Laparoscopic Management of Chylous Leakage Using a Direct Lymph Node Injection with Methylene Blue as a Leakage Point Location Strategy in a Patient with Retroperitoneal Extragonadal Seminoma

Background: The first-line treatment in cases of chylous leakage is conservative, and operation should be considered only in patients who fail to respond to this treatment. The main clinical concern is the difficulty of intraoperative localization of the site of leakage that can affect surgical outcome. Case Presentation: A 33-year-old man presented with a 4-month history of abdominal pain and weight loss. CT scan revealed enlarged retroperitoneal lymph nodes. Retroperitoneal lymph node biopsy was performed owing to the suspicion of lymphoproliferative disease, with a pathological result of nonspecific adenitis. Because of persistence of pain, an abdominal CT scan showed a large left retroperitoneal fluid collection that was found to be compatible with chyle after drainage. Conservative treatment was established, but because of its failure, surgical management was attempted by the laparoscopic approach. Intraoperative direct lymph node injection of methylene blue was used as a leakage point location strategy that allows selective ligation of the site of leakage. Thereafter a gradual reduction in chyle output to zero was observed. Conclusion: The laparoscopic approach could be a feasible and successful method for the management of chyle leakage in patients refractory to conservative treatment. Intraoperative direct lymph node injection of methylene blue could be a useful technique to facilitate detection of the site of leakage during operation

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Impacto clínico del carcinoma in situ en pacientes con tumor vesical no músculo invasor. Incidencia y factores predictivos de recurrencia, progresión y supervivencia cáncer específica

INTRODUCCIÓ: El CIS vesical és una lesió plana d'alt grau limitada a la mucosa que comparteix característiques genotípiques similars a les del tumor vesical múscul invasiu (TVMI). Sense tractament, fins un 50% dels pacients progressen a TVMI. Actualment, el BCG representa el tractament estàndard del CIS vesical recolzat per l'assaig SWOG 8507 i el protocol 30861 de la EORTC. JUSTIFICACIÓ CIENTÍFICA Els estudis que han avaluat els resultats a llarg termini dels pacients amb CIS vesical estan limitats per la mida de la mostra, immunoteràpia amb BCG sense manteniment, us de quimioteràpia intravesical, i anàlisis univariants no ajustats, la qual cosa ha donat lloc a resultats contradictoris. OBJECTIUS (1) Descriure els resultats oncològics en termes de recurrència vesical, progressió, i recurrència en el tracte urinari superior del pacients amb CIS tractats amb BCG. (2) Avaluar les implicacions pronòstiques de les classificacions clínica (primari, secundari i concomitant) i patològica (primari, cTa-CIS, cT1-CIS) del CIS vesical (3) Determinar el pronòstic de la resposta completa als 6 mesos després de l'inici del tractament adequat amb BCG en pacients amb CIS vesical. HIPOTESIS Amb els canvis de les guies de pràctica clínica en el tractament de pacients amb TVNMI (esquema de manteniment amb BCG, re-RTUv, definició adequada de no resposta), el pronòstic oncològic del CIS vesical ha canviat. (2) Presència d'heterogeneïtat en l'evolució dels pacients amb CIS vesical quan s'estratifiquen d'acord a les classificacions clínica i patològica. (3) Absència de resposta als 6 mesos després de l'inici del tractament adequat amb BCG, presenta implicacions pronòstiques per les decisions sobre tractaments posteriors. DISENY DE L'ESTUDI I POBLACIÓ Estudi observacional retrospectiu de centre únic de pacients amb CIS vesical amb o sense TVNMI exofític associat tractats amb BCG durant el període 2008-2015 (n=386). RESULTATS (1) Durant els primers 3 anys es van registrar 117/159 (73,6%) recurrències, 38/55 (69,1%) progressions a TVMI, i 15/31 (48,4%) recurrències al tracte urinari superior. Després de 5 anys de seguiment s'observà recurrència, progressió a TVMI i recurrència al tracte urinari superior en 26/159 (16,4%), 7/55 (12,7%) y 12/31 (38,7%) pacients, respectivament. (2) La regressió de Cox ajustada mitjançant un model de propensió mostrà que el tractament adequat amb BCG millora significativament la supervivència lliure de recurrència HR: 0.21 ((IC95%: 0.13-0.34), supervivència lliure de progressió HR: 0.46 (IC95%: 0.25-0.87) y supervivència lliure de tumor del tracto urinari superior HR: 0.24 (IC95%: 0.09-0.64). (3) La regressió de Cox multivariant mostrà que ni la classificació clínica ni patològica semblen ser factors predictius de resultats oncològics en el pacients amb CIS vesical. (4) La regressió de Cox ajustada mitjançant un model de propensió mostrà que aquells pacients que no varen respondre a BCG després d'un tractament adequat, presentaren pitjor supervivència lliure de progressió HR: 3,40 (IC95%: 1,59-7,27), supervivència lliure de cistectomia radical HR: 3,52 (IC95%: 1,77-7) y supervivència càncer específica HR: 4,42 (IC95%: 1,95-10,01). CONCLUSIONS (1) Els pacients amb CIS vesical presenten alt risc de recurrència, progressió i recurrència en el tracte urinari superior durant els primers tres anys de seguiment. Degut al risc de recurrència i progressió a més de 5 anys, la vigilància ha de continuar-se de forma prolongada. (2) L'exposició a un tractament "adequat" amb BCG millora els resultats oncològics dels pacients amb CIS vesical. (3) No existeix suficient evidència per recolzar l'ús de les classificacions clínica i patològica per guiar el tractament i/o el seguiment dels pacients amb CIS vesical. (4) Els pacients que no responen als 6 mesos de l'inici del tractament adequat amb BCG, presenten pitjors resultats oncològics a llarg termini.Introducción: El CIS vesical es una lesión plana de alto grado limitada a la mucosa que comparte características genotípicas similares a las del TVMI. Sin tratamiento, hasta el 50% de los pacientes progresan a TVMI. En la actualidad, el BCG representa el tratamiento estándar del CIS vesical respaldado por el ensayo SWOG 8507 y el protocolo 30861 de la EORTC. Justificación científica: Los estudios que han evaluado los resultados a largo plazo de los pacientes con CIS vesical están limitados por el tamaño muestral, inmunoterapia con BCG sin mantenimiento, uso de quimioterapia intravesical, y análisis univariantes no ajustados, lo que ha llevado a resultados contradictorios. Objetivos: (1) Describir los resultados oncológicos en términos de recurrencia vesical, progresión, y recurrencia en el tracto urinario superior de los pacientes con CIS vesical tratados con BCG. (2) Evaluar las implicaciones pronósticas de las clasificaciones clínica (primario, secundario y concomitante) y patológica (primario, cTa-CIS, cT1-CIS) del CIS vesical. (3) Determinar el pronóstico de la respuesta completa a los 6 meses después del inicio del tratamiento adecuado con BCG en pacientes con CIS vesical. Hipótesis: (1) Con los cambios de las guías de practica clínica en el tratamiento de pacientes con TVNMI (esquema de mantenimiento con BCG, Re-RTUv, definición adecuada de no respondedor), el pronóstico oncológico del CIS vesical ha cambiado. (2) Presencia de heterogeneidad en la evolución de los pacientes con CIS vesical cuando son estratificados de acuerdo con las clasificaciones clínica y patológica. (3) La ausencia de respuesta a los 6 meses después del inicio del tratamiento adecuado con BCG, presenta implicaciones pronósticas para las decisiones sobre tratamientos posteriores. Diseño del estudio y población: Estudio observacional retrospectivo de centro único de pacientes con CIS vesical con o sin TVNMI exofítico asociado tratados con BCG durante el periodo 2008-2015 (n=386). Resultados: (1) Durante los primeros 3 años se registraron 117/159 (73,6%) recurrencias, 38/55 (69,1%) progresiones a TVMI, y 15/31 (48,4%) recurrencias en el tracto urinario superior. Después de 5 años de seguimiento se observó recurrencia, progresión a TVMI y recurrencia en el tracto urinario superior en 26/159 (16,4%), 7/55 (12,7%) y 12/31 (38,7%) pacientes, respectivamente. (2) La regresión de Cox ajustada mediante un modelo de propensión mostró que el tratamiento adecuado con BCG mejora significativamente la supervivencia libre de recurrencia HR: 0.21 (IC95%: 0.13-0.34), supervivencia libre de progresión HR: 0.46 (IC95%: 0.25-0.87) y supervivencia libre de tumor del tracto urinario superior HR: 0.24 (IC95%: 0.09-0.64). (3) La regresión de Cox multivariante mostró que ni la clasificación clínica ni la patológica parecen ser factores predictivos de resultados oncológicos en los pacientes con CIS vesical. (4) La regresión de Cox ajustada mediante un modelo de propensión mostró que aquellos pacientes que no respondieron al BCG después de un tratamiento adecuado, presentaron peor supervivencia libre de progresión HR: 3,40 (IC95%: 1,59-7,27), supervivencia libre de cistectomía radical HR: 3,52 (IC95%: 1,77-7) y supervivencia cáncer específica HR: 4,42 (IC95%: 1,95-10,01). Conclusiones: (1) Los pacientes con CIS vesical presentan alto riesgo de recurrencia, progresión y recurrencia en el tracto urinario superior durante los tres primeros años de seguimiento. Debido al riesgo de recurrencia y progresión a mas de 5 años, la vigilancia debe continuarse de manera prolongada. (2) La exposición a un tratamiento "adecuado" con BCG mejora los resultados oncológicos de los pacientes con CIS vesical. (3) No existe suficiente evidencia para respaldar el uso de las clasificaciones clínica y patológica para guiar el tratamiento y/o el seguimiento de los pacientes con CIS vesical. (4) Los pacientes que no responden a los 6 meses del inicio del tratamiento adecuado con BCG, presentan peores resultados oncológicos a largo plazo.Background Carcinoma in situ (CIS) of the bladder is a high-grade flat lesion limited to the mucosa and morphometrically similar to muscle-invasive bladder cancer (MIBC). Without treatment, 50% of patients experience progression to MIBC and 90% experience recurrence. The standard treatment of bladder CIS is bacillus Calmette-Guerin (BCG) immunotherapy based on SWOG 8507 trial and EORTC 30861 protocol. Rationale of the study Studies exploring the long-term outcomes of CIS of the bladder have typically been limited by small sample size, BCG immunotherapy without maintenance, treatment based on intravesical chemotherapy, and unadjusted univariate analysis, which has led to conflicting results. Objective (1) To describe the oncological outcomes in patients with CIS of the bladder treated with BCG for bladder recurrence, progression, and upper urinary tract recurrence. (2) To assess the prognostic implicactions of clinical classification (primary, secondary, concomitant) and pathological classification (primary, cTa-CIS, cT1-CIS) of patients with CIS of the bladder treated with BCG. (3) To assess the prognostic of BCG responsiveness at 6 months after initiation of an adequate BCG treatment in patients with CIS of the bladder treated with BCG. Hypothesis (1) Changes in the clinical practice guidelines in the treatment of patients with NMIBC (maintenance with BCG, Re-TURB, adequate definition of non-responder), the oncological prognosis of bladder CIS has changed. (2) Presence of heterogeneity in the evolution of patients with CIS of the bladder when they are stratified according to the clinical and pathological classifications. (3) The absence of response at 6 months after the initiation of adequate BCG treatment has prognostic implications for further treatments. Study design and population Observational Retrospective single-center study of patients with bladder CIS with or without associated NMIBC treated with BCG during 2008-2015 (n = 386) Results (1) During the first 3-years 117/159 (73.6%) recurrences, 38/55 (69.1%) progressions to MIBC, and 15/31 (48.4%) upper urinary tract recurrences were registered. After 5-years follow-up, recurrence, progression to MIBC, and recurrence in the upper urinary tract were observed in 26/159 (16.4%), 7/55 (12.7%), and 12/31 (38.7%) patients, respectively. (2) Adjusted Cox regression analysis using a propensity score-weighted analysis showed that adequate BCG treatment significantly improves recurrence-free survival HR: 0.21 (95% CI: 0.13-0.34), progression-free survival HR: 0.46 (95% CI: 0.25-0.87) and upper urinary tract tumor-free survival HR: 0.24 (95% CI: 0.09-0.64). (3) Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for oncological outcomes in patients with CIS of the bladder. (4) Adjusted Cox regression analysis showed that patients who were unresponsive at 6 months following the initiation of adequate BCG treatment had worse PFS (IPW-HR: 3.40, 95% CI 1.59-7.27) , RCFS (IPW-HR: 3.52, 95% CI 1.77-7), and CSS (IPW-HR: 4.42, 95% CI 1.95-10.01), compared with BCG-responsive patients. Conclusions (1) Patients with CIS of the bladder have a high risk of recurrence, progression, and upper urinary tract recurrence during the first 3-years follow-up. Moreover, there is a non-negligible risk of recurrence and progression more than 5-years follow-up, therefore, surveillance should be continued for a long time. (2) Exposure to "adequate" BCG treatment improves oncological outcomes in patients with CIS of the bladder. (3) There is insufficient evidence to support the use of clinical and pathological classifications to guide the treatment and/or follow-up of patients with CIS of the bladder. (4) Unresponsive patients at 6-months after the initiation of an adequate BCG treatment have poorer oncological outcomes

Impacto clínico del carcinoma in situ en pacientes con tumor vesical no músculo invasor. Incidencia y factores predictivos de recurrencia, progresión y supervivencia cáncer específica

INTRODUCCIÓ: El CIS vesical és una lesió plana d’alt grau limitada a la mucosa que comparteix característiques genotípiques similars a les del tumor vesical múscul invasiu (TVMI). Sense tractament, fins un 50% dels pacients progressen a TVMI. Actualment, el BCG representa el tractament estàndard del CIS vesical recolzat per l’assaig SWOG 8507 i el protocol 30861 de la EORTC. JUSTIFICACIÓ CIENTÍFICA Els estudis que han avaluat els resultats a llarg termini dels pacients amb CIS vesical estan limitats per la mida de la mostra, immunoteràpia amb BCG sense manteniment, us de quimioteràpia intravesical, i anàlisis univariants no ajustats, la qual cosa ha donat lloc a resultats contradictoris. OBJECTIUS (1) Descriure els resultats oncològics en termes de recurrència vesical, progressió, i recurrència en el tracte urinari superior del pacients amb CIS tractats amb BCG. (2) Avaluar les implicacions pronòstiques de les classificacions clínica (primari, secundari i concomitant) i patològica (primari, cTa-CIS, cT1-CIS) del CIS vesical (3) Determinar el pronòstic de la resposta completa als 6 mesos després de l’inici del tractament adequat amb BCG en pacients amb CIS vesical. HIPOTESIS Amb els canvis de les guies de pràctica clínica en el tractament de pacients amb TVNMI (esquema de manteniment amb BCG, re-RTUv, definició adequada de no resposta), el pronòstic oncològic del CIS vesical ha canviat. (2) Presència d’heterogeneïtat en l’evolució dels pacients amb CIS vesical quan s’estratifiquen d’acord a les classificacions clínica i patològica. (3) Absència de resposta als 6 mesos després de l’inici del tractament adequat amb BCG, presenta implicacions pronòstiques per les decisions sobre tractaments posteriors. DISENY DE L’ESTUDI I POBLACIÓ Estudi observacional retrospectiu de centre únic de pacients amb CIS vesical amb o sense TVNMI exofític associat tractats amb BCG durant el període 2008-2015 (n=386). RESULTATS (1) Durant els primers 3 anys es van registrar 117/159 (73,6%) recurrències, 38/55 (69,1%) progressions a TVMI, i 15/31 (48,4%) recurrències al tracte urinari superior. Després de 5 anys de seguiment s’observà recurrència, progressió a TVMI i recurrència al tracte urinari superior en 26/159 (16,4%), 7/55 (12,7%) y 12/31 (38,7%) pacients, respectivament. (2) La regressió de Cox ajustada mitjançant un model de propensió mostrà que el tractament adequat amb BCG millora significativament la supervivència lliure de recurrència HR: 0.21 ((IC95%: 0.13-0.34), supervivència lliure de progressió HR: 0.46 (IC95%: 0.25-0.87) y supervivència lliure de tumor del tracto urinari superior HR: 0.24 (IC95%: 0.09-0.64). (3) La regressió de Cox multivariant mostrà que ni la classificació clínica ni patològica semblen ser factors predictius de resultats oncològics en el pacients amb CIS vesical. (4) La regressió de Cox ajustada mitjançant un model de propensió mostrà que aquells pacients que no varen respondre a BCG després d’un tractament adequat, presentaren pitjor supervivència lliure de progressió HR: 3,40 (IC95%: 1,59-7,27), supervivència lliure de cistectomia radical HR: 3,52 (IC95%: 1,77-7) y supervivència càncer específica HR: 4,42 (IC95%: 1,95-10,01). CONCLUSIONS (1) Els pacients amb CIS vesical presenten alt risc de recurrència, progressió i recurrència en el tracte urinari superior durant els primers tres anys de seguiment. Degut al risc de recurrència i progressió a més de 5 anys, la vigilància ha de continuar-se de forma prolongada. (2) L’exposició a un tractament “adequat” amb BCG millora els resultats oncològics dels pacients amb CIS vesical. (3) No existeix suficient evidència per recolzar l’ús de les classificacions clínica i patològica per guiar el tractament i/o el seguiment dels pacients amb CIS vesical. (4) Els pacients que no responen als 6 mesos de l’inici del tractament adequat amb BCG, presenten pitjors resultats oncològics a llarg termini.Introducción: El CIS vesical es una lesión plana de alto grado limitada a la mucosa que comparte características genotípicas similares a las del TVMI. Sin tratamiento, hasta el 50% de los pacientes progresan a TVMI. En la actualidad, el BCG representa el tratamiento estándar del CIS vesical respaldado por el ensayo SWOG 8507 y el protocolo 30861 de la EORTC. Justificación científica: Los estudios que han evaluado los resultados a largo plazo de los pacientes con CIS vesical están limitados por el tamaño muestral, inmunoterapia con BCG sin mantenimiento, uso de quimioterapia intravesical, y análisis univariantes no ajustados, lo que ha llevado a resultados contradictorios. Objetivos: (1) Describir los resultados oncológicos en términos de recurrencia vesical, progresión, y recurrencia en el tracto urinario superior de los pacientes con CIS vesical tratados con BCG. (2) Evaluar las implicaciones pronósticas de las clasificaciones clínica (primario, secundario y concomitante) y patológica (primario, cTa-CIS, cT1-CIS) del CIS vesical. (3) Determinar el pronóstico de la respuesta completa a los 6 meses después del inicio del tratamiento adecuado con BCG en pacientes con CIS vesical. Hipótesis: (1) Con los cambios de las guías de practica clínica en el tratamiento de pacientes con TVNMI (esquema de mantenimiento con BCG, Re-RTUv, definición adecuada de no respondedor), el pronóstico oncológico del CIS vesical ha cambiado. (2) Presencia de heterogeneidad en la evolución de los pacientes con CIS vesical cuando son estratificados de acuerdo con las clasificaciones clínica y patológica. (3) La ausencia de respuesta a los 6 meses después del inicio del tratamiento adecuado con BCG, presenta implicaciones pronósticas para las decisiones sobre tratamientos posteriores. Diseño del estudio y población: Estudio observacional retrospectivo de centro único de pacientes con CIS vesical con o sin TVNMI exofítico asociado tratados con BCG durante el periodo 2008-2015 (n=386). Resultados: (1) Durante los primeros 3 años se registraron 117/159 (73,6%) recurrencias, 38/55 (69,1%) progresiones a TVMI, y 15/31 (48,4%) recurrencias en el tracto urinario superior. Después de 5 años de seguimiento se observó recurrencia, progresión a TVMI y recurrencia en el tracto urinario superior en 26/159 (16,4%), 7/55 (12,7%) y 12/31 (38,7%) pacientes, respectivamente. (2) La regresión de Cox ajustada mediante un modelo de propensión mostró que el tratamiento adecuado con BCG mejora significativamente la supervivencia libre de recurrencia HR: 0.21 (IC95%: 0.13-0.34), supervivencia libre de progresión HR: 0.46 (IC95%: 0.25-0.87) y supervivencia libre de tumor del tracto urinario superior HR: 0.24 (IC95%: 0.09-0.64). (3) La regresión de Cox multivariante mostró que ni la clasificación clínica ni la patológica parecen ser factores predictivos de resultados oncológicos en los pacientes con CIS vesical. (4) La regresión de Cox ajustada mediante un modelo de propensión mostró que aquellos pacientes que no respondieron al BCG después de un tratamiento adecuado, presentaron peor supervivencia libre de progresión HR: 3,40 (IC95%: 1,59-7,27), supervivencia libre de cistectomía radical HR: 3,52 (IC95%: 1,77-7) y supervivencia cáncer específica HR: 4,42 (IC95%: 1,95-10,01). Conclusiones: (1) Los pacientes con CIS vesical presentan alto riesgo de recurrencia, progresión y recurrencia en el tracto urinario superior durante los tres primeros años de seguimiento. Debido al riesgo de recurrencia y progresión a mas de 5 años, la vigilancia debe continuarse de manera prolongada. (2) La exposición a un tratamiento “adecuado” con BCG mejora los resultados oncológicos de los pacientes con CIS vesical. (3) No existe suficiente evidencia para respaldar el uso de las clasificaciones clínica y patológica para guiar el tratamiento y/o el seguimiento de los pacientes con CIS vesical. (4) Los pacientes que no responden a los 6 meses del inicio del tratamiento adecuado con BCG, presentan peores resultados oncológicos a largo plazo.Background Carcinoma in situ (CIS) of the bladder is a high-grade flat lesion limited to the mucosa and morphometrically similar to muscle-invasive bladder cancer (MIBC). Without treatment, 50% of patients experience progression to MIBC and 90% experience recurrence. The standard treatment of bladder CIS is bacillus Calmette-Guerin (BCG) immunotherapy based on SWOG 8507 trial and EORTC 30861 protocol. Rationale of the study Studies exploring the long-term outcomes of CIS of the bladder have typically been limited by small sample size, BCG immunotherapy without maintenance, treatment based on intravesical chemotherapy, and unadjusted univariate analysis, which has led to conflicting results. Objective (1) To describe the oncological outcomes in patients with CIS of the bladder treated with BCG for bladder recurrence, progression, and upper urinary tract recurrence. (2) To assess the prognostic implicactions of clinical classification (primary, secondary, concomitant) and pathological classification (primary, cTa-CIS, cT1-CIS) of patients with CIS of the bladder treated with BCG. (3) To assess the prognostic of BCG responsiveness at 6 months after initiation of an adequate BCG treatment in patients with CIS of the bladder treated with BCG. Hypothesis (1) Changes in the clinical practice guidelines in the treatment of patients with NMIBC (maintenance with BCG, Re-TURB, adequate definition of non-responder), the oncological prognosis of bladder CIS has changed. (2) Presence of heterogeneity in the evolution of patients with CIS of the bladder when they are stratified according to the clinical and pathological classifications. (3) The absence of response at 6 months after the initiation of adequate BCG treatment has prognostic implications for further treatments. Study design and population Observational Retrospective single-center study of patients with bladder CIS with or without associated NMIBC treated with BCG during 2008-2015 (n = 386) Results (1) During the first 3-years 117/159 (73.6%) recurrences, 38/55 (69.1%) progressions to MIBC, and 15/31 (48.4%) upper urinary tract recurrences were registered. After 5-years follow-up, recurrence, progression to MIBC, and recurrence in the upper urinary tract were observed in 26/159 (16.4%), 7/55 (12.7%), and 12/31 (38.7%) patients, respectively. (2) Adjusted Cox regression analysis using a propensity score-weighted analysis showed that adequate BCG treatment significantly improves recurrence-free survival HR: 0.21 (95% CI: 0.13-0.34), progression-free survival HR: 0.46 (95% CI: 0.25-0.87) and upper urinary tract tumor-free survival HR: 0.24 (95% CI: 0.09-0.64). (3) Cox multivariate regression analysis showed that neither clinical classification nor pathological classification is an independent predictive factor for oncological outcomes in patients with CIS of the bladder. (4) Adjusted Cox regression analysis showed that patients who were unresponsive at 6 months following the initiation of adequate BCG treatment had worse PFS (IPW-HR: 3.40, 95% CI 1.59–7.27) , RCFS (IPW-HR: 3.52, 95% CI 1.77–7), and CSS (IPW-HR: 4.42, 95% CI 1.95–10.01), compared with BCG-responsive patients. Conclusions (1) Patients with CIS of the bladder have a high risk of recurrence, progression, and upper urinary tract recurrence during the first 3-years follow-up. Moreover, there is a non-negligible risk of recurrence and progression more than 5-years follow-up, therefore, surveillance should be continued for a long time. (2) Exposure to “adequate” BCG treatment improves oncological outcomes in patients with CIS of the bladder. (3) There is insufficient evidence to support the use of clinical and pathological classifications to guide the treatment and/or follow-up of patients with CIS of the bladder. (4) Unresponsive patients at 6-months after the initiation of an adequate BCG treatment have poorer oncological outcomes.Universitat Autònoma de Barcelona. Programa de Doctorat en Cirurgia i Ciències Morfològique

Current and Future Landscape of Perioperative Treatment for Muscle-Invasive Bladder Cancer

Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved in recent years. Immune checkpoint inhibitors and targeted agents, such as antibody-drug conjugates or FGFR inhibitors, are new therapeutic alternatives and have shown their benefit in advanced disease. Currently, several clinical trials are investigating the role of these drugs, as monotherapy and in combination with chemotherapy, in the neoadjuvant and adjuvant settings with promising outcomes. In addition, the development of predictive biomarkers could predict responses to neoadjuvant therapies

Current and Future Landscape of Perioperative Treatment for Muscle-Invasive Bladder Cancer

Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the current standard of care for muscle-invasive bladder cancer (MIBC). However, less than half of patients are candidates for this treatment, and 50% will develop metastatic disease. Adjuvant chemotherapy could be offered if neoadjuvant treatment has not been administered for suitable patients. It is important to reduce the risk of systemic recurrence and improve the prognosis of localized MIBC. Systemic therapy for metastatic urothelial carcinoma has evolved in recent years. Immune checkpoint inhibitors and targeted agents, such as antibody-drug conjugates or FGFR inhibitors, are new therapeutic alternatives and have shown their benefit in advanced disease. Currently, several clinical trials are investigating the role of these drugs, as monotherapy and in combination with chemotherapy, in the neoadjuvant and adjuvant settings with promising outcomes. In addition, the development of predictive biomarkers could predict responses to neoadjuvant therapies

Laparoscopic Management of Chylous Leakage Using a Direct Lymph Node Injection with Methylene Blue as a Leakage Point Location Strategy in a Patient with Retroperitoneal Extragonadal Seminoma

Background: The first-line treatment in cases of chylous leakage is conservative, and operation should be considered only in patients who fail to respond to this treatment. The main clinical concern is the difficulty of intraoperative localization of the site of leakage that can affect surgical outcome. Case Presentation: A 33-year-old man presented with a 4-month history of abdominal pain and weight loss. CT scan revealed enlarged retroperitoneal lymph nodes. Retroperitoneal lymph node biopsy was performed owing to the suspicion of lymphoproliferative disease, with a pathological result of nonspecific adenitis. Because of persistence of pain, an abdominal CT scan showed a large left retroperitoneal fluid collection that was found to be compatible with chyle after drainage. Conservative treatment was established, but because of its failure, surgical management was attempted by the laparoscopic approach. Intraoperative direct lymph node injection of methylene blue was used as a leakage point location strategy that allows selective ligation of the site of leakage. Thereafter a gradual reduction in chyle output to zero was observed. Conclusion: The laparoscopic approach could be a feasible and successful method for the management of chyle leakage in patients refractory to conservative treatment. Intraoperative direct lymph node injection of methylene blue could be a useful technique to facilitate detection of the site of leakage during operation

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease : a randomized, controlled clinical trial

Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer

Purpose: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk -adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy.Methods: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC).Results: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recur-rence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression.Conclusion: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis. (c) 2022 Published by Elsevier Inc