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1.
Can J Public Health ; 115(Suppl 1): 1-6, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38127242
2.
BMJ Case Rep ; 16(9)2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37751975

RESUMO

Seronegative villous atrophy (SNVA) is a diagnostic challenge for gastroenterologists, which is defined by villous atrophy and negative coeliac serology. Non-coeliac forms of SNVA, such as autoimmune enteropathy, can be life-threatening leading to intractable diarrhoea and severe malabsorption that require systemic immunosuppression. When all known causes have been excluded, it is termed idiopathic villous atrophy (IVA). We present a case of non-coeliac SNVA complicated by Kaposi sarcoma (KS). A previously well HIV-negative man in his 30s presented with a 4-month history of watery diarrhoea and 25 kg weight loss. After prolonged investigation, he was diagnosed with non-coeliac SNVA without an identified aetiology that would be consistent with IVA. Clinical recovery was achieved with parenteral nutrition for type II intestinal failure and immunosuppression using high-dose corticosteroids. On subsequent gastroscopy, he was diagnosed with localised intestinal KS prompting cessation of all immunosuppression but remained in clinical remission.


Assuntos
Doença Celíaca , Sarcoma de Kaposi , Masculino , Humanos , Doença Celíaca/diagnóstico , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/patologia , Intestinos , Diarreia , Atrofia/patologia
3.
Cardiovasc Revasc Med ; 52: 86-93, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36934006

RESUMO

Dilated Cardiomyopathy is a common myocardial disease characterized by dilation and loss of function of one or both ventricles. A variety of etiologies have been implicated including genetic variation. Advancement in genetic sequencing, and diagnostic imaging allows for detection of genetic mutations in sarcomere protein titin (TTN) and high resolution assessment of cardiac function. This review article discusses the role of cardiac MRI in diagnosing dilated cardiomyopathy in patients with TTN variant related cardiomyopathy.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Humanos , Conectina/genética , Conectina/metabolismo , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/genética , Mutação , Imageamento por Ressonância Magnética
4.
J Neuroendocrinol ; 34(10): e13184, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36121922

RESUMO

INTRODUCTION: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is considered to be a rare condition associated with lung neuroendocrine tumours (NET), and its natural history is poorly described. We aimed to assess the prevalence and clinicopathologic characteristics of DIPNECH in the lung NET population, and to investigate predictors of time-to-progression (TTP) and overall survival (OS). METHODS: We retrospectively identified patients diagnosed with DIPNECH between April 2005 and December 2020. Clinical data were collected from medical records. The relationship between baseline characteristics and TTP and OS was analysed using the Kaplan-Meier method. Univariate analysis was performed using the Cox proportional hazards model. RESULTS: Of 311 patients with well-differentiated lung NETs, 61 (20%) had DIPNECH and were included in the study. Baseline demographics described 95% female, 59% never smokers and mean body mass index 34.4 kg m-2 ; 77% were typical carcinoids (TC), 13% atypical carcinoids (AC), and 10% both TC and AC (multicentric). At presentation, 54% of patients were asymptomatic. Multicentric NETs were demonstrated in 16 (26%) on histopathology, and a further 32 (52%) had synchronous NETs suggested on imaging (multiple nodules ≥ 5 mm). Seven (11%) patients developed metastases and the median OS from time of first metastasis was 37 months. AC histopathology and NET TNM stage ≥ IIA were associated with poorer TTP and OS. Of the DIPNECH cohort, the 15-year survival rate was 86%. CONCLUSIONS: DIPNECH may be more prevalent in the lung NET population than previously appreciated, especially in women. Although our results confirm that DIPNECH is predominantly an indolent disease associated with TC, 23% developed AC and these patients may warrant closer observation.


Assuntos
Tumor Carcinoide , Pneumopatias , Neoplasias Pulmonares , Células Neuroendócrinas , Tumores Neuroendócrinos , Humanos , Feminino , Masculino , Hiperplasia/epidemiologia , Hiperplasia/complicações , Hiperplasia/patologia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/patologia , Prevalência , Estudos Retrospectivos , Pneumopatias/complicações , Pneumopatias/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Tumor Carcinoide/complicações , Tumor Carcinoide/patologia , Pulmão/patologia
5.
Am J Infect Control ; 50(6): 695-698, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35276310

RESUMO

This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) healthcare-associated infection (HAI) surveillance definitions. This specific case study focuses on the application of three of the surveillance concepts included in the Patient Safety Component, Chapter 2 - Identifying Healthcare-associated Infections (HAI) for NHSN Surveillance. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions and encourage accurate HAI event determination among Infection Preventionists (IPs).


Assuntos
Infecção Hospitalar , Confiabilidade dos Dados , Centers for Disease Control and Prevention, U.S. , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Humanos , Controle de Infecções , Estados Unidos
6.
J Gastrointest Cancer ; 53(2): 460-465, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33877570

RESUMO

PURPOSE: Pancreatic solid pseudopapillary neoplasms (SPNs) are rare borderline tumours mainly affecting young female patients. The number of patients diagnosed with SPNs has increased significantly in the last decades owing to the increased use of cross-sectional imaging investigating different abdominal symptoms, whilst a significant proportion are incidentally discovered during the process of evaluating other pathologies. We herein present our institutional experience of patients with SPN who underwent curative resection focusing on clinical, pathological features, and the long-term outcomes. METHODS: All patients undergoing pancreatectomy in our institution for SPN from January 2010 until December 2018 were included. Clinical, perioperative, histological, and long-term outcomes were collected and analysed. RESULTS: During the inclusion period, a total of 19 patients had a pathological diagnosis of SPNs after surgical resection. Sixteen of them were female (84%), while the median patient age was 30 (range 16-66) years. Nine patients (47%) underwent distal pancreatectomy and splenectomy, 2 (11%) underwent spleen preserving distal pancreatectomy, 6 (32%) underwent pancreatoduodenectomy, one (5%) underwent total pancreatectomy, and one (5%) central pancreatectomy. Seventeen patients underwent R0 resection. During a median follow-up of 23 months, no tumour recurrence or death was recorded. CONCLUSION: In our experience, SPNs are rare tumours with low malignant potentials. Surgical resection remains the gold standard treatment and is associated with good prognosis.


Assuntos
Neoplasias Pancreáticas , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Pâncreas/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Adulto Jovem
7.
J Clin Immunol ; 42(1): 46-59, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599484

RESUMO

Diarrhea is the commonest gastrointestinal symptom in patients with common variable immunodeficiency (CVID). Different pathologies in patients' bowel biopsies have been described and links with infections have been demonstrated. The aim of this study was to analyze the bowel histology of CVID patients in the Royal-Free-Hospital (RFH) London CVID cohort. Ninety-five bowel histology samples from 44 adult CVID patients were reviewed and grouped by histological patterns. Reasons for endoscopy and possible causative infections were recorded. Lymphocyte phenotyping results were compared between patients with different histological features. There was no distinctive feature that occurred in most diarrhea patients. Out of 44 patients (95 biopsies), 38 lacked plasma cells. In 14 of 21 patients with nodular lymphoid hyperplasia (NLH), this was the only visible pathology. In two patients, an infection with Giardia lamblia was associated with NLH. An IBD-like picture was seen in two patients. A coeliac-like picture was found in six patients, four of these had norovirus. NLH as well as inflammation often occurred as single features. There was no difference in blood lymphocyte phenotyping results comparing groups of histological features. We suggest that bowel histology in CVID patients with abdominal symptoms falls into three major histological patterns: (i) a coeliac-like histology, (ii) IBD-like changes, and (iii) NLH. Most patients, but remarkably not all, lacked plasma cells. CVID patients with diarrhea may have an altered bowel histology due to poorly understood and likely diverse immune-mediated mechanisms, occasionally driven by infections.


Assuntos
Imunodeficiência de Variável Comum , Gastroenteropatias , Imunodeficiência de Variável Comum/complicações , Imunodeficiência de Variável Comum/diagnóstico , Diarreia/complicações , Gastroenteropatias/patologia , Humanos , Inflamação/complicações , Plasmócitos/patologia
8.
Sci Rep ; 11(1): 14569, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267266

RESUMO

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.


Assuntos
Colágeno/metabolismo , Tecido Elástico/patologia , Cirrose Hepática/patologia , Falência Hepática Aguda/patologia , Adulto , Elastina/metabolismo , Matriz Extracelular/patologia , Feminino , Hepatócitos/patologia , Humanos , Imuno-Histoquímica , Cirrose Hepática/metabolismo , Falência Hepática Aguda/cirurgia , Masculino , Estudos Retrospectivos , Adulto Jovem
9.
BMC Gastroenterol ; 21(1): 268, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34182924

RESUMO

BACKGROUND: Alcohol is the main cause of chronic liver disease. The Enhanced Liver Fibrosis (ELF) test is a serological biomarker for fibrosis staging in chronic liver disease, however its utility in alcohol-related liver disease warrants further validation. We assessed the diagnostic and prognostic performance of ELF in alcohol-related liver disease. METHODS: Observational cohort study assessing paired ELF and histology from 786 tertiary care patients with chronic liver disease due to alcohol (n = 81) and non-alcohol aetiologies (n = 705). Prognostic data were available for 64 alcohol patients for a median of 6.4 years. Multiple ELF cut-offs were assessed to determine diagnostic utility in moderate fibrosis and cirrhosis. Survival data were assessed to determine the ability of ELF to predict liver related events and all-cause mortality. RESULTS: ELF identified cirrhosis and moderate fibrosis in alcohol-related liver disease independently of aminotransferase levels with areas under receiver operating characteristic curves of 0.895 (95% CI 0.823-0.968) and 0.923 (95% CI 0.866-0.981) respectively, which were non-inferior to non-alcohol aetiologies. The overall performance of ELF was assessed using the Obuchowski method: in alcohol = 0.934 (95% CI 0.908-0.960); non-alcohol = 0.907 (95% CI 0.895-0.919). Using ELF < 9.8 to exclude and ≧ 10.5 to diagnose cirrhosis, 87.7% of alcohol cases could have avoided biopsy, with sensitivity of 91% and specificity of 85%. A one-unit increase in ELF was associated with a 2.6 (95% CI 1.55-4.31, p < 0.001) fold greater odds of cirrhosis at baseline and 2.0-fold greater risk of a liver related event within 6 years (95% CI 1.39-2.99, p < 0.001). CONCLUSIONS: ELF accurately stages liver fibrosis independently of transaminase elevations as a marker of inflammation and has superior prognostic performance to biopsy in alcohol-related liver disease.


Assuntos
Cirrose Hepática , Hepatopatias , Biomarcadores , Biópsia , Estudos de Coortes , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Hepatopatias/patologia , Testes de Função Hepática , Prognóstico
10.
Front Oncol ; 11: 629665, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718208

RESUMO

AIM: Analysis of the pathophysiology of mesenteric fibrosis (MF) in small intestinal neuroendocrine tumors (SI-NETs) in an in vitro paracrine model and in human SI-NET tissue samples. METHODS: An indirect co-culture model of SI-NET cells KRJ-I and P-STS with stromal cells HEK293 was designed to evaluate the paracrine effects on cell metabolic activity, gene expression by RT2 PCR Profilers to analyse cancer and fibrosis related genes, and RNA sequencing. The integrin signaling pathway, a specific Ingenuity enriched pathway, was further explored in a cohort of human SI-NET tissues by performing protein analysis and immunohistochemistry. RESULTS: RT Profiler array analysis demonstrated several genes to be significantly up- or down-regulated in a cell specific manner as a result of the paracrine effect. This was further confirmed by employing RNA sequencing revealing multiple signaling pathways involved in carcinogenesis and fibrogenesis that were significantly affected in these cell lines. A significant upregulation in the expression of various integrin pathway - related genes was identified in the mesenteric mass of fibrotic SI-NET as confirmed by RT-qPCR and immunohistochemistry. Protein analysis demonstrated downstream activation of the MAPK and mTOR pathways in some patients with fibrotic SI-NETs. CONCLUSION: This study has provided the first comprehensive analysis of the crosstalk of SI-NET cells with stromal cells. A novel pathway - the integrin pathway - was identified and further validated and confirmed in a cohort of human SI-NET tissue featured by a dual role in fibrogenesis/carcinogenesis within the neoplastic fibrotic microenvironment.

11.
Transpl Infect Dis ; 23(4): e13589, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33617680

RESUMO

Liver transplant recipients are at high risk for surgical site infections (SSIs). Limited data are available on SSI epidemiology following liver transplant procedures (LTPs). We analyzed data on SSIs from 2015 to 2018 reported to CDC's National Healthcare Safety Network to determine rates, pathogen distribution, and antimicrobial resistance after LTPs and other hepatic, biliary, or pancreatic procedures (BILIs). LTP and BILI SSI rates were 5.7% and 5.9%, respectively. The odds of SSI after LTP were lower than after BILI (adjusted odds ratio = 0.70, 95% confidence interval 0.57-0.85). Among LTP SSIs, 43.1% were caused by Enterococcus spp., 17.2% by Candida spp., and 15.0% by coagulase-negative Staphylococcus spp. (CNS). Percentages of SSIs caused by Enterococcus faecium or CNS were higher after LTPs than BILIs, whereas percentages of SSIs caused by Enterobacteriaceae, Enterococcus faecalis, or viridans streptococci were higher after BILIs. Antimicrobial resistance was common in LTP SSI pathogens, including E. faecium (69.4% vancomycin resistant); Escherichia coli (68.8% fluoroquinolone non-susceptible and 44.7% extended spectrum cephalosporin [ESC] non-susceptible); and Klebsiella pneumoniae and K. oxytoca (39.4% fluoroquinolone non-susceptible and 54.5% ESC non-susceptible). National LTP SSI pathogen and resistance data can help prioritize studies to determine effective interventions to prevent SSIs and reduce antimicrobial resistance in liver transplant recipients.


Assuntos
Transplante de Fígado , Infecção da Ferida Cirúrgica , Antibacterianos/uso terapêutico , Enterococcus faecalis , Humanos , Klebsiella pneumoniae , Transplante de Fígado/efeitos adversos , Staphylococcus , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia
12.
Am J Infect Control ; 49(8): 1075-1077, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609589

RESUMO

This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) healthcare-associated infection (HAI) surveillance definitions. This specific case study focuses on the application of the Pneumonia (PNEU), Ventilator-associated event (VAE), and Bloodstream infections (BSI) surveillance definitions to a patient with COVID-19. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions among Infection Preventionists (IPs) and encourage accurate determination of HAI events.


Assuntos
COVID-19 , Infecções Relacionadas a Cateter , Infecção Hospitalar , Pneumonia Associada à Ventilação Mecânica , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Confiabilidade dos Dados , Atenção à Saúde , Humanos , Controle de Infecções , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , SARS-CoV-2 , Estados Unidos
13.
Neuroendocrinology ; 111(9): 863-875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32950978

RESUMO

BACKGROUND: The number of therapeutic options for patients with pancreatic neuroendocrine neoplasms (PNEN) has increased, but the optimal therapeutic algorithm has not been defined due to lack of randomised trials comparing different modalities. METHODS: We performed a retrospective study in patients with metastatic PNEN treated with ≥1 line of systemic therapy. The relationship between baseline characteristics, treatment type, and time to treatment failure (TTF), time to progression (TTP), and overall survival (OS) was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Two hundred and fifty-five patients with metastatic PNEN had 491 evaluable lines of therapy. Independent predictors of TTF included treatment type, Ki-67, tumour grade, and chromogranin A. To reduce selection bias, a subgroup of 114 patients with grade 2 (G2) metastatic pancreatic neuroendocrine tumours (PNET) was analysed separately. These patients had received 234 lines of treatment (105 chemotherapy, 82 molecular targeted therapy, and 47 peptide receptor radionuclide therapy [PRRT]). In the G2 cohort, TTF and TTP were superior for PRRT compared with both chemotherapy and molecular targeted therapy. OS in the G2 cohort was also superior for those that had received PRRT compared with those that had not (median 84 vs. 56 months; HR 0.55, 95% CI: 0.31-0.98, p = 0.04). CONCLUSIONS: This study suggests that PRRT is associated with superior clinical outcomes relative to other systemic therapies for G2 metastatic PNET. Prospective studies are required to confirm these observations.


Assuntos
Algoritmos , Antineoplásicos/farmacologia , Terapia de Alvo Molecular , Tumores Neuroendócrinos/terapia , Avaliação de Resultados em Cuidados de Saúde , Neoplasias Pancreáticas/terapia , Radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/secundário , Neoplasias Pancreáticas/secundário , Estudos Retrospectivos , Adulto Jovem
14.
Sci Rep ; 10(1): 20098, 2020 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-33208811

RESUMO

The literature on the contribution of elastic fibre deposition to alcohol-related liver disease (ARLD) is limited. We studied: (1) 180 liver biopsies from ARLD patients; (2) 20 ARLD explant livers; (3) 213 liver biopsies with non-ARLD injury. Elastic fibres were assessed in terms of their distribution around hepatocytes [pericellular elastosis (PCE)] and within bridging fibrous septa (septal elastosis) and scored using a semiquantitative system. We also investigated the composition of the elastic fibres (oxytalan, elaunin and mature elastic fibres) in 20 cases. PCE was associated with steatohepatitis in ARLD patients and with ARLD when compared to non-ARLD cases (p < 0.001). Oxytalan fibres were identified in PCE in ARLD biopsies and broken dense perisinusoidal mature elastic fibres in explanted livers. Septal elastosis increased from intermediate to advanced fibrosis stage. Early septal elastosis contained oxytalan fibres, whereas septal elastosis at more advanced stages contained mainly mature elastic fibres. PCE is a typical feature of steatohepatitis in ARLD and includes oxytalan fibres. Septal elastosis is a gradual process with a transition from oxytalan to mature elastic fibres usually present in explanted livers. There may be different dynamics in the assembly and reabsorption of pericellular and septal elastic fibres, and a potential role for stratification of patients with advanced stage ARLD.


Assuntos
Tecido Elástico/patologia , Hepatopatias Alcoólicas/patologia , Fígado/patologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Hepatopatias Alcoólicas/cirurgia , Masculino , Pessoa de Meia-Idade
15.
Artigo em Inglês | MEDLINE | ID: mdl-32729847

RESUMO

SUMMARY: Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are typically associated with poor outcomes. The mechanisms of their aggressiveness are still being investigated. Microsatellite instability (MSI) has recently been found in colorectal NECs showing aberrant methylation of the MLH1 gene and is associated with improved prognosis. We present a 76-year-old lady with an ascending colon tumour showing features of a pT3 N0 R0, large cell NEC (LCNEC) following right hemicolectomy. The adjacent mucosa showed a sessile serrated lesion (SSL) with low-grade dysplasia. Immunohistochemistry showed loss of expression for MLH1 and PMS2 in both the LCNEC and dysplastic SSL. Molecular analysis indicated the sporadic nature of the MLH1 mismatch repair (MMR) protein-deficient status. Our patient did not receive adjuvant therapy and she is alive and disease-free after 34 months follow-up. This finding, similar to early-stage MMR-deficient colorectal adenocarcinoma, is likely practice-changing and will be critical in guiding the appropriate treatment pathway for these patients. We propose that testing of MMR status become routine for early-stage colorectal NECs. LEARNING POINTS: Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are known to be aggressive and typically associated with poor outcomes. A subset of colorectal NECs can display microsatellite instability (MSI) with mismatch repair (MMR) protein-deficient status. MMR-deficient colorectal NECs have been found to have a better prognosis compared with MMR-proficient NECs. MMR status can be detected using immunohistochemistry. Immunohistochemistry for MMR status is routinely performed for colorectal adenocarcinomas. Immunohistochemical expression of MMR protein and MSI analysis should be performed routinely for early-stage colorectal NECs in order to identify a subgroup of MMR-deficient NECs which are associated with a significantly more favourable prognosis.

16.
Endocrine ; 69(2): 430-440, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32291735

RESUMO

PURPOSE: Surgical resection is the only effective curative strategy for small intestinal neuroendocrine neoplasms (SINENs). Nevertheless, the evaluation of residual disease and prediction of disease recurrence/progression remains a problematic issue. METHODS: We evaluated 13 SINENs that underwent surgical resection of the primary tumour and/or mesenteric mass. Patients were divided in three groups: (a) Group 1: SINENs that underwent resection with curative intent, (b) Group 2: SINENs treated with resection in the setting of metastatic disease, which remained stable and (c) Group 3: SINENs treated with resection in the setting of metastatic disease, with evidence of any progression at follow-up. NETest and chromogranin A were measured pre-operatively and post-operatively during a 22-month median follow-up period and compared with imaging studies. NETest score <20% was determined as normal, 20-40% low, 41-79% intermediate and ≥80% high score. RESULTS: NETest score was raised in all (100%) SINENs pre-operatively. Surgery with curative intent resulted in NETest score reduction from 78.25 ± 15.32 to 25.25 ± 1.75 (p < 0.05). Low NETest scores post-operatively were evident in all cases without clinical evidence of residual disease (Group 1). However, the low disease activity score suggested the presence of microscopic residual disease. In three cases (75%) with stable disease (Group 2) the NETest score was low consistent with indolent disease. In the progressive disease group (Group 3), a high NETest score was present in three cases (60%) and an intermediate NETest score in the remainder (40%). CONCLUSIONS: Blood NETest scores accurately identified SINENs and were significantly decreased by curative surgery. Monitoring NETest post-operatively may facilitate management by identifying the presence of residual/progressive disease.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Biomarcadores Tumorais , Cromogranina A , Humanos , Neoplasias Intestinais/cirurgia , Recidiva Local de Neoplasia , Tumores Neuroendócrinos/cirurgia , Estudos Retrospectivos
17.
Endocrine ; 67(1): 233-242, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31556004

RESUMO

PURPOSE: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS: The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS: The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos Cíclicos , Somatostatina/análogos & derivados , Tomografia Computadorizada por Raios X
18.
Endocrine ; 67(3): 718-726, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31598848

RESUMO

PURPOSE: Mesenteric fibrosis (MF) in small intestinal neuroendocrine neoplasms (SINENs) is often associated with significant morbidity and mortality. The detection of MF is usually based on radiological criteria, but no previous studies have attempted a prospective, multidimensional assessment of mesenteric desmoplasia to determine the accuracy of radiological measurements. There is also a lack of non-invasive biomarkers for the detection of image-negative MF. METHODS: A multidimensional assessment of MF incorporating radiological, surgical and histological parameters was performed in a prospective cohort of 34 patients with SINENs who underwent primary resection. Pre-operative blood samples were collected in 20 cases to evaluate a set of five profibrotic circulating transcripts-the "fibrosome"-that is included as an "omic" component of the NETest. RESULTS: There was a significant correlation between radiological and surgical assessments of MF (p < 0.05). However, there were several cases of image-negative MF. The NETest-fibrosome demonstrated an accuracy of 100% for the detection of microscopic MF. CONCLUSIONS: The detection of MF by radiological criteria has limitations. The NETest-fibrosome is a promising biomarker for fibrosis detection and further validation of these results would be needed in larger, multicentre studies.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Biomarcadores Tumorais , Fibrose , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Estudos Prospectivos
19.
Am J Infect Control ; 48(2): 207-211, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31326261

RESUMO

BACKGROUND: Surveillance of health care-associated, catheter-associated urinary tract infections (CAUTI) are the corner stone of infection prevention activity. The Centers for Disease Control and Prevention's National Healthcare Safety Network provides standard definitions for CAUTI surveillance, which have been updated periodically to increase objectivity, credibility, and reliability of urinary tract infection definitions. Several state health departments have validated CAUTI data that provided insights into accuracy of CAUTI reporting and adherence to CAUTI definition. METHODS: Data accuracy measures included pooled mean sensitivity, specificity, positive predictive value, and negative predictive value. Total CAUTI error rate was computed as proportion of mismatches among total records. The impact of 2015 CAUTI definition changes were tested by comparing pooled accuracy estimates of validations prior to 2015 with post-2015. RESULTS: At least 19 state health departments conducted CAUTI validations and indicated pooled mean sensitivity of 88.3%, specificity of 98.8%, positive predictive value of 93.6%, and negative predictive value of 97.6% of CAUTI reporting to the National Healthcare Safety Network. Among CAUTIs misclassified (121), 66% were underreported and 34% were overreported. CAUTI classification error rate declined significantly from 4.3% (pre-2015) to 2.4% (post-2015). Reasons for CAUTI misclassifications included: misapplication of CAUTI definition, misapplication of general health care-associated infection definitions, and clinical judgement over surveillance definition. CONCLUSIONS: CAUTI underreporting is a major concern; validations provide transparency, education, and relationship building to improve reporting accuracy.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Controle de Infecções/organização & administração , Controle de Infecções/normas , Infecções Urinárias/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Humanos , Reprodutibilidade dos Testes , Estados Unidos
20.
Transplant Proc ; 51(6): 1679-1683, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31301860

RESUMO

BACKGROUND: Accurate assessment of steatosis in procured livers is crucial to reduce the poor outcome associated with high-grade steatosis and to optimize the utilization of donor grafts. Clinical examination and digital image analysis (DIA) have been used for steatosis evaluation, but the validity of these methods is debated. This study aimed to compare these methods with standard histology for assessment of steatosis severity in human livers and to evaluate a revised classification system for automated fat measurement. METHODS: Clinical assessment of liver steatosis at time of retrieval and automated measurement were compared with standard histology in paraffinized and hematoxylin and eosin-stained slides, using a 4-grade scale for ordinal data and percentages for numerical values. RESULTS: Analysis of 42 human livers that were retrieved but not transplanted showed that clinical examination was not reliable for assigning steatosis grades (κw, 0.12; 95% CI, -0.06 to 0.30), overestimated steatosis severity, and had an accuracy of 67% for discriminating low- and high-grade steatosis. Digital image analysis had a substantial agreement on absolute fat percentage (intraclass correlation coefficient, 0.76; 95% CI, 0.63-0.84) and steatosis grades (κw, 0.70; 95% CI, 0.57-0.82), with 88% accuracy using the revised classification system. CONCLUSIONS: Clinical assessment of steatosis is inaccurate, and relying on this method alone could result in unnecessary discard of livers. Digital image analysis is feasible with higher accuracy and reliability, but further clinical studies are required to evaluate its clinical validity.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Transplante de Fígado , Fígado/diagnóstico por imagem , Transplantes/diagnóstico por imagem , Fígado Gorduroso/patologia , Feminino , Humanos , Fígado/patologia , Masculino , Reprodutibilidade dos Testes , Transplantes/patologia
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