Multifocal tDCS targeting the resting state motor network increases cortical excitability beyond traditional tDCS targeting unilateral motor cortex.

Scientists and clinicians have traditionally targeted single brain regions with stimulation to modulate brain function and disease. However, brain regions do not operate in isolation, but interact with other regions through networks. As such, stimulation of one region may impact and be impacted by other regions in its network. Here we test whether the effects of brain stimulation can be enhanced by simultaneously targeting a region and its network, identified with resting state functional connectivity MRI. Fifteen healthy participants received two types of transcranial direct current stimulation (tDCS): a traditional two-electrode montage targeting a single brain region (left primary motor cortex [M1]) and a novel eight-electrode montage targeting this region and its associated resting state network. As a control, 8 participants also received multifocal tDCS mismatched to this network. Network-targeted tDCS more than doubled the increase in left M1 excitability over time compared to traditional tDCS and the multifocal control. Modeling studies suggest these results are unlikely to be due to tDCS effects on left M1 itself, however it is impossible to completely exclude this possibility. It also remains unclear whether multifocal tDCS targeting a network selectively modulates this network and which regions within the network are most responsible for observed effects. Despite these limitations, network-targeted tDCS appears to be a promising approach for enhancing tDCS effects beyond traditional stimulation targeting a single brain region. Future work is needed to test whether these results extend to other resting state networks and enhance behavioral or therapeutic effects.

Retroperitoneal and transperitoneal laparoscopic cryotherapy for small renal masses.

OBJECTIVE: Cryotherapy is a minimally invasive ablative technique that is considered an alternative to conventional surgery for preserving renal function in small renal tumors and in selected cases. We present our results from laparoscopic renal cryotherapy. MATERIAL AND METHOD: We retrospectively analyzed 17 renal tumors diagnosed in 16 patients treated with cryotherapy. The patients' mean age was 66 years (43-80). The mean tumor size was 1.8cm (0.7-3.7cm). Cryotherapy with double-freeze cycle was performed laparoscopically in all cases (10 by transperitoneal approach and 7 by retroperitoneal approach). RESULTS: Perioperative biopsies were performed on all patients and were positive for malignancy in 10 cases (59%). The mean stay was 2.8 days. The mean operative time was 162 minutes. Only 1 case reverted to open surgery due to bleeding. One patient required a blood transfusion in the immediate postoperative period. The majority of complications were Clavien-Dindo grades I and II. Some 76.5% of the patients had no complications. After a mean follow-up of 31 months (6-102), 1 patient died from nontumor-related causes, and 12 patients (75%) still show no evidence of local recurrence or progression. One patient had tumor persistence and therefore underwent partial nephrectomy at 6 months. One patient had a metachronous recurrence in the same kidney at 36 months, and another patient had a recurrence at 23 months. CONCLUSIONS: Laparoscopic renal cryotherapy is a safe and feasible technique and is a good alternative to surgery for selected renal tumors.

Diagnostic and predictive value of urine PCA3 gene expression for the clinical management of patients with altered prostatic specific antigen.

OBJECTIVE: Analyze the impact of the introduction of the study of PCA3 gene in post-prostatic massage urine in the clinical management of patients with PSA altered, evaluating its diagnostic ability and predictive value of tumor aggressiveness. METHODS: Observational, prospective, multicenter study of patients with suspected prostate cancer (PC) candidates for biopsy. We present a series of 670 consecutive samples of urine collected post-prostatic massage for three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only indicated in cases with s-positive PCA3. RESULTS: The s-PCA3 was positive in 43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical small acinar proliferation was 54%, reaching 68,6% in s-PCA3≥100. Statistically significant relationship between the s-PCA3 and tumor grade was demonstrated. In cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason≥7), compared to 76.7% in cases with s-PCA3 over 50. There was a statistically significant correlation between s-PCA3 and cylinders affected. Both relationships were confirmed by applying a log-linear model. CONCLUSIONS: The incorporation of PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity increases the likelihood of a positive biopsy, especially in higher s-PCA3 100 (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides essential information in making treatment decisions.

La hibridación in situ fluorescente en la predicción de recurrencia del carcinoma urotelial / Fluorescent in situ Hybridization as a Predictor of Relapse in Urotelial Carcinoma

Objetivo: Evaluar la utilidad del estudio de alteraciones cromosómicas mediante hibridación in situ fluorescente en una serie de pacientes diagnosticados de carcinoma urotelial con un seguimiento mínimo de 24 meses, y analizar su posible efecto anticipador. Material y métodos: La serie global incluye 338 muestras procedentes de 98 pacientes con 84 episodios de carcinoma urotelial. Para evaluar la capacidad de predicción del test se estudió un subgrupo de 24 pacientes que presentaron como mínimo una recurrencia a lo largo del seguimiento (serie de recurrencia). Se consideraron 3 categorías (episodio coherente positivo, episodio coherente negativo y episodio no coherente) en función de la relación entre los resultados de la hibridación in situ fluorescente del estudio concomitante al nuevo episodio y las muestras precedentes. Resultados: La hibridación in situ fluorescente presentó mayor sensibilidad independientemente del grado, valor predictivo negativo y exactitud, mientras que la especificidad y el valor predictivo positivo fueron superiores para la citología convencional. En la serie de recurrencia 19/29 episodios resultaron coherentes, 11/19 fueron coherentes positivos, todos con carcinoma urotelial de alto grado, y 8/19 coherentes negativos, la mayoría de bajo grado. Conclusiones: La hibridación in situ fluorescente muestra una alta sensibilidad en un seguimiento de 24 meses, y es capaz de predecir recurrencias, especialmente en casos de alto grado. Nuestros datos demuestran también la existencia de carcinomas uroteliales sin alteraciones cromosómicas detectables con la metodología actualmente disponible. Los resultados apoyan un seguimiento multidisciplinar con la utilización combinada de la hibridación in situ fluorescente, citología y cistoscopia (AU)

Objective: To assess the value of the study of chromosomal alterations by fluorescent in situ hybridization in a series of patients diagnosed of urothelial carcinoma and a minimum follow up of twenty four months, as well as evaluate its putative predictive potential. Material and methods: The overall series includes 338 samples from 98 patients with 84 episodes of urothelial carcinoma. A subgroup of 24 patients who had at least one recurrence during the follow up was used to evaluate the predictive potential of the test. Three categories were considered (positive coherent episode, negative coherent episode, and incoherent episode) depending on the relationship between the fluorescent in situ hybridization result in the concomitant study of the new episode and those of the preceding samples. Results: Fluorescent in situ hybridization showed higher sensitivity regardless of grade, negative predictive value and accuracy, while specificity and positive predictive value were superior with conventional cytology. In the recurrence, series 19/29 episodes were coherent, 11/19 were positive coherent with urothelial carcinoma all high grade and 8/19 negative coherent, most low grade. Conclusions: Fluorescent in situ hybridization test shows good sensitivity during a follow up of twenty four months and is able to predict recurrence, especially in cases of high grade. Our data demonstrate the existence of urothelial carcinomas without detectable chromosomal abnormalities by currently available methodology. The results support a multidisciplinary follow up combining fluorescent in situ hybridization, cytology and cystoscopy (AU)

Fluorescent in situ hybridization as a predictor of relapse in urothelial carcinoma.

OBJECTIVE: To assess the value of the study of chromosomal alterations by fluorescent in situ hybridization in a series of patients diagnosed of urothelial carcinoma and a minimum follow up of twenty four months, as well as evaluate its putative predictive potential. MATERIAL AND METHODS: The overall series includes 338 samples from 98 patients with 84 episodes of urothelial carcinoma. A subgroup of 24 patients who had at least one recurrence during the follow up was used to evaluate the predictive potential of the test. Three categories were considered (positive coherent episode, negative coherent episode, and incoherent episode) depending on the relationship between the fluorescent in situ hybridization result in the concomitant study of the new episode and those of the preceding samples. RESULTS: Fluorescent in situ hybridization showed higher sensitivity regardless of grade, negative predictive value and accuracy, while specificity and positive predictive value were superior with conventional cytology. In the recurrence, series 19/29 episodes were coherent, 11/19 were positive coherent with urothelial carcinoma all high grade and 8/19 negative coherent, most low grade. CONCLUSIONS: Fluorescent in situ hybridization test shows good sensitivity during a follow up of twenty four months and is able to predict recurrence, especially in cases of high grade. Our data demonstrate the existence of urothelial carcinomas without detectable chromosomal abnormalities by currently available methodology. The results support a multidisciplinary follow up combining fluorescent in situ hybridization, cytology and cystoscopy.

Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. Spanish Oncology Genitourinary Group.

PURPOSE: To determine the maximum-tolerated dose and the antitumor activity of a combination of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, previously untreated, locally advanced or metastatic TCC and with Eastern Cooperative Oncology Group performance status < or = 2 and creatinine clearance > or = 55 mL/min were eligible. Cisplatin was given on day 1 at a fixed dose of 70 mg/m(2). Paclitaxel and gemcitabine were given on days 1 and 8 at increasing dose levels. Cycles were repeated every 21 days to a maximum of six cycles. RESULTS: Sixty-one patients were registered. In phase I, 15 patients were entered at four different dose levels. Dose-limiting toxicity consisted of early onset (after the first cycle) grade 2 asthenia (two of six patients) and grade 3 asthenia (one of six patients) at dose level 4. A paclitaxel dose of 80 mg/m(2) and gemcitabine 1,000 mg/m(2) was recommended for phase II, and 46 additional patients were entered at this level for a total of 49 patients. Main nonhematologic toxicity was grade 2 asthenia in 18 patients, with early onset in five patients, and grade 3 in four patients. Grade 3/4 neutropenia and thrombocytopenia occurred in 27 (55%) and 11 (22%) patients, respectively. Overall, febrile neutropenia was seen in 11 patients, and one toxic death occurred because of neutropenic sepsis. The combination was active at all dose levels. In total, 58 of 61 eligible patients were assessable for response; 16 complete responses (27.6%) and 29 partial responses (50%) were observed for an overall response rate of 77.6% (95% confidence interval, 60% to 98%). The median survival time (MST) available for the phase I part of the study is 24.0 months. MST has not been reached for the whole group with the current follow-up. CONCLUSION: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

M-CAVI, a neoadjuvant carboplatin-based regimen for the treatment of T2-4N0M0 carcinoma of the bladder.

Carboplatin, methotrexate, and vinblastine (M-CAVI) is an active and well-tolerated regimen for bladder cancer patients ineligible for cisplatin-based regimens. We treated 47 T2-4 N0 M0 bladder cancer patients with M-CAVI in a neoadjuvant phase II trial. These 47 patients are evaluable for clinical response and toxicity. Clinical overall response rate was 34%, for a 95% confidence interval (CI95%) of 21-49%. Pathological response was seen in 40% of the patients (CI95%, 26-56%) with a 26.5% rate of pathological complete response (CI95%, 15-42%). Factors associated with the achievement of a response to therapy were the initial TNM stage (pT3a or lower, greater than pT3a, p = 0.001) and a Karnofsky score greater or equal than 90%, which was marginally significant (p = 0.08). With a median follow-up of 14 months, the disease-specific actuarial survival at 2 years is 42%. No patient has relapsed beyond 21 months of follow-up in a disease-free status. Toxic effects have been moderate. In conclusion, M-CAVI is an active and well-tolerated regimen that should be compared in terms of response rate and survival with a cisplatin-based regimen for invasive bladder cancer.

[Type 1 fimbriae and P fimbriae in E. coli producing chronic prostatitis]. / Fimbrias tipo 1 y fimbrias P en E. coli productores de prostatitis crónica.

The fimbriated adhesines constitute a factor of virulence of E. coli in the urinary tract infections. The presence of type 1 fimbriae and fimbriae P was evaluated in 23 E. coli strains isolated with patients with chronic bacterial prostatitis. For the diagnosis of prostatitis the Stamey test was used. The detection of the type 1 fimbriae was carried out by agglutination of the E. coli strains with Saccharomyces cerevisiae and that of fimbriae P with PPA test. 95.7% of the evaluated strains had type 1 fimbriae and 52.2% had fimbriae P. It is concluded that type 1 fimbriae are common in all strains associated with urinary tract infection, without any relationship between their presence and the localization of infection, and that the presence of fimbriae P is not a constant feature of the E. coli strains associated with chronic prostatitis.

Renal leiomyosarcoma in a patient with tuberous sclerosis.

We report the case of a 16-year-old patient with tuberous sclerosis that presented as renal leiomyosarcoma. This is an exceptional form of presentation of this tumor. An angiomyolipoma has to be first suspected in this group of patients. If the diagnosis is not confirmed by the imaging studies, radical surgery is recommended.

Wilms' tumor in an adult patient.

We present herewith a case of Wilms' tumor in an adult patient. He underwent radical surgery, chemotherapy (adriamycin, actinomycin, vincristine and cyclophosphamide) and radiotherapy. He is alive and free of disease after 48 months of follow-up.