Revista Portuguesa de Cirurgia
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Identificação e Caracterização das Células Supressoras de Linhagem Mielóide (MDSC) Usando uma Abordagem Simples para Análise por Citometria de Fluxo Convencional
Full text linkIntroduction: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate under pathological conditions, such as cancer, and suppress immune responses through various mechanisms. Distinguishing MDSC populations remains challenging due to their shared surface markers with neutrophils and monocytes, complicating accurate identification and quantification. This study aimed to improve MDSC identification and quantification using conventional flow cytometry panels and assess their functional activity for integration into the cancer immunogram of cancer patients at the Immunology Department of IPO-Porto.
Methods: Identification and quantification of circulating MDSCs were performed by flow cytometry using an 8-color multiparametric panel.
Results: Cancer patients showed significantly higher levels of PMN-MDSCs (12-fold) and M-MDSCs (1.1-fold) than healthy donors. MDSC function was evaluated by qPCR after cell sorting (FACS), revealing increased transcriptional levels of NOS2 and TGFB1, which are associated with immunosuppressive activity. Moreover, reduced zeta chain (CD247) expression in T lymphocytes and NK cells was observed, with lower mean fluorescence intensity (MFI) ratios in cancer patients, indicating impaired immune signaling.
Conclusion: This study confirmed that circulating MDSC levels are elevated in cancer patients, reinforcing their relevance in the cancer immunogram. It also identified potentially useful phenotypic and functional MDSC markers that require validation in larger sample sets. The findings contribute to refining flow cytometry analysis panels, enabling more accurate and standardized identification of MDSC populations using conventional platforms.Introdução: As células mieloides supressoras (MDSCs) são uma população heterogénea de células mieloides imaturas que se acumulam em condições patológicas, como o cancro, e suprimem as respostas imunitárias através de vários mecanismos. A distinção entre populações de MDSC continua a ser um desafio devido à partilha de marcadores de superfície com neutrófilos e monócitos, dificultando a sua identificação e quantificação precisas. Este estudo teve como objetivo melhorar a identificação e quantificação das MDSCs utilizando painéis de citometria de fluxo convencional e avaliar a sua atividade funcional para integração no imunograma de cancro de doentes oncológicos no Serviço de Imunologia do IPO-Porto.
Métodos: A identificação e quantificação das MDSCs circulantes foram realizadas por citometria de fluxo utilizando um painel multiparamétrico de 8 cores.
Resultados: Os doentes com cancro apresentaram níveis significativamente mais elevados de PMN-MDSCs (12 vezes) e M-MDSCs (1,1 vezes) em comparação com dadores saudáveis. A função das MDSCs foi avaliada por qPCR após a separação celular (FACS), revelando níveis de transcrição aumentados de NOS2 e TGFB1, associados à atividade imunossupressora. Além disso, foi observada uma redução na expressão da cadeia zeta (CD247) em linfócitos T e células NK, com rácios de intensidade média de fluorescência (MFI) inferiores nos doentes com cancro, indicando um comprometimento na sinalização imunitária.
Conclusão: Este estudo confirmou que os níveis de MDSCs circulantes estão elevados em doentes com cancro, reforçando a sua relevância no imunograma de cancro. Também identificou uma combinação de marcadores fenotípicos e funcionais potencialmente úteis, que necessitam de validação em amostras de maior dimensão. Os resultados contribuem para o aperfeiçoamento dos painéis de análise por citometria de fluxo, permitindo uma identificação mais precisa e padronizada das populações de MDSCs em plataformas convencionais
Resposta Ganglionar Após Quimioterapia Neoadjuvante e Potenciais Alvos para Descalar Cirurgia Axilar em Doentes com Cancro de Mama
Full text linkIntroduction: Neoadjuvant chemotherapy (NAC) has the potential for tumor downstaging and surgery de-escalation. In the axilla, this approach is less established, especially in cN+→ycN0. Targeted axillary dissection is an option, but difficult to concretize. We aim to identify biological factors associated with nodal pathological complete response (pCR) and recognize potential candidates for a more conservative axillary approach after NAC, such as sentinel lymph node biopsy (SLNB).
Methods: Retrospective, single-center cohort of patients with node-positive breast cancer, treated with NAC followed by axillary lymph node dissection from 2017 to 2021. The primary outcome was nodal pCR, overall and by molecular subtypes. A logistic regression model was conducted to identify biological factors predicting nodal pCR.
Results: A total of 414 patients were included. Overall, the nodal pCR rate was 37.9%. It was higher in HR+/HER2+ (62.1%), HR-/HER2+ (61.0%) and HR-/HER2- (56.3%) tumors, whereas only 21.6% in HR+/HER2- (p<0.001). In patients without nodal pCR, HR+/HER2- had the highest median number of positive lymph nodes (p=0.038). In multivariate analysis, HR+/HER2+ (OR 5.157, 95% CI 2.768-9.608, p<0.001), HR-/HER2+ (OR 4.207, 95% CI 1.935-9.147, p<0.001), HR-/HER2- (OR 2.242, 95% CI 1.180-4.261, p=0.014), and differentiation grade 3 (OR 4.075, 95% CI 2.448-6.784, p<0.001) were independently associated with nodal pCR.
Conclusion: Our data reveal HER2+, triple-negative and grade 3 tumors as predictive factors for nodal pCR. Parallel to the breast, axillary surgery de-escalation may be guided by tumor intrinsic factors. Identifying these “good responders” could help identify the candidates for a simpler axillary approach after NAC, such as SLNB.Introdução: A quimioterapia neoadjuvante (QTNA) tem o potencial de downstaging tumoral, permitindo descalar cirurgia. Esta abordagem é menos estabelecida na axila, sobretudo em doentes cN+→ycN0. A linfadenectomia axilar seletiva é uma opção, mas difícil de concretizar. Pretendemos identificar fatores biológicos associados a resposta patológica completa (pCR) ganglionar e reconhecer potenciais candidatos para uma abordagem axilar após QTNA mais conservadora, como a biópsia do gânglio sentinela (BGS).
Métodos: Coorte retrospetiva unicêntrica de doentes com carcinoma da mama cN+, tratados com QTNA e linfadenectomia axilar de 2017 a 2021. O outcome primário foi a pCR ganglionar, global e por subtipo molecular. Foi desenvolvido um modelo de regressão logística para identificar fatores preditivos de pCR ganglionar.
Resultados: Incluídos 414 doentes. A pCR ganglionar global foi de 37,9%. Foi superior nos subtipos HR+/HER2+ (62,1%), HR-/HER2+ (61,0%) e HR-/HER2- (56,3%), e apenas 21,6% nos HR-/HER2- (p< 0,001). Entre aqueles sem pCR ganglionar, os HR+/HER2- apresentaram o maior número de gânglios positivos (p=0,038). Os subtipos HR+/HER2+ (OR 5,157; IC 95% 2,768–9,608; p<0,001), HR-/HER2+ (OR 4,207; IC 95% 1,935–9,147; p<0,001), HR-/HER2- (OR 2,242; IC 95% 1,180–4,261; p=0,014) e os tumores G3 (OR 4,075; IC 95% 2,448–6,784; p<0,001) associaram-se de forma independente com a pCR ganglionar.
Conclusão: Os tumores HER2+, triplo negativos e G3 foram identificados como fatores preditivos de pCR ganglionar. Paralelamente à mama, a biologia tumoral pode guiar o descalar da cirurgia axilar. A identificação destes “bons respondedores” poderá contribuir para selecionar candidatos a abordagens axilares mais conservadoras após QTNA, como a BGS
Gastrectomia Total com Linfadenectomia D2 Assistida por Robô no Cancro Gástrico
Full text linkGastric cancer remains one of the leading causes of cancer-related mortality. Robotic surgery has gained importance by providing three-dimensional vision, enhanced dexterity, and technical precision. We present a video of a robotic-assisted total gastrectomy with D2 lymphadenectomy, demonstrating the key surgical steps and its applicability in oncologic treatment.O cancro gástrico mantém-se como uma das principais causas de mortalidade oncológica. A cirurgia robótica tem ganho relevância pela visão tridimensional, maior precisão técnica e ergonomia. Apresentamos o vídeo de uma gastrectomia total com linfadenectomia D2 assistida por robô, demonstrando os passos essenciais da técnica e a sua aplicabilidade no tratamento oncológico
Iniquidades e Disparidades na Assistência Cirúrgica Oncológica Global: Um Apelo à Ação
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Determinação de Biomarcadores Sanguíneos no Traumatismo Cranioencefálico (TCE) Ligeiro, GFAP e UCH-L1, em Doentes Admitidos no Serviço de Urgência com Suspeita de TCE Ligeiro
Full text linkIntroduction: Traumatic brain injury (TBI) is one of the most common conditions in the emergency department (ED), representing a public health issue with substantial economic impact. The risk of severe acute intracranial injury increases the need for cranial computed tomography (CT). Serum biomarkers of acute brain injury, such as glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), have emerged as potential alternatives.
Methods: This was a screening study conducted in the ED in 2024. Adult patients admitted with mild TBI within 12 hours of injury, and meeting the criteria for cranial CT were included. For each participant, UCH-L1 and GFAP levels were assessed. The cranial CT scan was considered positive in the presence of brain injury. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated for the presence of both biomarkers combined and separately for UCH-L1 and GFAP.
Results: A total of 315 patients were enrolled, and 13 were excluded for not meeting the inclusion criteria. Acute traumatic intracranial lesions were diagnosed in 14 patients (4.6%). The use of UCH-L1 alone yielded a sensitivity of 50% and a NPV of 96%. GFAP demonstrated a sensitivity of 100% and a NPV of 100%. When considering the positivity of both biomarkers, sensitivity and NPV remained at 100%, with a potential reduction in cranial CT scans of 23.2%.
Conclusion: The findings of this study suggest that these serum biomarkers may be used to reliably rule out brain injury in patients with mild TBI, providing a strong level of confidence
Doença de Castleman Unicêntrica Retroperitoneal: A Cirurgia é Curativa
Full text linkCastleman disease (CD) comprises a group of rare nonclonal lymphoproliferative disorders. Unicentric Castleman disease (UCD) typically presents as isolated lymphadenopathy with progressive enlargement and an indolent course. Most patients are asymptomatic or may present symptoms related to a localized mass effect on organ function. Multicentric Castleman disease (MCD) affects various lymph node stations and leads to systemic constitutional symptoms and systemic cytokine dysregulation, resulting in laboratory abnormalities, hepatosplenomegaly, and complex organ dysfunction.We report a case of retroperitoneal UCD. Imaging studies showed a solitary, solid, right pararenal lesion causing anterior deviation of the inferior vena cava and renal pedicle. Complete surgical resection was performed, and histopathologic analyses confirmed the diagnosis of the hyaline-vascular subtype of UCD.Patients with UCD generally have an excellent prognosis following curative surgical resection. However, recurrence may occur, and long-term follow-up is advised.A doença de Castleman é um grupo de doenças raras linfoproliferativas não-clonais. A doença de Castleman unicêntrica (DCU) manifesta-se tipicamente como uma linfadenopatia isolada com crescimento progressivo e indolente. A maioria dos doentes são assintomáticos ou apresentam sintomas compressivos dos órgãos adjacentes. A doença de Castleman multicêntrica afecta várias regiões ganglionares e cursa com sintomas sistêmicos constitucionais, desregulação sistêmica das citoquinas, alterações laboratoriais, hepatoesplenomegalia e disfunção de órgão complexa.Apresentamos um caso clínico de DCU retroperitoneal. Os estudos imaginológicos revelaram uma lesão sólida para-renal direita que causa desvio anterior da veia cava inferior e do pedículo renal. O exame histopatológico da peça operatória confirmou DCU do subtipo hialino-vascular.O prognóstico após ressecção cirúrgica completa é favorável. A possibilidade de recidiva tardia preconiza um follow-up prolongado
Omental Thickening
Full text linkA 60-year-old man was admitted to the emergency department with diffuse abdominal discomfort, associated with hematochezia and changes in intestinal rhythm. He underwent abdominal computed tomography (CT), which demonstrated moderate ascites with diffuse thickening of the transverse mesocolon (Fig. 1). He underwent surgery which revealed: “omental thickening” (Figs. 2 e 3). Omental thickening or caking is an important finding to indicate peritoneal pathology and should trigger an alarm when present with no attributable primary cause. CT scan, significant omental thickening with a large peritoneal mass and numerous implants were observed, in addition to extensive ascites.
The most common solid masses that affect the mesentery are metastases and lymphoma, which are much more common than primary tumors. Metastases resulting from direct extension are most commonly those of pancreatic and gastric origin. In contrast, peritoneal and omental metastases (“carcinomatosis”) most commonly arise from ovarian, gastric, colorectal, and pancreatic cancers and is often accompanied by the development of malignant ascites. The histopathological examination demonstrated a larger omentum with an external surface with a lobulated appearance, yellowish-brown in color and an elastic-firm consistency. When cut, the surface has a grainy, yellowish appearance, with poorly defined and diffuse whitish areas. The immunohistochemical examination was conclusive for peritoneal infiltration of adenocarcinoma of colorectal origin (Fig. 4)
Sociedade Portuguesa de Cirurgia Minimamente Invasiva: História, Colaboração e Futuro de uma Revolução Cirúrgica
Full text linkMinimally invasive surgery has been radically transforming healthcare over the past decades. Procedures once performed through large incisões are now executed through small openings, using cameras and fine instruments that allow for more precise, less aggressive intervention with substantially reduced recovery times.A cirurgia minimamente invasiva tem vindo a transformar radicalmente os cuidados de saúde ao longo das últimas décadas. Procedimentos outrora realizados através de grandes incisões passaram a ser executados por pequenas aberturas, recorrendo a câmaras e instrumentos finos que permitem uma intervenção mais precisa, menos agressiva e com tempos de recuperação substancialmente reduzidos