Posterior transperitoneal robot-assisted partial nephrectomy in the treatment of renal tumors: Feasibility of a hybrid approach.

PURPOSE: Robot-assisted partial nephrectomy (RAPN) for posterior renal tumors may be performed through anterior (transperitoneal) or posterior (retroperitoneal) approach depending on surgeon's expertise. We propose herein a surgical artifice using daVinci Xi system to combine advantages of both approaches. MATERIALS AND METHODS: From November 2019 to November 2020, patients with posterior renal mass, candidate for RAPN were prospectively included after informed consent. After positioning patient in lateral position, daVinci Xi system was docked on tumor side, to initiate transperitoneal procedure. Posterolateral dissection of perinephric space along fascia retrorenalis was conducted until psoas major muscle was exposed. Three additional robotic ports were then inserted in lumbar space, and RAPN was resumed after rotating daVinci Xi boom. Demographics, tumor characteristics, perioperative outcomes, estimated glomerular filtration rate (eGFR) and follow-up data were analyzed. RESULTS: Ten consecutive patients underwent RAPN with the modified technique. All cases were performed robotically, without modification of port placement. Median (range) tumor diameter was 37 (21-48mm) with median RENAL score of 8 (4-10) Median operative time and warm ischemia time were respectively 128min (70-180min) and 19min (14-22). One patient had a Clavien-Dindo grade II complication. At median follow-up of 13 months (6-18), all patients had eGFR comparable to baseline. CONCLUSIONS: We report the feasibility and safety of a new hybrid posterior transperitoneal approach for RAPN using daVinci Xi system. Limitations include the absence of RENAL score>10 and pT2 tumors. Greater experience is needed to assess learning curve for surgeons untrained to robotic lomboscopy.

[Comparison of operative and oncologic results between partial nephrectomy and radiofrequency ablation for treatment of renal tumors in patients older than 75]. / Comparaison des résultats opératoires et oncologiques de la néphrectomie partielle et de l'ablation par radiofréquence pour traitement des tumeurs rénales chez les patients de plus de 75 ans.

INTRODUCTION: Elderly patients represent a growing part of our society for who treatment strategy for localized renal tumors has to be chosen knowing iatrogen effects and renal function morbidity. The aim was to analyze oncological and functional results of nephron sparing surgery (PN) versus radiofrequency ablation (RFA). MATERIALS AND METHODS: All patients aged more than 75 treated by partial nephrectomy or radiofrequency ablation between 2007 and 2014 in our centre were included. Patient and tumors data were compared and these criteria were analyzed: survival (overall and without recurrence) and loss of renal function (pre- and postoperative MDRD). RESULTS: In total, 100 patients were included (26 partial nephrectomies, group 1 and 74 radiofrequency ablation, group 2) with a 32-months medium follow-up. Medium age and tumor size were significantly different (respectively, 78 versus 81 years old, P=0.001, 38mm versus 29mm, P=0.003). Perioperative results showed no differences in complications. Transfusion rate and duration of hospital stay were significantly higher in the PN group. Median overall survival were 45 vs. 27 months (P=0.23) for PN and RFA and median recurrence-free survival were 28 vs. 10 months (P=0.34). On a multivariate analysis, operative technique (PN or RFA) were not significantly linked to survival (HR 2.37 [95% CI: 0.66-8.5]), P=0.19. Loss of renal function were 1.5±14mL/min/1.73m2 for PN and 3±14mL/min/1.73m2 for RFA (P=0.69). CONCLUSION: Our study showed better perioperative results for RFA than for PN, without significant different survival. Loss of renal function were little and similar. LEVEL OF EVIDENCE: 4.

Impact of the hypoxic microenvironment on spermatogonial stem cells in culture.

The stem cell niche plays a crucial role in the decision to either self-renew or differentiate. Recent observations lead to the hypothesis that O2 supply by blood and local O2 tension could be key components of the testicular niche of spermatogonial stem cells (SSCs). In this study, we investigated the impact of different hypoxic conditions (3.5%, 1%, and 0.1% O2 tension) on murine and human SSCs in culture. We observed a deleterious effect of severe hypoxia (1% O2 and 0.1% O2) on the capacity of murine SSCs to form germ cell clusters when plated at low density. Severe effects on SSCs proliferation occur at an O2 tension ≤1% and hypoxia was shown to induce a slight differentiation bias under 1% and 0.1% O2 conditions. Exposure to hypoxia did not appear to change the mitochondrial mass and the potential of membrane of mitochondria in SSCs, but induced the generation of mitochondrial ROS at 3.5% and 1% O2. In 3.5% O2 conditions, the capacity of SSCs to form colonies was maintained at the level of 21% O2 at low cell density, but it was impossible to amplify and maintain stem cell number in high cell density culture. In addition, we observed that 3.5% hypoxia did not improve the maintenance and propagation of human SSCs. Finally, our data tend to show that the transcription factors HIF-1α and HIF-2α are not involved in the SSCs cell autonomous response to hypoxia.

Male pattern baldness and the risk of prostate cancer.

BACKGROUND: Androgens play a role in the development of both androgenic alopecia, commonly known as male pattern baldness, and prostate cancer. We set out to study if early-onset androgenic alopecia was associated with an increased risk of prostate cancer later in life. PATIENTS AND METHODS: A total of 669 subjects (388 with a history of prostate cancer and 281 without) were enrolled in this study. All subjects were asked to score their balding pattern at ages 20, 30 and 40. Statistical comparison was subsequently done between both groups of patients. RESULTS: Our study revealed that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01, P = 0.0285]. The pattern of hair loss was not a predictive factor for the development of cancer. There was no association between early-onset alopecia and an earlier diagnosis of prostate cancer or with the development of more aggressive tumors. CONCLUSIONS: This study shows an association between early-onset androgenic alopecia and the development of prostate cancer. Whether this population can benefit from routine prostate cancer screening or systematic use of 5-alpha reductase inhibitors as primary prevention remains to be determined.

[The impact of partial nephrectomy on morbidity and on long-term oncological outcomes]. / Impact de l'indication impérative sur la morbidité et les résultats carcinologiques à long terme après néphrectomie partielle.

OBJECTIVE: To evaluate the impact of imperative indication on the rate of complications and long term carcinological results after partial nephrectomy (PN). PATIENTS AND METHOD: Between 1985 and 2005, all patients who had a PN for localized cancer in two centers were reviewed. The rates of global, hemorrhagic and urinary complications were compared between group I (elective indication) and group II (imperative indication). Rates of survival without recurrence and specific at 5, 10 and 20 years were compared between these two groups. A multivariate analysis using the Cox model was carried out to research factors associated with recurrence and death on the whole of the series. RESULTS: Three hundred and five patients were included in the study. No significant difference was found between group I and group II as far as global complications were concerned (17 vs 20%), the rate of hemorrhagic complications (3.5 vs 3.8%) and the rate of urinary complications (3.9 vs 2.5%). The patients who had been operated on for an imperative indication had survived specifically and without recurrence which was significantly lower at 5, 10 and 20 years. On the whole of the series, the imperative indication was the only independent factor associated with recurrence and death in a multivariate analysis. CONCLUSIONS: Even if the rate of complication does not appear to be significantly associated with the indication for operating, patients of imperative indication represented a heterogeneous group with a poorer prognosis. This factor should be taken into account in studies on the subject of PN.

[Conformal radiotherapy to 76Gy in localized prostate cancer. Therapeutic modalities and preliminary results]. / Radiothérapie conformationnelle à 76Gy des cancers localisés de la prostate. Modalités thérapeutiques et résultats préliminaires.

PURPOSE: To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity. PATIENTS AND METHOD: Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76Gy, seminal vesicles: 56 to 76Gy, and pelvic lymph nodes: 44Gy to 16.8% of patients. RESULTS: The five-year actuarial overall survival was 94% (95% IC: 90-97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG (P<10(-6) and P<10(-8)). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1-4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, (P=0.02), and for all grades, a correlation with smaller rectal wall volumes (P=0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75Gy (P=0.02, P=0.01, P=0.0007 and P=0.003, respectively). CONCLUSIONS: These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

[Permanent implant prostate cancer brachytherapy]. / La curiethérapie du cancer prostatique par implants permanents.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

[Place of nephrectomy in patients with autosomal dominant polycystic kidney disease waiting for renal transplantation]. / Place de la néphrectomie chez les patients atteints de polykystose rénale autosomique dominante de l'adulte en attente de transplantation rénale.

OBJECTIVE: To define the indications, results and place of nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) in relation to renal transplantation. MATERIAL AND METHODS: Between October 1998 and February 2006, 145 patients with ADPKD were followed in our institution; 38 of them underwent nephrectomy via a subcostal incision, mainly in preparation for renal transplantation. The decision to perform nephrectomy in preparation for renal transplantation was based on clinical examination and CT findings. RESULTS: Indications for nephrectomy were preparation for renal transplantation (n=28, 68%), severe urological complications (n=12) and malignant tumour (n=1). Forty-one nephrectomies were performed, pretransplantation in 36 cases (88%) and five post-transplantation nephrectomies in three patients. The nephrectomy rate was 26%. The median kidney weight was 2800 grams. The mean operating time was 100 minutes and mean blood loss was 76 ml. The overall morbidity was 36.6% with 7.3% of serious complications. The mean hospital stay was 14.5 days. No patient nephrectomized before transplantation (n=13) developed any complications of the contralateral native kidney with a mean follow-up of 33 months. The mean interval between initiation of dialysis and transplantation and between nephrectomy and transplantation was 30 and 16 months, respectively. CONCLUSIONS: The optimal timing and incision for nephrectomy for ADPKD are still a subject of debate. In the absence of urological complications, nephrectomy, associated with considerable morbidity, should only be performed when very large kidneys truly interfere with graft implantation. Systematic unilateral or bilateral nephrectomy must therefore no longer be proposed. To avoid the complications of the anephric state, it is preferable to wait, whenever possible, until the patient is placed on dialysis, but the development of pre-emptive transplantation raises the issue of concomitant nephrectomy and transplantation, which may be a feasible option.

[Laparoscopic partial nephrectomy: urology resident learning curve on a porcine model]. / Néphrectomie partielle laparoscopique: courbe d'apprentissage d'un interne en urologie sur un modèle porcin.

INTRODUCTION: Several teams have recently confirmed the technical feasibility of laparoscopic partial nephrectomy (LPN). However, this procedure is not widely performed because it is technically difficult and associated with a high rate of bleeding complications, even for experienced teams. The authors studied the LPN learning curve for urology residents using a porcine model based on analysis of the following criteria: operating time, warm ischaemia time and intraoperative and postoperative bleeding. MATERIALS AND METHODS: Forty LPN were performed by the same operator. All operations were performed after arterial clamping and heparinisation of the animal. The renal section was always the same, removing 40% of the kidney and always comprised the excretory tract. A continuous running suture on the excretory tract and interrupted sutures on the parenchyma were performed. Operating time and warm ischaemia time were recorded. Animals were monitored for ten days. Intraoperative and postoperative bleeding via drains was recorded and retrograde urography was performed on the 10th day to confirm the absence of excretory tract leaks. Linear regression statistical tests investigated a correlation between these various criteria and the number of cases performed. RESULTS: The mean total operating time, warm ischaemia time and total bleeding (intraoperative and postoperative) were 108 minutes (70-140 minutes), 38 minutes (22-50 minutes) and 95 ml (10-300 ml), respectively. Linear regression analysis revealed a direct correlation between the number of cases performed and intraoperative bleeding (p<0.001) and warm ischaemia time (p<0.001). These parameters became stable after the 10th operated case. Two cases of urine leaks were observed on D10 out of a series of 40 operations, with no correlation with the number of cases performed. CONCLUSION: The operating time and warm ischaemia time are directly correlated with the number of cases performed. Training on a porcine model appears to be a good way to reduce the learning curve in man. Ten operations are necessary to acquire the various steps of the procedure.

[PSA bounce after permanent implant prostate brachytherapy may mimic a biochemical failure]. / Influence sur les résultats des rebonds du PSA après curiethérapie de prostate: étude de 295 cas avec trois ans de suivi.

PURPOSE: To assess the frequency of the PSA "bouncing" phenomenon after a significant follow-up in a series of patients treated by permanent implant brachytherapy for a prostate cancer. To look for the clinical and dosimetric parameters possibly linked to this transitory secondary PSA increase. To evaluate in which percentage of cases this bouncing could have mimicked a biochemical relapse according to the ASTRO consensus criteria. PATIENTS AND METHODS: From January 1999, to December 2001, 295 patients were treated by a permanent prostate implantation (real-time technique, with free (125)I seeds- Isoseed Bebig-) by the Institut Curie-Hôpital Cochin-Hôpital Necker Paris group. The mean follow-up is 40.3 months (9-66 months). The PSA level was regularly checked, at least every 6 months. We defined as a "bouncing" all increase in PSA, starting at 0.1 ng/ml, subsequently followed by a spontaneous (without any treatment) decrease, with return to the previous level or lower. We particularly focused on the patients fulfilling the criteria for a biochemical relapse according to the ASTRO consensus (Three successive increases in PSA). A multivariate analysis tried to identify independent factors among the usual clinical and dosimetric parameters. RESULTS: In our series, 161 patients (55%) showed a transitory PSA increase (bouncing) of at least 0.1 ng/ml; 145 patients (49%) a bouncing of 0.2 ng/ml, 93 patients (32%) a bouncing of 0.4 ng/ml and 43 patients (15%) a bouncing of at least 1 ng/ml. Mean PSA bounce was 0.8 ng/ml (0.1-4.1), and mean time to bounce was 19 months. Thirty-two patients (11% of the total number) presented three successive PSA increases with a significant (3 months) interval between the dosages, and therefore were to be considered as being in biochemical relapse according to the ASTRO consensus criteria. Actually, among those 32 patients, 18 (56%) subsequently showed a complete normalization of their PSA, without any treatment. Ten patients went on increasing their PSA, and were considered to be really in biochemical relapse. For the last 4 patients, the situation still remains ambiguous. In multivariate analysis, age<70 years (P<0.00001) and D90>200 Gy (P<0.003) were identified as independent factors for a PSA bouncing of at least 0.4 ng/ml. CONCLUSIONS: The observed rate of 32% of patients showing a PSA bouncing of at least 0.4 ng/ml in our series is in good agreement with what has been previously reported in the literature. Age<70 years and D90>200 Gy were found to be independent factors predicting for such a secondary transitory increase in PSA. Interestingly, among 32 patients fulfilling the classical criteria of the ASTRO for a biochemical relapse, 18 (56%) subsequently showed a spontaneous PSA decrease, demonstrating that the ASTRO consensus is not well adapted to the biochemical follow-up of our patients undergoing permanent implant prostate Brachytherapy.

[Clinical and dosimetric analysis of 469 prostate cancer patients treated in France in 2005 by permanent implant brachytherapy using the Iodin 125 seeds IsoSeed Bebig: report to the French Economic committee of health products (CEPS)]. / Analyse clinique et dosimétrique de 469 patients traités en France en 2005 par implantation prostatique de grains d'iode 125 IsoSeed Bebig: rapport pour le Comité économique des produits de santé (CEPS).

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.

Second malignancies after permanent implant prostate cancer brachytherapy: A single-institution study of 675 patients treated between 1999 and 2003.

PURPOSE: To analyse the rate of secondary malignancies observed in a series of 675 prostate cancer patients who underwent a permanent implant brachytherapy between 1999 and 2003, and to compare the incidence with the expected rate in a matched general French population. MATERIAL AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125-iodine seeds and a prescription dose of 145Gy. The mean follow-up was 132 months. RESULTS: The 10-year overall survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The 10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second cancers were registered. When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61 (95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77-1.29). CONCLUSION: With a mean follow-up of more than 11 years, this series does not detect any excess risk of second cancers associated with permanent implant prostate brachytherapy. However, due to power limitation, a small increase in the risk of secondary malignancies cannot be totally ruled out.

Bisulfite genomic sequencing of microdissected cells.

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.

Long-term results of permanent implant prostate cancer brachytherapy: A single-institution study of 675 patients treated between 1999 and 2003.

PURPOSE: To analyse long-term overall survival, relapse-free survival and late toxicities in a series of 675 patients treated between 1999 and 2003, with a median follow-up of 132 months. PATIENTS AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125 iodine seeds. Hormone therapy, consisting most often of an anti-androgen alone, was given in 393 patients (58%). RESULTS: The 10-year overall survival was 92% (95% confidence interval [CI]: 90-94) without a significant difference between the low and the select intermediate-risk groups (P=0.17). The 10-year relapse-free survival rate for the entire cohort was 82% (95% CI: 79-85), and was significantly higher in the low-risk group than in the intermediate one (87 vs 71%; P<0.0001). Twenty-six percent of the relapses observed in this series occurred after more than 10 years of follow-up. The 10-year cumulative incidence of grade 3-4 urinary toxicity (whatever the delay and the recovery) was 5.78%. The cumulative incidence of grades 3-4 rectal toxicity in the present series was 1.65% at 10 years. As for sexual toxicity, 61% of our patients retained an erectile capacity at 10 years (with or without oral medication), with age being a major factor. CONCLUSION: With a median follow-up of more than 11 years, this series appears to confirm the excellent long-term results of low-dose rate prostate brachytherapy, both in terms of survival and in terms of toxicity.

[Squirting and female ejaculation in 2015?]. / Que sait-on des femmes fontaines et de l'éjaculation féminine en 2015?

Since Antiquity, women who expulse a large quantity of liquid during sexual stimulation have remained a mystery. This phenomena is usually called "squirting". Many physicians have proposed different explications, however, there are very few scientific publications and their conclusions are discordant. Today, squirting is fashionable in the media, and some recent studies have brought new information. Through medical publications, we present the conclusions concerning the origin and the nature of squirting, the psychological experience of these squirting women and the feelings of their partners.

Proinflammatory and antitumor properties of interleukin-18 in the gastrointestinal tract.

Interleukin-18 (IL-18) plays a central role in the immune response by acting on Th1 cell differentiation, cell-mediated cytotoxicity and inflammation. The role of IL-18 in cancers and inflammatory diseases is discussed in the light of our investigations on IL-18 synthesis in normal colonic mucosa, colonic cancer and Crohn's disease (CD).

IL-6 is a survival prognostic factor in renal cell carcinoma.

It has been reported that a high plasmatic concentration of interleukin-6 (IL-6) is correlated to a lack of response to immunotherapy in several malignancies, suggesting that IL-6 was either a marker of tumour aggressiveness or had only a predictive value of response to immunotherapy. To discriminate between these two possibilities, a retrospective study was performed in a series of 19 patients with metastatic renal cell carcinoma who did not respond to IL-2/IFNalpha/5-FU treatment. Serum levels of IL-6, C-reactive Protein (CRP), soluble IL-2-receptor (sIL-2R), M-CSF and neopterin were assayed before treatment. IL-6 showed a significant correlation with patients median survival time (P < 0.016), suggesting that serum concentration of IL-6 before treatment is a marker of tumour aggressiveness rather than a predictive parameter for an immunological response.

Identification of p53 peptides recognized by CD8(+) T lymphocytes from patients with bladder cancer.

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.

Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases.

OBJECTIVES: Detection of circulating tumor cells may improve the preoperative local staging of prostate cancers. The aim of this study was to perform enhanced reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific antigen (PSA) mRNA to define the predictive value of PSA-positive circulating cells in a large series of patients. METHODS: The study included 46 patients with Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and 51 (including 9 women) with nonprostatic disease. PSA-positive cells from peripheral blood samples were detected by Southern blot analysis of the RT-PCR products. Original oligonucleotide primers were defined to exclusively detect the three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in 8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA-positive circulating cells was significantly increased in patients with prostate cancer versus patients with BPH (P = 0.03). Among clinically localized prostate cancers with a Gleason score less than 8, a correlation was observed between PSA-positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%. CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging, this study demonstrated the absence of tissue and tumor specificity of PSA-positive circulating cells, accounting for the weak positive predictive value of this technique.