BACKGROUND: Patients undergoing radical cystectomy with urinary diversions (UD) are at increased risk of bone fractures compared to the general population. Although a loss of bone mineral density (BMD) has been described in patients with UD, we still do not know with certainty why these patients follow this tendency.
OBJECTIVE: We performed a systematic review of the available literature to analyze the prevalence of osteoporosis and bone alterations in patients with ileal UD and the possible associated risk factors.
METHODS: We systematically searched PubMed® and Cochrane Library for original articles published before December 2022 according to PRISMA guidelines.
RESULTS: A total of 394 publications were identified. We selected 12 studies that met the inclusion criteria with 496 patients included. Six of the twelve studies showed decreased BMD values. Prevalence of osteoporosis was specified in three articles, with values ranging ​​from 0% to 36%. Risk factors such as age, sex, body mass index, metabolic acidosis and renal function appear to have an impact on bone tissue reduction, while type of UD, follow-up, 25-hydroxyvitamin D and parathormone had less evidence or contradictory data. The heterogeneity of the studies analyzed could led to interpretation bias.
CONCLUSIONS: UD are associated with multiple risk factors for osteoporosis and bone fractures. Identifying patients at highest risk and establishing diagnostic protocols in routine clinical practice are essential to reduce the risk of fractures and the resulting complications.

Metabolic acidosis (MA) is a well-known complication in patients with ileal urinary diversions. It is common in the early postoperative stages and decreases over time. Our objective is to investigate the prevalence of MA after more than one year of follow-up, identify the associated risk factors, and analyze its secondary metabolic consequences.
We conducted an observational study between January 2018 and September 2022 following the STROBE guidelines. MA was defined as a serum bicarbonate level ​​<22mEq/L. Finally, we analyzed 133 patients with a mean follow-up of 55.24 ± 42.36 months.
MA was observed in 16 (12%) patients. Patients with and without MA were comparable in age, sex, and follow-up time. The group with MA presented a higher rate of anemia (68,75% vs 19,65%, p < 0.001) and renal failure (100% vs 45,29%, p < 0.001), statistically significant higher levels of serum creatinine, chloride, potassium, parathyroid hormone, and phosphorus but lower serum values ​​of hemoglobin, renal glomerular filtration rate, total cholesterol, vitamin D, calcium, and albumin (all p < 0.05). Renal glomerular filtration rate was the only independent risk factor related to the development of MA (OR 0.914; 95% CI 0.878-0.95; p < 0.0001), proving a close correlation with venous bicarbonate values ​​(r = 0.387, p < 0.001).
MA is a little prevalent disorder in ileal urinary diversions more than one year after radical cystectomy is performed but it has secondary consequences on hematologic, renal, protein, lipid, and bone metabolism. We recommend to a close follow-up in patients with renal failure for early diagnosis and treatment.

The objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment.
Quasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3).
Of the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001).
There are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC.

Urine contact with the mucosa of the urinary diversion (UD) after radical cystectomy (RC) produces different ion exchanges that favor the development of metabolic acidosis (MA). This phenomenon is a frequent cause of hospital readmission and short/long-term complications. We performed a systematic review of MA in RCs with ileal UD, analyzing its prevalence, diagnosis, risk factors and treatment. We systematically searched Pubmed® and Cochrane Library for original articles published before May 2022 according to PRISMA guidelines. A total of 421 articles were identified. We selected 25 studies that met the inclusion criteria involving 5811 patients. Obtaining precise data on the prevalence of MA is difficult, largely due to the heterogeneity of the diagnostic criteria used given the diversity of studies analyzed. Development of MA is multifactorial. In the early period, MA is more prevalent in patients with UD with longer ileal segments, better urinary continence, and impaired renal function. Age and diabetes are risk factors associated with MA in later periods. MA is the most common cause of second or more hospital readmissions. Prophylaxis with oral bicarbonate for three months in patients at risk could improve these results. Although MA after ileal UD is a well-known condition, this review highlights the need to implement homogeneous criteria for the diagnosis, follow-up, and treatment, in addition to protocolizing prevention/prophylaxis strategies in patients at risk.

Predicting response to definitive treatmentsis a fascinating challenge which develops throughthe evolution of a panel of convincing molecularbiomarkers capable of adding in clinical decissionsdespite interpatient and intratumoral heterogenicity.Muscle-invasive bladder cancer (MIBC) can be locallytreated either with radical cystectomy (RC) with or withoutneoadyuvant chemotherapy or bladder preservationapproaches such as trimodal therapy (TMT) includingmaximal transurethral resection of bladder tumor(TURBt) followed by external beam radiotherapy withconcurrent systemic radio-sensitizing chemotherapy.Conventional or novel/targeted systemic agents areessential parts of perioperative multidisciplinary managementconsidering both neoadjuvant and adjuvantsetting. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomicanalysis, provided novel insights to achieve a fullunderstanding of the biology behind MIBC helping toidentify emerging predictive signatures. Although severalprogresses have been made, real-world applicationof molecular biomarkers in MIBC scenario is hinderedby lack of standardization, and low reproducibility. Inthis review we aim to present the emerging role of novelmolecular biomarkers in predicting response to localtreatments and systemic agents in MIBC.
La predicción de respuesta a tratamientosdefinitivos en un tumor es un desafío fascinantemediada por un panel de biomarcadores quepuedieran aportar información para tomar decisionesterapéuticas, pese a la heterogenicidad entrepacientes e intratumoral. El tumor vesical infiltrante(TVI) puede tratarse con cistectomía radical (CR) cono sin neoadyuvancia (NAD) o estrategias de preservaciónvesical como la terapia trimodal (TMT), que incluyeresección transuretral (RTU) máxima seguidade radioterapia externa con una quimioterapia radiosensibilizadoraconcomitante. Las terapias convencionaleso dirigidas son esenciales dentro del manejomultidisciplinar necesario en sus facetas neo y adyuvantes.Los avances en biología molecular, como lasecuenciación moderna y el análisis transcriptómicodel genoma, han permitido empezar a entenderel comportamiento molecular del TVI ayudando aidentificar firmas predictivas. Aunque se han hechoprogresos, la aplicación asistencial de biomarcadores en TVI está frenada por la falta de estandarización yla baja reproducibilidad de distintos resultados esperanzadores.En esta revisión, pretendemos exponerel papel emergente de nuevos marcadores molecularesen la predicción de respuesta a tratamientos localesy sistémicos en el TVI.

BACKGROUND: Although in the recent years, laparoscopy and Enhanced Recovery After Surgery (ERAS) protocols have improved postoperative recovery in radical cystectomy (RC), the clinical efficacy of their association remains unclear. Our objective is to analyze the possible benefits obtained from laparoscopic RC (LRC) and its subsequent combination with an ERAS (ERAS-LRC) protocol compared to open RC (ORC).
METHODS: We analyzed 187 consecutive RCs with ileal conduit performed in our center, of which 139 met the inclusion criteria: 47 ORC, 39 LRC (both with conventional protocol) and 52 ERAS-LRCs.
RESULTS: No significant differences were found regarding age, sex, BMI and ASA score between groups. ERAS-LRC obtained a shorter length of stay than LRC and ORC (median 8 [7-10]) vs. 13 [10-17] vs. 15 [13-19.5] days, respectively; P<.001). ERAS-LRC had a shorter stay in the ICU and less days of nasogastric tube (P<.001). Postoperative complications and readmission rates were similar among groups. Multivariate logistic regression showed that absence of complications, younger age and ERAS behaved as independent factors for shorter hospital stay, while ERAS was the only independent factor of lower readmission rate at 90 days.
CONCLUSIONS: Although LRC presented perioperative benefits compared to ORC, the results were better after the implementation of an ERAS protocol. ERAS protocol had stronger impact on recovery than the surgical approach of the procedure.

BCG is currently the standard of care in intermediate and high risk non-invasive bladder tumors. In high-risk patients treated with BCG up to 30% will recurand 10% will progress within 2 years. Oncological outcomes with bladder preserving strategies are limited so radical cystectomy is recommended after BCG failure. Some promising treatments, such as check point inhibitors (PD1, PDL-1), are being studied for non-responders to BCG. Knowing the management of critical situations during BCG treatment its crucial in daily practice and clinical trials design. The aim of this study is to present these definitions and to remember some important aspect sof BCG management.
La BCG es en la actualidad el tratamiento de elección en tumores vesicales no músculo invasivo de riesgo intermedio y alto. De los pacientes de alto riesgo tratados con BCG, hasta un 30% recidivarán y un 10% progresarán en 2 años. Los resultados oncológicos de estos pacientes con estrategias de conservación vesical son modestos, por lo que la cistectomía radicales el tratamiento de elección tras fallo de BCG. Están siendo estudiadas diferentes opciones de tratamiento para pacientes no respondedores a BCG, como son los inhibidores de los puntos de control (PD1, PDL-1). Para el diseño de los ensayos clínicos (EC) y para homogeneizar nuestra práctica clínica diaria, es necesario tener clara la definición de una serie de situaciones, en las que nos podemos encontrar durante un tratamiento con BCG. El objetivo de este trabajo es revisar estas definiciones y recordar algunos aspectos del manejo de la BCG implicados en las mismas.

To evaluate the prevalence of preoperative anemia and its effect on oncological outcomes in patients undergoing radical cystectomy (RC) due to bladder cancer.
Retrospective single-center study with 176 RCs between May 2008 and July 2018. Anemia was defined according to the WHO classification (male<130mg/dL, female<120mg/dL). Kaplan-Meier test was used to estimate recurrence-free, cancer-specific and overall survival rates. Multivariate logistic regression was used to identify factors associated with overall mortality rates.
Overall, 89 (50.6%) patients had preoperative anemia, and 44 of them (49.4%) received neoadjuvant chemotherapy. Anemic patients resulted in higher rates of ASA (ASA>2: 54.6 vs. 27.5%; P=.003), ectasia rate previous to RC (41.6 vs. 19.5%; P=.002), treatment with neoadjuvant chemotherapy (49.4 vs. 19.5%; P<.001), blood transfusion rate (25.8 vs. 11.5%; P=.015) and pathological stage (pT>2: 49.4 vs. 33.3%; P=.03) compared to non-anemic patients. Median follow-up was 27.2 months (IQR 11.12-72.28). Median overall survival (105 vs. 34 months, log-rank; P=.001), cancer-specific survival (89 vs. 61 months; P=.004) and recurrence-free survival (85 vs. 57 months; P=.002) were significantly lower in anemic patients compared to the non-anemic group. In multivariable Cox analysis, preoperative anemia, pT>2 and N≥1 were independently associated with overall mortality.
Preoperative anemia was common in patients undergoing RC for bladder cancer, and it is related with a worse cancer prognosis. Anemia is a preoperative modifiable factor; we believe that the implementation of Patient Blood Management programs during prehabilitation may have a relevant role in improving the oncological outcomes in these patients.

Based on preoperative clinical and postoperative pathological variables, we aim to build a prediction model of cancer specific mortality (CSM) at 1, 3, and 5 years for patients with bladder transitional cell carcinoma treated with RC.
Retrospective analysis of 517 patients with diagnosis of cell carcinoma treated by RC (1986-2009). Demographic, clinical, surgical and pathological variables were collected, as well as complications and evolution after RC. Comparative analysis included Chi square test and ANOVA technique. Survival analysis was performed using Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using logistic regression to identify the independent predictors of CSM. The individual probability of CSM was calculated at 1, 3 and 5 years according to the general equation (logistic function). Calibration was obtained by the Hosmer-Lemeshow method and discrimination with the elaboration of a ROC curve (area under the curve).
BC was the cause of death in 225 patients (45%). One, three and five-year CSM were 17%, 39.2% and 46.3%, respectively. The pT and pN stages were identified as independent prognostic variables of CSM at 1, 3 and 5 years. Three prediction models were built. The predictive capacity was 70.8% (CI 95% 65-77%, p=.000) for the 1st year, 73.9% (CI95% 69.2-78.6%, p=.000) for the third and 73.2% (CI% 68.5-77.9%, p=.000) for the 5th.
The prediction model allows the estimation of CSM risk at 1, 3 and 5 years, with a reliability of 70.8, 73.9 and 73.2%, respectively.

Currently, the role of adjuvant chemotherapy (ADJ) in muscle invasive bladder tumor remains controversial.
To evaluate the effect of ADJ on cancer specific survival of muscle invasive bladder tumor after radical cystectomy (RC).
Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor pT3-4pN0 / + cM0 stage, treated with RC between 1986-2009. Total cohort was divided in two groups: 185 (63.4%) patients treated with ADJ and 107 (36.6%) without ADJ. Median follow-up was 40.5 months (IQR 55-80.5). Comparative analysis was performed with Chi-square test and Student\'s t test /ANOVA. Survival analysis was carried out with the Kaplan-Meier method and log-rank test. Multivariate analysis (Cox regression) was made to identify independent predictors of cancer-specific mortality (CSM).
42.8% of the series presented lymph node involvement after RC. At the end of follow-up, 22.9% were BC-free and 54.8% had died due to this cause. The median cancer specific survival was 30 months. No significant differences were observed in cancer specific survival regarding the treatment with ADJ in pT3pN0 (p=.25) or pT4pN0 (p=.29) patients, but it was significant in pT3-4pN+ (p=.001). Multivariate analysis showed pathological stage (p=.0001) and treatment with ADJ (p=.007) as independent prognostic factors for CSM. ADJ reduced the risk of CSM (HR:0.59,95% CI 0.40-0.87, p=.007).
pT and pN stages were identified as independent predictors of CSM after RC. The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM, although only pN+ patients were benefited in the stage analysis.