The impact of mpMRI-targeted vs systematic biopsy on the risk of prostate cancer downgrading at final pathology.

PURPOSE: Although targeted biopsies (TBx) are associated with improved disease assessment, concerns have been raised regarding the risk of prostate cancer (PCa) overgrading due to more accurate biopsy core deployment in the index lesion. METHODS: We identified 1672 patients treated with radical prostatectomy (RP) with a positive mpMRI and ISUP ≥ 2 PCa detected via systematic biopsy (SBx) plus TBx. We compared downgrading rates at RP (ISUP 4-5, 3, and 2 at biopsy, to a lower ISUP) for PCa detected via SBx only (group 1), via TBx only (group 2), and eventually for PCa detected with the same ISUP 2-5 at both SBx and TBx (group 3), using multivariable logistic regression models (MVA). RESULTS: Overall, 12 vs 14 vs 6% (n = 176 vs 227 vs 96) downgrading rates were recorded in group 1 vs group 2 vs group 3, respectively (p < 0.001). At MVA, group 2 was more likely to be downgraded (OR 1.26, p = 0.04), as compared to group 1. Conversely, group 3 was less likely to be downgraded at RP (OR 0.42, p < 0.001). CONCLUSIONS: Downgrading rates are highest when PCa is present in TBx only and, especially when the highest grade PCa is diagnosed by TBx cores only. Conversely, downgrading rates are lowest when PCa is identified with the same ISUP through both SBx and TBx. The presence of clinically significant disease at SBx + TBx may indicate a more reliable assessment of the disease at the time of biopsy potentially reducing the risk of downgrading at final pathology.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

A multicentric study on accurate grading of prostate cancer with systematic and MRI/US fusion targeted biopsies: comparison with final histopathology after radical prostatectomy.

OBJECTIVE: To evaluate the accuracy in histologic grading of MRI/US image fusion biopsy by comparing histopathology between systematic biopsies (SB), targeted biopsies (TB) and the combination of both (SB + TB) with the final histopathologic outcomes of radical prostatectomy specimens. MATERIALS AND METHODS: Retrospective, multicentric study of 443 patients who underwent SB and TB using MRI/US fusion technique (Urostation® and Trinity®) prior to radical prostatectomy between 2010 and 2017. Cochran's Q test and McNemar test were conducted as a post hoc test. Uni-multivariable analyses were performed on several clinic-pathological variables to analyze factors predicting histopathological concordance for targeted biopsies. RESULTS: Concordance in ISUP (International Society of Urological Pathology) grade between SB, TB and SB + TB with final histopathology was 49.4%, 51.2%, and 63.2% for overall prostate cancer and 41.2%, 48.3%, and 56.7% for significant prostate cancer (ISUP grade ≥ 2), respectively. Significant difference in terms of concordance, downgrading and upgrading was found between SB and TB (ISUP grade ≥ 2 only), SB and SB + TB, TB and SB + TB (overall ISUP grade and ISUP grade ≥ 2) (p < 0.001). Total number of cores and previous biopsies were significant independent predictive factors for concordance with TB technique. CONCLUSION: In this retrospective study, combination of SB and TB significantly increased concordance with final histopathology despite a limited additional number of cores needed.

Assessing the relationship between markers of glycemic control through flexible copula regression models.

Glycated haemoglobin (HbA1c) is a sensitive marker of blood glucose in patients with diabetes. However, levels can vary considerably, even amongst individuals with similar mean blood glucose concentrations. Other glycated proteins, such as fructosamine, can also act as blood sugar markers, but estimating HbA1c and fructosamine via independent models may lead to errors of interpretation regarding disease severity. From a clinical standpoint, it would be of great interest to know the factors that affect the mean concentration of both HbA1c and fructosamine, which influence the variability in the concentrations of these glycated markers and cause HbA1c/fructosamine discordance. Flexible models are required to illustrate the behaviour of these variables as well as the association between them. This work reviews existing models that might serve in this regard. Flexible copula regression models using splines were used to provide a better understanding of the behaviour of both glycated proteins and the relationship between them under the possible influence of different covariates. This work shows the usefulness of this type of models in practise and provides a basis for their clinical interpretation by means of an understandable case study. Ultimately, to better understand the effects of each continuous covariate, they are represented at the true scale of the response variables.

First urinary tract infections in children: the role of the risk factors proposed by the Italian recommendations.

AIM: In 2009, the Italian society for paediatric nephrology suggested the need for cystography, following a first febrile urinary tract infection (UTI), only in children at high risk for dilating vesicoureteral reflux or in the event of a second infection. The aim of this study was to evaluate the adequacy of the risk factors proposed by the Italian guidelines. METHODS: Children aged 2-36 months, managed by 10 Italian hospitals between 2009 and 2013, with a first febrile UTI were retrospectively evaluated. RESULTS: Four hundred and fourteen children were included: 51% female, mean age eight months. Escherichia coli was responsible of 84% UTIs. 269 children (65%) presented at least one risk factor, thus were further investigated: 44% had a reflux. The presence of a pathogen other than E. coli significantly predicted high-grade reflux, both in the univariate (Odd Ratio 2.52, 95% Confidence Interval 1.32-4.81, p < 0.005) and multivariate analysis (OR 2.74, 95% CI: 1.39-5.41, p: 0.003). 26/145 children (18%) with no risk factors experienced a second UTI, which prompted the execution of cystography, showing a dilating reflux in 11. CONCLUSION: Among the risk factors proposed by the Italian guidelines, only the presence of a pathogen other than E. coli significantly predicted reflux. Cystography can be postponed in children with no risk factors.

Test of Special Relativity Using a Fiber Network of Optical Clocks.

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

The Impact of Mental Illness on Uptake of Genetic Counseling for Hereditary Breast Cancer and Ovarian Cancer in a Multiethnic Cohort of Breast Cancer Patients.

We evaluated whether mental illness is a barrier to genetic counseling for hereditary breast and ovarian cancer (HBOC) in multiethnic breast cancer patients. We conducted a retrospective analysis of 308 women with newly diagnosed breast cancer and eligible for HBOC genetic testing seen in the breast clinic of an academic, urban medical center from 2007 to 2015. Uptake of genetic services and history of mental health disorder (MHD), defined as a psychiatric diagnosis or treatment with an antidepressant, mood stabilizer, anxiolytic, or antipsychotic medication, were ascertained by medical chart review. The mean age at breast cancer diagnosis was 56 years, with 44% non-Hispanic whites, 37% Hispanics, and 15% non-Hispanic blacks. Ninety-nine (32%) women met study criteria for MHD, 73% had a genetics referral, 57% had genetic counseling, and 54% completed BRCA testing. Uptake of genetic counseling services did not differ by race/ethnicity or presence of MHD. In multivariable analysis, younger age at diagnosis, Ashkenazi Jewish heritage, and family history of breast cancer were associated with HBOC genetic counseling. A relatively high proportion of breast cancer patients eligible for HBOC genetic testing were referred to a genetic counselor and referral status did not vary by MHD or race/ethnicity.

Transportable cavity-stabilized laser system for optical carrier frequency transmission experiments.

We report the design and performance of a transportable laser system at 1543 nm, together with its application as the source for a demonstration of optical carrier frequency transmission over 118 km of an installed dark fiber network. The laser system is based around an optical reference cavity featuring an elastic mounting that bonds the cavity to its support, enabling the cavity to be transported without additional clamping. The cavity exhibits passive fractional frequency insensitivity to vibration along the optical axis of 2.0×10(-11) m(-1) s(2). With active fiber noise cancellation, the optical carrier frequency transmission achieves a fractional frequency instability, measured at the user end, of 2.6×10(-16) at 1 s, averaging down to below 3×10(-18) after 20,000 s. The fractional frequency accuracy of the transfer is better than 3×10(-18). This level of performance is sufficient for comparison of state-of-the-art optical frequency standards and is achieved in an urban fiber environment.

Intraoperative technologies to assess margin status during radical prostatectomy - a narrative review.

Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.

Quality Improvement Framework to Examine Health Care Disparities in Behavioral Emergency Management in the Inpatient Medical Setting: A Consultation-Liaison Psychiatry Health Equity Project.

BACKGROUND: De-escalation of behavioral emergencies in the inpatient medical setting may involve restrictive clinical interventions that directly challenge patient autonomy. OBJECTIVE: We describe a quality improvement framework used to examine associations between patient characteristics and behavioral emergency de-escalation strategies. This project may inform other Consultation-Liaison Psychiatry teams seeking to promote equity in care. METHODS: We examined behavioral emergency response team (BERT) management at an urban, tertiary-care medical center in the United States over a 3-year period. BERT data from an existing dataset were combined with demographic information from the hospital's electronic medical record. Race and ethnic identities were categorized as Black, Hispanic, Asian, White, and unknown. BERT events were coded based on the most restrictive intervention utilized per unique patient. Cross-tabulations and adjusted odds ratios from multivariate logistic regression were used to identify quality improvement targets in this exploratory project. RESULTS: The sample included N = 902 patients and 1532 BERT events. The most frequent intervention reached was verbal de-escalation (n = 419 patients, 46.45%) and the least frequent was 4-point restraints (n = 29 patients, 3.2%). Half of BERT activations for Asian and a third for Hispanic patients required interpreter services. Anxiety and cognitive disorders and 2 BERT interventions, verbal de-escalation, and intramuscular/intravenous/ medications, were significantly associated with race/ethnic category. The most restrictive intervention for BERTs involving Black and Asian patients were verbal de-escalation (60.1%) and intramuscular/intravenous(53.7%), respectively. These proportions were higher compared with other race/ethnic groups. There was a greater percentage of patients from the unknown (6.3%) and Black (5.9%) race/ethnic groups placed in 4-point restraints compared with other groups (3.2%) that did not reach statistical significance. A logistic regression model predicting 4-point restraints indicated that younger age, multiple BERTs, and violent behavior as a reason for BERT activation, but not race/ethnic group, resulted in significantly higher odds. CONCLUSIONS: This project illustrates that a quality improvement framework utilizing existing clinical data can be used to engage in organizational introspection and identify potential areas of bias in BERT management. Our findings suggest opportunities for further exploration, enhanced education, and programmatic improvements regarding BERT intervention; 4-point restraints; interpreter services; and the influence of race on perception of psychopathology.

Mismatch repair deficiency: a temozolomide resistance factor in medulloblastoma cell lines that is uncommon in primary medulloblastoma tumours.

BACKGROUND: Tumours are responsive to temozolomide (TMZ) if they are deficient in O(6)-methylguanine-DNA methyltransferase (MGMT), and mismatch repair (MMR) proficient. METHODS: The effect of TMZ on medulloblastoma (MB) cell killing was analysed with clonogenic survival assays. Expression of DNA repair genes and enzymes was investigated using microarrays, western blot, and immunohistochemistry. DNA sequencing and promoter methylation analysis were employed to investigate the cause of loss of the expression of MMR gene MLH1. RESULTS: Temozolomide exhibited potent cytotoxic activity in D425Med (MGMT deficient, MLH1 proficient; IC(50)=1.7 µM), moderate activity against D341Med (MGMT proficient, MLH1 deficient), and DAOY MB cells (MGMT proficient, MLH1 proficient). MGMT inhibitor O(6)-benzylguanine sensitised DAOY, but not D341Med cells to TMZ. Of 12 MB cell lines, D341Med, D283Med, and 1580WÜ cells exhibited MMR deficiency due to MLH1 promoter hypermethylation. DNA sequencing of these cells provided no evidence for somatic genetic alterations in MLH1. Expression analyses of MMR and MGMT in MB revealed that all patient specimens (n=74; expression array, n=61; immunostaining, n=13) are most likely MMR proficient, whereas some tumours had low MGMT expression levels (according to expression array) or were totally MGMT deficient (3 out of 13 according to immunohistochemistry). CONCLUSION: A subset of MB may respond to TMZ as some patient specimens are MGMT deficient, and tumours appear to be MMR proficient.

Optical interferometry-based array of seafloor environmental sensors using a transoceanic submarine cable.

Optical fiber-based sensing technology can drastically improve Earth observations by enabling the use of existing submarine communication cables as seafloor sensors. Previous interferometric and polarization-based techniques demonstrated environmental sensing over cable lengths up to 10,500 kilometers. However, measurements were limited to the integrated changes over the entire length of the cable. We demonstrate the detection of earthquakes and ocean signals on individual spans between repeaters of a 5860-kilometer-long transatlantic cable rather than the whole cable. By applying this technique to the existing undersea communication cables, which have a repeater-to-repeater span length of 45 to 90 kilometers, the largely unmonitored ocean floor could be instrumented with thousands of permanent real-time environmental sensors without changes to the underwater infrastructure.

Comparing ultrastable lasers at 7 × 10-17 fractional frequency instability through a 2220 km optical fibre network.

Ultrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10-17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.

Prenatal Exposure to Bisphenols and Phthalates and Postpartum Depression: The Role of Neurosteroid Hormone Disruption.

CONTEXT: Postpartum depression (PPD) is a serious psychiatric disorder. While causes remain poorly understood, perinatal sex hormone fluctuations are an important factor, and allopregnanolone in particular has emerged as a key determinant. Although synthetic environmental chemicals such as bisphenols and phthalates are known to affect sex hormones, no studies have measured allopregnanolone and the consequences of these hormonal changes on PPD have not been interrogated. OBJECTIVE: To investigate associations of repeated measures of urinary bisphenols and phthalates in early and midpregnancy with serum pregnenolone, progesterone, allopregnanolone, and pregnanolone concentrations in midpregnancy and PPD symptoms at 4 months postpartum. METHODS: Prospective cohort study of 139 pregnant women recruited between 2016 and 2018. Bisphenols and phthalates were measured in early and midpregnancy urine samples. Serum sex steroid hormone concentrations were measured in midpregnancy. PPD was assessed at 4 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Multiple informant models were fit using generalized estimating equations. Serum levels of allopregnanolone, progesterone, pregnanolone, and pregnenolone were examined as log-transformed continuous variables. PPD symptoms were examined as continuous EPDS scores and dichotomously with scores ≥10 defined as PPD. RESULTS: Di-n-octyl phthalate (DnOP) and diisononyl phthalate (DiNP) metabolites were associated with reduced progesterone concentrations. Log-unit increases in ∑DnOP and ∑DiNP predicted 8.1% (95% CI -15.2%, -0.4%) and 7.7% (95% CI -13.3%, -1.7%) lower progesterone, respectively. ∑DnOP was associated with increased odds of PPD (odds ratio 1.48; 95% CI 1.04, 2.11). CONCLUSION: Endocrine disrupting chemicals may influence hormonal shifts during pregnancy as well as contribute to PPD.

A comprehensive cooperative project for children with renal diseases in Nicaragua.

In low-income countries renal diseases generally and chronic kidney disease (CKD) in particular represent a wide-spread and often underdiagnosed clinical problem. The aim of the cooperative project between the pediatric nephrology units of Milan, Italy, and Managua, Nicaragua was to improve the diagnosis and treatment of renal diseases and CKD in Nicaraguan children. When the project started, in 2000, there were many constraints in human and material resources in the Children's Hospital in Managua. Since 2001, a specialized Unit of Pediatric Nephrology and Urology has developed, offering free of charge basic clinical assistance to hospitalized children, and training abroad of the whole staff. Shared protocols, renovation of infrastructure and an information technology (IT) program were implemented. In 2003, renal replacement therapy (RRT) for selected children was initiated, along with a network of six department hospitals in 2005 and, in 2007, a CKD prevention program in the most peripheral Health Units, so that 61% of the Nicaraguan pediatric population is now covered by the project. To ensure implementation of the project, applications for funds to Italian private and public institutions were made and a Nicaraguan charity foundation was activated. The Nicaraguan Ministry of Health and the hospital directors were always involved in the plans of the development of the project and accepted the progressive transfer of the costs to the government, throughout the 9-year duration of the project. The IT program, inclusive of a database of children with kidney and other urinary tract (UT) diseases and a web connection between Milan and Managua, was crucial in monitoring the activities and providing epidemiological data, in order to better allocate resources. The clinical activities and the number of children managed in Managua in 2008 are similar to those of pediatric nephrology units worldwide and depict the level of clinical autonomy achieved. The sister-center model of cooperation and the top-down strategy we applied, along with the careful consideration of all the economic, logistic and political issues, were and are the key factors which explain the favorable results of this cooperative project.

A virtuous diagnostic and therapeutic roadmap triggered by a motivated and skilful urinary sediment examination.

In this paper we describe how an accurate urinary sediment examination, which revealed the presence of a severe 2,8-dihydroxyadenine crystalluria, opened the way to an articulate and successful diagnostic and therapeutic roadmap for a rare and potentially severe renal disease.

Outdoor spatial distribution and indoor levels of NO2 and SO2 in a high environmental risk site of the South Italy.

In the frame of the project EDOC@WORK3.0, Education and Work on Cloud, a monitoring plan has been carried out in the highly industrialized town of Taranto (one of the most polluted sites of Italy) in order to investigate contemporary indoor and outdoor concentrations of NO2 and SO2 by passive sampling devises (Radiello). Simultaneously indoor and outdoor samplings of NO2 and SO2 were performed from 2nd November 2015 to 2nd December 2015 in nine sites scattered in the investigated area at different quotes and distances from the industrial complex. Our findings show substantial differences between the spatial distributions of the two pollutants and support the hypothesis of two different prevalent sources for NO2 and SO2. In particular, we find diffusive sources of NO2 linked mainly to the vehicular traffic and secondarily to industrial sources. In contrast, SO2 was mainly associated to industrial sources present in the area, representing also a proxy of the mixture of air contaminants associated to industrial processes. Our hypothesis is also confirmed by analysis of data measured by ARPA air quality monitoring stations. Comparison between indoor and outdoor concentrations confirms that outdoor pollutants infiltrate to indoor environments, moreover it highlights potential NO2 indoor sources basically linked to cooking activities, representing adverse health effects for population risk categories such as children or cooks. Considering that urban people spend a lot of their time in indoors, attention should be paid both to outdoor pollutant sources and to indoor sources.

Voiding cystourethrography and 99MTC-MAG3 renal scintigraphy in pediatric vesicoureteral reflux: what is the role of indirect cystography?

BACKGROUND: Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS: The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS: A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS: 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.

Elastic fusion biopsy versus systematic biopsy for prostate cancer detection: Results of a multicentric study on 1,119 patients. / Evaluación de la biopsia de fusión elástica vs. biopsia sistemática para la detección del cáncer de próstata: resultados de un estudio multicéntrico en 1.119 pacientes.

OBJECTIVES: To assess the accuracy of targeted and systematic biopsies for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in the everyday practice, evaluating the need for additional systematic biopsies at the time of targeted biopsy. PATIENTS AND METHODS: From our multicentric database gathering data on 2,115 patients who underwent fusion biopsy with Koelis™ system between 2010 and 2017, we selected 1,119 patients who received targeted biopsies (a median of 3 for each target), followed by systematic sampling of the prostate (12 to 14 cores). Overall and clinically significant cancer detection rate (CDR) of Koelis™ fusion biopsies were assessed, comparing target and systematic biopsies. Secondary endpoint was the identification of predictors of PCa detection. RESULTS: The CDR of targeted biopsies only was 48% for all cancers and 33% for csPCa. The performance of additional, systematic prostate sampling improved the CDR of 15% for all cancers and of 12% for csPCa. PCa was detected in 35%, 69%, and 92% of patients with lesions scored as PI-RADS 3, 4 and 5, respectively. Elevated PI-RADS score and positive digital rectal examination were predictors of PCa, whereas biopsy-naïve status was associated with csPCa. CONCLUSION: In the everyday practice target biopsy with Koelis™ achieves a good CDR for all PCa and csPCa, which is significantly improved by subsequent systematic sampling of the prostate. The outstanding outcomes of fusion biopsy are confirmed also in biopsy-naïve patients. Elevated PI-RADS score and positive digital rectal examination are strongly associated with presence of PCa.

Competency in mismatch repair prohibits clonal expansion of cancer cells treated with N-methyl-N'-nitro-N-nitrosoguanidine.

The phenomenon of alkylation tolerance has been observed in cells that are deficient in some component of the DNA mismatch repair (MMR) system. An alkylation-induced cell cycle arrest had been reported previously in one MMR-proficient cell line, whereas a MMR-defective clone derived from this line escapes from this arrest. We examined human cancer cell lines to determine if the cell cycle arrest were dependent upon the MMR system. Growth characteristics and cell cycle analysis after MNNG treatment were ascertained in seven MMR-deficient and proficient cell lines, with and without confirmed mutations in hMLH1 or hMSH2 by an in vitro transcription/translation assay. MMR-proficient cells underwent growth arrest in the G2 phase of the cell cycle after the first S phase, whereas MMR-deficient cells escaped an initial G2 delay and resumed a normal growth pattern. In the HCT116 line corrected for defective MMR by chromosome 3 transfer, the G2 phase arrest lasted more than five days. In another MMR-proficient colon cancer cell line, SW480, cell death occurred five days after MNNG treatment. A competent MMR system appears to be necessary for G2 arrest or cell death after alkylation damage, and this cell cycle checkpoint may allow the cell to repair damaged DNA, or prevent the replication of mutated DNA by prohibiting clonal expansion.