Search

Maria José Temido,1,2,* Rui Caetano Oliveira,3– 6,* Ricardo Martins,2,4,5,7 Marco Serôdio,2,7 Beatriz Costa,2,5,7 César Carvalho,7 Eva Santos,2,7 Luís Ferreira,7 Paulo Teixeira,3,8 Maria Augusta Cipriano,3 José Guilherme Tralhão,2,4,5,7 Henrique Alexandrino2,5,7 1Gastroenterology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra 3000-075, Portugal; 2Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; 3Pathology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra 3000-075, Portugal; 4Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; 5Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra 3000-548, Portugal; 6Faculdade de Medicina da Universidade do Porto, Porto 4200-319, Portugal; 7Department of Surgery, Centro Hospitalar e Universitário de Coimbra, Coimbra 3000-075, Portugal; 8Department Biomedical Laboratory Sciences, ESTeSC- Coimbra Health School, Polytechnic Institute of Coimbra, Coimbra 3046-854, Portugal*These authors contributed equally to this workCorrespondence: Maria José TemidoCentro Hospitalar e Universitário de Coimbra, Praceta Professor Mota Pinto, Coimbra 3004-561, PortugalTel +351 910772166Email mariajosetemido@gmail.comPurpose: Hepatectomy (Hp) is an alternative approach for the treatment of gastric carcinoma liver metastases (GCLM). However, prognostic factors that may assist patient selection are still controversial. Several pathologic features, such as the growth pattern (GP), associated with prognosis in colorectal cancer liver metastases, were never investigated in GCLM. Our principal aim was to assess if the GP has prognostic impact on GCLM.Patients and Methods: Review of the clinical and pathological characteristics of 19 consecutive patients submitted to surgical resection of GCLM with curative intent at our department. Major potential prognostic factors considered were patients’ gender, age, timing and extent of Hp, postoperative course, as well as histopathological characteristics of primary and secondary tumors.Results: Major morbidity occurred in four patients, mortality in one. Median and 5-year overall survival were 17 months and 26.7%, respectively. Ten patients developed recurrent disease and two patients survived more than 10 years. Factors independently associated with overall survival were the absence of major morbidity, distal location of the primary tumor, and desmoplastic GP (p< 0.05).Conclusion: The selection of patients is crucial for the improvement of survival rates of GCLM. Consequently, we demonstrate for the first time that the desmoplastic GP of GCLM is associated with improved outcomes, prompting further research on tumor–host interactions.Keywords: liver metastases, gastric carcinoma, hepatectomy, growth pattern, prognosis

Abstract Background Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing HIV or achieving antiretroviral therapy (ART)-free HIV remission. Understanding the acceptability of ATI amongst people living with HIV (PLHIV) and their HIV healthcare providers (HHP) is limited. Methods Two online surveys for PLHIV and HHP assessed awareness and acceptability of ATI, and understanding of the prospect for HIV cure in the future. Responses were collected from July 2017–January 2018. A descriptive analysis was performed and similar questions across the two surveys were compared using χ squared test. Results 442 PLHIV and 144 HHP completed the survey. 105/400 (26%) PLHIV had ever interrupted ART, 8% of which were in a clinical trial. Altruistic motivations were drivers of participation of PLHIV in cure related research. 81/135 (60%) HHP would support their patients wishing to enrol in an HIV cure-focused trial, but fewer would promote and allow such participation (25% and 31% respectively). Compared to HHP, PLHIV were more likely to believe that an HIV cure would be achievable within 10 years (55% vs. 19%, p

Este trabalho objetivou analisar os processos judiciais que solicitavam medicamentos ao Estado do Rio Grande do Norte, Brasil, no período de 2013 a 2017, descrevendo suas características sociodemográficas, jurídicas e médico-sanitárias. Trata-se de um estudo descritivo, cuja unidade de análise foi o processo judicial individual de solicitação de medicamentos, em que o estado é réu. Os dados foram obtidos por meio de consulta ao sítio eletrônico do Tribunal de Justiça do Estado do Rio Grande do Norte. Foram analisados 987 processos em que a maioria dos autores é do sexo feminino (58,8%), com idade média de 48,3 anos e residentes no interior do estado (56,9%). Houve predomínio de assistência jurídica pública (52,8%) e origem da prescrição no setor privado (38,1%). Em 68% dos casos, houve acesso ao medicamento, sendo o autor responsável pela compra em 56,1% deles, via bloqueio de verbas públicas. As doenças crônicas predominaram, bem como a solicitação de medicamentos não disponibilizados pelo Sistema Único de Saúde (SUS). Foram solicitados 1.517 medicamentos, dos quais 936 (61,7%) não estavam na Relação Nacional de Medicamentos Essenciais (Rename). O medicamento mais solicitado foi a insulina glargina (74 pedidos). Dos 10 medicamentos com maior número de ações judiciais, 4 foram posteriormente incorporados ao SUS, com destaque para as insulinas análogas. Os resultados mostraram que a via judicial tem se consolidado como forma de acesso a medicamentos ainda não incorporados ao SUS, o que pode contribuir como forma de pressão para a incorporação. O bloqueio de verbas públicas para o cumprimento das decisões é preocupante para o gestor do SUS, pois compromete a execução das políticas de assistência farmacêutica programadas.

Introduction: Caring for people living with HIV is complex and requires ethical and skilled professionals able to offer humanized and comprehensive care at the different levels of the health system. Objective: Determine whether the academic training of health professionals at a university in Northeastern Brazil develops the skills and competencies to care for people living with HIV. Methodology: This is a qualitative study, conducted in two stages: (1) documental analysis of curricular methods, contents and activities performed in Nursing, Medicine and Dentistry courses and (2) focus groups composed of undergraduates and professors from the three courses. Data analysis was conducted according to Bardin. Results: Documental analysis identified few curricular components in the three courses specifically related to HIV. Focus group analysis showed that the issue is superficially and sporadically addressed, with few hours spent on the subject and methodologies that do not satisfactorily develop the skills and competencies required to care for HIV-infected patients. Conclusion: The current training model for health professionals is limited to technical-scientific knowledge of HIV/AIDS, with little practical experience.

El astroturismo, entendido como actividad lúdico-científica, ha crecido considerablemente en los últimos años. Se han puesto en valor importantes recursos naturales y culturales vinculados a la buena conservación de paisajes y patrimonios en el ámbito de la astronomía. Su práctica contribuye a la diseminación científica y la formación de capital humano, tanto entre los turistas usuarios como en las comunidades anfitrionas, por lo que puede contribuir al desarrollo. Los destinos turísticos con posibilidades para su articulación tienen características singulares, lo que permite un buen posicionamiento en los mercados, incluso a nivel internacional. Sin embargo, las exigencias de contenido en conocimiento y de calidad de los productos de astroturismo son altas, por lo que es recomendable un planteamiento profesional de esta actividad, valorando adecuadamente la estructura de factores, productos y servicios soporte del destino turístico considerado, y las medidas de política turística y gobernanza necesarias para su buen lanzamiento y desarrollo.

Transcurridos 20 años desde la Carta del Turismo Sostenible

Abstract The aim of this study was to obtain evidences of a possible analgesic role for palmitoylethanolamide (PEA) in chronic granulomatous inflammation sustained by mast cell (MC) activation in rats at 96 hours. PEA (200-400-800 μg/mL), locally administered at time 0, reduced in a concentration-dependent manner the expression and release of NGF in comparison with saline-treated controls. PEA prevented nerve formation and sprouting, as shown by histological analysis, reduced mechanical allodynia, evaluated by Von Frey filaments, and inhibited dorsal root ganglia activation. These results were supported by the evidence that MCs in granuloma were mainly degranulated and closely localized near nerve fibres and PEA significantly reduced MC degranulation and nerves fibre formation. These findings are the first evidence that PEA, by the modulation of MC activation, controls pain perception in an animal model of chronic inflammation, suggesting its potential use for the treatment of all those painful conditions in which MC activation is an initial key step.

Background: More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM., Methods: Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%., Results: A statistically significant association was found between tumor size and metastasis growth pattern (P = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (P = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (P = .011). The number of metastases was significantly higher (P = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (P = .017)., Conclusion: The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Lung cancer (LC) is a leading cause of cancer-related mortality worldwide. Lung Cancer Screening (LCS) programs that use low-dose computed tomography (LDCT) have been shown to reduce LC mortality by up to 25 % and are considered cost-effective. The European Health Union has encouraged its Member States to explore the feasibility of LCS implementation in their respective countries. The task force conducted a comprehensive literature review and engaged in extensive discussions to provide recommendations. These recommendations encompass the essential components required to initiate pilot LCS programs following the guidelines established by the World Health Organization. They were tailored to align with the specific context of the Portuguese healthcare system. The document addresses critical aspects, including the eligible population, methods for issuing invitations, radiological prerequisites, procedures for reporting results, referral processes, diagnostic strategies, program implementation, and ongoing monitoring. Furthermore, the task force emphasized that pairing LCS with evidence-based smoking cessation should be the standard of care for a high-quality screening program. This document also identifies areas for further research. These recommendations aim to guarantee that the implementation of a Portuguese LCS program ensures high-quality standards, consistency, and uniformity across centres., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disorder typically presenting in infancy with cholestasis and rapidly progressing to cirrhosis. PFIC has been associated with an elevated risk of hepatocellular carcinoma (HCC), a neoplasm that is uncommon in children. PFIC type 4 has the strongest link to this type of cancer, although a few cases have also been connected to PFIC2. Herein, we report the case of a 2-year-old boy who underwent liver transplantation due to PFIC2. Histological examination showed cirrhosis and four small HCCs. Over a 20-year period following the transplantation, there was no recurrence of the disease or HCC. Although rare, HCC development can occur in PFIC and may complicate the prognosis. Liver transplantation offers a potential cure for both the metabolic disease and the neoplasm.

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.

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., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

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 × 10 11 µ 2 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 × 10 11 µ 2 was significantly associated with an R0 resection ( p = 0.037). For stage III patients, a TSA > 1.9 × 10 11 µ 2 was significantly associated with a lower histological grade ( p = 0.031), and a TSA > 2E + 11 µ 2 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.

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.

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., (© 2023 S. Karger AG, Basel.)

Colorectal cancer (CRC) is one of the most common cancers worldwide, with liver metastasis being its main cause of death. This study harvested fresh biological material from non-tumor and tumor tissue from 47 patients with CRC liver metastasis after surgery, followed by mechanical cellular extraction and stain-lyse-wash direct immunofluorescence technique. Here, 60 different T-cell populations were characterized by flow cytometry. Tumor samples were also subdivided according to their growth pattern into desmoplastic and non-desmoplastic. When we compared tumor versus non-tumor samples, we observed a significantly lower percentage of T-lymphocyte infiltration in the tumor in which the CD4 + T-cell density increased compared to the CD8 + T cells. T regulatory cells also increased within the tumor, even with an activated phenotype (HLA-DR + ). A higher percentage of IL-17-producing cells was present in tumor samples and correlated with the metastasis size. In contrast, we also observed a significant increase in CD8 + follicular-like T cells (CD185 + ), suggesting a cytotoxic response to cancer cells. Additionally, most infiltrated T cells exhibit an intermediate activation phenotype (CD25 + ). In conclusion, our results revealed potential new targets and prognostic biomarkers that could take part in an algorithm for personalized medicine approaches improving CRC patients' outcomes., Competing Interests: The authors declare no conflicts of interest.

Competing Interests: Competing interests: None declared.

Background: The worldwide increase in pediatric overweight and obesity, in parallel with the global increase in the consumption of sucrose and fructose, is associated with non-alcoholic fatty liver disease (NAFLD). Elevated branched-chain amino acids (BCAAs) are a metabolic feature related to obesity and an early risk factor for insulin resistance and NAFLD. However, few studies have assessed metabolic risk factors and nutritional status in maple syrup urine disease (MSUD) patients under restricted BCAA and high carbohydrate diets., Methods and Results: Herein, we present a pilot report of a 17-year-old boy with classic MSUD with poor diet compliance and high fructose consumption, mainly during early adolescence. At that time, he was overweight and developed features of metabolic syndrome, including persistently elevated liver enzymes and hepatic steatosis. He underwent liver transplantation at the age of 13 years to prevent the risk of progressive cognitive impairment. Two months later, NAFLD relapsed in the graft, despite a better BCAA balance and weight loss. Nevertheless, 6 months after dietary restriction of fructose consumption, NAFLD had sustainably improved., Conclusion: Childhood overweight and fructose overconsumption are wellestablished driving forces in the development of pediatric NAFLD. However, their role in the early onset and progression of NAFLD in the allograft remains to be established. Furthermore, it is not known whether the dysmetabolic state associated with elevated BCAAs may be contributory. Further studies are required with a cohort of MSUD subjects to validate our findings and to ascertain the possible interaction between a BCAA imbalance and dietary intake in the development of NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor AIL declared a past co-authorship with the authors ES and EM., (Copyright © 2022 Moreira-Silva, Ferreira, Almeida, Gonçalves, Cipriano, Vizcaíno, Santos-Silva and Gomes-Martins.)

Background: Gallbladder carcinoma (GBC) is an uncommon neoplasm with poor long-term survival. Worldwide the incidence rates vary according to geographic area. The multifactorial aetiology and the rarity of the disease limits the studies to improve outcomes in patients, since the treatment remains mostly surgical. The aim of this study was to identify clinicopathological prognostic factors for survival in patients with GBC submitted to surgery in our institution-a tertiary centre in Portugal. Also, to assess the expression of possible biomarkers (HER2, CD44 and ALDH1) in GBC, as well as the frequency of microsatellite instability (MSI) tumours., Methods: Clinicopathological characteristics of 41 consecutive patients that underwent surgical resection for GBC (2008-2019) at our hospital were retrospectively reviewed. Clinicopathological factors were assessed and an immunohistochemical (IHC) analysis was done. Microsatellite stability (MSS) was considered if there was maintenance of nuclear expression of MLH1, MSH2, MSH6 and PMS2. Human epidermal growth factor receptor 2 (HER2) expression was evaluated according to the rules applied for gastric cancer and expression of CD44 and ALH1 was evaluated in order to detect cancer stem cells (CSC). Survival analysis was conducted using Kaplan-Meier and Cox regression was used to find prognostic factors., Results: Incidence of GBC in our cohort of patients was 0.45%, most commonly affecting females. Median overall survival (OS) was 23 months with a 39.6% 5-year survival rate. Stage > II [hazard ratios (HR) =8.58; P=0.007], lymphovascular invasion (LVI) (HR =4.06; P=0.045) and hepatic resection (HR =0.288; P=0.034) independently influenced survival. HER2 positivity and high expression of CD44 or ADLH1 did not show significant influence in survival (P=0.649, P=0.868 and P=0.914, respectively), although HER2 and ALDH1 positive patients showed a tendency to a shorter OS, compared to negative patients. We found no relation between these biomarkers expression and disease stage. All analysed samples had MSS., Conclusions: GBC patients with a worse prognosis can be identified. The overexpression of HER2 could select patients for targeted therapy and prompt tissue sampling in unresectable patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-61/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Antibiotics are known to cause adverse reactions, but multiple organ involvement associated with nonspecific symptoms can lead to a delay in diagnosis. A definitive correlation between each toxin and its effects is difficult to establish due to concomitant potential toxins in the circulation. This article highlights an uncommon case of concomitant nitrofurantoin-induced autoimmune hepatitis and lung fibrosis that fulfills the definitive clinical criteria for diagnosis, presenting histological, imagiological, and immunological evidence of nitrofurantoin-induced toxicity. It occurred in a 68-year-old woman with extended nitrofurantoin intake for urinary tract infection prophylaxis who presented with progressive exercise dyspnea and jaundice. Similar published cases are also reviewed in this article., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by Sociedade Portuguesa de Gastrenterologia Published by S. Karger AG, Basel.)

Adrenocortical carcinomas (ACC) are aggressive tumors with a poor prognosis. Histological scores are advised for the diagnosis, however, there are borderline cases that may be misjudged as adrenocortical adenomas (ACA). The three main scores used are: Weiss Modified System (WMS), Reticulin Algorithm (RA), and Helsinki Score (HS). We intend to compare the accuracy of the three scores in ACC diagnosis and to identify predictive factors of overall survival (OS). Retrospective study (2004-2016) at Centro Hospitalar e Universitário de Coimbra of the adrenal tumors, classified as ACC or ACA, with a history of posterior tumor relapse/metastases, without lesions in the contralateral adrenal gland: 13F and 6M, with a median age of 51 ± 12.41 years. Nodules' median size was 9.20 ± 6.2 cm. Patients had a median OS of 52 ± 18.6 months, with 57.9% and 46.3%, at 3 and 5 years. Seven patients had local recurrence and nine had metastases. Thirteen cases were in stage II. The WMS and the HS allowed a diagnosis of ACC in 15 cases and the RA defined ACC in 17 cases. All cases had, at least, focal disruption of the reticulin framework. More than 5 mitosis/50 HPF was associated with worse OS: 49.67 ± 21.43 versus 108.86 ± 14.02 months ( p  = 0.026). In patients with stage II, tumor size ⩾10 cm was associated with worse OS: 19.25 ± 7.15 versus 96.11 ± 16.7 months ( p  = 0.007), confirmed by multivariate analysis ( p  = 0.031). The correct diagnosis of ACC is a pathologist responsibility. The RA seems the most accurate. Any loss of the reticulin framework should raise awareness for malignancy. In patients on stage II, a size ⩾10 cm is a predictor of worse prognosis., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the third cause of cancer-related death. Current clinical/pathological criteria contribute to risk stratification, but are far from the desired on individualized medicine. Recently, HCC classifications have been published based on immunohistochemical and morphological features., Methods: A retrospective review of patients submitted to surgical treatment-partial hepatectomy (PH) or liver transplantation (LT), with pathological diagnosis of HCC, in a 9-year period (2007-2015) was performed., Results: Applying the classification of Srivastava et al. (#1), based on the expression of CD31, p53, AFP and CD44, tumour size and presence of vascular invasion, HCC were categorized as low- and high-risk HCC. With the classification of Tsujikawa et al. (#2), HCC were classified into biliary/stem cell marker positive, Wnt signalling positive and the "all negative" HCC, according to the expression of CK19, SALL4, β-catenin glutamine synthetase, EpCAM and p53. There were sixty-six patients (53 males; 13 females), with median age of 64.5 ± 9.46 years (range 38-86), with solitary HCC, comprehending 37 PH (56.1%) and 29 LT (43.9%). The mean overall survival (OS) was 75.4 ± 6.9 months. Biliary/stem cell type of HCC was a predictive factor of worse OS on the overall population (24.4 versus 78.3 months, p = 0.032) and in PH cohort (11.5 versus 64.01 months, p = 0.016), on uni- and multivariate analyses., Conclusion: These results support the relevance of a risk stratification classification of HCC. Classification #2 seems adequate to our reality demonstrating OS impact, allowing its application in future biopsies, prompting individualized medicine.

Primary sarcoma of the liver (PSL) is a rare entity accounting for less than 1% of all liver cancers, with unknown aetiology. Several subtypes have been recognized, with histology playing an essential role in patient tailoring and management. We are about to report a case of an unusual PSL, with peculiar morphologic and immunohistochemical properties. A 65-year-old female with a multicystic hepatic lesion underwent surgery due to spontaneous rupture. Pathology revealed dilated bile duct-like structures lined by benign cuboidal/columnar epithelium surrounded by neoplastic proliferation of spindle and epithelioid cells with interspersed osteoclast-like multinucleated giant cells, loosely arranged in a storiform pattern, positive for CD10. The conjugation of morphology and immunohistochemistry results provided the diagnosis of primary biliary adenosarcoma of the liver, biliary type. The patient experienced tumour relapse and died of disease 2 years and 7 months later.

Introduction: Mesenchymal tumors of the liver are rare, and in this group, myxoid leiomyomas are even rarer. So far, only 2 cases have been reported in the literature., Case Presentation: We aim to report the case of a 16-year-old female with a large lesion on the right hepatic lobe, grossly composed of gelatinous and heterogeneous tissue., Discussion: Histological evaluation revealed a benign mesenchymal neoplasm with expansive growth, paucicellular, with monotonous and dispersed spindle and ovoid cells, positive for α-smooth actin and h-caldesmon, without atypia or mitoses, consistent with the diagnosis of primary myxoid leiomyoma., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2019 by S. Karger AG, Basel.)

Neuroendocrine carcinoma of the gallbladder is a very rare neoplasia comprising only 0.2% of all the gastrointestinal neuroendocrine tumors. We present the case of an 85-year-old male with nonspecific gastrointestinal symptoms, progressive weight loss, and deterioration in the preceding 15 days. Imaging study showed a 5-cm polypoid mass localized at the gallbladder fundus, leading to a radical cholecystectomy. Pathology revealed the known lobulated polypoid lesion, on cut section, constituted by friable tissue without evident infiltration of the gallbladder wall and a contiguous friable, brown, flat lesion. Histological evaluation displayed a small cell neuroendocrine carcinoma, consisting of intermediate and small cells, rounded or spindle, with extensive areas of necrosis, with positivity for neuroendocrine immunomarkers, associated with intracystic papillary neoplasm with high and low dysplasia. This is an uncommon association with few cases presented in the literature., Competing Interests: The authors have no conflicts of interest to disclose.

The deep peribiliary glands (DPBG) are a niche of progenitor cells in the wall of the biliary duct (BD) and are the second line of multiplication when severe lesion of the epithelium occurs. Previous studies have identified DPBG injury as a cause of post-liver transplant (LT) biliary stenosis; this complication is a major cause of post-LT morbidity. The incidence of biliary stenosis in our center is high (38.1%). This study evaluates the lesion of DPBG in response to ischemia. Graft BD was collected in adult LT between August 2016-July 2017, from donation after brain death. Samples of 45 grafts were collected at 2 moments: BD1-during graft preparation and BD2-before biliary anastomosis. Histological analysis of the samples was performed and then classified according to degree of lesion (0, ≤50%, and >50%). A comparison was made between the degree of lesion and graft ischemia, graft histology, donor, and procurement variables. The DPBG lesion was more frequent in BD2 (20.9% vs 7%, P = .079). BD2 lesions with DPBG lesions had higher medians and means at all times of ischemia. The difference was greater in the warm ischemia time (0: 43.3 ± 12.53 minutes vs ≤50%: 52.4 ± 14.38 minutes, P = .068). The group of BD1 with DPBG lesion presented superior median cold ischemia time (CIT). In the analysis of the remaining variables there were also no statistically significant differences. We concluded that during the period of CIT there is already lesion of the DPBG, which increases after reperfusion of the graft, in greater association with longer warm ischemia time., (Copyright © 2019. Published by Elsevier Inc.)

Colorectal cancer is a major health burden and despite the recent advances in healthcare and screening programs, a great percentage of patients already present metastases once their disease is found. In those cases, liver surgery has an essential role, but even with neoadjuvant chemotherapy there is a high rate of intrahepatic recurrence. New prognostic factors are needed in order to decide the best surgical approach considering the biological behavior of the tumors in order to tailor the used therapies, moving towards individualized medicine/treatment. However, the majority of the factors described in literature are expensive, time consuming, and difficult to apply on a daily basis. Histological growth patterns have emerged over the past few years as a reproducible characteristic, an easy to apply one, and with very low costs since it only needs the standard Haematoxylin and Eosin stained slides of observation. In this article, we provide a review of the histological growth patterns of liver metastases and their prognostic significance, biological meaning, and therapeutic importance.

Introduction: Approximately 20% - 30% of histological lymph node-negative patients with colorectal cancer relapse at five years after surgical treatment. This recurrence is likely due to occult nodal disease undetected by standard histopathological practice which has implications in terms of the clinical management of patients., Material and Methods: Lymph nodes were collected from colectomy specimens. A central section from each lymph node was histologically examined following haematoxylin-eosin staining and the remaining tissue was subjected to OSNA - one step nucleic acid amplification analysis., Results: A total of 1046 lymph nodes from 59 pN0 patients were assessed. Of these, 753 lymph nodes were examined by both methods. The median number of lymph nodes assessed with OSNA - one step nucleic acid amplification was 12 (IQR: 7;16). Among pN0 patients, 17 had OSNA - one step nucleic acid amplification-positive lymph nodes, resulting in a positive molecular staging rate of 28.8% (95% CI: 17.8 - 42.1). Among these patients, 12 (70.59%) were molecular-staged as pN1 and 5 (29.41%) were molecular staged as pN2. The tumour burden of lymph nodes assessed with OSNA - one step nucleic acid amplification ranged from 270 to 17 000 cytokeratin 19 mRNA copies/μL. Most of these patients (88.2%) were found to have lymph nodes with micrometastases only (250 - 4999 copies/μL)., Discussion: We provide the results from the first study of the use of the OSNA - one step nucleic acid amplification assay in colorectal cancer patients in Portugal. Our results are in-line with other international studies, showing the improvement on patients' staging by molecular examination of lymph nodes., Conclusion: In our study, 28.8% of patients with histologically negative lymph nodes were found to have metastatic lymph nodes using OSNA - one step nucleic acid molecular assessment. OSNA - one step nucleic acid assay allows a more accurate staging of patients with colorectal cancer and standardizes lymph node assessment.

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.

Introduction: Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS)., Patients and Methods: Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP)., Results: The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis., Conclusion: The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)