Browsing by Author "Tralhão, JG"
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- Cholangiocarcinoma: from molecular biology to treatmentPublication . Brito, AF; Abrantes, AM; Encarnação, JC; Tralhão, JG; Botelho, MFCholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.
- Colangiocarcinoma Intra-HepáticoPublication . Castro e Sousa, F; Tavares da Silva, E; Tralhão, JG; Costa, B; Martins, M; Serôdio, M; Martins, RIntrodução: o colangiocarcinoma intra-hepático (CCIhp) é um tumor maligno raro, normalmente diagnosticado num estadio avançado. São objectivos deste estudo avaliar os resultados da terapêutica do CCIhp e os factores prognósticos com significado estatístico na sobrevida de doentes com esta entidade nosológica tratados no nosso Serviço. Material e métodos: Vinte e um doentes submetidos a tratamento por CCIhp nos últimos anos, dos quais onze foram operados com intuitos curativos: quatro hepatectomias esquerdas, duas hepatectomias esquerdas alargadas aos segmentos V e VIII, duas hepatectomias direitas, duas bissegmentectomias e uma trissegmentectomia. Resultados: a mortalidade per-operatória foi de 0% e a pós-operatória (três meses) de 6%. As sobrevidas cumulativas aos 5 anos foram de 14% no total da população, 26% nos doentes submetidos a cirurgia com intuitos curativos e 26% para a sobrevida cumulativa livre de doença. Observou-se recidiva tumoral hepática em cinco doentes, a qual ocorreu aos 1,09 ± 0,82 anos (limites: 0,24-2,08). Os factores que influenciaram a sobrevida da globalidade dos doentes foram o tratamento cirúrgico com intuitos curativos (p=0,028), a presença de invasão vascular (p=0,002) e o valor da fosfatase alcalina no momento do diagnóstico (p=0,044). Entre os doentes operados com intuitos curativos, a presença de invasão vascular influenciou a sobrevida global (p=0,025) e a sobrevida livre de doença (p=0,002). Conclusões: A ressecção cirúrgica com intuitos curativos aumentou, de forma estatisticamente significativa, a sobrevida dos doentes com CCIhp. No entanto, sendo o diagnóstico geralmente tardio, apenas uma pequena percentagem destes doentes pode beneficiar deste tratamento.
- Estudo experimental do impacto da clampagem selectiva da veia porta na função hepatocelularPublication . Tralhão, JG; Abrantes, AM; Gonçalves, C; Carvalho, C; Portela, I; Laranjo, M; Oliveiros, B; Cardoso, D; Ribeiro, AB; Botelho, MF; Castro e Sousa, FThe influence of selective clamping of the elements of hepatic pedicle in the hepatocellular function and viability were evaluated in our department. AIM: Study the effect of selective clamping of the portal vein (CPV) in hepatocellular function in an animal model with normal liver. METHOD: Three groups of Wistar rats (males, 2 months) were subjected a CPV for 60 min: group A (n=21) submitted to a continuous inflow occlusion; group B (n=12) underwent to a CPV for 30 min with 5 min of reperfusion; group C (n=10) underwent a CPV for 15 min with 5 min of reperfusion. The group D (n=9) was not subjected to a CPV. A hepatic biopsy was done at the end of surgery. The degree of tissue injury was evaluated using: 1) blood markers: AST, ALT, total bilirubin (TB), GGT alkaline-phosphatase, LDH and hepatic extraction fraction (HEF) by radioisotopic methods three days before laparotomy (BS) and after surgery (AS); 2) apoptosis, necrosis were investigated after collagenase cell isolation from hepatectomy pieces by flow-cytometry using the followed probes: propidium-iodide and annexin-V. Statistical analysis: variance analysis, post-hoc comparisons by Turkey-test (p<0.05). RESULTS: 1) Mortality: Group A - 62%, Group B - 17%, Group C - 30%, Group D - 0% (p<0.03). 2) We observed statistical differences in these parameters: ALT (p<0,025) and LDH (p<0,002) preferentially in groups A but without differences between the A,B,C and D Groups (ns). 3) We also verified a significant decrease in HEF values (p<0,0001) preferentially in group A without differences between the groups. 4) No difference were observed when analysed apoptosis and necrosis and cell viability between the groups. CONCLUSIONS: Postoperative liver failure is the leading cause of mortality after hepatectomy, however selective clamping of the portal vein, is reflected in an increase in cell viability and a decrease in the type of cell death (necrosis ou apoptosis) compared to studies carried out previously by us and thus may be regarded as an alternative to the Pringle maneuver. However, selective clamping of the portal vein for periods above 30' should be avoided, given the high mortality verified.
- Francisco José Franqueira de Castro e SousaPublication . Tralhão, JG
- Gastric neuroendocrine neoplasm with late liver metastasisPublication . Marques, B; Martins, RG; Tralhão, JG; Couto, J; Saraiva, S; Ferrão, H; Ribeiro, J; Santos, J; Martins, T; Cadime, AT; Rodrigues, FGastric neuroendocrine neoplasms (GNENs) are classified into three types according to their aetiology. We present a clinical case of a female patient of 66 years and a well-differentiated (grade 2), type 3 GNEN with late liver metastasis (LM). The patient underwent surgical excision of a gastric lesion at 50 years of age, without any type of follow-up. Sixteen years later, she was found to have a neuroendocrine tumour (NET) metastatic to the liver. The histological review of the gastric lesion previously removed confirmed that it was a NET measuring 8 mm, pT1NxMx (Ki67 = 4%). 68Ga-DOTANOC PET/CT reported two LM and a possible pancreatic tumour/gastric adenopathy. Biopsies of the lesion were repeatedly inconclusive. She had a high chromogranin A, normal gastrin levels and negative anti-parietal cell and intrinsic factor antibodies, which is suggestive of type 3 GNEN. She underwent total gastrectomy and liver segmentectomies (segment IV and VII) with proven metastasis in two perigastric lymph nodes and both with hepatic lesions (Ki67 = 5%), yet no evidence of local recurrence. A 68Ga-DOTANOC PET/CT was performed 3 months after surgery, showing no tumour lesions and normalisation of CgA. Two years after surgery, the patient had no evidence of disease. This case illustrates a rare situation, being a type 3, well-differentiated (grade 2) GNEN, with late LM. Despite this, it was possible to perform surgery with curative intent, which is crucial in these cases, as systemic therapies have limited efficacy. We emphasise the need for extended follow-up in these patients.
- Hepatectomy and liver regeneration: from experimental research to clinical applicationPublication . Tralhão, JG; Abrantes, AM; Hoti, E; Oliveiros, B; Cardoso, D; Faitot, F; Carvalho, C; Botelho, MF; Castro e Sousa, FBACKGROUND: The mechanisms and kinetics of hepatic growth have continuously been investigated. This study concerns liver regeneration in animal and patients who underwent partial hepatectomy evaluated by the hepatic extraction fraction (HEF) calculated through radioisotopic methods. METHODS: Thirty normal Wistar rats were submitted to an 85% hepatectomy, and 95 patients with primary and secondary liver tumours were included. In animal study, the liver regeneration kinetics was assessed by HEF using 99mTc-mebrofenin, the ratio liver/bodyweight and by using bromodeoxyuridine deoxyribonucleic acid incorporation. In patient study, the liver regeneration was evaluated by calculation of HEF before surgery, 5 and 30 days after hepatectomy. RESULTS: In animal, we verified a positive correlation between HEF kinetics and liver/bodyweight ratio or hepatocyte proliferation evaluated by bromodeoxyuridine deoxyribonucleic acid staining after 85% hepatectomy. In the clinical arm, no statistical differences of the HEF before hepatectomy, 5 and 30 days after hepatectomy, were observed. CONCLUSIONS: Our results support the view that human liver regeneration commences early, is fast, non-anatomical and functionally complete 5 days after hepatectomy. The fast functional liver regeneration may have a high clinical impact particularly concerning the post-operative oncological therapeutic approaches.
- Impact of splenic artery ligation after major hepatectomy on liver function, regeneration and viabilityPublication . Carrapita, J; Abrantes, AM; Campelos, S; Gonçalves, AC; Cardoso, D; Sarmento-Ribeiro, AB; Rocha, C; Santos, JN; Botelho, MF; Tralhão, JG; Farges, O; Barbosa, JMIt was reported that prevention of acute portal overpressure in small-for-size livers by inflow modulation results in a better postoperative outcome. The aim is to investigate the impact of portal blood flow reduction by splenic artery ligation after major hepatectomy in a murine model. Forty-eight rats were subjected to an 85% hepatectomy or 85% hepatectomy and splenic artery ligation. Both groups were evaluated at 24, 48, 72 and 120 post-operative hours: liver function, regeneration and viability. All methods and experiments were carried out in accordance with Coimbra University guidelines. Splenic artery ligation produces viability increase after 24 h, induces a relative decrease in oxidative stress during the first 48 hours, allows antioxidant capacity increment after 24 h, which is reflected in a decrease of half-time normalized liver curve at 48 h and at 72 h and in an increase of mitotic index between 48 h and 72 h. Splenic artery ligation combined with 85% hepatectomy in a murine model, allows portal inflow modulation, promoting an increase in hepatocellular viability and regeneration, without impairing the function, probably by inducing a less marked elevation of oxidative stress at first 48 hours.
- Impactação de prótese dentária no esófago torácico: tratamento cirúrgico. A propósito de um caso clínicoPublication . Alexandrino, A; Fernandes, M; Ferreira, L; Tralhão, JG; Castro e Sousa, F
- In vivo selective and distant killing of cancer cells using adenovirus-mediated decorin gene transferPublication . Tralhão, JG; Schaefer, L; Micegova, M; Evaristo, C; Schönherr, E; Kayal, S; Veiga-Fernandes, H; Danel, C; Iozzo, RV; Kresse, H; Lemarchand, PDecorin is a well-known, ubiquitous proteoglycan that is a normal component of the ECM. Upon transgenic expression of decorin, tumor cells with diverse histogenetic background overexpress p21WAF1, a potent inhibitor of cyclin-dependent kinase activity, become arrested in G1, and fail to generate tumors in immunocompromised animals. Because decorin is a secreted protein, it has been recently suggested that decorin could act as an autocrine and paracrine regulator of tumor growth. Here, we demonstrate that adenovirus (Ad)-mediated transfer and expression of human decorin cDNA induced in vivo apoptosis of xenograft tumor cells in nude mice. This oncolytic activity was observed when the Ad vector encoding the decorin cDNA was injected intratumorally (i.t.) or i.v. Importantly, i.t. injection of the decorin Ad vector led to growth inhibition of the injected tumor associated with similar growth inhibition of a distant contralateral tumor, demonstrating a distant decorin antitumoral effect. Immunochemistry against human decorin and decorin quantitation in tumors confirmed that decorin migrated to the tumor distant site. Furthermore, decorin effect was specific to tumor cells, because neither apoptosis nor growth inhibition were observed in nontumoral human cells such as hepatocytes, endothelial cells, and fibroblasts, despite p21 overexpression.
- Influence of P53 on the radiotherapy response of hepatocellular carcinomaPublication . Gomes, AR; Abrantes, AM; Brito, AF; Laranjo, M; Casalta-Lopes, JE; Gonçalves, AC; Sarmento-Ribeiro, AB; Botelho, MF; Tralhão, JGHepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines.