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OBJECTIVES: Intersystem variability in liver stiffness (LS) quantification with ultrasound shear wave elastography (SWE) precludes direct comparison of results obtained with different equipment. The aim of this study was to investigate the agreement between point-SWE and 2-dimensional-SWE with Esaote-MyLab 9 (p-QElaXto and 2D-QElaXto, respectively) and 2D-SWE with SuperSonic Imagine (SSI) in order to assess specific LS thresholds for fibrosis staging with QElaXto techniques, using SSI as a reference standard. METHODS: A total of 235 compensated chronic liver disease (CLD) patients without comorbidities potentially affecting LS were enrolled in the study. Among them, 101 patients underwent also liver biopsy. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while cut-off values were calculated with receiver operating characteristics analysis. RESULTS: Correlation between 2D-QElaXto and p-QElaXto with SSI resulted very good (r = 0.898 and r = 0.866), especially in precirrhotic stages, with a mean difference between LS values of -1.3 kPa for 2D-QElaXto and -0.6 kPa for p-QElaXto compared with SSI. Cut-off thresholds for diagnosing fibrosis ≥F2, ≥F3, and F4 in non-HBV-related CLD were, respectively, 5.5, 8.0, and 10.6 kPa for 2D-QElaXto and 6.1, 8.1, and 11.7 kPa for p-QElaXto. All three SWE techniques were effective in differentiating significant fibrosis ≥F2 from mild or absent fibrosis in the subgroup of patients submitted to biopsy and showed good feasibility. CONCLUSIONS: Correlation between QElaXto techniques and SSI in LS measurements is very good. Our study identifies for the first time cut-off thresholds for fibrosis staging in non-HBV-related CLD using two QElaXto techniques.
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Técnicas de Imagem por Elasticidade , Hepatopatias , Técnicas de Imagem por Elasticidade/métodos , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Hepatopatias/complicações , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , UltrassonografiaRESUMO
BACKGROUND & AIMS: Non-invasive scoring systems (NSS) are used to identify patients with non-alcoholic fatty liver disease (NAFLD) who are at risk of advanced fibrosis, but their reliability in predicting long-term outcomes for hepatic/extrahepatic complications or death and their concordance in cross-sectional and longitudinal risk stratification remain uncertain. METHODS: The most common NSS (NFS, FIB-4, BARD, APRI) and the Hepamet fibrosis score (HFS) were assessed in 1,173 European patients with NAFLD from tertiary centres. Performance for fibrosis risk stratification and for the prediction of long-term hepatic/extrahepatic events, hepatocarcinoma (HCC) and overall mortality were evaluated in terms of AUC and Harrell's c-index. For longitudinal data, NSS-based Cox proportional hazard models were trained on the whole cohort with repeated 5-fold cross-validation, sampling for testing from the 607 patients with all NSS available. RESULTS: Cross-sectional analysis revealed HFS as the best performer for the identification of significant (F0-1 vs. F2-4, AUC = 0.758) and advanced (F0-2 vs. F3-4, AUC = 0.805) fibrosis, while NFS and FIB-4 showed the best performance for detecting histological cirrhosis (range AUCs 0.85-0.88). Considering longitudinal data (follow-up between 62 and 110 months), NFS and FIB-4 were the best at predicting liver-related events (c-indices>0.7), NFS for HCC (c-index = 0.9 on average), and FIB-4 and HFS for overall mortality (c-indices >0.8). All NSS showed limited performance (c-indices <0.7) for extrahepatic events. CONCLUSIONS: Overall, NFS, HFS and FIB-4 outperformed APRI and BARD for both cross-sectional identification of fibrosis and prediction of long-term outcomes, confirming that they are useful tools for the clinical management of patients with NAFLD at increased risk of fibrosis and liver-related complications or death. LAY SUMMARY: Non-invasive scoring systems are increasingly being used in patients with non-alcoholic fatty liver disease to identify those at risk of advanced fibrosis and hence clinical complications. Herein, we compared various non-invasive scoring systems and identified those that were best at identifying risk, as well as those that were best for the prediction of long-term outcomes, such as liver-related events, liver cancer and death.
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Hepatopatia Gordurosa não Alcoólica/complicações , Valor Preditivo dos Testes , Projetos de Pesquisa/normas , Tempo , Adulto , Área Sob a Curva , Estudos Transversais , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/mortalidade , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Projetos de Pesquisa/tendências , Índice de Gravidade de DoençaRESUMO
Hepatic involvement in familial Mediterranean fever (FMF) ranges from a nonspecific increase in liver enzymes to cryptogenic cirrhosis, and the liver is mostly involved in patients bearing the M694V MEFV mutation in homozygosis. A 44-year-old Jewish woman with FMF developed nonalcoholic steatohepatitis during colchicine treatment (2,5 mg per day), confirmed by both elastography and liver biopsy. Therefore, combined therapy with the interleukin-1 (IL-1) blocking agent canakinumab (150 mg every four weeks) and colchicine (at a reduced dose of 1.5 mg per day) was started. Three months later, transaminases became normal, and after further six months, there was a marked improvement of liver fibrosis. IL-1 blockade has the power to halt or mitigate liver involvement in FMF patients. However, further experience is required to assess its therapeutic potential in the most severe patients with the hepatic disease who are partially responsive to long-term prophylaxis with colchicine.
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INTRODUCTION: We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). METHODS: ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. RESULTS: Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. DISCUSSION: Once AIH has been ruled out, the long-term outcomes and survival are unaffected by the presence of ANA in patients with NAFLD.
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Anticorpos Antinucleares/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Biópsia , Inglaterra/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Estudos Prospectivos , Análise de SobrevidaRESUMO
The characterization of breast cancer according to its proliferative activity and the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2 is a laboratory routine that has been adopted worldwide for prognostic and therapeutic purposes. By combining data on the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2, it is possible to obtain 8 tumor patterns categorized as triple-negative, nonluminal (i.e. positive for human epidermal growth factor receptor-2 with four subtypes) and luminal (negative for human epidermal growth factor receptor-2 and positive for estrogen receptor and/or progesterone receptor with three subtypes) tumors. In general, luminal tumors are associated with a higher degree of tumor differentiation and have more favorable clinical outcomes. One of the subtypes of luminal tumors has an ER-/PR+ profile. This is a rather rare tumor subtype that behaves aggressively. The aim of this work was to analyse the proliferative activity of the eight tumor subgroups to verify if the ER-/PR+ type has a higher proliferative activity than the other subtypes, which might be correlated with its more aggressive behavior. To accomplish this, we examined estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 and Ki67 data from 6643 cases of breast cancer. We found that the tumor type that was positive for only the progesterone receptor and negative for both the estrogen receptor and human epidermal growth factor receptor-2 (1.3% of all cases) had a proliferative activity that was consistently much higher than those of the other luminal subtypes.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: It is still unclear whether a positive surgical margin after resection of colorectal liver metastases remains a poor prognostic factor in the era of modern perioperative chemotherapy. The aim of this study was to evaluate whether preoperative chemotherapy has an impact on reducing local recurrence after R1 resection, and the impact of local recurrence on overall survival. METHODS: Between 2000 and 2014, a total of 421 patients underwent resection for colorectal liver metastases at our unit after preoperative chemotherapy. The overall number of analyzed resection areas was 1,428. RESULTS: The local recurrence rate was 12.8%, significantly higher after R1 resection than after R0 (24.5% vs 8.7%; P < .001). These results were also confirmed in patients with response to preoperative chemotherapy (23.1% after R1 vs 11.2% after R0; P < .001). At multivariate analysis, R1 resection was the only independent risk factor for local recurrence (P < .001). At the analysis of the 1,428 resection areas, local recurrence significantly decreased according to the increase of the surgical margin width (from 19.1% in 0 mm margin to 2.4% in ≥10 mm). At multivariable logistic regression analysis for overall survival, the presence of local recurrence showed a significant negative impact on 5-year overall survival (P < .001). CONCLUSION: Surgical margin recurrence after modern preoperative chemotherapy for colorectal liver metastases was still significantly higher after R1 resection than it was after R0 resection. Local recurrence showed a negative prognostic impact on overall survival. R0 resection should be recommended whenever technically achievable, as well as in patients treated by modern preoperative chemotherapy.
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Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-IdadeRESUMO
PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT-mutant settings but not in PDGFRA-mutant ones, challenging the precursor role of ICC for PDGFRA-driven GISTs. Telocytes are a recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered fibroblasts, they are found in many organs, including the GI tract where they are thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI wall "fibrosis" has been reported in germline PDGFRA-mutants. Taking the opportunity offered by its presence in a germline PDGFRA-mutant individual, we demonstrate that this lesion is sustained by hyperplastic telocytes, constituting the PDGFRA-mutant counterpart of germline KIT mutation-associated ICCH. Moreover, our findings support a pathogenetic relationship between telocyte hyperplasia and both IFPs and PDGFRA-mutant GISTs. We propose the term "telocytoma" for defining IFP, as it conveys both the pathogenetic (neoplastic) and histotypic ("telocytary") essence of this tumour, unlike IFP, which rather evokes an inflammatory-hyperplastic lesion.
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Tumores do Estroma Gastrointestinal/patologia , Inflamação/patologia , Leiomioma/patologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Antígenos CD34/genética , Tumores do Estroma Gastrointestinal/genética , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Mutação em Linhagem Germinativa/genética , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Inflamação/genética , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Leiomioma/genética , Proteínas Proto-Oncogênicas c-kit/genética , Transmissão Sináptica/genética , Telócitos/patologiaRESUMO
Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients.
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Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Micropartículas Derivadas de Células/metabolismo , Neoplasias Hepáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To correlate imaging parameters from baseline MRI diffusion-weighted imaging (DWI) and fludeoxyglucose (FDG) positron emission tomography (PET)-CT with synchronous and metachronous metastases in mucinous carcinoma (MC) and non-mucinous carcinoma (NMC) rectal cancer. METHODS: 111 patients with extraperitoneal locally advanced rectal cancer, who underwent pelvic MRI, DWI and FDG PET-CT, were stratified into MC (n = 23) and NMC (n = 88). We correlated adverse morphologic features on MRI [mT4, mesorectal fascia involvement, extramural venous invasion (mEMVI), mN2] and quantitative imaging parameters [minimum apparent diffusion coefficient (ADCmin), maximum standardized uptake value, total lesion glycolysis, metabolic tumour volume, T2 weighted and DWI tumour volumes] with the presence of metastatic disease. All patients underwent pre-operative chemoradiation therapy (CRT); 100/111 patients underwent surgery after CRT and were classified as pathological complete response (PCR) and no PCR [tumour regression grade (TRG)1 vs TRG2-5] and as ypN0 and ypN1-2. Median follow-up time was 48 months. Metastases were confirmed on FDG PET-CT and contrast-enhanced multidetector CT. RESULTS: The percentage of mucin measured by MRI correlates with that quantified by histology. On multivariate analysis, the synchronous metastases were correlated with mEMVI [odds ratio (OR) = 21.48, p < 0.01] and low ADCmin (OR = 0.04, p = 0.038) in NMC. The difference of metachronous recurrence between the MC group (10-90% mucin) and NMC group was significant (p < 0.01) (OR = 21.67, 95% confidence interval 3.8-120.5). Metachronous metastases were correlated with ypN2 (OR = 8.24, p = 0.01) in MC and in NMC. In NMC, mEMVI correlated with no PCR (p = 0.018) and ypN2 (p < 0.01). CONCLUSION: mEMVI could identify patients with NMC, who are at high risk of synchronous metastases. The MC group is at a high risk of developing metachronous metastases. Advances in knowledge: Patients at high risk of metastases are more likely to benefit from more aggressive neoadjuvant therapy.
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Adenocarcinoma Mucinoso/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Segunda Neoplasia Primária/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Retais/patologia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Valor Preditivo dos Testes , Estudos Prospectivos , Neoplasias Retais/diagnóstico , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Medição de Risco , Estatísticas não Paramétricas , Análise de SobrevidaRESUMO
INTRODUCTION: An accurate determination of human epidermal growth factor receptor 2 (Her2) status in women with breast cancer is mandatory to identify patients who will benefit from trastuzumab-based therapy. MATERIALS AND METHODS: Her2 immunohistochemical analysis (IHC) (performed with A0485 polyclonal antibody) on 943 invasive breast cancer cases was evaluated independently and blindly twice by 3 of us (V.A., I.P., and A.C.) according to DAKO scoring criteria. A total of 230 cases of invasive breast cancer scored 2+ at IHC and consequently evaluated by FISH were reviewed first independently, and then simultaneously by 3 of us (V.A., I.P., and A.C.) at a multiheaded microscope assessing the following parameters: overall signal intensity, granularity and continuity of membrane staining, and the presence of band-like membrane pattern in >25% of tumor cells. The frequencies of HER2 gene amplification for all the immunohistologic parameters (individually considered or in combination) were compared by Pearson χ analysis. RESULTS: Combinations of staining patterns did not give any statistically significant results, except when combining strong staining intensity and continuity of membrane signal. In fact, only 9 of the 86 cases with a weak-to-moderate staining intensity, which showed a fragmented membrane signal, resulted in being amplified by FISH, whereas 19 of the 51 cases presenting an overall strong IHC reaction and some extent of continuous membrane signal were FISH amplified (P=0.002). CONCLUSIONS: Combined intensity and linearity of membrane signal, although limited, resulted in the best aid (P=0.0002) in making the final score decision in borderline IHC Her2 tests similar to what is envisaged in the Her2 scoring system for gastric cancer.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Membrana Celular/metabolismo , Imuno-Histoquímica/normas , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Hibridização in Situ Fluorescente , Pessoa de Meia-Idade , Transporte Proteico , Receptor ErbB-2/imunologia , Padrões de Referência , Projetos de Pesquisa , TrastuzumabRESUMO
INTRODUCTION: The Y-box binding protein-1 (YB-1) is a multifunctional oncoprotein involved in the proliferation and aggressiveness of cancer cells. The aim of this study was to determine whether strong YB-1 expression in neoplastic cells of colorectal liver metastases (CRLM) may have an impact on liver disease-free survival following liver resection. MATERIALS AND METHODS: Immunohistochemistry was performed to evaluate YB-1 in 66 patients who underwent liver resection for CRLM. YB-1 expression was classified as weak (low-staining intensity) and strong (high-staining intensity). RESULTS: YB-1 expression was observed in the cytoplasm of all CRLM. YB-1 expression was weak in 17 patients (25.8%) and strong in 49 patients (74.2%). Liver recurrence rate was significantly higher in the strong than in the weak expression group: 55.1 vs. 23.5% (p = 0.023). Multivariable logistic regression analysis showed that YB-1 strong expression was the only independent risk factor for liver recurrence. The 5-year specific liver disease-free survival rate was 76.0% in the weak expression group and 41.5% in the strong expression group (p = 0.034). These results were not influenced by clinical prognostic factors of tumor recurrence. CONCLUSIONS: This is the first study showing that the degree of YB-1 expression in tissue specimens of CRLM predicts liver recurrence following liver resection.
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Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/patologia , Proteína 1 de Ligação a Y-Box/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Proteína 1 de Ligação a Y-Box/genéticaRESUMO
PURPOSE: To prospectively monitor the response in patients with locally advanced nonmucinous rectal cancer after chemoradiotherapy (CRT) using diffusion-weighted magnetic resonance imaging. The histopathologic finding was the reference standard. METHODS AND MATERIALS: The institutional review board approved the present study. A total of 62 patients (43 men and 19 women; mean age, 64 years; range, 28-83) provided informed consent. T(2)- and diffusion-weighted magnetic resonance imaging scans (b value, 0 and 1,000 mm(2)/s) were acquired before, during (mean 12 days), and 6-8 weeks after CRT. We compared the median apparent diffusion coefficients (ADCs) between responders and nonresponders and examined the associations with the Mandard tumor regression grade (TRG). The postoperative nodal status (ypN) was evaluated. The Mann-Whitney/Wilcoxon two-sample test was used to evaluate the relationships among the pretherapy ADCs, extramural vascular invasion, early percentage of increases in ADCs, and preoperative ADCs. RESULTS: Low pretreatment ADCs (<1.0 × 10(-3)mm(2)/s) were correlated with TRG 4 scores (p = .0011) and associated to extramural vascular invasion with ypN+ (85.7% positive predictive value for ypN+). During treatment, the mean percentage of increase in tumor ADC was significantly greater in the responders than in the nonresponders (p < .0001) and a >23% ADC increase had a 96.3% negative predictive value for TRG 4. In 9 of 16 complete responders, CRT-related tumor downsizing prevented ADC evaluations. The preoperative ADCs were significantly different (p = .0012) between the patients with and without downstaging (preoperative ADC ≥1.4 × 10(-3)mm(2)/s showed a positive and negative predictive value of 78.9% and 61.8%, respectively, for response assessment). The TRG 1 and TRG 2-4 groups were not significantly different. CONCLUSION: Diffusion-weighted magnetic resonance imaging seems to be a promising tool for monitoring the response to CRT.
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Quimiorradioterapia Adjuvante/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Retais/patologia , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
BACKGROUND: Two cases of acute hepatitis occurring during treatment with anastrozole have previously been reported, but the underlying mechanisms of liver injury are still uncertain. We report the case of anastrozole-related acute hepatitis with some autoimmune features. CASE PRESENTATION: A 70-year-old woman developed acute hepatitis associated with serum antinuclear antibodies during anastrozole treatment; after drug withdrawal, liver function parameters rapidly improved and serum auto-antibodies were no longer detectable. CONCLUSIONS: Anastrozole-induced hepatotoxicity is a very rare event. Drug-drug interactions or metabolically-mediated damage might be involved, with a possible role of individual susceptibility. Our report suggests that an immune-mediated mechanism may also be considered in anastrozole-related liver injury.
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Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/etiologia , Nitrilas/efeitos adversos , Triazóis/efeitos adversos , Doença Aguda , Idoso , Anastrozol , Anticorpos Antinucleares/sangue , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Feminino , Humanos , Nitrilas/uso terapêutico , Resultado do Tratamento , Triazóis/uso terapêuticoRESUMO
In recent years, preoperative therapy has become standard procedure for locally advanced rectal cancer. Tumor shrinkage due to preoperative chemotherapy-radiation therapy (CRT) is now a reality, and pathologically complete responses are not uncommon. Some researchers are now addressing organ preservation, thus increasing the demand for both functional and morphologic radiologic evaluation of response to CRT to distinguish responding from nonresponding tumors. On magnetic resonance (MR) images, post-CRT tumor morphologic features and volume changes have a high positive predictive value but a low negative predictive value for assessing response. Preliminary results indicate that diffusion-weighted MR imaging, especially at high b values, would be effective for prediction of treatment outcome and for early detection of tumor response. Some authors have reported that the use of apparent diffusion coefficient values in combination with other MR imaging criteria significantly improves discrimination between malignant and benign lymph nodes. Sequential determination of fluorodeoxyglucose uptake at positron emission tomography/computed tomography has proved useful in differentiating responding from nonresponding tumors during and at the end of CRT. However, radionuclide techniques have limitations, such as low spatial resolution and high cost. Large studies will be needed to verify the most effective morphologic and functional imaging modalities for post-CRT restaging of rectal cancer. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.303095085/-/DC1.
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Antineoplásicos/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Radioterapia Adjuvante , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Terapia Combinada , Humanos , Estadiamento de Neoplasias/métodos , Prognóstico , Resultado do TratamentoRESUMO
Hyaluronic acid (HA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are reliable markers of liver fibrosis and are closely linked to the proinflammatory status. In this pilot cohort study, we attempted to identify a clinical score that would predict the severity of nonalcoholic fatty liver disease (NAFLD) based on clinical variables and serum markers of fibrosis and inflammation. The cohort included 46 patients with histologically confirmed NAFLD (76.1% male; mean age, 43+/-13 years; mean body mass index [BMI], 27.8+/-3.5). Serum transforming growth factor beta (TGF-beta), HA, TIMP, and matrix metalloproteinase (MMP) levels were measured with commercial enzyme-linked immunoassay (ELISA) kits. Demographic features and clinical and laboratory findings were subjected to univariate and multivariate binary logistic regression analysis to construct the mathematical model. Receiver operating characteristic curve (ROC) analysis was used to identify a threshold value for diagnosis of NASH and to assess its sensitivity and specificity. Serum levels of HA and TIMP-1 were statistically different in patients with nonalcoholic steatohepatitis (NASH) (P<0.05). Logistic regression analysis of several clinical variables indicated patient age as the only independent predictor of NASH (odds ratio [OR], 1.129, 95% confidence interval [CI], 1.019-1.251, P=0.020). The mathematical model constructed on the basis of these results included age, TIMP-1, and HA levels. A value of 148.27 or more identified patients with NASH with 85.7% sensitivity, 87.1% specificity, and negative and positive predictive values of 96.4% and 60%, respectively. This model seems to represent a reliable noninvasive tool for excluding the presence of NASH. If validated in larger prospective cohort studies, it might be useful for determining when a liver biopsy is actually warranted in patients with NAFLD.
Assuntos
Fígado Gorduroso/sangue , Ácido Hialurônico/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Adolescente , Adulto , Fatores Etários , Estudos de Coortes , Fígado Gorduroso/diagnóstico , Feminino , Humanos , Testes de Função Hepática , Masculino , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Projetos Piloto , Análise de Regressão , Sensibilidade e Especificidade , Adulto JovemRESUMO
BACKGROUND/AIMS: The association between NAFLD and psoriasis has never been explored in prospective epidemiological studies. The aim of this 2-phase study was to study the clinical features of NAFLD in patients with psoriasis. METHODS: Phase 1: Investigation of prevalence and characteristics of NAFLD in an unselected cohort of 142 adult Italian outpatients with psoriasis vulgaris. Phase 2: Comparison of the psoriasis cohort subgroup with NAFLD and an age- and body mass index-matched retrospective cohort of 125 non-psoriasis patients with biopsy proven NAFLD. RESULTS: Based on histories, laboratory tests, and ultrasound studies, 84 (59.2%) received clinical diagnosis of NAFLD; 30 had factors potentially associated with liver disease other than NAFLD (e.g., viral hepatitis, significant ethanol, methotrexate use); and 28 (19.7%) had normal livers. Comparison of the normal-liver and NAFLD subgroups revealed that NAFLD in psoriasis patients (Ps-NAFLD) was significantly correlated with metabolic syndrome (p<0.05); obesity (p=0.043); hypercholesterolemia (p=0.029); hypertriglyceridemia (p<0.001); AST/ALT ratio >1 (p=0.019), and psoriatic arthritis (PsA) (p=0.036). The association with PsA remained significant after logistic regression analysis (OR=3.94 [CI, 1.07-14.46]). Compared with the retrospective non-psoriatic NAFLD cohort (controls), Ps-NAFLD patients (cases) were likely to have severe NAFLD reflected by non-invasive NAFLD Fibrosis Scores and AST/ALT >1. CONCLUSIONS: NAFLD is highly prevalent among psoriasis patients, where it is closely associated with obesity (overall and abdominal), metabolic syndrome, and PsA, and more likely to cause severe liver fibrosis (compared with nonPs-NAFLD). Routine work-up for NAFLD may be warranted in patients with psoriasis, especially when potentially hepatotoxic drug therapy is being considered.
Assuntos
Fígado Gorduroso/complicações , Psoríase/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/complicações , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Estudos Transversais , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/patologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Obesidade/complicações , Psoríase/patologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the accuracy of the water-immersion technique during upper endoscopy in recognizing the duodenal villous pattern in a series of children who were undergoing endoscopy to obtain duodenal biopsy for histological analysis. MATERIALS AND METHODS: The water-immersion technique was performed in 19 children. Endoscopic findings were compared with histology. Results were assessed on per biopsy analysis and per patient analysis, taking into account the worst endoscopic finding in each patient and correlating it with the worst histological diagnosis. RESULTS: Per biopsy analysis: A total of 57 biopsy specimens were obtained and assessed. The endoscopic duodenal investigation correctly identified 53 areas (93%), which corresponded to histology, giving it an accuracy rate of 93%. Per patient analysis: The worst histology of the duodenal bulb was predicted by endoscopy in 18 of the 19 enrolled patients (95%), whereas the worst histopathological lesion of the second portion of the duodenum was recognized in 100% of cases. On the whole, therefore, the endoscopist suggested a diagnosis of celiac disease in 11 patients, with both positive and negative predictive values of 100%. CONCLUSIONS: The water-immersion technique during upper endoscopy is highly accurate in recognizing the duodenal villous pattern in subjects who need a duodenal investigation. Our findings encourage a cost-saving and patient-retaining approach to the diagnosis of celiac disease by driving biopsy and reducing the number of duodenal samplings.
Assuntos
Doença Celíaca/patologia , Duodeno/patologia , Endoscopia Gastrointestinal/métodos , Mucosa Intestinal/patologia , Água , Adolescente , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Our objective was evaluate the outcome of primary clinical T4M0 extraperitoneal rectal cancer treated by neoadjuvant radiochemotherapy. Prognosis of clinical T4 rectal cancer is poor. Preoperative chemoradiation therapy may be beneficial. The results obtained are unclear due to lack of objective and strictly applied staging methods. METHODS: Patients with primary, clinical, T4MO, extraperitoneal rectal cancer, defined by transrectal ultrasonography, computed tomography or magnetic resonance imaging, were considered. Intraoperative radiotherapy and adjuvant chemotherapy were employed in some patients after curative resection (R0). Variables influencing the possibility to perform an R0 resection and a sphincter-saving procedure were investigated as predictors of outcome. RESULTS: 100 patients were included. R0 resection was performed in 78 patients. R0 resection rate was greater in females (93% vs 67%) and in responders to neoadjuvant chemoradiation (94% vs 60%). The ability to perform a sphincter-saving procedure was 57%, greater in middle rectal location (85% vs 51%) and in responders to the chemoradiation (70% vs 47%). Median follow-up was 31 months (range, 4-136). Local recurrences were found in 7 patients (10%). Five-year local control in R0 patients was 90% and better in the IORT group (100%). Distant relapse occurred in 24 patients (30%). Five-year overall survival was 59%, and was better after an R0 versus an R1 or R2 resection (68% vs 22%). Overall and disease free survival in R0 patients improved after overall downstaging. Adjuvant chemotherapy given in addition to the neoadjuvant therapy did not appear to offer benefit in improving survival. CONCLUSION: A multimodal approach enabled us to obtain a 5-year overall survival of about 60%. IORT increased local control. The role of adjuvant chemotherapy needs to be further investigated.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais/mortalidade , Neoplasias Retais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proctoscopia , Neoplasias Retais/patologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS: The general public's growing mistrust of the pharmaceutical industry and its perception of the lack of adverse effects of "natural" therapy have lead to the increasing use of "alternative drugs" for hypercholesterolemia. METHODS: A sixty-three year old woman presented with severe hypertransaminasemia that had developed progressively over a few weeks. For six months she had been taking Equisterol, an over-the-counter lipid-lowering product containing guggulsterol and red yeast rice extract. The product had been prescribed for hypercholesterolemia because the patient had developed hepatotoxicity while on lovastatin. RESULTS: Liver biopsy revealed severe lobular necroinflammatory changes with an eosinophilic infiltrate. The episode was regarded as an adverse drug reaction after exclusion of other possible causes of acute liver disease and the prompt normalization of liver function tests after Equisterol had been discontinued. Red yeast rice extract's cholesterol-lowering properties are largely due to fungal metabolites known as monacolins, one of which--monacolin K--is identical to lovastatin. CONCLUSIONS: The choice of an alternative medicine approach in this case subjected the patient to "re-challenge" with the official medicine agent that had previously caused mild hepatotoxicity. Physicians should keep in mind that "alternative" medicine is not always the safest alternative and sometimes it is not even "alternative."