Postoperative urinary extravasation does not impact anterior urethroplasty surgical outcomes: a Latin American large cohort study.

OBJECTIVE: To determine the prevalence of postoperative urinary extravasation (POUE) following anterior urethroplasty, to analyze factors associated with its occurrence, and to study the impact of POUE on surgical success. MATERIALS AND METHODS: Retrospective cohort study including all male patients who have undergone a urethroplasty at our center between 2011 and 2018. Subjects with posterior location stricture, those who did not undergo routine radiographic follow-up, or patients with inadequate follow-up were excluded. Urinary extravasation was defined as presence of evident contrast extravasation on the postoperative voiding cystourethrogram (VCUG). Impact was determined as "need-for-reoperation". Uni- and multivariate analysis were performed to determine clinical and demographic variables associated with occurrence of extravasation and postoperative stricture. RESULTS: A total of 783 men underwent a urethroplasty and 630 fulfilled inclusion criteria. Urinary extravasation prevalence was 12.2%, and there was a "need-for-reoperation" in 1.1% of cases. On uni- and multivariate analysis, greatest stricture length (HR: 1.07 (1-1.2), p = 0.05) and penile urethral location (HR: 2.29 (1.1-4.6), p = 0.021) showed to be POUE predictors. POUE did not show to be a risk factor for postoperative stricture (HR: 1.57, 95% CI (0.8-3), p = 0.173). However, reoperation group  showed to be a risk factor (HR: 6.6, 95% CI 1.4-31, p = 0.019). CONCLUSIONS: Prevalence of POUE was 12.2%. Stricture length and penile urethral strictures were POUE predictors. POUE occurrence with successful conservative management did not appear to have impact on urethroplasty outcomes as it did not predict re-stricture. POUE was reoperation cause in 1.1% of total cases.

Best practices in near-infrared fluorescence imaging with indocyanine green (NIRF/ICG)-guided robotic urologic surgery: a systematic review-based expert consensus.

PURPOSE: The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature review and to provide evidence-based expert recommendations on best practices in this field. METHODS: All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed®, Scopus® and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first "dynamic paper" that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience. RESULTS: Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (n = 13), robotic radical prostatectomy and lymphadenectomy (n = 7), robotic ureteral re-implantation and reconstruction (n = 5), robotic adrenalectomy (n = 4), robotic radical cystectomy (n = 3), penectomy and robotic inguinal lymphadenectomy (n = 2), robotic simple prostatectomy (n = 1), robotic kidney transplantation (n = 1) and robotic sacrocolpopexy (n = 1). CONCLUSION: NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.

Late age onset of amyotrophic lateral sclerosis is often not considered in elderly people.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease causing an upper and lower motor neuron loss. It is neurology textbook knowledge that the mean age of onset is about 60 years. However, recent investigations show an increasing incidence in older persons. We therefore evaluated whether ALS is potentially not considered in elderly people with ALS symptoms, respectively, not recognized. MATERIALS AND METHODS: We included retrospectively all patients with ALS diagnoses after work-up that were admitted to our neurological and geriatric departments from 2007 to 2010 and collected their clinical data. The diagnosis of ALS was based on the El Escorial criteria. Patients were grouped into three categories according to age (<50, between 50 and 70, >70), and differences in clinical and/ or biographical factors were investigated. RESULTS: We identified 35 patients (18 men and 17 women) with a median age at onset of 71.5 years (range: 36-87 years). When establishing the diagnosis, 51% were older than 70 years, 40% (14/35) between 50 and 70, and only 9% younger than 50. Only in 46 per cent of patients who were sent to our departments with ALS symptoms ALS was considered by the referring physician. CONCLUSION: Late age onset of ALS seems to be more common than formerly assumed and is presumably under-recognized in elderly patients. ALS needs to be considered as a differential diagnosis in older patients. Potential factors accounting for older people being underdiagnosed with ALS relate to frequent presentation with symptoms like dysphagia, frailty or general weakness for other reasons.

Haemostatic profile of reconstituted blood in a proposed 1:1:1 ratio of packed red blood cells, platelet concentrate and four different plasma preparations.

The concept of haemostatic resuscitation implies early and high-volume plasma transfusion. We investigated the haemostatic profile of reconstituted whole blood prepared in a 1:1:1 ratio of blood, platelets and plasma. This consisted of packed red blood cells, platelet concentrate and four different plasma variants: fresh frozen; solvent-detergent; lyophilised quarantine; and lyophilised methylene blue-inactivated plasma. Haematocrit, platelet count, endogenous thrombin potential and coagulation factor activity were significantly lower in reconstituted blood compared with citrated whole blood (p < 0.01). Except for lyophilised methylene blue-inactivated plasma, no substantial differences between plasma variants in coagulation factor activity, endogenous thrombin potential and standard coagulation tests were observed. After reconstitution, haematocrit and platelet counts were slightly above recommended transfusion triggers, most thromboelastometry (ROTEM(®)) parameters were within the normal range and fibrinogen concentrations were between 1.57 g.l(-1) and 1.91 g.l(-1). Reconstitution of whole blood in a 1:1:1 ratio resulted in significant dilution of haematocrit and platelet count, but values remained above limits recommended by transfusion guidelines. Fibrinogen concentrations of reconstituted whole blood were also significantly reduced, and these were below the threshold value for supplementation recommended by recent guidelines.

High interindividual variability in the CD4/CD8 T cell ratio and natalizumab concentration levels in the cerebrospinal fluid of patients with multiple sclerosis.

Strongly decreased leucocyte counts and a reduced CD4/CD8 T cell ratio in the cerebrospinal fluid (CSF) of natalizumab (NZB)-treated multiple sclerosis (MS) patients may have implications on central nervous (CNS) immune surveillance. With regard to NZB-associated progressive multi-focal leucoencephalopathy, we aimed at delineating a relationship between free NZB, cell-bound NZB, adhesion molecule (AM) expression and the treatment-associated shift in the CSF T cell ratio. Peripheral blood (PB) and CSF T cells from 15 NZB-treated MS patients, and CSF T cells from 10 patients with non-inflammatory neurological diseases and five newly diagnosed MS patients were studied. Intercellular adhesion molecule-1 (ICAM-1), leucocyte function antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), NZB saturation levels, and T cell ratios were analysed by flow cytometry. NZB concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Lower NZB saturation levels (P<0.02) and a higher surface expression of ICAM-1 and LFA-1 (P<0.001) were observed on CSF CD8 T cells. CSF T cell ratios (0.3-2.1) and NZB concentrations (0.01-0.42 µg/ml) showed a pronounced interindividual variance. A correlation between free NZB, cell-bound NZB or AM expression levels and the CSF T cell ratio was not found. Extremely low NZB concentrations and a normalized CSF T cell ratio were observed in one case. The differential NZB saturation and AM expression of CSF CD8 T cells may contribute to their relative enrichment in the CSF. The reduced CSF T cell ratio appeared sensitive to steady-state NZB levels, as normalization occurred quickly. The latter may be important concerning a fast reconstitution of CNS immune surveillance.

Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal?

BACKGROUND: More and more patients with multiple sclerosis (MS) switch from natalizumab to fingolimod because of the risk of progressive multifocal leukoencephalopathy. The duration of the treatment holiday is still under debate referring to a possible recurrence of disease activity. AIM OF THE STUDY: The aim of this study was to evaluate the prognostic value of natalizumab saturation on T cells for the recurrence of clinical and radiological disease activity. METHODS: Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from five patients with MS was determined before initiation of fingolimod by flow cytometry and related to clinical and MRI outcome during a 6-month follow-up. RESULTS: In two patients with either clinical or radiological disease activity, the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the remaining three patients with absence of disease activity had a median natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on CD8+ T cells. CONCLUSIONS: The data of this pilot study indicate that clinical and radiological disease activity is closely linked to natalizumab saturation at the time point of switch. The determination of natalizumab saturation may be an essential tool to monitor cessation of natalizumab treatment.

CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.

The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.

Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.

Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy.

BACKGROUND: The diagnosis of the isolated leptomeningeal involvement of a primary central nervous system B-cell lymphoma without parenchyma lesions may be difficult. Patients with leptomeningeal meningeosis lymphomatosa can present with various neurologic deficits. AIMS OF THE STUDY: To demonstrate the impact of cerebrospinal fluid (CSF) flow cytometry in the diagnosis of an isolated leptomeningeal manifestation of B-cell lymphoma by presenting an interesting case report. METHODS: Flow cytometric analysis of B-cell monoclonality of the CSF was performed as complementary diagnostic procedure in addition to CSF cytology. Final diagnosis was confirmed by necropsy. RESULTS: We suspected isolated leptomeningeal manifestation of B-cell lymphoma with palsy of the VI and VII cranial nerves in a 79-year-old male, because of mononuclear pleocytosis in CSF. Interestingly, the decisive diagnostic hint was given by implementation of flow cytometry of the CSF. Diagnosis was confirmed by postmortem autopsy. CONCLUSION: Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.

Molecular evidence of transient therapeutic effectiveness of natalizumab despite high-titre neutralizing antibodies.

Natalizumab is a humanized monoclonal antibody directed against the alpha-4 integrin subunit of very late activation antigen-4 (VLA-4). Natalizumab neutralizing antibodies (NAB) have been found to significantly reduce beneficial effects of natalizumab treatment in multiple sclerosis. We investigated interactions of NAB with natalizumab by serial measurements of alpha-4 integrin levels on peripheral blood mononuclear cells using flow cytometry. In addition, serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), the endothelial ligand of VLA-4, and serum NAB were serially determined. Natalizumab infusion led to a transient reduction in alpha-4 integrin levels on immune cells and serum sVCAM-1 levels along with serum negativity of NAB lasting for a few days post-infusion. Apparently, the high-dose effect of freshly infused natalizumab resulted in a transient neutralization of NAB possibly involving a transient therapeutic effectiveness.

The Interlaboratory RObustness of Next-generation sequencing (IRON) study: a deep sequencing investigation of TET2, CBL and KRAS mutations by an international consortium involving 10 laboratories.

Massively parallel pyrosequencing allows sensitive deep sequencing to detect molecular aberrations. Thus far, data are limited on the technical performance in a clinical diagnostic setting. Here, we investigated as an international consortium the robustness, precision and reproducibility of amplicon next-generation deep sequencing across 10 laboratories in eight countries. In a cohort of 18 chronic myelomonocytic leukemia patients, mutational analyses were performed on TET2, a frequently mutated gene in myeloproliferative neoplasms. Additionally, hotspot regions of CBL and KRAS were investigated. The study was executed using GS FLX sequencing instruments and the small volume 454 Life Sciences Titanium emulsion PCR setup. We report a high concordance in mutation detection across all laboratories, including a robust detection of novel variants, which were undetected by standard Sanger sequencing. The sensitivity to detect low-level variants present with as low as 1-2% frequency, compared with the 20% threshold for Sanger-based sequencing is increased. Together with the output of high-quality long reads and fast run time, we demonstrate the utility of deep sequencing in clinical applications. In conclusion, this multicenter analysis demonstrated that amplicon-based deep sequencing is technically feasible, achieves high concordance across multiple laboratories and allows a broad and in-depth molecular characterization of cancer specimens with high diagnostic sensitivity.

Adhesion molecules are promising candidates to establish surrogate markers for natalizumab treatment.

BACKGROUND: Natalizumab is the first monoclonal antibody therapy approved for multiple sclerosis (MS). Its therapeutic mechanism is the blockade of the α4-integrin subunit of the adhesion molecule (AM) very late activation antigen-4 (VLA-4), which leads to an inhibition of immune cell extravasation into the central nervous system (CNS). METHODS: We investigated changes in the expression levels of unblocked α4-integrin and further AM (intercellular adhesion molecule-1, -2, -3 (cICAM-1, -2, -3), leukocyte function associated antigen-1 (LFA-1)) on peripheral blood mononuclear cells (PBMC) determined by flow cytometry from 25 patients with MS before the first natalizumab infusion and before the fourth infusion. In 15 MS patients AM expression was evaluated every 3 months over 1 year. RESULTS: We found a significant decrease (p < 0.0001) of unblocked α4-integrin cell surface expression on all investigated PBMC subsets (T cells -61.7%, B cells -69.1%, monocytes/macrophages -46.4%) in the blood of MS patients after 3 months of natalizumab treatment. Moreover, a continuous decrease (p < 0.05) of unblocked α4-integrin expression levels was seen after 3, 6, 9, and 12 months. As a secondary effect, expression levels of the other investigated AM were differentially affected. CONCLUSIONS: Results show a sustained decrease of unblocked α4-integrin expression not only in all patients but also in all investigated PBMC subsets. This probably results in a continuously decreasing transmigration of PBMC into the CNS and may explain the improved clinical efficacy in the second treatment year and also the increasing risk of progressive multifocal leukoencephalopathy during long-term natalizumab therapy. We conclude that AM expression profiles are promising candidates for the development of a biomarker system to determine both natalizumab treatment response and patients at risk for opportunistic CNS infections.

Growth of Infants Born To HIV-Positive Mothers Fed a Whey-Adapted Acidified Starter Formula with Prebiotics and Nucleotides

Objectives: The objectives of this study were to evaluate whether infants born to known HIV-positive mothers; but who were not themselves infected with HIV and who were fed a chemically acidified starter formula with prebiotics with or without nucleotides during their first six months; displayed growth rates equal to uninfected infants fed a chemically acidified starter formula without prebiotics or nucleotides. Design: The design was a multi-centre; double-blinded randomised controlled trial. Setting: The study was carried out in four academic hospitals; three in Johannesburg and one in Cape Town; South Africa. Subjects and intervention: The subjects were newborn infants born to consenting HIV-positive women who had previously decided not to breast feed. The infants were randomised to receive one of three milk formulas. The intervention comprised chemically acidified formula without prebiotics or nucleotides; with prebiotics only; or with prebiotics and nucleotides. Outcome measures: The outcome measures were the growth parameters through the first six months of life. Results: Of the 150 randomised infants; 50 did not complete the study and 16 (12.8of those tested) were infected with HIV; leaving 84 infants available for analysis. All three formulas were tolerated well; with no differences in growth parameters seen with the addition of prebiotics and nucleotides. The growth rates of the study infants up to the age of six months were very good; showing an increase in Z-scores from negative values at the time of enrolment in the first week after birth to around zero for length and 0.5 for weight.Conclusions: The three chemically acidified formulas were tolerated well and resulted in good growth over the first six months of life. No benefits were seen with the addition of prebiotics or nucleotides. The growth rates were similar to those found in previous studies of ours on biologically acidified formulas. The chemical acidification of infant formulas appears to be a realistic alternative to biological acidification should an acidified formula be required

Growth of Infants Born To HIV-Positive Mothers Fed a Whey-Adapted Acidified Starter Formula with Prebiotics and Nucleotides

Objectives: The objectives of this study were to evaluate whether infants born to known HIV-positive mothers; but who were not themselves infected with HIV and who were fed a chemically acidified starter formula with prebiotics with or without nucleotides during their first six months; displayed growth rates equal to uninfected infants fed a chemically acidified starter formula without prebiotics or nucleotides. Design: The design was a multi-centre; double-blinded randomised controlled trial. Setting: The study was carried out in four academic hospitals; three in Johannesburg and one in Cape Town; South Africa. Subjects and intervention: The subjects were newborn infants born to consenting HIV-positive women who had previously decided not to breast feed. The infants were randomised to receive one of three milk formulas. The intervention comprised chemically acidified formula without prebiotics or nucleotides; with prebiotics only; or with prebiotics and nucleotides. Outcome measures: The outcome measures were the growth parameters through the first six months of life. Results: Of the 150 randomised infants; 50 did not complete the study and 16 (12.8of those tested) were infected with HIV; leaving 84 infants available for analysis. All three formulas were tolerated well; with no differences in growth parameters seen with the addition of prebiotics and nucleotides. The growth rates of the study infants up to the age of six months were very good; showing an increase in Z-scores from negative values at the time of enrolment in the first week after birth to around zero for length and 0.5 for weight.Conclusions: The three chemically acidified formulas were tolerated well and resulted in good growth over the first six months of life. No benefits were seen with the addition of prebiotics or nucleotides. The growth rates were similar to those found in previous studies of ours on biologically acidified formulas. The chemical acidification of infant formulas appears to be a realistic alternative to biological acidification should an acidified formula be required

The effects of dutasteride, tamsulosin, and the combination on storage and voiding in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the Combination of Avodart and Tamsulosin study.

This article reports the results of a post hoc analysis of the multicenter, randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) study, which aimed to investigate the effects of dutasteride (0.5 mg), tamsulosin (0.4 mg), and their combination on storage and voiding symptoms in 4844 men aged > or =50 years with moderate-to-severe lower urinary tract symptoms (International Prostate Symptom Score > or =12), prostate volume (PV) > or =30 cm(3) and PSA 1.5-10 ng ml(-1). After 24 months, combination treatment achieved significantly greater mean reductions in both voiding and storage symptoms than either monotherapy, in each of the three baseline PV tertiles (30 to <42, 42 to <58, > or =58 cm(3)). Dutasteride was as effective as tamsulosin for control of storage symptoms, but provided significantly greater relief of voiding symptoms than tamsulosin.

Safety and efficacy of a new extensively hydrolyzed formula for infants with cow's milk protein allergy.

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.

Experiencia preliminar con quimioterapia de inducción basada en docetaxel y estramustina en cáncer de próstata andrógeno-independeinte / Preliminary esperience with induction chemotherapy based on docetaxel and estramustine for androgen-independent prostate cancer

Introducción y Objetivos: El objetivo de este ensayo es analizar la eficacia de la quimioterapia (QMT) de primera línea basada en docetaxel y estramustina en pacientes con cáncer de próstata andrógeno-independiente (CPAI). Material y Métodos: Se realizo un análisis retrospectivo de 9 pacientes con CPAI tratados desde 03/2003 hasta 07/2005. Los pacientes eran naïve para QMT con al menos 1 sitio metastático documentado, performance store de 0 a 2 y habían recibido al menos entre 2 y 8 ciclos de QMT. El promedio de edad fue de 69 años y el PSA pre-QMT oscilo entre 22 y 649 ng/ml. El estadio clínico inicial y el Gleason también fueron valorados. Todos los pacientes recibieron el mismo esquema cada 21 días de docetaxel 70 mg/m2 más estramustina 280 mg cada 6 horas por 5 dosis. Se evaluó la respuesta clínica bioquímica cada 6 semanas y se analizo el grado de respuesta: parcial (RP), completa (RC), del PSA, enfermedad estable o progresión y el tiempo de progresión. Resultados: De los 9 pacientes, dos presentaron RC bioquímica, 3, RP y 4 tuvieron progresión intratratamiento. Cinco de los nueve pacientes tuvieron remisión clínica completa (control del dolor). La duración media de la respuesta terapéutica vario entre 4 y 11 mases. Fallecieron tres pacientes por progresión tumoral. Conclusión: Los resultados preliminares en esta reducida serie de pacientes son alentadores y justifican la continuidad del estudio. Los hallazgos demuestran la inequívoca eficacia de la QMT en el tratamiento del CPAI. Por lo tanto, es una alternativa válida y prometedora

Experiencia preliminar con quimioterapia de inducción basada en docetaxel y estramustina en cáncer de próstata andrógeno-independeinte / Preliminary esperience with induction chemotherapy based on docetaxel and estramustine for androgen-independent prostate cancer

Introducción y Objetivos: El objetivo de este ensayo es analizar la eficacia de la quimioterapia (QMT) de primera línea basada en docetaxel y estramustina en pacientes con cáncer de próstata andrógeno-independiente (CPAI). Material y Métodos: Se realizo un análisis retrospectivo de 9 pacientes con CPAI tratados desde 03/2003 hasta 07/2005. Los pacientes eran na´ve para QMT con al menos 1 sitio metastático documentado, performance store de 0 a 2 y habían recibido al menos entre 2 y 8 ciclos de QMT. El promedio de edad fue de 69 años y el PSA pre-QMT oscilo entre 22 y 649 ng/ml. El estadio clínico inicial y el Gleason también fueron valorados. Todos los pacientes recibieron el mismo esquema cada 21 días de docetaxel 70 mg/m2 más estramustina 280 mg cada 6 horas por 5 dosis. Se evaluó la respuesta clínica bioquímica cada 6 semanas y se analizo el grado de respuesta: parcial (RP), completa (RC), del PSA, enfermedad estable o progresión y el tiempo de progresión. Resultados: De los 9 pacientes, dos presentaron RC bioquímica, 3, RP y 4 tuvieron progresión intratratamiento. Cinco de los nueve pacientes tuvieron remisión clínica completa (control del dolor). La duración media de la respuesta terapéutica vario entre 4 y 11 mases. Fallecieron tres pacientes por progresión tumoral. Conclusión: Los resultados preliminares en esta reducida serie de pacientes son alentadores y justifican la continuidad del estudio. Los hallazgos demuestran la inequívoca eficacia de la QMT en el tratamiento del CPAI. Por lo tanto, es una alternativa válida y prometedora(AU)

Terapia intravesical con o sin mantenimiento de bacilo de Calmette-Guerin en carcinoma transicional T1G3 vesical / Intravesical bacillus Calmette-Guerin therapy with or without maintenance in transitional T1G3 bladder carcinoma

Introducción: La utilización del bacilo de Calmette-Guerin (BCG)ha mostrado una acción eficaz en la disminución de la recurrencia y la progresión en carcinomas de alto grado. Actualmente se discute el régimen más adecuado en el uso de BCG. Es el próposito del presente estudio comparar la evolución a largo plazo y tolerancia en pacientes con carcinoma transicional de alto grado T1G3, tratados mediante instilación intracavitaria de BCG, con o sin mantenimiento. Material y métodos:En el Centro de Urología CDU fueron tratados por carcinoma transicional de vejiga con resección transuretral (RTU-V) 213 pacientes entre marzo de 1993 y agosto de 2004. Se evaluaron 56 pacientes con diagnostico histopatológico de carcinoma transicional T1G3 con o sin carcinoma in situ asociado, informados por un mismo patólogo; 22 ingresaron en el esquema de inducción y mantenimiento con BCG, y 19 pacientes fueron tratados solo con inducción de BCG. Ocho pacientes no realizaron tratamiento posterior, 4 fueron tratados con mitomicina y 3 fueron perdidos en seguimiento. El tratamiento de BCG con mantenimiento se realizó según el esquema del Southwest Oncology Group (SWOG). Cada semana se registró los eventuales efectos adversos y de haberlos se los clasificó en leves, moderados o severos. Se analizaron los datos con test de Fisher para proporciones. Resultados: Promedio de seguimiento general de 50 meses (6-112). Fueron tratados con mantenimiento de BCG 22 pacientes. Se observó recidiva de la enfermedad en 8 pacientes, 3 de los cuales recayeron en 2 oportunidades siendo un total de 11 recidivas. Un solo caso progresó a un estadio T2. Diecinueve pacientes fueron tratados solo con seis dosis de BCG, observándose una recidiva en 8 pacientes recayendo dos pacientes en 2 oportunidades, siendo un total de 10 recidivas y progresión en 2 pacientes. No se observó diferencia en la recidiva ni en la progresión. Al evaluar los efectos adversos se observaron en 24 pacientes, 13 en el grupo de mantenimiento con solo un caso de efecto sistémico severo y 11 en el grupo de inducción con dos casos de toxicidad sistemica severa. Conclusión: El tratamiento de pacientes con carcinoma transicional T1G3 con BCG es una terapia efectiva en la reducción de las tasas de recidiva y progresión. No encontramos diferencia entre la terapia de mantenimiento o de inducción solamente en las tasas de recurrencia y progresión de la enfermedad. Los efectos adversos fueron similares en ambos grupos

Evolución de diferentes estrategias de biopsia prostática en pacientes con tacto rectal no sospechoso y antígeno prostático específico (APE) elevado: propuesta de un nuevo esquema "4X4" / Evolution of the different strategies of prostatic biopsy in patients with normal rectal examination and PSA rise: new technique

Introducción: Si bien el incremento del número de tomas de biopsias prodtáticas aumenta la positividad de las mismas, el esquema más ventajoso aún no está definido. Objetivos: Revisar los distintos esquemas utilizados en nuestra institución, presentar y evaluar el esquema de 16 biopsia, denominado 4X4, en pacientes con Tacto Rectal no sospechoso y elevación del APE. Materiales y métodos: Entre 1991 y 2003 se realizaron 3.021 biopsias prostáticas ecodirigidas a pacientes con sospecha de Cáncer de Próstata. Se tomaron muestras de las imágenes sospechosas, y de acuerdo con el esquema en curso, se completó con tomas randomizadas de diferentes zonas de la próstata. En los pacientes biopsiados con el esquema 4X4, el promedio (rango) de APE, Volúmen de Próstata y Densidad de APE fue 8,6ng/ml, 55,9ml y 0,171, respectivamente. Se tomaron un promedio de 15,9 tomas por paciente. Resultados: Se hallaron 421 CaP. El índice de positividad del sextante fue de 22,9 por ciento, el sextante lateral de 29,6 por ciento, 31,7 por ciento para el de 10 tomas, y el esquema 4X4 fue positivo en el 38,4 por ciento. La mayor diferencia se produjo en el subgrupo de APE entre 4 y 10ng/ml. Conclusiones: El aumento del número de punciones (16 tomas), 4 mediales y 4 laterales por lóbulo, tiene un índice de positividad mayor al sextante y otros esquemas