RESUMEN
BIRM is an anticancer herbal formulation from Ecuador. Previous study established its antitumor and antimetastatic activity against prostate cancer models. The activity of BIRM against human prostate cancer (PCa) cells was investigated to uncover its mechanism of antitumor activity. In androgen receptor (AR)-expressing PCa cells BIRM was 2.5-fold (250%) more cytotoxic in presence of androgen (DHT) compared to cells grown in the absence of DHT. In AR-positive cells (LAPC-4 and LNCaP) BIRM caused a dose and time-dependent down-regulation of AR and increased apoptosis. Exposing cells to BIRM did not affect the synthesis of AR and AR promoter activity but increased degradation of AR via proteasome-pathway. BIRM caused destabilization of HSP90-AR association in LAPC-4 cells. It induced apoptosis in PCa cells by activation of caspase-8 via death receptor and FADD-mediated pathways. A synthetic inhibitor of Caspase-8 cleavage (IETD-CHO) aborted BIRM-induced apoptosis. The effect of BIRM on AKT-mediated survival pathway in both AR+ and AR- negative (PC-3 and DU145) showed decreased levels of p-AKTser 473 in all PCa cell lines. BIRM dosed by oral gavage in mice bearing PC-3ML tumors showed selective efficacy on tumor growth; before tumors are established but limited efficacy when treated on existing tumors. Moreover, BIRM inhibited the LNCaP tumor generated by orthotropic implantation into dorsal prostate of nude mice. Partial purification of BIRM by liquid-liquid extraction and further fractionation by HPLC showed 4-fold increased specific activity on PCa cells. These results demonstrate a mechanistic basis of anti-tumor activity of the herbal extract BIRM.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 8/metabolismo , Preparaciones de Plantas/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Animales , Línea Celular Tumoral , Ecuador , Humanos , Kalanchoe/química , Masculino , Ratones Desnudos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/genética , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Neuroendocrine tumors occurring outside of the gastrointestinal tract or lungs are very few, and to find a primary neuroendocrine tumor of the infrahepatic inferior vena cava (IVC) is extremely rare. We present a case of a patient with a large, 7 × 4 cm neuroendocrine tumor of the IVC, where the IVC and renal veins were completely extirpated and not reconstructed. As a result, the liver was anastomosed to the intrapericardial IVC, and the patient relied on collateral drainage. After an initial postoperative period of anasarca and weight gain, she ultimately recovered fully with no evidence of recurrence in the IVC.
Asunto(s)
Tumores Neuroendocrinos/cirugía , Injerto Vascular , Neoplasias Vasculares/cirugía , Vena Cava Inferior/cirugía , Anastomosis Quirúrgica , Circulación Colateral , Femenino , Hemodinámica , Humanos , Persona de Mediana Edad , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/fisiopatología , Flebografía/métodos , Venas Renales/patología , Venas Renales/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Neoplasias Vasculares/diagnóstico por imagen , Neoplasias Vasculares/patología , Neoplasias Vasculares/fisiopatología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología , Vena Cava Inferior/fisiopatologíaRESUMEN
Recurrent renal cell carcinoma (RCC) that presents as a solitary metastasis to the bladder is extremely rare. We report our experience with two patients who presented with hematuria within 1 year of their radical nephrectomy. Both patients underwent endoscopic resection of the tumor metastasis. One patient developed a metastasis in the head of pancreas 12 months following endoscopic resection. The other patient developed bilateral femoral and spinal bone metastasis. Our aim is to report our experience, and discuss the proposed modes of spread, management and prognosis.
Asunto(s)
Carcinoma de Células Renales/secundario , Neoplasias Renales/patología , Neoplasias de la Vejiga Urinaria/secundario , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Células Neoplásicas Circulantes/patología , Pronóstico , Tomografía Computarizada por Rayos X , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Vena Cava Inferior/patologíaRESUMEN
OBJECTIVES: To evaluate LRN as treatment for high risk patients. Laparoscopic radical nephrectomy (LRN) is performed for renal tumors not amenable to nephron-sparing treatments. Indications are increasing to include higher risk patients including those with end-stage renal disease (ESRD) necessitating dialysis. METHODS: We performed a retrospective analysis of a patient cohort with clinical stage T1 renal tumors undergoing transperitoneal LRN. Parameters examined included patient demographics, medical comorbidities, tumor characteristics, operative outcomes, and complications. RESULTS: One hundred eighty-nine patients underwent 195 LRN. Sixteen patients (8.5%) had preexistent ESRD requiring dialysis. A higher American Society of Anesthiologists score (P<.05), higher age-adjusted Charlson comorbidity index (P=.003), higher incidence of previous abdominal surgery (P=.012), and higher incidence of hypertension (P=.025) were found for the ESRD group. Mean blood loss was 153.0 and 132.0 mL (P=.71) in the ESRD patients and non-ESRD patients, respectively. A longer stay (P=.02) was noted for ESRD patients. Mean tumor size in the ESRD patients and non-ESRD patients was 2.6 and 4.2 cm (P<.05), respectively. Renal cell carcinoma was the most common pathology in 14 of 20 (70.0%) ESRD patient renal units and 167 of 175 (95.4%) non-ESRD patient renal units (P=.001). Intraoperative and postoperative complication rates were 6.3% and 31.3% respectively for ESRD patients (P=.05), and 8.7% and 21.4% respectively for non-ESRD patients (P=.35). Most postoperative complications were minor. CONCLUSIONS: LRN, for the treatment of renal tumors in ESRD patients requiring dialysis, is feasible and safe with acceptable intraoperative and postoperative complication rates. Patients with ESRD may require longer hospital stay after LRN.
Asunto(s)
Fallo Renal Crónico/terapia , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Diálisis Renal/métodos , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Neoplasias Renales/complicaciones , Neoplasias Renales/patología , Laparoscopía/mortalidad , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Estadificación de Neoplasias , Nefrectomía/mortalidad , Nefronas/cirugía , Peritoneo/cirugía , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/mortalidad , Probabilidad , Valores de Referencia , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Laparoscopic radical nephrectomy (LRN) is considered standard of care for T1 renal tumors not amenable to nephron-sparing surgery. Indications are now expanding to include patients with T2 or T3 tumors. The purpose of this study is to evaluate LRN as a minimally invasive procedure for treatment of advanced stage renal tumors. MATERIALS AND METHODS: We performed a retrospective analysis of a cohort of consecutive patients with renal tumors undergoing LRN for clinical stages T1 to T3. Parameters examined included patient demographics, medical comorbidities, tumor characteristics, perioperative outcomes, and complications. RESULTS: In all, 252 kidneys were removed from 247 consecutive patients undergoing LRN; 246/252 (97.6%) kidneys contained renal-cell carcinoma and 55 (21.8%) patients had pT2/T3 disease. Mean pathologic tumor size in the T1 and T2/T3 groups was 4.1 and 7.8 cm, respectively. Compared with patients with T1 tumor, patients with T2/T3 tumor had higher body mass index (p = 0.010), higher specimen weight (p = 0.002), higher mean Fuhrman grade (p = 0.014), and more postoperative complications (p = 0.035). Mean blood loss for T1 and T2/T3 patients was 133 and 198 cc, respectively; 3/197 patients (1.5%) and 4/55 patients (7.3%) in the T1 and T2/T3 groups received blood transfusion, respectively (p < or = 0.05). CONCLUSIONS: LRN for the treatment of clinical stage T2 and T3 disease should be considered. LRN can be safely performed with good perioperative outcome. Blood transfusion and complication rates are higher for LRN in pT2/T3 patients. However, the decision to modify surgical technique should be considered when either oncologic efficacy or patient safety is a concern.
Asunto(s)
Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Laparoscopía , Nefrectomía/métodos , Atención Perioperativa , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del TratamientoRESUMEN
PURPOSE: Laparoscopic radical nephrectomy is commonly performed for renal tumors that are not amenable to nephron sparing treatment. A number of techniques for intact specimen extraction are used. The development of incisional hernias from the extraction site is a known but infrequent delayed complication. We analyzed different extraction sites and risk factors for such hernias. MATERIALS AND METHODS: We retrospectively analyzed a cohort of patients undergoing laparoscopic radical nephrectomy with intact specimen extraction through 3 sites. Patients and operation specific parameters were included with particular attention to factors predisposing patients to incisional hernia, including chronic obstructive pulmonary disease, diabetes mellitus, chronic steroid use and a high body mass index. RESULTS: A total of 181 nephrectomies were performed in 175 patients and 175 kidneys (96.7%) had malignancy. Mean tumor size was 4.9 cm. Mean followup was 28.8 months. Extraction was done from a lower quadrant site in 55 patients (31.4%), from the umbilical site in 58 (33.2%) and from a paramedian site in 62 (35.4%). Patients with paramedian and lower quadrant extraction sites were older (p = 0.016), and had a higher body mass index (p = 0.001) and greater specimen weight (p = 0.003). In 4 patients an incisional hernia developed. An incisional hernia was significantly associated with the paramedian extraction site (p = 0.015). CONCLUSIONS: Incisional hernias may occur as a delayed complication of laparoscopic radical nephrectomy. This complication most commonly develops at the extraction site. In patients with a high body mass index using a paramedian extraction site is a significant risk factor for incisional hernia formation.
Asunto(s)
Hernia Ventral/etiología , Laparoscopía/efectos adversos , Nefrectomía/métodos , Anciano , Anciano de 80 o más Años , Femenino , Hernia Ventral/epidemiología , Humanos , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: Ureteral access sheaths (UASs) are used to facilitate ureteroscopic procedures. Difficulties with use have been reported. Manufacturers have redesigned these devices to ameliorate these problems, including reinforcement of the sheath wall. This study compared reinforced (RUASs) and nonreinforced UASs (NRUASs) of the same manufacturer to determine whether RUASs expedite ureteroscopy and how relevant the reinforced structure is in terms of overall success. METHODS: We prospectively followed up patients undergoing ureteroscopy for urolithiasis with 1 of 2 UASs; the Applied NRUAS and the Applied RUAS. The demographics, operative parameters, and outcomes were assessed. Statistical analysis was performed. RESULTS: A total of 98 UASs were used in 68 male and 30 female patients (47 NRUASs and 51 RUASs). No significant differences were found between the groups in terms of demographic parameters, operative parameters, or successful sheath deployment. The overall success rate for sheath deployment was 95%. A pre-existing stent was significantly associated with successful deployment (P = .004). The sheath-specific limitations included kinking (NRUASs, 10%) and sheath angulation/deformity (RUASs, 21%). The mean follow-up time was 43.4 months; and 93.9% of the patients had radiologic follow-up. No ureteral strictures were noted. CONCLUSIONS: No significant difference was found in the overall success rates between the use of Applied NRUASs and RUASs. The presence of a pre-existing stent was significantly associated with successful sheath deployment. Each UAS design had its own unique limitations, seen with low frequency. Successful sheath use might relate to both the sheath itself and the patient/operative parameters.