Unresectable stage III non-small cell lung cancer: Insights from a Portuguese expert panel.

INTRODUCTION: The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. METHODS: A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. RESULTS: Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. CONCLUSIONS: A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

ECCO Position on Harmonisation of Crohn's Disease Mucosal Histopathology.

In inflammatory bowel disease [IBD], mucosal healing is a major therapeutic target and a reliable predictor of clinical course. However, endoscopic mucosal healing is not synonymous with histological healing, and the additional benefits of including histological remission as a target are unclear. In Crohn´s disease [CD], there are few studies highlighting the value of histological remission as a therapeutic target. Histological activity can persist in CD patients who are in endoscopic remission, and the absence of histological activity may be associated with lower relapse rates. Therefore, standardisation of procedures to evaluate CD histological activity is desirable. Topics that would benefit from standardisation and harmonisation include biopsy procedures, biopsy processing techniques, the content of histological scores, and the definitions of histological remission, histological response, and histological activity. In line with these needs, the European Crohn's and Colitis Organisation [ECCO] assembled a consensus group with the objective of developing position statements on CD histology based on published evidence and expert consensus. There was agreement that definitions of histological remission should include absence of erosion, ulceration, and mucosal neutrophils; that the absence of neutrophilic inflammation is an appropriate histological target in CD; that CD histological scores, such as the Global Histological Disease Activity Score, lack formal validation; and that histological scoring systems for ulcerative colitis, including the Geboes Score, Robarts Histopathology Index, and Nancy Histological Index, can be used for scoring intestinal biopsies in CD patients.

Intestinal Amyloidosis in Common Variable Immunodeficiency and Rheumatoid Arthritis.

We present a case of reactive amyloidosis that developed secondary to common variable immunodeficiency and rheumatoid arthritis. A 66-year-old woman, with prior history of common variable immunodeficiency and rheumatoid arthritis, was referred to our clinic for chronic diarrhea investigation. The patient was submitted to colonoscopy with ileoscopy, which did not show relevant endoscopic alterations. However, undertaken biopsies revealed amyloid deposition. Since amyloidosis with GI involvement is a rare cause of chronic diarrhea, this pathology should be considered in etiologic investigation, especially when associated with chronic inflammatory diseases.

Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation.

This study was designed to evaluate MEK5 and ERK5 expression in colon cancer progression and to ascertain the relevance of MEK5/ERK5 signalling in colon cancer. Expression of MEK5 and ERK5 was evaluated in 323 human colon cancer samples. To evaluate the role of MEK5/ERK5 signalling in colon cancer, we developed a stable cell line model with differential MEK5/ERK5 activation. Impact of differential MEK5/ERK5 signalling was evaluated on cell cycle progression by flow cytometry and cell migration was evaluated by wound healing and transwell migration assays. Finally, we used an orthotopic xenograft mouse model of colon cancer to assess tumour growth and progression. Our results demonstrated that MEK5 and ERK5 are overexpressed in human adenomas (P<0.01) and adenocarcinomas (P<0.05), where increased ERK5 expression correlated with the acquisition of more invasive and metastatic potential (P<0.05). Interestingly, we observed a significant correlation between ERK5 expression and NF-κB activation in human adenocarcinomas (P<0.001). We also showed that ERK5 overactivation significantly accelerated cell cycle progression (P<0.05) and increased cell migration (P<0.01). Furthermore, cells with overactivated ERK5 displayed increased NF-κB nuclear translocation and transcriptional activity (P<0.05), together with increased expression of the mesenchymal marker vimentin (P<0.05). We further demonstrated that increased NF-κB activation was associated with increased IκB phosphorylation and degradation (P<0.05). Finally, in the mouse model, lymph node metastasis was exclusively seen in orthotopically implanted tumours with overactivated MEK5/ERK5, and not in tumours with inhibited MEK5/ERK5. Our results suggested that MEK5/ERK5/NF-κB signalling pathway is important for tumour onset, progression and metastasis, possibly representing a novel relevant therapeutic target in colon cancer treatment.

Radiographic fetal osteometry: approach on age estimation for the Portuguese population.

The estimation of gestational age (GA) on fetal remains can be an important forensic issue. Forensic specialists usually use reference tables and regression equations derived from reference collections, which are quite rare in what fetuses are concerned. Since these tools are mostly grounded on ultrasonographic measurements, which are known to differ from real bones measurements or are based on ancient literature, this study aimed the construction of tables and regression equations for the Portuguese population on the basis of diaphyseal bone length measurements (femur, tibia and humerus) of 100 fetuses of known GA, using post-mortem radiographs. There is a strong correlation between the longitudinal length of studied bones and GA; the femur exhibits the strongest correlation (r=0.969; p=0.000), followed by the tibia (r=0.966; p=0.000) and the humerus (r=0.963; p=0.000). Therefore it was possible to obtain regression equations and to build tables with reference values for each of the diaphysis analyzed.

NF-kappaB and apoptosis in colorectal tumourigenesis.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) may play an important role in colorectal tumourigenesis, controlling cell cycle and apoptosis gene expression. In addition, imbalances between cell proliferation and cell death are thought to underlie neoplastic development. The aims of this study were to investigate apoptosis and expression of several apoptosis-related proteins, and to determine correlations with colorectal tumour progression. MATERIALS AND METHODS: Apoptosis was evaluated by the TUNEL assay in 48 patient samples, including adenomas, adenocarcinomas and adjacent normal mucosas. Immunohistochemistry was performed for Bcl-2 and NF-kappaB. Expression levels of p53, Bax and IkappaB proteins were determined by immunoblotting. Cultured human colon cancer cells were used to evaluate NF-kappaB expression and nuclear translocation by immunocytochemistry and immunoblotting. RESULTS: Apoptosis and NF-kappaB immunoreactivity were significantly higher in tumour tissue compared with normal mucosa (P < 0.01), increasing in association with histological tumour progression (P < 0.01). Bcl-2 was consistently higher in normal mucosa (P < 0.01) and inversely correlated with the percentage of apoptosis (P < 0.01). Phosphorylated p53 and Bax levels were similar in tumour tissue and normal mucosa; however, the NF-kappaB inhibitor, IkappaB, tended to decrease in tumours. In vitro, nuclear translocation of NF-kappaB was greater in proliferative than in resting phases of colon cancer cells. CONCLUSIONS: NF-kappaB expression and apoptosis are increased from adenoma to poorly differentiated adenocarcinoma tissues. Apoptosis is correlated with suppression of Bcl-2 expression, but appears to proceed through a p53- and Bax-independent pathway. Activation of NF-kappaB may play an important role in colorectal tumour progression.

[Adenocarcinoma of the Vater's ampulla associated with Von Recklinghausen's neurofibromatosis]. / Adenocarcinoma da ampola de Vater associado com neurofibromatose de von Recklinghausen.

Von Recklinghausen's Neurofibromatosis is an autosomal dominant disease of variable manifestations. Association with gastrointestinal and hepatobiliary tumours is well documented, most of them being benign neurofibromas. Other tumours, such as leiomyomas, sarcomas, ganglioneuromas and carcinoids are less frequent. Much rarer is the development of epithelial malignancies and an ontogenic relation is not clear. The authors reports a case of adenocarcinoma of Vater's Ampulla and duodenal neurofibromas, in a patient with Von Recklinghausen's disease, presenting obstructive jaundice.

[Perinatal morbidity and mortality related to gestational infection. The histological identification of chorioamnionitis and its incidence in the population studied]. / Morbilidade e mortalidade perinatal relacionadas com a infecção na gestação. Identificação histológica da corioamnionite e sua incidência na população estudada.

Infection of the embryo and foetus remains a major public health problem. It has been widely accepted as a major cause of spontaneous abortion, premature birth and morbidity and mortality of the newborn. Furthermore, many studies stress the role of chorioamnionitis in the onset of premature labor. We have found a significant incidence of chorioamnionitis in placentas examined in our laboratory, but we do not know the real prevalence of intra amniotic infection and the magnitude of its consequences. Furthermore, there is no data concerning the micro-organisms that can act as pathogens in our patients. The aim of this study was to better define the role of infection in pregnancy in our hospital. As a first approach we studied all the placentas that were sent to the Histopathology Department during 1993, trying to correlate histological findings with clinical data. We found that 38% of 280 placentas had histological criteria for chorioamnionitis, 33% of which were associated with fetal death. Only 13% of these cases had clinical signs of infection. These facts stress the need for a sensitive and selective method of identifying organisms that act as pathogens in intrauterine infection. It may be possible to prevent some of its complications if an earlier diagnosis and identification of the agent are done.