Prognostic significance of metallothionein expression in renal cell carcinoma

BACKGROUND: Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. PATIENTS AND METHODS: The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). RESULTS: Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. CONCLUSIONS: The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter

Multi-criteria optimization and decision-making in Radiotherapy

Introduction: La radiothérapie est une des branches de l'oncologie dont le but est la destruction des tumeurs tout en préservant les tissus sains . Avant de délivrer la dose au patient, un plan de traitement, spécifique au patient, est créé. Malgré les progrès technologiques, ce plan de traitement reste un compromis entre la protection des tissus sains et une irradiation suffisante de la tumeur. Un plan est appelé Pareto optimal s'il n'existe pas d'autre solution qui améliore au moins un critère sans péjorer un autre. Cette thèse avait pour objectif d'investiguer le processus de prise de décision à critères multiples dans l'incertitude pendant l'évaluation d'un plan de traitement, tout en tenant compte les composants visuels du processus. Matériaux et méthodes : initialement, les patterns d'évaluation visuels de décideurs ont été quantifiés par des techniques d'eye-tracking. Dans la deuxième partie de la thèse, les désaccords entre les plans dosimétriques de navigation basés sur la fluence et les plans finaux délivrés après que la dose soit calculée par le module d'optimisation à critères multiples d'un système de planification commercialisé. Finalement, des fronts Pareto ont été créés manuellement et une région cliniquement intéressante a été identifiée après une évaluation des plans. Résultats : Le processus d'évaluation, parallèlement à l'eye-tracking, a relevé des légères différences dans la qualité perçue des plans et par conséquence des différences dans lé choix des plans de traitement, acceptés ou rejetés. Pour les fronts Pareto automatiques, des désaccords dosimétriques entre les plans navigués et ceux délivrés ont été démontrés. Avec les fronts Pareto manuels, une région dans laquelle les plans Pareto optimaux sont considérés cliniquement équivalents a été identifiée. Discussion-conclusions: Bien qu'il existe un consensus parmi les décideurs sur une région cliniquement significative sur le front Pareto, des différ nces existent encore concernant la qualité perçue d'un plan de traitement. Les différences dosimétriques entre les plans de navigation basés _ sur la fluence et le plan délivrable peuvent encore limiter le bénéfice d'un choix d'un plan optimal en fonction des préférences cliniques. Ces éléments devraient être pris en considération pour la conception de la technologie d'un système d'aide décisionnelle, afin d'intégrer les informations relatives aux préférences cliniques dans ce système ou de utiliser ces informations lors de l'optimisation pour conduire la recherche vers les régions cliniquement préférées. -- Introduction: Radiation therapy is a discipline of oncology that aims at destroying the cancerous tumor while preserving healthy tissues. Before delivering the radiation dose to the patient, a treatment plan, specific to the patient, is created. That treatment plan remains a compromise between healthy tissue sparing and sufficient tumor irradiation, despite the advances in the technology available. Aplanis called "Pareto optimal" if there is no other solution that improves at least one criterion without deteriorating another. This thesis aimed to investigate the multi-criteria decision-making under uncertainty during treatment plan evaluation, while taking into consideration the visual componen_ts of the process. Material and methods: lnitially, the visual evaluation patterns of the decision makers were quantified with eye-tracking techniques. ln the second part of the thesis, dosimetric disagreements between fluence based navigated plans and the resulting deliverable plans after dose calculation in the multi-criteria optimization module of a commercial treatment planning system were evaluated. Finally, manual Pareto fronts were created and after pair plan evaluations a clinically interesting area on the Pareto front was identified. Results: The evaluation process, in parallel with the eye-tracking, revealed slight differences in the perceived quality of the plans and therefore differences in which plans were accepted or rejected. For the automated Pareto fronts, dosimetric disagreements between navigated and deliverable plans were shown. With the manuai Pareto fronts it was· sh own thatthere is an area in which Pareto optimal plans are considered clinically equivalent. Discussion-Conclusions: Although there is a consensus arriong decision makers on a clinically relevant area on the Pareto front, there are still differences concerning the perceived quality of a treatment plan. Dosimetric differences between navigated and deliverable plans may fLirther limit the benefit o( "fine-tuning" and choosing an optimal plan according to clinicat preferences. These elements should be taken into account when decision supp<:>rt technology is designed, in order to integrate information about clinical preferences into a decisiOn'-making support system or use it during optirnization in order to lead the search towards clinically preferred regions

Increasing diagnostic accuracy with a cell block preparation from thin layer endometrial cytology: a feasibility study

Objective: To investigate (1) the feasibility of preparing cell blocks by inverted filter sedimentation (IFS-CB) from endometrial samplings processed by the ThinPrep(r) (TP) technique (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), and (2) the possibility of increasing the diagnostic accuracy of TP endometrial cytology by examining the tissue architecture as an adjunctive method of detecting endometrial lesions. Study Design: Three hundred one endometrial samplings were obtained, using the Endogyn endometrial device (Biogyn S. n.c., Italy), from perimenopausal and postmenopausal women. The endometrial samplings were collected in a vial with liquid fixative for the TP processing. One TP slide was prepared from each case. If adequate material remained in the vial after the TP slide preparation, it was processed for IFS-CB preparation. Results: IFS-CB preparation was processed in 263 cases (87%) with adequate material. Diagnoses on IFS-CB preparations obtained by endometrial sampling matched those of the hysterectomy specimens. The addition of IFS-CB histology to the cytologic diagnosis by TP increased the diagnostic accuracy of endometrial cytology to 96.3% and 100% for benign/atrophic endometrium and adenocarcinoma, respectively (p=3D0.39 and 0.46). In hyperplasia without atypia and hyperplasia with atypia, the diagnostic accuracy increased significantly, to 96% and 95.3%, respectively (p=3D0.037 and <0.001). Conclusion: This study illustrates the merit of linking TP cytology with direct endometrial sampling, including small tissue fragments and material adequate for IFS-CB preparation. TP cytology provides an accurate cytologic diagnosis and the possibility of IFS-CB preparation, which could be a valuable diagnostic adjunct to TP cytolog

Exploration of clinical preferences in treatment planning of radiotherapy for prostate cancer using Pareto fronts and clinical grading analysis.

Radiotherapy treatment planning is a multi-criteria problem. Any optimization of the process produces a set of mathematically optimal solutions. These optimal plans are considered mathematically equal, but they differ in terms of the trade-offs involved. Since the various objectives are conflicting, the choice of the best plan for treatment is dependent on the preferences of the radiation oncologists or the medical physicists (decision makers).We defined a clinically relevant area on a prostate Pareto front which better represented clinical preferences and determined if there were differences among radiation oncologists and medical physicists. Pareto fronts of five localized prostate cancer patients were used to analyze and visualize the trade-off between the rectum sparing and the PTV under-dosage. Clinical preferences were evaluated with Clinical Grading Analysis by asking nine radiation oncologists and ten medical physicists to rate pairs of plans presented side by side. A choice of the optimal plan on the Pareto front was made by all decision makers. The plans in the central region of the Pareto front (1-4% PTV under-dosage) received the best evaluations. Radiation oncologists preferred the organ at risk (OAR) sparing region (2.5-4% PTV under-dosage) while medical physicists preferred better PTV coverage (1-2.5% PTV under-dosage). When the Pareto fronts were additionally presented to the decisions makers they systematically chose the plan in the trade-off region (0.5-1% PTV under-dosage). We determined a specific region on the Pareto front preferred by the radiation oncologists and medical physicists and found a difference between them

Odontogenic keratocyst expresses vascular endothelial growth factor: An immunohistochemical study

Background: Vascular endothelial growth factor (VEGF) expression may act as a sensitive measure of the angiogenic potential of a lesion. Furthermore, VEGF has been implicated in the pathogenesis of cystic tumors and inflammatory odontogenic cysts. Thus, we studied the expression of VEGF in the epithelium of odontogenic keratocyst (OK) in association with cell proliferation and apoptosis. Methods: Forty-two cases of OK, 26 cases of dentigerous cyst (DC), and 15 cases of residual cyst (RC) were retrospectively examined by immunohistochemistry for VEGF, Ki67/Mib-1 and anti-caspase-3. For VEGF and caspase-3, the intensity of immunostaining was qualitatively assessed, while for the evaluation of Ki67 the average number of positively stained nuclei in 10 high-power microscopic fields (×400) was calculated. Results: The VEGF expression was stronger in OK when compared with DC (P &lt; 0.007). The rate of nuclear Ki67 expression in OK was significantly higher than that in DC (P &lt; 0.001) and RC (P &lt; 0.001). Cytoplasmic caspase-3 expression was statistically more intense in RC than in OK (P = 0.001) or DC (P &lt; 0.001). A statistically significant correlation was seen in OK for Ki67 (P &lt; 0.001) and VEGF (P = 0.023), but not for caspase-3. Multiple regression analysis revealed a linear relationship between VEGF and Ki67. Conclusions: The VEGF was expressed in the epithelium of OK, DC, and RC with a variable intensity, and in OK VEGF expression was related to Ki67. It is suggested that VEGF expression by the odontogenic epithelium is not induced solely by inflammation. © 2009 John Wiley &amp; Sons A/S

Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the anti-bFGF antibody. In contrast, the same staining in terazosin-treated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis

Analysis of the treatment plan evaluation process in radiotherapy through eye tracking.

Treatment plan evaluation is a clinical decision-making problem that involves visual search and analysis in a contextually rich environment, including delineated structures and isodose lines superposed on CT data. It is a two-step process that includes visual analysis and clinical reasoning. In this work, we used eye tracking methods to gain more knowledge about the treatment plan evaluation process in radiation therapy. Dose distributions on a single transverse slice of ten prostate cancer treatment plans were presented to eight decision makers. Their eye movements and fixations were recorded with an EyeLink1000 remote eye-tracker. Total evaluation time, dwell time, number and duration of fixations on pre-segmented areas of interest were measured. The main structures receiving more and longer fixations (PTV, rectum, bladder) correspond to the main trade-offs evaluated in a typical prostate plan. Radiation oncologists made more fixations on the main structures compared to the medical physicists. Radiation oncologists fixated longer on the rectum when visited for the first time, while medical physicists fixated longer on the bladder. Our results quantify differences in the visual evaluation patterns between radiation oncologists and medical physicists, which indicate differences in their decision making strategies