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1.
J Surg Oncol ; 114(6): 764-768, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27562252

ABSTRACT

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Vena Cava, Inferior/pathology , Venous Thrombosis/etiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Retrospective Studies , Survival Analysis , Venous Thrombosis/pathology
2.
J Urol ; 193(2): 436-42, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25063493

ABSTRACT

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/mortality , Kidney Neoplasms/surgery , Neoplastic Cells, Circulating , Nephrectomy , Thrombectomy , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/secondary , Humans , Kidney Neoplasms/pathology , Middle Aged , Nephrectomy/methods , Survival Rate , Young Adult
3.
J Urol ; 194(2): 304-308, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25797392

ABSTRACT

PURPOSE: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplastic Cells, Circulating , Nephrectomy/methods , Thrombectomy/methods , Vena Cava, Inferior , Venous Thrombosis/surgery , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Cardiopulmonary Bypass , Female , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Retrospective Studies , Survival Rate/trends , United States/epidemiology , Venous Thrombosis/etiology , Venous Thrombosis/mortality
4.
Curr Urol Rep ; 15(5): 404, 2014 May.
Article in English | MEDLINE | ID: mdl-24682884

ABSTRACT

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplastic Cells, Circulating/pathology , Nephrectomy/adverse effects , Thrombectomy/methods , Vena Cava, Inferior , Venous Thrombosis , Carcinoma, Renal Cell/pathology , Humans , International Cooperation , Kidney Neoplasms/pathology , Venous Thrombosis/etiology , Venous Thrombosis/pathology , Venous Thrombosis/surgery
5.
Arch Esp Urol ; 73(10): 879-894, 2020 12.
Article in Spanish | MEDLINE | ID: mdl-33269707

ABSTRACT

Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of intravesica Bacillus de Calmette-Guérin (BCG) and the recentin corporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such tumors. Its extension and development at the present time covers all the locations of the wide spectrum of presentation and evolution of these tumors. Nowadays, apart for the low grade non muscle-invasive tumors, we are facingan unpredictable development of antitumoral immunotherapy in bladder cancer not only as an option in the primary treatment, but also in other scenarios such asnon-responders when it comes to BCG, or the situation of ineligibility for systemic chemotherapy indication. The main objective of this review article is trying to translate the current basic mechanisms involved in different phases of transitional cell carcinomas antitumoral response, regardless of whether they are muscle-invasive or not, and to establish the rationale for their therapeutic intravesical or systemic administration. The role of the interactions established between urothelial tumor cells and the cellular and molecular elements of the immune system of patients is described, incorporating the relevant and recent advances in immunobiology and the molecular characterization of these tumors thatwill undoubtedly introduce far-reaching modifications intherapeutic regimes that will contrast with the traditional options available. Investigational lines that are already active in the clinical research phase with BCG and, checkpoints inhibitors ofthe immune response are also analyzed, high lighting theneed to find predictive response markers as a real option for treatments personalization. The approach to the knowledge of the individual reactivity of the immune system of each patient as a determining factor to achieve it is proposed.


Los abordajes terapéuticos para los carcinomas de células transicionales del urotelio desarrollados en torno a la modulación del sistema inmune encuentran, en la contribución del Bacillus de Calmettey Guérin (BCG) intravesical y más reciente la de los fármacos inhibidores de los puntos de control de la respuesta inmunitaria, indiscutibles pruebas de concepto de la indicación inmunoterapia antitumoral. Su extensión y desarrollo en el momento actual abarca todas las localizaciones del amplio espectro de presentación y evolución de estos tumores. A excepción, por el momento, de los tumores no-músculo infiltrantes debajo grado, acudimos a un desarrollo impredecible de la inmunoterapia antitumoral en el cáncer de vejiga no solo como opción en el tratamiento primario de alguno de ellos sino también en pacientes no-respondedores cuando se trata del BCG, de la quimioterapia sistémicao la situación de no-elegibilidad para su indicación. El objetivo de este artículo de revisión es intentar trasladar los mecanismos básicos actuales implicados en las distintas fases de la respuesta antitumoral de los carcinomas de células transicionales con independencia de que sean o no músculo infiltrantes y establecer los fundamentos para su traslación terapéutica por vía intravesical o sistémica. Se describe el papel de las interacciones que se establecen entre las células tumorales uroteliales y los elementos celulares y moleculares del sistema inmune de los pacientes incorporando los relevantes y recientes avances de la inmunobiológica y la caracterización molecular de estos tumores que sin duda introducirán modificaciones de alcance en su evolución y tratamiento que contrastaran con las opciones hasta hace poco tiempo disponibles. También se analizan las líneas de futuro ya activas en fase de investigación clínica con BCG y con inhibidores de los puntos de control de la respuesta inmunitaria destacando la necesidad de avanzar en la búsqueda de marcadores predictivos de respuesta como opción real para la personalización de los tratamientos planteando la aproximación al conocimiento de la reactividad individual del sistema inmune de cada paciente como factor determinante para poder alcanzarla.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Urologic Neoplasms , Adjuvants, Immunologic/therapeutic use , Administration, Intravesical , BCG Vaccine/therapeutic use , Carcinoma, Transitional Cell/therapy , Humans , Immunotherapy , Urinary Bladder Neoplasms/drug therapy
6.
Eur J Surg Oncol ; 45(10): 1983-1992, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31155470

ABSTRACT

OBJECTIVES: Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi. METHODS: A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled. RESULTS: The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers). CONCLUSIONS: Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT.


Subject(s)
Blood Transfusion/methods , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Nephrectomy/adverse effects , Postoperative Complications/etiology , Thrombectomy/methods , Thrombosis/etiology , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/diagnosis , Female , Follow-Up Studies , Humans , Kidney Neoplasms/complications , Male , Middle Aged , Postoperative Complications/prevention & control , Retrospective Studies , Thrombosis/surgery , Vena Cava, Inferior
7.
Arch Esp Urol ; 71(4): 358-375, 2018 May.
Article in Spanish | MEDLINE | ID: mdl-29745925

ABSTRACT

The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we describe the various phases of its mechanism of action, namely fixation, internalization and triggering of the lytic cytotoxic antitumor response, and its integration in the current intravesical treatment regimens The implication of all these mechanisms in the varied capacity of clinical response observed in patients, reviewing the current status of knowledge of BCG mechanisms of action, leads unavoidably to the search of better clinical efficacy through eventual immune response markers and to set the approach to the knowledge of the individual reactivity of the immune system of each patient as a determinant factor to be able to adopt adjusted therapeutic patterns.


Subject(s)
Adjuvants, Immunologic/administration & dosage , BCG Vaccine/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Adjuvants, Immunologic/pharmacology , Administration, Intravesical , BCG Vaccine/pharmacology , Humans , Treatment Failure , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology
8.
Eur Urol ; 66(3): 577-83, 2014 Sep.
Article in English | MEDLINE | ID: mdl-23871402

ABSTRACT

BACKGROUND: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Venae Cavae/pathology , Venous Thrombosis/pathology , Adipose Tissue/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/surgery , Female , Humans , Kidney Neoplasms/surgery , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Nephrectomy , Prognosis , Retrospective Studies , Severity of Illness Index , Survival Rate , Venous Thrombosis/surgery , Young Adult
9.
Eur Urol ; 59(1): 120-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20980095

ABSTRACT

BACKGROUND: The prognostic significance of venous involvement and tumour thrombus level in renal cell carcinoma (RCC) remains highly controversial. In 2010, the American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) revised the RCC staging system (7th edition) based on tumour thrombus level, differentiating the T stage of tumours limited to renal-vein-only involvement. OBJECTIVE: We aimed to evaluate the impact of tumour thrombus extension in a multi-institutional cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: An international consortium of 11 institutions was established to retrospectively review a combined cohort of 1215 patients undergoing radical nephrectomy and tumour thrombectomy for RCC, including 585 patients with inferior vena cava (IVC) involvement or higher. MEASUREMENTS: Predictive factors of survival, including histology, tumour thrombus level, nodal status, Fuhrman grade, and tumour size, were analysed. RESULTS AND LIMITATIONS: A total of 1122 patients with complete data were reviewed. The median follow-up for all patients was 24.7 mo, with a median survival of 33.8 mo. The 5-yr survival was 43.2% (renal vein involvement), 37% (IVC below the diaphragm), and 22% with caval involvement above the diaphragm. On multivariate analysis, tumour size (hazard ratio [HR]: 1.64 [range: 1.03-2.59]; p=0.036), Fuhrman grade (HR: 2.26 [range: 1.65-3.1]; p=0.000), nodal metastasis (HR: 1.32 [range: 1.09-1.67]; p=0.005), and tumour thrombus level (HR: 2.10 [range: 1.53-3.0]; p=0.00) correlated independently with survival. CONCLUSIONS: Based on analysis of the largest known cohort of patients with RCC along with IVC and atrial thrombus involvement, tumour thrombus level is an independent predictor of survival. Our findings support the changes to the latest AJCC/UICC staging system.


Subject(s)
Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Neoplasm Staging/methods , Renal Veins/pathology , Vena Cava, Inferior/pathology , Venous Thrombosis/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/surgery , Chi-Square Distribution , Europe , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Invasiveness , Nephrectomy , Predictive Value of Tests , Proportional Hazards Models , Renal Veins/surgery , Retrospective Studies , Risk Assessment , Risk Factors , Societies, Medical , Survival Rate , Thrombectomy , Time Factors , Treatment Outcome , United States , Vena Cava, Inferior/surgery , Venous Thrombosis/mortality , Venous Thrombosis/surgery
10.
Arch. esp. urol. (Ed. impr.) ; 73(10): 879-894, dic. 2020. tab
Article in Spanish | IBECS (Spain) | ID: ibc-200617

ABSTRACT

Los abordajes terapéuticos para los carcinomas de células transicionales del urotelio desarrollados en torno a la modulación del sistema inmune encuentran, en la contribución del Bacillus de Calmette y Guérin (BCG) intravesical y más reciente la de los fármacos inhibidores de los puntos de control de la respuesta inmunitaria, indiscutibles pruebas de concepto de la indicación inmunoterapia antitumoral. Su extensión y desarrollo en el momento actual abarca todas las localizaciones del amplio espectro de presentación y evolución de estos tumores. A excepción, por el momento, de los tumores no-músculo infiltrantes de bajo grado, acudimos a un desarrollo impredecible de la inmunoterapia antitumoral en el cáncer de vejiga no solo como opción en el tratamiento primario de alguno de ellos sino también en pacientes no-respondedores cuando se trata del BCG, de la quimioterapia sistémica o la situación de no-elegibilidad para su indicación. El objetivo de este artículo de revisión es intentar trasladar los mecanismos básicos actuales implicados en las distintas fases de la respuesta antitumoral de los carcinomas de células transicionales con independencia de que sean o no músculo infiltrantes y establecer los fundamentos para su traslación terapéutica por vía intravesical o sistémica. Se describe el papel de las interacciones que se establecen entre las células tumorales uroteliales y los elementos celulares y moleculares del sistema inmune de los pacientes incorporando los relevantes y recientes avances de la inmunobiológica y la caracterización molecular de estos tumores que sin duda introducirán modificaciones de alcance en su evolución y tratamiento que contrastaran con las opciones hasta hace poco tiempo disponibles. También se analizan las líneas de futuro ya activas en fase de investigación clínica con BCG y con inhibidores de los puntos de control de la respuesta inmunitaria destacando la necesidad de avanzar en la búsqueda de marcadores predictivos de respuesta como opción real para la personalización de los tratamientos planteando la aproximación al conocimiento de la reactividad individual del sistema inmune de cada paciente como factor determinante para poder alcanzarla


Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of intravesical Bacillus de Calmette-Guérin (BCG) and the recent incorporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such tumors. Its extension and development at the present time covers all the locations of the wide spectrum of presentation and evolution of these tumors. Nowadays, apart for the low grade non muscle-invasive tumors, we are facing an unpredictable development of antitumoral immunotherapy in bladder cancer not only as an option in the primary treatment, but also in other scenarios such as non-responders when it comes to BCG, or the situation of ineligibility for systemic chemotherapy indication. The main objective of this review article is trying to translate the current basic mechanisms involved in different phases of transitional cell carcinomas antitumoral response, regardless of whether they are muscle-invasive or not, and to establish the rationale for their therapeutic intravesical or systemic administration. The role of the interactions established between urothelial tumor cells and the cellular and molecular elements of the immune system of patients is described, incorporating the relevant and recent advances in immunobiology and the molecular characterization of these tumors that will undoubtedly introduce far-reaching modifications in therapeutic regimes that will contrast with the traditional options available. Investigational lines that are already active in the clinical research phase with BCG and, checkpoints inhibitors of the immune response are also analyzed, highlighting the need to find predictive response markers as a real option for treatments personalization. The approach to the knowledge of the individual reactivity of the immune system of each patient as a determining factor to achieve it is proposed


Subject(s)
Humans , Carcinoma, Transitional Cell/therapy , Urinary Bladder Neoplasms/drug therapy , Urologic Neoplasms , Adjuvants, Immunologic/therapeutic use , Administration, Intravesical , BCG Vaccine/therapeutic use , Immunotherapy
11.
Arch. esp. urol. (Ed. impr.) ; 71(4): 358-375, mayo 2018. tab
Article in Spanish | IBECS (Spain) | ID: ibc-178413

ABSTRACT

Los abordajes terapéuticos desarrollados en torno a la modulación del sistema inmune encuentran, en la contribución terapéutica del Bacillus de Calmette y Guérin (BCG) intravesical en el carcinoma vesical de células transicionales, es desde hace poco más de treinta años, un ejemplo indiscutible como prueba de concepto de la inmunoterapia antitumoral. La modalidad de tratamiento inmunoterápico de los carcinomas uroteliales por vía intravesical se contempla con pautas de instilaciones intravesicales periódicas y las de mayor desarrollo histórico y difusión son las que se llevan a cabo con preparaciones en suspensión de la BCG, una cepa única obtenida del Mycobacterium bovis a finales del primer tercio del siglo XX y constituye la modalidad inmunoterapica con mayores logros históricos de toda la patología tumoral con un cuerpo de evidencia de alto nivel. Incluso actualmente acudimos a un potencial de desarrollo impredecible de esta modalidad terapéutica basada la inmunomodulación relacionada con la activación o supresión de los linfocitos T a través del bloqueo de los puntos de control del sistema inmunitario. Opción que en el momento actual supone un paso decisivo en el tratamiento del carcinoma urotelial metastático refractario a quimioterapia. En el mecanismo íntimo de acción de la BCG intravesical se ha avanzado en los últimos años, pero todavía son muchas las interrogantes abiertas y que solo podrán contestarse desde complejas plataformas de investigación básica y traslacional. El objetivo de este artículo de revisión es intentar trasladar los mecanismos básicos actuales implicados en las distintas fases de la respuesta antitumoral de la BCG a su utilización rutinaria en la práctica clínica. También analizar las líneas de futuro ya activas en fase de investigación clínica con y sin implicaciones con los mecanismos de acción de la BCG. Se describe el papel de las interacciones que basalmente se establecen entre las células tumorales uroteliales y los elementos celulares y moleculares del sistema inmune de los pacientes con ulterior capacidad efectora antitumoral. Tras el tratamiento con BCG intravesical y su interaccion se describen las diferentes fases de su mecanismo de acción, a saber, fijación, internalización y desencadenamiento de la respuesta lítica citotóxica antitumoral y también su integración en los regímenes de tratamientos intravesicales actuales. La implicación de todos estos mecanismos en la variada capacidad de respuesta clínica observada en los pacientes, repasando el estado actual del conocimien to de los mecanismos de acción de la BCG, conduce inexorablemente a la búsqueda de mayor eficacia clínica a través de eventuales marcadores inmunes de la respuesta y a plantear la aproximación al conocimiento de la reactividad individual del sistema inmune de cada paciente como factor determinante para poder adoptar pautas terapeuticas ajustadas


The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we escribe the various phases of its mechanism of action, namely fixation, internalization and triggering of the lytic cytotoxic antitumor response, and its integration in the current intravesical treatment regimens The implication of all these mechanisms in the varied capacity of clinical response observed in patients, reviewing the current status of knowledge of BCG mechanisms of action, leads unavoidably to the search of better clinical efficacy through eventual immune response markers and to set the approach to the knowledge of the individual reactivity of the immune system of each patient as a determinant factor to be able to adopt adjusted therapeutic patterns


Subject(s)
Humans , Adjuvants, Immunologic/administration & dosage , BCG Vaccine/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Adjuvants, Immunologic/pharmacology , Administration, Intravesical , BCG Vaccine/pharmacology , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathology , Treatment Failure
12.
Arch Esp Urol ; 61(9): 1157-62, 2008 Nov.
Article in Spanish | MEDLINE | ID: mdl-19140600

ABSTRACT

The use of laser technology in the field of urologic surgery has experienced great advances over the past 20 years. Since the beginning of this century robotic technology has landed in a determined manner in our specially and every day will be more and more indications on what is going to have a final deployment. The current combination of laser and surgical robots, can be focused on two distinct areas, but possibly complementary, the use of lasers to guide the surgical procedure, what we might call "landmarks and structures recognition" or "positioning" and laser use because of its ablative ability minimizing blood loss and increasing the resection accuracy. This paper reviews most recent articles and contributions on the combination of these two technologies.


Subject(s)
Laser Therapy/instrumentation , Laser Therapy/methods , Robotics/instrumentation , Urologic Diseases/surgery , Equipment Design , Humans
14.
Arch. esp. urol. (Ed. impr.) ; 61(9): 1157-1163, nov. 2008. ilus
Article in Es | IBECS (Spain) | ID: ibc-69500

ABSTRACT

El uso de la tecnología láser en el campo de la cirugía urológica ha vivido grandes avances en los últimos 20 años. Desde los comienzos de este siglo la tecnología robótica ha desembarcado de una manera decidida en nuestra especialidad y día tras día van siendo más y más las indicaciones en las cuáles está teniendo una implantación definitiva. Las actuales combinaciones del láser quirúrgico y los dispositivos robóticos, se pueden centrar en dos áreas claramente diferenciadas, pero posiblemente complementarias; la utilización del láser para guiar el procedimiento quirúrgico, lo que podríamos llamar «reconocimiento de estructuras» o «posicionamiento» y el uso de láser por su capacidad ablativa minimizando la pérdida sanguínea y aumentando la precisión de la resección. En este trabajo se revisan los artículos y aportaciones más recientes en la combinación de estas dos tecnologías (AU)


The use of laser technology in the field of urologic surgery has experienced great advances over the past 20 years. Since the beginning of this century robotic technology has landed in a determined manner in our specialty and every day will be more and more indications on what is going to have a final deployment. The current combination of laser and surgical robots, can be focused on two distinct areas, but possibly complementary, the use of lasers to guide the surgical procedure, what we might call «landmarks and structures recognition» or «positioning» and laser use because of its ablative ability minimizing blood loss and increasing the resection accuracy. This paper reviews most recent articles and contributions on the combination of these two technologies (AU)


Subject(s)
Humans , Robotics/methods , Robotics/trends , Lasers/classification , Lasers , Laser Therapy/methods , Technology/methods , Technology/trends , Neurosurgery/instrumentation , Neurosurgery/methods , Transurethral Resection of Prostate/instrumentation
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