ABSTRACT
BACKGROUND: Self-collection of cervical samples to detect high-risk human papillomavirus (hr-HPV) is a trending topic in primary cervical cancer screening. This study evaluates the applicability of a self-sampling device to routine molecular procedures for hr-HPV detection. METHODS: In a primary health care facility in Kinshasa, Congo, 187 self-collected samples (Evalyn Brush) were gathered and sent to Ghent University Hospital (UZ Ghent) and Algemeen Medisch Labo (AML) in Belgium where routine tests for hr-HPV were applied (Abbott RealTime hr-HPV and qPCR (E6/E7), respectively). Sample type effect was evaluated by comparing the internal control (IC) between the self-collected samples and routine, clinician-taken samples randomly selected from the UZ Ghent archive. RESULTS: In UZ Ghent an error was encountered in 9.1% (17/187) of self-collected samples due to a lack of IC signal. The hr-HPV prevalence in the remaining 170 samples was 18,8%. Comparing IC results between the self-collected and clinician-collected groups, a significant difference (p < 0,001) was found, with higher IC signals in the clinician-collected group. In AML, an error was encountered in 17.6% (33/187) of samples, including 16/17 of the UZ Ghent. The remaining sample with IC error gave a negative result in AML. Among the 154 samples without IC error at AML, a correlation of 90% was seen between both laboratories with a 77% negativity rate. CONCLUSION: Testing the self-collected specimens by 2 routine hr-HPV tests gave a high IC error rate (9.1-17.6%). A possible solution would be to differentiate cut-offs for IC values depending on sample type, as currently used cut-offs are set for clinician-taken samples.
Subject(s)
Leukemia, Myeloid, Acute , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Human Papillomavirus Viruses , Papillomavirus Infections/diagnosis , Early Detection of Cancer/methods , Papillomaviridae , Democratic Republic of the Congo , Specimen Handling/methods , Sensitivity and SpecificityABSTRACT
CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats. Wistar rats were divided in 3 groups. Group 1 (n = 6) had free access to drinking water (control group). Group 2 (n = 8) was water deprived for 10 h per 24 h, 5 days/week and placed in an incubator (37 °C) for 30 min/h during water deprivation. Group 3 (n = 8) underwent daily oral gavage with cyclosporine (40 mg/kg body weight). After 28 days, renal function, histopathology and proteomic signatures were analysed. Cyclosporine-treated rats developed focal regions of atrophic proximal tubules with associated tubulo-interstitial fibrosis. PASM staining revealed enlarged argyrophilic granules in affected proximal tubules, identified as lysosomes by immunofluorescent staining. Electron microscopy confirmed the enlarged and dysmorphic phenotype of the lysosomes. Overall, these kidney lesions resemble those that have been previously documented in farmers with CINAC. Dehydration resulted in none of the above histopathological features. Proteomic analysis revealed that dehydration and cyclosporine both induce injury pathways, yet of a clear distinct nature with a signature of toxicity only for the cyclosporine group. In conclusion, both cyclosporine and dehydration are injurious to the kidney. However, dehydration alone does not result in kidney histopathology as observed in CINAC patients, whereas cyclosporine administration does. The histopathological analogy between CINAC and calcineurin inhibitor nephrotoxicity in rats and humans supports the involvement of an as-yet-unidentified environmental toxin in CINAC etiology.
Subject(s)
Nephritis, Interstitial , Renal Insufficiency , Humans , Rats , Animals , Dehydration/metabolism , Calcineurin Inhibitors , Proteomics , Rats, Wistar , Nephritis, Interstitial/pathology , Kidney/metabolism , Cyclosporine/pharmacology , Renal Insufficiency/pathology , Immunosuppressive Agents/pharmacologyABSTRACT
The implementation of cervical screening based on human papillomavirus (HPV) continues to progress rapidly across countries. Evidence has shown that assays detecting high-risk human papillomavirus (hrHPV) deoxyribonucleic acid (DNA) are more effective than cytology-based screening. Validation of new hrHPV DNA assays requires both noninferior clinical accuracy compared to a standard comparator for cervical precancer and good reproducibility. This study builds upon previous diagnostic accuracy assessments of the RIATOL HPV genotyping qPCR assay and aims to evaluate the international validation criteria for reproducibility. The intra- and interreproducibility of the RIATOL-qPCR assay were assessed using 550 remnant cervical cell material from the cytology archive of the National Reference Center for HPV in Belgium. Specimens were collected in the context of cervical cancer screening and tested in two different laboratories. The international reproducibility criteria include the lower bound of 95% confidence interval of the intra- and interlaboratory agreement regarding the detection of hrHPV DNA exceeding 87% with kappa ≥0.50. The RIATOL-qPCR assay demonstrated excellent intralaboratory reproducibility, achieving an overall agreement of 98.2 (95% CI 96.6-99.1%) and a kappa of 0.96. Interlaboratory testing showed an overall agreement of 98.5 (95% CI 97.1-99.4%) with a kappa of 0.97. The RIATOL-qPCR assay fulfills the third criterion for HPV test reproducibility requirement for use in cervical cancer screening.
Subject(s)
Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Early Detection of Cancer , Uterine Cervical Neoplasms/diagnosis , Genotype , Papillomavirus Infections/diagnosis , Reproducibility of Results , Papillomaviridae/genetics , Human Papillomavirus Viruses , DNAABSTRACT
We describe the case of a woman with minimal glomerular changes on initial kidney biopsy. On long-term follow-up, the patient developed nephrotic proteinuria and a second kidney biopsy was performed, which revealed focal segmental glomerulosclerosis (FSGS). Findings from electron microscopy (EM) examination suggested a genetic form of FSGS. Next-generation sequencing showed heterozygosity for a mutation in COL4A3. Collagen IV nephropathies can be linked to late-onset FSGS. By establishing a genetic cause of FSGS, immunosuppressive treatment can be avoided. This case emphasizes the importance of re-biopsy in cases of a non-explained rise in proteinuria. EM can be helpful in differentiating between primary and secondary FSGS and informing treatment strategies. In cases of adult-onset FSGS that cannot be categorized by clinical-pathological assessment, genetic testing should be considered.
ABSTRACT
Hippocampal sclerosis (HS) is a common neuropathological finding and has been associated with advanced age, TDP-43 proteinopathy, and cerebrovascular pathology. We analyzed neuropathological data of an autopsy cohort of early-onset frontotemporal dementia patients. The study aimed to determine whether in this cohort HS was related to TDP-43 proteinopathy and whether additional factors could be identified. We examined the relationship between HS, proteinopathies in frontotemporal cortices and hippocampus, Alzheimer disease, cerebrovascular changes, and age. We confirmed a strong association between HS and hippocampal TDP-43, whereas there was a weaker association between HS and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Nearly all of the FTLD-TDP cases had TDP-43 pathology in the hippocampus. HS was present in all FTLD-TDP type D cases, in 50% of the FTLD-TDP A cohort and in 6% of the FTLD-TDP B cohort. Our data also showed a significant association between HS and vascular changes. We reviewed the literature on HS and discuss possible pathophysiological mechanisms between TDP-43 pathology, cerebrovascular disease, and HS. Additionally, we introduced a quantitative neuronal cell count in CA1 to objectify the semiquantitative visual appreciation of HS.
Subject(s)
Cerebrovascular Disorders/pathology , Frontotemporal Dementia/pathology , Hippocampus/pathology , Neurodegenerative Diseases/pathology , Aged , Aged, 80 and over , Cerebrovascular Disorders/metabolism , Cohort Studies , DNA-Binding Proteins/metabolism , Female , Frontotemporal Dementia/metabolism , Hippocampus/metabolism , Humans , Male , Middle Aged , Neurodegenerative Diseases/metabolism , Retrospective Studies , SclerosisABSTRACT
OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500âµg), followed by a 2.5 mL/h infusion (somatostatin: 250âµg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.
Subject(s)
End Stage Liver Disease/complications , End Stage Liver Disease/surgery , Hormones/therapeutic use , Hypertension, Portal/drug therapy , Liver Transplantation , Somatostatin/therapeutic use , Aged , Double-Blind Method , End Stage Liver Disease/physiopathology , Female , Humans , Hypertension, Portal/complications , Male , Middle Aged , Portal Pressure , Treatment OutcomeSubject(s)
Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Female , Humans , Middle Aged , Neoplasm Grading , Papillomavirus Infections/pathology , Papillomavirus Infections/virology , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virologyABSTRACT
OBJECTIVES: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, for which treatment is often limited to palliative combination chemotherapy. Multimodality-therapy, including radical surgery, is largely restricted to clinical trials, leaving its benefit currently unclear. This study aimed to get a comprehensive view on real-world MPM treatment at the Belgian population level, to assess survival and to identify prognostic factors. MATERIALS AND METHODS: The study period covered the incidence years 2004-2012 (N = 1453). Starting from the Belgian Cancer Registry, additional information regarding patient characteristics, diagnosis and treatment was retrieved from multiple data sources. Adjusted cox proportional-hazard regression models using time-dependent covariates were performed to assess survival in relation to treatment patterns and centre volume. RESULTS: Sixty-nine percent of patients underwent tumour-directed treatment, mostly cisplatin-pemetrexed chemotherapy. Radical surgery was mainly performed in younger patients with epithelioid subtype. Centre volume, surgery and chemotherapy showed a positive relation with survival in univariable analyses, but only chemotherapy remained significantly relevant in multivariable analyses. Younger patients, females, and epithelioid subtypes also independently had a better survival. CONCLUSION: This large population-based study provides insights in MPM treatment practice in Belgium. Centre volume and surgery being related to survival in univariable analyses, only chemotherapy remained prognostic after adjustment.
Subject(s)
Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Aged , Belgium , Cisplatin/therapeutic use , Combined Modality Therapy/methods , Drug Therapy, Combination/methods , Female , Humans , Incidence , Lung Neoplasms/economics , Male , Mesothelioma/economics , Mesothelioma, Malignant , Pemetrexed/therapeutic use , Prognosis , Proportional Hazards Models , RegistriesABSTRACT
OBJECTIVES: Malignant mesothelioma (MM) is a rare and aggressive cancer mostly caused by asbestos exposure, and for which the diagnosis is difficult. This study aimed to assess the completeness and correctness of MM registration using 3 independent national databases: the Belgian Cancer Registry (BCR), the population-based mortality statistics (certificates of death, COD), and the Belgian Mesothelioma Registry (BMR). METHODS: The study cohort included all MM reported to the BCR and diagnosed between 2004 and 2012 (nâ¯=â¯2292), all patients reviewed by the pathology commission of the BMR (2004-2012; nâ¯=â¯2019), and COD data for all Belgian citizens (2004-2013). Available data were compared in terms of registered cases, histological diagnosis, performed immunohistochemical (IHC) tests, and IHC test results. RESULTS: Comparison of BCR with BMR registrations showed 94.8% concordant cases. The proportion of MM diagnoses originally reported to BCR with unspecified MM morphology was reduced from 25.8% to less than 1%. RESULTS: from IHC tests were available for 95.3% of concordant MM cases. Different IHC patterns could be distinguished by MM histology. MM cases registered at BCR for which COD mentioned an MM as underlying cause of death represented 76.4% of deceased cases. MM long-term survivors (survival >3â¯years; 10.9%) were characterised by distinct clinical and biological characteristics. CONCLUSIONS: A comparison of independent Belgian MM registration databases elucidated under-registration and misclassification and revealed possible reasons for observed discordances. Combining all the available information resulted in enhanced completeness and correctness of MM registration in Belgium and allowed for the identification and characterisation of MM long-term survivors.
Subject(s)
Asbestos/adverse effects , Databases, Factual , Lung Neoplasms/epidemiology , Mesothelioma/epidemiology , Registries/statistics & numerical data , Aged , Belgium/epidemiology , Cohort Studies , Female , Humans , Lung Neoplasms/mortality , Male , Mesothelioma/mortality , Mesothelioma, Malignant , Middle Aged , Survival Analysis , SurvivorsABSTRACT
Peritoneal metastasis is a major cause of death and preclinical models are urgently needed to enhance therapeutic progress. This study reports on a hybrid hydrogel-polylactic acid (PLA) scaffold that mimics the architecture of peritoneal metastases at the qualitative, quantitative and spatial level. Porous PLA scaffolds with controllable pore size, geometry and surface properties are functionalized by type I collagen hydrogel. Co-seeding of cancer-associated fibroblasts (CAF) increases cancer cell adhesion, recovery and exponential growth by in situ heterocellular spheroid formation. Scaffold implantation into the peritoneum allows long-term follow-up (>14 weeks) and results in a time-dependent increase in vascularization, which correlates with cancer cell colonization in vivo. CAF, endothelial cells, macrophages and cancer cells show spatial and quantitative aspects as similarly observed in patient-derived peritoneal metastases. CAF provide long-term secretion of complementary paracrine factors implicated in spheroid formation in vitro as well as in recruitment and organization of host cells in vivo. In conclusion, the multifaceted heterocellular interactions that occur within peritoneal metastases are reproduced in this tissue-engineered implantable scaffold model.
Subject(s)
Peritoneal Neoplasms , Tissue Scaffolds , Tumor Microenvironment , Animals , Biomimetics , Cell Line, Tumor , Coculture Techniques , Female , Humans , Mice , Polyesters/chemistry , Tissue Engineering , Tissue Scaffolds/chemistryABSTRACT
BACKGROUND: In this paper, we describe the clinical and neuropathological findings of nine members of the Belgian progranulin gene (GRN) founder family. In this family, the loss-of-function mutation IVS1 + 5G > C was identified in 2006. In 2007, a clinical description of the mutation carriers was published that revealed the clinical heterogeneity among IVS1 + 5G > C carriers. We report our comparison of our data with the published clinical and neuropathological characteristics of other GRN mutations as well as other frontotemporal lobar degeneration (FTLD) syndromes, and we present a review of the literature. METHODS: For each case, standardized sampling and staining were performed to identify proteinopathies, cerebrovascular disease, and hippocampal sclerosis. RESULTS: The neuropathological substrate in the studied family was compatible in all cases with transactive response DNA-binding protein (TDP) proteinopathy type A, as expected. Additionally, most of the cases presented also with primary age-related tauopathy (PART) or mild Alzheimer's disease (AD) neuropathological changes, and one case had extensive Lewy body pathology. An additional finding was the presence of cerebral small vessel changes in every patient in this family. CONCLUSIONS: Our data show not only that the IVS1 + 5G > C mutation has an exclusive association with FTLD-TDP type A proteinopathy but also that other proteinopathies can occur and should be looked for. Because the penetrance rate of the clinical phenotype of carriers of GRN mutations is age-dependent, further research is required to investigate the role of co-occurring age-related pathologies such as AD, PART, and cerebral small vessel disease.
Subject(s)
Frontotemporal Lobar Degeneration/genetics , Loss of Function Mutation , Progranulins/genetics , Aged , Brain/diagnostic imaging , Brain/pathology , Cerebrovascular Disorders/diagnostic imaging , Cerebrovascular Disorders/genetics , Cerebrovascular Disorders/pathology , Family , Female , Frontotemporal Lobar Degeneration/diagnostic imaging , Frontotemporal Lobar Degeneration/pathology , Heterozygote , Humans , Male , Middle Aged , Pedigree , PhenotypeABSTRACT
OBJECTIVE: Human papillomavirus (HPV) testing is widely incorporated into cervical cancer screening strategies. Current screening requires pelvic examination for cervical sampling, which may compromise participation. The acceptance could be raised by introducing testing on vaginal swabs. We explored the interchangeability of vaginal swabs and cervical smears for HPV testing, by means of a prospective study conducted in female sex workers (FSWs). Besides, we report on the occurrence of 32 different HPV genotypes in FSW with low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL). METHODS: Paired physician-collected vaginal swabs and cervical smears from 303 FSW were tested for HPV using the Abbott RealTime High-Risk HPV assay. Cervical cytology was examined on cervical smears. In case of HSIL/LSIL cytological classification (n=52), both samples were genotyped using INNO-LiPa HPV Genotyping Extra II. RESULTS: The overall prevalence of high-risk (HR)-HPV was 51%. In FSW with HSIL/LSIL cervical cytology, the sensitivity and specificity of vaginal samples for the detection of HR-HPV was 100% and 70% and for probable HR-HPV 100% and 91%. The mean number of genotypes identified in vaginal samples (mean=3.5; 95% confidence interval [CI]=2.8-4.2) was significantly higher than in cervical smear samples (mean=2.6; 95% CI=2.1-3.0) (p=0.001). The most frequently encountered HR-HPV genotypes were HPV16, 31, 51, and 52. CONCLUSION: As our study shows that vaginal swabs are equivalent to cervical smears for the detection of (probable) HR-HPV, vaginal swabs can be used for HPV testing in cervical cancer screening strategies. Given the acceptance of vaginal sampling, this finding offers an opportunity to boost screening coverage.
Subject(s)
Cervix Uteri/pathology , Human Papillomavirus DNA Tests , Molecular Typing , Vagina/pathology , Vaginal Smears , Virology , Adult , Cervix Uteri/virology , DNA, Viral/analysis , Early Detection of Cancer/methods , Early Detection of Cancer/standards , Female , Human Papillomavirus DNA Tests/methods , Human Papillomavirus DNA Tests/standards , Humans , Middle Aged , Molecular Typing/methods , Molecular Typing/standards , Papanicolaou Test , Papillomaviridae/genetics , Papillomavirus Infections/diagnosis , Sensitivity and Specificity , Sex Workers , Squamous Intraepithelial Lesions of the Cervix/diagnosis , Squamous Intraepithelial Lesions of the Cervix/virology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Vagina/virology , Vaginal Smears/methods , Vaginal Smears/standards , Virology/methods , Virology/standards , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/virologyABSTRACT
OBJECTIVES: To describe the effects of cytoreductive nephrectomy (CN) on the natural course of metastatic renal cell carcinoma (mRCC). CN appears to stabilize metastatic lesions in mRCC in a subgroup of patients and we hypothesize that systemic treatment might be deferred in these patients with stable disease after CN. SUBJECTS AND METHODS: Overall, 45 patients with mRCC who underwent CN and subsequent oncologic follow-up were included in this retrospective, single-center analysis. After CN, patients were followed at least every 3 months with clinical evaluation, contrast-enhanced computerized tomography scan of chest and abdomen, with additional imaging if needed. At 3 months, patients were radiographically evaluated and categorized into nonresponders (death or progression) or responders (stable disease or remission). Kaplan-Meier and Cox proportional hazards regression statistics were used to describe prognostic factors for overall survival (OS) and systemic therapy-free survival (STFS). RESULTS: Median OS was 31(3-121) months. Further, 24 (53.3%) and 21 (46.7%) patients were classified as responders and nonresponders at 3 months, respectively. Responders had a significant better 2-year OS compared with nonresponders (81.7% vs. 26.5%, P = 0.005). Responders also had a better 2-year STFS (40.3% vs. 6.3%, P = 0.005). On Cox regression analysis, worse OS was found to be associated with low preoperative hemoglobin levels, the absence of postoperative radiographical response, and the presence of non-clear cell pathology. The presence of postoperative radiographical response, normal preoperative lactate dehydrogenase levels, the presence of a single metastasis, and performing metastasis-directed therapy was found to be associated with a longer systemic therapy-free period. CONCLUSION: A beneficial oncologic response is observed in approximately half of the patients undergoing CN. Absence of radiographic progression at 3 months is an important marker for OS and STFS. Therefore, systemic treatment might be postponed in selected patients.
Subject(s)
Carcinoma, Renal Cell/surgery , Cytoreduction Surgical Procedures/mortality , Kidney Neoplasms/surgery , Nephrectomy/mortality , Aged , Carcinoma, Renal Cell/secondary , Female , Follow-Up Studies , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Patient Selection , Prognosis , Retrospective Studies , Survival RateABSTRACT
OBJECTIVES: To evaluate the androgen receptor (AR) gene copy number in androgen deprivation therapy (ADT) treatment-naïve prostate cancer (PCa) patients and to evaluate the corresponding AR protein expression and assess the association between these features and prognostic factors. MATERIALS AND METHODS: Chromosome X and AR gene copy number, using fluorescence-in-situ-hybridization, and epithelial-stromal AR expression, using AR immunohistochemistry, were analyzed in 62 ADT treatment-naïve PCa patients and 8 castration-refractory patients. RESULTS: In ADT treatment-naïve PCa patients, the AR expression was higher in tumor epithelial cells versus surrounding stromal cells (p < 0.001) and versus normal epithelium in the same patient (p = 0.043). The difference between tumoral AR expression and expression in normal epithelium was higher in patients with ≥15% of tumor cells with increased AR copy number (p = 0.019). Peritumoral stroma had lower AR expression in patients with lymph-node or distant metastases compared to those without metastases (p = 0.038). CONCLUSIONS: This research evaluates the link between AR gene status, expression profile, and possible prognostic factors. Furthermore, it highlights the importance of the peritumoral environment in PCa. Additional research is needed to further clarify the role of stromal AR in PCa dissemination and identify possible therapeutic strategies to target this mechanism.
Subject(s)
Biomarkers, Tumor/genetics , DNA Copy Number Variations , Gene Dosage , Prostatic Neoplasms/genetics , Receptors, Androgen/genetics , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Chromosomes, Human, X , Epithelial Cells/chemistry , Epithelial Cells/pathology , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostatic Neoplasms/chemistry , Prostatic Neoplasms/pathology , Receptors, Androgen/analysis , Stromal Cells/chemistry , Stromal Cells/pathologyABSTRACT
OBJECTIVES: To identify the multiparametric magnetic resonance imaging (mpMRI) characteristics of normal, benign and malignant conditions in the prostate. METHODS: Fifty-six histopathological whole-mount radical prostatectomy specimens from ten randomly selected patients with prostate cancer (PC) were matched with corresponding transverse mpMRI slices. The mpMRI was performed prior to biopsy and consisted of T2-weighted imaging (T2-WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE) and magnetic resonance spectroscopic imaging (MRSI). RESULTS: In each prostate specimen, a wide range of histopathological conditions were observed. They showed consistent but overlapping characteristics on mpMRI. Normal glands in the transition zone showed lower signal intensity (SI) on T2-WI, lower ADC values and lower citrate peaks on MRSI as compared to the peripheral zone (PZ) due to sparser glandular elements and more prominent collagenous fibres. In the PZ, normal glands were iso-intense on T2-WI, while high SI areas represented cystic atrophy. Mimickers of well-differentiated PC on mpMRI were inflammation, adenosis, HG-PIN and post-atrophic hyperplasia. CONCLUSION: Each prostate is a unique mix of normal, benign and/or malignant areas that vary in extent and distribution resulting in very heterogeneous characteristics on mpMRI. Understanding the main concepts of this mpMRI-histopathological correlation may increase the diagnostic confidence in reporting mpMRI. KEYPOINTS: ⢠In each prostate specimen a wide range of histopathological conditions was observed. ⢠Interpretation of mpMRI may be difficult because benign conditions may mimic PC. ⢠High signal intensity areas in the PZ on T2-WI represented cystic atrophy. ⢠The TZ showed sparser glands and more collagenous fibres than the PZ.
Subject(s)
Prostate/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Aged , Biopsy , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging/methods , Humans , Image Enhancement/methods , Kallikreins/analysis , Magnetic Resonance Imaging/methods , Male , Middle Aged , Prostate/pathology , Prostate-Specific Antigen/analysis , Prostatectomy/methods , Prostatic Hyperplasia/diagnostic imaging , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgeryABSTRACT
We describe a 43-year-old patient with subacute appearance of neurological and atypical complaints of anergia, anorexia and weight loss six months earlier. In spite of several admissions in different hospitals, no underlying somatic cause could be found and he was admitted to a psychiatric hospital with a tentative diagnosis of major depressive disorder. Subsequently, he was referred to the unit of medically unexplained physical symptoms within the department of general internal medicine for assessment by the psychiatrist, involved in this programme. Based on clinical suspicion and red flag symptoms such as involuntary weight loss, a broader internal medicine reassessment, including FDG whole-body PET-CT was requested. Neurological clinical exam showed minor deviations, but neither brain imaging nor a lumbar puncture were contributory. However, FDG PET-CT revealed abnormal moderately to intensely FDG positive lymph nodes in the retroperitoneum. Laparoscopic lymph node biopsy indicated germ cell tumour metastasis. Anti-NMDA antibody positivity allowed a diagnosis of paraneoplastic anti-NMDA encephalitis. Treatment of the underlying disease, a pure seminoma stadium II, consisting of orchidectomy and chemotherapy, resulted in a spectacular regression of 'psychosomatic' symptoms with long-term ability to return to work, and documented disappearance of the anti-NMDA antibody response.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Seminoma/diagnosis , Testicular Neoplasms/diagnosis , Adult , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/etiology , Humans , Lymphatic Metastasis , Male , Psychophysiologic Disorders/diagnostic imaging , Retroperitoneal Space/pathology , Seminoma/complications , Seminoma/pathology , Testicular Neoplasms/complications , Testicular Neoplasms/pathologyABSTRACT
OBJECTIVE: This study aimed to evaluate whether circulating levels and/or visceral adipose tissue (VAT) expression of recently described adipokines associate with histopathological severity of nonalcoholic fatty liver disease (NAFLD), independent of obesity and insulin resistance. METHODS: Serum levels of adiponectin, omentin, chemerin, monocyte chemoattractant protein-1, and secreted frizzled-related protein 4 were measured using enzyme-linked immunosorbent assay in 81 patients with obesity and NAFLD and 18 lean control subjects. Expression in VAT was measured using real-time PCR and histopathological grading was scored using the NAFLD activity score (NAS). RESULTS: When NAFLD patients were subdivided into groups with simple steatosis, borderline nonalcoholic steatohepatitis (NASH), and NASH, adiponectin serum levels and omentin expression were lower in NASH versus simple steatosis patients. Serum adiponectin was generally lower with higher histopathological grading. Chemerin VAT expression was negatively associated with NAS (r = -0.331, P = 0.022) and steatosis score (r = -0.335, P = 0.020), independent of age, BMI, and HOMA-IR. In addition, adjusting for chemerin VAT expression in a multivariate model explained part of the association between NAS and HOMA-IR. CONCLUSIONS: These findings suggest that lower VAT expression of chemerin in patients with obesity may be involved in the pathophysiology of hepatic steatosis, potentially by modulating the link between insulin resistance and NAFLD.
Subject(s)
Chemokines/blood , Intercellular Signaling Peptides and Proteins/blood , Intra-Abdominal Fat/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/metabolism , Adipokines/blood , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Insulin Resistance , Male , Middle Aged , Severity of Illness IndexABSTRACT
PURPOSE: The purpose of this study was to evaluate the effectiveness on function preservation and tumor control of the treatment of glomus tympanicum tumors with pre-operative embolization followed by total surgical resection. MATERIAL AND METHODS: We describe a series of 6 patients with a glomus tympanicum tumor who were treated in our hospital using the same technique: the day before surgery selective tumor embolization due to denaturation with 96% ethanol. Following parameters were considered: tumor classification, tumor control, clinical and audiological outcome, effectiveness of embolization, percentage of tumor necrosis and treatment complications. RESULTS: There were no severe complications due to embolization or surgery. Tumor blush disappeared completely in 5 patients on DSA post embolization and histologic evaluation of the resected tissue showed a median of 69.2% of tumor necrosis. Pulsatile tinnitus disappeared in all patients and 3 patients had no symptoms at all. Hearing ameliorated in 4 patients, 1 patient without hearing loss pre- treatment still had normal hearing after treatment and 1 patient's hearing was worse after treatment. Average follow-up was 21.3months. CONCLUSIONS: Treatment of glomus tympanicum tumors by pre-operative embolization with ethanol and surgical resection has not been described before. Our results show that it is a safe procedure with a good long term tumor control, good clinical and audiological outcome.
Subject(s)
Embolization, Therapeutic , Glomus Tympanicum Tumor/surgery , Aged , Combined Modality Therapy , Female , Hearing , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies , Treatment OutcomeABSTRACT
Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1-c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)-both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD.
Subject(s)
Anemia/genetics , Heterozygote , Kidney Diseases/genetics , Mutation , SEC Translocation Channels/genetics , Adult , Aged , Alleles , Amino Acid Sequence , Animals , Biopsy , Child , Chronic Disease , Disease Progression , Endoplasmic Reticulum/metabolism , Exome/genetics , Female , Fetal Growth Retardation/genetics , Genes, Dominant , Golgi Apparatus/metabolism , Humans , Infant, Newborn , Kidney Diseases/pathology , Male , Middle Aged , Models, Molecular , Mutation, Missense/genetics , Neutropenia/genetics , Pedigree , Phenotype , RNA, Messenger/analysis , RNA, Messenger/genetics , SEC Translocation Channels/chemistry , Syndrome , Young Adult , Zebrafish/embryology , Zebrafish/geneticsABSTRACT
Poorly differentiated synovial sarcoma (PDSS) is a less common subtype of synovial sarcoma (SS) associated with a poor prognosis. We present a case of a SS with a poorly differentiated component that resembles Ewing sarcoma (ES). Initial immunohistochemical staining revealed a characteristic and strong expression of transducin-like enhancer of split 1 (TLE1) and weak to absent expression of integrase integrator 1 (INI1) staining. Stainings for keratin and epithelial membrane antigen (EMA) were negative in the tumoral lesion. Fluorescence In Situ Hybridization (FISH) analysis showed a rearrangement of the synaptotagmin (SYT) gene, confirming the diagnosis of SS. FISH analysis for the EWS RNA-binding protein 1 (EWSR1) gene revealed monoallelic loss of EWSR1. This finding was confirmed by an array comparative genomic hybridization (aCGH), showing complete loss of chromosome 22. Based on literature review, showing only a handful of cases of cytogenetically studied SS with loss of chromosome 22, this is probably a rare event in SS. Therefore, we assume that monoallelic loss of chromosome 22 cannot fully elaborate the underlying mechanism of the INI1 staining pattern in all SS, but it could account for the weak to absent INI1 staining in at least some cases.