Assessment of a new kind of surgical simulator. The physical surgical simulator

Abstract Purpose: To evaluate whether the use of the physical surgical simulator may benefit the development of laparoscopic skills. Methods: Ten medical students were divided into two groups: the first one performed ten weekly training sessions with a physical surgical simulator - ETX A2 LAP and, afterwards, one laparoscopic cholecystectomy in a porcine model, while the second group performed only a laparoscopic cholecystectomy. Both groups were compared regarding bleeding, total surgical time, time to perform each surgical step and qualitative parameters, based on a previously validated tool. Results: There was no difference in any of the evaluated parameters. Conclusion: We did not find any evidence of benefit in the use of the physical simulator for surgical performance in medical students.

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.

Carbonic Anhydrase IX is Not a Predictor of Outcomes in Non-Metastatic Clear Cell Renal Cell Carcinoma - A Digital Analysis of Tissue Microarray

Introduction The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). Materials and Methods This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop® software. Results: Th e mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). Conclusion Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma. .

Can the learning of laparoscopic skills be quantified by the measurements of skill parameters performed in a virtual reality simulator?

Purpose To ensure patient safety and surgical efficiency, much emphasis has been placed on the training of laparoscopic skills using virtual reality simulators. The purpose of this study was to determine whether laparoscopic skills can be objectively quantified by measuring specific skill parameters during training in a virtual reality surgical simulator (VRSS). Materials and Methods Ten medical students (with no laparoscopic experience) and ten urology residents (PGY3-5 with limited laparoscopic experience) were recruited to participate in a ten-week training course in basic laparoscopic skills (camera, cutting, peg transfer and clipping skills) on a VRSS. Data were collected from the training sessions. The time that individuals took to complete each task and the errors that they made were analyzed independently. Results The mean time that individuals took to complete tasks was significantly different between the groups (p < 0.05), with the residents being faster than the medical students. The residents' group also completed the tasks with fewer errors. The majority of the subjects in both groups exhibited a significant improvement in their task completion time and error rate. Conclusion The findings in this study demonstrate that laparoscopic skills can be objectively measured in a VRSS based on quantified skill parameters, including the time spent to complete skill tasks and the associated error rate. We conclude that a VRSS is a feasible tool for training and assessing basic laparoscopic skills. .

Correlation between Beta1 integrin expression and prognosis in clinically localized prostate cancer

Integrins are transmembrane glycoprotein receptors that regulate cell-matrix interactions, thus functioning as sensors from the environment. They also act as cell adhesion molecules that are responsible for the maintenance of the normal epithelial phenotype. Some studies have reported a correlation between carcinogenesis and changes in integrin expression, especially β1 integrin, however its role in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of β1 integrin in localized PC and to correlate the pattern of expression with recurrence after surgical treatment. Methods For this case-control study, we retrospectively selected surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Recurrence was defined as a PSA level exceeding 0.2ng/mL after surgery, and the median follow-up was 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered a case as positive when the expression was strong and diffusely present. Results: There was a loss of 11 cases during the tissue micro array assembling. β1 expression was positive in 79 of the 100 evaluated cases (79%). The univariate and multivariate analyses showed that the negative expression of β1 integrin was associated with biochemical recurrence (p = 0.047) and time to recurrence after radical prostatectomy (p = 0.023). When β1 was negative, the odds ratio for recurrence was 2.78 times higher than that observed in the positive cases [OR = 2.78, p = 0.047, IC 95% (1.01-7.66)]. Conclusions: The loss of β1 integrin immune expression was correlated with biochemical recurrence in patients treated with radical prostatectomy for localized PC.

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β- and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

OBJECTIVE: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MATERIALS AND METHODS: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. RESULTS: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (> 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). CONCLUSION: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.

Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer

OBJECTIVE: To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer. PATIENTS AND METHODS: TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of li patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels. RESULTS: In the majority of the tumor samples, TGF-β1 was underexpressed 67.0 percent of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores >7 when compared to patients with Gleason scores <7(p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3 percent had poor prognostic features. CONCLUSIONS: TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.

Análise da expressão de MMP-2, MMP-9, MT1-MMP (MMP-14), TIMP-1, TIMP-2, RECK, TGF-Beta e interleucina-8 em câncer de próstata / Expression of MMP-2, MMP-9, MT1-MMP (MMP-14), TIMP-1, TIMP-2, RECK, TGF-Beta e interleucina-8 genes in the prostate cancer

Introdução: O câncer de próstata (CaP) é o tumor mais freqüente do homem no Brasil tendo sido estimados mais de 52.350 novos casos em 2010, sendo a segunda causa de óbito por câncer em homens. O prognóstico depende fundamentalmente dos níveis séricos de Prostatic Specific Antigen (PSA) estádio tumoral (TNM) e grau de diferenciação histológica (Gleason). Porém esses têm sido insuficientes na definição do prognóstico da neoplasia. Por isso pesquisas têm sido direcionadas para a identificação de alterações moleculares que possam prever o potencial de agressividade do câncer de próstata. Metaloproteinases da matriz (MMP) são proteínas pertencentes a uma família de aproximadamente 30 enzimas proteolíticas ou endoproteinases que degradam vários componentes da matriz extracelular. A detecção de sua expressão tem sido estudada como marcador sensível e específico de vários tumores, principalmente as MMP pertencentes ao grupo das gelatinases MMP-2 e MMP-9. Objetivo: o objetivo deste nosso trabalho foi avaliarmos pela técnica de qRT-PCR e imuno-histoquímica os níveis de expressão dos genes das MMP pertencentes ao grupo das gelatinases, MMP-2 e MMP-9, bem como outros sabidamente envolvidos em suas vias de ativação (MMP-14, IL-8) e inibição (TIMP-1, TIMP-2, RECK e TGF-) no câncer localizado de próstata. Material e Métodos: O estudo consistiu na análise de espécimes de 79 pacientes com câncer da próstata submetidos a prostatectomia radical entre setembro de 1997 e fevereiro de 2000. Esses oito genes foram então testados quanto a seu valor prognóstico no câncer da próstata através da técnica de reação em cadeia da polimerase quantitativa com transcriptase reversa (qRT-PCR). Análise proteica foi feita a partir de 40 pacientes deste pool. O grupo controle foi composto de tecido de 11 pacientes com hiperplasia benigna da próstata (HPB) tratados cirurgicamente com prostatectomia retropúbica. Resultados: MMP-9 esteve superexpressa e MMP-2, TIMP-1, TIMP-2, MMP 14, IL-8, TGF-...

Introduction: Currently, Prostate cancer (PCa) is the most common tumor in men in Brazil. It was estimated that more than 52,350 new cases were diagnosed in 2010, being the second cause of death by cancer in man. The prognosis depends mainly on Prostate Specific Antigen (PSA) serum levels, tumor stage (TNM) and histological grade (Gleason), but these parameters, even combined, are insufficient to define the correct prognosis of PCa. Therefore research has been directed towards the identification of molecular alterations that may predict potential aggressiveness of PCa. Matrix metalloproteinases (MMPs) are proteins that belong to a family of about 30 proteolytic enzymes that degrade various components of the extracellular matrix. The analysis of MMPs expression has been studied as a sensitive and specific marker of prognosis of several tumors, and special attention was focused in the group of gelatinases, MMP-2 and MMP-9.Objective: The aim of this study was to evaluate the expression levels of MMP-2 and MMP-9 genes and proteins by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in localized PCa. We also evaluated the expression of genes that are involved in the control of MMP-2 and MMP as activators (MMP- 14, IL-8) or inhibitors (TIMP-1, TIMP-2, RECK and TGF-).Materials and Methods: The casuistic consisted of 79 surgical specimens from patients with localized PCa who underwent radical prostatectomy between September 1997 and February 2000. The control group was composed of specimens from 11 patients with benign prostatic hyperplasia (BPH) treated surgically with retropubic prostatectomy. The results of the 8 genes expression, through qRTPCR and immunohistochemistry, were correlated to the diagnosis and prognosis of PCa. The protein expression analysis was carried out in 40 patients of the casuistic. Results: The MMP-9 was overexpressed, while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8, and TGF- were underexpressed...