Biomedical subjects
Publications and source records attributed to A Vieillefond.
BHD, TP53, and HNF1beta on chromosome 17 were studied in 92 cases of renal cell carcinoma (46 chromophobe, 19 clear cell, 18 oncocytoma, and nine papillary). Six, thirteen, and zero cases had, respectively BHD, TP53, and HNF1beta mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.
New entities, confirmed either by cytogenetic findings or by new molecular markers, have been included in the WHO 2004 renal tumor classification. Moreover, imaging improvements provide a better radiologic description of tumors. In this article, we will discuss the WHO 2004 classification and focus on the new entities and their macroscopic appearance. We will especially insist on the following entities: multilocular clear cell renal carcinoma, Xp11 translocation carcinoma, low-grade mucinous tubular carcinoma, epithelioid angiomyolipoma, and benign mixed epithelial and stromal tumor. We also discuss the new concept of hybrid oncocytoma and chromophobe renal cell carcinoma, as well as the Birt-Hogg-Dube syndrome, which is associated with kidney tumors.
BACKGROUND: Spermatozoa can be retrieved from the testis and epididymis of men with obstructive azoospermia (OA) and used for ICSI. However, it is unknown whether the outcome of ICSI depends on the cause of obstruction or the origin of surgically retrieved spermatozoa. METHODS: A cohort of 171 men with OA and normal spermatogenesis were included in this retrospective study. They were divided into three groups according to the site and origin of obstruction: 83 men had congenital bilateral absence of vas deferens; 55 and 33 had acquired epididymal and deferent duct obstructions, respectively. The outcome of 368 ICSI cycles was determined and compared according to the origin of spermatozoa: epididymal (n = 253) or testicular (n = 115). RESULTS: Fertilization and clinical pregnancy rates did not differ between spermatozoa of different origin (58.9% versus 51.9% and 22.1% versus 24.3% with epididymal and testicular spermatozoa, respectively). However, the miscarriage rate was significantly higher for testicular spermatozoa (35.7% versus. 12.5% P < 0.05, chi2 test). Findings were similar whatever the aetiology of the OA. CONCLUSION: This study suggests that the use of testicular spermatozoa, even those generated during normal spermatogenesis, alters embryonic development and that epididymal spermatozoa should be preferentially used, irrespective of the aetiology of OA.
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Primary retroperitoneal tumors are rare and most of the time malignant. Because of the large space in which they grow, they are often discovered lately as they are large. CT and MR are the imaging techniques of choice for the primary diagnosis and the follow up of these tumors. Multiplanar reconstructions , signal and density resolution help for the nature diagnosis. The examinations allowed to find associated signs that helps also for the right diagnosis. The purpose of this paper is to answer a serie of questions: Is the mass in the retroperitoneal space? Are they imaging signs that helps for the diagnosis of nature? Are they associated signs that helps for the diagnosis of nature? What are the most common diagnosis? Is there any place for percutaneous biopsies? What is the role of imaging in the follow up? Are there any other processes that can mimic retroperitoneal tumors?
Fat containing renal tumours are usually considered as angiomyolipomas on imaging modalities. Some cases of renal cell carcinoma have been reported. Although it has been previously reported, angiomyolipomas containing calcifications are very rare. We report a case of a fatty renal tumour with calcification which was an angiomyolipoma. The calcification within the tumour was secondary to osseous metaplasia.
We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-gamma-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1.4 x 10(8) to 2.5 x 10(8) cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-gamma-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.
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Mapping of methylation patterns in CpG islands has become an important tool for understanding tissue-specific gene expression in both normal and pathological situations. However, the inherent cellular heterogeneity of any given tissues can affect the outcome and interpretation of molecular studies. In order to analyse genomic DNA methylation on a pure cell population from tissue sample, we have developed a simple technique of single-cell microdissection from cryostat sections which can be combined with bisulfite-mediated sequencing of 5-methylcytosine. We report here our results on the methylation status of the androgen receptor gene studied by bisulfite genomic sequencing on purified cells isolated from human testis.
To assess the prognostic value of CD44s and CD44v6 tumour expression for patients with T1-T2 conventional renal cell carcinomas, a retrospective immunohistochemical analysis of 95 patients was undertaken. These patients had undergone a radical nephrectomy, performed in three institutions in France between 1987 and 1993. The mean age of the patients was 62.9+/-10.2 years (range from 37 to 85 years) with 66.3% males. At the time of surgery, 84 patients had a T1 and 11 a T2 renal tumour. Fuhrman nuclear grading showed 44 (46.3%) tumours of grade 1, 39 (41.1%) of grade 2, and 12 (12.6%) of grade 3. The mean follow-up period was 58.1+/-36.1 months. At the end of follow-up, eight patients (8.4%) had metastatic disease and no local recurrence was seen. Immunohistochemistry showed that 26 tumours (27.4%) expressed CD44s, but none expressed CD44v6. Statistical analysis showed that CD44s expression was correlated with tumour size (p=0.006) and Fuhrman grading (p<10(-4)). Among the various parameters tested for the multivariate analysis, CD44s expression correlated only with disease-free survival (p=0.04). It is concluded that CD44s expression, but not CD44v6, is of potential prognostic interest in patients with localized T1-T2 conventional renal cell carcinomas.
In many types of cancer, p53 frequently accumulates in tumor cells and anti-p53 antibodies can be detected. However, only four CD8(+) T-cell epitopes from p53 have been identified in humans so far. To further analyze the development of a T-cell response against p53, peptides having binding motifs specific for HLA-A1, -A2, -A3, -A24, -B7, -B35, -B44, and -B51 molecules have been defined. The HLA-binding capacity of those peptides was tested, and the stability of formed complexes was defined. Thirteen peptides that bound to HLA-A24 and -B44 molecules are presented. The positive peptides were then used to detect the anti-p53 response of CD8(+) T lymphocytes from patients with bladder cancer. Six peptides, presented by HLA-A2, -B51, or -A24, were able to stimulate T cells from two patients (among 16) with tumor cells that strongly accumulated p53. On the contrary, p53 peptides systematically failed to stimulate T cells from healthy donors or patients with low or undetectable levels of p53 in their tumor cells. These results have led to the identification of four new potential T CD8(+) epitopes from p53: 194-203 associating with HLA-B51 and 204-212, 211-218, and 235-243 associating with HLA-A24.
The authors describe the pathological aspects of muscles of three patients infected with Trichinella murrelli. Biopsies were carried out at various intervals. Six weeks after infection, the muscular larvae were not encapsulated whereas encapsulation was seen 10 weeks after infection. Six years after infection, the larvae were still alive in a nurse cell surrounded by a very thick capsule. Fourteen years after infection, cuticular larvae remnants were seen in degenerating nurse cells. The late encapsulation of Trichinella murrelli in human muscles could explain some clinical differences noticed during the outbreak during which these three patients were infected.
PURPOSE: Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease progression in individuals with localized prostate cancer. In a search for predictive markers we evaluated the expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related proteins, and the angiogenic factor thymidine phosphorylase. MATERIALS AND METHODS: The study population included 43 men who presented with localized prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression was assessed by immunohistochemical testing. Results were analyzed in relation to pathological disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to 11.4 years after surgery (median 7.9). RESULTS: Disease did not progress in 17 of the 43 cases, while recurrence and/or metastasis developed in the other 26 at a median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43 samples, respectively, was significantly associated (p = 0.0001). Thymidine phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively). On multivariate analysis only the correlation of thymidine phosphorylase expression with recurrence remained statistically significant (p = 0.002). Co-expression of the 3 markers was observed in the samples of 10 of the 11 patients (90%) with bone metastases and only in 5 of the 17 (29%) who were disease-free. CONCLUSIONS: This study indicates that the expression of bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase determined at a clinically early stage of disease by a simple immunohistochemical technique would enable subgroups of patients to be identified that are at different risks of bone metastasis or recurrence. Detection of such markers would provide additional prognostic information that would be useful for patients with intermediate or low Gleason score or stage disease. These patients would benefit from a more adapted clinical follow-up.
The occurrence within the testis or paratesticular tissue of serous tumors, similar to ovarian tumors, is rare. This article reports a primary serous paratesticular cystadenocarcinoma in a 39 year-old man. From data of the literature, we offer guidelines for diagnosis, histogenesis and treatment of this rare tumor.
OBJECTIVE: To describe the clinical and histological characteristics and natural history of clear cell renal carcinoma. PATIENTS AND METHODS: The case files of 35 patients (22 men and 13 women, with a mean age of 58 +/- 13.8 years) operated for clear cell renal carcinoma were reviewed. The circumstances of diagnosis and the histological features of the tumour were analysed. The outcome of the patients was studied with a mean follow-up of 70 +/- 20.2 months. RESULTS: The diagnosis was incidental in 66% of cases. The macroscopic appearance of the tumour was characteristic: homogeneous and beige or white colour. On light microscopy, tumours were composed of variable proportions of clear cells and eosinophilic cells. The were classified as 15 predominantly eosinophilic tumours (43%), 9 predominantly clear cell tumours (26%) and 11 tumours composed of equal number of clear cells and eosinophilic cells (31%). Nuclei were irregular and indented. Hale stain was positive in every case. The majority of tumours were confined to the kidney (T1: 65% and T2: 29%) with a low nuclear grade (91% of grades 1 and 2). No patient developed local recurrence or metastasis during follow-up. The overall 5-year survival rate was 92%. No death related to the disease was reported. CONCLUSION: The histological diagnosis of clear cell renal cancer is now easy and can be suggested even on macroscopic examination of the operative specimen. This tumour appears to have a good prognosis, as it is usually confined to the kidney with a low nuclear grade.
The OGG1 gene, which codes for a DNA repair protein with antimutator activity, is located on chromosome 3p25, a frequent site of allelic deletions in many types of human tumors, including renal clear cell cancers. We present the analysis of 99 renal tumors for alterations in the OGG1 gene to determine its association with tumorigenesis. Loss of heterozygosity in the 3p25 region was found for 85% of the informative cases. We detected somatic missense mutations of the OGG1 gene in 4 of the 99 tumor samples. Biochemical analysis of the mutant proteins revealed that a substitution at codon 46 impairs the enzymatic activity. We also describe the occurrence of several polymorphisms as well as aberrantly spliced OGG1 transcripts.
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