Multidisciplinary consensus document on the current treatment of bacille Calmette-Guérin-unresponsive non-muscle invasive bladder tumor.

Radical cystectomy is the current treatment of choice for patients with BCG-unresponsive non-muscle invasive bladder tumor (NMIBC). However, the high comorbidity of this surgery and its effects on the quality of life of patients require the investigation and implementation of bladder-sparing treatment options. These must be evaluated individually by the uro-oncology committee based on the characteristics of the BCG failure, type of tumor, patient preferences and treatment options available in each center. Based on FDA-required oncologic outcomes (6-month complete response rate for CIS: 50%; duration of response in responders for CIS and papillary: 30% at 12 months and 25% at 18 months), there is not currently a strong preference for one treatment over another, although the intravesical route seems to offer less toxicity. This work summarizes the evidence on the management of BCG-unresponsive NMIBC based on current scientific evidence and provides consensus recommendations on the most appropriate treatment.

Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy.

INTRODUCTION AND OBJECTIVES: Although the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. PATIENTS AND METHODS: A retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. RESULTS: Asymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. CONCLUSIONS: Genitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

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.

Management of primary upper urinary tract carcinoma in situ diagnosed by ureteroscopic biopsy: Is bacillus Calmette-Guerin an alternative to nephroureterectomy?

BACKGROUND: Radical nephroureterectomy (RNU) represents the gold standard treatment for upper tract urothelial carcinoma (UTUC); however, attempts have been made to treat upper urinary tract CIS (UT-CIS) conservatively. The aim of this study was to compare the outcome of patients with primary UT-CIS treated in our center by means of RNU vs. bacillus Calmette-Guérin (BCG) instillations. METHODS: This retrospective study included patients with diagnosis of primary UT-CIS between 1990 and 2018. All patients had histological confirmation of UT-CIS in the absence of other concomitant UTUC. Histological confirmation was obtained by ureteroscopy with multiple biopsies. Patients were treated with BCG instillations, RNU or distal ureterectomy. Clinicopathological features and outcomes were compared between RNU and BCG groups. RESULTS: A total of 28 patients and 29 renal units (RUs) were included. Sixteen (57.1%) patients (17 RUs) received BCG. BCG was administered via nephrostomy tube in 4 patients, with a single-J ureteral stent in 5, and using a Double-J stent in 7. Complete response and persistence or recurrence were detected in ten (58.8%) and seven (41.2%) RUs treated with BCG, respectively. Eight (27.6%) RUs underwent RNU, and 4 (13.8%) Rus distal ureterectomy. No differences were found in recurrence-free survival (p=0.841) and cancer-specific survival (p=0.77) between the RNU and BCG groups. CONCLUSIONS: Although RNU remains the gold standard treatment for UT-CIS, our results confirm that BCG instillations are also effective. Histological confirmation of UT-CIS is mandatory before any treatment.

Treatment of severe multi-drug resistant Pseudomonas aeruginosa infections.

Pseudomonas aeruginosa is the microorganism most frequently involved in the main ICU-acquired infections, with special importance in ventilator associated pneumonia. Its importance lies, in addition to its high incidence in critically ill patients, in the severity of the infections it causes and in the difficulty of its antimicrobial treatment, directly related to the high percentage of resistance to antibiotics classically considered first-line. New active antibiotics have recently been developed against Pseudomonas aeruginosa, even against multi-drug resistant strains. This review analyzes both the differential characteristics of Pseudomonas aeruginosa infections and the new therapeutic options, focusing on multi-drug resistant Pseudomonas aeruginosa.

Infección diseminada por el bacilo vacunal Calmette-Guerin

RESUMEN Introducción: La infección diseminada por el bacilo vacunal Calmette-Guerin es una rara reacción adversa severa asociada a inmunodeficiencia. Objetivo: Describir una serie de cinco casos con infección vacunal diseminada. Presentación de casos: Se presentan cinco casos vacunados al nacer, predominio masculino 4 (80 %), promedio edad inicio: 8,4 meses 2 (15 %) y de edad al diagnóstico: 17,8 meses 6 (31 %). Cuadro clínico de huella vacunal ulcerada, linfadenitis axilar ipsilateral y en regiones distales, hepatosplenomegalia y afectación de otros órganos, con manifestaciones sistémicas y nutricionales. Existió consanguinidad en tres e historia familiar sospechosa de inmunodeficiencia en otros tres. Todos fallecieron: tres enfermos antes de los 3 años. Se realizaron estudios inmunológicos convencionales a todos los enfermos. Un paciente presentaba Inmunodeficiencia severa combinada, en los otros se sospechó enfermedad granulomatosa crónica en uno y síndrome de susceptibilidad mendeliana a micobacterias en tres. Conclusiones: Aunque la vacuna BCG raramente presenta diseminación del bacilo vacunal, debe sospecharse esta entidad en niños pequeños, con las características severas y sistémicas que se describen, con manifestaciones sugestivas de tuberculosis que no responden al tratamiento antituberculoso de primera línea.

ABSTRACT Introduction: The infection disseminated by the vaccine bacillus Calmette-Guerin is a rare severe adverse reaction associated with immunodeficiency. Objective: Describe a series of five cases with disseminated vaccine infection. Presentation of cases : There are five cases vaccinated at birth: predominance of the male sex in 4 (80%), average age onset: 8.4 months in 2 (15 %) and age at diagnosis: 17.8 months in 6 (31 %); clinical picture of ulcerated vaccine footprint, ipsilateral axillary lymphadenitis and in distal regions, hepatosplenomegaly, involvement of other organs, with systemic and nutritional manifestations. There was consanguinity in three of the patients and suspicious family history of immunodeficiency in three others. All died: three were sick before the age of 3. Conventional immunological studies were performed in all cases. One patient had severe combined immunodeficiency, chronic granulomatous disease was suspected in one, and Mendelian susceptibility syndrome to mycobacteria in three. Conclusions: Although the BCG vaccine rarely presents dissemination of the vaccine bacillus, this entity should be suspected in young children, with the severe and systemic characteristics described, with manifestations suggestive to tuberculosis that do not respond to first-line anti-tuberculous treatment.

Tuberculoma simulador de cáncer de ovario / Tuberculoma mimicking ovarian cancer

Resumen INTRODUCCIÓN: La tuberculosis sigue siendo un problema de salud pública global: alrededor de un cuarto de la población mundial está infectada con el bacilo de la tuberculosis, pero solo 5 a 15% realmente resultarán con la enfermedad. Pese a los esfuerzos por controlar la infección, hoy en día es la principal causa de muerte producida por un único agente infeccioso. La forma extrapulmonar es rara, y la genital suele manifestarse con esterilidad, en otros simula un cáncer de ovario avanzado, incluidas la masa anexial y la ascitis, pérdida de peso y elevación del marcador tumoral Ca125. El diagnóstico diferencial prequirúrgico es complejo, de ahí que a la mayoría de las pacientes se les indique una intervención quirúrgica innecesaria. CASO CLÍNICO: Paciente de 29 años con diagnóstico de formación anexial sospechosa de malignidad que se trató de manera conservadora hasta conseguir su regresión total. Además, se efectuó una revisión de la bibliografía relacionada con esta infrecuente entidad. CONCLUSIÓN: La conjunción de ascitis, masa pélvica y elevación del marcador Ca125 puede corresponder al diagnóstico de cáncer de ovario avanzado, ello sin olvidar la posibilidad de tuberculosis extraperitoneal en pacientes con antecedente de tuberculosis o procedentes de zonas endémicas. El diagnóstico es complejo, sobre todo por la baja incidencia en nuestro medio, que a menudo requiere laparoscopias exploradoras para confirmar el origen de las lesiones.

Abstract INTRODUCTION: Tuberculosis remains a global public health problem: about a quarter of the world's population is infected with the tuberculosis bacillus, but only 5-15% will actually develop the disease. Despite efforts to control the infection, today it is the leading cause of death from a single infectious agent. The extrapulmonary form is rare, and the genital form usually manifests with sterility, in others it simulates advanced ovarian cancer, including adnexal mass and ascites, weight loss and elevation of the tumor marker Ca125. The pre-surgical differential diagnosis is complex, hence most patients are indicated for unnecessary surgery. CLINICAL CASE: A 29-year-old patient with a diagnosis of adnexal formation suspicious for malignancy was treated conservatively until complete regression was achieved. In addition, a review of the existing literature related to this rare entity was performed. CONCLUSION: The conjunction of ascites, pelvic mass and elevated Ca125 marker may correspond to the diagnosis of advanced ovarian cancer, without forgetting the possibility of extraperitoneal tuberculosis in patients with a history of tuberculosis or from endemic areas. Diagnosis is complex, especially due to the low incidence in our environment, which often requires exploratory laparoscopy to confirm the origin of the lesions.

[Bladder cancer immunological background and biomarkers.] / Bases inmunológicas del cáncer vesical y biomarcadores.

Bladder cancer was one of the first to have a successful treatment based on immune system stimulation, recognized by patient survival and tumor recurrence data. In addition, bladder tumors are now known to have high antigenic load and are therefore considered to be susceptible to respond well to new immunotherapies. For these reasons, studying the mechanism of action of bladder cancer immunological-based treatments can provide valuable information both to improve their current use and to under stand why they work in some patients while others do not tolerate this therapy or have tumor progression. In this article, we will focus on the immune response generated by treatment of non-muscle invasive bladder tumors with BCG, as well as the relationship between this knowledge and new immunotherapies. We will first describe the main activities of the immune system, to continue with the treatment of bladder cancer with BCG, its mechanism of action and biomarkers. Finally, we will summarize the observations that led to the useof monoclonal antibody immunotherapy in cancer and will describe some of the new immunotherapies in use to treat bladder cancer patients.

El cáncer vesical fue uno de los primeros en tener un tratamiento de éxito basado en la estimulación del sistema inmunitario, apoyado por los datos de supervivencia de los pacientes y recurrencia de los tumores. Además, hoy día se sabe que los tumores de vejiga presentan alta carga antigénica y, por ello, se considera que son susceptibles de responder favorablemente a las nuevas inmunoterapias. Por estos motivos, estudiar el mecanismo de acción de los tratamientos inmunológicos de cáncer de vejiga nos puede aportar información muy valiosa tanto para mejorar su uso actual como para comprender por qué funcionan en unos pacientes mientras que otros no toleran la terapia o tienen progresión tumoral. En este artículo vamos a centrarnos en la respuesta inmunitaria generada por el tratamiento de los tumores devejiga no-músculo invasivos con BCG, así como la relación entre estos conocimientos y las nuevas inmunoterapias. Para ello, en primer lugar describiremos las principales actividades del sistema inmunitario para continuar con los fundamentos del tratamiento del cáncer devejiga con BCG, su mecanismo de acción y biomarcadores. Por último, recordaremos las observaciones que llevaron al uso de la inmunoterapia con anticuerpos monoclonales en cáncer y describiremos algunas de las nuevas inmunoterapias que se están introduciendo para tratar cánceres vesicales.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines.

Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines / SARS-CoV-2: coronavirus previos, respuesta inmune y desarrollo de vacunas

Abstract Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Resumen Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder. / Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3.

INTRODUCTION AND OBJECTIVES: Various studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. PATIENTS OR MATERIALS AND METHODS: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. RESULTS: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. CONCLUSIONS: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

Miliary tuberculosis induced by intravesical instillation of bacillus Calmette-Guérin. / Tuberculosis miliar inducida por instilación endovesical de bacilo de Calmette-Guérin.

The intravesical instillation of bacillus Calmette-Guérin (BCG) is an efficacious complementary treatment for superficial bladder cancer after transurethral resection. This treatment delays progression, decreases the probability that the patient will have to undergo cystectomy in the future, and improves survival; it is generally efficacious and well tolerated. Among the most common local complications are irritative symptoms, hematuria, local genitourinary infection. Systemic complications are much less common. We present the case of a 71-year-old man who developed miliary tuberculosis secondary to treatment with intravesical bacillus Calmette-Guérin for bladder cancer. This is exceptionally uncommon complication is potentially lethal and requires the immediate discontinuation of treatment.

Impact of removing sinks from an intensive care unit on isolations by gram-negative non-fermenting bacilli in patients with invasive mechanical ventilation. / Impacto de la retirada de los lavabos en una unidad de cuidados intensivos sobre los aislamientos por bacilos gramnegativos no fermentadores en pacientes con ventilación mecánica invasiva.

INTRODUCTION AND OBJECTIVE: Contamination of sinks, even due to their underuse, is associated with the transmission of non-fermenting gram-negative bacilli (NFGNB) to patients in Augmented Care Units. After previous monitoring with environmental and patient samples, we now explore the impact of removing sinks from ICU cubicles on incidental isolations related to health care in bronchoaspirate samples of patients with invasive mechanical ventilation (IMV). MATERIAL AND METHODS: Quasi-experimental study, before-and-after, pre-intervention annuities April 2014-2016 and post-intervention April 2016-2017. Incidence densities per 1,000 days of IMV were studied, comparing by the exact method based on the binomial distribution and estimating the incidence density ratio. RESULTS: The incidence densities per 1,000 days of IMV of isolations by NFGNB in bronchoaspirate samples of the pre and post-intervention periods were 11.28 and 1.9, respectively. This implies a post-intervention incidence density 5.90 times lower than before (95% CI: 1.49-51.05, P=.003). CONCLUSIONS: Despite of the limitations of the design, the removal of sinks showed a reduction of the isolations.

How Far Are we Away From an Improved Vaccine For Tuberculosis? Current Efforts and Future Prospects.

Tuberculosis still is a major public health problem worldwide, and vaccines may play a major role in its eradication. However, despite 20 years of intensive research, we still do not have a better vaccine than the Bacille Calmette-Guérin vaccine, which has been used since 1921 but exhibits only limited efficacy in the field. This effort has not, however, been entirely in vain as our understanding of TB vaccinology has been substantially expanded and there are currently 17 vaccine candidates in clinical development and several more in preclinical trials. This manuscript reviews the most important recent advances, concerns raised and future prospects in the TB vaccinology field.

Under-utilization of taps in intensive care unit as a cause of reservoirs of nonfermenting gram-negative bacilli. / La infrautilización de grifos en una unidad de cuidados intensivos como causa de reservorios de bacilos gramnegativos no fermentadores.

INTRODUCTION: The under-utilisation of taps is associated with the generation of reservoirs of non-fermenting gram-negative bacilli with the ability to disseminate. We describe the detection and approach of the problem in an ICU. METHODS: Observational descriptive study in an ICU with individual cubicles with their own sink. We collected clinical samples from patients and environmental samples from tap aerators and reviewed the unit's hygiene measures. RESULTS: We detected four cases due to Chryseobacterium indologenes, one to Elizabethkingia meningoseptica and another to Pseudomonas aeruginosa; they were identified both in clinical and the environmental samples. The healthcare professionals reported that almost every hand hygiene opportunity was performed with a hydroalcoholic solution. After considered the daily flushing of water outlets as inefficient, it was decided to remove them. CONCLUSIONS: National recommendations were insufficient for preventing, detecting and controlling tap contamination in units with a high risk of infection. The management of taps in these units needs to be improved.

Indication for early cystectomy in nonmuscle-invasive bladder cancer. Literature review. / Indicación de cistectomía precoz en el cáncer vesical no músculo infiltrante. Revisión de la literatura.

CONTEXT: High-risk nonmuscle-invasive bladder cancer is a disease that includes a heterogeneous group of patients, for whom close follow-up is recommended due to the risk of progression to a muscle-invasive tumour. The treatment of choice for these tumours is transurethral resection of the bladder tumour followed by a programme of bacillus Calmette-Guerin instillations. There is a subgroup of patients who have a greater risk of progression and who benefit from early radical treatment. OBJECTIVE: To identify which patient group with nonmuscle-invasive bladder cancer will benefit from early radical treatment. SEARCHING THE EVIDENCE: We performed a literature review to identify the risk factors for progression for these patients and thereby recommend a treatment that improves their survival rate. SYNTHESIS OF THE EVIDENCE: We identified the various prognostic factors associated with tumour progression: the persistence of T1 tumour in re-resection of the bladder tumour, the presence of carcinoma in situ, patients refractory to bacillus Calmette-Guerin treatment, patients older than 70 years, tumours larger than 3cm, the substaging of T1 tumours, the presence of lymphovascular invasion and the presence of a tumour in the prostatic urethra. Similarly, we comment on the advantages of radical versus conservative treatment, considering that the performance of an early cystectomy due to a high-risk noninvasive vesical tumour has a better cancer prognosis than those in which the operation is deferred until the progression. CONCLUSIONS: In this disease, it is important to individualise the patients to provide them personalized treatment. For patients with the previously mentioned characteristics, it is recommended that early cystectomy not be delayed.

Disfunción orgánica múltiple como complicación de la instilación intravesical de bacilo de Calmette-Guérin: comunicación de un caso y revisión de la literatura / Multiple organ dysfunction as a complication of Bacille Calmette-Guérin intravesical instillation (BCG): report of a case an literature review

La instilación intravesical de bacilo de Calmette-Guérin (BCG) es el tratamiento de primera línea para el carcinoma superficial de células transicionales de la vejiga. Aunque su uso es relativamente seguro, complicaciones graves como hepatitis granulomatosa, osteomielitis, neumonía, sepsis y disfunción orgánica múltiple se producen en algunos pacientes. Presentamos el caso de un paciente con diagnóstico de carcinoma de células de transición superficial de la vejiga (T1), que fallece como consecuencia de una complicación sistémica grave con severo compromiso del sistema nervioso central, secundaria a la instilación intravesical de BCG.

Bacille Calmette-Guérin intravesical instillation (BCG) is the main treatment for superficial transitional cell carcinoma of the bladder. In spite of it being a safe procedure, severe complications as granulomatous hepatitis, osteomyelitis, pneumonia, sepsis and multiple organ dysfunction syndrome occur in a few patients. The study presents the case of a patient with a diagnosis of superficial transitional cell carcinoma of the bladder (T1), who died as a consequence of a severe systemic compromise of the central nervous system, secondary to instravesical instillation of BCG.

A instilação intravesical de bacilo de Calmette-Guérin (BCG) é o tratamento de primeira linha para o carcinoma superficial de células transicionais de bexiga. Embora seu seja relativamente seguro, as complicações graves como hepatite granulomatosa, osteomielite, pneumonia, sepse e disfunção orgânica múltipla possam ocorrem em alguns pacientes. Apresentamos o caso de um paciente com diagnóstico de carcinoma de células de transição superficial de bexiga (T1), que falece como consequência de uma complicação sistêmica grave com severo compromisso do Sistema Nervoso Central, secundária à instilação intravesical de BCG.

Bladder cancer: Present and future. / Tumor vesical: presente y futuro.

Bladder cancer has a high incidence and involves high associated morbidity and mortality. Since its initial clinical suspicion, early diagnostic confirmation and multimodal treatment involve different medical specialties. For this reason, we consider it important to spread the current consensus for its management. Recent advances in immunology and Chemotherapy make it necessary to expose and reflect on future perspectives.

Performance of LED fluorescence microscopy for the detection of acid-fast bacilli from respiratory samples in peripheral laboratories in Argentina / Rendimiento de la microscopía de fluorescencia LED para la detección de bacilos ácido-alcohol resistentes en muestras respiratorias en laboratorios periféricos de Argentina

ABSTRACT Introduction: Light-emitting diode fluorescence microscopy (LED-FM) has been endorsed by the World Health Organization (WHO) for tuberculosis diagnosis, but its accuracy in HIV-infected patients remains controversial, and only some few studies have explored procedural factors that may affect its performance. Objective: To evaluate the performance of LED-FM for tuberculosis diagnosis in patients with and without HIV infection using a newer, less expensive LED lamp. Materials and methods: We compared the performance of LED-FM and Ziehl-Neelsen (ZN) microscopy on respiratory specimen smears from tuberculosis (TB) suspects and patients on treatment examined by different technicians blinded for HIV-status and for the result of the comparative test. We analyzed the effect of concentrating specimens prior to microscopy using different examination schemes and user-appraisal of the LED device. Results: Of the 6,968 diagnostic specimens collected, 869 (12.5%) had positive Mycobacterium tuberculosis cultures. LED-FM was 11.4% more sensitive than ZN (p<0.01). Among HIV-positive TB patients, sensitivity differences between LED-FM and ZN (20.6%) doubled the figure obtained in HIV-negative patients or in those with unknown HIV status (9.3%). After stratifying by direct and concentrated slides, the superiority of LED-FM remained. High specificity values were obtained both with LED-FM (99.9%) and ZN (99.9%).The second reading of a sample of slides showed a significantly higher positive detection yield using 200x magnification (49.4 %) than 400x magnification (33.8%) (p<0.05). The LED-device had a very good acceptance among the technicians. Conclusion: LED-FM better performance compared with ZN in HIV-infected patients and user-appraisal support the rapid roll-out of LED-FM. Screening at 200x magnification was essential to achieve LED-FM increased sensitivity.

RESUMEN Introducción. La microscopía de fluorescencia con lámpara LED (MF-LED) ha sido recomendada por la Organización Mundial de la Salud (OMS) para el diagnóstico de la tuberculosis, pero su precisión en pacientes con HIV continúa siendo controversial y en pocos estudios se han explorado los factores metodológicos que pueden afectar su utilidad. Objetivo. Evaluar el rendimiento de la MF-LED en el diagnóstico de la tuberculosis en pacientes con HIV y sin él mediante un novedoso dispositivo LED. Materiales y métodos. Se comparó el rendimiento de la MF-LED y la microscopía en frotis de muestras respiratorias con tinción de Ziehl-Neelsen (M-ZN) examinados por técnicos cegados en cuanto al estado de HIV y el resultado de la prueba comparativa. Se analizó el efecto de concentrar muestras antes de la microscopía, usar diferentes esquemas de observación y la valoración con el dispositivo LED. Resultados. De las 6.968 muestras recolectadas, 869 (12,5 %) resultaron con cultivo positivo para Mycobacterium tuberculosis. La MF-LED fue 11,4 % más sensible que la M-ZN (p<0,01). Entre los pacientes con tuberculosis positivos para HIV, la diferencia de sensibilidad entre la MF-LED y la M-ZN (20,6 %) duplicó la cifra obtenida en pacientes negativos para HIV o con estatus desconocido (9,3 %). Al estratificar los frotis en directos y concentrados, se mantuvo la superioridad de la MF-LED. Las especificidades de la MF-LED (99,9 %) y la M-ZN (99,9 %) resultaron elevadas. La lectura de una muestra de frotis mostró una positividad significativamente mayor con un aumento de 200X (49,4 %) que con uno de 400X (33,8 %) (p<0,05). El dispositivo LED tuvo una buena aceptación entre los técnicos. Conclusión. Debido al mejor desempeño de la MF-LED comparada con la M-ZN en pacientes con HIV y su fácil utilización, se recomienda su adopción. La utilización del aumento de 200X fue esencial para el incremento de la sensibilidad de la MF-LED.

Adjuvant intravesical treatment for nonmuscle invasive bladder cancer: The importance of the strain and maintenance. / Tratamiento adyuvante intravesical en cáncer de vejiga no músculo invasivo: importancia de la cepa y el mantenimiento.

BACKGROUND AND OBJECTIVE: Intravesical Bacille Calmette-Guérin (BCG) is essential for preventing the recurrence and progression of superficial bladder tumours. The aim of our study was to compare the efficacy and toxicity of the Connaught and Tice strains, as well as the importance of the maintenance regimen. MATERIAL AND METHODS: We retrospectively reviewed 110 patients with superficial bladder tumours who underwent adjuvant endovesical treatment. The patients were distributed into 3 groups, based on whether the treatment was with the Connaught strain, the Tice strain or both sequentially. We calculated the relapse-free survival rate in each group and compared the patients who completed the maintenance treatments against those who did not. To identify the predictors of relapse, we performed a multivariate analysis. We also assessed the toxicity by analysing the onset of BCGitis, urinary urgency, fever, urinary tract infection and treatment withdrawing due to adverse effects. RESULTS: We found no differences in the efficacy parameters. The patients in the Connaught group completed the maintenance to a lesser extent (38.4 vs. 72% for the Tice group and 76.3% for both groups; P=.010). The patients who completed the maintenance had better relapse-free survival at 60 months (88.5 vs. 74.2%; P=.036), regardless of the strain employed. The multivariate analysis identified a size larger than 3cm, more than 3 implants and not completing the maintenance as risk factors of relapse. The patients with the Connaught strain had higher rates of BCGitis, with no differences in the other events studied. CONCLUSION: Completing the maintenance phase is essential, regardless of the strain employed. The Connaught strain has a greater risk of BCGitis, and a sequential regimen could be useful in certain scenarios.