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1.
Rev Esp Enferm Dig ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832594

RESUMO

Endoscopic full-thickness resection (eFTR) is an emerging technique that enables effective and safe management of complex colorectal lesions. The full-thickness resection device (FTRD®, Ovesco, Germany) has primarily been used for non-exposed transmural resection of challenging subepithelial or epithelial lesions, where conventional methods may be limited. This technique represents an alternative to surgery in selected patients, and its applications are rapidly expanding. In recent years, eFTR has been described as an alternative to surgery for scars aiming to exclude residual tumors after non-curative endoscopic resection. We present a case of a 41-year-old woman with Lynch syndrome (dMLH1) with rectal adenocarcinoma at the age of 20 underwent anterior resection of the rectum and adjuvant chemoradiotherapy. At the age of 39, during endoscopic surveillance, she presented with a suspicious lesion (Paris 0-Is+IIa, NICE2, JNET2B) measuring 16mm in the hepatic angle, and underwent en bloc endoscopic mucosal resection (EMR). Histopathological analysis revealed a low-grade invasive adenocarcinoma with lymphoid stroma with deep invasion of the submucosa and resection margin involvement (vertical R1). After a multidisciplinary team discussion, complementary surgery was proposed but the patient refused, opting for close endoscopic and imaging surveillance. Two subsequent colonoscopies plus computed tomography (CT) scans showed no signs of macro or microscopic residual or recurrent tumor, even after extensive biopsies of the colonic scar. However, a CT scan 20months post-resection showed a de novo 2cm thickening of the parietal wall in the hepatic angle, consistent with the location of the previous endoscopic resection. Suspecting deep parietal tumor recurrence without superficial endoscopic findings, a transmural endoscopic resection using FTRD® of the EMR scar was performed, whose histology revealed no transparietal tumor recurrence.

2.
Pathobiology ; 90(6): 417-421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37290407

RESUMO

INTRODUCTION: Recent studies have highlighted the presence of hepatic progenitor cells (HPCs) in metastatic liver carcinomas. We provide further evidence of this phenomenon, presenting a case of a gastrointestinal stromal tumour (GIST) liver metastasis with evidence of intra- and peritumoral HPC. CASE DESCRIPTION: A 64-year-old man presented with a gastric mass diagnosed as a high-risk KIT-mutated GIST. The patient was treated with imatinib, recurring 5 years later with a liver mass. Liver biopsy disclosed a GIST metastasis, hallmarked by a proliferation of ductular structures without cytological atypia intermingled with the tumour cells, with a CK7/CK19/CD56-positive immunophenotype and rare CD44 positivity. The patient underwent liver resection, and the same ductular structures were present in the tumour interior and at its periphery. CONCLUSION: We document for the time the presence of HPC in the form of ductular structures in a GIST liver metastasis, further supporting their role in the liver metastatic niche.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Tumores do Estroma Gastrointestinal/genética , Mesilato de Imatinib/uso terapêutico , Células-Tronco/patologia
3.
Rev Esp Enferm Dig ; 115(2): 100, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35748462

RESUMO

Iron-deficiency anemia is a prevalent condition usually treated with iron supplementation. Iron pill-induced gastritis is an under-recognized, albeit serious potential complication of iron pill ingestion in the upper gastrointestinal tract. This entity must be identified by healthcare providers who prescribe iron. The diagnosis of this unusual drug-induced disease is based on endoscopic findings and histopathological examination, because the clinical symptoms are vague and non-specific. Herein we report a case of a 79-year-old woman with iron-deficiency anemia taking oral ferrous sulfate with multiple congestive and eroded polypoid lesions. Histology showed an H. pylori-negative erosive gastritis with iron deposition, confirming the diagnosis of iron pill-induced gastritis. The aim of this report is to highlight that iron pill-induced gastritis is an under-diagnosed entity that must be kept in mind when patients undergo chronic iron-pill therapy because it can lead to serious complications of the upper gastrointestinal tract.


Assuntos
Anemia Ferropriva , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Trato Gastrointestinal Superior , Feminino , Humanos , Idoso , Ferro/efeitos adversos , Anemia Ferropriva/tratamento farmacológico , Anemia Ferropriva/complicações , Gastrite/induzido quimicamente , Gastrite/diagnóstico , Gastrite/complicações , Trato Gastrointestinal Superior/patologia , Infecções por Helicobacter/tratamento farmacológico
4.
Semin Cancer Biol ; 71: 42-51, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32679190

RESUMO

Colorectal cancer is highly incident worldwide and presents a health burden with elevated mortality rate despite prevention, detection, and treatment, mainly due to metastatic liver disease. Histological growth patterns of colorectal cancer liver metastases have emerged as a reproducible prognostic factor, with biological implications and therapeutic windows. Nonetheless, the histological growth patterns of colorectal cancer liver metastases are only known after pathological examination of a liver resection specimen, thus limiting the possibilities of pre-surgical decision. Predicting the histological growth pattern of colorectal cancer liver metastases would provide valuable information for patient-tailored medicine. In this article, we perform a review of the histological growth patterns and their implications, with a focus on the possibilities for their prediction.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Animais , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia
5.
Int J Mol Sci ; 19(9)2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208622

RESUMO

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.


Assuntos
Antioxidantes/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Tióctico/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Fígado Gorduroso/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
6.
Rev Esp Enferm Dig ; 109(5): 393, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28247771

RESUMO

A 48-year old female patient was admitted to the emergency department with upper gastrointestinal bleeding. Endoscopy showed large esophageal varices that were treated with band ligation. She had been treated with cyclophosphamide, melphalan, lenalidomide and corticosteroids for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy or edema, M protein, skin changes). She had no other risk factors for chronic liver disease. Laboratory and radiological examinations could not confirm the etiology of portal hypertension. The liver biopsy suggested hepatoportal sclerosis, compatible with idiopathic portal hypertension (IPH). Under a band ligation program, with beta-blocker, diuretics and prophylactic anticoagulation, the patient remains stable. In POEMS syndrome, a rare multi-systemic disease, the most frequent liver manifestation is hepatomegaly(1). To the best of authors' knowledge, IPH has been reported only 3 times in POEMS syndrome(2,3,4) and this is the second case reporting the occurrence of histological findings compatible with IPH. As the precise etiopathogenesis of IPH is not fully elucidated and as it is an extremely uncommon manifestation in POEMS, it is not yet certain whether IPH is part of the syndrome or whether it develops independently. While some investigators believe that there is a congenital vascular anomaly involving the changes in the portal tract, the majority support an acquired vascular defect hypothesis(5). The acquired IPH hypothesis emphasizes a possible role of various pathogenic determinants: infections, prothrombotic states, prolonged exposure to several medications and toxins, immunological basis and progressive fibrosis of the portal veins (5). In this hypothesis, a hepatic circulation defect secondary to POEMS syndrome, which includes pro-inflammatory (VEGF, interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, tumor growth factor-ß) and pro-thrombotic factors (aberrations in the thrombin-antithrombin complex)(1) which have been documented in the IPH and POEMS syndrome, may contribute to a possible association between these entities. Although the association between these two entities is yet to be confirmed, the authors present this case in order to contribute to its elucidation.


Assuntos
Hipertensão Portal/etiologia , Cirrose Hepática/etiologia , Síndrome POEMS/complicações , Pancitopenia/etiologia , Esplenomegalia/etiologia , Feminino , Humanos , Hipertensão Portal/diagnóstico , Cirrose Hepática/diagnóstico , Pessoa de Meia-Idade , Pancitopenia/diagnóstico , Fatores de Risco , Esplenomegalia/diagnóstico , Hipertensão Portal não Cirrótica Idiopática
7.
Rev Esp Enferm Dig ; 109(6): 465-468, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28376623

RESUMO

Autoimmune cholangitis (AIC) was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC), but who were antimitochondrial (AMA) negative and antinuclear antibodies (ANA) positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1). AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA) but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2). In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH). The diagnostic differentiation between these diseases (AIC, PBC and AIH) is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases.


Assuntos
Doenças Autoimunes/terapia , Colangite/terapia , Adulto , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/patologia , Biópsia , Colangite/diagnóstico por imagem , Colangite/patologia , Feminino , Humanos , Fígado/patologia , Pessoa de Meia-Idade , Ultrassonografia
8.
BMC Cancer ; 15: 247, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25886004

RESUMO

BACKGROUND: Oxaliplatin based chemotherapy is often used as adjuvant therapy in colon and rectal cancer. A reported side effect is Sinusoidal Obstruction Syndrome which is characterized by a spectrum of pathologic changes, from sinusoidal dilation, peri-sinusoidal haemorrhage, peliosis and nodular regenerative hyperplasia. Very rarely it can cause the development of liver nodules mimicking liver metastases. Herein, we report a case of Sinusoidal Obstruction Syndrome causing a liver nodule suspicious of liver metastasis on imaging. This is the third reported case of this complication of oxaliplatin toxicity, in which resection was performed and pathological diagnosis confirmed. CASE PRESENTATION: We report the case of a 59 year old man with stage III colon cancer who underwent sigmoidectomy followed by adjuvant chemotherapy with oxaliplatin. One year after surgery a liver nodule was detected and the patient underwent right hepatectomy. Pathology showed no liver nodule and diagnosed sinusoidal obstruction syndrome. CONCLUSION: We describe the third reported case of a liver lesion mimicking a liver metastasis after oxaliplatin-based chemotherapy for colon cancer. We suggest that in patients heavily treated with oxaliplatin with de novo liver nodules, this differential diagnosis should be considered. In particular, in this population of patients an intense imagiologic evaluation and even a preoperative biopsy should be pursued to confirm the diagnosis of malignancy and avoid overtreatment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Colorretais/complicações , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Fígado/efeitos dos fármacos , Fígado/patologia , Compostos Organoplatínicos/efeitos adversos , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Tomografia Computadorizada por Raios X
9.
BMC Gastroenterol ; 15: 23, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25886722

RESUMO

BACKGROUND: Empiric triple treatments for Helicobacter pylori (H. pylori) are increasingly unsuccessful. We evaluated factors associated with failure of these treatments in the central region of Portugal. METHODS: This single-center, prospective study included 154 patients with positive (13)C-urea breath test (UBT). Patients with no previous H. pylori treatments (Group A, n = 103) received pantoprazole 40 mg 2×/day, amoxicillin 1000 mg 12/12 h and clarithromycin (CLARI) 500 mg 12/12 h, for 14 days. Patients with previous failed treatments (Group B, n = 51) and no history of levofloxacin (LVX) consumption were prescribed pantoprazole 40 mg 2×/day, amoxicillin 1000 mg 12/12 h and LVX 250 mg 12/12 h, for 10 days. H. pylori eradication was assessed by UBT 6-10 weeks after treatment. Compliance and adverse events were assessed by verbal and written questionnaires. Risk factors for eradication failure were determined by multivariate analysis. RESULTS: Intention-to-treat and per-protocol eradication rates were Group A: 68.9% (95% CI: 59.4-77.1%) and 68.8% (95% CI: 58.9-77.2%); Group B: 52.9% (95% CI: 39.5-66%) and 55.1% (95% CI: 41.3-68.2%), with 43.7% of Group A and 31.4% of Group B reporting adverse events. Main risk factors for failure were H. pylori resistance to CLARI and LVX in Groups A and B, respectively. Another independent risk factor in Group A was history of frequent infections (OR = 4.24; 95% CI 1.04-17.24). For patients with no H. pylori resistance to CLARI, a history of frequent infections (OR = 4.76; 95% CI 1.24-18.27) and active tobacco consumption (OR = 5.25; 95% CI 1.22-22.69) were also associated with eradication failure. CONCLUSIONS: Empiric first and second-line triple treatments have unacceptable eradication rates in the central region of Portugal and cannot be used, according to Maastricht recommendations. Even for cases with no H. pylori resistance to the used antibiotics, results were unacceptable and, at least for CLARI, are influenced by history of frequent infections and tobacco consumption.


Assuntos
2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Levofloxacino/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Testes Respiratórios , Farmacorresistência Bacteriana/genética , Quimioterapia Combinada/métodos , Feminino , Helicobacter pylori/genética , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Nitroimidazóis/uso terapêutico , Pantoprazol , Portugal , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Falha de Tratamento , Adulto Jovem
10.
Dig Dis Sci ; 60(1): 74-85, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25142169

RESUMO

BACKGROUND: Outcome of Helicobacter pylori (H. pylori) infection results from interaction of multiple variables including host, environmental and bacterial-associated virulence factors. AIM: This study aimed to investigate the correlation of cagA, cagE, vacA, iceA and babA2 genotypes with gastric histopathology and disease phenotype in the central region of a South-European country. METHODS: This prospective study involved 148 infected patients (110 female; mean age 43.5 ± 13.4 years) submitted to endoscopy with corpus and antrum biopsies. H. pylori was cultured and DNA extracted from the isolates. Genotypes were determined by PCR. Histopathological features were graded according to the updated Sydney system and OLGA/OLGIM classification. Only patients with single H. pylori genotypes and complete histopathological results were included. RESULTS: Antrum samples presented higher degrees of atrophy, intestinal metaplasia, chronic inflammation and neutrophil activity. Genotype distribution was as follows: cagA-31.8 %; cagE-45.9 %; vacA s1a-24.3 %; vacA s1b-19.6 %; vacA s1c-0.7 %; vacA s2-55.4 %; vacA m1-20.9 %; vacA m2-79.1 %; vacA s1m1-18.9 %; vacA s1m2-25.7 %; vacA s2m1-2 %; vacA s2m2-53.4 %; iceA1-33.8 %; iceA2-66.2 %; babA2-12.2 %. CagA genotype was significantly associated with higher degrees of intestinal metaplasia, neutrophil activity, chronic inflammation and OLGIM stages. BabA2 was linked with higher H. pylori density. Strains with vacA s1m1 or vacA s1m1 + cagA positive genotypes had a significant association with peptic ulcer and vacA s2m2 with iron-deficient anemia. CONCLUSIONS: cagA, vacA s1m1 and babA2 genotypes are relatively rare in the central region of Portugal. cagA-positive strains are correlated with more severe histopathological modifications. This gene is commonly associated with vacA s1m1, and such isolates are frequently found in patients with peptic ulcer.


Assuntos
Proteínas de Bactérias/genética , Gastrite/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Adesinas Bacterianas/genética , Adolescente , Adulto , Idoso , Antígenos de Bactérias/genética , Feminino , Gastrite/genética , Gastrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Portugal , Estudos Prospectivos , Estudos Soroepidemiológicos , Estômago/patologia , Virulência , Adulto Jovem
11.
Scand J Gastroenterol ; 49(10): 1219-29, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25157637

RESUMO

BACKGROUND: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer (CRC). Aberrant crypt foci (ACF) are important biomarkers of sporadic CRC risk. Their correlation with the risk of intraepithelial neoplasia (IN) in UC remains unclear. AIMS: To assess whether ACF are a risk factor for IN in long-standing UC and to investigate any correlation between the clinico-epidemiological characteristics and prevalence/number of ACF in these patients. METHODS: Seventy-six patients with long-standing UC were prospectively screened by colonoscopy with chromoendoscopy-guided endomicroscopy. ACF were sought in the lower rectum. RESULTS: Eight INs were detected in seven (9.2%) patients. The ACF prevalence and mean number were 60.5% and 2.4 ± 2.8, respectively. The number of ACF was independently associated with the risk of having IN (odds ratio = 1.338; 95% confidence interval 1.030-1.738). ACF number revealed a good calibration (area under the receiver operating characteristic curve = 0.829) and discriminative ability (p = 0.205, Hosmer-Lemeshow test) for the prediction of synchronous IN. Patients with ≥3 ACF have a significantly higher prevalence of IN than patients with <3 ACF (22.6% vs. 0%, p = 0.001). Using this cut-off value, the performance of ACF in predicting the presence of IN was as follows: sensitivity = 100%, specificity = 65.2%, positive predictive value = 22.6%, and negative predictive value = 100%. Age >40 years, family history of CRC, and increased body mass index (BMI) were associated with a significantly higher number of ACF. CONCLUSION: Long-standing UC patients with ≥3 ACF have a significantly higher likelihood of having IN. Age >40 years, family history of CRC, and increased BMI have significant positive associations with the number of ACF.


Assuntos
Focos de Criptas Aberrantes/patologia , Carcinoma in Situ/patologia , Colite Ulcerativa/patologia , Neoplasias Colorretais/patologia , Focos de Criptas Aberrantes/complicações , Focos de Criptas Aberrantes/epidemiologia , Focos de Criptas Aberrantes/genética , Adulto , Fatores Etários , Idoso , Área Sob a Curva , Índice de Massa Corporal , Carcinoma in Situ/complicações , Carcinoma in Situ/epidemiologia , Colite Ulcerativa/complicações , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Estudos Transversais , Feminino , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Curva ROC , Reto , Fatores de Risco
13.
Rev Esp Patol ; 57(2): 141-145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599736

RESUMO

Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour with a high local and distant metastasis rate and limited response to chemotherapy. Meckel's diverticulum is the most frequent congenital anomaly, and it is associated with a considerable risk of malignant transformation. In this case report, we describe a 50-year-old female patient with a history of extraskeletal myxoid chondrosarcoma of the lower limb and metastasis to the forearm who went to the emergency department with abdominal pain. The investigations revealed a caecal volvulus. A lesion in the middle third of the ileum was incidentally discovered and removed during surgery. Pathology examination revealed a Meckel's diverticulum adenocarcinoma, with metastasis of extraskeletal myxoid chondrosarcoma. Resection was complete; however, the patient had diffuse metastatic pulmonary disease and died eight months later due to disease progression. This mechanism of tumour-to-tumour metastasis is described in other locations, but, regarding the Meckel's diverticulum, this is a unique situation, previously unreported in the literature.


Assuntos
Adenocarcinoma , Condrossarcoma , Divertículo Ileal , Neoplasias de Tecido Conjuntivo e de Tecidos Moles , Feminino , Humanos , Pessoa de Meia-Idade , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Íleo/patologia , Adenocarcinoma/patologia , Progressão da Doença , Condrossarcoma/complicações
16.
Diagnostics (Basel) ; 13(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36832145

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) has a dense stroma, responsible for up to 80% of its volume. The amount of stroma can be associated with prognosis, although there are discrepancies regarding its concrete impact. The aim of this work was to study prognostic factors for PDAC patients submitted to surgery, including the prognostic impact of the tumor stroma area (TSA). A retrospective study with PDAC patients submitted for surgical resection was conducted. The TSA was calculated using QuPath-0.2.3 software. Arterial hypertension, diabetes mellitus, and surgical complications Clavien-Dindo>IIIa are independent risk factors for mortality in PDAC patients submitted to surgery. Regarding TSA, using >1.9 × 1011 µ2 as cut-off value for all stages, patients seem to have longer overall survival (OS) (31 vs. 21 months, p = 0.495). For stage II, a TSA > 2 × 1011 µ2 was significantly associated with an R0 resection (p = 0.037). For stage III patients, a TSA > 1.9 × 1011 µ2 was significantly associated with a lower histological grade (p = 0.031), and a TSA > 2E + 11 µ2 was significantly associated with a preoperative AP ≥ 120 U/L (p = 0.009) and a lower preoperative AST (≤35 U/L) (p = 0.004). Patients with PDAC undergoing surgical resection with preoperative CA19.9 > 500 U/L and AST ≥ 100 U/L have an independent higher risk of recurrence. Tumor stroma could have a protective effect in these patients. A larger TSA is associated with an R0 resection in stage II patients and a lower histological grade in stage III patients, which may contribute to a longer OS.

17.
Cancers (Basel) ; 15(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37370832

RESUMO

Colorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression. We conducted a study on tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis, using flow cytometry to phenotypically characterize innate immune cells. Our findings showed an increase in the expression of CD274 on classical, intermediate, and non-classical monocytes when comparing tumor with non-tumor samples. Furthermore, tumor samples with a desmoplastic growth pattern exhibited a significantly decreased percentage of CD274- and CD206-positive cells in all monocyte populations compared to non-desmoplastic samples. We found a correlation between a lower expression of CD206 or CD274 on classical, intermediate, and non-classical monocytes and increased disease-free survival, which points to a better prognosis for these patients. In conclusion, our study has identified potential new targets and biomarkers that could be incorporated into a personalized medicine approach to enhance the outcome for colorectal cancer patients.

18.
Appl Immunohistochem Mol Morphol ; 31(5): 318-323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37093706

RESUMO

Breast cancer is a major health burden, and up to one-third of patients with breast cancer develop brain metastases, which are linked to a very poor prognosis. Few biomarkers are available to predict the prognosis of patients with metastases. Assessment by immunohistochemistry may be used as a tool to predict the behavior of these tumors. A retrospective transversal study including 114 patients (diagnosed between 2000 and 2016) with breast cancer brain metastases was carried out using archival biological material from 114 patients with breast cancer brain metastases. Expression of CD44, HER2, ER, PR, CA9, PDL-1, CD133, ALDH1, PTEN, AKT, PI3K, and AR markers was assessed by immunohistochemistry. The overexpression of CD44 and AKT was associated with worse overall survival ( P =0.047 and P =0,034, respectively), on univariate analysis, in the cohort of parenchymal and bone metastases; the impact of AKT expression was also evident in the parenchymal cohort on uni ( P =0.021) and multivariate analysis ( P =0.027). The remaining markers did not exhibit a statistical correlation. Immunohistochemistry markers such as CD44 and AKT may have a prognostic impact on survival in patients with breast cancer brain metastases. The conjugation with other markers may help with the stratification of patients and therapy.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Proteínas Proto-Oncogênicas c-akt , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Receptores de Hialuronatos
19.
J Pediatr Surg ; 58(3): 587-594, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36150932

RESUMO

BACKGROUND: Biliary atresia is a neonatal disease characterized by choledochal obstruction and progressive cholangiopathy requiring liver transplantation in most patients. Hypoxia-ischemia affecting the biliary epithelium may lead to biliary obstruction. We hypothesized that ischemic cholangiopathy involving disruption of the peribiliary vascular plexus could act as a triggering event in biliary atresia pathogenesis. METHODS: Liver and porta hepatis paraffin-embedded samples of patients with biliary atresia or intrahepatic neonatal cholestasis (controls) were immunohistochemically evaluated for HIF-1alpha-nuclear signals. Frozen histological samples were analyzed for gene expression in molecular profiles associated with hypoxia-ischemia. Prospective clinical-laboratory and histopathological data of biliary atresia patients and controls were reviewed. RESULTS: Immunohistochemical HIF-1alpha signals localized to cholangiocytes were detected exclusively in liver specimens from biliary atresia patients. In 37.5% of liver specimens, HIF-1alpha signals were observed in biliary structures involving progenitor cell niches and peribiliary vascular plexus. HIF-1alpha signals were also detected in biliary remnants of 81.8% of porta hepatis specimens. Increased gene expression of molecules linked to REDOX status, biliary proliferation, and angiogenesis was identified in biliary atresia liver specimens. In addition, there was a trend towards decreased GSR expression levels in the HIF-1alpha-positive group compared to the HIF-1alpha-negative group. CONCLUSION: Activation of the HIF-1alpha pathway may be associated with the pathogenesis of biliary atresia, and additional studies are necessary to confirm the significance of this finding. Ischemic cholangiopathy and REDOX status disturbance are putative explanations for HIF-1alpha activation. These findings may give rise to novel lines of clinical and therapeutic investigation in the BA field.


Assuntos
Atresia Biliar , Colestase Intra-Hepática , Colestase , Humanos , Recém-Nascido , Atresia Biliar/genética , Atresia Biliar/cirurgia , Atresia Biliar/complicações , Estudos Prospectivos , Colestase/etiologia , Colestase Intra-Hepática/complicações , Isquemia , Hipóxia
20.
Pediatr Radiol ; 42(2): 201-4, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22002843

RESUMO

BACKGROUND: Acoustic radiation force impulse-imaging (ARFI) uses sound waves to interrogate the mechanical stiffness of a tissue. OBJECTIVE: To determine the usefulness of ARFI for estimating liver fibrosis in children. MATERIALS AND METHODS: A prospective masked study of children with chronic liver disease (CLD) and/or before liver transplant (LT) comparing ARFI with histopathological analysis. Children with no history of liver disease served as a control group. ARFI was performed with Virtual Touch software using ACUSON S2000. Share wave velocities (SWV) of several regions within the liver were measured. RESULTS: Fifty-two children were studied (mean age 8 years; range 1-16 years). The abnormal group included 10 children (31%) with CLD and 22 (69%) planned for LT. There were 20 normal controls. Mean SWV was 1.42 m/s in the abnormal group and 1.11 m/s [corrected] in the controls. For diagnosis of fibrosis stage ≥ F1, ≥F2 and F4, the areas under the receiver-operator characteristics curves were 0.834, 0.818 and 0.983, respectively. CONCLUSION: SWV is related to the degree of liver fibrosis in children, and may be a non-invasive alternative to biopsy.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Cirrose Hepática/diagnóstico por imagem , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , Curva ROC , Software , Estatísticas não Paramétricas
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