RESUMEN
Liver and liver/kidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF. Differently, biomarkers of mitochondrial dysfunction (lactate, alanine, and related ratios) significantly decreased in CSF. Neurocognitive evaluation documented significant higher post-transplant developmental/cognitive scores and maturation of executive functions corresponding to improvement of brain atrophy, cortical thickness, and white matter maturation indexes at MRI. Three patients presented post-transplantation reversible neurological events, which were differentiated, by means of biochemical and neuroradiological evaluations, into calcineurin inhibitor-induced neurotoxicity and metabolic stroke-like episode. Our study shows that transplantation has a beneficial impact on neurological outcome in methylmalonic aciduria. Early transplantation is recommended due to the high risk of long-term complications, high disease burden, and low quality of life.
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Errores Innatos del Metabolismo de los Aminoácidos , Trasplante de Hígado , Humanos , Calidad de Vida , Biomarcadores , Ácido Láctico , Ácido MetilmalónicoRESUMEN
We retrospectively compared long-term biochemical recurrence rates (BCR) in pN1 PCa patients that underwent adjuvant radiotherapy (aRT) vs. no aRT/early salvage (esRT) after robot-assisted radical prostatectomy and extended pelvic lymphadenectomy. All PCa pN1 M0 patients treated at a single high-volume center between 2010 and 2020 were analyzed. Patients with <10 LNs yield, or >10 positive LNs, or persistently detectable PSA after RARP were excluded. Kaplan-Meier (KM) plots depicted BCR rates. Multivariable Cox regression models (MCRMs) focused on predictors of BCR. The cumulative incidence plot depicted BCR rates after propensity score (PS) matching (ratio 1:1). 220 pN1 patients were enrolled, 133 (60.4%) treated with aRT and 87 (39.6%) with no-aRT/esRT. aRT patients were older, with higher rates of postoperative ISUP grade group 4-5, and higher rates of pT3b stage. The actuarial BCR was similar (aRT 39.8% vs. no-aRT/esRT 40.2%; p=1). Median time to BCR was 62 vs. 38 months in aRT vs. no-aRT/esRT patients (p=0.001). In MCRMs, patients managed with no-aRT/esRT were associated with higher rates of BCR over time (hazard ratio [HR]: 3.27, p<0.001). ISUP grade group 5 (HR: 2.18, p<0.01) was an independent predictor of BCR. In PS-matched cumulative incidence plots, the BCR rate was significantly higher in the aRT group (76.4 vs. 40.4%; p<0.01). Patients managed with no-aRT/esRT experienced BCR approximately two years before the aRT group. Despite, the important BCR benefit after aRT, this treatment strategy is underused in daily practice.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Terapia Recuperativa/efectos adversos , Radioterapia Adyuvante , Prostatectomía/efectos adversos , Recurrencia Local de Neoplasia/cirugíaRESUMEN
Children are prone to bloodstream infections (BSIs), the rapid and accurate diagnosis of which is an unmet clinical need. The T2MR technology is a direct molecular assay for identification of BSI pathogens, which can help to overcome the limits of blood culture (BC) such as diagnostic accuracy, blood volumes required, and turnaround time. We analyzed results obtained with the T2Bacteria (648) and T2Candida (106) panels in pediatric patients of the Bambino Gesù Children's Hospital between May 2018 and September 2020 in order to evaluate the performance of the T2Dx instrument with respect to BC. T2Bacteria and T2Candida panels showed 84.2% and 100% sensitivity with 85.9% and 94.1% specificity, respectively. The sensitivity and specificity of the T2Bacteria panel increased to 94.9% and 98.7%, respectively, when BC was negative but other laboratory data supported the molecular result. T2Bacteria sensitivity was 100% with blood volumes <2 mL in neonates and infants. T2Bacteria and T2Candida provided definitive microorganism identification in a mean time of 4.4 and 3.7 h, respectively, versus 65.7 and 125.5 h for BCs (P < 0.001). T2 panels rapidly and accurately enable a diagnosis of a pediatric BSI, even in children under 1 year of age and for very small blood volumes. These findings support their clinical use in life-threatening pediatric infections, where the time to diagnosis is of utmost importance, in order to improve survival and minimize the long-term sequalae of sepsis. The T2 technology could be further developed to include more bacteria and fungi species that are involved in the etiology of sepsis.
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Micosis , Sepsis , Recién Nacido , Humanos , Niño , Cultivo de Sangre/métodos , Espectroscopía de Resonancia Magnética/métodos , Bacterias , Sepsis/diagnóstico , TecnologíaRESUMEN
OBJECTIVES: To assess upgrading rates in patients on active surveillance (AS) for prostate cancer (PCa) after serial multiparametric magnetic resonance imaging (mpMRI). METHODS: We conducted a retrospective analysis of 558 patients. Five different criteria for mpMRI progression were used: 1) a Prostate Imaging Reporting and Data System (PI-RADS) score increase; 2) a lesion size increase; 3) an extraprostatic extension score increase; 4) overall mpMRI progression; and 5) the number of criteria met for mpMRI progression (0 vs 1 vs 2-3). In addition, two definitions of PCa upgrading were evaluated: 1) International Society of Urological Pathology Grade Group (ISUP GG) ≥2 with >10% of pattern 4 and 2) ISUP GG ≥ 3. Estimated annual percent changes methodology was used to show the temporal trends of mpMRI progression criteria. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI progression criteria were also analysed. Multivariable logistic regression models tested PCa upgrading rates. RESULTS: Lower rates over time for all mpMRI progression criteria were observed. The NPV of serial mpMRI scans ranged from 90.5% to 93.5% (ISUP GG≥2 with >10% of pattern 4 PCa upgrading) and from 98% to 99% (ISUP GG≥3 PCa upgrading), depending on the criteria used for mpMRI progression. A prostate-specific antigen density (PSAD) threshold of 0.15 ng/mL/mL was used to substratify those patients who would be able to skip a prostate biopsy. In multivariable logistic regression models assessing PCa upgrading rates, all five mpMRI progression criteria achieved independent predictor status. CONCLUSION: During AS, approximately 27% of patients experience mpMRI progression at first repeat MRI. However, the rates of mpMRI progression decrease over time at subsequent mpMRI scans. Patients with stable mpMRI findings and with PSAD < 0.15 ng/mL/mL could safely skip surveillance biopsies. Conversely, patients who experience mpMRI progression should undergo a prostate biopsy.
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Próstata , Neoplasias de la Próstata , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Clasificación del Tumor , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Espera VigilanteRESUMEN
We describe a 9-year-old boy with acute liver failure of unknown etiology, unresponsive to standard medical therapy, with increasing hyperammonemia blood level, lactate elevation, a pediatric end liver stage of 20, a hepatic encephalopathy (HE) score of 2, and scheduled for emergent liver transplantation on the waiting list. We admitted him in the pediatric intensive care unit and managed him in the early stages with continuous renal replacement therapy and therapeutic plasma exchange as soon as neurologic impairment started to worsen. He recovered from his HE after 3 days of blood purification and was removed from the transplantation waiting list due to progressive liver function improvement.
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Terapia de Reemplazo Renal Híbrido , Fallo Hepático Agudo/terapia , Hígado/patología , Niño , Encefalopatía Hepática/complicaciones , Encefalopatía Hepática/patología , Encefalopatía Hepática/terapia , Humanos , Terapia de Reemplazo Renal Híbrido/métodos , Hiperamonemia/complicaciones , Hiperamonemia/patología , Hiperamonemia/terapia , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/patología , Masculino , Intercambio Plasmático/métodosRESUMEN
We describe a 2 weeks corrected gestational age infant admitted in pediatric intensive care unit (PICU) for severe acute respiratory distress syndrome (ARDS) associated to Bordetella pertussis and Coronavirus infection. He developed leukocytosis as soon as ARDS required intubation and aggressive mechanical ventilation: hence he underwent 3 early therapeutic leukapheresis treatments in order to avoid the worsening of related cardiopulmonary complications, according to recent literature on pertussis infection in infants. The infant was discharged from PICU healthy.
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Bordetella pertussis/aislamiento & purificación , Coinfección/complicaciones , Infecciones por Coronavirus/complicaciones , Coronavirus/aislamiento & purificación , Leucaféresis , Leucocitosis/terapia , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Tos Ferina/complicaciones , Coinfección/sangre , Coinfección/microbiología , Coinfección/virología , Terapia Combinada , Presión de las Vías Aéreas Positiva Contínua , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/virología , Humanos , Lactante , Leucocitosis/etiología , Masculino , Respiración Artificial , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Tos Ferina/sangreRESUMEN
OBJECTIVES: To evaluate whether low PI-RADS v2 assessment categories are effective at excluding extraprostatic extension (EPE) of prostate cancer (≥pT3a PCa). METHODS: The local institutional ethics committee approved this retrospective analysis of 301 consecutive PCa patients. Patients were classified as low- or intermediate/high-risk based on clinical parameters and underwent pre-surgical multiparametric magnetic resonance imaging. A PI-RADS v2 assessment category and ESUR EPE score were assigned for each lesion by two readers working in consensus. Histopathologic analysis of the whole-mount radical prostatectomy specimen was the reference standard. Univariate and multivariate analyses were performed to evaluate the association of PI-RADS v2 assessment category with final histology ≥pT3a PCa. RESULTS: For a PI-RADS v2 assessment category threshold of 3, the overall performance for ruling out (sensitivity, negative predictive value, negative likelihood ratio) ≥pT3a PCa was 99%/98%/0.04 and was similar in both the low-risk (96%/97%/0.12; N = 137) and the intermediate/high-risk groups (100%/100%/0.0; N = 164). In univariate analysis, all clinical and tumor characteristics except age were significantly associated with ≥pT3a PCa. In multivariate analysis, PI-RADS v2 assessment categories ≤ 3 had a protective effect relative to categories 4 and 5. The inclusion of ESUR EPE score improved the AUC of ≥pT3a PCa prediction (from 0.73 to 0.86, p = 0.04 in the overall cohort). The impact of PI-RADS v2 assessment category is reflected in a nomogram derived on the basis of our cohort. CONCLUSIONS: In our cohort, low PI-RADS v2 assessment categories of 3 or less confidently ruled out the presence of ≥pT3a PCa irrespective of clinical risk group. KEY POINTS: ⢠Our analysis of 301 mp-MRI and RARP specimens showed that the addition of PI-RADS v2 assessment categories to clinical parameters improves the exclusion of ≥pT3a (extraprostatic) prostate cancer. ⢠PI-RADS v2 assessment categories of 1 to 3 are useful for excluding ≥pT3a prostate cancer with a NPV of 98%; such patients can be considered as candidates for less invasive approaches. ⢠The ability to exclude ≥pT3a prostate cancer may improve confidence in choosing nerve-sparing surgery or in avoiding pelvic nodal dissections, and similarly for patients undergoing radiotherapy, in adopting short-course adjuvant hormonal therapy or foregoing prophylactic nodal irradiation.
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Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Anciano , Biopsia , Estudios de Cohortes , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Nomogramas , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Several biochemical and clinical markers have been proposed for selecting patients for active surveillance (AS). However, some of these are expensive and not easily accessible. Moreover, currently about 30% of patients on AS harbor aggressive disease. Hence, there is an urgent need for other tools to accurately identify patients with low-risk prostate cancer (PCa). PATIENTS: We retrospectively reviewed the medical records of 260 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/mL, 2 or fewer cores involved with cancer, Gleason score (GS) ≤6 grade, and prostate-specific antigen density < 0.2 ng/mL/cc. METHODS: Univariate and multivariate analyses were performed to evaluate the association of patient and tumor characteristics with reclassification, defined as upstaged (pathological stage >pT2) and upgraded (GS ≥7) disease. A base model (age, prostate-specific antigen, prostate volume, and clinical stage) was compared with models considering neutrophil to lymphocyte ratio (NLR) or platelets to lymphocyte ratio (PLR), monocyte to lymphocyte (MLR), and eosinophil to lymphocyte ratio (ELR). OR and 95% CI were calculated. Finally, a decision curve analysis was performed. RESULTS: Univariate and multivariate analyses showed that NLR, PLR, and ELR upgrading were significantly associated with upgrading (ORs ranging from 2.13 to 4.13), but not with upstaging except for MLR in multivariate analysis, showing a protective effect. CONCLUSION: Our results showed that NLR, PLR, and ELR are predictors of Gleason upgrading. Therefore, these inexpensive and easily available tests might be useful in the assessment of low-risk PCa, when considering patients for AS.
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Plaquetas/citología , Eosinófilos/citología , Linfocitos/citología , Neutrófilos/citología , Neoplasias de la Próstata/sangre , Anciano , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Estadificación de Neoplasias , Próstata/patología , Antígeno Prostático Específico/sangre , Prostatectomía , Estudios Retrospectivos , RiesgoRESUMEN
Aims of this study were to assess sexual recovery after robotic-assisted radical prostatectomy (RARP) and to build a nomogram predicting 1-year sexual function. From May 2015 to July 2016, all patients eligible for RARP at our institution were invited to enter the study. The Expanded Prostate cancer Index Composite (EPIC) questionnaire was administered pre-operatively, then at 45 days, and at 3, 6, 9, and 12 months post-operatively. According to sexual function scores, patients were divided into four classes. Multivariate analysis was used to investigate the influence of patient- and disease-related features on sexual recovery. A total of 643 patients were included. Age was associated with baseline potency (p < .0001). Bioptic Gleason score (GS; p = .0002), American Society of Anesthesiologists (ASA) score ( = .002ASA Physical Status Classification System ) and Charlson Comorbidity Index (CCI; p = .02) were negatively associated with potency. Baseline sexual function was associated with potency recovery. A nomogram resulted from fitting a proportional odds logistic model for ordinal outcomes, with 1-year sexual function as a dependent variable and baseline sexual potency, age, body mass index (BMI), clinical stage, biopsy GS, initial prostate-specific antigen (iPSA), ASA score, and CCI as predictors. After further validation, this nomogram could be a useful tool for the pre-operative counselling.
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Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Recuperación de la Función/fisiología , Procedimientos Quirúrgicos Robotizados/métodos , Conducta Sexual/fisiología , Anciano , Estudios de Factibilidad , Humanos , Italia , Masculino , Persona de Mediana Edad , Nomogramas , Periodo Posoperatorio , Próstata/cirugía , Neoplasias de la Próstata/fisiopatología , Calidad de Vida , Encuestas y Cuestionarios/estadística & datos numéricos , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the oncological and functional outcomes of patients diagnosed with penile cancer undergoing conservative treatment through thulium-yttrium-aluminium-garnet (Tm:YAG) laser ablation. METHODS: Twenty-six patients with a penile lesion underwent ablation with a RevoLix 200 W continuous-wave laser. The procedure was carried out with a pen-like laser hand piece, using a 360 µm laser fiber and 15-20 W of power. Median (IQR) follow-up time was 24 (15-30) months. Recurrence rate and post-operative sexual function were assessed. RESULTS: Median age at surgery was 61 years. Median (inter quartile range) size of the lesions was 15 [10-20] mm. Overall, 11 (47.8%) and 12 (52.2%) at the final pathology presented in situ and invasive squamous cell carcinoma (SCC), respectively. The final pathological stage was pTis, pT1a, pT2, and pT3 in 11 (47.8%), 7 (30.4%), 3 (13.0%), and 2 (8.7%) patients, respectively. Moreover, four (17.4%) patients had a recurrence of which three (13.0%) and one (4.3%) patients developed an invasive or in situ recurrence, respectively. After treatment 6 (26.1%) patients reported a conserved penile sensitivity, while 13 (56.5%) and 4 (17.4%) patients experienced a better or worse sensitivity after ablation, respectively. Post-treatment sexual activity was achieved within the first month after laser ablation in 82.6% of the patients. CONCLUSION: Early stage penile carcinomas can be effectively treated with an organ preservation strategy. Tm:YAG conservative laser treatment is easy, safe and offers good functional outcome, with a minor impact on patient's quality of life.
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Carcinoma in Situ/cirugía , Carcinoma de Células Escamosas/cirugía , Terapia por Láser/métodos , Neoplasias del Pene/cirugía , Anciano , Aluminio , Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Erección Peniana , Neoplasias del Pene/patología , Calidad de Vida , Salud Sexual , Tulio , Resultado del Tratamiento , ItrioRESUMEN
BACKGROUND: To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification. MATERIALS: From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP. RESULTS: PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively. CONCLUSIONS: MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions.
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Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Próstata/diagnóstico por imagen , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Anciano , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Prospectivos , Próstata/patología , Neoplasias de la Próstata/patología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Ultrasonografía IntervencionalRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of the Virtue® male sling (Coloplast, Humlebaek, Denmark) in a cohort of patients affected by post-prostatectomy stress urinary incontinence (SUI). METHODS: All 29 consecutive patients treated with a Virtue male sling at our Institution between July 2012 and October 2013 were included in the present prospective, non-randomized study. Patients were evaluated preoperatively and at 1, 3, 6, 12, 24 and 36 months after surgery using a 24-h pad weight test, the International Consultation on Incontinence short-form questionnaire (ICIQ-SF), Urinary Symptom Profile (USP) questionnaire, a bladder diary, uroflowmetry and the Patient Global Impression of Improvement (PGI-I) and Patient Global Impression of Severity questionnaires. RESULTS: The mean patient age was 65.5 years. A total of 72.4% of patients had preoperative mild incontinence (1-2 pads/day), while nine patients used 3-5 pads/day. There were a total of 17 complications, which occurred in 29 patients (58.6%); all were Clavien-Dindo grade I. At 12-month follow-up patients showed a significant improvement in 24-h pad test (128.6 vs 2.5 g), number of pads per day (2 vs 0), ICIQ-SF score (14.3 vs 0.9) and USP score for SUI (4 vs 0), and outcomes remained stable at 36 months. At last follow-up, the median score on the PGI-I questionnaire was 1 (very much better). CONCLUSION: The Virtue male sling is an effective treatment option for low to moderate post-prostatectomy incontinence.
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Complicaciones Posoperatorias/cirugía , Prostatectomía , Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Anciano , Humanos , Masculino , Estudios Prospectivos , Diseño de Prótesis , Cabestrillo Suburetral/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Single limb stance instability is a risk factor for lower extremity injuries. Therefore, the development of proprioception may play an important role in injury prevention. This investigation considered a professional basketball team for 6 years, integrating systematic proprioceptive activity in the training routine. The purpose was to assess the effectiveness of proprioceptive training programs based on quantifiable instability, to reduce ankle sprains, knee sprains, and low back pain through developing refined and long-lasting proprioceptive control. Fifty-five subjects were studied. In the first biennium (2004-2006), the preventive program consisted of classic proprioceptive exercises. In the second biennium (2006-2008), the proprioceptive training became quantifiable and interactive by means of electronic proprioceptive stations. In the third biennium (2008-2010), the intensity and the training volume increased while the session duration became shorter. Analysis of variance was used to analyze the differences in proprioceptive control between groups, years, and bienniums. Injury rates and rate ratios of injury during practices and games were estimated. The results showed a statistically significant reduction in the occurrence of ankle sprains by 81% from the first to the third biennium (p < 0.001). Low back pain showed similar results with a reduction of 77.8% (p < 0.005). The reduction in knee sprains was 64.5% (not significant). Comparing the third biennium with the level of all new entry players, proprioceptive control improved significantly by 72.2% (p < 0.001). These findings indicate that improvements in proprioceptive control in single stance may be a key factor for an effective reduction in ankle sprains, knee sprains, and low back pain.
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Traumatismos en Atletas/prevención & control , Baloncesto/lesiones , Terapia por Ejercicio/métodos , Propiocepción , Adolescente , Adulto , Traumatismos del Tobillo/etiología , Traumatismos del Tobillo/prevención & control , Estudios de Seguimiento , Humanos , Italia , Traumatismos de la Rodilla/etiología , Traumatismos de la Rodilla/prevención & control , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/prevención & control , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Esguinces y Distensiones/etiología , Esguinces y Distensiones/prevención & control , Resultado del Tratamiento , Adulto JovenRESUMEN
Islet transplantation is a poorly investigated long-term strategy for insulin replacement and for treatment of complications in patients with diabetes. We investigated whether islet transplantation and insulin treatment can relieve diabetic neuropathy and rescue the residual endogenous pancreatic ß cells. We used a multimodal approach, with five groups of Sprague-Dawley rats studied for 8 months: control rats, diabetic rats, insulin-treated diabetic rats with moderate or mild hyperglycemia, and diabetic rats transplanted with microencapsulated islets. Islet transplantation normalized glycemia and increased body and muscle weight; it was also effective in reducing proteinuria and altered liver function. Transplantation significantly improved tail nerve conduction velocity, Na(+)-K(+)-ATPase activity, and morphological alterations in the sciatic nerve as evidenced by decrease in g-ratio; it also restored thermal and ameliorated mechanical nociceptive thresholds. Morphometric analysis of pancreas indicated a significant ß-cell volume increase in transplanted rats, compared with mildly and moderately hyperglycemic rats. Thus, allogeneic islet transplantation had a positive systemic effect in diabetic rats and induced regression of the established neuropathy and restitution of the typical characteristics of the islets. These findings strongly reinforce the need for improving glycemic control, not only to reverse established diabetic complications but also to improve ß-cell status in diabetic pancreas.
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Complicaciones de la Diabetes/patología , Complicaciones de la Diabetes/terapia , Células Secretoras de Insulina/patología , Insulina/administración & dosificación , Trasplante de Islotes Pancreáticos , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/fisiopatología , Glucagón/metabolismo , Prueba de Tolerancia a la Glucosa , Hiperglucemia/complicaciones , Hiperglucemia/patología , Insulina/farmacología , Insulina/uso terapéutico , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/enzimología , Masculino , Conducción Nerviosa/efectos de los fármacos , Nocicepción/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Proteinuria/complicaciones , Proteinuria/patología , Ratas , Ratas Endogámicas Lew , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/patología , Nervio Ciático/fisiopatología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Adulto , Humanos , Carcinoma de Células Renales/genética , Mucina-1/genética , Mucinas , Antígenos de NeoplasiasRESUMEN
OBJECTIVE: To report oncological outcomes after thulium-yttrium-aluminum-garnet (Tm:YAG) laser ablation for penile cancer patients. MATERIALS AND METHODS: We retrospectively analyzed 71 patients with ≤cT1 penile cancer (2013-2022). All patients underwent Tm:YAG ablation with a RevoLix 200W continuous-wave laser. First, Kaplan-Meier plots and multivariable Cox regression models tested local tumor recurrence rates. Second, Kaplan-Meier plots tested progression-free survival (≥T3 and/or N1-3 and/or M1). RESULTS: Median (interquartile range) follow-up time was 38 (22-58) months. Overall, 33 (50.5%) patients experienced local tumor recurrence. Specifically, 19 (29%) vs 9 (14%) vs 5 (7.5%) patients had 1 vs 2 vs 3 recurrences over time. In multivariable Cox regression models, a trend for higher recurrence rates was observed for G3 tumors (hazard ratio:6.1; P = .05), relative to G1. During follow-up, 12 (18.5%) vs 4 (6.0%) vs 2 (3.0%) men were retreated with 1 vs 2 vs 3 Tm:YAG laser ablations. Moreover, 11 (17.0%) and 3 (4.5%) patients underwent glansectomy and partial/total penile amputation. Last, 5 (7.5%) patients experienced disease progression. Specifically, TNM stage at the time of disease progression was: (1) pT3N0; (2) pT2N2; (3) pTxN3; (4) pT1N1 and (5) pT3N3, respectively. CONCLUSION: Tm:YAG laser ablation provides similar oncological results as those observed by other penile-sparing surgery procedures. In consequence, Tm:YAG laser ablation should be considered a valid alternative for treating selected penile cancer patients.
Asunto(s)
Aluminio , Terapia por Láser , Láseres de Estado Sólido , Neoplasias del Pene , Itrio , Masculino , Humanos , Femenino , Neoplasias del Pene/cirugía , Tulio , Láseres de Estado Sólido/uso terapéutico , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Progresión de la EnfermedadRESUMEN
BACKGROUND: Multiple and heterogeneous techniques have been described for orthotopic neobladder (ONB) reconstruction after robot-assisted radical cystectomy. Nonetheless, a systematic assessment of all the available options is lacking. OBJECTIVE: To provide the first comprehensive step-by-step description of all the available techniques for robotic intracorporeal ONB together with individual intraoperative, perioperative and functional outcomes based on a systematic review of the literature. DESIGN, SETTING, AND PARTICIPANTS: We performed a systematic review of the literature, and MEDLINE/PubMed, Embase, Scopus, and Web of Science databases were searched to identify original articles describing different robotic intracorporeal ONB techniques and reporting intra- and perioperative outcomes. Studies were categorized according to ONB type, providing a synthesis of the current evidence. Video material was provided by experts in the field to illustrate the surgical technique of each intracorporeal ONB. SURGICAL PROCEDURE: Nine different ONB types were identified: Studer, Hautmann, Y shape, U shape, Bordeaux, Pyramid, Shell, Florence Robotic Intracorporeal Neobladder, and Padua Ileal Neobladder. MEASUREMENTS: Continuous and categorical variables are presented as mean ± standard deviation and as frequencies and proportions, respectively. RESULTS AND LIMITATIONS: Of 2587 studies identified, 19 met our inclusion criteria. No cohort studies or randomized control trials comparing different neobladder types are available. Available techniques for intracorporeal robotic ONB reconstruction have similar operative time, estimated blood loss, intraoperative complications, and length of stay. Major variability exists concerning postoperative complications and functional outcomes, likely related to reporting bias. CONCLUSIONS: Several techniques are described for intracorporeal ONB during robot-assisted radical cystectomy with comparable perioperative outcomes. We provide the first step-by-step surgical atlas for robot-assisted ONB reconstruction. Further comparative studies are needed to assess any advantage of one technique over others. PATIENT SUMMARY: Patients elected for radical cystectomy should be aware that multiple techniques for robotic orthotopic neobladder are available, but that current evidence does not favor one type over the others.