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1.
Int J Colorectal Dis ; 39(1): 77, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38782770

RESUMO

PURPOSE: The diagnostic accuracy of Narrow Band Imaging (NBI) in the endoscopic surveillance of ulcerative colitis (UC) has been disappointing in most trials which used the Kudo classification. We aim to compare the performance of NBI in the lesion characterization of UC, when applied according to three different classifications (NICE, Kudo, Kudo-IBD). METHODS: In a prospective, real-life study, all visible lesions found during consecutive surveillance colonoscopies with NBI (Exera-II CV-180) for UC were classified as suspected or non-suspected for neoplasia according to the NICE, Kudo and Kudo-IBD criteria. The sensitivity (SE), specificity (SP), positive (+LR) and negative (-LR) likelihood ratios of the three classifications were calculated, using histology as the reference standard. RESULTS: 394 lesions (mean size 6 mm, range 2-40 mm) from 84 patients were analysed. Twenty-one neoplastic (5%), 49 hyperplastic (12%), and 324 inflammatory (82%) lesions were found. The diagnostic accuracy of the NICE, Kudo and Kudo-IBD classifications were, respectively: SE 76%-71%-86%; SP 55-69%-79% (p < 0.05 Kudo-IBD vs. both Kudo and NICE); +LR 1.69-2.34-4.15 (p < 0.05 Kudo-IBD vs. both Kudo and NICE); -LR 0.43-0.41-0.18. CONCLUSION: The diagnostic accuracy of NBI in the differentiation of neoplastic and non-neoplastic lesions in UC is low if used with conventional classifications of the general population, but it is significantly better with the modified Kudo classification specific for UC.


Assuntos
Colite Ulcerativa , Colonoscopia , Imagem de Banda Estreita , Humanos , Colite Ulcerativa/diagnóstico por imagem , Colite Ulcerativa/patologia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/classificação , Imagem de Banda Estreita/métodos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Colonoscopia/métodos , Idoso , Vigilância da População
3.
Children (Basel) ; 10(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-38002862

RESUMO

BACKGROUND: In children, laparoscopic cholecystectomy (LC) is now considered the gold standard for gallbladder (GB) removal. In the past, hemolytic disorders associated with cholelithiasis represented the most frequent conditions requiring LC; this is being overtaken by cholelithiasis and biliary conditions in overweight or ex-premature children. AIMS: This study aims to describe current indications and timing for LC in pediatric patients. METHODS: Retrospective study. Data on previous medical therapy, ultrasound, pre- and intraoperative aspects, and histology were collected for patients treated in 2020-2023. RESULTS: In total, 45 patients were enrolled: 15 who underwent urgent surgery and 30 electives. Groups differed in terms of obesity rate, symptoms, ultrasound features, and intraoperative status. The most relevant risk factors for surgical complexity were age and pubertal stage, elevated cholestasis indexes, and gallbladder wall thickness > 3 mm at ultrasound. GB wall thickening ≥3 mm, US Murphy sign, fluid collections, and gallbladder distention on ultrasound correlated with high surgical scores. CONCLUSIONS: Indications for laparoscopic cholecystectomy in children seem to evolve caused by changing characteristics of the pediatric population. Patients with overweight/obesity may develop more complex GB diseases. Asymptomatic patients should be considered for surgery after observation, considering age and/or pubertal maturation when other risk factors are absent.

4.
Ital J Pediatr ; 48(1): 175, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109763

RESUMO

BACKGROUND: Cholestasis in extremely premature infants (EPI) constitutes a nutritional challenge and maltodextrins have been reported as a possible strategy for hypoglycaemia. We aim to describe the nutritional management of an EPI with non-syndromic bile duct paucity (NSBDP) and feeding intolerance. CASE PRESENTATION: A patient, born at 27 weeks of gestational age, presented cholestatic jaundice at 20 days of life with a clinical picture of NSBDP. Patient's growth was insufficient with formula rich in medium-chain triglyceride (MCT) and branched-chain amino acids (BCAA). Due to frequent fasting hypoglicemic episodes, maltodextrins supplements were provided. He subsequently presented severe abdominal distension and painful crises, which required hospital admission and withdrawal of maltodextrins. Hypercaloric extensively hydrolysed formula provided weight gain, glycemic control, and parallel improvement in cholestasis. CONCLUSIONS: Our case suggests caution with the use of maltodextrins in infants, especially if premature. Commercial preparations for hepatopatic patients contain higher concentrations of MCTs and BCAAs, but personalized strategies must be tailored to each patient.


Assuntos
Colestase , Hipersensibilidade a Leite , Aminoácidos de Cadeia Ramificada , Animais , Ductos Biliares , Bovinos , Feminino , Humanos , Recém-Nascido , Masculino , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Polissacarídeos , Triglicerídeos
5.
J Surg Case Rep ; 2022(6): rjac305, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35755016

RESUMO

Intestinal tuberculosis (ITB) represents an important diagnostic challenge in the clinical setting, as it generally can occur as a chronic condition often mimicking other diseases such as Crohn's disease (CD), and can present itself with acute onset, which can be life-threatening. A 29-years-old Chinese woman coming to ER with abdominal pain, fever and weight loss. Computed tomography and colonoscopy images were not diagnostic. Despite medical therapy, the patient progressively worsened developing sepsis requiring emergency surgery. Pathological and microbiological examination of the colon both pointed towards gastrointestinal tuberculosis involvement. Although ITB is generally a chronic-wasting condition, it can also occur as acute abdomen representing an absolute surgical emergency. Although caseation and necrosis in granulomas can be used for diagnosis of ITB, preoperative diagnosis is still challenging. Endoscopic biopsies targeted to ulcerous lesions could be an essential diagnostic tool, contrary to those targeted to the ulcers' edges as performed in CD.

7.
Tumori ; 107(2): 150-159, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32522106

RESUMO

BACKGROUND: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III ß-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. METHODS: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. RESULTS: Patients with TUBB3 protein levels >750 and <750 amol/µg were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%; p = 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%; p = 0.09), with a statistically significant interaction between TUBB3 and treatment (p = 0.049). CONCLUSIONS: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Tubulina (Proteína)/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Docetaxel/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Masculino , Prognóstico , Neoplasias Gástricas/metabolismo , Pesquisa Translacional Biomédica/métodos
8.
J Natl Compr Canc Netw ; 18(10): 1327-1336, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022642

RESUMO

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.


Assuntos
Melanoma , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas , Adolescente , Adulto , Criança , Intervalo Livre de Doença , Humanos , Metástase Linfática , Melanoma/diagnóstico , Mitose , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico , Adulto Jovem
9.
Liver Int ; 40(9): 2110-2116, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32654359

RESUMO

SARS2-CoV-2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post-mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID-19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS-CoV-2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS-CoV-2 triggers a series of reactions leading to striking vascular alterations.


Assuntos
Infecções por Coronavirus/patologia , Fígado/patologia , Pneumonia Viral/patologia , Veia Porta/patologia , Insuficiência Respiratória/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Insuficiência Respiratória/virologia , SARS-CoV-2
10.
Lancet Infect Dis ; 20(10): 1135-1140, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526193

RESUMO

BACKGROUND: COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. METHODS: We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. FINDINGS: All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. INTERPRETATION: The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. FUNDING: None.


Assuntos
Infecções por Coronavirus/patologia , Pulmão/patologia , Pneumonia Viral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Doença da Membrana Hialina , Inflamação , Itália/epidemiologia , Pulmão/irrigação sanguínea , Pulmão/ultraestrutura , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Alvéolos Pulmonares/irrigação sanguínea , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/ultraestrutura , Alvéolos Pulmonares/virologia , Artéria Pulmonar/patologia , SARS-CoV-2 , Trombose
11.
Oncologist ; 25(3): e460-e468, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32162808

RESUMO

BACKGROUND: Patients with high microsatellite instability (MSI) gastric cancer (GC) show improved survival and no benefit or harm from adjuvant and/or perioperative chemotherapy. The role of immune microenvironment in GC is largely unknown. MATERIALS AND METHODS: In the present study, 256 tumor tissue blocks were centrally collected from patients enrolled in ITACA-S, a randomized adjuvant trial of 5-FU/LV versus sequential FOLFIRI and cisplatin-docetaxel. MSI status was assessed by multiplex PCR, inflammatory reaction by H&E morphological assessment, and programmed death-ligand 1 (PD-L1) expression by immunohistochemistry. RESULTS: Overall, 9% patients had MSI-high tumors, 23% had high inflammatory reaction, 11% had tumor PD-L1 ≥ 1%, and 11% had stromal PD-L1 ≥ 1%. A significant association with disease-free survival (DFS) and overall survival (OS) was found for MSI-high (hazard ratio [HR], 0.43; p = .02; HR, 0.40; p = .02) and high inflammatory reaction (HR, 0.55; p = .010; HR, 0.53; p = .008) but not for PD-L1. At multivariable analysis, only MSI showed an independent association with both DFS (p = .02) and OS (p = .01), whereas inflammatory reaction showed an independent association only with OS (p = .04). Patients with tumor PD-L1 ≥ 1% had a significantly longer DFS in sequential chemotherapy than in than 5-FU/LV arm (interaction p = .04) and a trend for OS (interaction p = .12). CONCLUSION: Our data suggest that MSI status could be a useful prognostic biomarker in patients with radically resected stage II-III GC and should be used as stratification factor in future trials. Tumor PD-L1 ≥ 1% should be further investigated as a potential predictor of benefit from intensive chemotherapy. IMPLICATIONS FOR PRACTICE: In this post hoc analysis of patients with radically resected gastric cancer randomized to an intensive sequential chemotherapy regimen versus 5-FU/LV monotherapy as adjuvant treatment in the ITACA-S trial, MSI-high status was independently associated with better disease-free survival and overall survival (OS) and inflammatory reaction was independently associated with better OS. Moreover, tumor PD-L1 expression ≥1% was associated with greater benefit from intensive sequential chemotherapy compared with 5-fluorouracil plus leucovorin (5-FU/LV), whereas PD-L1 expression <1% was not, conditioning a statistically significant interaction between such biomarker and treatment arms. The meta-analysis of individual patients' data from available studies could yield data on the role of MSI status that could inform clinical decisions.


Assuntos
Instabilidade de Microssatélites , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/genética , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Docetaxel/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Microambiente Tumoral
12.
BJR Case Rep ; 5(2): 20180036, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31501694

RESUMO

Solid tumors of the spleen are rare, with an incidence of 0.007% in all operating and autopsy specimens. In terms of microscopic structure and function, the spleen consists of two parts: the white pulp, which plays an important role in the immune system and the red pulp, which filters the blood.Primary splenic neoplasms can be classified into lymphoid neoplasms arising from the white pulp, and vascular neoplasms which arise from the red pulp.Primary tumors arising from vascular elements include benign lesions such as hemangioma, lymphangioma and hamartoma, intermediate lesions such as hemangioendothelioma, hemangiopericytoma and littoral cell angioma as well as the frankly malignant hemangiosarcoma.It is usually difficult to distinguish a benign from a malignant lesion with preoperative imaging studies and cytological exam by fine-needle aspiration (FNA), that is not easily obtained because of the risk of bleeding.Therefore a splenectomy should be necessary for a definitive diagnosis of splenic tumors.Martel and all for the first time described the sclerosing angiomatoid nodular transformation (SANT), like a vascular lesion of the spleen, with benign clinical course consisting by altered red pulp tissue that has been entrapped by a non-neoplastic stromal proliferative process.We describe a rare case of benign splenic mass documented with FDG/PET-CT (referred as equivocal), CT and MRI.

13.
Liver Int ; 39(1): 158-167, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30218633

RESUMO

BACKGROUND AND AIMS: Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI. METHODS: By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images. RESULTS: All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy). CONCLUSIONS: OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.


Assuntos
Adenoma de Células Hepáticas/diagnóstico , Hiperplasia Nodular Focal do Fígado/diagnóstico , Neoplasias Hepáticas/diagnóstico , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Membro 1B3 da Família de Transportadores de Ânion Orgânico Carreador de Soluto/genética , Adenoma de Células Hepáticas/genética , Adulto , Transporte Biológico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Meios de Contraste/metabolismo , Diagnóstico Diferencial , Feminino , Hiperplasia Nodular Focal do Fígado/genética , Gadolínio DTPA/metabolismo , Humanos , Aumento da Imagem , Imuno-Histoquímica , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
15.
Clin Cancer Res ; 24(5): 1082-1089, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29208673

RESUMO

Purpose: Refining the selection of HER2-positive metastatic gastric cancer patient candidates for trastuzumab is a challenge of precision oncology. Preclinical studies have suggested several genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than HER2 or downstream signaling pathways.Experimental Design: We carried out this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of candidate genomic alterations (AMNESIA panel), including EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications. Hypothesizing a prevalence of candidate alterations of 30% and 0% in resistant and sensitive HER2-positive patients, respectively, 20 patients per group were needed.Results: AMNESIA panel alterations were significantly more frequent in resistant (11 of 20, 55%) as compared with sensitive (0% of 17) patients (P < 0.001), and in HER2 IHC 2+ (7 of 13, 53.8%) than 3+ (4 of 24, 16.7%) tumors (P = 0.028). Patients with tumors bearing no candidate alterations had a significantly longer median progression-free [5.2 vs. 2.6 months; HR, 0.34; 95% confidence interval (CI), 0.07-0.48; P = 0.001] and overall survival (16.1 vs. 7.6 months; HR, 0.38; 95% CI, 0.09-0.75; P = 0.015). The predictive accuracy of the AMNESIA panel and HER2 IHC was 76% and 65%, respectively. The predictive accuracy of the combined evaluation of the AMNESIA panel and HER2 IHC was 84%.Conclusions: Our panel of candidate genomic alterations may be clinically useful to predict primary resistance to trastuzumab in patients with HER2-positive metastatic gastric cancer and should be further validated with the aim of molecularly stratifying HER2-addicted cancers for the development of novel treatment strategies. Clin Cancer Res; 24(5); 1082-9. ©2017 AACR.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Gástricas/tratamento farmacológico , Trastuzumab/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Seleção de Pacientes , Medicina de Precisão/métodos , Intervalo Livre de Progressão , Estudos Prospectivos , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Critérios de Avaliação de Resposta em Tumores Sólidos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico
17.
Oncology ; 93(5): 279-286, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28881354

RESUMO

OBJECTIVES: This phase II trial was aimed at assessing the safety and activity of capecitabine, oxaliplatin, and irinotecan (COI regimen) as a preoperative treatment for resectable gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. METHODS: Patients affected by T3-T4/N0-N+/M0 GC/GEJ cancer were treated with the COI regimen for 4 cycles followed by restaging and gastroresection with D2 lymphadenectomy. Four postoperative cycles were scheduled. The primary endpoint was pathological response rate according to Becker et al. [Cancer 2003;98:1521-1530]. The potential role of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a predictive biomarker of pathological tumor response was assessed in a subgroup of 19 evaluable patients. RESULTS: Between January 2011 and October 2015, a total of 40 patients were enrolled. After the preoperative phase, 36 out of 40 patients (90%) were considered eligible for surgery: 12 patients (30%) achieved a pathological response. The most frequent grade 3/4 adverse events were diarrhea (27%), nausea (25%), and fatigue (17%). Grade 3 neutropenia occurred in 7.5% of patients. A lower standard uptake value at baseline FDG-PET/CT was associated with pathological response. CONCLUSION: COI combination is active with a manageable toxicity profile in patients with resectable GC or GEJ cancer. FDG-PET/CT imaging as a surrogate biomarker of pathological response in this setting appears fascinating but should be further investigated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Junção Esofagogástrica/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Capecitabina/administração & dosagem , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/metabolismo , Junção Esofagogástrica/patologia , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cuidados Pós-Operatórios/métodos , Cuidados Pré-Operatórios/métodos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
18.
Gastric Cancer ; 19(2): 412-420, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25862567

RESUMO

A correlation between osteopontin, E-cadherin, ß-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, ß-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal ß-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Osteopontina/metabolismo , Neoplasias Gástricas/cirurgia , beta Catenina/metabolismo , Idoso , Antígenos CD , Ciclo-Oxigenase 2/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
19.
Cardiovasc Intervent Radiol ; 38(1): 129-34, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24870698

RESUMO

PURPOSE: To evaluate the short-term safety and efficacy of the new generation of 70-150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT). METHODS: Forty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response. RESULTS: All patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1-6) and 43 mm (range 10-190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2-4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures). CONCLUSION: DEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Doxorrubicina/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Microesferas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Meios de Contraste , Feminino , Humanos , Iopamidol , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Intensificação de Imagem Radiográfica , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto Jovem
20.
Med Oncol ; 30(3): 610, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23700226

RESUMO

Our group and numerous others have shown in both preclinical and clinical studies that the proapoptotic mediator BAX may be deregulated through gene mutation or loss of protein expression, affecting resistance to chemotherapy and radiotherapy in several cancer types. However, BAX is also involved in cancer development and may related to prognosis, independently of treatment outcome. The clinical impact of BAX status in gastrointestinal malignancies remains controversial, although it is generally hypothesized that high expression may be a positive prognostic factor and predict increased efficacy of chemotherapy (with particular regard to platinum derivatives). The present review aims to provide updated information on BAX as potential prognostic and/or predictive biomarker in gastroesophageal and colorectal cancers, as well as in other less studied gastrointestinal malignancies.


Assuntos
Neoplasias Gastrointestinais/patologia , Proteína X Associada a bcl-2/genética , Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/genética , Humanos , Prognóstico , Resultado do Tratamento
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