RESUMEN
Several microRNAs (miRNAs) have been identified as cell-free biomarkers for detecting renal cell carcinoma (RCC). Droplet digital polymerase chain reaction (ddPCR) is a unique technology for nucleic acid quantification. It has the potential for superior precision, reproducibility, and diagnostic performance in identifying circulating miRNA biomarkers compared to conventional quantitative real-time PCR (qRT-PCR). This study aims to evaluate the performance of ddPCR compared to qRT- PCR in identifying miRNA biomarkers that differentiate malignant from benign renal masses. Potential biomarkers of RCC were identified from a literature review. RNA was extracted from the plasma of 56 patients. All the samples underwent analysis via ddPCR as well as qRT-PCR, and expression levels were recorded for the following miRNAs: miR-93, -144, -210, -221, and -222. Tumors were grouped into low-grade ccRCC, high-grade ccRCC, papillary RCC, and benign masses (primarily angiomyolipoma). The miRNA miR-210 (p = 0.034) and the combination of miRs-210 and miR-222 (p = 0.003) were expressed at significantly higher rates among those with RCC than those with benign masses, as measured by ddPCR. Using the combination of miR-210 and miR-222, ddPCR identified significant differences between the subgroups: papillary RCC versus benign (p = 0.03), low-grade ccRCC versus benign (p = 0.026), and high-grade ccRCC versus benign (p = 0.002). The only significant difference between these subgroups using qRT-PCR was between high-grade ccRCC and benign (p = 0.045). All the AUCs were significant when comparing each RCC subgroup with benign for both PCR technologies. Using a combination of miR-210 and miR-222, ddPCR identified significant differences between benign and malignant renal masses that were not identified as significant by conventional qRT-PCR.
RESUMEN
Increased understanding of molecular pathophysiology has led to the detection of clinically applicable biomarkers across medicine, which allow for minimally invasive detection, management, and monitoring of disease processes. Although biomarkers have traditionally played a more significant role in malignancy, these goals also pertain to benign disease. Herein, the authors review ongoing research into biomarker investigation and application in urethral stricture disease, benign prostatic hyperplasia, bladder outlet obstruction, and overactive bladder. No biomarkers for these entities are currently in clinical use; however, numerous physiologic pathways provide targets for current and future study.
Asunto(s)
Estrechez Uretral , Vejiga Urinaria Hiperactiva , Humanos , Estrechez Uretral/diagnóstico , Constricción Patológica , BiomarcadoresRESUMEN
BACKGROUND: Rectourethral fistulas are a rare yet severe complication of prostate surgery, pelvic irradiation therapy, or both. Multiple surgical repairs exist with widely varying success rates. OBJECTIVE: This study aimed to present our institutional multidisciplinary algorithm for rectourethral fistula repair and its outcomes. DESIGN: This was a retrospective, pre- and postintervention, quasi-experimental design, comparing the frequency of fistula healing and reversal of urinary and fecal diversion before and after implementation of our algorithm. SETTING: All patients who presented to the Duke University with rectourethral fistula between 2002 and 2019 were included. PATIENTS: This study included 79 patients treated for rectourethral fistula: 36 prealgorithm and 43 postalgorithm. INTERVENTIONS: Our multidisciplinary algorithm was implemented in 2012. Patients with fistulas <2 cm and without history of radiation therapy underwent York-Mason repair, whereas those with fistulas 2-3 cm or with prior irradiation underwent transperineal repair with gracilis flap interposition. Those with nonrepairable fistulas (>3 cm or fixed tissues) underwent pelvic exenteration. Before repair, the algorithm recommended all patients to undergo urinary and bowel diversion. MAIN OUTCOME MEASURES: The 2 primary outcomes were rectourethral fistula healing, defined as both radiographic and clinical resolutions, and reversal of urinary and fecal diversions. RESULTS: Frequency of fistula healing improved in the post- versus prealgorithm subgroups (93.1% vs 71.9%; p = 0.04). The relative risk of fistula healing pre- versus postintervention was 0.77 (0.61-0.98; p = 0.04) among the overall cohort. Eighteen patients (22.8%) underwent pelvic exenteration for nonrepairable fistulas and were not included in primary outcome measures. LIMITATIONS: Limitations include the study's retrospective nature, possible selection bias because of algorithmic patient selection, and small sample size. CONCLUSIONS: Implementation of a multidisciplinary institutional algorithm improved rectourethral fistula repair success with high rates of ostomy reversal. Proper patient selection and multidisciplinary involvement are paramount to this success. See Video Abstract at http://links.lww.com/DCR/B955 . RESULTADOS DE UN ABORDAJE ALGORTMICO Y MULTIDISCIPLINARIO PARA LA REPARACIN DE FSTULAS RECTOURETRALES UN ESTUDIO CUASIEXPERIMENTAL PREVIO Y POSTERIOR A LA INTERVENCIN: ANTECEDENTES:Las fístulas rectouretrales son una complicación rara pero grave de la cirugía de próstata, la radiación pélvica o ambas. Existen múltiples reparaciones quirúrgicas con tasas de éxito muy variables.OBJETIVO:Presentar el algoritmo multidisciplinario de nuestra institución para la reparación de fístulas rectouretrales y sus resultados.DISEÑO:Este fue un diseño retrospectivo, previo y posterior a la intervención, cuasiexperimental, que comparó la frecuencia de curación de la fístula y la reversión de la derivación urinaria y fecal antes y después de la implementación de nuestro algoritmo.ESCENARIO:Se incluyeron todos los pacientes que acudieron a Duke con fístula rectouretral entre 2002 y 2019.PACIENTES:Setenta y nueve pacientes fueron tratados por fístula rectouretral; 36 pre-algoritmo y 43 post-algoritmo.INTERVENCIONES:Nuestro algoritmo multidisciplinario se implementó en 2012. Los pacientes con fístulas <2 cm y sin antecedentes de radiación se sometieron a reparación de York-Mason, mientras que aquellos con fístulas de 2-3 cm o radiación pélvica previa se sometieron a reparación transperineal con interposición de colgajo de gracilis. Aquellos con fístulas no reparables (> 3 cm o tejidos fijos) fueron sometidos a exenteración pélvica. Antes de la reparación, el algoritmo recomomendó que todos los pacientes se sometieran a una derivación urinaria y fecal.PRINCIPALES MEDIDAS DE RESULTADO:Los dos resultados primarios fueron la curación de la fístula rectouretral, definida como la resolución radiográfica y clínica, y la reversión de las derivaciones urinaria y fecale.RESULTADOS:La frecuencia de curación de la fístula mejoró en el subgrupo post-algoritmo vs. pre-algoritmo (93.1% vs. 71.9%, p = 0.04). El riesgo relativo de curación de la fístula antes de la intervención en comparación con después de la intervención fue de 0.77 (0.61-0.98, p = 0.04) entre la cohorte general. Dieciocho pacientes (22.8%) se sometieron a exenteración pélvica por fístulas no reparables y, por lo tanto, no se incluyeron en las medidas de resultado primarias.LIMITACIONES:Las limitaciones de este estudio incluyen su naturaleza retrospectiva, posible sesgo de selección debido a la selección algorítmica de pacientes y un tamaño de muestra pequeño.CONCLUSIONES:La implementación de un algoritmo institucional multidisciplinario mejoró el éxito en la reparación de la fístula rectouretral con altas tasas de reversión de la ostomía. La selección adecuada de pacientes y la participación multidisciplinaria son fundamentales para este éxito. Consulte Video Resumen en http://links.lww.com/DCR/B955 . (Traducción-Dr. Jorge Silva Velazco ).
Asunto(s)
Exenteración Pélvica , Fístula Rectal , Fístula Urinaria , Masculino , Humanos , Estudios Retrospectivos , Fístula Rectal/cirugía , Pelvis , Fístula Urinaria/etiología , Fístula Urinaria/cirugíaRESUMEN
OBJECTIVE: To investigate the impact of pelvic exenteration (PelvEX) on patient-reported pain, distress, and quality of life along with physiologic indicators of health in cancer survivors with radiated, non-repairable rectourethral fistula (RUF). MATERIALS AND METHODS: We reviewed a prospectively maintained quality improvement database of RUF patients at our institution from 2012 to 2020. Patients with radiated, non-repairable RUF who underwent PelvEX and had follow up to 1 year were included. Pain and distress scores were collected preoperatively and at 1-year follow up. Number of narcotic prescriptions in the 3 months before surgery and the year after surgery were abstracted. Short Form 12 surveys were administered in the postoperative period. Serum albumin, creatinine, carbon dioxide, hematocrit, and glucose were abstracted from electronic health records. Statistical analysis was performed using Wilcoxon signed-rank and Mann-Whitney tests. RESULTS: Eleven patients met inclusion criteria. Patient-reported pain significantly decreased at 1 year follow-up compared to preoperative scores (median pre: 4 vs 1 year post: 0, Pâ¯=â¯.0312). Patient-reported distress significantly decreased pre- versus post-PelvEX (median pre: 5 vs post: 0, Pâ¯=â¯.0156). At the time of postoperative pain and distress surveys, 9 (82.8%) patients did not have narcotic prescriptions. Postoperative Short Form 12 scores were similar to an age-matched United States population (mental: Pâ¯=â¯.3125; physical: Pâ¯=â¯.1484). Serum-based indicators of health were not different in the pre- versus postoperative period (all P >.05). CONCLUSION: PelvEX may be a valuable treatment option to decrease patient-reported pain and distress without compromising quality of life or physiologic health in patients with radiated, non-repairable RUF.
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Exenteración Pélvica , Fístula Rectal , Enfermedades Uretrales , Fístula Urinaria , Humanos , Narcóticos , Dolor Postoperatorio , Medición de Resultados Informados por el Paciente , Calidad de Vida , Fístula Rectal/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Enfermedades Uretrales/cirugía , Fístula Urinaria/cirugíaRESUMEN
PURPOSE: We evaluated the success of minimally invasive management of lichen sclerosus with topical and intraurethral clobetasol, as defined by improvement in patient reported outcome measures and nonprogression to surgery. MATERIALS AND METHODS: We conducted a review of our prospective ongoing quality improvement study to determine outcomes of our current standard practice for males with penile and urethral biopsy proven lichen sclerosus. Data were collected between 2011 and 2019, and included patient demographic information, medical and surgical histories, and location and extent of lichen sclerosus related pathology. The primary outcomes for this study were voiding function and voiding related quality of life, and were assessed using the AUASS (American Urological Association Symptom Score) and quality of life bother index, respectively. RESULTS: We identified 42 patients with biopsy proven lichen sclerosus related urethral stricture disease. Of these patients 85.7% were treated with intraurethral steroids alone and did not require surgical intervention. Median AUASS significantly improved from 12 to 8, and median quality of life bother index improved from 4 ("mostly dissatisfied") to 2 ("mostly satisfied"). Average stricture length of those with penile urethral disease and bulbar urethral disease was 4.8 cm (SD 3.0) and 16.2 cm (SD 6.5), respectively. Median followup was 8.4 months (IQR 2.6-26.4). CONCLUSIONS: Lichen sclerosus related urethral stricture disease can be effectively managed with intraurethral steroids. This minimally invasive management strategy improves patient reported voiding symptoms and voiding quality of life.