El desabastecimiento de BCG para instilación intravesical se asocia a la recidiva tumoral precoz en pacientes con tumor vesical no-músculo invasor de alto riesgo / BCG shortage for intravesical instillation is associated with early tumor recurrence in patients with high-risk non-muscle-invasive bladder tumors

Introducción Durante 2019 se produjo una escasez mundial de cepas de BCG para instilación intravesical, limitando la disponibilidad de esquemas de dosis completas para la fase de mantenimiento. El objetivo principal del estudio fue analizar el impacto del desabastecimiento de BCG sobre la recidiva tumoral en nuestro centro. Los criterios de valoración secundarios incluyeron las tasas de recidiva y supervivencia libre de progresión y las características específicas de la recidiva tumoral. Métodos Estudio de cohortes retrospectivo que incluye a 158 sujetos (64 tratados durante 2019 y 94 durante 2017) con cáncer vesical no infiltrante de alto riesgo y tratados con una combinación de resección transuretral de vejiga (RTUV) seguida de instilación intravesical de BCG adyuvante en un hospital terciario de España. Se analizaron las características basales de ambos grupos. El periodo transcurrido hasta el evento de interés (recaída; incluyendo recurrencia o progresión) se estimó con el análisis de supervivencia de Kaplan-Meier. Las tasas de supervivencia libre de enfermedad se analizaron mediante un modelo multivariable de regresión de Cox de riesgos proporcionales. Resultados La mediana del tiempo de seguimiento fue de 24 y 50 meses en las muestras de 2019 y 2017, respectivamente, con una mediana del número de instilaciones de 8 y 12, respectivamente. Se observó una mediana de tiempo hasta la recurrencia de 285 días (145-448) durante 2019 y de 382 días (215-567) en 2017 (log-rank p=0,025). Un análisis multivariable adicional reveló un HR proporcional para la tasa de supervivencia libre de enfermedad de 1,87 (IC 95%: 1,04-3,37 p=0,036). No se observaron diferencias estadísticamente significativas en las características de la recaída tumoral (AU)

Introduction During 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective was to analyze the impact on tumoral relapse secondary to BCG shortage in our center. Secondary outcomes included recurrence and progression–free survival rates and tumoral relapse specific characteristics. Methods Retrospective cohort study including 158 subjects (64 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG in a tertiary hospital in Spain. Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated with Kaplan-Meier survival analysis. Disease-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. Results Median follow-up in the 2019 sample was 24 months and 50 months in the 2017 group with a median number of instillations of 8 and 12 respectively. Median time to relapse of 285 days (145-448) during 2019 and 382 days (215-567) in 2017 were observed (logRank P=.025). Further multivariable analysis revealed a proportional hazard ratio (HR) for disease-free survival rate of 1.87 (95% CI: 1.04-3.37 P=.036). No statistically significant differences in tumoral relapse characteristics were observed. Conclusion BCG shortage and subsequent reduced-dose schemes used for intravesical instillation due to limited availability, increase early tumoral relapse rates. These findings are consistent with available evidence, showing the need for full-dose BCG courses (AU)

BCG shortage for intravesical instillation is associated with early tumoral recurrence in patients with high-risk non-muscle invasive bladder tumours.

INTRODUCTION: During 2019 there was a worldwide shortage of BCG strains for intravesical instillation, limiting the availability of full dose schemes for maintenance courses. The main objective was to analyze the impact on tumoral relapse secondary to BCG shortage in our center. Secondary outcomes included recurrence and progression-free survival rates and tumoral relapse specific characteristics. METHODS: Retrospective cohort study including 158 subjects (64 treated during 2019 and 94 during 2017) with high-risk non-muscle invasive bladder cancer and treated with a combination of Transurethral bladder resection (TURB) followed by adjuvant intravesical instillation with BCG in a tertiary hospital in Spain. Basal characteristics of both groups were analyzed. Times to event of interest (relapse; including recurrence and/or progression) were estimated with Kaplan-Meier survival analysis. Disease-free survival rates were analyzed using a multivariable Cox regression model of proportional hazards. RESULTS: Median follow-up in the 2019 sample was 24 months and 50 months in the 2017 group with a median number of instillations of 8 and 12 respectively. Median time to relapse of 285 days (145-448) during 2019 and 382 days (215-567) in 2017 were observed (logRank p = 0.025). Further multivariable analysis revealed a proportional hazard ratio (HR) for disease-free survival rate of 1.87 (95% CI: 1.04-3.37 p = 0.036). No statistically significant differences in tumoral relapse characteristics were observed. CONCLUSION: BCG shortage and subsequent reduced-dose schemes used for intravesical instillation due to limited availability, increase early tumoral relapse rates. These findings are consistent with available evidence, showing the need for full-dose BCG courses.

Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma.

Pancreatic Ductal Adenocarcinoma (PDAC) has a five-year survival under 10%. Treatment is compromised due to a fibrotic-like stromal remodeling process, known as desmoplasia, which limits therapeutic perfusion, supports tumor progression, and establishes an immunosuppressive microenvironment. These processes are driven by cancer-associated fibroblasts (CAFs), functionally activated through transforming growth factor beta1 (TGFß1). CAFs produce a topographically aligned extracellular matrix (ECM) that correlates with reduced overall survival. Paradoxically, ablation of CAF populations results in a more aggressive disease, suggesting CAFs can also restrain PDAC progression. Thus, unraveling the mechanism(s) underlying CAF functions could lead to therapies that reinstate the tumor-suppressive features of the pancreatic stroma. CAF activation involves the f-actin organizing protein palladin. CAFs express two palladin isoforms (iso3 and iso4) which are up-regulated in response to TGFß1. However, the roles of iso3 and iso4 in CAF functions remain elusive. Using a CAF-derived ECM model, we uncovered that iso3/iso4 are required to sustain TGFß1-dependent CAF activation, secrete immunosuppressive cytokines, and produce a pro-tumoral ECM. Findings demonstrate a novel role for CAF palladin and suggest that iso3/iso4 regulate both redundant and specific tumor-supportive desmoplastic functions. This study highlights the therapeutic potential of targeting CAFs to restore fibroblastic anti-tumor activity in the pancreatic microenvironment.

Using online tools at the Bovine Genome Database to manually annotate genes in the new reference genome.

With the availability of a new highly contiguous Bos taurus reference genome assembly (ARS-UCD1.2), it is the opportune time to upgrade the bovine gene set by seeking input from researchers. Furthermore, advances in graphical genome annotation tools now make it possible for researchers to leverage sequence data generated with the latest technologies to collaboratively curate genes. For many years the Bovine Genome Database (BGD) has provided tools such as the Apollo genome annotation editor to support manual bovine gene curation. The goal of this paper is to explain the reasoning behind the decisions made in the manual gene curation process while providing examples using the existing BGD tools. We will describe the sources of gene annotation evidence provided at the BGD, including RNA-seq and Iso-Seq data. We will also explain how to interpret various data visualizations when curating gene models, and will demonstrate the value of manual gene annotation. The process described here can be applied to manual gene curation for other species with similar tools. With a better understanding of manual gene annotation, researchers will be encouraged to edit gene models and contribute to the enhancement of livestock gene sets.

Fifty ways to improve presentations in urology. / Cincuenta consejos para mejorar las presentaciones en urología.

BACKGROUND: Our profession permanently demands intercommunication of medical knowledge among colleagues; either in small environments such as hospitals or at larger ones such as congresses or academic courses. New technologies such as PowerPoint® are not developed enough to provide good presentations, and its employment does not always grant effective results. OBJECTIVE: In order to improve our academic presentations, we present several tools that may help us avoid the most common mistakes. EVIDENCE ACQUISITION: Literature search in PubMed and Google Scholar. We have divided the analysis into 3 sections: structure of the presentation, slide design, presentation to the audience. Each section includes a list of 50 short tips. RESULTS: Fifty tips following the study objectives. CONCLUSIONS: The scientific evidence that supports the information on how to improve presentations is mostly based on expert opinions. However, almost every work agrees that presentations must use simple structures which does not make them less scientific; their content must be developed for a specific audience, and it must be the speaker, not the slides, who captures the audience attention. Making a simple and didactic presentation of complex content supported by multimedia tools is one of the speaker's highest intellectual challenges of these days.

Characterization and application studies of ProxyPhos, a chemosensor for the detection of proximally phosphorylated peptides and proteins in aqueous solutions.

Proximal phosphorylation on proteins appears to have functional significance and has been associated with several diseases, including Alzheimer's and cancer. While much remains to be learned about the role of proximal phosphorylation in biological systems, no simple and/or affordable technique is available for its detection. To this end, we have previously developed a ProxyPhos chemosensor, which detects proximally phosphorylated peptides and proteins over mono- and non-phosphorylated motifs in aqueous solutions. In this follow-up work, we performed extensive characterization of peptide and protein ProxyPhos assay conditions to achieve enhanced detection, and further explored the selectivity of ProxyPhos, and its potential off-targets. As a result of characterization studies, selective sensing of proximally phosphorylated over mono-phosphorylated peptides and proteins was achieved. Moreover, studies demonstrated that ProxyPhos was compatible with the detection of all commonly phosphorylated residues (i.e. tyrosine, serine and threonine residues). Under optimized conditions, ProxyPhos efficiently discriminated between peptides derived from the activated (proximally phosphorylated, disease-relevant) and inactive (mono-phosphorylated) forms of JAK2, SYK and MAPK1 kinases. In addition, ProxyPhos can be used to probe phosphatase activity on peptides and proteins via detecting changes in proximal phosphorylation, demonstrating immediate utility of this chemosensing system.

Structural insights into the ene-reductase synthesis of profens.

Reduction of double bonds of α,ß-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.

Dynamic Response and Residual Helmet Liner Crush Using Cadaver Heads and Standard Headforms.

Biomechanical headforms are used for helmet certification testing and reconstructing helmeted head impacts; however, their biofidelity and direct applicability to human head and helmet responses remain unclear. Dynamic responses of cadaver heads and three headforms and residual foam liner deformations were compared during motorcycle helmet impacts. Instrumented, helmeted heads/headforms were dropped onto the forehead region against an instrumented flat anvil at 75, 150, and 195 J. Helmets were CT scanned to quantify maximum liner crush depth and crush volume. General linear models were used to quantify the effect of head type and impact energy on linear acceleration, head injury criterion (HIC), force, maximum liner crush depth, and liner crush volume and regression models were used to quantify the relationship between acceleration and both maximum crush depth and crush volume. The cadaver heads generated larger peak accelerations than all three headforms, larger HICs than the International Organization for Standardization (ISO), larger forces than the Hybrid III and ISO, larger maximum crush depth than the ISO, and larger crush volumes than the DOT. These significant differences between the cadaver heads and headforms need to be accounted for when attempting to estimate an impact exposure using a helmet's residual crush depth or volume.

Natural Product Biosynthesis in Escherichia coli: Mentha Monoterpenoids.

The era of synthetic biology heralds in a new, more "green" approach to fine chemical and pharmaceutical drug production. It takes the knowledge of natural metabolic pathways and builds new routes to chemicals, enables nonnatural chemical production, and/or allows the rapid production of chemicals in alternative, highly performing organisms. This route is particularly useful in the production of monoterpenoids in microorganisms, which are naturally sourced from plant essential oils. Successful pathways are constructed by taking into consideration factors such as gene selection, regulatory elements, host selection and optimization, and metabolic considerations of the host organism. Seamless pathway construction techniques enable a "plug-and-play" switching of genes and regulatory parts to optimize the metabolic functioning in vivo. Ultimately, synthetic biology approaches to microbial monoterpenoid production may revolutionize "natural" compound formation.

Relative Importance of the Arcuate and Anteroventral Periventricular Kisspeptin Neurons in Control of Puberty and Reproductive Function in Female Rats.

Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.

Cardiovascular mortality in patients with prostate cancer exposed to androgen deprivation therapy.

INTRODUCTION: A relationship between the administration of GnRH agonists and the risk of acute myocardial infarction (AMC) in patients with prostate cancer has been showed in the third observational study published in April 2014. The association AMC-orchiectomy was not found in any of these studies. OBJECTIVE: Define risk factors for cardiovascular disease in patients treated with GnRH agonist. Their probable underlying pathogenic mechanism in the myocardium and peripheral vascular tree was also analyzed. EVIDENCE ACQUISITION: English articles cited in PubMed were reviewed. No time period is specified. The last search date was 11/30/14. EVIDENCE SYNTHESIS: In patients with coronary history of AMC or congestive heart failure, hormonal neoadjuvant therapy increased cardiovascular mortality rates (HR: 1.96, IC 95%: 1.04-3.71; P=.04) as well as cardiovascular-specific mortality rates (AHR: 3.28; IC 95%: 1.01-10.64; P=.048). Two possible mechanisms can be involved: a) direct mechanism through myocardial receptor for GnRH/PKA along with atherogenic plaques; and b) indirect mechanism related with metabolic disturbances. CONCLUSIONS: Patients with AMC or congestive heart failure history could present a higher risk of death related to the use of GnRH agonists. In these cases, should carefully consider appropriateness of such treatment. These effects can explained by a direct mechanism on myocardium and peripheral vascular tree and indirect ones related with modified metabolic syndrome.

L-cysteine suppresses ghrelin and reduces appetite in rodents and humans.

BACKGROUND: High-protein diets promote weight loss and subsequent weight maintenance, but are difficult to adhere to. The mechanisms by which protein exerts these effects remain unclear. However, the amino acids produced by protein digestion may have a role in driving protein-induced satiety. METHODS: We tested the effects of a range of amino acids on food intake in rodents and identified l-cysteine as the most anorexigenic. Using rodents we further studied the effect of l-cysteine on food intake, behaviour and energy expenditure. We proceeded to investigate its effect on neuronal activation in the hypothalamus and brainstem before investigating its effect on gastric emptying and gut hormone release. The effect of l-cysteine on appetite scores and gut hormone release was then investigated in humans. RESULTS: l-Cysteine dose-dependently decreased food intake in both rats and mice following oral gavage and intraperitoneal administration. This effect did not appear to be secondary to behavioural or aversive side effects. l-Cysteine increased neuronal activation in the area postrema and delayed gastric emptying. It suppressed plasma acyl ghrelin levels and did not reduce food intake in transgenic ghrelin-overexpressing mice. Repeated l-cysteine administration decreased food intake in rats and obese mice. l-Cysteine reduced hunger and plasma acyl ghrelin levels in humans. CONCLUSIONS: Further work is required to determine the chronic effect of l-cysteine in rodents and humans on appetite and body weight, and whether l-cysteine contributes towards protein-induced satiety.

Dynamics of locomotor transitions from arboreal to terrestrial substrates in Verreaux's sifaka (Propithecus verreauxi).

Most primates are able to move with equal facility on the ground and in trees, but most use the same quadrupedal gaits in both environments. A few specialized primates, however, use a suspensory or leaping mode of locomotion when in the trees but a bipedal gait while on the ground. This is a rare behavioral pattern among mammals, and the extent to which the bipedal gaits of these primates converge and are constrained by the anatomical and neurological adaptations associated with arboreal locomotion is poorly understood. Sifakas (Propithecus), primates living only in Madagascar, are highly committed vertical clingers and leapers that also spend a substantial amount of time on the ground. When moving terrestrially sifakas use a unique bipedal galloping gait seen in no other mammals. Little research has examined the mechanics of these gaits, and most of that research has been restricted to controlled captive conditions. The energetic costs associated with leaping and bipedal galloping are unknown. This study begins to fill that gap using triaxial accelerometry to characterize and compare the dynamics of sifakas' leaping and bipedal galloping behavior. As this is a relatively novel approach, the first goal of this article is to explore the feasibility of collecting such data on free-roaming animals and attempt to automate the identification of leaping and bipedal behavior within the output. The second goal is to compare the overall accelerations of the body and to use that as an approximation of aspects of energetic costs during leaping and bipedalism. To achieve this, a lightweight accelerometer was mounted on freely moving sifakas. The resulting acceleration profiles were processed, and sequences of leaps (bouts) were automatically extracted from the waveforms with 85% accuracy. Both vector dynamic body acceleration and overall dynamic body acceleration (ODBA) were used to characterize locomotor patterns and energy expenditure during leaping and bipedalism. The unique kinematics of the gait of sifakas, and the mechanics of bouts involving a string of successive leaps or gallops, appear to minimize redirections of the center of mass as well as the number of acceleration peaks and ODBAs. These results suggest that bipedal galloping is not only a reflection of the unique anatomical configuration of a leaping primate, but it may also provide a musculoskeletal and an energetic advantage to sifakas. In that sense, bipedal galloping represents an advantageous way for sifakas to move when transitioning from arboreal leaping to terrestrial locomotion.

Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone.

Relaxin-3 is a member of the insulin superfamily. It is expressed in the nucleus incertus of the brainstem, which has projections to the hypothalamus. Relaxin-3 binds with high affinity to RXFP1 and RXFP3. RXFP3 is expressed within the hypothalamic paraventricular nucleus (PVN), an area central to the stress response. The physiological function of relaxin-3 is unknown but previous work suggests a role in appetite control, stimulation of the hypothalamic-pituitary-gonadal axis and stress. Central administration of relaxin-3 induces c-fos expression in the PVN and increases plasma ACTH levels in rats. The aim of this study was to investigate the effect of central administration of human relaxin-3 (H3) on the hypothalamic-pituitary-adrenal (HPA) axis in male rodents in vivo and in vitro. Intracerebroventricular (i.c.v) administration of H3 (5 nmol) significantly increased plasma corticosterone at 30 min following injection compared with vehicle. Intra-PVN administration of H3 (1.8-1620 pmol) significantly increased plasma ACTH at 1620 pmol H3 and corticosterone at 180-1620 pmol H3 at 30 min following injection compared with vehicle. The stress hormone prolactin was also significantly raised at 15 min post-injection compared with vehicle. Treatment of hypothalamic explants with H3 (10-1000 nM) stimulated the release of corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), but H3 had no effect on the release of ACTH from in vitro pituitary fragments. These results suggest that relaxin-3 may regulate the HPA axis, via hypothalamic CRH and AVP neurons. Relaxin-3 may act as a central signal linking nutritional status, reproductive function and stress.

The physiological role of arcuate kisspeptin neurons in the control of reproductive function in female rats.

Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity.

Survival of HIV-positive individuals with hepatitis B and C infection in Michigan.

We sought to estimate mortality and associated factors in HIV-hepatitis co-infected individuals in Michigan using a retrospective cohort study. For the study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals were matched to hepatitis B and C cases. In the final Cox proportional hazards regression model, individuals of other [hazard ratio (HR) 2·2, 95% confidence interval (CI) 1·4-3·2] and black (HR 1·3, 95% CI 1·1-1·6) race had decreased survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2·1, 95% CI 1·6-2·6), men who have sex with men (MSM)/IDUs (HR 1·5, 95% CI 1·1-2·2), individuals with undetermined risk (HR 1·5, 95% CI 1·2-1·9) and heterosexual practices (HR 1·4, 95% CI 1·1-1·8) had decreased survival compared to MSM. Additionally, an interaction was found between current HIV status and co-infection. Mortality in HIV-hepatitis co-infected individuals remains a continuing problem. Our study can help in planning interventions to reduce mortality in HIV-infected individuals.

Usefulness of the Memorial Sloan Kettering Cancer Center nomogram in the prognosis of patients treated with radical cystectomy for invasive bladder cancer.

OBJECTIVES: To evaluate the usefulness of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for prediction of recurrence probability in our series of patients who have undergone radical cystectomy for bladder cancer. METHODS: 397 patients underwent radical cystectomy for bladder cancer between 1986 and 2005. 165 patients were excluded:21 due to exitus in the immediate postoperative period, 32 due to previous radiation therapy, 6 due to neoadjuvant chemotherapy, 5 due to inability to complete follow-up, 15 that did not undergo lymphadenectomy and 86 who were alive at the time of review with less than 5 years of follow-up. Patients were classified into recurrence risk groups: organ-confined tumors (pT0-2 pN0 ), extra-bladder involvement (pT3-4 pN0) and lymph node involvement (pN+). Survival analysis was performed using the Kaplan-Meier method. Five-year recurrence-free survival by risk groups in our series was compared with the one estimated using the MSKCC nomogram using a ROC curve. RESULTS: We analyzed 232 patients. Follow-up in patients who died of cancer was 25 ± 25 months. For alive patients and those who died of other causes, follow-up was 120 ± 39 months. Pathology studies revealed 42.7% organ-confined tumors , 33.2% with extra-bladder involvement and 24.1% with lymph node involvement. The five-year recurrence free survival analysis according to the Kaplan-Meier method stratified by risk groups was: pT0-2 76%, pT3-4 51%, pN+ 31%. The probability of recurrence free survival according to the MSKCC nomogram in the same risk groups was: 85% ± 5%, 62% ± 10% and 25% ± 13%, respectively. The area under the ROC curve was 0.795 (95% CI 0.739-0.852) CONCLUSION: In our series, the MSKCC nomogram constitutes a useful tool for predicting 5-year cancer free survival in patients who undergo radical cystectomy.

Utilidad del nomograma del Memorial Sloan Kettering Cancer Center en el pronóstico de los pacientes tratados con cistectomía radical por cáncer vesical infiltrante / Usefulness of the Memorial Sloan Kettering Cancer Center Nomogram in the prognosis of patients treated with radical cystectomy for invasive bladder cancer

OBJETIVO: Valorar la utilidad del nomograma del Memorial Sloan Kettering Cancer Center (MSKCC) para predecir la probabilidad de recidiva en nuestra serie de pacientes sometidos a cistectomía radical por cáncer de vejiga. MÉTODOS: Un total de 397 pacientes fueron sometidos a cistectomía radical por carcinoma vesical entre los años 1986 y 2005 ambos inclusive. Excluimos 165 pacientes: 21 por exitus en el postoperatorio inmediato, 32 por radioterapia previa, 6 por quimioterapia neoadyuvante, 5 por imposibilidad de seguimiento, 15 en los que no se realizó linfadenectomía y 86 vivos en el momento de la revisión con un seguimiento inferior a cinco años. Los pacientes fueron clasificados según grupos de riesgo de recidiva en: tumor órganoconfinado (pT0-T2 N0), localmente avanzado (pT3-T4 N0) y afectación ganglionar (pN+). Realizamos un análisis de supervivencia mediante el método Kaplan-Meier y comparamos mediante una curva ROC la supervivencia libre de recidiva a cinco años por grupos de riesgo de nuestra serie, con la estimada mediante el nomograma del MSKCC. RESULTADOS: Analizamos 232 pacientes. El 90% fueron varones y la edad media 62,5 años. El estudio anatomopatológico reveló 99 (42,7%) tumores organoconfinados, 77 (33,2%) con afectación extravesical y 56 (24,1%) con afectación ganglionar. El seguimiento en los pacientes muertos por cáncer fue de 25 ± 25 meses, con una mediana de 17. En los pacientes vivos o muertos por otras causas el seguimiento fue de 120 ± 39 meses, y la mediana 115,5. La mortalidad cáncer especifica fue del 59,5%. La supervivencia libre de recidiva a cinco años estimada y estratificada por grupos de riesgo fue: pT0-2 76%, pT3-4 51%, pN+ 31%. La probabilidad de supervivencia libre de recidiva según el nomograma del MSKCC en los mismos grupos fue: 85% ±5% en tumores organoconfinados, 62% ± 10% en casos de afectación extravesical, y 25% ± 13% en pacientes con metástasis ganglionares. El área bajo la curva ROC obtenida fue 0.795 (IC 95% 0.739-0.852). CONCLUSIÓN: En nuestra serie, el nomograma del MSKCC constituye una herramienta útil para predecir la supervivencia libre de recidiva a 5 años en los pacientes sometidos a cistectomía radical (AU)

OBJECTIVES: To evaluate the usefulness of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for prediction of recurrence probability in our series of patients who have undergone radical cystectomy for bladder cancer. METHODS: 397 patients underwent radical cystectomy for bladder cancer between 1986 and 2005. 165 patients were excluded: 21 due to exitus in the immediate postoperative period, 32 due to previous radiation therapy, 6 due to neoadjuvant chemotherapy, 5 due to inability to complete follow-up, 15 that did not undergo lymphadenectomy and 86 who were alive at the time of review with less than 5 years of follow-up. Patients were clasified into recurrence risk groups: organ-confined tumors (pT0-2 pN0), extra-bladder involvement (pT3-4 pN0) and lymph node involvement (pN+). Survival analysis was performed using the Kaplan-Meier method. Five-year recurrence-free survival by risk groups in our series was compared with the one estimated using the MSKCC nomogram using a ROC curve. RESULTS: We analyzed 232 patients. Follow-up in patients who died of cancer was 25 ± 25 months. For alive patients and those who died of other causes, follow-up was 120 ± 39 months. Pathology studies revealed 42.7% organ-confined tumors , 33.2% with extra-bladder involvement and 24.1% with lymph node involvement. The five-year recurrence free survival analysis according to the Kaplan-Meier method stratified by risk groups was: pT0-2 76%, pT3-4 51%, pN+ 31%. The probability of recurrence free survival according to the MSKCC nomogram in the same risk groups was: 85% ± 5%, 62% ± 10% and 25% ± 13%, respectively. The area under the ROC curve was 0.795 (95% CI 0.739-0.852). CONCLUSION: In our series, the MSKCC nomogram constitutes a useful tool for predicting 5-year cancer free survival in patients who undergo radical cystectomy (AU)