RESUMO
The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument to screen, assess and monitor malnutrition and risk factors, and to triage for interventions. After having translated and culturally adapted the original PG-SGA for the Italian setting, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles, we tested linguistic validity, i.e., perceived comprehensibility and difficulty, and content validity (relevance) of the Italian version of the PG-SGA in patients with cancer and a multidisciplinary sample of healthcare professionals (HCPs). METHODS: After the translation and cultural adaptation of the original PG-SGA for the Italian setting, the patient component (i.e., PG-SGA Short Form (SF) was tested for linguistic validity (i.e., comprehensibility ad difficulty) in 120 Italian patients with cancer and 81 Italian HCPs. The full PG-SGA, i.e., patient and professional component of the PG-SGA, was tested for content validity, i.e., relevance, in 81 Italian HCPs. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Through item and scale indices we evaluated the comprehensibility (I-CI, S-CI), difficulty (I-DI, S-DI) and content validity (I-CVI, S-CVI). Scale indices 0.80-0.89 were considered acceptable, and scale indices ≥0.90 were considered excellent. RESULTS: Patients perceived comprehensibility and difficulty of the PG-SGA SF (Boxes) as excellent (S-CI = 0.98, S-DI = 0.96). Professionals perceived comprehensibility of the professional component (Worksheets) as excellent (S-CI = 0.92), difficulty as acceptable (S-DI = 0.85), and content validity of the full PG-SGA as excellent (S-CVI = 0.92). Dietitians gave higher scores (indicating better scores) on comprehensibility, difficulty, and content validity of Worksheet 4 (physical exam) than the other professions. In Worksheet 4, four items were considered most difficult to complete and were considered below acceptable range. Relevance was perceived as excellent by professionals for both the patient component (S-CVI = 0.93) and the professional component (S-CVI = 0.90), resulting in S-CVI = 0.92 for the full PG-SGA. Slight textual modifications were implemented resulting in the final version of the Italian PG-SGA. CONCLUSIONS: Translation and cultural adaptation of the original PG-SGA resulted in the Italian version of the PG-SGA that maintained its original purpose and meaning and can be completed adequately and easily by patients and professionals. The Italian PG-SGA is considered relevant for screening, assessing and monitoring malnutrition and risk factors, as well as triaging for interventions by Italian HCPs.
Assuntos
Desnutrição , Neoplasias , Humanos , Estado Nutricional , Avaliação Nutricional , Desnutrição/diagnóstico , Neoplasias/diagnóstico , Neoplasias/complicações , LinguísticaRESUMO
BACKGROUND: The role and the durability of the immunogenicity of the third dose of vaccine against COVID-19 variants of concern in cancer patients have to be elucidated. PATIENTS AND METHODS: We have prospectively evaluated the immunogenicity of the third dose of the SARS-CoV-2 BNT162b2 messenger RNA vaccine in triggering both humoral and cell-mediated immune response in patients with solid tumors undergoing active treatment 6 months after the booster. Neutralizing antibody (NT Ab) titers and total anti-spike immunoglobulin G concentrations were measured in serum. Heparinized whole blood samples were used for the SARS-CoV-2 interferon-γ release assay (IGRA). RESULTS: Six months after the third dose only two patients (2.4%) showed negative spike-specific immunoglobulin G antibody levels (<33.8 BAU/ml). The median level of SARS-CoV-2 NT Abs decreased and only 39/83 (47%) subjects showed maximum levels of NT Abs. T-cellular positive response was observed in 38/61 (62.3%) patients; the highest median level of response was observed 21 days after the third dose (354 mIU/ml, interquartile range 83.3-846.3 mIU/ml). The lowest median level of NT Ab response was observed against the Omicron variant (1 : 10, interquartile range 1 : 10-1 : 40) with a significant reduced rate of responder subjects with respect to the wild-type strain (77.5% versus 95%; P = 0.0022) and Delta variant (77.5% versus 93.7%; P = 0.0053). During the follow-up period, seven patients (8%) had a confirmed post-vaccination infection, but none of them required hospitalization or oxygen therapy. CONCLUSIONS: Our work highlights a significant humoral and cellular immune response among patients with solid tumors 6 months after the third BNT162b2 vaccine dose, although a reduction in neutralizing activity against Omicron was observed.
Assuntos
COVID-19 , Neoplasias , Vacinas Virais , Humanos , Vacinas contra COVID-19/farmacologia , Vacina BNT162 , Estudos Longitudinais , Anticorpos Antivirais , Vacinas Virais/genética , SARS-CoV-2 , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Imunoglobulina G , Imunidade Celular , Neoplasias/tratamento farmacológico , Oxigênio , Vacinas de mRNARESUMO
BACKGROUND: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. PATIENTS AND METHODS: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. RESULTS: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). CONCLUSIONS: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity.
Assuntos
COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , Imunoglobulina G/uso terapêutico , Neoplasias/tratamento farmacológico , Estudos Prospectivos , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNARESUMO
BACKGROUND: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. PATIENTS AND METHODS: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. RESULTS: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). CONCLUSIONS: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors.
Assuntos
Antígeno B7-H1 , Vacina BNT162 , COVID-19 , Inibidores de Checkpoint Imunológico , Neoplasias , Receptor de Morte Celular Programada 1 , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Vacina BNT162/administração & dosagem , Vacina BNT162/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Seguimentos , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/imunologia , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , SARS-CoV-2/imunologiaRESUMO
BACKGROUND: Very few cancer patients were enrolled in coronavirus disease-2019 vaccine studies. In order to address this gap of knowledge, real-world studies are mandatory. The aim of this study was to assess both humoral and cellular response after a messenger RNA vaccination schedule. PATIENTS AND METHODS: Eighty-eight consecutive cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors were enrolled from the beginning of the vaccination campaign for frail patients. Blood samples for humoral and cell-mediated immune response evaluation were obtained before vaccination (T0), before the second administration (T1) and 21 days after the second dose (T2). The primary endpoint was the evaluation of the percentage of participants showing a significant increase in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells, measured by an enzyme-linked immunospot assay, after the second dose of BNT162b2 vaccine. The proportion of patients who reached the primary endpoint is computed together with its exact binomial 95% confidence interval. RESULTS: In SARS-CoV-2-naïve subjects, spike-specific T-cell response was almost undetectable at T0 [median 0.0 interferon-γ (IFN-γ) spot forming units (SFU)/million peripheral blood mononuclear cell (PBMC) interquartile range (IQR) 0-7.5] and significantly increased at T1 and T2 (median 15.0 IFN-γ SFU/million PBMC, 25th-75th 0-40 versus 90 IFN-γ SFU/million PBMC, 25th-75th 32.5-224, respectively) (P < 0.001). Focusing on naïve and experienced SARS-CoV-2 subjects, no differences were reported both in terms of CD4- and CD8-specific T-cell response, suggesting that BNT162b2 is able to elicit both adaptive responses after complete vaccination schedule, regardless of previous SARS-CoV-2 exposure. The level of SARS-CoV-2 neutralizing antibodies was low at T1 in SARS-CoV-2-naïve subjects [median 1 : 5 (IQR 1 : 5-1 : 20)] but reached a significantly higher median of 1 : 80 (25th-75th 1 : 20-1 : 160) at T2 (P < 0.0001). Moreover, no COVID-19 cases were documented throughout the period of study. CONCLUSIONS: Our data have demonstrated that the administration of a full course of BNT162b2 vaccine elicited a sustained immune response against SARS-CoV-2 regardless of the type of cancer and/or the type of immune checkpoint inhibitors.
Assuntos
COVID-19 , Neoplasias , Anticorpos Antivirais , Vacina BNT162 , Vacinas contra COVID-19 , Estudos de Coortes , Humanos , Inibidores de Checkpoint Imunológico , Leucócitos Mononucleares , Estudos Longitudinais , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , SARS-CoV-2RESUMO
BACKGROUND: In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacy versus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emission tomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial. PATIENTS AND METHODS: Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized 1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity. RESULTS: PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients (252 of 257) had ≥2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in the nab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best response at any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56; P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolic response rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%, P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone, including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%; P < 0.001). CONCLUSION: Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher for nab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associated with longer survival, and more patients experienced a metabolic response than a RECIST-defined response. CLINICALTRIALSGOV: NCT00844649.
Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. PATIENTS AND METHODS: Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. RESULTS: Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. CONCLUSION: This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Antígeno CA-19-9/sangue , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Biomarcadores Farmacológicos/sangue , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , GencitabinaRESUMO
The aim of this study is to describe the synthesis of, relaxometric characterization of, pharmacokinetic properties of, and animal imaging experiments with a new, low molecular weight gadolinium complex with high binding affinity toward serum albumin. The gadolinium(III) chelate (B25716/1) is based on the structure of the heptadentate ligand 1,4-bis(hydroxycarbonylmethyl)-6-[bis(hydroxycarbonylmethyl)]amino-6 methylperhydro-1,4-diazepine (AAZTA) covalently conjugated to an analogue of deoxycholic acid. The study was conducted as a comparison with that of an analogous complex based on the octadentate diethylenetriaminepentaacetic acid ligand B22956/1 (whose albumin binding properties were previously assessed). The structural modification with respect to B22956/1 leads to a system that can host two coordinated water molecules in fast exchange with bulk water with potential higher efficiency as an MRI contrast agent. On interaction with human serum albumin the expected-field-independent-relaxation enhancement is not observed, possibly as a consequence of the displacement of one of the two inner-sphere water molecules of the gadolinium complex. At clinically relevant magnetic fields, however, the plasma relaxivity of B25716/1 is markedly higher than that shown by B22956/1, owing to concomitant synergistic contributions from the electronic correlation time and water molecules in the second coordination sphere. The capability of B25716/1 to enhance tumor regions in magnetic resonance images was assessed in vivo at 3 T on a xenograft tumor mouse model prepared with PC-3 cells. B25716/1 displays signal enhancements approximately double those observed for B22956/1, in agreement with the findings of the in vitro relaxivity investigations.
Assuntos
Meios de Contraste/química , Gadolínio/química , Imageamento por Ressonância Magnética/métodos , Animais , Humanos , Masculino , Camundongos , Neoplasias da Próstata/diagnósticoRESUMO
AIM: The aim of this paper was to compare and analyze the therapeutic effects and PSA variation levels with treatment with finasteride-tamsulosin and dutasteride-tamsulosin for benign prostatic hyperplasia for 2 years and the risk to developing prostate cancer for patients with PSA<4 ng/mL. METHODS: We retrospectively investigated 288 patients who suffered from BPH and PSA>4 ng/mL between January 2003 and July 2010. For treatment groups, we divided the patients into two groups: one was treated with tamsulosin and finasteride and the other with tamsulosin and dutasteride. At the beginning of treatment, the patients underwent transrectal ultrasonography and prostate mapping, measurement of urine flow rate, PSA, and International Prostate Symptom Score (IPSS). A total of 288 patients were able to be. RESULTS: Both finasteride and dutasteride rduced PSA and prostate volume significantly. The comparison between the 2 groups showed a significant difference at 3 months for IPSS; uroflussimetry and prostate volume in the dutasteride group, but at 6 months did not differ significantly between the groups. Patients with a PSA reduction more than half presented a good response and didn't request surgical theraphy. CONCLUSION: 5 alpha Reductase inhibitors for BPH treatment reduced PSA and prostate volume significantly after 6 months of theraphy and after 3 months only for dutasteride. PSA reduction is directly correlated with response to theraphy. Didn't were evidenced statistically differences on prostate cancer presence during theraphy.
Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Azasteroides/uso terapêutico , Finasterida/uso terapêutico , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Dutasterida , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Anterior urethral valves in the fossa navicularis is an exceptionally uncommon causes of lower urinary tract obstruction in newborn. The authors report a case of anterior urethral valves in thefossa navicularis in an 5 days-old boy, that observation of the voided stream revealed a filiform micturition and marked ballooing of the penile urethra. The meatus was located normally and of normal calibre. Voiding cystourethrography showed obstruction at the fossa navicularis, and a hyghly trabeculated bladder. Ultrasonography showed a severe bilateral hydroureteronephrosis. After a temporary soprapubic cystostomy, the urethroscopy revealed a valve on the floor of the fossa navicularis, excised with tenotomy scissor. Postoperatively ,urethral obstruction was relieved immediately by a good urinary stream. At 6 months follow-up the patient voided with a good stream and ultrasonography revealed complete disappearance of hydroureteronephrosis.
Assuntos
Uretra/anormalidades , Uretra/cirurgia , Humanos , Recém-Nascido , MasculinoRESUMO
Aquaporin-9 (AQP-9) regulates tissue hydration by promoting transmembrane exchanges of both water and solutes, such as lactate. The latter is a key metabolite of primary spermatocytes and of maturing haploid germ cells (h-GCs). The present investigation was aimed at immunolocalising human AQP-9 in both normal and varicocele testes. Histology and immmunocytochemistry were investigated in archival biopsies from 20 varicocele testes and in eight unaffected ones. AQP-9 immunostaining was performed using a rabbit antibody, and either focal or diffuse cell membrane labelling was recorded. Varicocele testes showed disarranged tubular compartments, with sloughing h-GCs, tissue hyperhydration, spermiogenesis failure and fibrosis. AQP-9 immunohistology of the control testes showed a diffuse cell membrane staining of the primary spermatocytes and h-GCs, without any positive reaction of spermatogonia and Sertoli cells. AQP-9 cell expression in the varicocele testes was focal or lacking in both adluminal and sloughing GCs. AQP-9 expression occurs in normal human testis, at cell membrane of primary spermatocytes and h-GCs, suggesting a possible role of AQP-9 in the water and lactate transport from Sertoli cells to GCs. AQP-9 is focal or lacking in adolescent varicocele testes, and this suggests AQP-9 to be downregulated in such testicular disorder, leading to lactate deprivation with subsequent hypospermatogenesis.
Assuntos
Aquaporinas/metabolismo , Hipóxia Celular/fisiologia , Espermatócitos/metabolismo , Espermatogênese/fisiologia , Testículo/metabolismo , Varicocele/metabolismo , Adolescente , Biópsia , Estudos de Casos e Controles , Membrana Celular/metabolismo , Matriz Extracelular/metabolismo , Humanos , Masculino , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Espermátides/metabolismo , Espermátides/patologia , Espermatócitos/patologia , Espermatozoides/metabolismo , Espermatozoides/patologia , Testículo/patologia , Varicocele/patologiaRESUMO
This case report is about a 4-year-old patient with a IIA2 ''Y-type'' duplication, with the accessory urethra arising from the anterior orthotopic urethra and exiting in perineal-scrotal position, in association with posterior urethral valves (PUV). Cystourethroscopy through the ventral urethra revealed a type III urethral valve (diaphragm) and this was fulgurated. Duplicated dorsal urethra was excised surgically. Postoperative period was uneventful. This case is unique, because it shows PUV in a child with a very rare type of ''Y-type'' duplication. The presence of PUV in patients with urethral duplication is probably not an incidental finding but, to date, embryology of this rare association is not known.
Assuntos
Uretra/anormalidades , Fístula Urinária/diagnóstico , Pré-Escolar , Cistoscopia , Humanos , Masculino , Uretra/cirurgia , Fístula Urinária/cirurgia , Transtornos Urinários/etiologia , Procedimentos Cirúrgicos Urológicos MasculinosRESUMO
INTRODUCTION: Depending on the type and size of the syringocele and the age of the patient, syringocele is treated medically or surgically, with endoscopy or open surgery. We report our experience in 10 "open" consecutive cases of syringocele, propose a clinical classification and discuss the management. MATERIAL AND METHODS: In all patients (pts), diagnosis was achieved through voiding cystourethrography. All pts performed multichannel urodynamic studies. Pts with impaired compliance and/or detrusor instability (4 pts out of 10) underwent endoscopic unroofing. They were followed up until to 24 months after the endoscopic procedure. Pts with normal urodynamic findings were treated medically and followed with clinical examination. All pts performed an urinalysis every 2 weeks for the first three months and monthly for an year. RESULTS: In endoscopic treated pts, voiding cystourethrography showed a normal profile of the urethra at 3 months follow-up. Pts with UTI, but with normal urodynamic parameter were treated with antibiotic therapy. At serial follow-up, all pts were completely symptom-free. Urinalysises were normal, negative for infection or haematuria. DISCUSSION: In the literature to date, there isn't accordance if and when treated "open" syringoceles. In our opinion, it is useful to classify "open" syringocele based on urodynamic findings. Syringocele needs endoscopic surgical treatment if it is obstructed or a cause of dysfunctional alteration of the bladder, in order to avoid unnecessary surgery in syringocele without urodynamic abnormality.
Assuntos
Glândulas Bulbouretrais , Doenças Uretrais , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Endoscopia , Enurese/etiologia , Seguimentos , Humanos , Masculino , Cooperação do Paciente , Fatores de Tempo , Doenças Uretrais/diagnóstico , Doenças Uretrais/fisiopatologia , Doenças Uretrais/cirurgia , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Urodinâmica , Urografia/métodosRESUMO
AIM: Most patients with advanced prostate cancer respond to androgen inhibition with or without antiandrogens. Progression to androgen-independent prostate cancer takes 5-7 years and is characterized by biochemical or diagnostic changes, despite testosteronemia levels similar to those after castration. Dutasteride, a 5-alfa-reductase types 1 and 2 inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). In prostate cancer, 5-alfa-reductase type 1 expression is greater than in BPH, but no differences in 5-alfa-reductase type 2 expression have been observed between metastatic prostate cancer and BPH. The higher levels of the two isozymes in metastatic and in recurrent prostate cancer after androgen withdrawal may reflect a selective adaptive mechanism to the amplification of remaining androgen signals. The aim of this prospective study was to evaluate the clinical utility of dutasteride in the treatment of hormone refractory prostate cancer. METHODS: Between March 2005 and December 2007, 8 patients with hormone refractory prostate cancer were evaluated prospectively. Following antiandrogen withdrawal and subsequent increase in PSA, 5 patients received docetaxel plus prednisone and 3 received ketoconazole plus hydrocortisone. The regimen was a single administration of 2 tablets of 0.5 mg dutasteride/die. Therapeutic response was defined as a >50% reduction in PSA or a 75% reduction at 4 weeks after the start of therapy. RESULTS: The mean duration of follow-up was 9 months (range, 21-24 months). A reduction >50% or >75% in PSA was noted in 4 and 6 patients, respectively. Bone scintigraphy detected no normalization of bone lesions; computed tomography scanning showed no partial response to treatment. The mean duration of response was 6.9 months (range, 0-21 months). Two (25%) of the 8 patients died at 6 and 10 months, respectively, neither of which had responded to dutasteride treatment. Only 1/8 patients reported experiencing dyspepsia during the study period. CONCLUSION: The activity of 5-alfa-reductase types 1 and 2 is expressed in the epithelial cells of the prostate, the stroma, and the prostate tumor. The genetic expression of fatty acid synthesis is influenced by dutasteride, which inhibits it by blocking the pathway that regulates sterol protein binding which, in turn, regulates androgen stimulation. The addition of a dual inhibitor of 5-a-reductase types 1 and 2 to antiandrogen therapy may further inhibit tumor growth, thus reducing the concentration of intracellular dihydrotestosterone, which is the primary androgen mediator of PSA gene expression in prostate tumor cell lines. These data support the rationale for the use of dutasteride in the treatment of hormone refractory prostate cancer. The study findings show that dutasteride is useful in the treatment of hormone refractory prostate cancer.
Assuntos
Azasteroides/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Dutasterida , Humanos , Masculino , Estudos Prospectivos , Falha de TratamentoRESUMO
Isolated congenital fistula of the penile urethra is extremely rare. A case of congenital urethral fistula with an intact glandular urethra without chordee is reported with a discussion of the possible etiology and management.
Assuntos
Doenças do Pênis/diagnóstico , Doenças Uretrais/diagnóstico , Fístula Urinária/diagnóstico , Humanos , Lactente , Masculino , Doenças do Pênis/cirurgia , Resultado do Tratamento , Doenças Uretrais/cirurgia , Fístula Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
AIM: Recent reports have shown an altered density of interstitial cells of Cajal (ICCs) and peripherin immunoreactive nerve fibres in uretopelvic junction obstruction. The aim was to investigate ICCs immunoexpression and ureteral innervation in primary obstructive megaureter (POM). METHODS: Eight specimens of POM were obtained during tailoring. Restricted segments of ureters were divided from dilated segments. C-kit and peripherin immunohistochemistry were performed. RESULTS: A normal distribution of ICCs was observed in both the circular and longitudinal muscle layers of the dilated segments. Marked muscle hypoplasia and sparse or no ICCs occurred in the longitudinal muscle layer of the restricted ureteral segments. A normal distribution of peripherin positive fibres was present in both the dilated and restricted segments. CONCLUSIONS: Our data confirm defective muscularization in restricted aperistaltic POM. The lack of ICCs in the longitudinal muscular layer is probably due to the absence of c-kit positive muscle embryological precursors. No alteration in the peripherin immunoreactive nerve fibres network was observed in either the dilated or the restricted ureteral segments.
Assuntos
Corpos Enovelados/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Músculo Liso/patologia , Proteínas Proto-Oncogênicas c-kit/metabolismo , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia , Feminino , Humanos , Lactente , Masculino , Músculo Liso/metabolismo , Fibras Nervosas/patologia , Proteínas do Tecido Nervoso/metabolismoRESUMO
HPV infection is the most common sexually transmitted disease today and is strongly related to cervical cancer. We studied 1500 women in a limited area of the Calabria region to determine the best method of screening for cevical cancer.
Assuntos
Colposcopia , Programas de Rastreamento/métodos , Infecções por Papillomavirus/diagnóstico , Esfregaço Vaginal , Feminino , Humanos , Itália/epidemiologia , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologiaRESUMO
Inflammatory myofibroblastic tumor (IMT) of the ileum is a rare, usually solitary lesion, that frequently presents small-intestinal intussusception and obstruction. We describe an IMT of the ileum in a 4.5-year old child who presented a small bowel intussusception. During laparotomy, an annular mass around the ileum was resected, and the IMT was histologically diagnosed. Three months after the operation, the patients were hospitalized with the symptoms of intestinal obstruction. Laparotomy showed a ileal intussusception. Along the previous suture line of anastomosis, a smooth polypoid tumor was evident. Segmental resection of the ileum, including the tumor mass, was performed. The IMT was immunohistochemically diagnosed. The patient was asymptomatic at 3 year follow-up. A review of the literature for this rare entity emphasizes the importance of immunohistochemical confirmation of its benign nature. Because of the risk of local recurrence, IMT cases should have a long-term follow-up.