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1.
Biomark Res ; 12(1): 75, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090707

ABSTRACT

Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions.Ki67 immunoscore, GSTP1 and KLF8 promoter methylation levels (me) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms).Higher Ki67 index correlated with worse BCR-free survival, whereas higher KLF8me levels were associated with improved overall survival, especially in patients with lower-grade tumors. GSTP1me levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator - ProstARK (including Ki67 and clinicopathologic parameters) - disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability.Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results.

2.
Histopathology ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075659

ABSTRACT

AIMS: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. METHODS AND RESULTS: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. CONCLUSION: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.

3.
J Pathol ; 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39072726

ABSTRACT

Brain metastases are one of the most serious clinical problems in breast cancer (BC) progression, associated with lower survival rates and a lack of effective therapies. Thus, to dissect the early stages of the brain metastatic process, we studied the impact of brain organotropic BC cells' secretomes on the establishment of the brain pre-metastatic niche (PMN). We found that BC cells with specific tropism to the brain caused significant blood-brain barrier (BBB) disruption, as well as microglial activation, in both in vitro and in vivo models. Further, we searched for a brain-organotropic metastatic signature, as a promising source for the discovery of new biomarkers involved in brain metastatic progression. Of relevance, we identified VGF (nerve growth factor inducible) as a key mediator in this process, also impacting the BBB and microglial functions both in vitro and in vivo. In a series of human breast tumors, VGF was found to be expressed in both cancer cells and the adjacent stroma. Importantly, VGF-positive tumors showed a significantly worse prognosis and were associated with HER2 (human epidermal growth factor receptor 2) overexpression and triple-negative molecular signatures. Further clinical validation in primary tumors from metastatic BC cases showed a significant association between VGF and the brain metastatic location, clearly and significantly impacting on the prognosis of BC patients with brain metastasis. In conclusion, our study reveals a unique secretome signature for BC with a tropism for the brain, highlighting VGF as a crucial mediator in this process. Furthermore, its specific impact as a poor prognostic predictor for BC patients with brain metastasis opens new avenues to target VGF to control the progression of brain metastatic disease. © 2024 The Pathological Society of Great Britain and Ireland.

5.
Hum Pathol ; 148: 66-71, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38782099

ABSTRACT

Spermatocytic tumors are rare testicular tumors occurring predominantly in older men. Most show a classical tripartite morphology (different from seminoma) and are benign. However, well-documented cases of malignant spermatocytic tumors exist. Our previous work showed that a subset of spermatocytic tumors exhibiting TP53 mutations, DNA methylation profiles closer to seminomas, and/or gains in chromosome 12p exhibited aggressive characteristics, including sarcomatoid transformation and metastatic dissemination. The microRNA-371-373 cluster is a promising biomarker which is upregulated in non-teratoma germ cell tumors with malignant behavior. In this work we analyze microRNAs-371-373 b y quantitative real-time polymerase chain reaction in 18 spermatocytic tumors representative of the whole clinical spectrum, including 6 with aggressive features (sarcomatoid transformation, metastases, or gains in chromosome 12p). The levels of microRNAs-371-373 were significantly higher in non-teratoma germ cell tumors compared to spermatocytic tumors, overall (p < 0.0001). Importantly, levels of microRNA-371-373 were higher in spermatocytic tumors with aggressive features compared to non-aggressive neoplasms. The highest levels were observed in one tumor showing isochromosome 12p. These results further support our previous findings that a subset of spermatocytic tumors are intermediate between so-called type II and type III germ cell tumors and that embryonic microRNAs play a role in aggressive behavior in spermatocytic tumors. Accordingly, this subset of tumors may behave aggressively and require close follow up. In the future, this opens an opportunity for microRNA testing in serum of spermatocytic tumor patients for risk stratification purposes.


Subject(s)
Biomarkers, Tumor , MicroRNAs , Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Humans , Male , MicroRNAs/genetics , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/pathology , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Middle Aged , Aged , Real-Time Polymerase Chain Reaction , Gene Expression Regulation, Neoplastic , Young Adult
6.
J Infect Public Health ; 17(6): 1057-1064, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705058

ABSTRACT

BACKGROUND: Cervical cancer screening remains an essential preventive tool worldwide. First line high-risk Human Papillomavirus (HrHPV) genotyping became gold standard for cervical cancer screening, and has been adopted by several countries, including Portugal. Herein, we aimed to assess the early outcomes of the regional Cervical Cancer Screening Program of Northern Portugal. METHODS: The analysis of a representative set of cases evaluated during a one-month period (January 2020), with adequate follow-up was performed. Descriptive analysis was performed. RESULTS: Overall, 7278 samples were received, of which 15.2% were HrHPV positive, most of these disclosing a negative result in subsequent liquid-based cytology. Nearly half of the HrHPV-positive women were referred to colposcopy. Within this group, HPV16/18+ cases depicted the higher frequency of high-grade squamous intraepithelial lesion (HSIL) or worse, compared with abnormal cytology or persistent HrHPV infection. Among women with non-HPV16/18 HrHPV infection and negative cytology, which are eligible for repeat sampling in one year, 65% were re-tested. Importantly, nearly half of these cleared HrHPV infection. Furthermore, referral to colposcopy due to HPV16/18 infection and/or abnormal cytology results were associated with > 40% risk for HSIL or worse lesion. CONCLUSIONS: Our study confirmed the reliability and effectiveness of first line HrHPV genotyping in the Cervical Cancer Screening Program of Northern Portugal. Nonetheless, it also raised concerns about excessive referral to colposcopy, with the inherent human and financial costs. Thus, further improvement and optimization are key to ensure the sustainability of the program.


Subject(s)
Colposcopy , Early Detection of Cancer , Papillomavirus Infections , Uterine Cervical Neoplasms , Humans , Female , Portugal , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Early Detection of Cancer/methods , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Adult , Middle Aged , Genotype , Human papillomavirus 16/genetics , Human papillomavirus 16/isolation & purification , Human papillomavirus 18/genetics , Human papillomavirus 18/isolation & purification , Aged , Mass Screening/methods
7.
Mod Pathol ; 37(6): 100492, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38614322

ABSTRACT

Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.


Subject(s)
Exome Sequencing , Juxtaglomerular Apparatus , Kidney Neoplasms , Humans , Male , Female , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Adult , Juxtaglomerular Apparatus/pathology , Middle Aged , Young Adult , ras Proteins/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Mutation , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/physiology , Adolescent
8.
Andrology ; 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38380739

ABSTRACT

BACKGROUND: Testicular germ cell tumors remain the most frequent solid malignancies in young males. Despite excellent prognosis, the fact that only 60% of patients at diagnosis have elevated serum tumor markers (dependent on stage and histology) and the poor quality of life of patients who develop resistance to chemotherapy cannot be neglected. Consequently, it is mandatory to bring out novel biomarkers. OBJECTIVES: The main goal was to evaluate EZH2 and EHMT2/G9a immunoexpression in a well-characterized patients' cohort of primary and metastatic testicular germ cell tumors, seeking associations with clinicopathological features and discovering differential immunoexpression patterns among specific subtypes. MATERIALS AND METHODS: First, an in silico analysis of the Cancer Genome Atlas database was performed regarding EZH2 and EHMT2/G9a. Then, immunohistochemistry for EZH2 and EHMT2/G9a was carried out in a cohort of testicular germ cell tumor patients, comprising 155 chemo-naïve primary tumors and 11 chemo-treated metastases. Immunoexpression was evaluated using a digital pathology analysis software. RESULTS: Higher EZH2 and EHMT2/G9a expression levels were found in non-seminoma in the in silico analysis, particularly in embryonal carcinoma. Through digital pathology analysis, non-seminomas showed significantly higher EZH2 and EHMT2/G9a immunoexpression, with embryonal carcinoma showing higher expression. Moreover, mixed tumors with 50% or more of embryonal carcinoma component revealed the highest nuclei positivity for both biomarkers. Cisplatin-exposed metastases demonstrated a higher EZH2-positive nuclei and H-score, as well as higher EHMT2/G9a-positive nuclei. DISCUSSION AND CONCLUSION: Overall, our data suggest that EZH2 and EHMT2/G9a might be associated with greater aggressiveness and, eventually, involved in the metastatic setting, paving the way for testing targeted therapies.

10.
Curr Opin Urol ; 34(1): 20-26, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37916954

ABSTRACT

PURPOSE OF REVIEW: Genitourinary (GU) malignancies are a real burden in global health worldwide. Each model has its own clinical challenges, and the early screening and/or detection of occult cancer in follow-up is transversal to all of them. MicroRNAs (miRNAs) have been proposed as minimally invasive liquid biopsy cancer biomarkers, due to their stability and low degradation. RECENT FINDINGS: The different GU tumor models are in different stages concerning miRNAs as biomarkers for cancer detection. Testicular germ cell tumors (TGCTs) already have a specific defined target, miR-371a-3p, that has shown high sensitivity and specificity in different clinical settings, and is now in final stages of preanalytical testing before entering the clinic. The other GU malignancies are in a different stage, with many liquid biopsy studies (both in urine and plasma/serum) being currently performed, but there is not an agreeable miRNA or set of miRNAs that is ready to follow the footsteps of miR-371a-3p in TGCTs. SUMMARY: Further studies with proper molecular characterization of miRNA profiles of GU malignancies and standardization of sampling, biobanking and formal analysis may aid in the advance and choosing of specific target sets to be used for occult cancer detection.


Subject(s)
MicroRNAs , Neoplasms, Germ Cell and Embryonal , Urogenital Neoplasms , Humans , Male , Biological Specimen Banks , Biomarkers, Tumor/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/genetics , Testicular Neoplasms/diagnosis , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Urogenital Neoplasms/diagnosis , Urogenital Neoplasms/genetics , Urogenital Neoplasms/pathology , Liquid Biopsy
11.
Eur J Dent ; 18(3): 796-807, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38158209

ABSTRACT

OBJECTIVES: Maxillary lateral incisor agenesis (MLIA), treated orthodontically by space opening, requires complimentary aesthetic rehabilitation. Resin-bonded bridges (RBBs) can be equated as interim rehabilitation until skeletal maturity is achieved to place an implant-supported crown or as definitive rehabilitation in case of financial restrictions or implant contraindications. Scientific evidence of the best material must be confirmed in specific clinical situations. Computer-aided design and computer-aided manufacturing (CAD/CAM) materials are promising versatile restorative options. This study aimed to identify a straightforward material to deliver interim or definitive RBBs for nonprepared tooth replacement in MLIA. MATERIALS AND METHODS: Single-retainer RBB made from CAD/CAM ceramic blocks (Vita Enamic [ENA], Suprinity [SUP], and zirconia [Y-ZPT]) and a three-dimensional (3D) printed material (acrylonitrile butadiene styrene [ABS]) were evaluated by shear bond strength (SBS) and mode of failure, after adherence to an artificial tooth with RelyX Ultimate used in a three-step adhesive strategy. STATISTICAL ANALYSIS: The load to fracture (N) was recorded, and the mean shear stress (MPa) was calculated with standard deviations (SD) for each group and compared between materials using boxplot graphics. One-way analysis of variance (ANOVA) followed by the Tukey-Kramer post hoc test was used to compare the differences (α = 0.05). A meta-analysis focusing on CAD/CAM materials evaluated the magnitude of the difference between groups based on differences in means and effect sizes (α = 0.05; 95% confidence interval [CI]; Z-value = 1.96). Failure mode was determined by microscopic observation and correlated with the maximum load to fracture of the specimen. RESULTS: The mean ± SD SBS values were ENA (24.24 ± 9.05 MPa) < ABS (24.01 ± 1.94 MPa) < SUP (29.17 ± 4.78 MPa) < Y-ZPT (37.43 ± 12.20 MPa). The failure modes were mainly adhesive for Y-ZPT, cohesive for SUP and ENA, and cohesive with plastic deformation for ABS. CONCLUSION: Vita Enamic, Suprinity, Y-ZPT zirconia, and 3D-printed ABS RBBs are optional materials for rehabilitating MLIA. The option for each material is conditioned to estimate the time of use and necessity of removal for orthodontic or surgical techniques.

12.
Autops. Case Rep ; 11: e2020198, 2021. tab, graf
Article in English | LILACS | ID: biblio-1142401

ABSTRACT

Merkel cell carcinoma is an aggressive malignancy that frequently recurs/disseminates, but metastases to the genitourinary tract are rare. Only eight cases of Merkel cell carcinoma metastatic to the testis are reported. We describe the ninth case of this event and provide a review of the literature. A 58-year-old man diagnosed with Merkel cell carcinoma of the wrist, presented, 37 months later, a recurrence in the form of a testicular metastasis. The tumor consisted of a monotonous proliferation of small, blue, round cells, with immunoexpression of neuroendocrine markers and the typical dot-like paranuclear immunostaining for cytokeratin 20, in the absence of immunostaining for cytokeratin 7. The patient is alive with no evidence of disease. Clinicians should be aware of the possibility of metastatic dissemination to the testis since genital examination/imaging is not part of routine follow-up for these patients, but timely orchiectomy may be curative.


Subject(s)
Humans , Male , Middle Aged , Testicular Neoplasms/complications , Carcinoma, Merkel Cell/complications , Neuroendocrine Tumors/pathology , Neoplasm Metastasis
13.
Rev. esp. enferm. dig ; 112(5): 367-372, mayo 2020. ilus, tab
Article in English | IBECS | ID: ibc-195590

ABSTRACT

INTRODUCTION AND AIM: hereditary diffuse gastric cancer (HDGC) can be caused by a CDH1 mutation. It often presents as multiple foci of signet ring cell carcinoma (SRCC) that is rarely detected by gastroscopy. Prophylactic total gastrectomy is recommended at a young age. The aim of this study was to determine the adequacy of gastroscopy according to the Cambridge protocol in patients with a CDH1 mutation. METHODS: patients with a CDH1 mutation admitted to our department between September 2016 and October 2018 were evaluated. All patients underwent a baseline gastroscopy according to the Cambridge protocol, followed by a recommended total gastrectomy. Endoscopic findings, the number of biopsies and histological evaluation of biopsy samples were registered. Postoperative histopathological assessment was compared with endoscopic findings in patients that underwent a total gastrectomy (n = 13). RESULTS: twenty-five patients were included and 35 gastroscopies performed. On these, 996 gastric biopsies were performed, which included 952 random and 44 targeted. Only three patients had SRCC foci in random biopsies and one also had SRCC lesions in two targeted biopsies. In our cohort, 332 random and 22 targeted biopsies were needed to identify a single SRCC focus. Total gastrectomy was performed in 13 patients and SRCC foci were identified in 12 surgical specimens, the remaining specimen had a precursor lesion of HDGC. DISCUSSION: gastroscopy has a poor sensitivity to detect SRCC. Even with Cambridge protocol, gastroscopy has a very limited role in the surveillance of patients with a CDH1 mutation and prophylactic total gastrectomy is the most advisable option. Nevertheless, endoscopic protocols should be optimized to favor targeted biopsies over a high number of random biopsies


No disponible


Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Clinical Protocols , Gastroscopy , Cdh1 Proteins/genetics , Mutation/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Sensitivity and Specificity , Stomach Neoplasms/pathology , Stomach Neoplasms/prevention & control , Gastrectomy , Prospective Studies , Cohort Studies , Random Allocation , Biopsy
14.
Rev. bras. ortop ; 55(2): 185-190, Mar.-Apr. 2020. tab
Article in English | LILACS | ID: biblio-1137997

ABSTRACT

Abstract Objective In the present study, we present the results with at least 10 years of follow-up of the cervical disc prosthesis implanted in a single level. Methods Retrospective study of patients undergoing single-level total cervical disc replacement (TCDR). Clinical results included the neck disability index (NDI) and the visual analogue scale (VAS) in the preoperative period, one year postoperatively, and a minimum of 10 years of follow-up. The radiographic parameters included cervical mobility, segmental lordosis, C2-C7 angle, heterotopic ossification (HO), facet and joint degeneration (FJD) and adjacent segment disease (ASD). Results We identified 22 patients, 16 women and 6 men with mean age of 39.7 years old (26-51 years old), of which fifteen completed a minimum follow-up of 10 years. There was a statistically significant improvement of NDI and VAS (p < 0.001) between the preoperative and the postoperative periods (1 year or > 10 years). At the end of 10 years, HO was observed in 59% of the cases. The mobility of the implant was preserved in 80% of the patients. Radiological evidence of ASD was recorded in 6 patients (40%). There was no correlation between the clinical parameters evaluated and the presence of ASD or the different classes of HO. Conclusion Clinical improvement in all evaluated parameters, which persists over time. Most implants maintained mobility, as has already been demonstrated in other studies with shorter follow-ups. In a significant percentage of cases, ASD was observed, questioning the concept of motion preserving technology. However, we did not have any surgical intervention for this reason, since there was no correlation with worse clinical results.


Resumo Objetivo No presente estudo, apresentamos os resultados com um acompanhamento mínimo de 10 anos da artroplastia total do disco cervical (ATDC) em um nível. Métodos Estudo retrospectivo de pacientes submetidos a ATDC em um nível. Os resultados clínicos incluíram o índice de incapacidade relacionada ao pescoço (IIRP) e a escala visual analógica (EVA) no período pré-operatório, um ano pós-operatório e um mínimo de 10 anos de acompanhamento. Os parâmetros radiográficos incluíram a mobilidade cervical, lordose segmentar, ângulo C2-C7, ossificação heterotópica (OH), degeneração facetária e articular (DFA) e doença do segmento adjacente (DSA). Resultados Identificados 22 pacientes, 16 mulheres e 6 homens com média de idade de 39,7 anos (26-51 anos), dos quais 15 tiveram um acompanhamento mínimo de 10 anos. Foi verificada melhoria estatisticamente significativa do IIRP e EVA (p < 0,001) entre pré-operatório e pós-operatório. (1 ano ou > 10 anos). Ao final de 10 anos, OH foi observada em 59% dos casos. A mobilidade do implante foi preservada em 80% dos pacientes. Houve evidência radiológica de DSA em 6 pacientes (40%). Não houve correlação entre os parâmetros clínicos avaliados e a presença de DSA ou as diferentes classes de OH. Conclusão Melhoria clínica em todos os parâmetros avaliados, que persiste ao longo do tempo. A maioria dos implantes manteve a mobilidade, como já demonstrado em estudos anteriores com acompanhamentos mais curtos. Numa percentagem significativa, a DSA estava presente, questionando o conceito da tecnologia de preservação de movimento. No entanto, sem nenhuma intervenção cirúrgica por esse motivo, uma vez que não houve correlação com piores resultados clínicos.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Arthroplasty , Prostheses and Implants , Surgical Procedures, Operative , Cervical Vertebrae , Retrospective Studies , Ossification, Heterotopic , Total Disc Replacement , Joints
15.
Mem. Inst. Oswaldo Cruz ; 115: e190364, 2020. tab, graf
Article in English | LILACS | ID: biblio-1091242

ABSTRACT

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.


Subject(s)
Animals , Male , Female , Adult , Aspartate Aminotransferases/blood , Protein C/analysis , Factor VIIa/analysis , Chagas Disease/physiopathology , Alanine Transaminase/blood , Liver/physiopathology , Brazil/epidemiology , Biomarkers/blood , Case-Control Studies , Acute Disease , Prospective Studies , Chagas Disease/enzymology , Chagas Disease/blood , Chagas Disease/transmission , Parasite Load , Liver/enzymology , Middle Aged
16.
Autops. Case Rep ; 9(1): e2018071, Jan.-Mar. 2019. ilus
Article in English | LILACS | ID: biblio-987535

ABSTRACT

Intestinal lipomatosis is rare and often asymptomatic but can present with intestinal obstruction. Occasionally, metastatic breast cancer is identified in the ovary before a breast primary is discovered. We report the case of a 50-year-old woman diagnosed with synchronous intestinal obstruction due to lipomatosis, and incidental ovarian metastases from breast cancer. The patient presented with a 12-day history of nausea, diffuse abdominal pain, and constipation. An abdominal x-ray showed air-fluid levels, and computed tomography documented small bowel distention. An explorative laparotomy was performed, which revealed small bowel distention, an obstructive lesion of the ileocecal valve, three terminal ileum lesions, ascites, and heterogeneous ovaries. Right ileocolic resection and left oophorectomy were performed. The pathological diagnosis revealed lipomatous submucosal lesion of the ileocecal valve and ileum, and 17 lymph nodes, which were all negative for malignant cells. The oophorectomy revealed ovarian metastasis from breast carcinoma. Ascitic fluid was positive for malignant cells. Mammography and breast/axillary ultrasonography showed a solid nodule of the left breast, ductal carcinoma, and multiple enlarged left axillary lymph nodes, which were positive for neoplastic cells. Immunohistochemical evaluation showed hormonal receptor positivity and C-erb2 negativity. Breast magnetic resonance imaging showed a 14 mm left nodule and a positron emission tomography scan revealed 18F-FDG uptake in the left breast, left axillary lymph nodes, right ovary, and peritoneum. The tumor was staged as stage IV ductal breast carcinoma, cT1N1M1, Grade 2, Luminal B-like. The multidisciplinary oncological meeting proposed chemotherapy, and a re-staging breast MRI after chemotherapy, which showed a complete response. The patient started treatment with letrozole and remains disease-free 22 months after finishing chemotherapy.


Subject(s)
Humans , Female , Middle Aged , Breast Neoplasms/diagnosis , Incidental Findings , Lipomatosis/therapy , Intestinal Obstruction/therapy , Lymph Nodes , Neoplasm Metastasis
17.
Rev. bras. ortop ; 53(5): 532-536, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-977896

ABSTRACT

ABSTRACT Objective: To evaluate the clinical and radiological outcomes of the surgical treatment in patients diagnosed with odontoid fracture who underwent open reduction and internal fixation (ORIF) with screws. Methods: This was a retrospective study with nine patients. Pain (visual analog scale [VAS]) and neurological status (Frankel scale) were assessed. The neck disability index (NDI) and the post-operative cervical range of motion were calculated. The cervical spine was radiologically evaluated (X-ray and CT) pre- and postoperatively. Results: The mean age of patients was 70 years. All patients presented type IIb (Grauer classification) fractures, with a mean deviation of 2.95 mm. Two patients had subaxial lesions. The mean follow-up was 30 months. The mean time from trauma to surgery was seven days. The pre-operative Frankel score was E in all except one patient (B), in whom a post-operative improvement from B to D was observed. Post-operative pain was 2/10 (VAS). A total of 77% of patients presented a mild or moderate disability (NDI). Six patients regained full range of cervical movement, and bone union required approximately 14 weeks. Pseudarthrosis complications were observed in two patients (77% union rate), one patient presented screw repositioning and one case, dysphonia. Conclusion: Delayed diagnosis is still an issue in the treatment of odontoid fractures, especially in elderly patients. Concomitant lesions, especially in younger patients, are not uncommon. The literature presents high fusion rates with ORIF (≥80%), which was also observed in the present study. However, surgical success depends on proper patient selection and strict knowledge of the technique. This pathology presents a reserved functional prognosis in the medium-term, especially in the elderly.


RESUMO Objetivo: Avaliar os resultados clínicos e radiológicos do tratamento cirúrgico em pacientes com diagnóstico de fratura do processo odontoide submetidos a redução aberta e fixação interna (RAFI) com parafusos. Métodos: Estudo retrospectivo com nove pacientes. Avaliada a dor (escala visual analógica [EVA]) e o estado neurológico (escala de Frankel). O Neck Disability Index (NDI) e a amplitude de movimento cervical pós-operatória foram calculados. A coluna cervical foi avaliada radiologicamente (raios X e TC) nos períodos pré- e pós-operatório. Resultados: A idade média dos pacientes foi de 70 anos. Todos apresentaram fraturas do tipo IIb (classificação de Grauer), com desvio médio de 2,95 mm. Dois apresentaram lesões subaxiais. O seguimento médio foi de 30 meses. O tempo médio entre trauma e cirurgia foi de sete dias. O escore pré-operatório de Frankel foi E em todos, exceto em um paciente (B), no qual se observou uma melhoria pós-operatória de B para D. A dor pós-operatória foi 2/10 (EVA). Apresentaram incapacidade leve ou moderada (NDI) 77% pacientes. Seis pacientes recuperaram toda a amplitude de movimento cervical; a consolidação óssea levou aproximadamente 14 semanas. Foram observadas complicações de pseudartrose em dois pacientes (taxa de consolidação: 77%), um paciente necessitou reposicionamento do parafuso e um paciente, disfonia. Conclusão: O diagnóstico tardio ainda é um problema no tratamento de fraturas do odontoide, especialmente em pacientes idosos. As lesões concomitantes, especialmente em pacientes mais jovens, não são incomuns. A literatura apresenta altas taxas de consolidação com RAFI (≥ 80%), o que também foi observado no presente estudo. No entanto, o sucesso cirúrgico depende da seleção adequada do paciente e do conhecimento rigoroso da técnica. Essa patologia apresenta um prognóstico funcional reservado em médio prazo, especialmente em idosos.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Bone Screws , Cervical Plexus/injuries , Spinal Fractures , Odontoid Process
19.
J. bras. nefrol ; 32(2): 156-164, abr.-jun. 2010. tab
Article in English, Portuguese | LILACS | ID: lil-551678

ABSTRACT

INTRODUÇÃO: Peritonite é a principal complicação relacionada com a diálise peritoneal (DP). OBJETIVO: Avaliar possíveis preditores para o seu desenvolvimento em pacientes em programa crônico na modalidade. MÉTODO: Realizou-se estudo de coorte retrospectivo em 330 pacientes (média de idade 53 ± 19 anos) em programa de DP na Clínica de Nefrologia de Sergipe (Clinese), em Aracaju/ SE, Brasil, entre 1.º de janeiro de 2003 e 31 de dezembro de 2007. Variáveis sociodemográficas e clínicas foram avaliadas comparativamente entre pacientes que apresentaram (141 por cento - 42,7 por cento) ou não (189 por cento - 57,3 por cento) peritonite. Na análise estatística, utilizaramse teste t de Student, qui-quadrado e modelo de regressão com múltiplas variáveis. RESULTADOS : Ocorreu um episódio de peritoniteacada28,4pacientes/mês(0,42episódio/ paciente/ano). O Staphylococcus aureus foi o agente etiológico mais frequente (27,8 por cento). Não se utilizava antibioticoterapia profilática e 136 pacientes (41,2 por cento) haviam apresentado previamente infecção de sítio de saída do cateter peritoneal (ISSCP). Identificou-se maior risco de peritonite nos pacientes com albuminemia < 3,0 g/dL no início do tratamento [risco relativo (RR) = 2,0; intervalo de confiança (IC) de 95 por cento = 1,21 - 3,43; p < 0,01], escolaridade < 4 anos (RR = 2,15; IC = 1,09 - 4,24; p = 0,03) e com histórico de ISSCP (RR = 2,63; IC = 1,57 - 4,41; p < 0,01). Não houve diferença significante entre os grupos no tocante a gênero, idade, renda familiar, procedência, presença ou não de diabetes, forma de início do tratamento (se eletiva ou emergencial), tipo de cateter e tipo de implante. CONCLUSÕES: Hipoalbuminemia, menor escolaridade e ISSCP mostraram-se como fatores preditores independentes de peritonite. Embora os índices de peritonite observados sigam os padrões internacionais, recomendam-se estratégias profiláticas para ISSCP.


INTRODUCTION: Peritonitis remains a major complication of peritoneal dialysis (PD). OBJECTIVE: Evaluate peritonitis incidence, etiology and outcome in cronic PD patients. METHODS: A retrospective cohort study was carried out on 330 patients (mean age of 53 ± 19 years) who had been treated by PD in a dialysis center in Aracaju/SE, Brazil between January 1st, 2003 and December 31th, 2007. Data of patients with and without peritonitis were compared using Student's ttest, chi-squared statistic and multiple logistic regression. RESULTS: There were 213 peritonitis among 141 patients (1.51 episode/patient) resulting in a rate of 28.44 patient/episode/ month (0.42 patient/episode/year). Staphylococcus aureus was the most frequent micro-organism isolated (27.8 percent), followed by Escherichia coli (13.4 percent) and 32.5 percent were culture-negative peritonitis. A greater risk of peritonitis was identified at the patients with hypoalbuminemia [relative risk (RR) = 2.0; 95 percent confidence interval (CI) = 1.21 - 3.43; p < 0,01], < 4 school years (RR = 2.15; CI = 1.09 - 4.24; p = 0.03) and catheter's exit site infection (RR = 2.63; IC = 1.57 - 4.41; p < 0.01). There were no significant difference among gender, age, family income, diabetes mellitus, type of dialysis treatment, type of catheter and its surgical implant. CONCLUSIONS: Hypoalbuminemia, low schooling and catheter's exit site infection were associated with greater risk to peritonitis. Although peritonitis rate follow international pattern, prophylactic strategies are recommended.


Subject(s)
Aged , Humans , Middle Aged , Peritoneal Dialysis , Peritonitis , Cohort Studies , Peritonitis/epidemiology , Peritonitis/etiology , Retrospective Studies
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