Métodos e instrumentos de evaluación en los programas de formación de pares para personas con problemas de salud mental: revisión documental / Métodos e instrumentos de avaliação em programas de formação por pares para pessoas com problemas de saúde mental: revisão documental / Methods and instruments of evaluation in peer training programs for people with mental health problems: documentary review

La formación de las personas con enfermedad mental favorece la inclusión social y laboral. La evaluación de estos programas es fundamental para determinar su alcance. El objetivo es identificar los métodos e instrumentos de evaluación empleados en los programas de formación de pares para personas con enfermedad mental. Se realiza una revisión documental. Según los criterios de inclusión y elegibilidad, se seleccionaron 56 programas para su análisis. Los métodos de evaluación utilizados son muy heterogéneos y la información proporcionada es limitada. Encontramos que la mayoría de los programas evalúa conocimientos, pero no las competencias adquiridas con la formación. Para una adecuada evaluación de competencias, es necesario que se recoja información en diferentes momentos y con estrategias que se complementen; de no actuar de esta forma sería complicado afirmar que la persona cuenta con las competencias necesarias para su desempeño.(AU)

Training people with mental illnesses promotes social and labour market inclusion. The evaluation of these programs is essential to determine their scope. The aim is to identify the methods and instruments used in the evaluation of peer education programs for people with mental illness. A documentary review has been carried out. According to the inclusion and eligibility criteria, 56 programs were selected for the analysis. We found that the evaluation methods used are very heterogeneous and the provided information is limited; most of the programs evaluate knowledge, but not the acquired competences through training. It is necessary to collect information at different times and with complementary strategies for an adequate evaluation of the competences. If this is not done, it would be difficult to affirm that the person has developed the necessary competences for their tasks.(AU)

A formação de pessoas com doenças mentais favorece a inclusão social e laboral. A avaliação destes programas é fundamental para determinar o seu alcance. O objetivo é identificar os métodos e instrumentos de avaliação utilizados nos programas de formação de pares para pessoas com doenças mentais. É realizada uma revisão documental. De acordo com os critérios de inclusão e elegibilidade, 56 programas foram selecionados para análise. Os métodos de avaliação utilizados são muito heterogêneos e a informação fornecida é limitada. Verificamos que a maioria dos programas avalia os conhecimentos, mas não as competências adquiridas através da formação. Para uma avaliação adequada das competências, é necessário recolher informações em momentos diferentes e com estratégias complementares; se isto não for feito, seria difícil afirmar que a pessoa tem as competências necessárias para o seu desempenho.(AU)

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.

The concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute to tumor progression, and could counteract therapeutic effects. Additionally, cancer therapies can induce cellular and molecular responses in the tumor and host that allow them to escape therapy and promote tumor progression. In this study, we describe the vascular network, tumor-infiltrated immune cells, and cancer-associated fibroblasts as sources of heterogeneity and plasticity in the tumor microenvironment, and their influence on cancer progression. We also discuss tumor and host responses to the chemotherapy regimen, at the maximum tolerated dose, mainly targeting cancer cells, and a multimodal metronomic chemotherapy approach targeting both cancer cells and their microenvironment. In a combination therapy context, metronomic chemotherapy exhibits antimetastatic efficacy with low toxicity but is not exempt from resistance mechanisms. As such, a better understanding of the interactions between the components of the tumor microenvironment could improve the selection of drug combinations and schedules, as well as the use of nano-therapeutic agents against certain malignancies.

Diagnostic accuracy of liver and spleen stiffness measured by fibroscan® in the prediction of esophageal varices in HCV-related cirrhosis patients treated with oral antivirals.

INTRODUCTION: The aim of this study was to investigate the accuracy of liver and spleen stiffness measurement by transient elastography for the prediction of gastroesophageal varices in patients with HCV-associated cirrhosis treated with new direct-acting antiviral agents. PATIENTS AND METHODS: This cross-sectional observational study included patients with compensated HCV-related cirrhosis and sustained virological response after direct-acting antiviral therapy. Patients underwent liver and spleen stiffness measurement, abdominal ultrasound and oesophago-gastroduodenoscopy. Clinical and laboratory data and non-invasive markers such as the liver stiffness-spleen diameter to platelet ratio score, variceal risk index and platelet count to spleen diameter ratio were analyzed. RESULTS: Ninety-seven consecutive patients were included. Liver stiffness measurement (12.2 vs 16; p=0.02), spleen stiffness measurement (39.4 vs 46.05; p=0.04), liver stiffness-spleen diameter to platelet ratio score (1.21 vs 2.02; p=0.008), platelet count to spleen diameter ratio (1102.19 vs 829.7; p=0.04) and variceal risk index (-3.4 vs -1.02; p=0.01) showed significant differences between patients without/with gastroesophageal varices. The best cut-off value to discard the presence of gastroesophageal varices was 12.3kPa for liver stiffness measurement and 27kPa for spleen stiffness measurement. However, diagnostic accuracy was moderate (AUROC: 0.671 and 0.624 respectively). Combining different non-invasive parameters did not significantly improve the overall performance. DISCUSSION: Liver and spleen stiffness measurement showed suboptimal results for non-invasive assessment of gastroesophageal varices in HCV cirrhotic patients treated with direct-acting antiviral agents. Our results suggest that non-invasive methods cannot substitute standard procedures for predicting gastroesophageal varices in this population.

A double safety lock tumor-specific device for suicide gene therapy in breast cancer.

The complexity and continuous evolution of cancer make the design of novel strategies of treatment a constant challenge in biomedicine. Moreover, most of cancer treatments are still not tumor-specific and provoke high systemic toxicity. Herein we have developed a novel selective nanodevice to eliminate tumor cells while leaving healthy ones intact. To achieve this objective, a polyplex carrier, comprising an elastin like-recombinamer covalently conjugated to an aptamer and complexed with therapeutic DNA, was tested. This carrier forms a double-lock multifunctional device due to specific binding to a tumor cell marker and the selective expression of therapeutic DNA inside human breast-cancer cells. Due to the stability provided by ELRs, the homogeneous population of polyplexes obtained showed selective toxicity against cancer cells in in vitro and in vivo assay. Inhibition of tumor progression was detected early being very significant at the end point, with a dose-dependent reduction in tumor mass. Histological studies revealed a specific reduction in tumor parenchyma and in specific tumor cell markers. These results represent an important step toward the rational development of an efficient, safe and more specialized gene-delivery device for tumor therapy.

Different Lifestyle Interventions in Adults From Underserved Communities: The FAMILIA Trial.

BACKGROUND: The current trends of unhealthy lifestyle behaviors in underserved communities are disturbing. Thus, effective health promotion strategies constitute an unmet need. OBJECTIVES: The purpose of this study was to assess the impact of 2 different lifestyle interventions on parents/caregivers of children attending preschools in a socioeconomically disadvantaged community. METHODS: The FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) study is a cluster-randomized trial involving 15 Head Start preschools in Harlem, New York. Schools, and their children's parents/caregivers, were randomized to receive either an "individual-focused" or "peer-to-peer-based" lifestyle intervention program for 12 months or control. The primary outcome was the change from baseline to 12 months in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco (Fuster-BEWAT Score [FBS]), ranging from 0 to 15 (ideal health = 15). To assess the sustainability of the intervention, this study evaluated the change of FBS at 24 months. Main pre-specified secondary outcomes included changes in FBS subcomponents and the effect of the knowledge of presence of atherosclerosis as assessed by bilateral carotid/femoral vascular ultrasound. Mixed-effects models were used to test for intervention effects. RESULTS: A total of 635 parents/caregivers were enrolled: mean age 38 ± 11 years, 83% women, 57% Hispanic/Latino, 31% African American, and a baseline FBS of 9.3 ± 2.4 points. The mean within-group change in FBS from baseline to 12 months was ∼0.20 points in all groups, with no overall between-group differences. However, high-adherence participants to the intervention exhibited a greater change in FBS than their low-adherence counterparts: 0.30 points (95% confidence interval: 0.03 to 0.57; p = 0.027) versus 0.00 points (95% confidence interval: -0.43 to 0.43; p = 1.0), respectively. Furthermore, the knowledge by the participant of the presence of atherosclerosis significantly boosted the intervention effects. Similar results were sustained at 24 months. CONCLUSIONS: Although overall significant differences were not observed between intervention and control groups, the FAMILIA trial highlights that high adherence rates to lifestyle interventions may improve health outcomes. It also suggests a potential contributory role of the presentation of atherosclerosis pictures, providing helpful information to improve future lifestyle interventions in adults.

Suppressive impact of metronomic chemotherapy using UFT and/or cyclophosphamide on mediators of breast cancer dissemination and invasion.

Metronomic chemotherapy using the 5-FU prodrug uracil-tegafur (UFT) and cyclophosphamide (CTX) was previously shown to only modestly delay primary tumor growth, but nevertheless markedly suppressed the development of micro-metastasis in an orthotopic breast cancer xenograft model, using the metastatic variant of the MDA-MB-231 cell line, 231/LM2-4. Furthermore, a remarkable prolongation of survival, with no toxicity, was observed in a model of postsurgical advanced metastatic disease. A question that has remained unanswered is the seemingly selective anti-metastatic mechanisms of action responsible for this treatment. We assessed the in vivo effect of metronomic UFT, CTX or their combination, on vascular density, collagen deposition and c-Met (cell mediators or modulators of tumor cell invasion or dissemination) via histochemistry/immunohistochemistry of primary tumor sections. We also assessed the effect of continuous exposure to low and non-toxic doses of active drug metabolites 5-fluorouracil (5-FU), 4-hydroperoxycyclophosphamide (4-HC) or their combination, on 231/LM2-4 cell invasiveness in vitro. In the in vivo studies, a significant reduction in vascular density and p-Met[Y1003] levels was associated with UFT+CTX treatment. All treatments reduced intratumoral collagen deposition. In the in vitro studies, a significant reduction of collagen IV invasion by all treatments was observed. The 3D structures formed by 231/LM2-4 on Matrigel showed a predominantly Mass phenotype under treated conditions and Stellate phenotype in untreated cultures. Taken together, the results suggest the low-dose metronomic chemotherapy regimens tested can suppress several mediators of tumor invasiveness highlighting a new perspective for the anti-metastatic efficacy of metronomic chemotherapy.

Self-Assembling ELR-Based Nanoparticles as Smart Drug-Delivery Systems Modulating Cellular Growth via Akt.

This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug-delivery system based on elastin-like block recombinamers. The DNA recombinant techniques allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH, and blockage of cellular growth by a small peptide inhibitor. The recombinant polymer reversibly self-assembled when the temperature was increased above 15 °C into nanoparticles with a diameter of 72 nm and negative surface charge. Furthermore, smart nanoparticles were shown to enter in the cells via clathrin-dependent endocytosis and properly blocked phosphorylation and consequent activation of Akt kinase. This system provoked apoptosis-mediated cell death in breast and colorectal cancer cells, which possess higher expression levels of Akt, whereas noncancerous cells, such as endothelial cells, fibroblasts, and mesenchymal stem cells, were not affected. Hence, we conclude that the conformational complexity of this smart elastin-like recombinamer leads to achieving successful drug delivery in targeted cells and could be a promising approach as nanocarriers with bioactive peptides to modulate multiple cellular processes involved in different diseases.

Exogenous γ-aminobutyric acid treatment improves the cold tolerance of zucchini fruit during postharvest storage.

This work examines the effect of a treatment with 1 mM of γ-aminobutyric acid (GABA) on zucchini fruit during postharvest cold storage. Specifically, the effect of GABA on postharvest quality was measured, as well as its implication in the GABA shunt and other related metabolic pathways. The treatments were performed in Sinatra, a variety of zucchini highly sensitive to low-temperature storage. The application of GABA improved the quality of zucchini fruit stored at 4 °C, with a reduction of chilling-injury index, weight loss, and cell death, as well as a lower rate of electrolyte leakage. GABA content was significantly higher in the treated fruit than in the control fruit at all times analyzed. At the end of the storage period, GABA-treated fruit had higher contents of both proline and putrescine. The catabolism of this polyamine was not affected by exogenous GABA. Also, over the long term, the treatment induced the GABA shunt by increasing the activities of the enzymes GABA transaminase (GABA-T) and glutamate decarboxylase (GAD). GABA-treated fruit contained higher levels of fumarate and malate than did non-treated fruit, as well as higher ATP and NADH contents. These results imply that the GABA shunt is involved in providing metabolites to produce energy, reduce power, and help the fruit to cope with cold stress over the long term.

A different approach for the analysis of grapes: Using the skin as sensing element.

In this work, an alternative method to monitor the phenolic maturity of grapes was developed. In this approach, the skins of grapes were used to cover the surface of carbon paste electrodes and the voltammetric signals obtained with the skin-modified sensors were used to obtain information about the phenolic content of the skins. These sensors could easily detect differences in the phenolic composition of different Spanish varieties of grapes (Mencía, Prieto Picudo and Juan García). Moreover, sensors were able to monitor changes in the phenolic content throughout the ripening process from véraison until harvest. Using PLS-1 (Partial Least Squares), correlations were established between the voltammetric signals registered with the skin-modified sensors and the phenolic content measured by classical methods (Glories or Total Polyphenol Index). PLS-1 models provided additional information about Brix degree, density or sugar content, which usually used to establish the harvesting date. The quality of the correlations was influenced by the maturation process and the structural and mechanical skin properties. Thus the skin sensors fabricated with Juan García and Prieto Picudo grapes (that showed faster polyphenolic maturation and a higher amount of extractable polyphenols than Mencía), showed good correlations and therefore could be used to monitor the ripening.

A new family of fullerene derivatives: Fullerene-curcumin conjugates for biological and photovoltaic applications.

The synthesis and characterization of a family of [60]fullerocurcuminoids obtained via Bingel reactions is reported. The new C60 derivatives include curcumin and curcuminoids with a variety of end groups. Preliminary biological experiments show the potential activity of the compound containing a curcumin addend, which exhibits moderate anti-HIV-1 and radical scavenger properties, but no anti-cancer activity. In addition, the new fullerocurcuminoids exhibit HOMO/LUMO energy levels that are reasonably matched with those of perovskites and when they were tested in perovskite solar cells (PSCs) as the electron transporting material (ETM), photoconversion efficiencies ranging from 14.04%-14.95% were obtained, whereas a value of 16.23% was obtained for [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) based devices.

Effectiveness, safety and clinical outcomes of direct-acting antiviral therapy in HCV genotype 1 infection: Results from a Spanish real-world cohort.

BACKGROUND & AIMS: Clinical trials evaluating second-generation direct-acting antiviral agents (DAAs) have shown excellent rates of sustained virologic response (SVR) and good safety profiles in patients with chronic hepatitis C virus (HCV) genotype 1 infection. We aimed to investigate the effectiveness and safety of two oral DAA combination regimens, ombitasvir/paritaprevir/ritonavir plus dasabuvir (OMV/PTV/r+DSV) and ledipasvir/sofosbuvir (LDV/SOF), in a real-world clinical practice. METHODS: Data from HCV genotype 1 patients treated with either OMV/PTV/r+DSV±ribavirin (RBV) (n=1567) or LDV/SOF±RBV (n=1758) in 35 centers across Spain between April 1, 2015 and February 28, 2016 were recorded in a large national database. Demographic, clinical and virological data were analyzed. Details of serious adverse events (SAEs) were recorded. RESULTS: The two cohorts were not matched with respect to baseline characteristics and could not be compared directly. The SVR12 rate was 96.8% with OMV/PTVr/DSV±RBV and 95.8% with LDV/SOF±RBV. No significant differences were observed in SVR according to HCV subgenotype (p=0.321 [OMV/PTV/r+DSV±RBV] and p=0.174 [LDV/SOF]) or degree of fibrosis (c0.548 [OMV/PTV/r/DSV±RBV] and p=0.085 [LDV/SOF]). Only baseline albumin level was significantly associated with failure to achieve SVR (p<0.05) on multivariate analysis. Rates of SAEs and SAE-associated treatment discontinuation were 5.4% and 1.7%, in the OMV/PTV/r+DSV subcohort and 5.5% and 1.5% in the LDV/SOF subcohort, respectively. Hepatocellular carcinoma (HCC) recurred in 30% of patients with a complete response to therapy for previous HCC. Incident HCC was reported in 0.93%. CONCLUSIONS: In this large cohort of patients managed in the real-world setting in Spain, OMV/PTV/r+DSV and LDV/SOF achieved high rates of SVR12, comparable to those observed in randomized controlled trials, with similarly good safety profiles. LAY SUMMARY: In clinical trials, second-generation direct-acting antiviral agents (DAAs) have been shown to cure over 90% of patients chronically infected with the genotype 1 hepatitis C virus and have been better tolerated than previous treatment regimens. However, patients enrolled in clinical trials do not reflect the real patient population encountered in routine practice. The current study, which includes almost 4,000 patients, demonstrates comparable rates of cure with two increasingly used DAA combinations as those observed in the clinical trial environment, confirming that clinical trial findings with DAAs translate into the real-world setting, where patient populations are more diverse and complex.

CD8 down-regulation on cytotoxic T lymphocytes of patients with endometrioid endometrial carcinomas.

Carcinogenesis is a multistep process in which cancer cells and tumor stroma cells play important roles. T lymphocytes are immune constituents of tumor stroma and play a crucial function in anti-tumor response. By immunohistochemistry and flow cytometry, we studied T cytotoxic (CTLs) and T helper lymphocyte distribution and percentage in the tumor microenvironment and peripheral blood from 35 patients with endometrioid endometrial carcinomas (EEC). We also studied 23 healthy donors' blood samples as a control group. Tumor and non-tumoral endometrium samples were obtained. Immunohistochemistry revealed a high number of CTLs and T helper lymphocytes in the tumor stroma of myoinvasive EECs. T lymphocytes were mostly located in the invasive front. By flow cytometry, the percentages of CTLs and T helper lymphocytes were significantly higher in the tumor compared with the non-neoplastic endometrium (P = .0492 and P = .002). The mean fluorescence intensity of CD8 staining was lower in the tumor compared to the non-neoplastic endometrium (P = .001). There was also reduction of the mean fluorescence intensity of CD8 staining on peripheral blood from patients with grade 3 EECs compare to the peripheral blood from healthy donors (P = .0093). No alterations in the expression of granzymes A and B were found in the CTLs from the EEC cases. Finally, in a proteome profiler cytokine array we found that the growth differentiation factor 15 (GDF15) increased in blood in parallel to the tumor grade. EECs are capable of down-regulating CD8 expression of CTLs. Most likely, this effect is mediated by a soluble molecule present in plasma and is not a result of anergy or exhaustion state.

In vitro and in vivo effects of an anti-mouse endoglin (CD105)-immunotoxin on the early stages of mouse B16MEL4A5 melanoma tumours.

TGF-beta superfamily co-receptors are emerging as targets for cancer therapy, acting both directly on cells and indirectly on the tumour neovasculature. Endoglin (CD105), an accessory component of the TGF-beta receptor complex, is expressed in certain melanoma cell lines and the endothelial cells of tumour neovessels. Targeting endoglin with immunotoxins is an attractive approach for actively suppressing the blood supply to tumours. Here, we report evidence indicating that endoglin is expressed in mouse melanoma B16MEL4A5 and mouse fibroblast L929 cell lines. We prepared an immunotoxin to target endoglin by coupling the rat anti-mouse MJ7/18 (IgG2a) monoclonal antibody (mAb) to the non-toxic type 2 ribosome-inactivating protein nigrin b (Ngb) with N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP) as a linker with a molar nigrin b at a MJ7/18 stoichiometry of 2:1. The MJ7-Ngb immunotoxin generated killed both cell lines, with IC50 values of 4.2 × 10(-9) M for B16MEL4A5 and 7.7 × 10(-11) M for L929 cells. For in vivo assays of the immunotoxin, B16MEL4A5 cells were injected subcutaneously into the right flanks of 6-week-old C57BL/6 J mice. When the animals developed palpable solid tumours, they were subjected to treatment with the immunotoxin. While treatment with either MJ7/18 mAb or Ngb did not affect tumour development, treatment with the immunotoxin completely and steadily blocked tumour growth up to 7 days, after which some tumours re-grew. Thus, vascular-targeting therapy with this anti-vascular immunotoxin could promote the destruction of newly created tumour vessels at early stages of B16MEL4A5 tumour development and readily accessible CD105+ B16MEL4A5 melanoma cells.

Transient injury-dependent up-regulation of CD105 and its specific targeting with an anti-vascular anti-mouse endoglin-nigrin b immunotoxin.

Endoglin (CD105), a cell-surface co-receptor for transforming growth factor-beta (TGF-ß) superfamily members, is over-expressed in tumor neovasculature and can be targeted with anti-endoglin antibodies, thus becoming an important tool for anti-tumoral therapy. Injury of the mouse tail induced the transient expression of endoglin, this peaking at three days after injury and disappearing six days later. An immunotoxin containing the anti-mouse endoglin rat monoclonal antibody MJ7/18 and the non-toxic ribosome-inactivating protein nigrin b (Ngb) was found to be very active in targeting mouse endoglin in the L929 fibroblast cell line (IC(50) of 4 x 10(-11) M). At that concentration, the immunotoxin lacked unspecific activity. Upon induction of endoglin after injury, the MJ7-Ngb immunotoxin strongly attacked and deranged the injured tail, inducing tissue damage. Such effects were dependent on the age of the animals and were evident in six-week-old mice, but not in eight-month-old mice. Our results indicate that endoglin is up-regulated in newly formed vessels upon injury and can be targeted by the MJ7-Ngb immunotoxin; thus, it could be a useful tool for tumor ablation research.

Insulation failure in robotic and laparoscopic instrumentation: a prospective evaluation.

OBJECTIVE: The purpose of this study was to detect the incidence, prevalence, and location of insulation failures (IFs) in laparoscopic and robotic instruments. STUDY DESIGN: In phase A, a total of 78 robotic and 298 laparoscopic instruments were tested at 20 W and 2.64 kV at Mayo Clinic in Arizona. In phase B, 60 robotic and 308 laparoscopic instruments were tested at 20 W/1 kV and 20 W/4.2 kV, respectively. RESULTS: In phase A, the robotic group showed a higher prevalence (25/78; 32%) and incidence of IFs after 10 uses (35/44 instruments; 80%) when compared with laparoscopy (prevalence, 39/298 [13%]; incidence, 68/189 [36%]; P<.05). In phase B, IFs were detected in 81.7% of the robotic instruments and in 19.5% of the laparoscopic instruments (P<.005). CONCLUSION: There is a high incidence and prevalence of IF in endoscopic instrumentation that is more common in the robotic group.

The value of p16 in ASCUS cases: a retrospective study using frozen cytologic material.

This study scans the efficacy of p16 immunostain on gynecological cytologies for the detection of high-grade lesions in ASCUS cases. This is a retrospective study that evaluates p16 immunostaining using frozen material from 109 cases diagnosed as ASCUS and followed for an average of 16 months. The diagnosis of ASCUS was made using liquid-based cytology (Thin Prep, Hologic, Marlborough, MA). High-risk HPV using Hybrid Capture II was performed. The immunohistochemical evaluation of p16 immunoreactivity was done following Wentzensen criteria. In the series p16 immunoreactivity showed a sensitivity and negative predictive value for HSIL, of 82.3 and 94.5% with specificity and positive predictive value of 100%. The sensitivity was similar to that found using the HC-II, though the specificity was much higher. The use of p16 immunostain in cytologic specimens applying the Wentzensen criteria helps to focus the attention in positive cells evaluating the cell changes, helps to detect some cells suspicious or diagnostic of HSIL, and could help to reclassify the ASCUS cases.

Robotic adnexectomy compared with laparoscopy for adnexal mass.

OBJECTIVE: To evaluate whether the application of robotic technology in the performance of adnexectomy resulted in benefits for the patient when compared with patients operated by laparoscopy. METHODS: Evaluation of 85 patients undergoing robotic adnexectomy and comparison with a group of 91 patients operated on by laparoscopy during the same period of time and by the same surgeons. Patients were compared by age, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, indications, unilateral compared with bilateral adnexectomy, adhesions, size or weight or both of the adnexal mass, and previous abdominal or pelvic surgery. Univariate and multivariate analysis was used to determine factors favorable to each technique. Comparison between the groups was evaluated using the Fisher exact test from a one-way analysis of variance. RESULTS: The robotic group had an increased number of obese (BMI 30 or more) and higher anesthetic risk (ASA classification 2 and 3) patients as compared with laparoscopy patients. The mean operating time was 12 minutes longer in the robotic group (P=.01). The mean blood loss (80 mL robotic, 71 mL laparoscopic), length of hospital stay (0.15 days robotic, 0.28 days laparoscopic), intraoperative complications (1% robotic, 2% laparoscopic), and postoperative complications (12% robotic, 11% laparoscopic) were similar in both groups. CONCLUSION: : Laparoscopy and robotics provided similar results for the performance of adnexectomy, with similar blood loss, intraoperative and postoperative complications, and length of hospital stay. Robotics mean operating time was 12 minutes longer. LEVEL OF EVIDENCE: II.

3q26 (hTERC) gain studied by fluorescence in situ hybridization as a persistence-progression indicator in low-grade squamous intraepithelial lesion cases.

Gains of 3q26 chromosome region, where the human telomerase RNA gene (hTERC) is located, have been previously documented in cervical carcinomas and preneoplastic lesions. The aim of our study was to define the value of 3q26 gains related to persistence-progression in cervical specimens with cytologic diagnosis for low-grade squamous intraepithelial lesions, using liquid-based cytology (ThinPrep; Hologic, Marlborough, MA) and fluorescence in situ hybridization. For these purposes, 55 patients were included in the study: 25 cases with a negative cytologic diagnosis for squamous intraepithelial lesion or malignancy (20 premenopausal and 5 postmenopausal women, used as control negative cases) and 30 low-grade squamous intraepithelial lesion cases. The follow-up was performed using cytology at 6, 12, and 24 months after the low-grade squamous intraepithelial lesion diagnosis. When the cytology result showed a high-grade lesion, colposcopy and biopsy were performed. Fluorescence in situ hybridization technique with a 3q26 2-color commercial probe was performed to determine the number of hTERC copies. There were no differences between premenopausal and postmenopausal normal cases. Low-grade squamous intraepithelial lesion cases with regression in the follow-up at 6, 12, and 24 months showed a percentage of cells with 3q26 gains similar to the control cases and lower than low-grade squamous intraepithelial lesion cases with persistence or progression (P < .05). Fluorescence in situ hybridization results were similar in preserved and frozen samples. However, in frozen samples, the number of cells suitable to be evaluated by fluorescence in situ hybridization was lower than in preserved (nonfrozen) cases. In conclusion, the determination by fluorescence in situ hybridization of 3q26 gains in low-grade squamous intraepithelial lesion cases could be useful to predict the persistence-progression of such cervical lesions using both preserved and frozen cervical material.

On the development of models in mice of advanced visceral metastatic disease for anti-cancer drug testing.

It is well known clinically that advanced, bulky visceral metastatic disease is generally much less responsive to most anti-cancer therapies, compared to microscopic metastatic disease. This problem is exacerbated when treating cancers that have been previously exposed to multiple lines of therapy, and which have acquired a 'refractory' phenotype. However, mimicking such clinical treatment situations in preclinical mouse models involving the testing of new or existing cancer therapies is extremely rare. Treatment of 'metastasis', in retrospect, usually involves minimal residual disease and therapy naïve tumors. This could account in many instances for the failure to reproduce highly encouraging preclinical results in subsequent phase I or phase II clinical trials. To that end, we have embarked on an experimental program designed to develop models of advanced, visceral metastatic disease, in some cases involving tumors previously exposed to various therapies. The strategy first involves the orthotopic transplantation of a human cancer cell line, such as breast cancer cell line, into the mammary fat pads of immune deficient mice, followed by surgical resection of the resultant primary tumors that develops. Recovery of distant macroscopic metastases, usually in the lungs, is then undertaken, which can take up to 4 months to visibly form. Cell lines are established from such metastases and the process of orthotopic transplantation, surgical resection, and recovery of distant metastases is undertaken, at least one more time. Using such an approach highly metastatically aggressive variant sublines can be obtained, provided they are once again injected into an orthotopic site and the primary tumors removed by surgery. By waiting sufficient time after removal of the primary tumors, about only 1 month, mice with extensive metastatic disease in sites such as the lungs, liver, and lymph nodes can be obtained. An example of therapy being initiated in an advanced stage of such disease development is illustrated. Metastases that eventually stop responding to a particular therapy can be removed as a source of variant cell lines which have both 'refractory' and highly metastatic phenotypes. Such models may provide a more accurate picture of the potential responsiveness to an experimental therapy so that a high degree of responsiveness observed could be a factor in deciding whether to move a particular therapy forward into phase I/phase II clinical trial evaluation. An example of this is illustrated using doublet metronomic low-dose chemotherapy for the treatment of advanced metastatic breast cancer, using two conventional chemotherapy drugs, namely, cyclophosphamide and UFT, a 5-FU oral prodrug.