Nicolas Thiounn

Papillary renal cell carcinoma

A series of 43 papillary renal cell carcinomas (PRCCs) were analyzed to investigate the prognostic value of the morphological subtyping (type 1/type 2) proposed by Delahunt and Eble [6]. Twenty-six cases were type 1 (small cuboid cells arranged in single or double layers), 13 cases were type 2 (voluminous eosinophilic cells with irregular pseudostratification pattern), and four cases with oncocytic cells (large eosinophilic cells with round regular nuclei) were distinct from type 2 and grouped apart. All type-1 and oncocytoid-type PRCCs were staged pT1 or pT2, whereas 8/13 type-2 PRCCs were staged pT3 or pT4. Follow-up information (range, 3–113 months; median, 43 months) showed 12 deaths from disease: 2 in the type-1 group,10 in the type-2 group, 0 in the oncocytoid-type group. The Kaplan-Meier analysis showed that pejorative outcome was associated (P<0.001) with high stage (pT3/pT4), high nuclear grade (3/4), morphological type 2, absence of foam cells, and abundant fibrous stroma. The multivariate analysis showed that stage and morphological type were independently associated with survival (P<0.05). These results support the clinical interest of morphological subtyping of PRCCs in the prognosis evaluation of the patients. The four oncocytoid-type PRCCs had a favorable outcome, but additional data are required to evaluate this type of neoplasm.

Risk factors for adult renal cell carcinoma: a systematic review and implications for prevention

RCC accounts for < 3% of cancers in adults and < 85% of all primary malignant kidney tumours. The incidence of RCC has been steadily increasing for several years. In France, the incidence of RCC according to cancer registers was 12 per 100 000 men and 6 per 100 000 women in 1995, and mortality rates were over 7.5 per 100 000 men and 4.0 per 100 000 women, similar to reports from other European countries [1,2]. About half the cases of RCC diagnosed are currently discovered by chance during ultrasonography. This suggests that these tumours could be detected more frequently by simple imaging techniques at earlier stages of the disease, when surgical treatment is curative. The 5year survival rate is 88±100% for localized tumours but only 20% or less for metastatic tumours [3]. As patients with localized RCC survive longer than those with disseminated disease, it is likely that a screening programme for RCC would improve disease prognosis. However, in the absence of known high-risk populations, systematic early detection of RCC may not be cost-effective. Several potential risk factors for RCC have been identi®ed in previous epidemiological studies. Discrepancies between these studies and the weakness of associations between various types of exposure and RCC make it dif®cult to identify unequivocally the true risk factors. We attempted to rank the most consistent associations and to de®ne populations at high-risk of RCC by systematically reviewing published analytical epidemiological studies.

Modulation of interleukin-18 expression in human colon carcinoma: Consequences for tumor immune surveillance

The production in colon cancer of interferon‐gamma (IFN‐γ), a type‐1 T‐helper (TH1) cytokine, is considered as a marker of good prognosis. We asked whether interleukin‐18 (IL‐18), which strongly induces IFN‐γ and regulates Fas ligand (Fas‐L)‐dependent cytotoxicity, may play a role in colon homeostasis, and if its expression was modulated in colon adenocarcinomas. We analyzed 14 specimens of colon adenocarcinomas, 6 of normal colon mucosa of the series, and 6 colon‐tumor cell lines. The expression of IL‐18, of ICE protease, involved in the processing of this cytokine, and of the downstream effectors of IL‐18, IFN‐γ and Fas‐L was analyzed by RT‐PCR. We further performed IL‐18 immunostaining of normal and tumor specimens. The results were correlated with tumor dissemination and clinical outcome. We report the synthesis of IL‐18 in human normal colon, mainly by epithelial cells of the mucosa. Out of the 6 tumor cell lines, 4 expressed IL‐18 transcripts, but neither ICE mRNA nor secreted forms of IL‐18 were detected. We observed decreased or abolished synthesis of IL‐18 in colon adenocarcinomas, as compared with normal mucosa. Thus, half of the colon‐cancer tissues (7/14 cases) expressed neither IFN‐γ nor Fas‐L. This feature was correlated with the existence of distant metastases (Fischers exact test, p = 0.02) and an unfavorable outcome. These findings suggest that production of IL‐18 in human colon may play a role in homeostasis and in tumor immune surveillance, by enhancing IFN‐γ production and Fas‐L‐dependent cytotoxicity of immune cells. Int. J. Cancer (Pred. Oncol.) 84:326–330, 1999.

COLOR DOPPLER-GUIDED PROSTATE BIOPSIES IN 591 PATIENTS WITH AN ELEVATED SERUM PSA LEVEL: IMPACT ON GLEASON SCORE FOR NONPALPABLE LESIONS

OBJECTIVES To compare results of color Doppler-guided ultrasonography (CDUS) versus those of systematic biopsies in 591 patients with an elevated serum PSA level and to correlate them with digital rectal examination (DRE) findings. METHODS Biopsies were directed into hypervascularized (CDUS+) or hypovascularized (CDUS-) hypoechoic peripheral zone nodules (443 cases). When transrectal ultrasound (TRUS) was normal (148 cases), biopsies were directed into hypervascular area. Six additional posterior biopsies were also performed in every patient, together with four anterior biopsies in 117 patients with normal DRE and prostate weight above 40 g. RESULTS Biopsies were positive in 339 patients (57%). Positive biopsy rate (PBR) of directed biopsies was 84% in hypervascular abnormalities (264 of 316) and 17% in hypovascular nodules (23 of 134) (P < 0.001). PBR of combined biopsies was 84% in CDUS+ patients (266 of 316) and 26% in CDUS- patients (73 of 275) (P < 0.001). Comparison of TRUS and CDUS showed a sensitivity of 0.9 and 0.78, respectively, and a specificity of 0.46 and 0.8, respectively. Of the 131 patients with a PSA level between 4 and 10 ng/mL and a normal DRE, PBR was 59% (22 of 37) when CDUS was positive and 11% (10 of 94) when it was negative, regardless of TRUS abnormalities (P < 0.001). Nonpalpable cancers with a negative CDUS showed a significantly (P < 0.001) lower Gleason score (5.5 +/- 0.9) than that of CDUS+ cancer (6.5 +/- 1.1). Eleven cancers were diagnosed by only anterior positive biopsies. All of them had a negative CDUS and a PSA level above 10 ng/mL. CONCLUSIONS CDUS does not modify prostate biopsy policy except in patients with negative CDUS, normal DRE, and PSA level between 4 and 10 ng/mL, where deferment of biopsy can be advocated. Anterior biopsies are only useful in patients with a PSA level above 10 ng/mL and a negative CDUS.

Intermittent androgen suppression in patients with prostate cancer

To evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression.

Mutations in BHD and TP53 genes, but not in HNF1β gene, in a large series of sporadic chromophobe renal cell carcinoma

BHD, TP53, and HNF1β 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 HNF1β mutations, (84% mutations involved chromophobe), suggesting a role for BHD and TP53 in chromophobe subtype.

Corporeal Plication for Surgical Correction of Penile Curvature

Objective: To evaluate the efficacy of tunica albuginea plication without excision in patients with congenital and acquired penile curvature. Methods: Results were retrospectively analyzed in 60 consecutive patients treated from 1982 to 1996. Mean age was 42.8 years (range 16–77). 25 patients had congenital curvature and 35 patients had acquired curvature (29 Peyronie’s disease, 5 postoperative and 1 posttrauma). All patients had penile curvature with angulation over 30° and major intercourse difficulties. Results: Postoperatively, 52 patients (87%) had satisfactory cosmetic results and 49 (82%) had satisfactory functional results. All patients (100%) with congenital or postoperative curvature had satisfactory cosmetic results and satisfactory functional results. Patients with Peyronie’s disease had a lower success rate with 81% satisfactory cosmetic results and 62% satisfactory functional results. Conclusion: Tunica albuginea plication is a more simple procedure than tunica albuginea resection (Nesbit procedure) with a comparable success rate and minimal morbidity.

Genomic expression and single-nucleotide polymorphism profiling discriminates chromophobe renal cell carcinoma and oncocytoma

BackgroundChromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC.MethodsGene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors.ResultsA novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities.ConclusionsGene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Renal cell carcinoma of the grafted kidney: how to improve screening and graft tracking.

Renal cell carcinoma of transplanted kidneys is rare. We report three such cases among 1,250 kidney grafts that were performed or followed from 1968 to 2002. A strategy to diagnose these lesions is needed because of their rarity, late detection, and therapeutic repercussions. At the least, the strategy should include annual ultrasonography of the graft throughout its lifespan. Because the risk of tumor development in another organ from the same donor is not negligible, a national registry should be established to rapidly alert graft recipients with the same donor and other transplantation centers about the risk of graft tumors.

Low predictive accuracy of the Kattan postoperative nomogram for renal cell carcinoma recurrence in a population of French patients

The aim of the current study was to establish the predictive accuracy of the Kattan postoperative nomogram for nonmetastatic renal cell carcinoma (RCC) by comparing predictions with actual disease recurrence in patients who underwent surgery in a single center in France.