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2.
Can Urol Assoc J ; 18(4): 121-128, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38381941

RESUMEN

INTRODUCTION: We investigated the incidence of secondary bladder (BCa) and rectal cancers (RCa) after external beam radiotherapy (EBRT) for prostate cancer (PCa) compared to radical prostatectomy (RP) alone, and compared cancer-specific survival (CSS) of these secondary neoplasms to their primary counterparts. METHODS: This retrospective cohort study included men in the SEER cancer registry with a diagnosis of non-metastatic, clinically node-negative PCa treated with either RP or EBRT from 1995-2011 and allowed a minimum five-year lag period for the development of secondary BCa or RCa. Patients were divided into two eras, 1995-2002 and 2003-2011, to examine differences in incidence of secondary malignancies over time. Univariable and multivariable competing risk analyses with Fine-Gray subdistribution hazard and cause-specific hazard models were used to examine the risk of developing a secondary BCa or RCa. Competing risks analyses were used to compare CSS of primary vs. secondary BCa and RCa. RESULTS: A total of 198 184 men underwent RP and 190 536 underwent EBRT for PCa. The cumulative incidence of secondary BCa at 10 years was 1.71% for RP, and 3.7% for EBRT (p<0.001), while that of RCa was 0.52% for RP and 0.99% for EBRT (p<0.001). EBRT was associated with almost twice the risk of developing a secondary BCa and RCa compared to RP. The hazard of secondary BCa following EBRT delivered during 2003-2011 was 20% less than from 1995-2002 (p<0.09, Fine-Gray model), while that of secondary RCa was 31% less (p<0.001) (hazard ratio 0.78, p<0.001) for Fine-Gray and cause-specific hazard models. In the Fine-Gray model, the risk of death from BCa was 27% lower for secondary BCa after RP compared to primary BCa, while the risk of death was 9% lower for secondary BCa after EBRT compared to primary BCa. There was no difference in RCa-specific survival between primary or secondary RCa after RP or EBRT. CONCLUSIONS: The risk of BCa and RCa is almost twice as high for men undergoing EBRT for localized PCa vs. RP, but that risk is declining, likely reflecting advances in radiation delivery. The development of secondary RCa or BCa does not confer elevated risk of death compared to their primary counterparts.

3.
Urology ; 157: 168-173, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34129893

RESUMEN

OBJECTIVE: To characterize proportion of patients receiving adrenalectomy, adrenal involvement prevalence and oncologic outcomes of routine adrenalectomy in contemporary practice. Ipsilateral adrenalectomy was once standard during radical nephrectomy. However, benefit of routine adrenalectomy has been questioned because adrenal involvement of renal cell carcinoma (RCC) is low. METHODS: All patients receiving radical nephrectomy in the Canadian Kidney Cancer information system, a collaborative prospective cohort populated by 14 major Canadian centers, between January 2011 to February 2020 were included. Patients were excluded if they had non-RCC histology, multiple tumors, contralateral tumors, metastatic disease or previous history of RCC. Patient demographic, clinical, and surgical information were summarized and compared. Cox-proportional hazards was used for multivariable analysis. RESULTS: During study period, 2759 patients received radical nephrectomy, of these, 831(30.1%) had concomitant adrenalectomy. Pathological adrenal involvement was identified in 102 (3.7%overall; 12.3%of adrenalectomy). Median follow-up was 21.6months (Interquartile range 7.0-46.5). Patients with adrenalectomy had higher venous tumor thrombus (30.3% vs 9.6%; P <.0001), higher T stage (71.1% vs 43.4% pT3/4; P <.0001), lymph node metastases (17.6% vs 10.7%; P = .0035), Fuhrman grades (71.4% of Fuhrman grades 3/4 vs 56.2%; P <.0001) and increased proportion of clear cell histology (79.3% vs 74.5%; P = .0074) compared to the no adrenalectomy group. Adrenalectomy patients had higher risk of recurrence (HR 1.23; 95% CI 1.04-1.47; P = .019) and no difference in survival (HR 1.09, 95% CI 0.86-1.38, P = .48). CONCLUSION: Adrenalectomy is not associated with better oncological outcome of recurrence/survival. Adrenalectomy should be reserved for patients with radiographic adrenal involvement and/or intra-operative adrenal involvement.


Asunto(s)
Glándulas Suprarrenales/patología , Adrenalectomía/estadística & datos numéricos , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Venas Renales , Trombosis de la Vena/etiología , Glándulas Suprarrenales/diagnóstico por imagen , Anciano , Canadá , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/secundario , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Renales/complicaciones , Neoplasias Renales/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Nefrectomía/estadística & datos numéricos , Tasa de Supervivencia , Carga Tumoral
4.
Urology ; 154: 33-39, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33716036

RESUMEN

OBJECTIVE: To determine if a modified cystoscopy technique utilizing the peak-end rule cognitive bias decreases pain and anxiety during flexible cystoscopy in patients who undergo cystoscopy. METHODS: A total of 85 participants undergoing their first diagnostic cystoscopy were enrolled in a blinded single-center, prospective, randomized controlled trial. Patients with lower urinary tract abnormalities, prior radiation and chronic pelvic pain were excluded. Participants were randomized to a standard cystoscopy (arm A) or a modified cystoscopy (arm B) where a two-minute period at the end of the procedure was completed during which the cystoscope was left in the bladder without being manipulated. Following the cystoscopy, participants completed a standard pain and anxiety questionnaire. Differences in mean pain and anxiety score between arms were evaluated using a Mann-Whitney test with a two-sided alpha of 0.05. RESULTS: Eighty-five patients were randomized and underwent flexible cystoscopy. Three participants were ineligible, one required secondary procedures, and two did not complete the questionnaires. Among the 82 eligible patients, 45 were randomized to standard cystoscopy (arm A) and 37 to the modified cystoscopy (arm B) with mean pain scores of 23.20 and 11.97, respectively (P = .039). Mean anxiety scores were 2.09 and 0.88 for arm A and B, respectively (P = .013). CONCLUSION: This study demonstrated a clinically meaningful decrease in pain and anxiety for patients undergoing flexible cystoscopy when employing the modified cystoscopy technique versus the standard practice. This free and straightforward method to improve patient comfort and decrease stress during first time flexible cystoscopy should be considered by clinicians.


Asunto(s)
Ansiedad/prevención & control , Cistoscopía/métodos , Dolor Asociado a Procedimientos Médicos/prevención & control , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Método Simple Ciego
5.
Auton Neurosci ; 232: 102785, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33610007

RESUMEN

The aortic plexus serves as the primary gateway for sympathetic fibers innervating the pelvic viscera. Damage to this plexus and/or its associated branches can lead to an assortment of neurogenic complications such as bladder dysregulation or retrograde ejaculation. The neuroanatomy of this autonomic plexus has only recently been clarified in humans; as such, the precise function of its constituent fibers is still not clear. Further study into the functional neuroanatomy of the aortic plexus could help refine nerve-sparing surgical procedures that risk debilitating neurogenic complications, while also advancing understanding of peripheral sympathetic circuitry. To this end, the current study employed an in vivo electrostimulation paradigm in a porcine model, in combination with lipophilic neuronal tracing experiments in fixed, post-mortem human tissues, to further characterize the functional neuroanatomy of the aortic plexus. Electrostimulation results demonstrated that caudal lumbar splanchnic nerves provide primary control over the porcine bladder neck in comparison to other constituent fibers within the aortic plexus. Ex vivo human data revealed that the prehypogastric ganglion contains a significant number of neurons projecting to the superior hypogastric plexus, and that these neurons are arranged in a topographic manner within the ganglion. Altogether, these findings suggest that a pivotal sympathetic pathway mediating bladder neck contraction courses through the caudal lumbar splanchnic nerves, prehypogastric and inferior mesenteric ganglia and superior hypogastric plexus.


Asunto(s)
Plexo Hipogástrico , Neuroanatomía , Animales , Ganglios Simpáticos , Humanos , Masculino , Pelvis , Nervios Esplácnicos , Porcinos
7.
Can Urol Assoc J ; 15(8): E386-E392, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33410740

RESUMEN

INTRODUCTION: This study aims to assess the longer-term functional, anatomical, and metabolic outcomes of patients who underwent Studer neobladder (SNB) urinary diversion. METHODS: A retrospective review of patients who underwent SNB at a single center from 1995-2017 (n=116) was performed. Demographics, comorbidities, pathological data, and longer-term functional, anatomical, and metabolic outcomes were collected from hospital records. The primary outcome was voiding function of patients at most recent followup. Secondary outcomes included postoperative complications, renal function, nephrolithiasis, infections, and metabolic outcomes. RESULTS: Excluding those with incomplete followup data, 72 patients with a minimum followup of one year were included for analysis. Median followup was 70±11 months, with 52.8% of patients having ≥5 years of followup. Clean intermittent catheterization (CIC) was used by 22.2% of patient at most recent followup, which was mostly necessitated by bladder overdistension, deteriorating renal function, or recurrent urosepsis despite timed voiding. Patients experienced more daytime and nighttime urinary incontinence in the early postoperative setting, which improved over time. Generally, renal function declined over time; poorer long-term renal function was predicted by hydronephrosis within one year (p=0.002). CONCLUSIONS: Longer-term followup of SNB reveals significant but manageable complications. Gradual decline in renal function was common. Strict adherence to bladder emptying protocols (e.g., timed voiding or CIC) may reduce incidence of renal deterioration, metabolic disorders, and urinary dysfunction. Early onset (<1 year) of hydronephrosis may indicate a need for intervention to preserve long-term renal function.

8.
Can Urol Assoc J ; 14(10): E499-E506, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33275557

RESUMEN

INTRODUCTION: The Canadian Kidney Cancer information system (CKCis) has prospectively collected data on patients with renal tumors since January 1, 2011 from 16 sites within 14 academic centers in six provinces. Canadian kidney cancer experts have used CKCis data to address several research questions. The goal of this study was to determine if the CKCis cohort is representative of the entire Canadian kidney cancer population, specifically regarding demographic and geographic distributions. METHODS: The CKCis prospective cohort was analyzed up to December 31, 2018. Baseline demographics and tumor characteristics were analyzed, including location of patients' residence at the time of CKCis entry. Geographic data is presented by province, rural vs. urban via postal code information (2nd digit=0) and by Canadian urban boundary files. To determine the proportion of renal cell carcinoma (RCC) patients that CKCis captures, CKCis accruals were compared to projected Canadian Cancer Society RCC incidence in 2016-2017 and the incidence from the 2016 Canadian Cancer Registry. To determine if the CKCis baseline data is representative, it was compared to registry data and other published data when registry data was not available. RESULTS: This CKCis cohort includes 10 298 eligible patients: 66.6% male, median age 62.6 years; 14.6% had metastatic disease at the time of diagnosis and 70.4% had clear-cell carcinomas. The CKCis cohort captures about 1250 patients per year, which represents approximately 20% of the total kidney cancer incidence. The proportion of patients captured per province did vary from 13-43%. Rural patients make up 17% of patients, with some baseline differences between rural and urban patients. There appears to be no major differences between CKCis patient demographics and disease characteristics compared to national data sources. Canadian heat maps detailing patient location are presented. CONCLUSIONS: CKCis contains prospective data on >10 000 Canadian kidney cancer patients, making it a valuable resource for kidney cancer research. The baseline demographic and geographic data do appear to include a broad cross-section of patients and seem to be highly representative of the Canadian kidney cancer population. Moving forward, future projects will include determining if CKCis cancer outcomes are also representative of the entire Canadian kidney cancer population and studying variations across provinces and within rural vs. urban areas.

9.
J Surg Oncol ; 122(8): 1785-1790, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32914446

RESUMEN

BACKGROUND & OBJECTIVES: Radical inguinal lymph node dissections (rILND) for penile cancer risk significant postoperative lymphocele and lymphedema. However, reducing the risk of lymphatic complications is limited by our understanding of lymphatic anatomy. Therefore, this study aims to elucidate the lymphatic anatomy within the current surgical borders of a rILND. METHODS: To visualize the position of the lymph nodes, tissue packets excised from the inguinal region of five fresh, male cadavers were imaged using microcomputed tomography (µCT). To standardize the position, rotation and size between specimens, each lymph node packet was aligned using a Generalized Procrustes analysis. RESULTS: There was a median of 13.5 lymph nodes (range = 8-18) per packet, with the majority (99%) clustered within a 6 cm radius of the saphenofemoral junction; a region 39%-41% smaller than current surgical borders. No difference existed between the number of nodes between sides, or distribution around the saphenofemoral junction. CONCLUSIONS: This study provides the first 3D, in situ, standardized characterization of lymph node anatomy in the inguinal region using µCT. By using knowledge of the normal lymphatic anatomy, this study can help inform the reduction in borders of rILND to limit disruption and ensure a complete lymphadenectomy.


Asunto(s)
Conducto Inguinal/patología , Conducto Inguinal/cirugía , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Neoplasias del Pene/patología , Neoplasias del Pene/cirugía , Anciano , Cadáver , Estudios de Seguimiento , Humanos , Conducto Inguinal/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Masculino , Neoplasias del Pene/diagnóstico por imagen , Pronóstico , Microtomografía por Rayos X
10.
Eur Urol Open Sci ; 22: 54-60, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34337478

RESUMEN

BACKGROUND: Testis cancer (TC) patients are young with excellent cancer prognosis. Hence, the risk of late-onset treatment-related morbidity and mortality is of concern due to longer survival after treatment. OBJECTIVE: We set to characterize long-term survival of TC patients through a Canadian population dataset. DESIGN SETTING AND PARTICIPANTS: We used a population-based dataset, the Canadian Census Health and Environment Cohort (CanCHEC), to identify individuals diagnosed with TC between 1991 and 2010. We compared them with all other male individuals without TC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was mortality due to cardiovascular disease (CVD) or nontesticular malignancy. Mann-Whitney or chi-square test was used where applicable. Data were analyzed using a Cox proportional hazard model with and without matching. RESULTS AND LIMITATIONS: We identified 1950 individuals with TC. We compared them with 1 300 295 men with no TC. There were 335 deaths in the study group during the study period (17.2%) with a mean follow-up of 19.6 yr. TC patients were at increased risk of death from secondary malignancies (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.39-1.91; p < 0.0001) with specific risks for hematologic neoplasms (HR 3.86, 95% CI 2.78-5.37; p < 0.001) and other malignancies (HR 2.41, 95% CI 1.76-3.29; p < 0.001). Gastrointestinal, hematologic, and respiratory toxicities were the most common secondary malignancies leading to death. When stratified according to histology, nonseminoma (NS) patients were at significantly increased risk of death from CVD (HR 2.03, 95% CI 1.27-3.25; p = 0.0032). Individuals with seminoma were at increased risk of death from other nontestis neoplasms (HR 1.46, 95% CI 1.17-1.82; p = 0.0007), specifically hematologic neoplasms (HR 2.09, 95% CI 1.18-3.72; p = 0.0118). CONCLUSIONS: NS patients are at increased risk of CVD-related death, whereas seminoma patients are at increased risk of death from non-testis-related malignancies. PATIENT SUMMARY: We report long-term mortality following diagnosis of testis cancer. Nonseminoma patients have an increased risk of death from cardiovascular disease, while seminoma patients have an increased risk of death from secondary malignancies.

11.
Curr Oncol ; 28(1): 78-85, 2020 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-33704177

RESUMEN

Extragonadal germ cell tumors account for 2-5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16-36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14-56) and median mass size at diagnosis was 9 cm (range, 3.4-19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months-28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5-122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.


Asunto(s)
Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Ontario/epidemiología , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/tratamiento farmacológico
12.
Lymphat Res Biol ; 18(2): 166-173, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31483190

RESUMEN

Background: Surgical excision and/or radiation targeting of regional lymph nodes are an essential component in the clinical management of cancer. Importantly, a more accurate understanding of lymphatic anatomy could enable refinement of present treatment strategies. Given the spatial resolution limitations of contemporary imaging methods, our group sought to utilize noncontrast-enhanced microcomputed tomography (µCT) imaging to clarify regional lymphatic anatomy. Methods and Results: This study was conducted with embalmed en bloc lymphatic tissue packets from six donors (three females and three males: medianage of death = 78 years). All specimens were investigated with noncontrast-enhanced µCT imaging using a conebeam-CT imaging system. Adipose and lymphatic tissues were segmented by radiodensity based on sampling regions of interest. To confirm the observations from µCT, lymph nodes from each packet were exposed to hematoxylin and eosin staining and anti-D240 immunostaining. Following µCT imaging, mean peak radiodensities of -203.14 ± 19.35 Hounsfield units (HU) and 37.25 ± 31.95 HU were revealed for adipose and lymphatic tissues, respectively (p < 0.01). By analyzing histograms of the radiodensity distributions, we determined a threshold of -82.42 HU to differentiate adipose and lymphatic tissue, to generate three-dimensional renderings, and to calculate quantitative metrics. On average, adipose tissue comprised 9.62 ± 3.60 cm3 (73.6%) of the total packet volume, whereas lymphatic tissue comprised 3.47 ± 2.71 cm3 (26.4%). Moreover, each en bloc packet contained four small lymph nodes (1-5 mm) and three to four large lymph nodes (>5 mm). Histology corroborated the observations from µCT. Conclusions: Altogether, a precise understanding of regional lymphatic anatomy elucidated by the present imaging modality may help refine clinical cancer treatment strategies.


Asunto(s)
Ganglios Linfáticos , Vasos Linfáticos , Microtomografía por Rayos X , Anciano , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Vasos Linfáticos/diagnóstico por imagen , Masculino
13.
Eur Urol Focus ; 5(6): 930-934, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31628080
14.
Eur Urol Focus ; 5(6): 977-979, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31029560

RESUMEN

Our recently reported phase III trial demonstrated that patients undergoing nephron-sparing surgery (NSS) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m2 who received mannitol had no improvement in renal function at 6 mo compared with those who received placebo. Some authors have suggested that benefit is restricted to subgroups, such as those with comorbidities. We assessed whether preoperative eGFR, or other patient and surgical factors modified the effect of mannitol on postoperative outcomes at 6 mo and with extended follow-up. We also assessed whether mannitol was associated with differences in long-term GFR years after surgery. No significant difference between the mannitol or placebo groups (mean eGFR difference: 1.4; 95% confidence interval: -2.6, 5.3; p = 0.5) was found in the 134 patients with known eGFR at 3 yr after NSS. At both 6 mo and 3 yr, the effect of mannitol was not significantly modified by patient or surgical factors including preoperative eGFR. In summary, we validated our original trial conclusions by finding that intraoperative use of mannitol does not improve either short- or long-term renal function in patients undergoing NSS. Specifically, there is no evidence that comorbidities, including lower preoperative eGFR, modify the effect of mannitol. PATIENT SUMMARY: Use of mannitol at the time of partial nephrectomy does not improve either short- or long-term renal function even in patients with comorbidities, including lower preoperative renal function. The routine use of intraoperative mannitol should be discontinued.


Asunto(s)
Diuréticos Osmóticos/administración & dosificación , Neoplasias Renales/cirugía , Manitol/administración & dosificación , Nefronas/fisiopatología , Tratamientos Conservadores del Órgano/métodos , Comorbilidad , Diuréticos Osmóticos/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Cuidados Intraoperatorios/estadística & datos numéricos , Manitol/farmacología , Nefrectomía/métodos , Nefronas/efectos de los fármacos , Nefronas/cirugía , Evaluación de Resultado en la Atención de Salud , Placebos/administración & dosificación , Periodo Posoperatorio , Periodo Preoperatorio
15.
Surg Radiol Anat ; 41(8): 973-976, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30820646

RESUMEN

The spermatic ganglia are collections of sympathetic neuron cell bodies located within the cords of the infrarenal aortic plexus, positioned at the origin of the testicular arteries in males. During routine dissection of the aortic plexus at our institution, one specimen exhibited a second (accessory) testicular artery on the right side that coursed retrocaval. Histology was used to confirm the presence of an accessory right spermatic ganglion at the base of the accessory retrocaval testicular artery. Interestingly, the accessory spermatic ganglion was also supplied by its own right lumbar splanchnic nerve. This is the first case to describe the anatomy of an accessory spermatic ganglion in a specimen that exhibits an accessory testicular artery on the right side. This neurovascular variation is of interest to surgeons who aim to perform nerve-sparing retroperitoneal lymph node dissections for malignancy.


Asunto(s)
Ganglios Simpáticos/anomalías , Plexo Lumbosacro/anomalías , Testículo/inervación , Anciano , Variación Anatómica , Cadáver , Disección , Ganglios Simpáticos/embriología , Humanos , Plexo Lumbosacro/embriología , Escisión del Ganglio Linfático/métodos , Masculino , Espacio Retroperitoneal/cirugía , Testículo/irrigación sanguínea
16.
Can Urol Assoc J ; 13(8): 260-265, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30526804

RESUMEN

INTRODUCTION: Small cell carcinoma of the bladder (SmCC) is a rare and aggressive genitourinary malignancy. The paucity of clinical trials and outcome data provide no standard treatment guidelines. Accordingly, patient prognosis is poor. Our goal was to present the first comprehensive in-depth analysis of SmCC in a tertiary Canadian centre. METHODS: We retrospectively reviewed all patients diagnosed with primary SmCC at the London Regional Cancer Program between January 1990 and 2016. The primary outcome was overall survival (OS). We examined a number of secondary outcomes and baseline characteristics. RESULTS: We identified 15 men and six women (median age 72 years) with a SmCC diagnosis (median followup 11.33 months). Median Charlson Comorbidity Index score was 7 (interquartile range [IQR] 5-10) and 15 patients had a smoking history. Most common presentation was gross hematuria (18 patients, 86%), and pT2 stage at transurethral resection of the bladder tumour (TURBT) (n= 7/21, 33%), although five patients had cT4 (24%). Pure SmCC was found in nine individuals (43%), whereas 12 had mixed differentiation (57%). From initial staging, 15 patients had extravesical disease (71%), 10 had positive pelvic lymphadenopathy (48%), and distant metastases occurred in six (29%). In our series, five individuals (24%) underwent cystectomy, 18 (86%) received radiation, and 14 (67%) received adjuvant chemotherapy. The median OS was 15 months (two-year OS was 19%). CONCLUSIONS: SmCC is a rare and aggressive form of bladder cancer. Despite multimodal therapy, prognosis remains guarded, with little improvement seen over the study's 25-year duration. An understanding of study limitations is warranted in interpretation of results.

18.
Dis Model Mech ; 11(11)2018 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-30082495

RESUMEN

Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.


Asunto(s)
Drosophila melanogaster/metabolismo , Ensayos Analíticos de Alto Rendimiento/métodos , Cálculos Renales/tratamiento farmacológico , Modelos Biológicos , Animales , Arbutina/análisis , Arbutina/farmacología , Arbutina/uso terapéutico , Birrefringencia , Calcio/metabolismo , Oxalato de Calcio , Difosfonatos , Evaluación Preclínica de Medicamentos , Heces , Células HEK293 , Humanos , Iones , Nanopartículas
19.
Eur Urol ; 73(1): 53-59, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28822586

RESUMEN

BACKGROUND: Mannitol is currently used as a renal protective agent to mitigate the effects of renal ischemia during nephron-sparing surgery (NSS). This routine practice lacks rigorous methodological study. OBJECTIVE: To assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS. DESIGN, SETTING, PARTICIPANTS: This prospective, randomized, placebo-controlled, double-blind trial included 199 patients with a preoperative estimated glomerular filtration rate (eGFR) >45ml/min/1.73m2 scheduled for NSS; the trial was conducted between July 2012 and July 2015. INTERVENTION: Patients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the difference in eGFR (renal function) between the two groups at 6 mo following surgery assessed with an analysis of covariance model using preoperative eGFR, treatment group, and surgical approach as covariates. RESULTS AND LIMITATIONS: At baseline, the median age of the patients was 58 yr, and the median eGFR was 88ml/min/1.73m2. Comparing placebo with mannitol infusion, the adjusted difference of 0.2 eGFR units at 6 mo was not significant (p=0.9), with the upper bound of the 95% confidence interval (-3.1 to 3.5) excluding a clinically relevant effect of mannitol. Limitations include evaluation of a single mannitol dose and patients all had excellent preoperative renal function. CONCLUSIONS: Intraoperative 12.5g mannitol infusion during NSS has no demonstrable clinical benefit when compared with standardized fluid hydration in patients with normal preoperative renal function, and its use in this setting is not warranted. PATIENT SUMMARY: In this randomized trial, patients with normal kidney function who received mannitol during surgery to remove part of their kidney had no better kidney function 6 mo after surgery than those who did not receive mannitol. We conclude that this routine practice should be discontinued.


Asunto(s)
Carcinoma de Células Renales/cirugía , Diuréticos/administración & dosificación , Tasa de Filtración Glomerular/efectos de los fármacos , Neoplasias Renales/cirugía , Riñón/efectos de los fármacos , Riñón/cirugía , Manitol/administración & dosificación , Nefrectomía/métodos , Complicaciones Posoperatorias/prevención & control , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Diuréticos/efectos adversos , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Riñón/patología , Riñón/fisiopatología , Neoplasias Renales/patología , Neoplasias Renales/fisiopatología , Masculino , Manitol/efectos adversos , Persona de Mediana Edad , Nefrectomía/efectos adversos , Tratamientos Conservadores del Órgano , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
20.
J Anat ; 232(1): 124-133, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29159805

RESUMEN

Injury to the nerves of the aortic- and superior hypogastric plexuses during retroperitoneal surgery often results in significant post-operative complications, including retrograde ejaculation and/or loss of seminal emission in males. Although previous characterizations of these plexuses have done well to provide a basis for understanding the typical anatomy, additional research into the common variations of these plexuses could further optimize nerve-sparing techniques for retroperitoneal surgery. To achieve this, the present study aimed to document the prevalence and positional variability of the infrarenal lumbar splanchnic nerves (LSNs) through gross dissection of 26 human cadavers. In almost all cases, two LSNs were observed joining each side of the aortic plexus, with 48% (left) and 33% (right) of specimens also exhibiting a third joining inferior to the left renal vein. As expected, the position of the LSNs varied greatly between specimens. That said, the vast majority (98%) of LSNs joining the aortic plexus were found to originate from the lumbar sympathetic trunk above the level of the inferior mesenteric artery. It was also found that, within specimens, adjacent LSNs often coursed in parallel. In addition to these nerves, 85% of specimens also demonstrated retroaortic LSN(s) that were angled more inferior compared with the other LSNs (P < 0.05), and exhibited a unique course between the aorta/common iliac arteries and the left common iliac vein before joining the superior hypogastric plexus below the aortic bifurcation. These findings may have significant implications for surgeons attempting nerve-sparing procedures of the sympathetic nerves in the infrarenal retroperitoneum such as retroperitoneal lymphadenectomies. We anticipate that the collective findings of the current study will help improve such retroperitoneal nerve-sparing surgical procedures, which may assist in preserving male ejaculatory function post-operatively.


Asunto(s)
Espacio Retroperitoneal/anatomía & histología , Espacio Retroperitoneal/cirugía , Nervios Esplácnicos/anatomía & histología , Anciano , Anciano de 80 o más Años , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad
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