RESUMEN
BACKGROUND: In CheckMate 227 Part 1, first-line nivolumab plus ipilimumab prolonged overall survival (OS) in patients with metastatic non-small-cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% versus chemotherapy. We report results from CheckMate 227 Part 2, which evaluated nivolumab plus chemotherapy versus chemotherapy in patients with metastatic NSCLC regardless of tumor PD-L1 expression. PATIENTS AND METHODS: Seven hundred and fifty-five patients with systemic therapy-naive, stage IV/recurrent NSCLC without EGFR mutations or ALK alterations were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus chemotherapy or chemotherapy. Primary endpoint was OS with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC. OS in all randomized patients was a hierarchically tested secondary endpoint. RESULTS: At 19.5 months' minimum follow-up, no significant improvement in OS was seen with nivolumab plus chemotherapy versus chemotherapy in patients with nonsquamous NSCLC [median OS 18.8 versus 15.6 months, hazard ratio (HR) 0.86, 95.62% confidence interval (CI) 0.69-1.08, P = 0.1859]. Descriptive analyses showed OS improvement with nivolumab plus chemotherapy versus chemotherapy in all randomized patients (median OS 18.3 versus 14.7 months, HR 0.81, 95.62% CI 0.67-0.97) and in an exploratory analysis in squamous NSCLC (median OS 18.3 versus 12.0 months, HR 0.69, 95% CI 0.50-0.97). A trend toward improved OS was seen with nivolumab plus chemotherapy versus chemotherapy, regardless of the tumor mutation status of STK11 or TP53, regardless of tumor mutational burden, and in patients with intermediate/poor Lung Immune Prognostic Index scores. Safety with nivolumab plus chemotherapy was consistent with previous reports of first-line settings. CONCLUSIONS: CheckMate 227 Part 2 did not meet the primary endpoint of OS with nivolumab plus chemotherapy versus chemotherapy in patients with metastatic nonsquamous NSCLC. Descriptive analyses showed prolonged OS with nivolumab plus chemotherapy in all-randomized and squamous NSCLC populations, suggesting that this combination may benefit patients with untreated metastatic NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Nivolumab/efectos adversos , Antígeno B7-H1/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas/inducido químicamente , Carcinoma de Células Escamosas/tratamiento farmacológicoRESUMEN
BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Ipilimumab/farmacología , Ipilimumab/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nivolumab/farmacología , Nivolumab/uso terapéuticoRESUMEN
In the last decade our understanding of the processes that govern growth and differentiation has become quite sophisticated. A variety of tumor suppressor genes and more than 100 oncogenes have been identified. The roles of developmental genes in shaping the expression of neoplasia and of defective housekeeping genes in allowing mutations to persist and be transcribed have been appreciated. These advances have revolutionized our ability to diagnose and to formulate prognoses for patients with cancer. However, successful gene therapy for cancer has been elusive. This review highlights the current approaches to gene therapy for cancer and their scientific bases. The requirement that the therapy repair or destroy every cancer cell seems an insurmountable hurdle. Environmental manipulation through systemic administration of exogenous antisense may circumvent this problem in cases where it is appropriate. The more practical application of the technology of genetic engineering to facilitate cancer chemotherapy and immunotherapy is also reviewed. Particularly encouraging are the preclinical and clinical results of in vivo, in situ gene transfer. It remains to be determined if this local approach impacts favorably on survival.
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Terapia Genética , Neoplasias/terapia , Técnicas de Transferencia de Gen , Genes Supresores , Ingeniería Genética , Humanos , Neoplasias/genética , OncogenesRESUMEN
Combination antimicrotubule therapy with estramustine phosphate (EMP) and vinblastine has reproducible activity in metastatic hormone-refractory prostate cancer (HRPC) with an objective response rate of 31%. Although paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion was inactive in HRPC, 0.5 to 1.0 nmol/L concentrations of paclitaxel combined with EMP exerted synergistic cytotoxicity in DU-145 androgen-independent human prostate cancer cell lines. Based on these results, we treated 24 patients with HRPC using the combination of paclitaxel 120 to 140 mg/m2 by 96-hour intravenous infusion every 3 weeks plus daily oral EMP at 600 mg/m2/d. Of seven patients with measurable soft tissue metastases, three have attained partial responses and a fourth patient is nearing partial response status. Of 16 patients with bone-only disease evaluated by change in serum prostate-specific antigen levels, 11 patients (68.8%) have had decreases of > or = 50% from pretreatment baseline. The prostate-specific antigen decrease has exceeded 80% in six of 16 (37.5%) patients. For all 23 evaluable patients, the prostate-specific antigen has decreased by > or = 50% in 15 (65.2%) and by > or = 80% in eight (34.7%). Grade 4 leukopenia occurred in one of 21 patients treated at the paclitaxel dose of 120 mg/m2/96 hr and one of three patients treated at 140 mg/m2/96 hr. The incidence of nausea (50%) and peripheral edema (37.5%) was similar to that associated with single-agent EMP. These results demonstrate that 96-hour paclitaxel plus EMP is active in HRPC and provide further evidence that the rational combination of antimicrotubule agents leads to synergistic antitumor activity in HRPC.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundario , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Diarrea/inducido químicamente , Esquema de Medicación , Resistencia a Antineoplásicos , Estramustina/administración & dosificación , Fatiga/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , Hormonas/farmacología , Humanos , Masculino , Náusea/inducido químicamente , Paclitaxel/administración & dosificación , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/diagnóstico , Resultado del TratamientoRESUMEN
The bonafide albeit infrequent examples of tumor regression observed with whole tumor cell vaccines give evidence for the hypothesis that active specific immunization can induce a therapeutically effective immune response in melanoma patients. A dinitrophenyl-conjugated autologous whole tumor cell plus bacille Calmette-Guérin (BCG) vaccine administered in conjunction with low dose cyclophosphamide has produced clinically significant prolongation of disease free survival when used as a postsurgical adjuvant in patients with stage III melanoma. However, tumor cell-based vaccines are cumbersome and consequently of limited applicability. Improvements in our understanding of the antimelanoma immune response and technological advances have allowed investigators to explore better defined immunogens and antigenic targets; these include anti-idiotypic antibodies, gangliosides, and tumor associated/specific proteins and derived peptides. The rationale for, promise of, and progress to date with these materials are reviewed.
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Vacunas contra el Cáncer/uso terapéutico , Melanoma/terapia , Neoplasias Cutáneas/terapia , Adyuvantes Inmunológicos/uso terapéutico , Antígenos de Neoplasias/inmunología , Vacuna BCG/uso terapéutico , Ciclofosfamida/inmunología , Humanos , Antígenos Específicos del Melanoma , Proteínas de Neoplasias/inmunología , Inducción de Remisión , Linfocitos T Citotóxicos/inmunología , Vacunas Conjugadas/uso terapéutico , Vacunas Sintéticas/uso terapéuticoRESUMEN
We conducted a phase II trial of bleomycin+vincristine+lomustine+dacarbazine (BOLD) with intercycle alpha interferon-2b in previously untreated patients with metastatic uveal melanoma. Objective tumor response and toxicity were assessed. Twenty-three patients with histologically verified metastatic uveal melanoma were enrolled into this study between November 1992 and August 1995. Chemotherapy was administered in the following fashion: dacarbazine (DTIC), 200 mg/m2 intravenously on days 1-5; vincristine, 1 mg/m2 (not to exceed 2 mg) intravenously on days 1 and 4; bleomycin, 15 mg intravenously on days 2 and 5; lomustine (CCNU), 80 mg orally on day 1; and alpha interferon-2b, 3 x 10(6) IU subcutaneously on days 8, 10, 12, 15, 17, 19. A cycle was 28 days, and patients were reevaluated after every 2 cycles. Among twenty evaluable patients, four objective responses were observed (RR = 20%). Hematologic toxicity was modest by comparison to some other combination chemotherapy regimens in common use. Neurotoxicity was frequently observed, but it was seldom severe. An unexpected and unpredictable severe pulmonary toxicity was observed in 3 patients, the etiology of which remains unclear. The regimen of BOLD+interferon is active in the treatment of metastatic uveal melanoma. The precise role of the regimen has to be defined in light of its toxicity, particularly the unpredictable pulmonary toxicity. The pattern of occurrence of these pulmonary events is most consistent with either an acquired hypersensitivity reaction or a cumulative toxic effect of 2 or more of the agents. Patients considered for treatment with this regimen must be judiciously selected. Those with no clear contraindications may benefit from a trial of this regimen, but they must be monitored closely.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/terapia , Neoplasias de la Úvea/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Lomustina/administración & dosificación , Enfermedades Pulmonares/inducido químicamente , Masculino , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Proteínas Recombinantes , Neoplasias de la Úvea/tratamiento farmacológico , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND: Standard treatment options are limited for the management of non-metastatic castration-resistant prostate cancer (CRPC). This study, part of the ENTHUSE (EndoTHelin A USE) phase III programme, evaluated the efficacy and safety of the oral specific endothelin (ET)A receptor antagonist zibotentan vs placebo in patients with non-metastatic CRPC (non-mCRPC). METHODS: This was a multicentre, randomized, double-blind, phase III study. Patients (n=1421) with non-mCRPC and biochemical progression (determined by rising serum PSA levels) were randomized to receive zibotentan 10 mg or placebo once daily. Based on the lack of efficacy signal in another ENTHUSE phase III study, an interim analysis was performed to determine whether the study was likely to achieve the co-primary objectives of improved overall survival (OS) and progression-free survival (PFS). RESULTS: Criteria for continuation of this study were not met. A total of 79 deaths and 293 progression events were recorded at final data cutoff. Zibotentan-treated patients did not significantly differ from placebo-treated patients for OS (hazard ratio (HR): 1.13; 95% confidence interval (CI): 0.73-1.76, P=0.589) or PFS (HR: 0.89; 95% CI: 0.71-1.12, P=0.330). The most commonly reported adverse events in zibotentan-treated patients were peripheral oedema (37.7%), headache (26.2%) and nasal congestion (24.9%); each occurred with >15% higher incidence than in the placebo group. CONCLUSIONS: This trial was terminated early because of failure at interim analysis of the efficacy data to meet the defined criteria for continuation. Owing to the absence of demonstrable survival benefits in the ENTHUSE clinical studies, zibotentan is no longer under investigation as a potential treatment for prostate cancer.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Pirrolidinas/administración & dosificación , Adenocarcinoma/mortalidad , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Método Doble Ciego , Esquema de Medicación , Edema/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Pirrolidinas/efectos adversos , Resultado del TratamientoAsunto(s)
Antineoplásicos/uso terapéutico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Inmunoterapia/métodos , Melanoma/cirugía , Melanoma/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/terapiaRESUMEN
The patient with surgically incurable melanoma presents a difficult problem for the medical oncologist. Single chemotherapeutic agents at conventional doses produce bona fide but infrequent remissions. The most active single agent for the treatment of metastatic melanoma is dacarbazine (DTIC). Until recently, combinations of drugs yielded no real improvement over treatment with the individual components. The combination of DTIC + carmustine (BCNU) + cisplatin + tamoxifen (the "Dartmouth regimen") appears to be more effective than DTIC alone, but prospective randomized trials comparing the two are still in progress. The contribution of tamoxifen to the observed results continues to be evaluated. Biological agents, such as interferon and interleukin-2, have lower overall response rates compared to chemotherapy regimens, but response duration appears to be longer. Chemotherapy combined with biotherapy offers the promise of higher response rates and long-term durable remissions. The results from high-dose regimens that use autologous bone marrow or peripheral stem cell support have not been sufficient to justify the added toxicity. Although advanced melanoma often is not curable with systemic therapy, the considered use of currently available regimens can induce clinically significant remissions and, possibly, prolong life in some patients.
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Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Terapia Combinada , Humanos , Interferones/uso terapéutico , Interleucina-2/uso terapéutico , Melanoma/secundario , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: We describe a technique of bladder neck detachment and augmented closure incorporating total prostatectomy and urinary diversion in men with complex bladder and urethral pathology due to fistula, radiation and neurogenic dysfunction. MATERIALS AND METHODS: We retrospectively reviewed the records of 5 men 38 to 61 years old who presented with unsalvageable urethral pathology, including prostate cancer in 2. All 5 patients underwent radical prostatectomy and augmented bladder neck closure with creation of a continent catheterizable stoma in 4 and chimney diversion in 1. RESULTS: Bladder neck closure was performed with interposition of an ileocecal patch in 4 cases and sigmoid colon in 1. At a mean followup of 6 months no fistula, recanalization or urinoma developed. Delayed complications included stomal stenosis, stomal incontinence requiring collagen injection and rupture of the augmented bladder in 1 case each. The 2 men with prostate cancer had undetectable prostate specific antigen. CONCLUSIONS: Prostatectomy facilitated mobilization of the bladder neck away from the urethral pathology and interposition of an intestinal segment at the bladder neck allowed healing. In addition to cases of complicated urethrovesical pathology, this technique may have applications in salvage prostatectomy after pelvic irradiation for carcinoma.
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Colon/trasplante , Prostatectomía , Enfermedades Uretrales/cirugía , Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Procedimientos Quirúrgicos Urológicos , Adulto , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Reflejo Anormal , Enfermedades de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: In early trials of paclitaxel administered as a 24-hour infusion, an overall response rate of 16% was reported for patients with metastatic melanoma. Paclitaxel is a natural product-based agent and is thus subject to the problem of multidrug resistance (MDR). Tamoxifen is an agent that can abrogate MDR and potentially enhance the effect of paclitaxel. A Phase II trial of the combination was undertaken with previously treated patients. METHODS: Patients with metastatic cutaneous or mucosal melanoma who were previously treated with the Dartmouth chemotherapy regimen (dacarbazine, carmustine, cisplatin, and tamoxifen) were evaluated. Paclitaxel was administered at a dose of 225 mg/m(2) intravenously over 3 hours every 3 weeks. All patients also took tamoxifen 40 mg orally daily. Treatment continued until disease progression. RESULTS: Twenty-one patients completed at least two cycles of paclitaxel and were evaluable for response. Five responses were observed, 1 complete response, and 4 partial responses, for an overall response rate of 24%. The combination was well tolerated. The most common nonhematologic side effects were myalgia and paresthesia. Hematologic toxicity was mild. No patients developed neutropenic fever. CONCLUSIONS: This is the first report of a Phase II trial evaluating paclitaxel as a 3-hour infusion in melanoma patients. The 3-hour infusion is well tolerated and results in little myelosuppression and minimal neurotoxicity. The contribution of tamoxifen is difficult to evaluate because plasma levels were not measured. It is possible that a higher response rate might be observed with larger doses of tamoxifen. Further investigation of paclitaxel in the treatment of patients with metastatic melanoma is warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/secundario , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Membrana Mucosa , Paclitaxel/administración & dosificación , Tamoxifeno/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: We prospectively examined whether the fixed urethral resistance of the perineal male sling for the treatment of stress incontinence causes significant bladder outlet obstruction or de novo voiding dysfunction. MATERIALS AND METHODS: A total of 22 patients (average age 67 years old) were evaluated before and after surgery with videourodynamics, the self-administered UCLA Prostate Cancer Index incontinence section and pad score. RESULTS: Mean followup was 25 months (range 6 to 42). All patients complained of a moderate to severe problem before surgery. After surgery 16 (73%) reported a very small problem/no problem, 3 (14%) a moderate problem and 3 (14%) reported a big problem. Average pad use +/- SD decreased from 4.6 +/- 2.5 to 0.74 +/- 1.0 pads (p <0.01). Median UCLA Prostate Cancer Index incontinence score increased from 82 to 313, p <0.001. Mean retrograde leak point pressure (RLPP) increased from 30.4 +/- 15.9 to 59.9 +/- 9.7 cm water. Bladder outlet obstruction did not develop in any patients after surgery. Average maximum flow rate did not change significantly (17.7 +/- 6.5 vs 19.2 +/- 9.7 ml per second, p = 0.6). Nor was there a significant change in detrusor pressure at maximum flow rate (40.3 +/- 9.2 vs 45.8 +/- 14.7 cm water, p = 0.3). While de novo urgency or urge incontinence did not develop in any patients, 2 of 5 patients with a moderate/big leakage problem demonstrated postoperative detrusor overactivity on cystometry. Both individuals requiring more than 3 pads daily had a postoperative RLPP of less than 50 cm water. CONCLUSIONS: Pad use, leak point pressure and urinary incontinence scores are significantly improved after sling surgery. Fixed resistance does not lead to bladder outlet obstruction. Postoperative RLPP less than 50 cm water and urodynamic detrusor overactivity are associated with increased pad use and bother.
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Incontinencia Urinaria de Esfuerzo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostatectomía/efectos adversos , Prótesis e Implantes , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/fisiopatología , UrodinámicaRESUMEN
PURPOSE: Stress urinary incontinence after prostate surgery can be a bothersome problem, adversely affecting quality of life. We performed a prospective study of the male perineal sling for the treatment of stress urinary incontinence with a minimum 1-year followup. MATERIALS AND METHODS: A total of 36 patients (average age 67 years old) underwent male sling surgery. Patients underwent preoperative and postoperative evaluation for bother due to urinary incontinence using the UCLA Prostate Cancer Index urinary function section as well as pad score. RESULTS: Median followup was 25 months (range 12 to 42). After surgery 24 (67%) patients were pad-free, 5 (14%) used 1 pad, 4 (11%) used 2 pads and 3 (8%) continued to use 3 or more pads daily. Overall, mean pad use +/- SD decreased from 4.6 +/- 2.5 to 0.64 +/- 1.0 pads daily (p <0.001). A total of 30 (83%) patients reported a small to no bother from urine leakage after surgery, 3 (8%) considered leakage a moderate problem, while 3 (8%) continued to consider it a big problem. The median UCLA Prostate Cancer Index urinary function score was improved from 33 before surgery to 330 after surgery (p <0.001). There were no instances of erosion, infection or prolonged retention. CONCLUSIONS: Medium term results for the male sling demonstrate a success rate comparable to that of the artificial urinary sphincter (67% pad-free rate and 92% improvement). This technique has established a low morbidity and has not been associated with any significant complications. Longer followup will ultimately establish whether this technique represents a viable long-term alternative to artificial urinary sphincter for the treatment of bothersome stress urinary incontinence in men.
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Prótesis e Implantes , Incontinencia Urinaria de Esfuerzo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostatectomía/efectos adversos , Encuestas y Cuestionarios , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/fisiopatología , UrodinámicaRESUMEN
Neonatal alloimmune thrombocytopenia (NAIT) most commonly involves antibodies directed against the PlA1 antigen, but other platelet specific alloantigens have been associated with it. We describe the case of a mother whose first three infants developed NAIT secondary to anti-Bak(a) antibodies, while her fourth infant did not. The three affected infants were treated postnatally with platelet transfusions. The fourth infant was treated antenatally with one dose of intravenous immunoglobulin (IVIg) given to the mother. Postpartum analysis revealed the infant's platelets to be Bak(a)-positive but negative for elevated IgG. Maternal serum reacted with neonatal platelets in vitro, but cord serum was negative for antiplatelet antibodies. These clinical observations do not prove the efficacy of IVIg; however, they raise several questions: Why wasn't this infant thrombocytopenic? Why didn't the umbilical cord contain maternal antibody? Was the single dose of IVIg responsible for preventing NAIT? IVIg is currently under investigation in a clinical trial evaluating its effectiveness in preventing NAIT in mothers with anti-PlA1 antibodies, where it has shown some success. There have been no reports of the use against anti-Bak(a) antibodies. We suggest that a weekly dose schedule may not be necessary for all affected pregnancies, and antibodies with specificity other than anti-PlA1 may require less vigorous therapy.
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Antígenos de Plaqueta Humana/inmunología , Plaquetas/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Isoantígenos/inmunología , Trombocitopenia/inmunología , Trombocitopenia/prevención & control , Adulto , Femenino , Humanos , Inmunoglobulina G/sangre , Recién Nacido , Integrina beta3 , Masculino , Intercambio Materno-Fetal , Transfusión de Plaquetas , EmbarazoRESUMEN
BACKGROUND: The objective of this study was to evaluate the usefulness of resection of metastatic uveal melanoma and to analyze the characteristics of patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve patients underwent surgical removal of metastasis between 1976 and 1998. Data regarding primary uveal melanoma, systemic metastasis, surgical procedures, and outcomes were reviewed retrospectively. RESULTS: There were seven patients with liver metastases, two with lung metastases, one with brain metastasis, and two patients with metastases in the liver and other organs. Median time to systemic metastasis was 8 years. Seven of 12 patients were asymptomatic when they were found to have metastasis. Ten patients underwent complete resection of metastasis. No significant surgical complications were experienced. Median recurrence free and overall survival periods after complete resection were 19 months (range, 6-78 months) and greater than 27 months (range, 11-86 months), respectively. Recurrence free and overall 5-year survival rates of those patients were 15.6% and 53.3%, respectively. Three of these patients had no further systemic recurrence. All patients whose time to systemic metastasis was within 5 years developed further systemic recurrence within 2 years after surgery. In contrast, in 8 patients whose time to systemic metastases was greater than 5 years, 4 patients either were recurrence free or developed second metastasis more than 4 years after surgery. CONCLUSIONS: Complete surgical removal of metastatic uveal melanoma provided unexpectedly long survival without significant morbidity for the selected patients. These results are encouraging and justify a trial in which patients eligible for resection are randomized between standard treatment and surgery.
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Neoplasias Encefálicas/secundario , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Melanoma/cirugía , Neoplasias de la Úvea/cirugía , Adolescente , Adulto , Femenino , Humanos , Melanoma/secundario , Persona de Mediana Edad , Morbilidad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Neoplasias de la Úvea/patologíaRESUMEN
BACKGROUND: Thrombospondin is a high molecular weight glycoprotein, originally described as a secretion product of platelets, that functions as an adhesive protein in cell-cell and cell-substratum interactions. It promotes metastases in the murine model. Plasma thrombospondin has been shown to be elevated in patients with disseminated breast, lung, and gastrointestinal malignancies. METHODS: Blood samples were collected by venipuncture into cubes containing ethylenediamine tetraacetic acid as anticoagulant. They were placed on ice immediately and centrifuged under refrigerated conditions. Plasma was removed and frozen until thrombospondin was quantitated by a competitive enzyme-linked immunosorbent assay. Wilcoxon's two-sample rank-sum test was used to evaluate differences between the patient and control groups. RESULTS: The median plasma thrombospondin level was significantly higher in the patient group compared with the control group, and it was directly correlated with stage of disease. There was no correlation between platelet count and thrombospondin level. CONCLUSIONS: Tumor-synthesized thrombospondin could explain the elevated levels in the patent group and also the observation of the correlation between the thrombospondin level and tumor burden. Its function as an adhesive protein may allow it to act as the mediator of metastases. thrombospondin may promote or mediate the metastatic process through its function in cell adhesion.