Prostate cancer: update

The study of mitotic transduction of the signal showed that overexpression of pAkt and reduction in pERK expression would be associated a biological relapse. For tumors T1-3 N0M0 at the high risk of local relapse after prostatectomy, an immediate radiotherapy compared with a differed radiotherapy (at the time of PSA relapse), showed a significant reduction in the rate of local relapse and an ameliorated progression free survival. The effectiveness of the docetaxel was confirmed in two phase III randomized clinical trials : TAX-327 with 3 arms compared docetaxel every 21 days, docetaxel every 7 days and mitoxantrone. All arms were prednisone-based. An increase in overall survival, PSA progression free survival, PSA response rate and a pain reduction were highlighted in the docetaxel arm every 21 days. Docetaxel obtained at the end of this study the marketing authorization in this indication and became the treatment of reference. The SWOG 99-16 study compared the docetaxel estramustine association with the same arm of reference, mitoxantrone and prednisone, with similar results. The addition of estramustine to the docetaxel seems to improve the PSA response rate and progression free survival, but with a greater embolic toxicity. The addition of an antiangiogenic agent, the thalidomide, to docetaxel, improves progression free survival and overall survival. PSA responses were observed with an inhibitor of the proteasome, the bortezomib, in monotherapy, contrary to the imatinib which in monotherapy didn't have any effectiveness. Studies in association with docetaxel are ongoing. Some biological responses were observed with a vaccine anti MUC-1 and must be confirmed on a greater series of patients. The docetaxel impact on localized disease is actually evaluated.     

Inhibition of osteoporosis in autoimmune disease prone MRL/Mpj-Fas(lpr) mice by N-3 fatty acids

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease involving the breakdown of cartilage and juxta-articular bone, which is often accompanied by decreased bone mineral density (BMD) and increased risk of fracture. Anti-inflammatory omega-3 fatty acids may prevent arthritis and bone loss in MRL/lpr mice model of arthritis and in humans. METHODS: In this study, the effect of long term feeding of 10% dietary n-3 (fish oil (FO)) and n-6 (corn oil (CO)) fatty acids begun at 6 weeks of age on bone mineral density (BMD) in different bone regions in an MRL/lpr female mouse model of RA was measured at 6, 9, and 12 months of age by dual energy x-ray absorptiometry (DEXA). After sacrificing the mice at 12 months of age, antioxidant enzyme activities were measured in spleen, mRNA for receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) was measured by RT-PCR in lymph nodes, and synovitis was measured in leg joints. RESULTS: At 6, 9 and 12 months of age, BMD was significantly higher (p < 0.05) in distal femur, proximal tibia, and lumbar spine of FO fed mice than those of CO fed mice. Spleen catalase (CAT) and superoxide dismutase (SOD) activities were also significantly higher (p < 0.01) in FO fed mice than in CO fed mice. Histology of knee joints revealed mild synovitis in CO fed mice, which was not present in FO fed mice. RT-PCR analysis of lymph nodes revealed decreased RANKL mRNA (p < 0.001) expression and enhanced OPG mRNA expression (p < 0.01) in FO fed mice compared to CO fed mice. CONCLUSIONS: These results suggest beneficial effects of long-term FO feeding in maintaining higher BMD and lower synovitis in this mouse model. These beneficial effects may be due, in part, to increased activity of antioxidant enzymes, decreased expression of RANKL, and increased expression of OPG in FO fed mice thereby altering the RANKL/OPG ratio. These significant beneficial effects on BMD suggest that FO may serve as an effective dietary supplement to prevent BMD loss in patients with RA.     

Comparison of Prosthetic Materials in Incisional Hernia Repair

Purpose Incisional hernias are not uncommon after abdominal surgery, but their repair is associated with a high risk of complications, including adhesions and recurrence. Many different types of meshes and adhesion barriers have been developed in an attempt to overcome these problems, some of which we have assessed in a rat model.Methods We made a full-thickness 1.5 × 2.5-cm abdominal wall defect in 30 Sprague-Dawley rats, which were divided into three groups according to the materials used for repair: 2 × 3-cm polypropylene mesh (group 1); expanded polytetrafluoroethylene (PTFE) with double-layer polypropylene mesh (group 2); or polypropylene mesh with oxidized cellulose adhesion barriers (group 3). We assessed adhesion formation, tensile strength, and histopathologic findings.Results The mean adhesion scores were 3.3, 1.3, and 0.7, in groups 1, 2, and 3, respectively (P < 0.001). The area involved by adhesions was significantly greater in group 1 than in groups 2 or 3 (P < 0.01, P < 0.05), but there was no significant difference between groups 2 and 3 (P < 0.05). The tensile strength in group 2 was less than that in groups 1 or 3 (P < 0.01, P < 0.05), but there was no significant difference between groups 1 and 3 (P > 0.05).Conclusion Although there was less adhesion formation with PTFE and oxidized cellulose, PTFE not only impaired the tensile strength, but also induced fibrosis and inflammation. An oxidized cellulose adhesion barrier can be safely used in incisional hernia repair to prevent intra-abdominal adhesions.     

Influence of age of onset on clinical features in obsessive-compulsive disorder

We compared early-onset and late-onset obsessive-compulsive disorder (OCD) patients in terms of demographic and clinical features. One hundred sixteen outpatients whose primary diagnosis was OCD according to DSM-IV diagnostic criteria were recruited. Early-onset (n=50) and late-onset (n=66) OCD groups were compared with respect to demographic variables and scores obtained on various scales. A male gender predominance was found in early-onset OCD group. Symmetry/exactness obsessions, religious obsessions, hoarding/saving obsessions, and hoarding/collecting compulsions also were significantly more frequent in the early-onset group than in the late-onset group. The results may suggest a phenotypic difference between the two groups. Further studies are needed to investigate the differences between early-onset and late-onset OCD groups to examine the hypothesis that early-onset OCD is a distinct subtype of the disorder.     

Immunohistochemical evaluation of p53 expression and proliferative activity in children with Helicobacter pylori associated gastritis

OBJECTIVES: The aim of this study was to evaluate the significance of p53 expression and proliferative activity of glandular epithelium and intestinal metaplasia in Helicobacter pylori associated gastritis of pediatric patients. METHODS: The study included endoscopic gastric biopsies of 54 children with dyspeptic complaints. Immunohistochemistry was performed for evaluation of p53 expression and Ki-67 labeling index, an indicator of proliferative activity. Grading of H. pylori density, intestinal metaplasia and inflammatory cell infiltration were performed in histologic tissue sections stained with hematoxylin-eosin, Giemsa and Alcian-blue. RESULTS: Of 54 children, 35 (64%) were infected by H. pylori. Positive immunostaining for p53 was observed in 11 of 54 cases (20.4%). H. pylori infection was found in 10 (91%) of the p53-positive patients. There was a positive correlation between H. pylori density and Ki-67 labeling index in H. pylori infected children. H. pylori density, Ki-67 labeling index and inflammatory cell infiltration in the p53-positive group were significantly higher than in the p53-negative group. Although intestinal metaplasia was more common in H. pylori infected children (n = 11; 31.4%), there was no difference in the rate of intestinal metaplasia between the p53-positive and p53-negative groups. CONCLUSIONS: The present study shows that p53 mutations and higher proliferative activity of glandular epithelium may be related to H. pylori associated gastritis in children. Because p53 mutation does not appear to be associated with intestinal metaplasia, a precursor for gastric cancer in adults, we think that H.pylori associated p53 alterations do not initiate and promote gastric cancer that may occur in adulthood.     

Abdominal confluence of lymph trunks: detectability and morphology on heavily T2-weighted images

OBJECTIVE: Our aims were to evaluate the detectability, configuration, location, and dimensions of the cisterna chyli on heavily T2-weighted images obtained with a single-shot fast spin-echo technique and to determine whether the disorders that have the potential to affect the abdominal lymphatic drainage could change the cisternal dimensions. MATERIALS AND METHODS: Thin-collimated axial and coronal images that were originally obtained for MR cholangiopancreatography in 125 patients were reviewed by three observers individually for the presence of abdominal lymphatic confluence. The configuration, location, and dimensions of hyperintense ductal or saccular structures immediately anterior to the vertebral bodies below the diaphragma were recorded. The differences between the mean values of the diameters of the cisterna chyli obtained in the control group and in groups in which lymphatic drainage was expected to be abnormally high were compared using a one-way analysis of variance test. RESULTS: Abdominal confluence of the lymphatics was shown in 96% of patients. The most common configuration of the cisterna chyli was tubular (42.5%). It was located at the level of L1-2 in 33% of cases and at the midline in 70%. Mean longitudinal, anteroposterior, and transverse diameters of the duct were 33.45 +/- 1.74 (SD) mm, 5.23 +/- 0.13 mm, and 5.23 +/- 0.15 mm, respectively. No significant difference was found in the mean values of antero-posterior, transverse, and longitudinal diameters of the cisterna chyli in the control group and in the groups expected to have an increased flow into the cisterna chyli. CONCLUSION: Abdominal confluence of lymphatics seems to be present on most of the heavily T2-weighted images. Its morphologic details and extensions can be visualized on images reconstructed with a maximum-intensity-projection algorithm. Any disorder does not necessarily lead to dilatation of these lymphatic structures.