Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Esophagopleural fistula due to empyema necessitans.

Empyema necessitans is a rare entity that consists on the development of an abscess that begins in the pleural space and then extends to the adjacent tissues. This case shows a rare and very late complication of a total pneumonectomy, emphasizing the importance of the multidisciplinary approach and the potential of endoscopic therapy with over-the-scope clips.

Terminal ileitis - When all factors come together.

A 45-year-old male, with a recent surgery for odontoid fracture, presented to the emergency department with a 15-days history of abdominal pain associated with fever and weight loss. He reported a recent history of antibiotic therapy due to respiratory infection and a frequent use of anti-inflammatory drugs (NSAIDs) in the last three months.

Endoscopic ampullectomy of a giant pedunculated ampullary adenoma.

The authors present a case of a 72-year-old woman with a personal history of arterial hypertension, dyslipidemia and gallstones. For suspected choledocholithiasis, a MR-Cholangiopancreatography was performed, which revealed the presence of an endoluminal polypoid structure in the third duodenal portion.

A rare cause of obscure gastrointestinal bleeding.

A 62-year-old woman was referred to Gastroenterology appointment due to severe iron deficiency anemia (5.9 g/dL), complaining of asthenia and requiring blood transfusion. The patient denied blood loss. Initial blood test showed a severe iron deficiency, with ferritin of 5ng/mL and transferrin saturation of 2.7%. Folic acid and vitamin B12 were normal. Upper gastroscopy and colonoscopy didn't show any lesions. Abdominopelvic CT and capsule endoscopy were, also, normal.

An uncommon colonic polyp.

A 50-year-old male was referred to a Gastroenterology appointment after a screening colonoscopy with a 25mm exophytic lesion, with a depressed central area, on the transverse colon. Histologic examination of the biopsy specimen showed low-grade dysplasia. The patient was submitted to a new colonoscopy and what was seen was a flat lesion with central depression, with no lift-sign (Figure 1a and 1b) and, therefore, endoscopic resection was not performed. New endoscopic biopsies were taken and showed no dysplasia.

Integrin ß1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells.

BACKGROUND: Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell-cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM). METHODS: To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA). RESULTS: Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin ß1 activation. Integrin ß1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin ß1 crosstalk was validated in Drosophila models and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin ß1 levels. CONCLUSIONS: Integrin ß1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.

Impact of Portuguese propolis on keratinocyte proliferation, migration and ROS protection: Significance for applications in skin products.

OBJECTIVE: Propolis has been used since antiquity, but recent reports of its biological properties hint that it could be employed as a topical pharmaceutical and cosmetic ingredient. This work aims to probe the action of Portuguese propolis extracts on skin cells, providing mechanistic insights into its mode of action and preliminarily assessing its applicability as a skin repair ingredient. METHODS: The total phenolic content of propolis extracts was measured by the Folin Ciocalteu method. The cytotoxic effect of propolis extracts in human keratinocytes was determined and non-cytotoxic concentrations of the extracts were used to study the impact on collective cell migration, cell cycle and intracellular ROS levels. RESULTS: o significant impact was observed in collective cell migration, but one of the extracts mildly increased G2 phase while reducing the % of sub-G1 at a non-cytotoxic concentration. The two extracts with higher phenolic content strongly prevented intracellular cellular ROS accumulation upon exposure to TBHP. Collectively, these results indicate that the putative beneficial effects of propolis extracts in skin repair may not be attributable to induction of collective cell migration but could be partially ascribed to the protection from oxidative stress, which could act in synergy with its well-known antimicrobial activity. CONCLUSION: These data support the applicability of this material in topical and cosmetic formulations and further in vivo assays should be conducted to fully characterize its efficacy and safety.

OBJECTIF: la propolis est utilisée depuis l'Antiquité, mais des rapports récents sur ses propriétés biologiques suggèrent qu'elle pourrait être utilisée comme ingrédient pharmaceutique et cosmétique topique. Ce travail de recherche vise à explorer l'effet d'extraits de propolis portugaise sur les cellules cutanées, en fournissant des informations sur le plan mécanique relatives à son mode d'action et en évaluant de manière préliminaire son applicabilité en tant qu'ingrédient de réparation cutanée. MÉTHODES: la teneur en substance phénolique totale d'extraits de propolis a été mesurée par la méthode de Folin-Ciocalteu. L'effet cytotoxique d'extraits de propolis dans les kératinocytes humains a été déterminé, et des concentrations non cytotoxiques de ces extraits ont été utilisées pour étudier l'impact sur la migration cellulaire collective, le cycle cellulaire et les taux de ROS intracellulaires. RÉSULTATS: un impact significatif a été observé sur la migration cellulaire collective, mais l'un des extraits a légèrement augmenté la phase G2 tout en réduisant le % de sub-G1 à une concentration non cytotoxique. Les deux extraits présentant une teneur phénolique plus élevée ont fortement prévenu l'accumulation de ROS intracellulaires lors de l'exposition à l'hydroperoxyde de tert-butyle (TBHP). Collectivement, ces résultats indiquent que les effets bénéfiques présumés des extraits de propolis dans la réparation cutanée pourraient ne pas être attribuables à l'induction de la migration cellulaire collective, mais partiellement à la protection contre le stress oxydatif, qui pourrait agir en synergie avec son activité antimicrobienne bien connue. CONCLUSION: ces données étayent l'applicabilité de cette substance dans les formulations topiques et cosmétiques, et des tests in vivo supplémentaires doivent être réalisés afin de caractériser plus précisément son efficacité et sa sécurité d'emploi.

Germ cell tumor with duodenal involvement: a rare case of gastrointestinal bleeding.

A 19-year-old male presented to the emergency department with a 7-day history of melena, anorexia and asthenia. Blood tests revealed a hemoglobin of 5.8 g/dL. Upper endoscopy showed a large ulcerated and stenosing lesion in the duodenum. The histologic examination of the biopsy specimen showed a neoplasia with epithelioid cells, accentuated atypia and pleomorphism, expressing MNF 116 cytokeratin, CD30, glypican 3 and alpha-fetoprotein on immunohistochemistry, suggesting of a germ cell tumor metastasis.

Pyoderma gangrenosum in ulcerative colitis - An exuberant and painful complication.

A 41-years-old female, with ulcerative colitis, presented to the emergency department with 7-days history of abdominal pain, bloody stools (> 10/day). The patient referred the appearance of a cutaneous lesion, on her left thigh, with subsequent appearance of similar lesions on the lower limbs. No improvement after amoxicillin/clavulanic acid. On admission, she was febrile (38.2 ºC) and tachycardic. She had three cutaneous lesions, the largest one with 8cm in the left thigh - a deep and painful lesion, with extensive ulceration, necrosis, exudative edges and with marked pathergia, compatible with pyoderma gangrenosum.

A rare endoscopic pattern in a patient with gastroesophageal reflux disease.

A 21-year-old man, with personal history of asthma and no usual medication, was referred to gastroenterology appointment due to dysphagia for solids and previous episodes of food impaction in the last 5 months. He also reported nocturnal heartburn without any other warning signs. Upper gastroscopy revealed a peptic stenosis in the distal esophagus. Histopathologic examination showed hyperplasia and numerous intraepithelial eosinophils, without dysplasia or malignancy. Therapy with a double-dose proton pump inhibitor (PPI) was started.

One appendix too many: a severe IBD-U case in remission after appendectomy.

A 39-year-old female was diagnosed with inflammatory bowel disease unclassified (IBD-U) in 2011, during the post-partum period, after developing chronic bloody diarrhea and marked weight loss. She underwent colonoscopy showing erosive ileitis and pancolitis. Biopsies were compatible with unspecified chronic ileocolitis.

Sleep Disturbance in Inflammatory Bowel Disease Is Associated with Disease Activity and Adverse Outcome.

BACKGROUND: There is growing evidence about the relationship between sleep quality (SQ) and disease activity in inflammatory bowel disease (IBD). This study aimed to identify the prevalence of sleep disturbance in IBD and its predictive factors and to assess its association with worse outcome. METHODS: IBD patients were prospectively enrolled. Clinical activity, inflammatory activity (high C-reactive protein or fecal calprotectin), and SQ (assessed using the Pittsburgh Sleep Quality Index) were evaluated, and logistic regression was used to identify predictors of poor SQ at baseline. The development of disability or disease progression at 6 months (surgery, hospitalization, development of stenosis, penetrating or perianal disease, steroid dependency, or start/change immunosuppression) was compared between patients with and without poor SQ. RESULTS: Two hundred and five patients were enrolled, with 44.9% (n = 92) reporting poor SQ. On multivariate analysis, current smoking (OR 2.80), extraintestinal manifestations (OR 2.68), clinical activity (OR 3.31), and inflammatory activity (OR 4.62) were predictive factors of poor SQ. Cox proportional hazards model showed that poor SQ was predictive of worse prognosis at 6 months (HR 2.470). CONCLUSION: There is a high prevalence of poor SQ in IBD patients, highlighting the importance of its inclusion in patient-reported outcomes. Sleep disturbance seems to have prognostic value in IBD.

Aquaculture wastewater treatment through microalgal. Biomass potential applications on animal feed, agriculture, and energy.

The use of microalgae to remediate raw effluent from brown crab aquaculture was evaluated by performing batch mode growth tests using separately the microalgae Chlorella vulgaris (Cv), Scenedesmus obliquus (Sc), Isochrysis galbana (Ig), Nannocloropsis salina (Ns), and Spirulina major (Sp). Removal efficiencies in batch growth were 100% for total nitrogen and total phosphorus for all microalgae. Chemical oxygen demand (COD) remediations were all above 72%. Biomass productivity varied from 20.9 mg L-1 day-1 (N. salina) to 146.4 mg L-1 day-1 (C. vulgaris). The two best performing algae were C. vulgaris and S. obliquus and they were tested in semi-continuous growth, reaching productivities of 879.8 mg L-1 day-1 and 811.7 mg L-1 day-1, respectively. The bioremediation of the effluent was tested with a transfer system consisting of three independent containers and compared with the use of a single container. The single container had the same capacity and received weekly the same volume of effluent as the three containers together. The remediation capacity of the 3 containers was much higher than the single one. The supplementation with NaNO3 was tested to improve the nutrient removal microalgae' capacity, with positive results. The removal efficiencies were 100% for total nitrogen and total phosphorus and higher than 96% for COD. The obtained C. vulgaris and S. obliquus biomass were composed of 31 and 35% proteins, 6 and 8% lipids, 39 and 30% carbohydrates, respectively. The composition of these biomass suggest that it can be used as novel and sustainable ingredients in aquaculture feeds. The algal biomass of Cv and Sc were used as biostimulants in the germination of wheat and watercress, and very promising results were attained, with increases in the germination index for Cv and Sc of 175% and 48% in watercress and 84% and 98% in wheat, respectively. The biomasses of Cv and Sc were also subjected to a torrefaction process with 72.5 ± 1.7% char yields. The obtained biochars were tested as biostimulants for germination seeds (wheat and watercress) and as bio-adsorbent of dye solutions.

Predicting the Functional Impact of CDH1 Missense Mutations in Hereditary Diffuse Gastric Cancer.

The role of E-cadherin in Hereditary Diffuse Gastric Cancer (HDGC) is unequivocal. Germline alterations in its encoding gene (CDH1) are causative of HDGC and occur in about 40% of patients. Importantly, while in most cases CDH1 alterations result in the complete loss of E-cadherin associated with a well-established clinical impact, in about 20% of cases the mutations are of the missense type. The latter are of particular concern in terms of genetic counselling and clinical management, as the effect of the sequence variants in E-cadherin function is not predictable. If a deleterious variant is identified, prophylactic surgery could be recommended. Therefore, over the last few years, intensive research has focused on evaluating the functional consequences of CDH1 missense variants and in assessing E-cadherin pathogenicity. In that context, our group has contributed to better characterize CDH1 germline missense variants and is now considered a worldwide reference centre. In this review, we highlight the state of the art methodologies to categorize CDH1 variants, as neutral or deleterious. This information is subsequently integrated with clinical data for genetic counseling and management of CDH1 variant carriers.

Perinatal outcome of dichorionic-triamniotic as compared to trichorionic triplets.

OBJECTIVE: To evaluate if the perinatal outcomes of dichorionic-triamniotic (DC) triplets are significantly different than that of trichorionic (TC) triplets. STUDY DESIGN: Comparison of maternal and neonatal data of 44 DC to 46 TC triplets, using univariate analysis. RESULTS: DC triplets were significantly more common after spontaneous conception but all other maternal characteristics as well complications and cesarean section rates were similar. Both groups had similar incidence of birth at <32 and <28 weeks as well as similar incidence of very low and extremely low birth weight. There was similar incidence of neonatal morbidity except for twin-twin transfusion syndrome (13.6%) in the DC group. The stillbirth rate was 45/1000 and 29/1000, the early neonatal mortality rates were 63/1000 and 45/1000, and the perinatal mortality rate was 106/1000 and 72/1000 for DC and TC triplets, respectively (all not significantly different). CONCLUSIONS: Our data indicate that DC twins are not significantly disadvantaged compared to TC triplets and the similar outcomes might be reassuring for those who consider continuing their DC triplet pregnancy.

Epithelioid Hemangioendothelioma in a Liver Transplant Recipient: A Case Report of an Extremely Rare Tumor.

Epithelioid hemangioendothelioma is a very rare vascular neoplasm, which is often multifocal or metastatic at diagnosis. Most frequently arises in the liver, followed by the lung and bones. The authors present a case of a liver transplant recipient who developed a pattern of hepatic cholestasis associated with the appearance of a proliferative hepatic lesion with infiltrative growth. Histological examination and immunohistochemical study were compatible with the diagnosis of epithelioid hemangioendothelioma. Pulmonary micronodules were detected and lung metastases were hypothesized. Therefore, bronchoscopy was performed, which turned out to be normal, and cytology was negative for neoplastic cells. After a multidisciplinary discussion, liver re-transplantation was decided. After 8 years of follow-up, the patient is clinically stable, with no graft dysfunction, no neoplastic recurrence, and dimensional stability of the pulmonary micronodules. Patients with organ transplant have higher risk of developing carcinoma compared to the general population. The development of cancer is a multifactorial process and little is known about the etiology of epithelioid hemangioendothelioma. No standard treatment strategy has been defined yet, and the natural course of the disease is heterogenous and the individual prognosis unpredictable. Complete surgical resection is offered to patients with unifocal disease, and those with unresectable disease should be evaluated for orthotopic liver transplantation.

O hemangioendotelioma epitelióide é uma neoplasia vascular extremamente rara, muitas vezes multifocal ou metastática ao diagnóstico. O local mais frequente afetado é o fígado, seguido pelo pulmão e ossos. Os autores apresentam o caso de uma doente com antecedentes de transplante hepático que desenvolveu um padrão de colestase associado ao aparecimento de uma lesão hepática proliferativa e de crescimento infiltrativo. O exame histológico e o estudo imuno-histoquímico foram compatíveis com hemangioendotelioma epitelióide. Foram detetados micronódulos pulmonares, tendo sido colocada a hipótese de se tratarem de metástases pulmonares. Assim, foi realizada broncoscopia, que não revelou alterações, estando a citologia negativa para células neoplásicas. Após discussão multidisciplinar, foi decidido o retransplante hepático. Após 8 anos de seguimento, a doente encontra-se clinicamente estável, sem disfunção do enxerto, sem recidiva neoplásica e com estabilidade dimensional dos micronódulos pulmonares. Doentes submetidos a transplante têm maior risco de desenvolver neoplasias em comparação com a população geral. O desenvolvimento da neoplasia é um processo multifatorial, sendo a etiologia do hemangioendotelioma epitelióide ainda pouco compreendida. Não existe uma estratégia terapêutica standard, sendo o curso natural da doença heterogêneo e o prognóstico individual imprevisível. A ressecção cirúrgica é a primeira opção terapêutica nos doentes com doença unifocal, aqueles com doença irressecável devem ser avaliados para transplante hepático.

Polydimethylsiloxane Surface Modification of Microfluidic Devices for Blood Plasma Separation.

Over the last decade, researchers have developed a variety of new analytical and clinical diagnostic devices. These devices are predominantly based on microfluidic technologies, where biological samples can be processed and manipulated for the collection and detection of important biomolecules. Polydimethylsiloxane (PDMS) is the most commonly used material in the fabrication of these microfluidic devices. However, it has a hydrophobic nature (contact angle with water of 110°), leading to poor wetting behavior and issues related to the mixing of fluids, difficulties in obtaining uniform coatings, and reduced efficiency in processes such as plasma separation and molecule detection (protein adsorption). This work aimed to consider the fabrication aspects of PDMS microfluidic devices for biological applications, such as surface modification methods. Therefore, we studied and characterized two methods for obtaining hydrophilic PDMS surfaces: surface modification by bulk mixture and the surface immersion method. To modify the PDMS surface properties, three different surfactants were used in both methods (Pluronic® F127, polyethylene glycol (PEG), and polyethylene oxide (PEO)) at different percentages. Water contact angle (WCA) measurements were performed to evaluate the surface wettability. Additionally, capillary flow studies were performed with microchannel molds, which were produced using stereolithography combined with PDMS double casting and replica molding procedures. A PDMS microfluidic device for blood plasma separation was also fabricated by soft lithography with PDMS modified by PEO surfactant at 2.5% (v/v), which proved to be the best method for making the PDMS hydrophilic, as the WCA was lower than 50° for several days without compromising the PDMS's optical properties. Thus, this study indicates that PDMS surface modification shows great potential for enhancing blood plasma separation efficiency in microfluidic devices, as it facilitates fluid flow, reduces cell aggregations and the trapping of air bubbles, and achieves higher levels of sample purity.