Boroxine benzaldehyde complex for pharmaceutical applications probed by electron interactions.

RATIONALE: 2,4,6-Tris(4-formylphenyl)boroxine (TFPB) is a substituted boroxine containing a benzaldehyde molecule bonded to each boron atom. Boroxine cages are an emerging class of functional nanostructures used in host-guest chemistry, and benzaldehyde is a potential radiosensitizer. Reactions initiated by low-energy electrons with such complexes may dictate and bring new fundamental knowledge for biomedical and pharmaceutical applications. METHODS: The electron ionization properties of TFPB are investigated using a gas-phase electron-molecule crossed beam apparatus coupled with a reflectron time-of-flight mass spectrometer in an orthogonal geometry. Ionization and threshold energies are experimentally determined by mass spectra acquisition as a function of the electron energy. RESULTS: The abundance of the molecular precursor cation in the mass spectrum at 70 eV is significantly lower than that of the most abundant fragment C7 H5 O+ . Twenty-nine cationic fragments with relative intensities >2% are detected and identified. The appearance energies of six fragment cations are reported, and the experimental first ionization potential is found at 9.46 ± 0.11  eV. Moreover, eight double cations are identified. The present results are supported by quantum chemical calculations based on bound state techniques, electron ionization models and thermodynamic thresholds. CONCLUSIONS: According to these results, the TPFB properties may combine the potential radiosensitizer effect of benzaldehyde with the stability of the boroxine ring.

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

Formation of Temporary Negative Ions and Their Subsequent Fragmentation upon Electron Attachment to CoQ0 and CoQ0 H2.

Ubiquinone molecules have a high biological relevance due to their action as electron carriers in the mitochondrial electron transport chain. Here, we studied the dissociative interaction of free electrons with CoQ0 , the smallest ubiquinone derivative with no isoprenyl units, and its fully reduced form, 2,3-dimethoxy-5-methylhydroquinone (CoQ0 H2 ), an ubiquinol derivative. The anionic products produced upon dissociative electron attachment (DEA) were detected by quadrupole mass spectrometry and studied theoretically through quantum chemical and electron scattering calculations. Despite the structural similarity of the two studied molecules, remarkably only a few DEA reactions are present for both compounds, such as abstraction of a neutral hydrogen atom or the release of a negatively charged methyl group. While the loss of a neutral methyl group represents the most abundant reaction observed in DEA to CoQ0 , this pathway is not observed for CoQ0 H2 . Instead, the loss of a neutral OH radical from the CoQ0 H2 temporary negative ion is observed as the most abundant reaction channel. Overall, this study gives insights into electron attachment properties of simple derivatives of more complex molecules found in biochemical pathways.

Excited States of Bromopyrimidines Probed by VUV Photoabsorption Spectroscopy and Theoretical Calculations.

We report absolute photoabsorption cross sections for gas-phase 2- and 5-bromopyrimidine in the 3.7-10.8 eV energy range, in a joint theoretical and experimental study. The measurements were carried out using high-resolution vacuum ultraviolet synchrotron radiation, with quantum chemical calculations performed through the nuclear ensemble approach in combination with time-dependent density functional theory, along with additional Franck-Condon Herzberg-Teller calculations for the first absorption band (3.7-4.6 eV). The cross sections of both bromopyrimidines are very similar below 7.3 eV, deviating more substantially from each other at higher energies. In the 7.3-9.0 eV range where the maximum cross-section is found, a single and broad band is observed for 5-bromopyrimidine, while more discernible features appear in the case of 2-bromopyrimidine. Several π* ← π transitions account for the most intense bands, while weaker ones are assigned to transitions involving the nitrogen and bromine lone pairs, the antibonding σ*Br orbital, and the lower-lying Rydberg states. A detailed comparison with the available photo-absorption data of bromobenzene is also reported. We have found significant differences regarding the main absorption band, which is more peaked in bromobenzene, becoming broader and shifting to higher energies in both bromopyrimidines. In addition, there is a significant suppression of vibrational structures and of Rydberg states in the pair of isomers, most noticeably for 2-bromopyrimidine.

Methylation patterns in dysplasia in inflammatory bowel disease patients.

Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.

Endoscopic ultrasound with fine needle aspiration is useful in pancreatic cysts smaller than 3 cm.

BACKGROUND: In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation). OBJECTIVE: To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm. METHODS: Retrospective study of PCLs < 3 cm (2007-2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed. RESULTS: We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging-AUC = 0.80 versus AUC = 60. CONCLUSION: EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.

The Role of Electron Transfer in the Fragmentation of Phenyl and Cyclohexyl Boronic Acids.

In this study, novel measurements of negative ion formation in neutral potassium-neutral boronic acid collisions are reported in electron transfer experiments. The fragmentation pattern of phenylboronic acid is comprehensively investigated for a wide range of collision energies, i.e., from 10 to 1000 eV in the laboratory frame, allowing some of the most relevant dissociation channels to be probed. These studies were performed in a crossed molecular beam set up using a potassium atom as an electron donor. The negative ions formed in the collision region were mass analysed with a reflectron time-of-flight mass spectrometer. In the unimolecular decomposition of the temporary negative ion, the two most relevant yields were assigned to BO- and BO2-. Moreover, the collision-induced reaction was shown to be selective, i.e., at energies below 100 eV, it mostly formed BO-, while at energies above 100 eV, it mostly formed BO2-. In order to further our knowledge on the complex internal reaction mechanisms underlying the influence of the hybridization state of the boron atom, cyclohexylboronic acid was also investigated in the same collision energy range, where the main dissociation channel yielded BO2-. The experimental results for phenyl boronic acid are supported by ab initio theoretical calculations of the lowest unoccupied molecular orbitals (LUMOs) accessed in the collision process.

Colorectal cancer surveillance in Portuguese families with lynch syndrome: a cohort study.

PURPOSE: Lynch syndrome (LS) is associated with a high risk of colorectal cancer (CRC). The aim of this study was to assess the cumulative risk for the development of colorectal adenomas or carcinomas in a LS CRC surveillance program and to audit the quality of the endoscopic procedures. METHODS: We evaluated 147 asymptomatic LS mutation carriers, without previous CRC, in a surveillance program with colonoscopy every 12-18 months, between 2005 and 2016. Data was obtained by retrospective review of colonoscopy reports and hospital clinical files. The main outcome was assessed using Kaplan-Meier curves. Logistic regression was used to study the risk of developing adenomas. RESULTS: Patients were under surveillance for 1092 observation years (mean, 7.7 years/patient). Most exams presented adequate bowel preparation (83.5%) and 99.2% achieved cecal intubation. The estimated risk for adenomas at age 60 was 75.6% in men (95%CI, 60.5-88.3) and 65.5% in women (95%CI, 50.8-79.7). Male gender (OR 2.4; 95%CI, 1.2-4.9; p = 0.018) and age at start of surveillance > 40 years (OR 3.7; 95%CI, 1.8-7.7; p < 0.001) were independent risk factors for adenoma detection. CRC was diagnosed in 11 patients with an estimated cumulative risk at age 60 of 18.4% (95%CI, 9.2-34.8%); 72.7% of CRC were classified as stage I; no patient died from CRC. CONCLUSION: A colonoscopic surveillance program in LS patients allowed the detection of adenomas in a large group of mutation carriers and diagnosis of early-stage carcinomas. Our findings may help other teams to adopt similar strategies or to refer patients early to specialized centers.

Data analysis of the influence of microstructure, composition, and loading conditions on stress corrosion cracking behavior of Mg alloys.

Stress corrosion cracking (SCC) can be a crucial problem in applying rare earth (RE) Magnesium alloys in environments where mechanical loads and electrochemical driven degradation processes interact. It has been proven already that the SCC behavior is associated with microstructural features, compositions, loading conditions, and corrosive media, especially in-vivo. However, it is still unclear when and how mechanisms acting on multiple scales and respective system descriptors predictable contribute to SCC for the wide set of existing Mg alloys. In the present work, suitable literature data along SCC of Mg alloys has been analyzed to enable the development of a reliable SCC model for MgGd binary alloys. Pearson correlation coefficient and linear fitting are utilized to describe the contribution of selected parameters to corrosion and mechanical properties. Based on our data analysis, a parameter ranking is obtained, providing information on the SCC impact with regard to ultimate tensile strength (UTS) and fracture elongation of respective materials. According to the analyzed data, SCC susceptibility can be grouped and mapped onto Ashby type diagrams for UTS and elongation of respective base materials tested in air and in corrosive media. The analysis reveals the effect of secondary phase content as a crucial materials descriptor for our analyzed materials and enables better understanding towards SCC model development for Mg-5Gd alloy based implant.

Endoscopic Approach to Duodenal Adenomas in Familial Adenomatous Polyposis: A Retrospective Cohort.

Introduction: Over 90% of the patients with familial adenomatous polyposis (FAP) will develop duodenal adenomas. Aim: The aim of this study was to evaluate the effectiveness and safety of endoscopic excision of large duodenal adenomas in FAP patients. Methods: All FAP patients from a familial risk clinic submitted to endoscopic therapy for duodenal adenomas ≥10 mm between January 2010 and February 2021 were included. Results: From 151 FAP families, 22 patients (50 lesions) were included: 54.5% female; median follow-up 8.5 (IQR: 5.8-12.3) years after the first endoscopy. First therapeutic endoscopy occurred at a median age of 41.0 years (IQR: 33.0-58.2). Repeat therapeutic endoscopy was required in 54.5% of patients. Median size of the largest adenoma was 15 mm (IQR: 10-18 mm); resection was piecemeal in 63.1% and en bloc in the remaining. In 2 cases, the resection was incomplete (fibrosis due to previous resection and difficult positioning). Complications occurred in 6.3% of the resected lesions (4 patients): 2 immediate (bleeding, perforation); 4 in the first week (1 bleeding, 2 mild pancreatitis, 1 perforation requiring surgery; the latter two after ampullectomy). Histology revealed low-grade dysplasia adenomas in 90.1%; no adenocarcinomas were found. One patient with Spigelman stage IV disease not amenable to endoscopic control underwent elective duodenopancreatectomy (without duodenal cancer). Conclusion: Endoscopic surveillance and treatment of duodenal adenomas in FAP patients was safe and effective in the prevention of duodenal cancer.

Introdução: Mais de 90% dos doentes com Polipose Adenomatosa Familiar (PAF) desenvolvem adenomas duodenais. Objetivo: Avaliar a eficacia e seguranca da excisao endoscopica de adenomas duodenais em doentes com PAF. Métodos: Incluidos todos os doentes com PAF submetidos a terapeutica endoscopica de adenomas duodenais ≥10 mm entre janeiro/2010-fevereiro/2021. Resultados: Em 151 familias com PAF, incluidos 22 doentes (50 lesoes): 54.5% mulheres; mediana do follow-up 12.3 (IQR: 6.0­19.0) anos. Primeira endoscopia terapeutica (ressecao de polipos duodenais ≥10 mm) ocorreu numa mediana de idades 41.0 (IQR: 33.0­58.2) anos. Em 54.5% dos casos, foi necessaria uma nova endoscopia terapeutica. Dimensao mediana do maior adenoma: 15 mm (IQR: 10­18 mm); ressecao realizada em piecemeal em 63.1% e em bloco nos restantes. Em dois casos, a ressecao endoscopica foi incompleta (fibrose em local de ressecao previa:1; posicionamento: 1). Complicacoes em 6.3% das lesoes ressecadas (4 doentes): 2 imediatas (hemorragia e perfuracao, manejadas endoscopicamente); 4 na primeira semana (1 hemorragia controlada endoscopicamente, 2 pancreatites ligeiras tratadas conservadoramente, 1 perfuracao com necessidade de cirurgia; as duas ultimas apos ampulectomia). A avaliacao histologica revelou adenomas com displasia de baixo grau em 90.1%; nenhum adenocarcinoma. Um doente com doenca Spigelman IV nao controlavel endoscopicamente realizou duodenopancreatectomia (sem cancro). Conclusão: A vigilancia e tratamento endoscopicos de adenomas duodenais em doentes com PAF revelaram-se seguros e eficazes na prevencao de cancro duodenal.

Digestive α-L-fucosidase activity in Rhodnius prolixus after blood feeding: effect of secretagogue and nutritional stimuli.

Introduction: Rhodnius prolixus (Hemiptera: Reduviidae) is an important vector of Trypanosoma cruzi, the causative agent of Chagas Disease. This insect is a model for the study of insect physiology, especially concerning the digestion of blood. Among the enzymes produced in the midgut of R. prolixus after blood feeding there is a α-L-fucosidase activity. There are very few studies on α-L-fucosidase of insects, and the role of R. prolixus α-L-fucosidase is still not clear. In this work, we tested if the mechanism for production of this enzyme is similar to the observed for proteases, a secretatogue mechanism that respond to the protein contents of the meal. Methods: We tested if specific proteins or sugars elicit this response, which may help to understand the nature of the physiological substrate for this enzyme. Results: In general, our results showed that the Anterior Midgut was the only midgut fraction that responds to the blood meal in terms of α-L-fucosidase production. Besides that, this response was not triggered by midgut distension or by ingestion of the blood cell fraction. Conversely, the enzyme was produced after feeding with the plasma fraction. However, the production of α-L-fucosidase was also triggered by different biochemical stimuli, as protein or fucoidan ingestion. Discussion: This suggested that the production of the enzyme in the anterior midgut was a general physiological response under control of different convergent signals. Besides that, the comparison between different treatments for artificial blood feeding showed that heparinated blood was the choice with minor side effects for the study of the midgut α-L-fucosidase, when compared to defibrinated or citrated blood.

Dysplasia Surveillance in Inflammatory Bowel Disease: A Cohort Study.

INTRODUCTION: Patients with colonic inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer (CRC), whereby surveillance colonoscopy is recommended. AIM: To study the clinical and endoscopic variables associated with dysplasia in IBD patients. METHODS: A cohort study was conducted on IBD patients who were part of a colonoscopy surveillance program between 2011 and 2016. RESULTS: A total of 342 colonoscopies were performed on 162 patients (105 with ulcerative colitis [UC] and 57 with Crohn's disease). Random biopsies were performed at least once on 81.5% of patients; 33.3% of the patients underwent chromoendoscopy (CE) at least once. Endoscopically resectable lesions were detected in 55 patients (34%), and visible lesions deemed unfit for endoscopic resection were found in 5 patients (3.1%). Overall, 62 dysplastic visible lesions (58 with low-grade dysplasia and 3 with high-grade dysplasia) and 1 adenocarcinoma were found in 34 patients. Dysplasia in random biopsies was present in 3 patients, the yield of random biopsies for dysplasia being 1.85%/patient (3/162), 1.75%/colonoscopy (6/342), and 0.25%/biopsy (9/3,637). Dysplasia detected in random biopsies was significantly associated with a personal history of visible dysplasia (p = 0.006). Upon univariate analysis, dysplasia was significantly associated with the type of IBD, the performance of random biopsies, and CE (p = 0.016/0.009/0.05, respectively). On multivariate analysis, dysplasia was associated with duration of disease. CONCLUSION: Our data confirm that patients with long-standing IBD, in particular UC, should be enrolled in dysplasia surveillance programs, and that performing CE and random biopsies seems to help in the detection of colonic neoplastic lesions.

INTRODUÇÃO: Nos doentes com doença inflamatória intestinal (DII) está recomendada vigilancia por colonoscopia para detetar e tratar lesões neoplásicas iniciais, dado o risco aumentado de cancro colo-rectal (CCR). O objetivo do trabalho foi estudar variáveis clínicas e endoscópicas associadas a displasia. MÉTODOS: Estudo coorte − doentes com DII integrados num programa de vigilância de displasia entre 2011­2016. RESULTADOS: Um total de 342 colonoscopias foi realizado em 162 doentes, 105 com colite ulcerosa (CU) e 57 com doença de Crohn (DC). Foram efetuadas biopsias aleatorias (BA) em 81,5% dos doentes (média: 27.5 ± 6.4 biopsias/colonoscopia) e 33.3% realizaram cromoendoscopia. 55 doentes apresentaram lesões endoscopicamente ressecáveis e 5 doentes lesões irressecáveis. No total, em 34 doentes, foram identificadas 6 lesões displásicas visíveis (58 com displasia de baixo grau e 3 com displasia de alto grau) e um adenocarcinoma. Foi detetada displasia em BA em 3 doentes sendo o rendimento das BA de 1.85% por doente (3/162), 1.75% por colonoscopia (6/342) e 0.25% por biopsia (9/3,637). A displasia em BA associou-se à historia pessoal de lesões displásicas (p = 0.006). A presença de displasia associouse, na análise univariada, com: tipo de DII (p = 0.016), realização de BA (p = 0.009) e cromoendoscopia (p = 0.05). Na anàlise multivariada, verificou-se associação com a duração da doença. CONCLUSÃO: Doentes com DII de longa duração deverão ser incluidos num programa de vigilància de displasia. A realizado de cromoendoscopia e BA é útil na deteção de lesões displásicas do cólon.

Electron Driven Reactions in Tetrafluoroethane: Positive and Negative Ion Formation.

In the search for alternatives to chlorine-containing gases, tetrafluoroethane, CF3CH2F (R134a), a widely used refrigerant gas, has been recognized as a promising substitute for dichlorodifluoromethane, CCl2F2 (R12). When R12 is replaced by R134a, the global warming potential drops from 8100 to 1430, the ozone depletion potential changes from 1 to 0, and the atmospheric lifetime decreases from 100 to 14 years. Electron interactions in the gas phase play a fundamental role in the atmospheric sciences. Here, we present a detailed study on electron-driven fragmentation pathways of CF3CH2F, in which we have investigated processes induced by both electron ionization and electron attachment. The measurements allow us to report the ion efficiency curves for ion formation in the energy range of 0 up to 25 eV. For positive ion formation, R134a dissociates into a wide assortment of ions, in which CF3+ is observed as the most abundant out of seven ions with a relative intensity above 2%. The results are supported by quantum chemical calculations based on bound state techniques, electron-impact ionization models, and electron-molecule scattering simulations, showing a good agreement. Moreover, the experimental first ionization potential was found at 13.10 ± 0.17 eV and the second at around 14.25 eV. For negative ion formation, C2F3- was detected as the only anion formed, above 8.3 eV. This study demonstrates the role of electrons in the dissociation of R134a, which is relevant for an improvement of the refrigeration processes as well as in atmospheric chemistry and plasma sciences.

Polyelectrolyte Based Sensors as Key to Achieve Quantitative Electronic Tongues: Detection of Triclosan on Aqueous Environmental Matrices.

Triclosan (TCS) is a bacteriostatic used in household items that promotes antimicrobial resistance and endocrine disruption effects both to humans and biota, raising health concerns. In this sense, new devices for its continuous monitoring in complex matrices are needed. In this work, sensors, based on polyelectrolyte layer-by-layer (LbL) films prepared onto gold interdigitated electrodes (IDE), were studied. An electronic tongue array, composed of (polyethyleneimine (PEI)/polysodium 4-styrenesulfonate (PSS))5 and (poly(allylamine hydrochloride/graphene oxide)5 LbL films together with gold IDE without coating were used to detect TCS concentrations (10-15-10-5 M). Electrical impedance spectroscopy was used as means of transduction and the obtained data was analyzed by principal component analysis (PCA). The electronic tongue was tested in deionized water, mineral water and wastewater matrices showing its ability to (1) distinguish between TCS doped and non-doped solutions and (2) sort out the TCS range of concentrations. Regarding film stability, strong polyelectrolytes, as (PEI/PSS)n, presented more firmness and no significant desorption when immersed in wastewater. Finally, the PCA data of gold IDE and (PEI/PSS)5 sensors, for the mineral water and wastewater matrices, respectively, showed the ability to distinguish both matrices. A sensitivity value of 0.19 ± 0.02 per decade to TCS concentration and a resolution of 0.13 pM were found through the PCA second principal component.

Intensive Follow-Up After Curative Surgery for Colorectal Cancer.

INTRODUCTION: The purpose of postoperative surveillance programs after curative treatment for colorectal cancer is to detect asymptomatic recurrences with the premise that an important rate will be eligible for curative resection, improving overall survival. We have implemented a surveillance program for patients with colorectal cancer, stages II-III, with periodic clinical, carcinoembryonic antigen and cancer antigen-19-9 assessment, computed tomography and colonoscopy. The aim of this study was to assess the rate of curative treatment of recurrence, colorectal cancer mortality and clinical characteristics associated with non-resectable recurrence. MATERIAL AND METHODS: Open cohort study, single center. All patients on the intensive surveillance program between March 2008 and January 2015 were included. STATISTICS: chi-square, Wilcoxon rank sum test, logistic regression, Kaplan-Meier log-rank test (SPSS20®). RESULTS: We had a total 404 patients evaluated; 59.6% male; mean age of 65 ± 10 years; 50.7% rectal tumor; 56.2% stage III. The average time of follow-up was 37 months and the recurrence rate was 12.9% (n = 52), mostly detected in the first three years (88.4%). The pattern of recurrence was associated with the site of the primary tumor (p < 0.001). Twenty-one patients underwent curative resection. Factors associated with non-resectable recurrence were aged ≥ 70 years (p = 0.022), disease location in the colon (p = 0.033) and cancer antigen-19-9-9 elevation (p = 0.024). The overall rate of cancer-specific mortality was 2.2% (n = 9). DISCUSSION: The association between colon cancer and non-resectable recurrence is explained by the higher rate of disseminated disease in these patients. Cancer antigen-19-9 added no benefit to the surveillance program. CONCLUSION: This intensive real-world postoperative surveillance program allowed performing curative surgery to 40.3% of patients with recurrence.

Introdução: A vigilância intensiva pós-operatória do carcinoma colo-retal permite a deteção da recorrência em fase assintomática, aumentando o número de doentes que podem beneficiar de nova cirurgia. Implementámos um programa de vigilância de doentes com carcinoma colo-retal estádios II-III, operados com intenção curativa, com avaliação clínica, tomografia computorizada e colonoscopia. O presente estudo teve como objectivos avaliar a taxa de cirurgia de intenção curativa, a taxa de mortalidade por cancro e identificar características clínicas associadas à irresecabilidade da recidiva. Material e Métodos: Estudo de coorte, unicêntrico. Foram incluídos todos os doentes com carcinoma colo-retal integrados em programa de vigilância entre março de 2008 e janeiro de 2015. Análise estatística: qui-quadrado, Wilcoxon, regressão logística, Kaplan-Meier (SPSS20®). Resultados: Avaliámos 404 doentes; idade média: 65 ± 10 anos, 59,6% sexo masculino, 50,7% reto, 56,2% estádio III. O tempo médio de vigilância foi 37 meses e a taxa de recidiva foi 12,9% (n = 52), a maioria detetada nos primeiros três anos (88,4%). O padrão de recidiva associou-se à localização do tumor primário (p < 0,001). Vinte e um doentes foram submetidos a cirurgia curativa. Os fatores associados a recidiva irressecável foram: idade ≥ 70 anos (p = 0,022), carcinoma colo-retal localizado no cólon (p = 0,033) e elevação de antigénio carboidrato 19-9 (p = 0,024). A taxa global de mortalidade específica por cancro foi 2,2% (n = 9). Discussão: A associação entre neoplasia do cólon e recidiva irressecável deve-se à taxa mais elevada de doença disseminada nestes doentes. O antigénio carboidrato 19-9 não trouxe benefício acrescido ao programa de vigilância. Conclusão: Este estudo confirma o interesse clínico da vigilância intensiva na deteção de recidiva assintomática, permitindo alcançar cirurgia curativa em 40,3% dos doentes com recidiva.

A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro).

Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.