Papers by Helder Mansinho
Acta Médica Portuguesa, Feb 1, 2023
PubMed, May 1, 1994
We report a case of femoral osteosarcoma with brain metastases in a female patient with longstand... more We report a case of femoral osteosarcoma with brain metastases in a female patient with longstanding von Recklinghausen disease. Osteosarcoma of a long bone has not yet, to our best knowledge, been reported in association with type I Neurofibromatosis. Central nervous system metastases occur very rarely in osteosarcoma.
PubMed, Aug 1, 1993
A case of a 62 year old white patient with mild dyspeptic symptoms and nodular hepatomegaly is pr... more A case of a 62 year old white patient with mild dyspeptic symptoms and nodular hepatomegaly is presented. The histologic examination of a liver biopsy revealed a hepatocellular carcinoma clear cell variant. There were no signs of chronic hepatic failure. The disease showed an indolent clinical behaviour, thus the beginning of chemotherapy was delayed until clinical deterioration was obvious. Clinical improvement was obtained with adriamycin. A review of the literature on this rare histologic variant of hepatocellular carcinoma is made.
DOAJ (DOAJ: Directory of Open Access Journals), Sep 1, 1993
A case of a 62 year old white patient with mild dyspeptic symptoms and nodular hepatomegaly is pr... more A case of a 62 year old white patient with mild dyspeptic symptoms and nodular hepatomegaly is presented. The histologic examination of a liver biopsy revealed a hepatocellular carcinoma clear cell variant. There were no signs of chronic hepatic failure. The disease showed an indolent clinical behaviour, thus the beginning of chemotherapy was delayed until clinical deterioration was obvious. Clinical improvement was obtained with adriamycin. A review of the literature on this rare histologic variant of hepatocellular carcinoma is made.
Revista Portuguesa de Cirurgia, Jan 20, 2021
Respiratory medicine case reports, 2021
Ectopic secretion of beta-subunit of human chorionic gonadotropin (β-HCG) in pulmonary pleomorphi... more Ectopic secretion of beta-subunit of human chorionic gonadotropin (β-HCG) in pulmonary pleomorphic carcinoma is remarkably rare. Such unusual ectopic hormone production by lung cancer may be initially misinterpreted as extragonadal choriocarcinoma or germ cell tumor. We report a 56-year-old postmenopausal female, smoker, who presented a 5-month history of progressive dyspnea, dry paroxysmal cough, and significant weight loss. She was referred by a local hospital with the preliminary diagnosis of gestational trophoblastic neoplasia due to a rapidly growing thoracic tumor with persistently elevated serum β-HCG. Computed tomography of the chest showed a lung mass in the right upper lobe associated with homolateral pleural effusion. Positron emission tomography showed pathological 2-[18F]FDG uptake at the mass lesion. Biopsies were performed. Histological examination described pleomorphic carcinoma with positive immunostaining for β-HCG. The serum levels of β-HCG were also elevated indicating ectopic secretion. The patient had rapid clinical deterioration and deceased before chemotherapy initiation. Only a few cases of paraneoplastic β-HCG secretion have been reported in the literature. Previous studies suggested that the ability to secrete β-hCG in tumors may correlate to some extent to chemoresistance; thus, it might be useful as a prognosis marker.
DOAJ (DOAJ: Directory of Open Access Journals), May 1, 1994
We report a case of femoral osteosarcoma with brain metastases in a female patient with longstand... more We report a case of femoral osteosarcoma with brain metastases in a female patient with longstanding von Recklinghausen disease. Osteosarcoma of a long bone has not yet, to our best knowledge, been reported in association with type I Neurofibromatosis. Central nervous system metastases occur very rarely in osteosarcoma.
Journal of Clinical Oncology, May 20, 2019
TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they ... more TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021.
International Journal of Oncology, Dec 2, 2021
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being th... more Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5-year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease-related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi-omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.
Value in Health, 2016
A611 terize hospitalizations, mortality, and chemotherapy treatment in the US for older adults wi... more A611 terize hospitalizations, mortality, and chemotherapy treatment in the US for older adults with newly diagnosed AML. Methods: We used 2010-2012 Medicare Limited Data Set files to identify patients with newly diagnosed AML (ICD-9 205.0) who were continuously enrolled in Medicare Fee-for-Service for 6+ months before and 12+ months after diagnosis, or until they died. We calculated monthly mortality and hospitalization rates and hospitalization payments for all patients, and separately, for those who received chemotherapy (identified using MS-DRGs, HCPCS, revenue center, and ICD9 procedure codes). Results: Of 8,701 patients, 65% (5,641/8,701) died within 6 months after diagnosis; only 22% (1,941/8,701) survived at least 12 months. Monthly hospitalization rates were higher for patients who died within 6 months (.85/month), compared to those who survived (.35/month). Study patients had 19,738 hospitalizations; 5,757 included chemotherapy. Among patients treated with chemotherapy (3,071), 36% survived 12+ months (vs. 16% of untreated patients), but their initial hospitalizations (H) had higher payments, longer lengths-of-stay and higher ICU admission rates, compared to untreated patients (e.g.
RESUMO Os autores apresentam as recomendações para a análise mutacional de GISTs, aprovadas por u... more RESUMO Os autores apresentam as recomendações para a análise mutacional de GISTs, aprovadas por unanimidade por um grupo multidisciplinar em 20 de Julho de 2012. O estado mutacional de genes como o KIT e o PDGFRA permite identificar alvos terapêuticos para inibidores da tirosinacínase (ITKs) e, por isso, a boa prática clínica nas decisões bioterapêuticas de doentes com GISTs deve incluir a análise do estado mutacional. A análise mutacional da doença primária não é recomendada na rotina diagnóstica da generalidade dos GISTs; no entanto, pode ter valor prognóstico e ser útil na seleção de doentes, após ressecção completa de GIST primário e é considerada experimental na doença progressiva sob tratamento com ITKs. A análise mutacional deve considerar-se nos casos selecionados descritos neste texto e ser realizada em laboratórios em conformidade com padrões elevados de garantia de qualidade, atendendo ao seu elevado impacto sobre as decisões clínicas.
Purpose:Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) me... more Purpose:Cetuximab is an EGFR-targeted therapy approved for the treatment of RAS wild-type (WT) metastatic colorectal cancer (mCRC). However, about 60% of these patients show innate resistance to cetuximab. To increase cetuximab efficacy, it is crucial to successfully identify responder patients, as well as to develop new therapeutic approaches to overcome cetuximab resistance.Experimental Design:We evaluated the value of EGFR effector phospholipase C gamma 1 (PLCγ1) in predicting cetuximab responses, by analyzing progression-free survival (PFS) of a multicentric retrospective cohort of 94 treated patients with mCRC (log-rank test and Cox regression model). Furthermore, we used in vitro and zebrafish xenotransplant models to identify and target the mechanism behind PLCγ1-mediated resistance to cetuximab.Results:In this study, levels of PLCγ1 were found increased in RAS WT tumors and were able to predict cetuximab responses in clinical samples and in vitro and in vivo models. Mechanis...
Supplementary Data from Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mech... more Supplementary Data from Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mechanism of Cetuximab Resistance in Metastatic Colorectal Cancer
International Journal of Oncology, 2021
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being th... more Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumor types, being the sixth leading cause of mortality worldwide and the fourth in Europe. Globally, it has a mortality/incidence ratio of 98%, and the 5-year survival rate in Europe is only 3%. Although risk factors, such as obesity, diabetes mellitus, smoking, alcohol consumption and genetic factors, have been identified, the causes of PDAC remain elusive. Additionally, the only curative treatment for PDAC is surgery with negative margins. However, upon diagnosis, ~30% of the patients already present with locally advanced disease. In these cases, a multidisciplinary approach is required to improve disease-related symptoms and prolong patient survival. In the present article, a comprehensive review of PDAC epidemiology, physiology and treatment is provided. Moreover, guidelines on patient treatment are suggested. Among the different available therapeutic options for the treatment of advanced PDAC, results are modest, most likely due to the complexity of the disease, and so the prognostic remains poor. Molecular approaches based on multi-omics research are promising and will contribute to groundbreaking personalized medicine. Thus, economic investment that promotes research of pancreatic cancer will be critical to the development of more efficient diagnostic and treatment strategies.
Supplementary Figure from Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Me... more Supplementary Figure from Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mechanism of Cetuximab Resistance in Metastatic Colorectal Cancer
International Journal of Infectious Diseases
Objectives: The performance of a new point-of-care CE-IVD-marked isothermal lab-on-phone COVID-19... more Objectives: The performance of a new point-of-care CE-IVD-marked isothermal lab-on-phone COVID-19 assay was assessed in comparison to a gold standard real-time reverse transcriptase-PCR method. Methods: The study was conducted following a nonprobability sampling of ≥16-year-old volunteers from three different laboratories, using direct mouthwash (N = 24) or nasopharyngeal (N = 191) clinical samples. Results: The assay demonstrated 95.19% sensitivity and 100% specificity for detection of SARS-CoV-2 in direct nasopharyngeal crude samples and 78.95% sensitivity and 100% specificity in direct mouthwash crude samples. It also successfully detected currently predominant SARS-CoV-2 variants of concern (Beta B.1.351, Delta B.1.617.2, and Omicron B.1.1.529) and demonstrated to be inert against potential cross-reactions of other common respiratory pathogens that cause infections that present similar symptoms to COVID-19. Conclusion: This lab-on-phone pocket-sized assay relies on an isothermal amplification of SARS-CoV-2's N and E genes, taking just 50 minutes from sample to result, with only 2 minutes of hands-on time. It presents good performance when using direct nasopharyngeal crude samples, enabling a low-cost, realtime, rapid, and accurate identification of SARS-CoV-2 infections at the point of care, which is important for both clinical management and population screening, as a tool to break the chain of transmission of COVID-19 pandemic, especially in low-resources environments.
Journal of Clinical Oncology, May 26, 2019
TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they ... more TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clinical trial. Untreated patients with wild-type RAS mCRC (determined locally), primary L-sided and unresectable will be screened for this trial. Eligible patients will be randomized 1:1 to receive first-line (1L) panitumumab plus FOLFOX and then bevacizumab plus FOLFIRI as second-line (2L) treatment (Seq. 1) or bevacizumab plus FOLFOX as 1L and then panitumumab plus FOLFIRI as 2L treatment (Seq. 2). Randomization will be stratified by number of metastatic organs involved (1 vs > 1). Primary objective is the comparison of the progression free survival (PFS) rate at 35 months (m) of Seq 1 vs Seq. 2. Secondary objectives: PFS from randomization to 2nd progression or death, OS rate at 35 months and OS of Seq. 1 vs Seq. 2; PFS, objective response rate, disease control rate, early tumour shrinkage, Depth of Response, duration and time to response and safety in 1L treatment and in 2L treatment in each Sequence arm. Exploratory objectives: impact of baseline biomarkers predictive of the efficacy in each Sequence arm and the clinical impact of clonal dynamics by longitudinal analysis of circulating tumour deoxyribonucleic acid (ctDNA) in plasma. The trial is in progress; 28 of up to 370 planned patients have been recruited at the end of January 2019 (first patient in 31 October 2018). Clinical trial information: NCT03635021.
Journal of Clinical Oncology, 2019
TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they ... more TPS3618 Background: Both anti-EGFR and anti-VEGF therapies have shown clinical benefit when they are added in first and second-line in L-sided CRC. The conflicting results in anti-VEGF vs. anti-EGFR studies (FIRE-3, PEAK and CALGB/SWOG 80405 studies) suggest that the sequence of targeted therapies added to FOLFOX or FOLFIRI regimens in first- and second-line treatment could be an important factor in the overall survival (OS) of mCRC patients. Currently, there are no randomized data on the sequential use of an anti-EGFR followed by an anti-VEGF or vice versa. Therefore, the aim of this randomized clinical trial is to compare the efficacy of two treatment sequences, panitumumab followed by bevacizumab versus bevacizumab followed by panitumumab in combination with FOLFOX chemotherapy in first-line and with FOLFIRI in second-line in patients with wild-type RAS, primary L-sided, metastatic colorectal cancer (mCRC). Methods: A phase III, multicentre, open-label and randomized two-arm clin...
New biotechnology, Jan 28, 2018
Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metast... more Circulating tumour cells (CTCs) originating from a primary tumour, lymph nodes and distant metastases hold great potential for liquid biopsies by providing a molecular fingerprint for disease dissemination and its temporal evolution through the course of disease management. CTC enumeration, classically defined on the basis of surface expression of Epithelial Cell Adhesion Molecule (EpCAM) and absence of the pan-leukocyte marker CD45, has been shown to correlate with clinical outcome. However, existing approaches introduce bias into the subsets of captured CTCs, which may exclude biologically and clinically relevant subpopulations. Here we explore the overexpression of the membrane protein O-glycan sialyl-Tn (STn) antigen in advanced bladder and colorectal tumours, but not in blood cells, to propose a novel CTC isolation technology. Using a size-based microfluidic device, we show that the majority (>90%) of CTCs isolated from the blood of patients with metastatic bladder and color...
Uploads
Papers by Helder Mansinho