Publications by authors named "Matteo Brunelli"

277 Publications

Multitarget fluorescence in situ hybridization diagnostic applications in solid and hematological tumors.

Expert Rev Mol Diagn 2021 Feb 22:1-13. Epub 2021 Feb 22.

Department of Mental and Physic Health and Preventive Medicine, Pathology Unit, University of Campania Luigi Vanvitelli , Napoli, Italy.

: Multitarget FISH (mFISH) is a technique allowing for simultaneous detection of multiple targets sequences on the same slide through the choice of spectrally distinct fluorophore labels. The mFISH could represent a useful tool in the field of precision oncology. : This review discusses the potential applications of mFISH technology in the molecular diagnosis of different solid and hematological tumors, including non-small cell lung cancers, melanomas, renal cell carcinomas, bladder carcinomas, germ cell tumors, and multiple myeloma, as commonly required in the clinical practice. : In this emerging era of the tailored therapies and newer histo-molecular classifications, there are increasing numbers of predictive and diagnostic biomarkers required for effective clinical care. The mFISH approach may have several applications in the common clinical practice, improving the molecular diagnosis in terms of time, cost and preservation of biomaterial for tumors with a limited amount of tumor available. The mFISH provides several advantages compared to other high-throughput technologies; however, it requires high level of expertise required to interpret complex results.
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http://dx.doi.org/10.1080/14737159.2021.1887733DOI Listing
February 2021

Consultation between forensic and clinical pathologists for histopathology examination after forensic autopsy.

Med Sci Law 2021 Jan;61(1_suppl):25-35

Department of Diagnostics and Public Health, Pathology Unit, University and Hospital Trust of Verona, Italy.

The magnitude of the diagnostic benefit conferred by performing histopathological examinations after medico-legal/forensic autopsies remains debatable. We have tried to address this issue by reviewing a series of histopathology referrals concerning medico-legal autopsies in real-world routine practice. We present an audit of the consultations provided to forensics by clinical pathologists at our institute between 2015 and 2018. Over this period, 493 post-mortem examinations were performed by forensic pathologists. Of these cases, 52 (11%) were referred for histopathology. Gross assessment was requested in 22/52 (42%) cases. Histopathology examination was performed on single organs in 15/52 (29%) cases, primarily on the lung and heart, whereas parenchymatous multi-organ analysis was carried out in 14/52 (27%) cases. Bone-marrow sampling was studied in 4/52 (8%) cases. Immunohistochemistry was needed in 16/52 (31%) cases, special stains in 9/52 (21%) cases and molecular analysis in 4/52 (8%) cases. Focusing on technical processes, standard methodology on pre-analytical procedures was changed in 10/52 (19%) cases in order to answer specific diagnostic questions. We showed that although most of the time the diagnosis is clear by the end of dissection on the basis of the macroscopic findings, histopathology can provide, modify or confirm the cause of death in many medico-legal/forensic cases. Therefore, it is desirable that forensic pathologists and clinical pathologists establish robust working relationships in a cooperative environment. We conclude that it is important to implement guidelines based on real-world routine practice in order to identify cases where histopathology can provide useful contributions, which in our experience applied to 11% of forensic cases.
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http://dx.doi.org/10.1177/0025802420965763DOI Listing
January 2021

Sudden death in a 39-year-old woman due to three-vessel coronary artery disease: A case report and literature review.

Med Sci Law 2021 Jan;61(1_suppl):150-154

Department of Diagnostics and Public Health - Legal Medicine and Forensic Pathology Unit, University of Verona, Italy.

Coronary atherosclerosis may be underestimated in previously asymptomatic and apparently healthy young people, although it has been reported in various epidemiological studies. Between 7% and 21% of sudden cardiac deaths in previously asymptomatic people aged <45 years are due to three-vessel coronary artery disease. So, clinical services need to vigilant for this condition. We report a single case of sudden death in a young woman who was affected by three-vessel coronary artery disease. This 39-year-old woman attended an emergency department for non-specific chest pain. After a brief observation period, in the absence of signs of an acute myocardial event, she self-discharged. However, she died suddenly the next day. The subsequent autopsy did not show significant pathological findings, although macroscopic examination of the heart revealed critical three-vessel coronary artery disease. Standard histological examination confirmed an atheromatous plaque obstructing >75% of the lumen of the anterior descending artery, complicated by haemorrhagic phenomena, with diffuse calcified and sub-totally occluded atherosclerotic plaques in the other vascular sections, without ischaemic signs of the cardiomyocytes or fibrosis. When young people present with chest pain, they must be carefully evaluated. Risks need to be clearly explained, particularly when self-discharge is requested.
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http://dx.doi.org/10.1177/0025802420929210DOI Listing
January 2021

Predictors of complications occurring after open and robot-assisted prostate cancer surgery: a retrospective evaluation of 1062 consecutive patients treated in a tertiary referral high volume center.

J Robot Surg 2021 Feb 9. Epub 2021 Feb 9.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale Stefani 1, 37126, Verona, Italy.

To investigate factors associated with the risk of major complications after radical prostatectomy (RP) by the open (ORP) or robot-assisted (RARP) approach for prostate cancer (PCa) in a tertiary referral center. 1062 consecutive patients submitted to RP were prospectively collected. The following outcomes were addressed: (1) overall postoperative complications: subjects with Clavien-Dindo System (CD) one through five versus cases without any complication; (2) moderate to major postoperative complications: cases with CD < 2 vs.  ≥ 2, and 3) major post-operative complications: subjects with CDS CD ≥  3 vs.  < 3. The association of pre-operative and intra-operative factors with the risk of postoperative complications was assessed by the logistic regression model. Overall, complications occurred in 310 out of 1062 subjects (29.2%). Major complications occurred in 58 cases (5.5%). On multivariate analysis, major complications were predicted by PCa surgery and intraoperative estimated blood loss (EBL). ORP compared to RARP increased the risk of major CD complications from 2.8 to 19.3% (OR = 8283; p < 0.0001). Performing ePLND increased the risk of major complications from 2.4 to 7.4% (OR = 3090; p < 0.0001). Assessing intraoperative blood loss, the risk of major postoperative complications was increased by BL above the third quartile when compared to subjects with intraoperative blood loss up to the third quartile (10.2% vs. 4.6%; OR = 2239; 95%CI: 1233-4064). In the present cohort, radical prostatectomy showed major postoperative complications that were independently predicted by the open approach, extended lymph-node dissection, and excessive intraoperative blood loss.
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http://dx.doi.org/10.1007/s11701-021-01192-wDOI Listing
February 2021

Stimulator of interferon genes (STING) immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.

Pathology 2021 Jan 15. Epub 2021 Jan 15.

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy; Department of Pathology, Pederzoli Hospital, Peschiera del Garda, Verona, Italy. Electronic address:

Angiomyolipoma is the prototype of renal perivascular epithelioid cell (PEC) lesions whose pathogenesis is determined by mutations affecting TSC genes, with eventual deregulation of the mTOR pathway. It is well known that mTOR complex protein is involved in autophagy, and recently the role of STING in this process has been demonstrated. Based on this background, we sought to investigate STING immunohistochemical expression in a series of PEC lesions of the kidney. Fifty classic angiomyolipomas, 14 epithelioid angiomyolipomas/pure epithelioid PEComas, two angiomyolipomas with epithelial cysts (AMLEC), and two intraglomerular PEC lesions were collected. Immunostaining for STING was carried out in all cases and FISH analysis using dual colour break apart TFE3 and TFEB probes was performed in all pure epithelioid PEComas and AMLEC. Control cases including 20 normal adult kidneys, five fetal kidneys, and 30 MiT family translocation renal cell carcinomas (the main differential diagnosis with epithelioid angiomyolipoma/pure epithelioid PEComa) were also immunohistochemically stained with STING. Strong and diffuse cytoplasmic expression of STING was observed in 100% of classic angiomyolipomas, AMLEC, and intraglomerular lesions, and in 79% (11/14) of epithelioid angiomyolipomas/pure epithelioid PEComas. TFE3 gene rearrangement was demonstrated in two epithelioid angiomyolipomas/pure epithelioid PEComas, both completely negative for STING. None of the MiT family translocation renal cell carcinomas expressed STING. In conclusion, we demonstrate the expression of STING in almost all PEC lesions of the kidney. This result provides novel insights into the possible role of autophagy in PEC lesions of the kidney. Moreover, this finding may be useful for diagnostic purposes, particularly in distinguishing epithelioid angiomyolipoma/pure epithelioid PEComa from MiT family translocation renal cell carcinoma and detecting intraglomerular PEC lesions.
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http://dx.doi.org/10.1016/j.pathol.2020.09.025DOI Listing
January 2021

HLA-G expression in melanomas.

Int Rev Immunol 2021 Jan 11:1-21. Epub 2021 Jan 11.

Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.

Objective: Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule involved in inducing tolerance at the feto-maternal interface and in escape of immune response by tumor cells. The aim of the study is to review the published literature on the expression of HLA-G in malignant melanomas and its clinicopathological and prognostic correlates.

Methods: A systematic search was carried out in electronic databases. Studies dealing with HLA-G expression in surgically-removed human samples were retrieved and analyzed.

Results: Of 1737 retrieved articles, 16 were included. The main themes regarded HLA-G expression in malignant melanocytic lesions, assessed by immunohistochemistry (IHC), soluble or molecular techniques, and its relationship with clinicopathological features, such as tumor thickness and malignant behavior. Overall significant HLA-G expression was found in 460/843 tumors (55%), and specifically in 251/556 melanomas (45%) evaluated with IHC, in 208/250 cases (83%) examined with soluble methods and in 13/23 melanoma lesions (57%) tested with polymerase chain reaction. Despite the correlation with parameters indicating an aggressive behavior, no studies demonstrated any prognostic value of HLA-G expression. Furthermore, uveal melanomas were constantly negative for this biomarker.

Conclusion: Overall, published data indicate that while HLA-G is involved in the interactions between melanomas and the immune system, it is unlikely to be the only factor to play such a role, therefore making it difficult to designate it as a prognostically relevant molecule. Evidence further suggests that HLA-G is not implicated in the immunobiology of uveal melanomas.
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http://dx.doi.org/10.1080/08830185.2020.1869732DOI Listing
January 2021

Endogenous testosterone as a predictor of prostate growing disorders in the aging male.

Int Urol Nephrol 2021 Jan 3. Epub 2021 Jan 3.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Piazzale Aristide Stefani 1, 37126, Verona, Italy.

Objective: To investigate the associations of endogenous testosterone with prostate growing disorders (PGD) including benign prostatic hyperplasia (BPH) and prostate cancer (PCA).

Methods: The study population was composed by 1176 cases including 371 BPH subjects (31.5%) without cancer who underwent prostate transurethral resection from January 2017 to November 2019 and 805 patients (68.5%) with PCA who underwent surgery from November 2014 to December 2019. The association of endogenous testosterone, which was measured before surgery, with the risk of PGD was evaluated by statistical methods.

Results: In the study population, endogenous testosterone levels were significantly lower in PCA cases compared to BPH patients who were older with larger prostates but lower prostate-specific antigen (PSA) levels. On multivariate analysis, the risk of PCA decreased by endogenous testosterone (odds ratio, OR = 0.957; 95% CI 0.930-0.984; p = 0.002) as by age (OR = 0.955; 95% CI  0.933-0.984; p < 0,0001) and prostate volume (OR = 0.930; 95% CI 0.919-0.940; p < 0.0001) but increased by PSA (OR = 1.652; 95% CI 1.542-1.769; p < 0.0001). On multivariate linear regression analysis, endogenous testosterone inversely associated with body mass index (BMI) (regression coefficient, b =  - 0.279; p = 0.002) and PCA (b =  - 2.935; p < 0.0001).

Conclusions: In the aging male, endogenous testosterone independently predicted malignant prostate disorders, which associated with decreased hormone levels along BMI categories. Endogenous testosterone is a further marker for evaluating prostate growing disorders in clinical practice; however, controlled studies are required.
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http://dx.doi.org/10.1007/s11255-020-02747-wDOI Listing
January 2021

Cytokine-, Neurotrophin-, and Motor Rehabilitation-Induced Plasticity in Parkinson's Disease.

Neural Plast 2020 26;2020:8814028. Epub 2020 Nov 26.

Department of Diagnostic and Public Health, University of Verona, Verona, Italy.

Neuroinflammation and cytokine-dependent neurotoxicity appear to be major contributors to the neuropathology in Parkinson's disease (PD). While pharmacological advancements have been a mainstay in the treatment of PD for decades, it is becoming increasingly clear that nonpharmacological approaches including traditional and nontraditional forms of exercise and physical rehabilitation can be critical adjunctive or even primary treatment avenues. Here, we provide an overview of preclinical and clinical research detailing the biological role of proinflammatory molecules in PD and how motor rehabilitation can be used to therapeutically modulate neuroinflammation, restore neural plasticity, and improve motor function in PD.
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http://dx.doi.org/10.1155/2020/8814028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714573PMC
November 2020

Calcium cytotoxicity sensitizes prostate cancer cells to standard-of-care treatments for locally advanced tumors.

Cell Death Dis 2020 12 7;11(12):1039. Epub 2020 Dec 7.

Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.

Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.
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http://dx.doi.org/10.1038/s41419-020-03256-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721710PMC
December 2020

Clinical-Pathological, Immunohistochemical, and Genetic Characterization of a Series of Posterior Pituitary Tumors.

J Neuropathol Exp Neurol 2021 Jan;80(1):45-51

ARC-Net Research Centre, University and Hospital Trust of Verona, Verona (AS), Italy.

Posterior pituitary tumors are supposed to represent the morphological spectrum of a single entity. Herein, we report the clinical-pathological, immunohistochemical, and genetic features of 5 spindle cell oncocytomas (SCOs), 3 pituicytomas, and 1 granular cell tumor (GCT). SCOs had the highest local invasiveness and affected older subjects. The 3 histotypes differed in the content of spindle cells (predominant in pituicytoma and absent in GCT), presence of lymphocytic infiltrate (in SCO and GCT, but not in the pituicytoma) and EMA/GFAP staining (negative in GCT; EMA-positive/GFAP-negative in 4/5 SCO and GFAP-positive in 3/3 pituicytomas). Three SCOs and 1 pituicytoma analyzed with next-generation sequencing had no mutations in 409 genes. However, 1 SCO had previously unreported homozygous deletion of CDKN2A/B and another of SMARCA4, SMARCB1, and NF2. All 3 SCOs had loss of heterozygosity of chromosome 1p, while the pituicytoma had chromosome 19 homozygous loss and chromosomes 10, 13q, and 18q loss of heterozygosity. Since 1p and 13q losses were previously reported in 1 pituicytoma and 1 SCO, respectively, our data demonstrate that posterior pituitary tumors share common genetic alterations. The possibility that posterior pituitary tumors are SMARCA4/SMARCB1-deficient should be kept in mind in the differential diagnosis toward other entities.
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http://dx.doi.org/10.1093/jnen/nlaa139DOI Listing
January 2021

TFEB rearranged renal cell carcinoma. A clinicopathologic and molecular study of 13 cases. Tumors harboring MALAT1-TFEB, ACTB-TFEB, and the novel NEAT1-TFEB translocations constantly express PDL1.

Mod Pathol 2020 Nov 18. Epub 2020 Nov 18.

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy.

Renal cell carcinomas with t(6;11) chromosome translocation has been classically characterized by the rearrangement of the TFEB gene, located on chromosome 6, and MALAT1 gene, located on chromosome 11. Recently, a few other genes have been described as fusion partners in TFEB rearranged renal cell carcinomas. Although most of TFEB rearranged renal cell carcinomas have an indolent behavior, in the rare cases of advanced metastatic disease targeted therapy and predictive markers remain lacking. In the present study, we collected 13 TFEB rearranged renal cell carcinomas, confirmed by FISH, analyzing their morphology and exploring the novel gene partners. Looking for predictive markers, we have also performed PDL1 immunohistochemical analysis by using four different assays (E1L3N, 22C3, SP142, and SP263). MALAT1 gene rearrangement has been found in ten tumors, five cases showing classical biphasic morphology with "rosettes", five cases without "rosettes" mimicking other renal cell carcinomas or epithelioid angiomyolipoma/pure epithelioid PEComa. We identified two different partner genes, ACTB and NEAT1, the latter previously unreported and occurring in a tumor with an unusual solid and cystic appearance. In both cases, the "rosettes" were absent. In one case no gene partner was identified. Overall, in 12 of 13 TFEB-rearranged renal cell carcinomas staining for PDL1 SP263 was observed, whereas the other antibodies were less reliable or more difficult to interpret. In conclusion, we described the third case of ACTB-TFEB rearranged renal cell carcinoma and a novel NEAT1-TFEB rearranged renal cell carcinoma, both without the distinctive biphasic morphology typical of t(6;11) renal cell carcinoma. Finally, PDL1 SP263 was constantly expressed in TFEB rearranged renal cell carcinoma with possible clinical benefit which requires further investigations.
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http://dx.doi.org/10.1038/s41379-020-00713-6DOI Listing
November 2020

MDM2 gene amplification as selection tool for innovative targeted approaches in PD-L1 positive or negative muscle-invasive urothelial bladder carcinoma.

J Clin Pathol 2020 Nov 3. Epub 2020 Nov 3.

Division of Urology, University and Hospital Trust of Verona, Verona, Italy.

Aims: According to The Cancer Genome Atlas (TCGA), around 9% of bladder carcinomas usually show abnormalities of the murine double minute 2 (MDM2) gene, but a few studies have been investigated them. We profiled MDM2 gene amplification in a series of urothelial carcinomas (UC) considering the molecular subtypes and expression of programmed death ligand 1 (PD-L1).

Methods: 117 patients with muscle-invasive UC (pT2-3) without (N0) or with (N+) lymph-node metastases were revised. Only cases with availability of in toto specimens and follow-up were studied. Tissue microarray was built. p53, ER, RB1, GATA-3, CK20, CK5/6, CD44 and PD-L1 (clone sp263) immunoexpression was evaluated. Fluorescent in situ hybridisation was assessed by using the HER-2/neu, FGFR-3, CDKN2A and MDM2 probes. True (ratio 12q/CEP12 >2) MDM2 gene amplification was distinguished from polyploidy/gains (ratio <2, absolute copy number of MDM-2 >2). MDM2 and PD-L1 values were correlated to the TCGA molecular phenotypes. Statistical analysis was performed.

Results: 6/50 (12%) cases (5 N0 and 1 N+) were amplified for MDM2 without matching to molecular phenotypes. Of 50, 14 (37%) cases expressed PD-L1 at 1% cut-off; 3/50 (9%) at >50% cut-off; of these, 2 cases on side of neoplasia among inflammatory cells. Only one out of six (17%) cases amplified for MDM2 showed expression (>50% cut-off) of PD-L1. MDM2 amplification was independent to all documented profiles (k test=0.3) and was prevalent in recurrent UC.

Conclusion: MDM2 amplification has been seen in both PD-L1 positive and negative muscle-invasive bladder UC independently from the TCGA molecular phenotypes. MDM2 and PD-L1 might be assessed in order to predict a better response to combo/single targeted therapies.
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http://dx.doi.org/10.1136/jclinpath-2020-207089DOI Listing
November 2020

Angiomyolipoma of the kidney: from simple hamartoma to complex tumour.

Pathology 2021 Jan 31;53(1):129-140. Epub 2020 Oct 31.

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Verona, Italy; Department of Pathology, Pederzoli Hospital, Peschiera, Italy. Electronic address:

Angiomyolipoma is the most common mesenchymal tumour of the kidney, even if for a long time it has been viewed as a hamartoma rather than a neoplasm. It belongs to a family of neoplasms, named PEComa, characterised by the constant presence of perivascular epithelioid cells that co-express smooth muscle and melanogenesis markers. Angiomyolipoma can occur in patients with tuberous sclerosis, a hereditary syndrome due to the alteration of TSC1 or TSC2 genes, or sporadically. Angiomyolipoma and its variants are indolent tumours; however, some epithelioid angiomyolipomas/pure epithelioid PEComas are aggressive, and criteria for malignancy have been proposed to identify those cases. Although typical angiomyolipoma is a straightforward diagnosis, pathologists should be aware of the wide morphological spectrum of its variants which could be tricky in routine clinical practice and could require immunohistochemical analysis for resolution. The differential diagnosis may range from an inflammatory process (for instance xanthogranulomatous pyelonephritis) to the most common renal cancers and sarcomas. The immunoexpression of melanogenesis markers (HMB45 and Melan-A) and cathepsin K is extremely helpful in the majority of cases. Recently, a subset of epithelioid angiomyolipoma/pure epithelioid PEComa harbouring TFE3 gene fusions has been described, raising questions about its relationship with the family of perivascular epithelioid cell tumour. The activation of the mTOR pathway due to genetic alterations of tuberous sclerosis complex in TSC1 or TSC2 genes in angiomyolipoma has also been reported as well as the subsequent therapeutic implications.
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http://dx.doi.org/10.1016/j.pathol.2020.08.008DOI Listing
January 2021

Predictors of Lymph Node Invasion in Patients with Clinically Localized Prostate Cancer Who Undergo Radical Prostatectomy and Extended Pelvic Lymph Node Dissection: The Role of Obesity.

Urol Int 2020 Oct 15:1-8. Epub 2020 Oct 15.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Objective: In patients with intermediate- and high-risk localized prostate cancer (PCa), improving the detection of occult lymph node metastases could play a pivotal role for therapeutic counseling and planning. The recent literature shows that several clinical factors may be related to PCa aggressiveness. The aim of this study is to investigate the potential associations between clinical factors and the risk of multiple lymph node invasion (LNI) in patients with intermediate- and high-risk localized PCa (cT1/2, cN0, and ISUP grading group >2 and/or prostate-specific antigen (PSA) >10 ng/mL) who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Materials And Methods: In a period ranging from January 2014 to December 2018, 880 consecutive patients underwent RP with ePLND for PCa. Among these, 481 met the inclusion criteria and were selected. Data were prospectively collected within an institutional dataset and retrospectively analyzed. Age (years), body mass index (BMI; kg/m2), PSA (ng/mL), prostate volume (mL), and biopsy positive cores (BPC; %) were recorded for each case. BMI and BPC were considered continuous and categorical variables, respectively. The logistic regression models evaluated the association of clinical factors with the risk of nodal metastases.

Results: LNI was detected in 73/418 patients (15.2%) of whom 40/418 (8.3%) harbored multiple LNI (median 2, IQR: 3-4). On multivariate analysis, BMI was independently associated with the risk of multiple LNI in the pathological specimen when compared with patients without LNI (OR = 1.147; p = 0.018), as well as the percentage of biopsy positive cores (OR = 1.028; p < 0.0001) and European Association of Urology high-risk class (OR = 5.486; p < 0.0001). BMI was the only predictor of multiple LNI when compared with patients with 1 positive node (OR = 1.189, p = 0.027).

Conclusions: In intermediate- and high-risk localized PCa, BMI was an independent predictor of the risk of multiple lymph node metastases. The inclusion of BMI within LNI risk calculators could be helpful, and a detailed counseling in obese patients should be required.
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http://dx.doi.org/10.1159/000510008DOI Listing
October 2020

Prostatic chronic inflammation and prostate cancer risk at baseline random biopsy: Analysis of predictors.

Arab J Urol 2020 May 13;18(3):148-154. Epub 2020 May 13.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Objective: To evaluate predictors of prostatic chronic inflammation (PCI) and prostate cancer (PCa) in patients undergoing transperineal baseline random prostatic needle biopsies (BNB).

Patient And Methods: According to BNB outcomes, patients were divided into four groups: cases without PCI or PCa (Control group), cases with PCI only (PCI group), cases with PCa and PCI (PCa+PCI group) and cases with PCa only (PCa group). A multinomial logistic regression model was used to evaluate the association of clinical factors with BNB outcomes. Additionally, clinical factors associated with the risk of PCa in the overall population were investigated using a multivariable logistic regression model (univariate and multivariate analysis).

Results: Overall, 945 patients were evaluated and grouped as follows: Control group, 308 patients (32.6%); PCI group, 160 (16.9%); PCa+PCI group, 45 (4.8%); and PCa group, 432 (45.7%). Amongst these, PCa was independently predicted by age (odds ratio [OR] 1.081), prostate specific-antigen level (PSA; OR 1.159), transition zone volume (TZV; OR 0.916), and abnormal digital rectal examination (DRE; OR 1.962). PCa and PCI (4.8%) were independently predicted by age (OR 1.081), PSA level (OR 1.122) and TZV (OR 0.954). In the group without PCa, the PSA level was the only factor associated with the risk of PCI when compared to the control group (OR 1.051, = 0.042). Among patients with PCa, independent factors associated with the risk of only PCa compared to cases with PCA+PCI were TZV (OR 0.972) and number of positive cores (OR 1.149). In the overall population, PCI was the strongest predictor of a decreased risk of PCa (multivariate model, OR 0.212; < 0.001).

Conclusions: At BNB, PCI was associated with both a decreased risk of PCa and less aggressive tumour biology amongst patients with PCa. The presence of PCI on biopsy cores should be reported because of its implications in clinical practice.

Abbreviations: BGG: biopsy Gleason Group; BPC: biopsy positive (cancer) cores; BMI: body mass index; FGF-2: fibroblast growth factor 2; IL: interleukin; ISUP: International Society of Urologic Pathology; NIH: National Institutes of Health; OR: odds ratio; PCa: prostate cancer; PCI: prostatic chronic inflammation; TGF: transforming growth factor; TPV: total prostate volume; TZV: transition zone volume.
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http://dx.doi.org/10.1080/2090598X.2020.1757335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473292PMC
May 2020

Donor-Transmitted Cancers in Transplanted Livers: Analysis of Clinical Outcomes.

Liver Transpl 2021 01 15;27(1):55-66. Epub 2020 Sep 15.

Pathology Unit, Sant'Orsola-Malpighi University Hospital of Bologna, Bologna, Italy.

The risk of transmission of malignancy from donor to recipient is low. However, this occurrence has dramatic consequences. Many reports of donor-derived cancers in liver transplant recipients have been published, but they have not been systematically summarized into a lucid and unified analysis. The present study is an attempt to provide clarity to this unusual but clinically important problem. We systematically reviewed all patient reports, patient series, and registries published on cancer transmission events through the end of December 2019. We identified a total of 67 publications with 92 transmission events. The most frequently transmitted cancers were lymphomas (30; 32.6%), melanomas (8; 8.7%), and neuroendocrine tumors (8; 8.7%). Most of the melanomas were metastasizing, whereas most of the lymphomas were localized to the graft. The median time to cancer diagnosis after transplantation was 7 months, with 78.1% of diagnoses established in the first year. Melanoma carried the worst prognosis, with no recipients alive at 1 year after cancer diagnosis. Lymphoma recipients had a better outcome, with more than 75% surviving at 2 years. A metastatic cancer carries a worse prognosis for recipients, and recipients with localized cancer can benefit from the chance to undergo transplantation again. The findings confirm the need to pay attention to donors with a history of melanoma but also suggest the need for a more careful evaluation of groups of donors, such as those dying from cerebral hemorrhage. Finally, recipients of organs from donors with cancer should be carefully followed to detect potential transmission.
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http://dx.doi.org/10.1002/lt.25858DOI Listing
January 2021

Basal total testosterone serum levels predict biopsy and pathological ISUP grade group in a large cohort of Caucasian prostate cancer patients who underwent radical prostatectomy.

Ther Adv Urol 2020 Jan-Dec;12:1756287220929481. Epub 2020 Jun 24.

Department of Urology, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale Civile Maggiore, Polo Chirurgico Confortini, Piazzale Stefani 1, 37126, Verona, Italy.

Aims: The study aimed to evaluate associations of preoperative total testosterone (TT) with the risk of aggressive prostate cancer (PCA).

Materials & Methods: From 2014 to 2018, basal TT levels were measured in 726 consecutive PCA patients. Patients were classified according to the International Society of Urologic Pathology (ISUP) system. Aggressive PCA was defined by the detection of ISUP > 2 in the surgical specimen. The logistic regression model evaluated the association of TT and other clinical factors with aggressive PCA.

Results: On univariate analysis, there was a significant association of basal TT with the risk of aggressive PCA as well as age, prostate-specific antigen (PSA), percentage of biopsy positive cores (BPC), tumor clinical stage (cT), and biopsy ISUP grade groups. On multivariate analysis, two models were considered. The first (model I) excluded biopsy ISUP grading groups and the second (model II) included biopsy ISUP grade groups. Multivariate model I, revealed TT as well as all other variables, was an independent predictor of the risk of aggressive disease [odds ratio (OR) = 1.585; 95% confidence interval (CI): 1.113-2.256;  = 0.011]. Elevated basal PSA greater than 20 µg/dl was associated with the risk of aggressive PCA. Multivariate model II revealed that basal TT levels maintain a positive association between aggressive PCA, whereas age, BPC, and clinical stage cT3 lost significance. In the final adjusted model, the level of risk of TT did not change from univariate analysis (OR = 1.525; 95% CI: 1.035-2.245;  = 0.011).

Conclusion: Elevated preoperative TT levels are associated with the risk of aggressive PCA in the surgical specimen. TT may identify patients who are at risk of aggressive PCA in the low and intermediate European Association of Urology (EAU) risk classes.
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http://dx.doi.org/10.1177/1756287220929481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318822PMC
June 2020

Obesity strongly predicts clinically undetected multiple lymph node metastases in intermediate- and high-risk prostate cancer patients who underwent robot assisted radical prostatectomy and extended lymph node dissection.

Int Urol Nephrol 2020 Nov 30;52(11):2097-2105. Epub 2020 Jun 30.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale Civile Maggiore, Polo Chirurgico Confortini, Piazzale Stefani 1, 37126, Verona, Italy.

Objective: To evaluate the association between obesity and risk of multiple lymph node metastases in prostate cancer (PCa) patients with clinically localized EAU intermediate and high-risk classes staged by extended pelvic lymph-node dissection (ePLND) during robot assisted radical prostatectomy (RARP).

Materials And Methods: 373 consecutive PCa intermediate or high-risk patients were treated by RARP and ePLND. According to pathology results, extension of LNI was classified as absent (pN0 status) or present (pN1 status); pN1 was further categorized as one or more than one (multiple LNI) lymph node metastases. A logistic regression model (univariate and multivariate analysis) was used to evaluate the association between significant categorized clinical factors and the risk of multiple lymph nodes metastases.

Results: Overall, after surgery lymph node metastases were detected in 51 patients (13.7%) of whom 22 (5.9%) with more than one metastatic lymph node and 29 (7.8%) with only one positive node. Comparing patients with one positive node to those without, EAU high-risk class only predicted risk of single LNI (OR = 2.872; p = 0.008). The risk of multiple lymph node metastases, when compared to cases without LNI, was independently predicted by BMI ≥ 30 (OR = 6.950; p = 0.002) together with BPC ≥ 50% (OR = 3.910; p = 0.004) and EAU high-risk class (OR = 6.187; p < 0.0001). Among metastatic patients, BMI ≥ 30 was the only factor associated with the risk of multiple LNI (OR = 5.250; p = 0.041).

Conclusions: In patients with clinically localized EAU intermediate and high-risk classes PCa who underwent RARP and ePLND, obesity was a risk factor of multiple LNI.
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http://dx.doi.org/10.1007/s11255-020-02554-3DOI Listing
November 2020

Digital pathology for second opinion consultation and donor assessment during organ procurement: Review of the literature and guidance for deployment in transplant practice.

Transplant Rev (Orlando) 2020 10 13;34(4):100562. Epub 2020 Jun 13.

Department of Pathology, UPMC Shadyside Hospital, University of Pittsburgh, Pittsburgh, PA, USA.

Telepathology has been an important application for second opinion consultation ever since the introduction of digital pathology. However, little is known regarding teleconsultation for second opinion in transplantation. There is also limited literature on telepathology during organ donor procurement, typically utilized when general pathologists on-call request back-up to help assess donor biopsies for organ suitability or to diagnose newly discovered tumors with urgent time constraints. In this review, we searched Pubmed/Embase and websites of transplant organizations to collect and analyze published evidence on teleconsultation for donor evaluation and organ procurement. Of 2725 records retrieved using the key terms 'telepathology', 'second opinion' and 'transplantation', 26 suitable studies were included. Most records were from North America and included validation studies of telepathology being used for remote frozen section interpretation of donor biopsies with whole slide imaging. The data from these published studies supports the transition towards digital teleconsultation in transplant settings where consultations among pathologists are still handled by pathologists being called on site, via telephone and/or email.
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http://dx.doi.org/10.1016/j.trre.2020.100562DOI Listing
October 2020

Prevalence of PD-L1 expression in head and neck squamous precancerous lesions: a systematic review and meta-analysis.

Head Neck 2020 Oct 22;42(10):3018-3030. Epub 2020 Jun 22.

Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.

Background: Studies concerning programmed death-ligand 1 (PD-L1) expression in precancerous lesions of head and neck (HN) region have shown variable results.

Methods: We systematically reviewed the published evidence on PD-L1 expression in HN precancerous lesions.

Results: Of 1058 original articles, 14 were included in systematic review and 9 in meta-analysis. The pooled estimate of PD-L1 expression was 48.25% (confidence interval [CI] 21.07-75.98, I 98%, tau2 0.18). PD-L1 expression appeared to be more frequent in precancerous lesions than in normal mucosa (risk ratio [RR] 1.65, CI 0.65-4.03, I 91%, tau2 0.82) and less frequent than in invasive squamous cell carcinoma (RR 0.68, CI 0.43-1.08, I 91%, tau2 0.22).

Conclusions: PD-L1 expression could reflect a point of balance between host immune response and cancer escape ability. High heterogeneity and moderate quality suggest that further studies with larger sample size and more rigorous case selection will allow more precise assessment of PD-L1 expression in HN precancerous lesions.
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http://dx.doi.org/10.1002/hed.26339DOI Listing
October 2020

Topological framework for directional amplification in driven-dissipative cavity arrays.

Nat Commun 2020 Jun 19;11(1):3149. Epub 2020 Jun 19.

Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, UK.

Directional amplification, in which signals are selectively amplified depending on their propagation direction, has attracted much attention as key resource for applications, including quantum information processing. Recently, several, physically very different, directional amplifiers have been proposed and realized in the lab. In this work, we present a unifying framework based on topology to understand non-reciprocity and directional amplification in driven-dissipative cavity arrays. Specifically, we unveil a one-to-one correspondence between a non-zero topological invariant defined on the spectrum of the dynamic matrix and regimes of directional amplification, in which the end-to-end gain grows exponentially with the number of cavities. We compute analytically the scattering matrix, the gain and reverse gain, showing their explicit dependence on the value of the topological invariant. Parameter regimes achieving directional amplification can be elegantly obtained from a topological 'phase diagram', which provides a guiding principle for the design of both phase-preserving and phase-sensitive multimode directional amplifiers.
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http://dx.doi.org/10.1038/s41467-020-16863-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305208PMC
June 2020

Serum testosterone and obesity in prostate cancer biology: a call for health promotion in the ageing male.

Aging Clin Exp Res 2020 Jun 17. Epub 2020 Jun 17.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Piazzale Stefani 1, 37126, Verona, Italy.

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http://dx.doi.org/10.1007/s40520-020-01625-wDOI Listing
June 2020

Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

Ther Adv Med Oncol 2020 26;12:1758835920915303. Epub 2020 May 26.

Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, Parma, 43126, Italy.

Background: Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC.

Methods: We conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible.

Results: In all, 15 studies were included in our analysis, including a total of 318 nccRCC patients treated with pazopanib. Most studies were retrospective ( = 12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5 months and median overall survival of 17.3-31.0 months. Grade 3-4 adverse events rates were 21-55%.

Conclusion: The present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.
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http://dx.doi.org/10.1177/1758835920915303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278098PMC
May 2020

Parvalbumin immunohistochemical expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.

Virchows Arch 2020 Jun 10. Epub 2020 Jun 10.

Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Largo L. Scuro 10, 37134, Verona, Italy.

Parvalbumin is a cytosolic calcium-binding protein expressed in the distal convoluted tubule of the renal nephron. Among epithelial renal tumors, the reactivity for parvalbumin is observed in chromophobe renal cell carcinomas and frequently in oncocytomas. On the other hand, there are no data available on parvalbumin expression in the mesenchymal tumors of the kidney. Therefore, the purpose of this study was to evaluate the expression of parvalbumin in the spectrum of PEC (perivascular epithelioid cells) lesions of the kidney. Sixty-six PEC lesions (37 classic angiomyolipomas, 10 microscopic angiomyolipomas, 7 epithelioid angiomyolipomas/pure epithelioid PEComas, 5 leiomyoma-like angiomyolipomas, 3 lipoma-like angiomyolipomas, 2 intraglomerular lesions, 1 angiomyolipoma with epithelial cysts (AMLEC), and 1 sclerosing angiomyolipoma) were immunohistochemically stained with parvalbumin. Overall, parvalbumin immunostain was found in fifty-six PEC lesions (85%) and absent in the remaining ten cases (15%). Classic angiomyolipomas were positive in almost all cases (97%). Intraglomerular lesions and AMLEC showed parvalbumin immunolabeling as well. None of the 7 epithelioid angiomyolipomas/pure epithelioid PEComas or the only sclerosing angiomyolipoma expressed parvalbumin. In conclusion, we demonstrated the immunolabeling of parvalbumin in almost all PEC lesions of the kidney, but not in the epithelioid angiomyolipoma/pure epithelioid PEComa. This finding could shed light on some biological characteristics observed in the PEC lesions such as the plasticity of their cellular component. Moreover, parvalbumin may be another useful tool in the differential diagnosis among epithelioid angiomyolipoma/pure epithelioid PEComa with other renal eosinophilic tumors, such as oncocytoma and chromophobe renal cell carcinoma.
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http://dx.doi.org/10.1007/s00428-020-02856-yDOI Listing
June 2020

Programmed Death-Ligand 1 (PD-L1) Is a Potential Biomarker of Disease-Free Survival in Papillary Thyroid Carcinoma: a Systematic Review and Meta-Analysis of PD-L1 Immunoexpression in Follicular Epithelial Derived Thyroid Carcinoma.

Endocr Pathol 2020 Sep;31(3):291-300

Department of Pathology and Diagnostics, University and Hospital Trust of Verona, P.le Stefani n. 1, 37126, Verona, Italy.

The expression of programmed death-ligand 1 (PD-L1) is an established prerequisite for the administration of checkpoint inhibitor therapy and is of prognostic value in several cancer types. Data concerning the potential effect of PD-L1 on the prognosis of thyroid carcinoma are limited. Therefore, this study aimed to provide a systematic review of the published data on this topic. The literature was reviewed to gather and quantify evidence on the prognostic role of PD-L1 in follicular epithelial derived thyroid carcinomas and determine its association with clinicopathological parameters. A meta-analysis was performed using the DerSimonian-Laird random-effects model. The quality of studies was evaluated with the Newcastle-Ottawa Scale and a modified GRADE approach used to rate the quality of evidence. Out of 445 papers, 18 were included and 15 provided adequate data for meta-analysis. The quality of evidence ranged from low to high. PD-L1 expression was significantly associated with a reduced disease-free survival (DFS) (RR 1.63, CI 1.04-2.56, p = 0.03, I 68%, τ 0.19 and HR 1.90, CI 1.33-2.70, p< 0.001, I 0%, τ 0.00); however, no association was found with the overall survival (OS). Furthermore, a significant association was found with respect to underlying chronic lymphocytic thyroiditis and BRAFV600E mutation status in papillary thyroid carcinomas. In the subgroup analysis, the association of PD-L1 and DFS remained strong in papillary thyroid carcinoma when compared with dedifferentiated thyroid carcinomas (anaplastic and poorly differentiated thyroid carcinomas) that failed to demonstrate a significant association with respect to PD-L1. These findings underscore the role of PD-L1 immunohistochemistry as a potential prognostic biomarker of disease recurrence in patients with papillary thyroid carcinoma.
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http://dx.doi.org/10.1007/s12022-020-09630-5DOI Listing
September 2020

Association between Basal Total Testosterone Levels and Prostate Cancer D'Amico Risk Classes.

Urol Int 2020 27;104(9-10):716-723. Epub 2020 May 27.

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy,

Objective: To test the hypothesis that basal total testosterone (TT) serum levels are associated with the D'Amico risk classification at diagnosis of prostate cancer (PCA).

Materials And Methods: From November 2014 to March 2018, preoperative basal levels of TT and prostate-specific antigen (PSA) were measured in 601 consecutive PCA patients who were not under androgen deprivation therapy or undergoing prior prostate surgery. Patients were classified into low (reference group), intermediate, and high risk classes according to biopsy findings. The association of TT and other clinical factors with risk classes was evaluated using a multivariate multinomial logistic regression model.

Results: According to the D'Amico classification, 124 patients (24%) were low risk, 316 (52.6%) were intermediate risk, and 141 (23.4%) were high risk. Median basal TT circulating levels were significantly increased along clinical risk classes. TT along with PSA, percentage of biopsy positive cores, and tumor clinical stage were independently associated with a high risk (OR = 1.002; p = 0.022) but not with an intermediate risk of PCA when compared to the low risk class. In the intermediate-risk group, endogenous TT together with PSA were independently associated with tumor grade groups 2 (OR = 1.003; p = 0.022) and 3 (OR = 1.003; p = 0.043) compared to grade group 1 cancers.

Conclusions: Basal TT levels are positively associated with the D'Amico risk classification, but the association is significant for the high-risk group compared to the low-risk group.
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http://dx.doi.org/10.1159/000506525DOI Listing
May 2020

Thyroid Fine-Needle Aspiration Cytology: Focusing on Adherence to Guidelines and Hospital Organization.

Am J Case Rep 2020 Apr 10;21:e920933. Epub 2020 Apr 10.

Pathology Unit, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.

BACKGROUND The complications of fine-needle aspiration cytology (FNAC) are rare but can be challenging for performing physicians to diagnose and manage. This type of procedure is perceived as routine and devoid of substantial risks, but uncommon complications can occur and need to be addressed with careful workup. CASE REPORT A FNAC procedure for a young female patient with multiple thyroid nodules was requested by her general practitioner. After the FNAC thyroid procedure, a carotid wall hematoma was suspected and could not be excluded with ultrasound (US) alone. Thus, the patient underwent a computed tomography angiogram (CTA) that excluded blood extravasation from the carotid, confirming the suspicion of perivascular blood accumulation. As a precaution, the patient was hospitalized, with US follow-up; she was dismissed the day after her hospital admission with a diagnosis of a benign thyroid nodule in multinodular goiter according to SIAPEC-IAP classification. CONCLUSIONS This case highlights how a routine-perceived procedure such as FNAC could present a challenge to the performing physicians, pathologist, and radiologist, raising the suspicion of a severe complication that needs to be addressed with a readily available emergency service that may be accessible only within a central hospital-level organization. This case reinforces the point that more careful adherence to clinic-radiological guidelines is needed to avoid potentially inappropriate and harmful procedures. A review of the literature concerning guidelines for FNAC procedure, diagnostic classifications, and reported complications is provided as part of this case report.
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http://dx.doi.org/10.12659/AJCR.920933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171366PMC
April 2020

Impact of image analysis and artificial intelligence in thyroid pathology, with particular reference to cytological aspects.

Cytopathology 2020 09 7;31(5):432-444. Epub 2020 May 7.

Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.

Objective: Thyroid pathology has great potential for automated/artificial intelligence algorithm application as the incidence of thyroid nodules is increasing and the indeterminate interpretation rate of fine-needle aspiration remains relatively high. The aim of the study is to review the published literature on automated image analysis and artificial intelligence applications to thyroid pathology with whole-slide imaging.

Methods: Systematic search was carried out in electronic databases. Studies dealing with thyroid pathology and use of automated algorithms applied to whole-slide imaging were included. Quality of studies was assessed with a modified QUADAS-2 tool.

Results: Of 919 retrieved articles, 19 were included. The main themes addressed were the comparison of automated assessment of immunohistochemical staining with manual pathologist's assessment, quantification of differences in cellular and nuclear parameters among tumour entities, and discrimination between benign and malignant nodules. Correlation coefficients with manual assessment were higher than 0.76 and diagnostic performance of automated models was comparable with an expert pathologist diagnosis. Computational difficulties were related to the large size of whole-slide images.

Conclusions: Overall, the results are promising and it is likely that, with the resolution of technical issues, the application of automated algorithms in thyroid pathology will increase and be adopted following suitable validation studies.
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http://dx.doi.org/10.1111/cyt.12828DOI Listing
September 2020

Elevated prostate volume index and prostatic chronic inflammation reduce the number of positive cores at first prostate biopsy set: results in 945 consecutive patients.

Int Braz J Urol 2020 Jul-Aug;46(4):545-556

Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.

Objective: To assess the association between prostate volume index (PVI), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA). PVI is the ratio between the central transition zone volume (CTZV) and the peripheral zone volume (PZV).

Materials And Methods: Parameters evaluated included age, prostate specific antigen (PSA), total prostate volume (TPV), PSA density (PSAD), digital rectal exam (DRE), PVI, PCI and number of positive cores (NPC). All patients underwent baseline 14-core, trans-perineal random biopsies. Associations of parameters with the NPC were investigated by univariate and multivariate linear regression analysis.

Results: Between September 2010 to September 2017, 945 patients were evaluated. PCA was detected in 477 cases (50.7%), PCI in 205 cases (21.7%). PCA patients, compared to negative cases, were older (68.3 vs. 64.4 years) with smaller TPV (36 vs. 48.3mL) and CTZV (19.2 vs. 25.4), higher PSAD (0.24 vs. 0.15ng/mL/mL), further PVI values were lower (0.9 vs. 1.18) and biopsy cores less frequently involved by PCI (9.4% vs. 34.2%). High PVI and the presence of PCI were independent negative predictors of NPC in model I considering PSA and TVP (PVI, regression coefficient, RC -0,6; p=0.002) and PCI (RC -1,4; p<0.0001); and in model II considering PSAD (PVI:RC -0,7; p<0,0001; and PCI: RC -1,5; p<0.0001).

Conclusions: High PVI and the presence of PCI lowered the mean rate of NPC and is associated with less aggressive tumor biology expressed by low tumor burden. PVI can give prognostic information before planning baseline random biopsies. Confirmatory studies are required.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2019.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239280PMC
December 2020