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BACKGROUND: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC). METHODS: CA209-9JC was an open-label, single-arm, phase 2 study to evaluate the safety and/or efficacy of nivolumab in systemic treatment-naive patients with aCSCC. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or 12 months of treatment. The primary end point was the best objective response rate (BORR) as per RECIST 1.1 criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-four patients with aCSCC were enrolled with a median age of 74 years (range, 48-93). Among the 24 patients evaluable for response, the BORR was 58.3% (14/24); there were no complete responses. With a median follow-up of 17.6 months, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 months, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p = .035, univariate analysis). Treatment-related adverse events of any grade and grade ≥ 3 occurred in 21 (87.5%) and six (25%) patients, respectively, and one patient discontinued nivolumab due to toxicities. CONCLUSIONS: Nivolumab resulted in robust antitumor activity, sustained responses, and good tolerability in systemic treatment-naive patients with aCSCC. These data provide further evidence to support the use of ICI as the standard treatment of aCSCC.
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Carcinoma de Células Escamosas , Nivolumab , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Nivolumab/efectos adversos , Carcinoma de Células Escamosas/inducido químicamente , Supervivencia sin Progresión , Criterios de Evaluación de Respuesta en Tumores Sólidos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: Everolimus-induced pneumonitis (EiP) has been poorly studied in patients with neuroendocrine neoplasms (NEN) outside clinical trials. The aim of this study was to evaluate the incidence, risk factors, and outcomes of EiP in patients with NENs using real-world data. METHODS: Retrospective study of everolimus-treated patients with advanced NENs. Imaging reports were systematically reviewed for the presence of pneumonitis. Clinical features and treatment profiles for EiP were summarized. Overall survival (OS) was calculated from the initiation of everolimus to the date of death or last follow-up using the Kaplan-Meier method. RESULTS: A total of 122 patients were included. Median age at start of everolimus was 62 (19-86) years, 62% (76/122) were male, and half were from pancreatic origin (62, 51%). Twenty-eight patients (23%) developed EiP: 82% grade (G)1 or G2, 14% G3 and 4% G4. The median time to EiP was 3.6 (0.8-51) months. Primary tumor site, concurrent lung disease, smoking history, and prior therapies were not associated with the onset of EiP. Patients who developed EiP had longer time on everolimus treatment (median 18 months vs 6 months; P = .0018) and OS (77 months vs 52 months; P = .093). Everolimus-induced pneumonitis was a predictor of improved OS by multivariable analysis (HR 0.39, 95% CI 0.19-0.82; P = .013). CONCLUSION: Everolimus-induced pneumonitis in the real-world clinical setting is present in one quarter of patients with NENs receiving everolimus and often occurs early. While risk factors for EiP were not identified, patients with EiP had improved survival.
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Tumores Neuroendocrinos , Neumonía , Everolimus/efectos adversos , Femenino , Humanos , Masculino , Tumores Neuroendocrinos/patología , Neumonía/inducido químicamente , Neumonía/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: The incidence of infections is poorly studied in patients with neuroendocrine tumors (NET) treated with everolimus outside of clinical trials. We aimed to evaluate the frequency of and risk factors for opportunistic infections (Opl) or any serious infection in eligible patients. METHODS: This was a retrospective multicenter study of a Latin American cohort of consecutive patients with advanced NET treated with everolimus. Duration of everolimus, comorbidities, Charlson comorbidity score, type of prior treatment, institution, and concurrent immunosuppressive conditions were tested for possible associations with serious (grade 3-5) infections in univariate and multivariable logistic regression models. RESULTS: One hundred eleven patients from 5 centers were included. The median duration of everolimus was 8.9 months. After a median follow-up of 32.9 months, 34 patients (30.6%; 95% CI 22.2-40.1) experienced infections of any grade, with 24 (21.6%; 95% CI 14.8-30.4) having a serious infection and 7 (6.3%; 95% CI 2.6-12.6) having at least 1 OpI (Candida sp., Toxoplasma gondi, Pneumocystis sp., Herpes sp., and Cryptococcus sp.). Four patients (3.6%) died from infections, but only 2 deaths (1.8%) were deemed to be related to everolimus. The multivariable analysis identified everolimus duration (every 6-month increase; OR = 1.28; 95% CI 1.02-1.60; p = 0.03) as an independent risk factor for serious infection. CONCLUSION: Infections are more frequent in NET patients using everolimus than previously reported in clinical trials. Patients on everolimus should be closely monitored for infections, especially those receiving it for several months.
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Everolimus/efectos adversos , Inmunosupresores/efectos adversos , Tumores Neuroendocrinos/tratamiento farmacológico , Infecciones Oportunistas/etiología , Adulto , Anciano , Anciano de 80 o más Años , Everolimus/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Recent studies indicate an association between immunosuppression for immune-related adverse events (irAEs) and impaired survival in patients who received immune checkpoint inhibitors. Whether this is related to corticosteroids or second-line immunosuppressants is unknown. In the largest cohort thus far, we assessed the association of immunosuppressant type and dose with survival in melanoma patients with irAEs. METHODS: Patients with advanced melanoma who received immunosuppressants for irAEs induced by first-line anti-PD-1 ± anti-CTLA-4 were included from 18 hospitals worldwide. Associations of cumulative and peak dose corticosteroids and use of second-line immunosuppression with survival from start of immunosuppression were assessed using multivariable Cox proportional hazard regression. RESULTS: Among 606 patients, 404 had anti-PD-1 + anti-CTLA-4-related irAEs and 202 had anti-PD-1-related irAEs. 425 patients (70 %) received corticosteroids only; 181 patients (30 %) additionally received second-line immunosuppressants. Median PFS and OS from starting immunosuppression were 4.5 (95 %CI 3.4-8.1) and 31 (95 %CI 15-not reached) months in patients who received second-line immunosuppressants, and 11 (95 %CI 9.4-14) and 55 (95 %CI 41-not reached) months in patients who did not. High corticosteroid peak dose was associated with worse PFS and OS (HRadj 1.14; 95 %CI 1.01-1.29; HRadj 1.29; 95 %CI 1.12-1.49 for 80vs40mg), while cumulative dose was not. Second-line immunosuppression was associated with worse PFS (HRadj 1.32; 95 %CI 1.02-1.72) and OS (HRadj 1.34; 95 %CI 0.99-1.82) compared with corticosteroids alone. CONCLUSIONS: High corticosteroid peak dose and second-line immunosuppressants to treat irAEs are both associated with impaired survival. While immunosuppression is indispensable for treatment of severe irAEs, clinicians should weigh possible detrimental effects on survival against potential disadvantages of undertreatment.
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Corticoesteroides , Inhibidores de Puntos de Control Inmunológico , Inmunosupresores , Melanoma , Humanos , Masculino , Femenino , Melanoma/tratamiento farmacológico , Melanoma/inmunología , Melanoma/mortalidad , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Persona de Mediana Edad , Anciano , Corticoesteroides/uso terapéutico , Corticoesteroides/efectos adversos , Adulto , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Anciano de 80 o más AñosRESUMEN
Background: Nearly 30% of neuroendocrine tumors (NETs) have evidence of immunohistochemical (IHC) expression of estrogen (ER) and/or progesterone (PR) receptors. Therefore, targeting ER/PR may offer an effective NET-directed treatment to select patients. Methods: We conducted a multicenter Simon two-stage single-arm phase II trial of tamoxifen in patients with metastatic, progressive NETs. Eligible patients had positive IHC expression of ER and/or PR ⩾ 1%. Prior therapy with somatostatin analogs was required for progressing/functioning cases. Main exclusion criterion was aggressive disease requiring cytotoxic therapy. The primary end point was disease control rate (DCR) at week 24 by Response Evaluation Criteria in Solid Tumors version 1.1. We planned to enroll 23 patients in the first stage, to reach a DCR at week 24 of 70% (versus 50%); if ⩾12 patients reached the primary end point, a total of 37 would be included. Results: From February 2019 to February 2022, 23 out of 59 patients were eligible and enrolled: 15 (65%) were females; the most common sites were pancreas (11; 48%) and small bowel (6; 26%). In all, 13 patients (56.5%) had G2 NETs. At a median follow-up of 27 months, 13 patients (56.5%) had stable disease at week 24 and median progression-free survival (PFS) was 7.9 months [interquartile range (IQR): 3.7-12.1]. The best response was stable disease in 13 patients, with most patients experiencing minor tumor growth. Median PFS times were not significantly different according to ER/PR < or ⩾30% (p = 0.49) or ER versus PR expression (p = 0.19). One patient experienced grade 2 constipation. Conclusion: Tamoxifen for ER-/PR-positive NETs patients is safe but offers modest antitumor effects. Trial registry name: Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression (HORMONET). URL: https://clinicaltrials.gov/ct2/show/NCT03870399?term=03870399&draw=2&rank=1. Registration number: NCT03870399.
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Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.
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Mutación de Línea Germinal , Tumores Neuroendocrinos , Adulto Joven , Humanos , Mutación , Tumores Neuroendocrinos/genética , Tumores Neuroendocrinos/patología , Pérdida de Heterocigocidad , Predisposición Genética a la Enfermedad , Proteína de la Xerodermia Pigmentosa del Grupo DRESUMEN
The 2019 Word Health Organization (WHO) subclassified grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) into neuroendocrine carcinoma (NEC) or tumours (G3 NET) based on morphology and proliferation. Yet, few data exist on molecular profiles for G3 NEN. We compared clinicopathological and molecular characteristics of these two groups. We retrospectively reviewed consecutive G3 GEP NEN patients and had their tumour tissues reviewed, reclassified as per the WHO 2019, and analyzed by a next-generation sequencing (NGS) panel. Between 2000 and 2019, 43 patients had pathology revision: 29 (67%) were NEC and 14 (33%) were G3 NET, with a 23% change in diagnosis. Median overal survival for G3 NET and NEC patients was 55.6 and 11.9 months, respectively (hazard ratio = 2.78 [95% confidence interval = 1.09-7.11], p = .042), which was confirmed by an adjusted analysis (hazard ratio = 2.90 NEC vs. G3 NET; p = .03). NGS was performed in 32 cases: 21 NEC and 11 G3 NET. Mutations in RB1 and PTEN were exclusively encountered in NEC. Median tumour mutational burden was 5 (0-67) mutations per megabase in NEC and 4.5 (0-9) among G3 NET. Microsatellite instability was found in 3 (14.3%) NEC cases. In conclusion, pathology revision is essential to estimate prognosis and therapeutic plan. G3 GEP NEN generally harbour low tumor mutation burden and fewer actionable mutations, but 14% of NEC cases were microsatellite unstable and could benefit from immune checkpoint inhibitors.
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Neoplasias Gastrointestinales , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Humanos , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/tratamiento farmacológico , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: The standard treatment for localized squamous-cell carcinoma of the anal canal is definitive chemoradiotherapy. A meta-analysis of published studies conducted by our group showed significantly lower rates of disease-free survival (DFS) and overall survival at 3 years among HIV-positive patients. We aimed to compare detailed treatment outcomes between the groups of HIV-positive and -negative patients. PATIENTS AND METHODS: We performed a retrospective multicenter study of a comparative cohort of consecutive patients with histologic diagnosis of localized squamous-cell carcinoma of the anal canal who received definitive chemoradiotherapy. Patients' characteristics and outcomes were compared according to HIV status. The primary end points were time to complete response (CR) and DFS time. RESULTS: From June 2001 to September 2018, a total of 185 patients were included; 43 (30.2%) were HIV positive and 142 (69.8%) were HIV negative. The overall CR rates were 67.4% and 91.5% for HIV-positive and -negative patients, respectively (P < .001). The median follow-up was 47.8 months and the median time to experience CR was 7.8 months (95% confidence interval [CI], 5.7-10.5) for HIV-positive versus 4.89 months (95% CI, 4.54-5.25) for HIV-negative (P < .001) patients. The median DFS times were 79.7 months (95% CI, 56.8-102.6) and 127.9 months (95% CI, 112.6-143.2) for HIV-positive and -negative patients, respectively (P = .02). There was a trend toward greater grade 3/4 toxicity in the HIV-positive group. CONCLUSION: HIV-positive patients take longer to experience CR and present worse DFS. These findings have clinical implications because waiting longer to define CR among these patients may prevent unnecessary anorectal amputations.
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Neoplasias del Ano/terapia , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/estadística & datos numéricos , Infecciones por VIH/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/patología , Neoplasias del Ano/mortalidad , Argentina/epidemiología , Brasil/epidemiología , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Hyperactivation of mTOR pathway and angiogenesis have been implicated in the pathogenesis of neuroendocrine tumors (NETs). Everolimus, an oral inhibitor of mTOR, and sunitinib, an antiangiogenic drug, are effective targeted therapies approved to treat locally advanced/metastatic pancreatic neuroendocrine tumors (pNETs). Most pNETs are sporadic and mutations in genes involved directly or indirectly in mTOR pathway regulation have been implicated, including somatic mutation in MEN1 in 44% of cases. About 10% of pNETs can be part of hereditary syndromes, e.g., multiple endocrine neoplasia type 1 (MEN1) and Von-Hippel Lindau (VHL), and these patients are underrepresented in pivotal phase III trials. We hypothesized that everolimus would be particularly effective in patients with MEN1-associated pNETs. Likewise, we inferred that sunitinib would also be beneficial to patients with VHL-associated pNETs. METHODS: We conducted a multicenter retrospective and comparative study to assess the efficacy of everolimus and/or sunitinib in a cohort of patients with advanced pNETs with or without known MEN1 or VHL syndrome. The evaluation of the germline mutational status of VHL and MEN1 genes was retrospectively collected from the medical records. The primary endpoints were progression free survival (PFS) and time to treatment failure (TTF) of patients who received at least one month of sunitinib or everolimus in monotherapy. RESULTS: Thirty-three patients were identified from September 2009 to April 2018. Most were male 60.6%. Median Ki67 was 9%, liver metastases were present in 97%. The majority of tumors were non-functioning. Thirty-one patients received everolimus, of them 8 patients had germline mutations (6 in MEN1 and 2 in VHL genes). Nine patients received sunitinib, of them 3 had germline mutation (2 in MEN1 and 1 in VHL genes). In a median follow up of 26 months, among everolimus-treated patients, mTTF and mPFS were numerically superior in patients with germline mutations compared with those with sporadic pNETs (mTTF: 16.1 vs. 9.9 months, P=0.888; mPFS: 33.1 vs. 12.3 months, P=0.383). The disease control rate with everolimus was numerically higher in favor of germline mutated tumors compared to sporadic ones (87.5% vs. 68.4%). Sunitinib was used by 1 patient with VHL syndrome, achieving a PFS of 17.6 months. In the subgroup of sporadic pNETs, sunitinib was used by 6 patients reaching a mPFS of 18 months (range, 5-25 months), predominantly in second line. CONCLUSIONS: Our study suggests that everolimus may offer a prolonged tumor control in pNETS with germline mutations (MEN1 or VHL) compared to sporadic ones. The small number of patients and the retrospective nature of this study precludes any definitive conclusions.
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The background to this study was that factors associated with carcinoid heart disease (CHD) and its impacts on overall survival (OS) are scantly investigated in patients (pts) with neuroendocrine tumors (NETs). In terms of materials and methods, a retrospective multicenter cohort study was conducted of factors associated with CHD in advanced NET pts with carcinoid syndrome (CS) and/or elevated urinary 5-hidroxyindole acetic acid (u5HIAA). CHD was defined as at least moderate right valve alterations. The results were the following: Among the 139 subjects included, the majority had a midgut NET (54.2%), 81.3% had CS, and 93% received somatostatin analogues. In a median follow-up of 39 months, 48 (34.5%) pts developed CHD, with a higher frequency in pts treated in public (77.2%) versus private settings (22.9%). In a multivariate logistic regression, unknown primary or colorectal NETs (Odds Ratio (OR) 4.35; p = 0.002), at least 50% liver involvement (OR 3.45; p = 0.005), and being treated in public settings (OR 4.76; p = 0.001) were associated with CHD. In a Cox multivariate regression, bone metastases (Hazard Ratio {HR} 2.8; p = 0.031), CHD (HR 2.63; p = 0.038), and a resection of the primary tumor (HR 0.33; p = 0.026) influenced the risk of death. The conclusions were the following: The incidence of CHD was higher in pts with a high hepatic tumor burden and in those treated in a public system. Delayed diagnosis and limited access to effective therapies negatively affected the lives of NET patients.
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The objective of this study was to evaluate the role of urolithiasis, infection, and bladder dysfunction in the pathogenesis of renal failure in rats subjected to supratrigonal cystectomy. One group of Sprague-Dawley rats was submitted to supratrigonal cystectomy, a second to cystectomy during which a suspension of Proteus mirabilis was injected into the bladder stump, and a third to sham surgery (controls). The animals were sacrificed two months after surgery. Blood pressure and serum urea and creatinine were measured before surgery and at sacrifice when a careful inspection of the urinary tract was performed to determine the presence of hydronephrosis and calculi. Microbiological analyses were performed on urine aspirated from the bladder and on the kidneys. Significant differences were found between values of systolic blood pressure and serum urea and creatinine recorded prior to the surgical procedure and those recorded at sacrifice in each group except the control group. Renal failure was present in all animals subjected to cystectomy. Urinary calculi were documented in 5/10 animals subjected to cystectomy only and in all rats inoculated with P. mirabilis. Hypertension was documented in 43.75% of animals subjected to cystectomy. Pyelonephritis was diagnosed only in animals with urinary calculi, in each of which urine culture was also positive. No cases of renal failure, hypertension, calculi, and/or pyelonephritis were detected in the sham group. The findings of this study indicate that kidney failure in rats subjected to supratrigonal cystectomy is related to the severe bladder dysfunction induced by the surgical procedure.
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Cistectomía , Insuficiencia Renal/etiología , Vejiga Urinaria/fisiopatología , Cálculos Urinarios/complicaciones , Animales , Pielonefritis/fisiopatología , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal/fisiopatología , Cálculos Urinarios/fisiopatologíaRESUMEN
Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
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Although urinary tract infections (UTI) represent the most common infection caused by enterococci, some aspects remain to be fully clarified. The aim of this study was to determine the clinical characteristics present in UTI caused by Enterococcus spp. in patients followed up at the Prof. Edgard Santos Teaching Hospital of the Federal University of Bahia. All patients consecutively examined between 1997 and 2005, who received a diagnosis of UTI caused by Enterococcus spp. were included in the study. UTI was defined as the presence of > or = 10(5) colony-forming units per mL of urine. Standard microbiological techniques were used. During the study period, 6.2% of the urine cultures were positive for Enterococcus spp. The mean age of the patients was 48.9 years and 57% were male. At initial evaluation, 13% of the patients had complaints suggestive of UTI. Nineteen patients had a history consistent with obstructive uropathy and 26 with neurogenic bladder. At final evaluation, UTI was the diagnosis in 48 patients. In 36 patients (29%), the primary diagnosis was related to urogenital diseases, consisting of obstructive uropathy in 23 of these cases, while in 32 patients (25.8%) primary diagnosis was related to neurologic diseases, frequently neurogenic bladder. UTI caused by Enterococcus spp. is not infrequent, is usually associated with few or no symptoms and occurs in sick patients who have anatomical or functional obstructive uropathy associated or not with urinary tract catheterization or instrumentation. The diagnosis of enterococcal UTI may indicate a urinary tract abnormality yet to be diagnosed.
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Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones Urinarias/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Recuento de Colonia Microbiana , Enterococcus/efectos de los fármacos , Femenino , Infecciones por Bacterias Grampositivas/diagnóstico , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Infecciones Urinarias/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: The present study aims at assessing the occurrence of pyelonephritis and long-term complications in rats submitted to surgical reduction of bladder capacity. MATERIALS AND METHODS: Sprague-Dawley rats were submitted to supratrigonal cystectomy (animals) or sham operation ( animals) and sacrificed 2, 4 and 6 months after the surgical procedure. The arterial blood pressure and serum creatinine levels were assessed before the surgery and at the time of the sacrifice. After the sacrifice a careful inspection of the urinary apparatus was performed to the characterization of the hydronephrosis and for the detection of the presence of calculi. With sterile technique, the urine was aspirated from the bladder and the kidneys removed and sent to a microbiologic study. RESULTS: Pyelonephritis was frequent in animals submitted to supratrigonal cystectomy. The most frequent and isolated microorganisms were Staphylococcus sp. and E. coli. The presence of urinary calculi was correlated significantly to the presence of urinary tract infection (p < 0.003). Arterial hypertension was frequent amongst animals submitted to supratrigonal cystectomy. Serum creatinine was high in 72.4% of the animals in the group submitted to supratrigonal cystectomy. The presence of calculi and pyelonephritis were frequent in rats presenting renal insufficiency and in hypertensive rats. CONCLUSIONS: The long-term course of urinary infection in rats submitted to supratrigonal cystectomy was characterized by a high incidence of renal insufficiency and arterial hypertension that seem to be related to dysfunction and bladder obstruction induced by an extensive surgical procedure and the presence of urolithiasis and pyelonephritis.
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Cistectomía/efectos adversos , Hipertensión/etiología , Enfermedades Urológicas/etiología , Animales , Modelos Animales de Enfermedad , Masculino , Complicaciones Posoperatorias , Pielonefritis/etiología , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal/etiología , Factores de Tiempo , Cálculos Urinarios/etiología , Infecciones Urinarias/etiologíaRESUMEN
OBJECTIVE: To assess the results of an upper pole nephrectomy technique on 5 children. MATERIALS AND METHODS: Upper pole nephrectomy was performed on 5 children, including 4 females and 1 male. Age ranged from 3 to 6 years old. The technique was performed without initial dissection of the renal pedicle. The upper pole is incised and removed. Upon its complete dissection, the segment that drains the upper pole is easily identified, clamped and sectioned. RESULTS: Three children with ureterocele and 2 with ectopic ureter underwent this procedure. There was no intra- or postoperative complication with this technique. DSMA scintigraphy showed no decrease in renal function in the remaining kidney following the procedure. CONCLUSION: The polar nephrectomy technique is simple, and has the advantage of not approaching the renal hilum, which makes surgery less laborious and prevents risk of renal damage, hemorrhage and decreased function in the remaining renal portion.
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Riñón/anomalías , Riñón/cirugía , Nefrectomía/métodos , Niño , Preescolar , Femenino , Humanos , Masculino , Resultado del Tratamiento , Ureterocele/etiologíaRESUMEN
Although urinary tract infections (UTI) represent the most common infection caused by enterococci, some aspects remain to be fully clarified. The aim of this study was to determine the clinical characteristics present in UTI caused by Enterococcus spp. in patients followed up at the Prof. Edgard Santos Teaching Hospital of the Federal University of Bahia. All patients consecutively examined between 1997 and 2005, who received a diagnosis of UTI caused by Enterococcus spp. were included in the study. UTI was defined as the presence of 10(5) colony-forming units per mL of urine. Standard microbiological techniques were used. During the study period, 6.2 percent of the urine cultures were positive for Enterococcus spp. The mean age of the patients was 48.9 years and 57 percent were male. At initial evaluation, 13 percent of the patients had complaints suggestive of UTI. Nineteen patients had a history consistent with obstructive uropathy and 26 with neurogenic bladder. At final evaluation, UTI was the diagnosis in 48 patients. In 36 patients (29 percent), the primary diagnosis was related to urogenital diseases, consisting of obstructive uropathy in 23 of these cases, while in 32 patients (25.8 percent) primary diagnosis was related to neurologic diseases, frequently neurogenic bladder. UTI caused by Enterococcus spp. is not infrequent, is usually associated with few or no symptoms and occurs in sick patients who have anatomical or functional obstructive uropathy associated or not with urinary tract catheterization or instrumentation. The diagnosis of enterococcal UTI may indicate a urinary tract abnormality yet to be diagnosed.
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Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Enterococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones Urinarias/microbiología , Recuento de Colonia Microbiana , Enterococcus/efectos de los fármacos , Infecciones por Bacterias Grampositivas/diagnóstico , Hospitales Universitarios , Infecciones Urinarias/diagnóstico , Adulto JovenRESUMEN
OBJECTIVES: To determine the prevalence of prostate cancer and to assess potential associations between race and prostate adenocarcinoma according to age in patients followed in an outpatient service of general urology in an university hospital. MATERIALS AND METHODS: Retrospective study of men aged from 40 to 79 years, followed during the period from 1999 to 2001. Patients were classified according to race in White, Mulatto and Black. Those with abnormal digital rectal examination and/or serum level of prostate specific antigen (PSA) > 4.0 ng/ml, underwent a transrectal prostate biopsy. RESULTS: 580 patients with mean age of 60.7 +/- 10.0 years were studied, with 116 Whites (20.0%), 276 Mulattos (47.6%) and 188 Blacks (32.4%). There was no significant difference regarding the mean age (p = 0.62), serum level of PSA (p = 0.65) and prevalence of prostate adenocarcinoma between Whites, Mulattos and Blacks (p = 0.36). While studying the association between race classified in 2 groups (Whites versus Mulattos and Blacks) and prostate adenocarcinoma according to age, no association was found when the total group was assessed, neither among those with age above 60 years old. In the group between 40 and 60 years, even though without statistical significance, the estimate of prevalence ratio was 2.2 (CI 95%: 0.52 to 9.0; p = 0.38). CONCLUSION: Prostate adenocarcinoma was found in 16.6% of the patients aged between 40 and 79 years. We did not find a racial influence in our population.
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PURPOSE: Children with lower urinary tract dysfunction and vesicoureteral reflux, at cystography assessment, frequently present alterations in the lower urinary tract anatomy such as dilated posterior urethra, irregularity of the bladder wall and diverticula. However, the significance of these findings is unknown. The objective of this study is to evaluate the incidence of these findings, their time of disappearance and their correlation with the severity of the reflux. MATERIALS AND METHODS: 193 children with vesicoureteral reflux, considered simple, in the age group above 5 years at the moment of diagnosis, were analyzed. The recommendation for follow-up of these patients was one voiding cystoureterography (VCUG) each year. Only patients with a minimum of 2 VCUGs performed in a period of at least 6 months were considered. The VCUGs were classified as positive and negative in relation to findings that were characteristic of lower urinary tract dysfunction (LUTD). RESULTS: From the 193 children analyzed, 50 (26%) presented positive VCUG and 143 negative VCUG. From the patients without symptoms of lower urinary tract dysfunction (n = 135), 12 (9%) presented positive VCUG and 123 (91%) a negative VCUG. From the patients with negative VCUG, 68 (48%) presented unilateral reflux and 75 (52%) presented bilateral reflux. From those with positive VCUG, 26 (52%) had unilateral reflux and 24 bilateral reflux (48%). This difference was not statistically significant. A higher incidence of grade II reflux was more evident in patients with negative VCUG and degree III in patients with positive VCUG (p < 0.05). CONCLUSIONS: Our study demonstrated that 64% of the patients with LUTD and reflux presented findings in the VCUG that suggest dysfunction.
Asunto(s)
Uretra/fisiopatología , Vejiga Urinaria/fisiopatología , Reflujo Vesicoureteral/fisiopatología , Niño , Dilatación Patológica , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: The present study aims at assessing the occurrence of pyelonephritis and long-term complications in rats submitted to surgical reduction of bladder capacity. MATERIALS AND METHODS: Sprague-Dawley rats were submitted to supratrigonal cystectomy (29 animals) or sham operation (15 animals) and sacrificed 2, 4 and 6 months after the surgical procedure. The arterial blood pressure and serum creatinine levels were assessed before the surgery and at the time of the sacrifice. After the sacrifice a careful inspection of the urinary apparatus was performed to the characterization of the hydronephrosis and for the detection of the presence of calculi. With sterile technique, the urine was aspirated from the bladder and the kidneys removed and sent to a microbiologic study. RESULTS: Pyelonephritis was frequent in animals submitted to supratrigonal cystectomy. The most frequent and isolated microorganisms were Staphylococcus sp. and E. coli. The presence of urinary calculi was correlated significantly to the presence of urinary tract infection (p < 0.003). Arterial hypertension was frequent amongst animals submitted to supratrigonal cystectomy. Serum creatinine was high in 72.4 percent of the animals in the group submitted to supratrigonal cystectomy. The presence of calculi and pyelonephritis were frequent in rats presenting renal insufficiency and in hypertensive rats. CONCLUSIONS: The long-term course of urinary infection in rats submitted to supratrigonal cystectomy was characterized by a high incidence of renal insufficiency and arterial hypertension that seem to be related to dysfunction and bladder obstruction induced by an extensive surgical procedure and the presence of urolithiasis and pyelonephritis.