Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma / 细胞与分子免疫学杂志

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

Immunotherapy Based on Tumor Microenvironment in Renal Cell Carcinoma / 中国医学科学院学报

Renal cell carcinoma (RCC) is a common lethal urological cancer,the distant metastasis of which is the leading cause of death.Although targeted agents have remarkably improved the overall prognosis of RCC patients,nearly all the patients eventually acquire therapeutic resistance.With the advent of immune checkpoint inhibitors,immunotherapy based on tumor microenvironment (TME) has shown a broad scope in clinical application.The deepening understanding of TME leads to the changes of therapeutic strategies for advanced RCC,and the combination of targeted therapy and immunotherapy is exhibiting a promising prospect.Herein,we reviewed the TME characteristics,candidate predictive biomarkers,and possible targets for future development of drugs against RCC.

Consideration in the management of renal cell carcinoma during the COVID-19 Pandemic

ABSTRACT Introduction: Recently the COVID-19 pandemic became the main global priority; main efforts and health infrastructures have been prioritized in favor of COVID-19 battle and the treatment of benign diseases has been postponed. Renal cell cancer (RCC) patients configure a heterogenous populations: some of them present indolent cases which can safely have postponed their treatments, others present aggressive tumors, deserving immediate care. These scenarios must be properly identified before a tailored therapeutic choice. Objectives We propose a risk- based approach for patients with RCC, to be used during this unprecedented viral infection time. Materials and Methods: After a literature review focused in COVID-19 and current RCC treatments, we suggest therapeutic strategies of RCC in two sections: surgical approach and systemic therapy, in all stages of this malignance. Results: Patients with cT1a tumors (and complex cysts, Bosniak III/IV), must be put under active surveillance and delayed intervention. cT1b-T2a/b cases must be managed by partial or radical nephrectomy, some selected T1b-T2a (≤7cm) cases can have the surgery postponed by 60-90 days). Locally advanced tumors (≥cT3 and or N+) must be promptly resected. As possible, minimally invasive surgery and early hospital discharge are encouraged. Upfront cytoreduction, is not recommendable for low risk oligometastatic patients, which must start systemic treatment or even could be put under surveillance and delayed therapy. Intermediate and poor risk metastatic patients must start target therapy and/or immunotherapy (few good responders intermediate cases can have postponed cytoreduction). The recommendation about hereditary RCC syndromes are lacking, thus we recommend its usual care. Local or loco regional recurrence must have individualized approaches. For all cases, we suggest the application of a specific informed consent and a shared therapeutic choice. Conclusion: In the pandemic COVID -19 times, a tailored risk-based approach must be used for a safe management of RCC, aiming to not compromise the oncological outcomes of the patients.

Metástasis bilateral de húmero, en paciente con cáncer renal, tratado con inmunoterapia y cirugía: reporte de un caso / Bilateral Humeral metastases, in a patient with renal cancer, treated with immunotherapy and surgery: case report

El carcinoma de células renales es el 7mo cáncer en frecuencia a nivel mundial con más de 300.000 casos nuevos al año y es la 3era malignidad genitourinaria más frecuente. El sitio más común de metástasis es el pulmón mientras que el esqueleto ocupa el segundo lugar con una frecuencia que varía entre un 20% a un 35%. Se ha reportado una sobrevida de 12 meses en promedio luego de la aparición de metástasis óseas. Reporte del caso de un paciente con diagnóstico de cáncer renal de células claras y metástasis óseas (en columna, pelvis y ambos húmeros), que evoluciona con fractura de ambos brazos. El paciente es aceptado en un ensayo clínico de tratamiento con inmunoterapia y además se somete a una reducción y osteosíntesis bilateral de húmero con clavo endomedular, logrando la consolidación de ambas fracturas y, por ende, la regresión de la enfermedad.

Renal cell carcinoma is ranked 7th in frequent cancer worldwide with more than 3000.000 new cases per year, as well as it's ranked 3rd in frequent genitourinary malignancy. The most common area of metastases is lung followed by skeleton in second place. The frequency of skeleton metastases varies from 20% to 35%. A survival average time of 12 months is generally observed after the appearance of bone metastases. This case report is about a patient diagnosed with clear cell renal cancer and bone metastases (in the spine, pelvis and both humerus) that evolves with fracture of both arms. The patient undergoes a clinical trial with immunotherapy and also a reduction and osteosynthesis of both arms with intramedullary nail, achieving consolidation of both fractures and regression of the disease.

Manejo laparoscópico del carcinoma renal con trombo en vena cava: detalles técnicos / Laparoscopic management of renal carcinoma with caval vein thrombus: technical details

Introducción. El trombo vascular es frecuente en el carcinoma de células renales, pudiendo extenderse a lavena cava inferior hasta un 15 % de los pacientes. La cirugía radical es el único tratamiento con potencialcurativo. La supervivencia cáncer específica a 5 años alcanza el 64 %. La cirugía laparoscópica es una opciónreproducible con buenos resultados iniciales. El objetivo es mostrar y describir los detalles técnicos de la resección laparoscópica de tumor renal con extensión a la vena cava inferior del lado derecho. Material y métodos.De enero de 2014 a julio de 2017, realizamos 8 cirugías laparoscópicas por carcinoma de células renales del ladoderecho con trombo venoso tumoral extendido a la vena cava inferior. La técnica fue transperitoneal pura, conclampaje venoso intracorpóreo. Se incluyeron a pacientes con tumor renal y trombo tumoral hasta el diafragma, sin conglomerados adenopáticos hiliares. Pacientes con metástasis viscerales no fueron excluidos. Serecogieron y analizaron datos demográficos, perioperatorios,y patológicos. Todos fueron incluidos en protocolo de seguimiento oncológico.Resultados. Se operaron 5 hombres (62 %) y 3 mujeres (28 %) con edad promedio de 56 (48u 68) años. Laextensión vascular del trombo fue de 3,3 centímetros (2-5,4). No hubo conversión a cirugía abierta. El tiempopromedio de clampeo fue de 30 minutos (20 a 45). El tiempo quirúrgico fue de 146 minutos (80-310). El valor de creatinina sérica postoperatoria fue de 1,3 mg/dL (0,7 -3). El tiempo de internación fue de 5 días (3-8).Ocurrieron 2 complicaciones, hemorragia (grado I de Clavien) de afluente lumbar de vena cava, y linforrea(grado II de Clavien). Todos fueron adenocarcinomas renales. En el seguimiento de 6 meses promedio (2-24meses), hubo 1 caso de progresión pulmonar y no tuvimos recurrencia local ... (AU)

Introduction. Vascular thrombus is frequent in renal cell carcinoma, and it may extend to the inferior vena cava inup to 15% of patients. Radical surgery is the only treatment with curative potential. 5 year specific cancer survivalreaches 64%. Laparoscopic surgery is a reproducible option with good initial results. The objective is to show anddescribe the technical details of the laparoscopic resection of right sided renal tumor with extension to the inferior venacava. Material and methods. From January 2014 to July 2017, we performed 8 laparoscopic surgeries of renal cellcarcinoma with tumor venous thrombus extended to the inferior vena cava on the right side. The technique wasonly transperitoneal, with intracorporeal venous clamping. Patients with renal tumor and tumor thrombus up tothe diaphragm, without hilar adenopathic conglomerates were included. Patients with visceral metastases were notexcluded. Demographic, perioperative, and pathological data were collected and analyzed. All were included in anoncology follow up protocol.Results. Five men (62%) and three women (28%) were operated on with an average age of 56 (48 - 68) years.The vascular extension of the thrombus was 3.3 centimeters (2 - 5.4). There was no conversion to open surgery. Theaverage clamp time was 30 minutes (20 to 45). The surgical average time was 146 minutes (80 - 310). Postoperativeserum creatinine was 1.3 mg / dL (0.7 - 3). The hospitalization time was 5 days (3 - 8). Two complications occurred,hemorrhage (grade I of Clavien) of lumbar tributary of vena cava, and lymphorea (grade II of Clavien). All wererenal adenocarcinomas. At the 6-month follow-up mean (2-24 months), there was 1 case of lung progression and wedid not have local recurrence... (AU)

Validation of preoperative variables and stratification of patients to help predict benefit of cytoreductive nephrectomy in the targeted therapy ERA

ABSTRACT Objectives To further elucidate which patients with metastatic renal cell carcinoma (mRCC) may benefit from cytoreductive nephrectomy (CN) before targeted therapy (TT), and to assess the overall survival of patients undergoing CN and TT versus TT alone. Materials and Methods We identified 88 patients who underwent CN at our institution prior to planned TT and 35 patients who received TT without undergoing CN. Preoperative risk factors described in the literature were assessed in our patient population (serum albumin, liver metastasis, symptomatic metastasis, clinical ≥T3 disease, retroperitoneal and supradiaphragmatic lymphadenopathy). Patients were stratified by number of pretreatment risk factors and overall survival (OS) was compared. Results TT patients had significantly more risk factors compared to CN patients (3.06 vs. 2.11, p<0.01). Patients who received TT alone had median OS of 5.8 months. All but one patient receiving TT alone had two or more risk factors. A comparison of the CN and TT groups was performed by constructing Kaplan-Meier curves. There was no significant difference in median OS for those patients with exactly two risk factors (447 vs. 389 days, p=0.24), and those with three or more risk factors (184 vs. 155 days, p=0.87). Conclusions Using previously described pretreatment risk factors we found that patients with two or more risk factors derived no significant survival advantage from CN in the TT era. These risk factors should be incorporated in the assessment of patients for CN.

Diagnostic relevance of metastatic renal cell carcinoma in the head and neck: An evaluation of 22 cases in 671 patients

ABSTRACT Purpose Renal cell carcinoma (RCC) is a malignant tumor that metastasizes early, and patients often present with metastatic disease at the time of diagnosis. The aim of our evaluation was to assess the diagnostic and differential diagnostic relevance of metastatic renal cell carcinoma (RCC) with particular emphasis on head and neck manifestations in a large patient series. Patients and methods We retrospectively evaluated 671 consecutive patients with RCC who were treated in our urology practice between 2000 and 2013. Results Twenty-four months after diagnosis, 200/671 (30%) of RCC had metastasized. Distant metastases were found in 172 cases, with 22 metastases (3.3%) in the head and neck. Cervical and cranial metastases were located in the lymph nodes (n=13) and in the parotid and the thyroid gland, tongue, the forehead skin, skull, and paranasal sinuses (n=9). All head and neck metastases were treated by surgical excision, with 14 patients receiving adjuvant radiotherapy and 9 patients receiving chemotherapy or targeted therapy at some point during the course of the disease. Five patients (23%) survived. The mean time of survival from diagnosis of a head and neck metastasis was 38 months, the shortest period of observation being 12 months and the longest 83 months. Discussion and conclusion Our findings show that while RCC metastases are rarely found in the neck, their proportion among distantly metastasized RCC amounts to 13%. Therefore, the neck should be included in staging investigations for RCC with distant metastases, and surgical management of neck disease considered in case of resectable metastatic disease. Similarly, in patients presenting with a neck mass with no corresponding tumor of the head and neck, a primary tumor below the clavicle should be considered and the appropriate staging investigations initiated.

Brazilian data of renal cell carcinoma in a public university hospital

ABSTRACT Purpose Among renal malignancies, renal cell carcinoma (RCC) accounts for 85% of cases. Stage is a relevant prognostic factor; 5-year survival ranges from 81% to 8% according to the stage of disease. The treatment is based on surgery and molecularly targeted therapy has emerged as a choice for metastatic disease. Materials and Methods Retrospective study by reviewing the medical records of patients with RCC treated in the last 10 years at UNIFESP. The primary end point of this trial was to evaluate the overall survival (OS) of the patients. The secondary end point was to evaluate the progression-free survival (PFS) after nephrectomy. Results 118 patients with RCC were included. The mean age was 58.3 years, 61.9% men; nephrectomy was performed in 90.7%, clear cell was the histology in 85.6%, 44 patients were classified as stage IV at diagnosis. Among these, 34 had already distant metastasis. 29 patients were treated with sunitinib. The median OS among all patients was 55.8 months. The median PFS after nephrectomy was 79.1 months. Sarcomatoid differentiation HR29.74 (95% CI, 4.31-205.26), clinical stage IV HR1.94 (95% CI, 1.37-2.75) and nephrectomy HR0.32 (95% CI, 0.15-0.67) were OS prognostic factors. Sunitinib had clinical activity. Conclusions Patients treated in our hospital achieved median OS compatible with literature. Nevertheless, this study has shown a high number of patients with advanced disease. For patients with advanced disease, treatment with sunitinib achieved median OS of 28.7 months, consistent with the literature.

Male Genitourinary Tumors : 14 Years Experience in Garhwal Region of India.

Genitourinary tumors may show varied clinical presentation and frequency in different regions of the world. The present study was therefore conducted to analyze the frequency, clinical presentation and the histopathological types of the various male genitourinary tumors diagnosed over a period of 14 years in a major teaching institute of north Himalayan region of India. Material and Methods: Retrospective study was undertaken in the Pathology department of the Institute which included all the cases of male genitourinary tumors which were diagnosed on histopathology from the time period between 1 Jan 1997 till 31st Dec. 2010. Results: The study showed that prostate was the most common site for male genitourinary tumors with prostatic adenocarcinoma as the most common histopathological type of tumor. Testicular Non- Hodgkin’s lymphoma constituted about 8% of total tumors in testes which mostly presented in elderly age group. Renal cell carcinoma (66.2%) was the most common tumor in kidney with much lower frequency of Wilm’s tumor (16.9%). Occasional rare tumors such as hemangioma of urinary bladder and schwannoma of penis were also seen over 14 years. Conclusion: The study concludes clinically patients were associated with more severe symptoms as they presented late to the hospital from the remote areas of this Himalayan region leading to late detection of tumors. Prostatic adenocarcinoma was the most common tumor while renal cell carcinoma was most common tumor in kidney. The present study provides valuable information to clinicians and pathologists regarding frequency, clinical presentation and histopathological types of male genitourinary tumors in this region which can be further used to formulate strategies for better management of these tumors.

Nuevos agentes terapéuticos en cáncer renal avanzado / New therapeutic agents in advanced renal cancer

El carcinoma de células renales es responsable del 80 al 85 por cien de todas las neoplasias renales y su diagnóstico trae consigo la necesidad de intervención oportuna por las altas tasas de morbimortalidad relacionadas con esta patología. Es conocida la posibilidad de curación con el tratamiento quirúrgico cuando la enfermedad está organoconfinada, sin embargo, en un porcentaje no despreciable de pacientes aún con este tipo de intervención pueden desarrollar metástasis o recaídas posteriores a la cirugía. El desarrollo de nuevas estrategias terapéuticas enfocadas al manejo fisiopatológico de esta enfermedad comienza a demostrar en medianos plazos respuestas que son alentadoras y que se han constituido en la herramienta terapéutica más adecuada posterior al manejo quirúrgico citorreductor. Está por definirse el papel de las terapias blanco como alternativas neoadyuvantes.

Metástase vaginal como manifestação inicial de carcinoma de células renais / Vaginal metastasis as initial manifestation of renal cell carcinoma

A ocorrência de metástases de carcinoma de células renais para a vagina é rara. Ocorre principalmente em mulheres na pós-menopausa e o principal fator prognóstico é se essa metástase apresenta-se ou não isolada. Poucos casos foram relatados na literatura mundial e a maioria destes envolve metástases originadas no rim esquerdo. Os autores apresentam um caso de metástase vaginal de carcinoma de células renais em uma paciente de 53 anos de idade cuja apresentação clínica inicial foi de uma massa pediculada com bordas irregulares na parede posterior da vagina. Realizou-se a retirada cirúrgica da lesão que revelou tratar-se de adenocarcinoma de células claras. A ultrasonografia abdominal evidenciou presença de massa incidental no rim esquerdo e foi realizada a nefrectomia deste rim. O estudo imunoistoquímico realizado demonstrou tratar de lesão neoplásica primária do rim com metástase para a vagina. A paciente, então, recebeu radioterapia adjuvante na vagina e na pelve. Após oito meses do início do tratamento, realizou-se imunoterapia com interferon 2 devido ao aparecimento de metástase também para ofígado. A paciente encontra-se viva 17 meses após a cirurgia.

Sarcomatoid differentiation in renal cell carcinoma: prognostic implications

INTRODUCTION: Renal cell carcinoma with sarcomatoid differentiation is a tumor with aggressive behavior that is poorly responsive to immunotherapy. The objective of this study is to report our experience in the treatment of 15 patients with this tumor. MATERIALS AND METHODS: We retrospectively analyzed 15 consecutive cases of renal cell carcinoma with sarcomatoid differentiation diagnosed between 1991 and 2003. The clinical presentation and the pathological stage were assessed, as were the tumor's pathological features, use of adjuvant immunotherapy and survival. The study's primary end-point was to assess survival of these individuals. RESULTS: The sample included 8 women and 7 men with mean age of 63 years (44 - 80); follow-up ranged from 1 to 100 months (mean 34). Upon presentation, 87 percent were symptomatic and 4 individuals had metastatic disease. Mean tumor size was 9.5 cm (4 - 24) with the following pathological stages: 7 percent pT1, 7 percent pT2, 33 percent pT3, and 53 percent pT4. The pathological features showed high-grade tumors with tumoral necrosis in 87 percent of the lesions and 80 percent of intratumoral microvascular invasion. Disease-free and cancer-specific survival rates were 40 and 46 percent respectively, with 2 cases responding to adjuvant immunotherapy. CONCLUSIONS: Patients with sarcomatoid tumors of the kidney have a low life expectancy, and sometimes surgical resection associated with immunotherapy can lead to a long-lasting therapeutic response.

Medullary renal cell carcinoma case report

This is a case report of a medullary renal carcinoma in a sickle cell trait patient. The clinical, histological, and radiological features of this tumor are described, and the chemotherapeutic regimens used in this disease are discussed. Treatment modalities have proved largely unsuccessful in advanced disease. Medullary renal cell carcinoma is characterized by a lack of early warning signs, diverse clinical manifestations and resistance to radiotherapy and chemotherapy. Awareness and early diagnosis may prove essential in improving the survival rate

Tratamento do carcinoma renal metastático / Treatment of the metastic renal cell carcinoma

O carcinoma de células renais (COR) é a sétíma principal causa de câncer, respondendo por 3por cento dos tumores malignos no homem. Em um terço dos casos se apresenta como doença avançada e até 50por cento dos pacientes tratados cirurgicamente terão recidiva tumoral Acomete os homens duas vezez mais frequentemente que as mulheres e é mais comum entre a quinta e a sétima década de vida. O CCR teve sua incidência aumentada a partir da década de 70 devido ao uso rotineiro do ultra-som e aumento dos fatores de risco na população como fumo, obesidade e hipertensão. Pacientes com CCR metastático não tratados têm uma sobrevida média de seis a dez meses e apenas 10por cento a 20por cento estarão vivos após dois anos. Atualmente, com um melhor estudo da biologia e história natural do CCR, muitos avanços têm ocorrido nas áreas da genética molecular e ímunologia. Os autores fazem uma revisão das atuais modalidades terapêuticas do CCR avançado.

Carcinoma de células renales metastásico a la glándula tiroides / Metastasic renal cells carcinoma to the tryroid gland

Los tumores metastásicos localizados en la glándula tiroides son muy infrecuentes. El carcinoma de células renales es el responsable de muchas de las metástasis a la glándula tiroides y comúnmente ocurre muchos años después de haberse removido la lesión primaria. El primer caso fue descrito por Elliot y Frantz en 1960. Reportamos el caso de una paciente femenina de 66 años de edad con un carcinoma de células renales metastásico a la glándula tiroides que apareció catorce años después de una nefrectomía radical

Carcinoma renal de células claras quístico multiloculado: reporte de un caso y revisión de la literatura / Multilocular cystic clear cell renal carcinoma: case report and bibliographical review

El carcinoma de células renales quístico multiloculado es una forma común de cáncer, de diagnóstico preoperatorio díficil y pronóstico favorable. Se presenta el caso de una paciente femenina de 33 años quien consulta por dolor lumbar, sin hematuria y cuyos estudios imagenológicos revelaron la presencia de una masa quística compleja en polo renal derecho (Bosniak III). La paciente fue intervenida realizándose resección de la lesión, con diagnóstico de benignidad por biopsia peroperatoria. El estudio histopatológico reportó una masa quística multiloculada de 5,5 cm en dimensión mayor con presencia en los septos y pared de los quistes, de células claras de bajo grado nuclear (Fuhrman I). El diagnóstico histopatológico definitivo" fue carcinoma renal de células claras quístico multiloculado". Se concluye que estas neoplasias constituyen entidades clínico patológicas definitivas con características clínicas y patológicas particulares cuyo diagnóstico preoperatorio es dificil y que su mejor pronóstico se debe al escaso volumen tumoral para el momento del diagnóstico y su grado nuclear bajo

Renal Artery Embolization Using a New Liquid Embolic Material Obtained by Partial Hydrolysis of Polyvinyl Acetate (Embol):Initial Experience in Six Patients

OBJECTIVE: To evaluate the therapeutic efficacy of a new liquid embolic materi-al,Embol, in embolization of the renal artery. MATERIALS AND METHODS: Embol is a new embolic material obtained by partial hydrolysis of polyvinyl acetate mixed in absolute ethanol and Iopromide 370 and manufactured by Schering Korea, Kyonggido, Korea. Six patients who underwent embolization of the renal artery using Embol were evaluated. Four were male and two were female and their ages ranged from 11 to 70 (mean, 53) years. Clinical and radiologic diagnoses referred for renal artery embolization were renal cell carcinoma (n = 3), renal angiomyolipoma (n = 2) and pseudoaneurysm of the renal artery (n = 1). After selective renal angiography, Embol was injected through various catheters, either with or without a balloon occlusion catheter. Changes in symptoms and blood chemistry which may have been related to renal artery embolization with Embol were analyzed. RESULTS: The six patients showed immediate total occlusion of their renal vas-cular lesions. One of the three in whom renal cell carcinoma was embolized with Embol underwent radical nephrectomy, and the specimen thus obtained revealed 40% tumor necrosis. In the two patients with angiomyolipomas, the tumors decreased in size and abdominal pain subsided. Bleeding from pseudoaneurysm of the renal artery was successfully controlled. Four patients showed symptoms of post-embolization syndrome, and one of these also showed increased levels of blood urea nitrogen and creatinine. One patient experienced transient hyperten-sion. CONCLUSION: Embol is easy to use, its radiopacity is adequate and it is a safe and effective embolic material which provides immediate and total occlusion of renal vascular lesions.