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 < 0.007). The rate of nuclear Ki67 expression in OK was significantly higher than that in DC (P < 0.001) and RC (P < 0.001). Cytoplasmic caspase-3 expression was statistically more intense in RC than in OK (P = 0.001) or DC (P < 0.001). A statistically significant correlation was seen in OK for Ki67 (P < 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 & Sons A/S

Human papilloma virus (HPV) is possibly involved in laryngeal but not in lung carcinogenesis

Data on human papilloma virus (HPV) involvement in preneoplastic and neoplastic lesions of the larynx and lung are limited and conflicting. The presence of HPV was investigated in a series of laryngeal specimens and non-small cell lung carcinomas (NSCLCs). The laryngeal samples (154) comprised 14 cases with hyperplasia without dysplasia, 49 with dysplasia, and 91 squamous cell carcinomas (SqCCs). The NSCLCs included 31 SqCCs, 32 adenocarcinomas, and 5 undifferentiated large cell carcinomas. Furthermore, we examined, for HPV DNA sequences, 14 bronchial metaplastic squamous lesions located next to cancerous areas. We used a sensitive nested polymerase chain reaction assay (NPCR), dot blotting, and in situ hybridization. The findings were correlated with clinicopathologic features of the patients. In the laryngeal specimens, NPCR analysis showed HPV DNA in 20 (13%) of the 154 specimens. Notably, 19 of 20 HPV-positive cases were carcinomas and only one was a mild dysplastic lesion. Typing of the carcinomas showed single HPV 6, 16, 18, and 33 infection in 1 (1.1%), 12 (13.2%), 2 (2.2%), and 1 (1.1%) samples, respectively, and HPV 6/33, 16/33, and 6/18 coinfection in three carcinomas. In situ hybridization findings were in agreement with PCR results, with the exception of two cases in which HPV 18 DNA was detected only by PCR. HPV was more frequently observed in heavy smokers than in patients with low daily cigarette consumption and nonsmokers (P = .03). There was no correlation between virus infection and gender grade, and lymph node status of the carcinomas. None of the NSCLCs or adjacent metaplastic squamous epithelium contained HPV DNA sequences. The presented data suggest a contributory role of HPV in late stages of laryngeal carcinogenesis, because all premalignant lesions were negative but one. This study does not support a potential role of HPV in the development of NSCLCs. HUM PATHOL 30:274-283. Copyright (C) 1999 by W.B. Saunders Company

ANGIOMYOLIPOMA OF THE LEFT URETEROVESICAL JUNCTION ASSOCIATED WITH IPSILATERAL RENAL AGENESIS

To our knowledge we report the first case of retroperitoneal angiomyolipoma located at the left ureterovesical junction associated with ipsilateral renal agenesis. Radiologically, the mass had the characteristics of a cystic soft tissue tumor. Final diagnosis was determined by histopathological examination, which revealed the specific characteristics of angiomyolipoma. The tumor is theorized to be a result of developmental malformation of fetal mesenchymal elements along the ureteral bud during fetal development since it was associated with ipsilateral renal agenesis

Expression of c-jun oncogene in hyperplastic and carcinomatous human prostate

Objectives. To investigate c-jun oncoprotein (JUN) expression in diseases of the human prostate gland at the tissue level and to determine its relationship to clinicopathologic variables. Methods. The expression of JUN was studied using immunohistochemistry in archival tissue from benign prostatic hyperplasia (BPH) (n = 16) and prostate adenocarcinoma (PCa) (n = 36) specimens. Results. JUN-specific positive nuclear immunostaining was observed in 13 (81.25%) of 16 BPH and 31 (86.1%) of 36 PCa specimens. JUN-specific immunostaining was significantly stronger in the PCa than in the BPH tissue (P = 0.006). In the PCa tissue, no significant correlation was found between JUN immunohistochemical expression and tumor histologic grade (Gleason score) or serum prostate-specific antigen level. Conclusions. JUN expression may play a role in normal cell function of the prostatic epithelium and is expressed in most BPH and PCa samples. The finding that JUN-specific immunostaining intensity was stronger in the vast majority of PCa than in the BPH samples implies that the role of c-jun may be enhanced during malignant transformation

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

In vivo effect of the lipido-sterolic extract of Serenoa repens (Permixon) on mast cell accumulation and glandular epithelium trophism in the rat prostate

The Serenoa repens lipido-sterolic extract (SRLSE, Permixon, Pierre Fabre Medicament, Castres, France) is used to treat benign prostate hyperplasia. We studied the in vivo effect of SRLSE on mast cell accumulation and the histological characteristics of the rat ventral prostate. Adult Wistar rats received either tocopherol or SRLSE (50 and 100 mg/kg body weight, respectively) every second day for 90 days. Histological features were studied in hematoxylin-eosin stained tissue sections while mean mast cell numbers were determined in Giemsa-stained sections. The central region of the ventral prostate in treated animals showed significant changes with acinar epithelium becoming flat or low cuboidal. In the same region, mean mast cell number per optical field in the control, low-dose and high-dose groups were, respectively, 4.7 +/- 0.7, 3.4 +/- 1.0 and 2.4 +/- 0.6, showing a dose-dependent, statistically significant decrease. Administering SRLSE significantly reduces mast cell accumulation and provokes epithelium atrophy within the central area of the rat ventral prostate. These phenomena may participate in the clinical activity of the drug

The effect of intravesical Bacillus Calmette-Guerin instillations on the expression of inducible nitric oxide synthase in humans

The activation of the inducible isoform of nitric oxide synthase (NOS) is associated with the production of large quantities of nitric oxide in response to cytokine stimulation. Bacillus Calmette-Guerin (BCG) mode of action against bladder carcinoma remains unclear, although a plethora of local and systemic events may follow its intravesical instillation. The present study was designed to investigate the expression of inducible NOS in normal and neoplastic urothelium and its alteration following tumor resection and subsequent intravesical immunotherapy. Bladder carcinoma and autologous normal bladder tissue specimens were procured from 36 patients undergoing transurethral resection. Tissue specimens were obtained from the same patients at first cystoscopy following six weekly intravesical instillations. Inducible NOS protein expression was assessed by immunohistochemistry in all tissue specimens. Immunostaining of normal urothelium for iNOS before treatment was negative in all but four cases. BCG treatment induced iNOS expression in tumor-free bladder tissue in 24 cases (66.6%). There were only four early tumor recurrences; interestingly, they corresponded to the cases with tumor cells expressing iNOS before BCG treatment, while novel tumors were also iNOS immunoreactive. BCG upregulated iNOS expression in normal human urothelial cells in vivo suggesting a role for nitric oxide in BCG mediated antitumor activity. Inducible NOS was detected in certain tumor specimens before and after BCG treatment implying a possible involvement in pro-tumor action. (c) 2005 Elsevier Inc. All rights reserved