Photodynamic cystoscopy for bladder cancer diagnosis and for NMIBC follow-up: An overview of systematic reviews and meta-analyses.

INTRODUCTION: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up. MATERIAL AND METHODS: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC. RESULTS: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear. CONCLUSIONS: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed.

[RHESOU (Registry in HErault Specialized in Onco-Urology) : the first French Registry specialized in Onco-Urology. One-year experience]. / RHESOU (Registre de l'Hérault spécialisé en onco-urologie) : le premier registre français spécialisé en onco-urologie. Un outil méthodologique de recueil de données en onco-urologie. Bilan de faisabilité sur un an d'expérience.

PURPOSE: In 2016, the Herault tumor registry collected 1961cancers in urology (21.4 % from all Herault cancers this year). RHESOU was created to complete RTH' data with specific parameters in onco-urology. The aim of this study is to describe RHESOU and to give some examples with our first results. MATERIAL AND METHODS: In November 2018, RHESOU (Registry HErault Specialised in Onco-Urology) was founded with the same registry recommendations. It collects specific oncologic parameters and also complete RTH's data. For each urological cancer, a specific survey with different choices was performed to collect a maximum of data which could be present in patients' file. These surveys were used for urological cancers cases that live in Herault in 2017. RESULTS: In 2017, we collected 970 prostate cancers, 581 bladder cancers, 212 kidney cancers, 51 upper excretory tract cancers, 28 testicle cancers and 9 penil cancers. Our urological data collection gives many possibilities to create many requests for detailed analysis in urological cancers. In this article, we reported data from kidney, bladder and prostate cancers. CONCLUSIONS: RHESOU is a new tool opened to the different urologic corporations (urologists, pathologists, oncologists, radiotherapists, radiologists) that permits an overview in urological cancers in Herault. Finally, one important aim is that this tool will be adapted when new treatments or new important parameters appear in the years ahead. LEVEL OF EVIDENCE: 3.

Impact of a tailored oral vitamin D supplementation regimen on serum 25-hydroxyvitamin D levels in early breast cancer patients: a randomized phase III study.

BACKGROUND: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. RESULTS: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. CONCLUSION: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. CLINICAL TRIAL NUMBER: NCT01480869.

[The PSA caught out]. / Le PSA pris en défaut.

INTRODUCTION: With the widespread use of prostate specific antigen (PSA) prescription and despite the automatization of PSA assessment, clinicians should not forget the analytical interference of PSA immunoassays due to the presence of heterophilic autoantibodies in a patient. MATERIAL AND METHODS: This article details some clinical cases, mechanisms involved in the interference and how to overcome this problem. RESULTS: The reported and documented interferences led to useless explorations even erroneous diagnosis. CONCLUSION: Before any unexpected PSA value in relation to the clinical symptomatology, it is strongly recommended to verify the absence of any interference before any invasive procedure or therapy modification.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

[UPA/PAI-1: a tool for breast cancer treatment individualization. Biology, clinical implications and quantification assays]. / uPA/PAI-1 : un outil d'individualisation de la prise en charge des cancers du sein. Biologie, implications cliniques et méthodes de dosage.

The several options for therapy in breast cancer underline the difficulties to determine the reliable population which can be treated by a specific adjuvant therapy, and the population in which that therapy could generate morbidity, mortality, "medical surcharge" without prognosis improvement. This problem is particularly accurate in node-negative breast cancer patients. Adjuvant therapy has been proved to be more efficient, so a better definition of the prognosis and the response to adjuvant treatments could allow the selection of a sub-group of patients who can be spared chemotherapy. The quantification of the uPA/PAI-1 tumor content is one of the most relevant prognostic factors in this clinical setting. The integration of the uPA/PAI-1 prognostic information gathered in the multidisciplinary medical consensus meetings could be used to select the node-negative good/prognosis population in which chemotherapy could be avoided. This review will focus on the uPA/PAI-1 system, its biological role and its clinical implications in breast oncology. The different ways to analyse the uPA and PAI-1 content in tumor cells will be also presented and commented.

Serum protein signature may improve detection of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is part of a spectrum of preinvasive lesions that originate within normal breast tissue and progress to invasive breast cancer. The detection of DCIS is important for the reduction of mortality from breast cancer, but the diagnosis of preinvasive breast tumors is hampered by the lack of an adequate detection method. To identify the changes in protein expression during the initial stage of tumorigenesis and to identify the presence of new DCIS markers, we analysed serum from 60 patients with breast cancer and 60 normal controls using mass spectrometry. A 23-protein index was generated that correctly distinguishes the DCIS and control groups with sensitivities and specificities in excess of 80% in two independent cohorts. Two candidate peptides were purified and identified as platelet factor 4 (PF-4) and complement C3a(desArg) anaphylatoxin (C3a(desArg)) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In an independent serum set of 165 patients, PF-4 and C3a(desArg) were significantly upregulated in DCIS compared with non-cancerous controls, as validated using western blot and enzyme-linked immunosorbent assay. We conclude that our serum protein-based test, used in conjunction with image-based screening practices, could improve the sensitivity and specificity of breast cancer detection.

Reliability and discriminant validity of HER2 gene quantification and chromosome 17 aneusomy analysis by real-time PCR in primary breast cancer.

There is an increasing demand for the evaluation of HER2 status in breast cancer. In this study, sections from fixed tissues and triton extracts of tissue homogenates were obtained from 163 malignant breast tumors and analyzed in parallel using immunohistochemistry combined with fluorescence in situ hybridization, as gold standard tests, and an ELISA test (c-erbB2/c-neu Rapid Format ELISA, Oncogene Research Products, USA). Tumor DNA was employed to evaluate two quantitative PCR methods: the HER2/neu DNA Quantification Kit (Roche Diagnostics GmbH, Germany), which uses the gastrin chromosome 17 reference gene, and our recently developed Oncolab qPCR assay, where both a chromosome 17 gene (somatostatin receptor type II (SSTR2)) and a non-chromosome 17 reference gene (glyceraldehyde-3-phosphate deshydrogenase (GAPDH)) were used to detect an increase in HER2 gene copy number and to evaluate the aneusomy of chromosome 17, respectively. By IHC/FISH and ELISA, HER2 was overexpressed in 27 (16.6%) and 24 (14.7%) samples, respectively. With the Roche and Oncolab qPCR assays, 29 (17.8%) samples showed a ratio of HER2/gastrin > or = 2.0 and 26 (16.0%) showed a ratio of HER2/SSTR2 > or = 2.0, respectively. In samples presenting HER2/SSTR2 <2.0 and HER2/GAPDH > or = 2.0, which was indicative of a chromosome 17 polysomy, we observed a modest increase in HER2 protein expression. Complete agreement between the four methods for HER2 status determination was obtained for 154 (94.5%) samples. Overall, these results demonstrate that quantitative PCR is a reliable method for analyzing HER2 status and chromosome 17 polysomy.

Serum EGF-receptor and HER-2 extracellular domains and prognosis of non-small-cell lung cancer.

This retrospective study aimed at evaluating the prognostic impact of high serum levels of either the HER-2 extracellular domain (ECD) or the epidermal growth factor receptor (EGFR) ECD measured using two specific ELISAs in 221 patients with non-small-cell lung cancer (NSCLC) receiving conventional therapy and 41 nonmalignant pulmonary diseases patients. It was not possible to discriminate between lung cancer and benign lung disease owing to the lack of sensitivity-specificity relationship of HER-2 and EGFR ECD levels. Neither HER-2 nor EGFR ECD specific levels were associated with a particular prognosis of NSCLC patients receiving conventional therapy.

Analysis of the potential contribution of estrogen receptor (ER) beta in ER cytosolic assay of breast cancer.

Estrogen receptor (ER) content is the most useful parameter for predicting hormone response therapy in breast cancer. Assays available for detecting ER in breast tumor cytosol are ligand-binding assay (LBA), which detects both ERalpha and ERbeta, and the enzymatic immunoassay (EIA), in which monoclonal antibodies are directed against ERalpha. As shown in several studies, the 2 assays correlate and both are used routinely. However, some discrepancies between the 2 assays were found and explanations remain controversial. We evaluated ERalpha and ERbeta mRNA coexpression in breast tumors in order to study whether the presence of ERbeta could account for differences between LBA and EIA in the determination of ER protein level. Using HeLa cell lines transfected with either ERalpha or ERbeta, we confirmed that EIA, using H222 and D547 monoclonal antibodies, recognizes only ERalpha expression, whereas LBA detects both isoforms. In 119 breast tumor cytosols, the correlation between ER-EIA and ER-LBA was high (r = 0.72), although some discrepancies were found. When analyzing ER mRNA expression of samples with higher LBA values, no overexpression of ERbeta mRNA relatively to ERalpha mRNA were observed. There was a difference in ERbeta/ERalpha ratio between ER-negative and ER-positive samples, with a 10-fold increased median ratio in ER-negative samples (p = 0.01). We thus confirmed that the major form of ER in breast cancer is the ERalpha at both the protein and mRNA levels. Moreover, our data do not support the hypothesis that ERbeta expression could explain differences between LBA and EIA in the determination of ER protein level.

Measles virus exploits dendritic cells to suppress CD4+ T-cell proliferation via expression of surface viral glycoproteins independently of T-cell trans-infection.

Dendritic cells (DC) have been proposed to play a pivotal role in transient immune suppression induced by measles virus (MV) infection. In the present study, we show that DC-induced suppression of T-cell proliferation was not mediated by IL-10 or IFNalpha/beta, which are released following infection of DC, but required cell contacts between MV-infected DC and T cells. Human sera containing neutralizing anti-MV antibodies, as well as anti-MV hemagglutinin (HA) or fusion protein (F) mAbs, were found (i) to reverse suppression and (ii) to restore DC allostimulatory capacity. Interestingly, DC-induced T-cell suppression was associated with both phenotypic and functional DC maturation, as demonstrated by IL-12 production and chemotaxis to MIP-3beta. These data suggest that MV infection turns on the maturation program of DC allowing migration to draining lymph nodes, where potent T-cell immune suppression might be achieved via cell surface expression of HA and F glycoproteins, independently of T cell trans-infection.

Pro-gastrin-releasing peptide, neuron specific enolase and chromogranin A as serum markers of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) yields neuroendocrine properties. Pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE) and chromogranin A (CGA) are therefore putative serum markers in this disease. AIM: To assess any difference in the sensitivity-specificity relationship between these neuroendocrine markers regarding various control populations and disease extent. METHOD: A total of 146 patients were prospectively assessed clinically and biologically. Serum marker titrations were performed using commercial immunoradiometric assays (NSE, CGA) or ELISA (ProGRP). Areas under receiver operating characteristic curves (AUC-ROC) were calculated in order to assess the sensitivity-specificity relationship of each marker and to compare marker accuracy. Maximum Youden indices were used to determine marker thresholds able to produce the best overall diagnostic information. RESULTS: Assessing the sensitivity in the SCLC population and the specificity in benign lung disease, ProGRP demonstrated the best sensitivity relationship in as much as its AUC-ROC was significantly greater than the ones calculated using NSE and CGA (respective values, 0.95, 0.89, 0.70; two-tailed Z-test <0.05). The ProGRP threshold value, which offered the best sensitivity-specificity relationship was 53 pg/ml corresponding to a 0.80 sensitivity and a 0.96 specificity. In addition, when specificity was assessed in NSCLC and again the sensitivity in the whole SCLC population, ProGRP continued to demonstrate a greater AUC-ROC in comparison with other markers. Using the 53 pg/ml threshold the specificity of this marker was excellent with no false positives in NSCLC. On the other hand, none of the markers were able to discriminate limited from extensive SCLC as suggested by the fact that AUC-ROC, constructed when sensitivity was defined as a positive test in extensive disease and specificity as a true negative test in limited disease, did not reach the upper left octant (AUC 0.65, 0.71 and 0.63 for ProGRP, NSE and CGA, respectively). CONCLUSION: ProGRP yields the best sensitivity-specificity feature in SCLC, a result deserving further studies designed to evaluate the clinical applicability of this marker.