in 41%/5% of patients during treatment and 22%/1% at 6 months. However, 12% of patients reported ‘quite a bit' or ‘very much' pain/numbness/tingling in hands/feet 2 years after chemotherapy. Mature follow-up confirms high efficacy for two courses of cisplatin-based adjuvant chemotherapy in HRCS1 NSGCT. Substituting vincristine for etoposide decreases alopecia, but gives a low incidence of significant neuropathy. There are no clearcut advantages to 2 × BOP over 2 × BEP, except for patients who wish to maximise the chance of avoiding significant alopecia

Simple optical apparatus for trepanning and percussion microdrilling using pulsed green Nd:YAG laser

Laser microdrilling is becoming an important tool in a wide spectrum of industrial applications due to the possibility to produce microholes in almost any type of materials. The purpose of this study was to create a simple and efficient optical apparatus that could produce microdrillings by either percussion or trepanning methods. The developed system is composed by a nanosecond Nd:YAG laser operating at 532 nm and one convergent lens with off-center optical axis of 1′. For the trepanning method the lens spins in its geometrical center at constant angular speed of 350 rpm. Typical microholes diameters obtained in metallic aluminum were in the range of 22 to 95 μm and 70 to 150 μm for the percussion and trepanning methods, respectively. Typical drilling velocities were in the order of 10 μm/s for applied fluences ranging from 22 to 150 J/cm2 for both methods. The values of the ratio between input and output diameters were 0.30 and 0.25 for microholes obtained by percussion and trepanning methods, respectively. The best microholes morphology was obtained using the trepanning method. The results for both methods are discussed based on the optical and thermal properties of the material processed and the constructed apparatusFAPESPCNP

FUNCTIONS, FUNCTIONING AND OPTIMIZED POSITIONING OF PRESSURE CONTROL VALVES IN OIL-HYDRAULIC CIRCUITS

The pressure control valves can perform different functions in the hydraulic systems, such as: establish maximum pressure, reduce pressure in some circuit lines, and establish sequence movements, among other functions. The main operation of these valves consists of providing a balance between pressure and the force load on a spring. Most of these valves can be positioned in many different levels, between totally open and totally closed, depending on the flow and on the pressure differential. The pressure control valves are usually named according to their primary functions, e.g., lock wire valve, sequence valve, safety valve, etc. and, their basic function is limit or to determine the pressure of the hydraulic system for the attainment of a certain function of the equipment in motion. They are also classified by the type of connections, by the size and by the selected pressure band. Instead of relief and security, discharge, counterbalance, sequence, reducing and shock suppressor valves represent the pressure control devices. In this paper, oil-hydraulic circuits are suggested for practical lessons of Hydraulic and Pneumatic Commands where they regulate valves of pressure, by acting in the following situations: limiting the maximum pressure of the system, determining a level of pressure, determining two different levels of pressure, determining at the same time two distinct levels of pressure, unloading the pump. The functions of these devices will be discussed and analyzed as an attempt to improve their position in the circuit

Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study

<p>Abstract</p> <p>Background</p> <p>To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs).</p> <p>Methods</p> <p>A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve years earlier, had participated in a long-term follow-up survey which assessed the prevalence of self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A→G polymorphism at bp 304 in <it>GSTP1</it>, and deletions in <it>GST-M1 </it>and <it>GST-T1</it>. Evaluation of associations between GST polymorphisms and self-reported toxicities included adjustment for prior treatment.</p> <p>Results</p> <p>All six evaluated toxicities were significantly associated with the cumulative dose of cisplatin and/or bleomycin. Compared to TCSs with either <it>GSTP1-AG </it>or <it>GSTP1</it>-<it>AA</it>, the 37 TCSs with the genotype <it>GSTP1-GG</it>, were significantly less bothered by paresthesias in fingers and toes (p = 0.039, OR 0.46 [0.22–0.96] and p = 0.023, OR 0.42 [0.20–0.88], respectively), and tinnitus (p = 0.008, OR 0.33 [0.14–0.74]). Furthermore, absence of functional GSTM1 protected against hearing impairment (p = 0.025, OR 1.81 [1.08–3.03]).</p> <p>Conclusion</p> <p>In TCSs long-term self-reported chemotherapy-induced toxicities are associated with functional polymorphisms in <it>GSTP1 </it>and <it>GSTM1</it>. Hypothetically, absence of GST-M1 leaves more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of pro-apoptotic mediators represents a possible explanation of our findings. Genotyping of these GSTs might be a welcomed step towards a more individualized treatment of patients with metastatic testicular cancer.</p

Perfusion CT is a valuable diagnostic method for prostate cancer: a prospective study of 94 patients

Purpose: The aim of this study is to assess the usefulness of perfusion computer tomography (pCT) in prostate cancer (PCa) diagnostics. Copyright:Materials and Methods: 94 patients with biopsy-proven PCa were enrolled in the study. Dynamic pCT of the prostate gland was performed for 50 seconds after an intravenous injection of contrast medium. Blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were computed in the suspected PCa area and in normal prostatic tissue.Results: PCa was visible in pCT in 90 of the 94 examined patients as a focal peripheral CT enhancement. When PCa was located in the peripheral zone (PZ), it was visible on perfusion maps, mostly showing an early peak followed by wash-out. The average values of all perfusion parameters were higher for tumour than for normal prostate tissue (p 7). In high-grade PCa, the mean BF value was significantly higher (p = 0.001) than the mean value of BF low- and medium-grade PCa (p = 0.011). Similar results were obtained regarding the mean values of BV; the more aggressive the cancer grade, the higher the mean BV value (p = 0.04).Conclusion: CT quantitative perfusion imaging allows PCa to be distinguished from normal prostate tissue. The highest values for BF and BV were observed in the most aggressive PCa grade

GAMEC – a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours

There is no consensus as to the management of untreated poor prognosis or relapsed/refractory germ cell tumours. We have studied an intensive cisplatin-based regimen that incorporates high-dose methotrexate (HD MTX) and actinomycin-D and etoposide every 14 days (GAMEC). Sixty-two patients were enrolled in a phase 2 study including 27 who were untreated (IGCCCG, poor prognosis) and 35 with progression despite conventional platinum based chemotherapy. The pharmacokinetics of the drugs were correlated with standard outcome measures. Twenty of the untreated patients were progression free following GAMEC and appropriate surgery, as were 18 individuals in the pretreated group. None of the established prognostic factors for therapy for pretreated patients could identify a poor-prognosis group. Five out of nine late relapses to prior chemotherapy were progression free following GAMEC and appropriate surgery. All patients had at least one episode of febrile neutropenia and there were five (8%) treatment-related deaths. PK values were not predictive of efficacy or toxicity, although the dose intensity in the pretreated group of patients, especially of HD MTX, was significantly correlated with progression-free survival (PFS). GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity. For those in whom it fails, further therapy is still possible with durable responses being seen