Risk of second primary cancers among patients with a first primary gastric cancer: A population-based study in North Portugal

Background: The growing number of incident cases of gastric cancer along with improved survival result in a rising population of survivors at risk of second primary cancers (SPC). We estimated the cumulative incidence of metachronous (diagnosed >2 months after first primary cancer [FPC]) SPC in gastric FPC patients and compared the incidence of metachronous SPC with that expected in the general population. Methods: A cohort of gastric FPC patients from the North Region Cancer Registry of Portugal, diagnosed in 2000–2006 (n = 7427) was followed to 31 December 2010 for synchronous and metachronous SPCs. Cumulative incidence of metachronous SPCs taking into account death as a competing event and standardized incidence ratios (SIR) of metachronous SPCs were estimated. Results: Overall, 331 (4.5%) patients developed an SPC (26.9% synchronous and 73.1% metachronous). Over half of the SPCs occurred in digestive organs. Among men, the most frequent were colon, prostate, and trachea, bronchus and lung; in women, colon, breast and thyroid were the most common. The 10-year cumulative incidence of metachronous SPC for males was 5.7% and for females 3.5%. The SIR for all cancers was 1.30 in males and 1.20 in females. Among both sexes, significantly higher SIRs were observed for cancers of the oesophagus (males: 4.99; females: 8.03), small intestine (males: 11.04; females: 13.09) and colon (males: 2.42; females: 2.58). Conclusions: Patients with a gastric FPC were found to be at increased risk of developing SPC, mainly in digestive organs, when compared to the general population. Close surveillance of these patients may allow early detection of SPC.This study was funded by FEDER (European Regional Development Fund) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology − FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia − Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). An individual PhD grant attributed to SM (SFRH/BD/102585/2014) was funded by FCT and the “Programa Operacional Capital Humano” (POCH/FSE)

Three-dimensional culture of single embryonic stem-derived neural/stem progenitor cells in fibrin hydrogels: neuronal network formation and matrix remodelling

In an attempt to improve the efficacy of neural stem/progenitor cell (NSPC) based therapies, fibrin hydrogels are being explored to provide a favourable microenvironment for cell survival and differentiation following transplantation. In the present work, the ability of fibrin to support the survival, proliferation, and neuronal differentiation of NSPCs derived from embryonic stem (ES) cells under monolayer culture was explored. Single mouse ES-NSPCs were cultured within fibrin (fibrinogen concentration: 6 mg/ml) under neuronal differentiation conditions up to 14 days. The ES-NSPCs retained high cell viability and proliferated within small-sized spheroids. Neuronal differentiation was confirmed by an increase in the levels of ßIII-tubulin and NF200 over time. At day 14, cell-matrix constructs mainly comprised NSPCs and neurons (46.5% ßIII-tubulin + cells). Gamma-aminobutyric acid (GABA)ergic and dopaminergic/noradrenergic neurons were also observed, along with a network of synaptic proteins. The ES-NSPCs expressed matriptase and secreted MMP-2/9, with MMP-2 activity increasing along time. Fibronectin, laminin and collagen type IV deposition was also detected. Fibrin gels prepared with higher fibrinogen concentrations (8/10 mg/ml) were less permissive to neurite extension and neuronal differentiation, possibly owing to their smaller pore area and higher rigidity. Overall, it is shown that ES-NSPCs within fibrin are able to establish neuronal networks and to remodel fibrin through MMP secretion and extracellular matrix (ECM) deposition. This three-dimensional (3D) culture system was also shown to support cell viability, neuronal differentiation and ECM deposition of human ES-NSPCs. The settled 3D platform is expected to constitute a valuable tool to develop fibrin-based hydrogels for ES-NSPC delivery into the injured central nervous system.The authors would like to acknowledge Prof. Domingos Henrique (Instituto de Medicina Molecular, Lisbon) for providing the ES 46C cell line. This work was supported by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE (FCOMP‐01–0124‐FEDER‐021125) and by National funds FCT – Fundação para a Ciência e a Tecnologia (PTDC/SAU‐BMA/118869/2010). A.R.B. and M.J. Oliveira are supported by FCT (SFRH/BD/86200/2012; Investigator FCT)

Evolutionary Constraints in the b-Globin Cluster: The Signature of Purifying Selection at the d-Globin (HBD) Locus and Its Role in Developmental Gene Regulation

Human hemoglobins, the oxygen carriers in the blood, are composed by two α-like and two β-like globin monomers. The β-globin gene cluster located at 11p15.5 comprises one pseudogene and five genes whose expression undergoes two critical switches: the embryonic-to-fetal and fetal-to-adult transition. HBD encodes the δ-globin chain of the minor adult hemoglobin (HbA2), which is assumed to be physiologically irrelevant. Paradoxically, reduced diversity levels have been reported for this gene. In this study, we sought a detailed portrait of the genetic variation within the β-globin cluster in a large human population panel from different geographic backgrounds. We resequenced the coding and noncoding regions of the two adult β-globin genes (HBD and HBB) in European and African populations, and analyzed the data from the β-globin cluster (HBE, HBG2, HBG1, HBBP1, HBD, and HBB) in 1,092 individuals representing 14 populations sequenced as part of the 1000 Genomes Project. Additionally, we assessed the diversity levels in nonhuman primates using chimpanzee sequence data provided by the PanMap Project. Comprehensive analyses, based on classic neutrality tests, empirical and haplotype-based studies, revealed that HBD and its neighbor pseudogene HBBP1 have mainly evolved under purifying selection, suggesting that their roles are essential and nonredundant. Moreover, in the light of recent studies on the chromatin conformation of the β-globin cluster, we present evidence sustaining that the strong functional constraints underlying the decreased contemporary diversity at these two regions were not driven by protein function but instead are likely due to a regulatory role in ontogenic switches of gene expression

The impact of the COVID-19 pandemic on cancer screening

Letter to the editorThis study was funded by the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) in collaboration with the Agency for Clinical Research and Biomedical Innovation (AICIB), under the scope of the project ‘Impacto da pandemia COVID-19 nos cuidados prestados a doentes oncológicos’ (Research 4 COVID 174_596850546), and national funding from FCT, under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). SM was also funded under the scope of the project ‘NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline’ (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017), which is funded by FEDER through the Operational Programme Competitiveness and Internationalization, and national funding from FCT. The funding sources had no involvement in the conduct of the research and/or preparation of the article

The impact of the COVID-19 pandemic on the short-term survival of patients with cancer in Northern Portugal

The COVID-19 pandemic led to potential delays in diagnosis and treatment of cancer patients, which may negatively affect the prognosis of these patients. Our study aimed to quantify the impact of COVID-19 on the short-term survival of cancer patients by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. All cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, and prostate, from the Portuguese Oncology Institute of Porto (IPO-Porto) and diagnosed between 2 March and 1 July of 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Information regarding sociodemographic, clinical and treatment characteristics were collected from the cancer registry database and clinical files. Vital status was assessed to 31 October of the respective years. Cox proportional hazards regression was used to estimate crude and propensity score-adjusted hazards ratio (HR) and 95% confidence intervals (95% CIs) of death. During follow-up to 31 October, there were 154 (11.8%) deaths observed before COVID-19 and 131 (17.2%) after COVID-19, corresponding to crude and adjusted HRs (95% CI) of 1.51 (1.20-1.91) and 1.10 (0.86-1.40), respectively. Significantly higher adjusted hazards of death were observed for patients with Stage III cancer (HR = 2.37; 95% CI: 1.14-4.94) and those undergoing surgical treatment (HR = 3.97; 95% CI: 1.14-13.77) or receiving radiotherapy (HR = 1.96; 95% CI: 1.96-3.74), while patients who did not receive any treatment had a lower mortality hazards (HR = 0.62; 95% CI: 0.46-0.83). The higher overall short-term mortality observed during the COVID-19 pandemic largely reflects the effects of the epidemic on the case-mix of patients being diagnosed with cancer.Funding information: European Regional Development Fund through the Operational Programme Competitiveness and Internationalization & Fundação para a Ciência e a Tecnologia, Grant/Award Number: POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358; Fundação para a Ciência e a Tecnologia, Grant/Award Number: info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT; Fundação para a Ciência e a Tecnologia & Agency for Clinical Research and Biomedical Innovation, Grant/Award Number: RESEARCH 4 COVID-19 174_59685054

The impact of the coronavirus disease 2019 pandemic on the diagnosis and treatment of cancer in Northern Portugal

Objectives The coronavirus disease 2019 (COVID-19) pandemic has affected the availability of healthcare resources, and adjustments to cancer care have been necessary considering the risk of morbidity by COVID-19 and of cancer progression. This study aims to quantify the impact of the COVID-19 pandemic on the care of patients with cancer by comparing a period of 4 months after the outbreak began (2 March 2020) with an equal period from 2019. Methods Cancer cases of the esophagus, stomach, colon and rectum, pancreas, lung, skin-melanoma, breast, cervix, prostate, non-Hodgkin lymphoma, and leukemia from the Portuguese Oncology Institute of Porto, and diagnosed between 2 March and 1 July 2019 (before COVID-19) and 2020 (after COVID-19) were identified. Those with the first treatment outside the Portuguese Oncology Institute of Porto were excluded. Sociodemographic, clinical and treatment characteristics were obtained from the cancer registry database and clinical files. Results The absolute number of new cancer cases decreased nearly 40% after the COVID-19 pandemic (from 1430 to 866). The largest decreases were observed for cervical (-74.3%) and prostate (-71.7%) cancers. Cases were more often diagnosed at more advanced stages in 2020 (P = 0.001), and the proportion of patients not starting any treatment until 1 July was just under 20% in 2019 and nearly 40% in 2020. The median times from symptoms onset, first medical exam and first appointment to diagnosis, and from diagnosis to first appointment, multidisciplinary tumor board meeting and first treatment were shorter after COVID-19. Conclusions There was a notable overall decrease in cancer diagnoses after COVID-19, with changes in the characteristics of incident cases. © 2022 Lippincott Williams and Wilkins. All rights reserved.This study was funded by the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) in collaboration with the Agency for Clinical Research and Biomedical Innovation (AICIB), under the scope of the project “Impacto da pandemia COVID-19 nos cuidados prestados a doentes oncológicos” (Research 4 COVID 174_596850546), and national funding from FCT, under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020). SM was funded under the scope of the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017), which is funded by the European Regional Development Fund through the Operational Programme Competitiveness and Internationalization, and national funding from FCT. The funding sources had no involvement in the conduct of the research or preparation of the article

Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients

Introduction: The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa. Methods: Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC. Results: Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47–0.90%) and among SPCs, 7.21% (4.99–9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61–5.07). Discussion/Conclusion: The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.This work was supported by national funds from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020). S.M. was funded by FEDER through the Operational Program Competitiveness and Internationalization and national funding from FCT under the scope of the project “NEON-PC – Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017) and received funding from the EPIUnit – Junior Research – Prog Financing (UIDP/04750/2020). The funding sources had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

An unusual cause of acute cardiogenic shock in the operating room

A 51-year-old man with a renal carcinoma with inferior vena cava (IVC) invasion was referred to our hospital for the performance of a radical nephrectomy with IVC thrombus excision. To prevent embolism, an IVC filter was implanted the day before surgery below the suprahepatic veins. On nephrectomy completion, the clinical status of the patient started to deteriorate and an unsuccessful attempt was made to excise the IVC thrombus. The patient developed profound refractory hypotension without significant bleeding and worsening splanchnic stasis was noted. A transesophageal echocardiogram was immediately performed in the operating room, revealing a hemispheric mass protruding from the IVC ostium to the right atrium, completely blocking all venous return. Volume depletion was evident by low left and right atrial volumes and increased septum mobility. No other abnormalities were found that could explain the shock, namely ventricular dysfunction or valvular disease. Cardiac surgery consultation was immediately obtained, ultimately deciding to perform a median sternotomy with direct exploration of right atrium. Under cardiopulmonary bypass, a 6-cm long thrombotic mass was identified, involving the IVC filter, blocking all lower body venous return; the removal of the mass reversed the shock. The patient had an uneventful recovery. Adverse outcomes associated with IVC filters are common. Our case highlights the importance of a team approach to rapid changes in hemodynamic status in the operating room, including the surgeon, the anesthesiologist, and the cardiologist. It also emphasizes the pivotal role of transesophageal echocardiogram in the clinical evaluation of severely unstable patien

Incidence rates and trends of lip, oral and oro-pharyngeal cancers in Portugal

Objectives: To analyse the trends and patterns of lip, oral and oro‐pharyngeal cancer incidence in Portugal between 1998 and 2007. Patients and Methods: Data on lip, oral and oro‐pharyngeal cancers was collected from the databases maintained at the three main Regional Cancer Registries of Portugal (1998–2007). The data were analysed by gender, age and by site. Incidence rates were age standardized by the direct method, and joinpoint regression was used to estimate trends in incidence. Results: During this 10‐year period, a total of 9623 cases of lip, oral and oropharynx cancers were reported, 7565 (78.6%) in males and 2058 (21.4%) in females. There was an increase in the age‐standardized incidence of oral cancers by 1.96% per year for both sexes grouped together and an increase of 4.34% per year for the female group. Oro‐pharyngeal cancer showed an increase incidence trend of 3.49% per year for both sexes grouped together and an increase of 3.49% per year for male group among the sites analysed. Lip cancer showed a decrease in its incidence rate. Conclusion: In view of rising trends, it is necessary to implement policies on oral cancer control by initiating campaigns on oral cancer awareness and screening and to harness political measures on tobacco and alcohol control for the Portuguese population