Impact of Percutaneous Endoscopic Gastrostomy Tube Feeding on Nutritional Status in Patients Undergoing Chemoradiotherapy for Oesophageal Cancer.

Introduction: Oesophageal cancer causes dysphagia and weight loss. Malnutrition further worsens with multimodal treatment. Aim: The aim of the study was to evaluate the impact of percutaneous endoscopic gastrostomy (PEG) placement in the nutritional status of patients with oesophageal cancer requiring chemoradiotherapy (CRT). Methods: A comparative study with a prospective arm and a historical cohort was conducted. Oesophageal cancer patients undergoing CRT with dysphagia grade >2 and/or weight loss >10% were submitted to PEG-tube placement (pull method) before CRT. Stoma seeding was evaluated through a swab obtained after placement and, in surgical patients, the resected stoma. A matched historical cohort without PEG placement was used as control (trial ACTRN12616000697482). Results: Twenty-nine patients (intervention group, IG) were compared to 30 patients (control group, CG). Main outcomes did not differ in the IG and CG: weight loss during CRT 8.1 ± 5.5 kg versus 9.1 ± 4.2 kg (p = 0.503); 6-month mortality after CRT or surgery 17.2% versus 26.7% (p = 0.383); perioperative complication rate 54.5% versus 55.6% (p = 1.000); unplanned hospital admissions 34.5% versus 40.0% (p = 0.661). In the CG, during CRT, 14 (46.7%) patients presented with dysphagia grade 3-4, of whom 12 required nasogastric tube feeding (n = 10), surgical gastrostomy (n = 1), and oesophageal dilation (n = 1). In the IG, 89.7% used the PEG tube during CRT, sometimes exclusively in 51.7%. Adverse events were mainly minor (n = 12, 41.4%), mostly late peristomal infections, 1 major complication (exploratory laparotomy due to suspected colonic interposition, not confirmed). There was no cytological or histological evidence of stomal tumour seeding. Conclusion: Weight loss, hospital admissions, surgical complications, and mortality were identical in oesophageal cancer patients referred for CRT, regardless of prophylactic PEG. However, half of the patients required exclusive enteral nutritional support, making PEG-tube placement an alternative to consider.

Introdução: A neoplasia do esófago associa-se a disfagia e perda ponderal, sendo a desnutrição agravada pelo tratamento multimodal. Objetivo: Avaliar o impacto da colocação de gastrostomia percutânea endoscópica (PEG) no estado nutricional de doentes com neoplasia do esófago propostos para quimiorradioterapia (QRT). Métodos: Estudo comparativo com braço prospetivo e controlo retrospetivo. Incluídos doentes com neoplasia do esófago propostos para QRT definitiva ou neoadjuvante, com disfagia grau >2 e/ou perda de peso <10%. Colocada PEG (método pull) antes do início de QRT. Avaliada sementeira tumoral por zaragatoa e histologia. Como controlo, utilizada coorte histórica de doentes sem PEG. Registo ACTRN12616000697482. Resultados: 29 doentes (grupo intervenção, GI) foram comparados com 30 controlos (GC). Sem diferença significativa nos principais outcomes: perda de peso durante a QRT 8.1 ± 5.5 kg versus 9.1 ± 4.2 kg (p = 0.503); mortalidade aos 6 meses após QRT ou cirurgia 17.2% versus 26.7% (p = 0.383); taxa de complicações perioperatórias 54.5% versus 55.6% (p = 1.000); admissões hospitalares não planeadas 34.5% versus 40.0% (p = 0.661). No GC, durante a QRT, 14 (46.7%) apresentaram disfagia graus 3­4, dos quais 12 necessitaram de nutrição por sonda nasogástrica (n = 10), gastrostomia cirúrgica (n = 1) ou dilatação esofágica (n = 1). No GI, 89.7% utilizaram a PEG durante QRT, em algum momento de forma exclusiva em 51.7%. Os eventos adversos foram sobretudo minor (n = 12; 41.4%), sobretudo infeções tardias peri-estoma; 1 complicação major (laparotomia exploradora por suspeita de interposição de cólon, não confirmada). Sem evidência citológica ou histológica de sementeira tumoral no estoma. Conclusão: Embora não se tenham observado diferenças na perda de peso, complicações cirúrgicas e mortalidade entre grupos, metade dos utentes necessitou de nutrição entérica exclusiva, tornando a colocação de PEG uma alternativa a considerar.

Endoscopic submucosal dissection: a country dissemination experience and outcomes.

OBJECTIVE: An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal. METHODS: All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center. RESULTS: All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81-96.8) and 87% (IQR, 74-93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25-6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions. CONCLUSION: Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.

Should Colorectal Cancer Screening in Portugal Start at the Age of 45 Years? A Cost-Utility Analysis.

BACKGROUND AND OBJECTIVE: Colorectal cancer (CRC) is one of the most common cancers in Europe. Recently, new data from the USA and Europe revealed an increase in the incidence of CRC in individuals aged <55 years and a reduction in those aged >65 years. Mortality rate was stable in patients aged <55 years and decreased after the age of 55 years. Based on the USA data, the American Cancer Society (ACS) published a qualified recommendation advocating the start of CRC screening at the age of 45 years. We aimed to evaluate if the changes in the CRC incidence/mortality observed in the USA and the rest of Europe also occur in Portugal, and then perform a cost-utility analysis of CRC screening that starts at 45 years of age. METHODS: We evaluated the incidence of CRC by age group using data from the National Cancer Registry, and the mortality rate according to the National Statistics Institute in the periods 1993-2010 and 2003-2016. A cost-utility analysis was performed with a decision tree from a societal perspective comparing biennial fecal immunochemical test (FIT) or a single colonoscopy screening versus nonscreening at the age of 45 years in Portugal. RESULTS: In Portugal, in 1993-2010, there was an increase in CRC incidence of 17% (from 25 to 30/100,000), 35% (from 39 to 54/100,000), and 71% (from 52 to 97/100,000) in patients aged 45-49 years, 50-54 years, and 55-59 years, respectively. The mortality rate of patients aged 45-54 years remained stable between 2003 and 2016 (12/100,000) as a counterpoint to a moderate decrease in those aged 55-64 years (from 38 to 35/100,000) and a sharp reduction in those aged 65-75 years (from 93 to 75/100,000). Screening for CRC at the age of 45 years has no cost utility with the current incidence. FIT screening provided an ICUR of EUR 84,304/quality-adjusted life years (QALY) while colonoscopy provided an ICUR of EUR 3,112,244/QALY. On one-way sensitivity analysis, FIT screening would only have cost utility at the present cost of colonoscopy under sedation (EUR 150) and acceptance rates if the incidence rate rises above 47.5/100,000; colonoscopy at this age would have no cost utility despite changes in costs and/or incidence rates. CONCLUSION: In Portugal, the incidence of CRC in patients aged 45-55 years has been increasing with a stable mortality rate, in contrast to the decrease in mortality in the age groups covered by the current CRC screening program. However, at present, CRC screening in Portugal at the age of 45 years has no cost utility and will only have this if the incidence rate rises above 47.5/100,000 (vs. the actual incidence of 30/100,000).

INTRODUÇÃO E OBJETIVOS: O cancro colorretal (CCR) é uma das neoplasias mais comuns na Europa. Recentemente, temos observado um aumento da incidencia de cancro colorretal (CCR) em individuos <50 anos (não abrangidos pelos programas de rastreio), tanto na europa como nos Estados Unidos da América (EUA). Simultaneamente, a taxa de mortalidade (TM) permaneceu estável em doentes <55 anos e diminuiu >55 anos. Baseado nestes dados, a American Cancer Society (ACS) publicou uma recomendação qualificada advogando o inicio do rastreio aos 45 anos. Avaliar se as alterações na incidência/mortalidade de CCR observadas nos EUA/Europa também ocorrem em Portugal e realizar uma análise de custo-utilidade do início do rastreio de CCR aos 45 anos. MÉTODOS: Avaliamos a incidencia de CCR por faixa etária usando dados do Registro Oncológico Nacional (1993­2010) e TM de acordo com o Instituto Nacional de Estatística (2003­2016). A análise de custo-utilidade foi realizada com uma árvore de decisão sob uma perspetiva social, comparando o teste imunoquímico fecal bienal (FIT) com a realização de uma colonoscopia total aos 45 anos. RESULTADOS: Em Portugal (1993­2010) observou-se um aumento na incidencia de CRC de 17% (25/100.000 vs. 30/100.000), 35% (39/100.000 vs. 54/100.000) e 71% (52/100.000 vs. 97/100.000) em doentes com 45­49 anos, 50­54 anos e 55­59 anos, respetivamente. A TM de indivíduos com 45­54 anos permaneceu estável (12/100.000) ao contrário da diminuição moderada em indivíduos com 55­64 (38/100.000 vs. 35/100.000) e uma acentuada redudo em 65­75 (93/100.000 vs. 75/100.000). O rastreio de CCR aos 45 anos não teve custo-utilidade na presente incidencia (FIT/colonoscopia total). O rastreio com FIT forneceu um RCEI de € 84.304/QALY, enquanto a colonoscopia forneceu um RCEI de € 3.112.244/OALY. Em análise de sensibilidade unilateral, o rastreio com FIT apresentaria custo-utilidade com o custo atual da colonoscopia sob sedação (€ 150) e taxas de aceitado apenas se a incidencia subir acima de 47,5/100.000; o rastreio com colonoscopia nesta idade nunca teria custo-utilidade, apesar das mudanças nos custos e/ou taxas de incidencia. CONCLUSÃO: Em Portugal, a incidencia de CCR em doentes com idades entre 45­55 anos tem aumentado (TM estável). Este cenário é semelhante ao descrito nos EUA/restante europa. No entanto, o inicio do rastreio do CCR aos 45 anos em Portugal apenas terá custo-utilidade se incidencia for >47.5/100.000 (vs. 30/100.000).

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.

Use of the Boston Bowel Preparation Scale in the real life setting: what affects it?

Adequacy of bowel cleansing is a quality measure for colonoscopy, affecting both its safety and diagnostic accuracy. Among several bowel preparation quality scales referred to in literature, the Boston Bowel Preparation Scale (BBPS) is regarded as one of the most valid and reliable. However, BBPS is conditioned by a partially subjective appraisal. We report the results of a retrospective study that evaluated the quality of bowel preparation using BBPS and the factors associated with cleansing in routine clinical practice, in a series of consecutive examinations performed in a tertiary care hospital.

A second endoscopic ultrasound with fine-needle aspiration for cytology identifies high-risk pancreatic cysts overlooked by current guidelines.

BACKGROUND: Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended for diagnosis of pancreatic cystic lesions (PCLs). Its role in surveillance is unclear. Our goal was to determine if a second EUS-FNA changes diagnosis or management of PCLs. METHODS: A retrospective analysis of an EUS database, searching for EUS-FNAs in PCLs from 2007 to 2017 was performed. Demographics, cyst characteristics, and FNA results were compared in patients under surveillance, performing a single or two consecutive EUS-FNAs. RESULTS: Of 203 PCLs referred for EUS-FNA, surveillance was decided in 128 (63%). Data of 105 (82%) patients with a single EUS-FNA were compared with 23 (18%) with two EUS-FNAs during surveillance. Patients were younger in this latter group (P = .055), whereas CEA levels were marginally higher (P = .078) and a mass/nodule were more frequent (P = .006). The mean time between EUS-FNAs was 38 months (4.7-118.8) for 18 patients maintaining surveillance vs 18 months (2.9-56.9) in the four referred for surgery (P = NS) after two EUS-FNAs (two NETs, one IPMN-HGD, and one MCN-LG). A high correlation in CEA level between consecutive EUS-FNAs (r2 = 0.945, P < .01) was present, with a change of category observed (cut-off level = 192 ng/mL) in two patients only. Of four patients with a second EUS-FNA with conclusive cytology, two had NETs confirmed on resection. CONCLUSIONS: Repeating EUS-FNA in surveillance of PCLs with clinical suspicion of malignancy increased neoplasm diagnoses, changing decision toward surgery in almost 20% of patients while excluding IPMNs with mucin nodules from unnecessary resections. A second EUS-FNA for cytology appears justified in some PCLs, particularly for diagnosing NETs.

Methylation changes at the GNAS imprinted locus in pancreatic cystic neoplasms are important for the diagnosis of malignant cysts.

BACKGROUND: Guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations are characteristic of intraductal papillary mucinous neoplasms (IPMNs). Pancreatic ductal adenocarcinomas (PDACs) harboring GNAS mutations originate in IPMNs. GNAS is a complex imprinted locus that produces five transcripts regulated by differential methylated regions, NESP55, GNASAS, GNASXL, GNAS1A, and GNAS. AIM: To evaluate if methylation changes in the differential methylated regions of GNAS locus contributed to malignant progression of pancreatic cysts. METHODS: GNAS locus methylation was analyzed in archival pancreatic cyst fluid (PCF) obtained by endoscopic ultrasound with fine-needle aspiration by methylation specific-multiplex ligation dependent probe amplification. Results were normalized and analyzed using Coffalyser.Net software. RESULTS: Fifty-two PCF samples obtained by endoscopic ultrasound with fine-needle aspiration and previously characterized for KRAS and GNAS mutations were studied. The final diagnoses were surgical (11) and clinicopathological (41), including 30 benign cysts, 14 pre-malignant cyst, and eight malignant cysts. Methylation changes at NESP55, GNASAS, GNAS1A, and especially GNASXL were more frequent in malignant cysts, and NESP55 and GNASAS were useful for diagnosis. A combined variable defined as "GNAS locus methylation changes" was significantly associated with malignancy (6/8 malignant cysts and only 2/20 benign cysts) and improved classification. Hypermethylation in both maternally (NESP55) and paternally (GNASXL) derived promoters was found in 3/3 PDACs. CONCLUSION: This is the first study to identify methylation changes in the GNAS locus, improving the diagnosis of malignant pancreatic cysts and suggesting a role in progression to PDAC.

Pediatric Colorectal Cancer: A Heterogenous Entity.

INTRODUCTION: Colorectal cancer (CRC) is extremely rare in pediatric age. A poor outcome has been reported. AIMS: We aimed to characterize a group of pediatric CRC patients. MATERIALS AND METHODS: All patients with CRC below 18 years old registered in our Familial Cancer Risk Clinic (2002-2016) were included. Clinical and histologic features were evaluated. Germline mutations, microsatellite instability, and DNA mismatch repair proteins expression were analyzed. RESULTS: Five patients were included (3 males; mean age at diagnosis: 14.2 years (range, 9 to 17 y) and 4/5 had family history of cancer in second-degree relatives. With a maximum follow-up of 5.6 years, 2/5 patients died after 10 and 24 months, and 1 recurred after 15 months. All tumors were ≥pT3N2 and 3/5 presented signet ring cells/mucinous histology, corresponding to cases with stronger family history of cancer. Nevertheless, all CRCs analyzed (n=4) were microsatellite stable and/or expressed all mismatch repair proteins. Loss of heterozygosity for the 3 Bethesda dinucleotide markers was detected in 1/3 informative CRCs. A likely pathogenic germline MSH2 mutation was identified in only 1 patient. CONCLUSIONS: Pediatric CRC presented advanced disease and poor prognosis. These tumors had distinct histologic and molecular presentations, resembling features from different carcinogenic pathways, thus suggesting a heterogenous nature.

Real-Time Optical Diagnosis of Colorectal Polyps in the Routine Clinical Practice Using the NICE and WASP Classifications in a Nonacademic Setting.

BACKGROUND: Narrow-band imaging (NBI) allows "in vivo" classification of colorectal polyps. OBJECTIVES: We evaluated the optical diagnosis by nonexpert community-based endoscopists in routine clinical practice, the impact of training, and whether the endoscopists could achieve the threshold for the "do not resect" policy. METHODS: This was an observational study performed in two periods (P1 and P2). Endoscopists had no prior experience in NBI in P1 and applied the technique on a daily basis for 1 year before participation in P2. Lesions were classified by applying the NBI International Colorectal Endoscopic (NICE) and Workgroup serrAted polypS and Polyposis (WASP) classifications, simultaneously. RESULTS: A total of 290 polyps were analyzed. The overall accuracy of optical diagnosis was 0.75 (95% CI 0.68-0.81) in P1, with an increase to 0.82 (95% CI 0.73-0.89) in P2 (p = 0.260). The accuracy of the NICE/WASP classifications to differentiate adenomatous from nonadenomatous histology was 0.78 (95% CI 0.72-0.84) in P1 and 0.86 (95% CI 0.77-0.92) in P2 (p = 0.164); assignments made with a high confidence level achieved statistical significance (13% improvement, 95% CI 3-22%; p = 0.022). The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 81% (95% CI 64-93%) and 80% (95% CI 59-93%) in P1 and P2, respectively. CONCLUSIONS: Nonexpert endoscopists achieved moderate accuracy for real-time optical diagnosis of colorectal lesions with the NICE/WASP classifications. The overall performance of the endoscopists improved after sustained use of optical diagnosis, but did not achieve the standards for the implementation of the "do not resect" strategy.

INTRODUÇÃO: O narrow-band imaging (NBI) permite a classificação "in-vivo" dos pólipos colo-rectais. OBJECTIVOS: Avaliámos o diagnóstico óptico na prática clínica diária em endoscopistas da comunidade, sem experiência prévia em NBI, o impacto do treino e se estes conseguiam atingir o limiar da estratégia de "não ressecar". MÉTODOS: Estudo observacional, realizado em dois períodos (P1 e P2). Os endoscopistas não apresentavam experiência prévia em NBI em P1 e aplicaram a técnica diariamente durante um ano antes da participação em P2. As lesões foram classificadas aplicando as classificações NBI International Colorectal Endoscopic (NICE) e Workgroup serrAted polypS and Polyposis (WASP), simultaneamente. RESULTADOS: Foram analisados 290 pólipos. A acuidade global do diagnóstico óptico foi de 0.75 (IC 95%, 0.68-0.81) em P1, aumentando para 0.82 (IC 95%, 0.73-0.89) em P2 (p = 0.260). A acuidade das classificações de NICE/WASP na diferenciação de histologia adenomatosa de não-adenomatosa foi de 0.78 (IC 95%, 0.72-0.84) em P1, e 0.86 (IC 95%, 0.77-0.92) em P2 (p = 0.164); as predições realizadas com alto grau de confiança alcançaram significado estatístico (melhoria de 13%, IC 95%, 3-22%; p = 0.022). O valor preditivo negativo para histologia adenomatosa dos pólipos diminutos recto-sigmóides foi de 81% (IC 95%, 64-93%) e 80% (IC 95%, 59-93%), em P1 e P2, respetivamente. CONCLUSÕES: Endoscopistas sem experiência em NBI alcançaram acuidade moderada no diagnóstico óptico em tempo real de lesões colo-rectais, utilizando as classificações de NICE/WASP. O desempenho global melhorou após a utilização contínua do diagnóstico óptico, mas não alcançou o limiar definido para a implementação da estratégia de "não ressecar".

Endoscopic Full-Thickness Resection of Colorectal Lesions with the New FTRD System: Single-Center Experience.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is an emerging technique for the treatment of various conditions for which classic endoscopic resection techniques have failed or were considered to be at high risk for perforation. The full-thickness resection device (FTRD) is an over-the-scope system which allows a single-step EFTR. The aim of our study is to describe our experience in EFTR of colorectal lesions using the FTRD. METHODS: Nine patients (10 colorectal lesions) were proposed for EFTR. Safety, R0 resection and endoscopic treatment success were evaluated. RESULTS: Reasons for referral included nonlifting adenomas (n = 4), nonlifting adenoma recurrence (n = 5), and submucosal lesion (n = 1). EFTR was technically successful in all patients. The mean duration of the procedure was 55 min. R0 resection was obtained in all patients. No major complications were detected. All lesions were successfully treated by the endoscopic technique and no patient was referred for surgery. In patients with available follow-up (n = 6), no recurrence was detected. CONCLUSIONS: EFTR is a feasible, reasonable time-consuming, safe, and promising endoscopic resection technique. KEY MESSAGES: FTRD is an additional tool for difficult-to-treat colorectal lesions.

INTRODUÇÃO E OBJETIVOS: A ressecção endoscópica transmural (RET) é uma técnica promissora para o tratamento de várias lesões não passíveis de ressecção endoscópicapelas técnicas convencionais ou naquelas em que estes procedimentos apresentam elevado risco de complicações.O "full-thickness resection device" (FTRD) é um sistema pré-montado, que se acopla ao colonoscópio e que permite efetuar RET com um procedimento único. Pretende-se descrever a experiência do nosso centro na realização de RET com o FTRD. MÉTODOS: Nove doentes (10 lesões cólicas) foram propostos para RET. Foram avaliadas a segurança, ressecção R0 e taxa de sucesso do procedimento endoscópico. RESULTADOS: As indicações para o procedimento incluíram adenomas (n = 4), recidivas de adenomas (n = 5) sem elevação após injeção submucosa e lesão submucosa (n = 1). A RET foi tecnicamente bemsucedida em todos os doentes. A duração média dos procedimentos foi de 55 minutos. Ressecções R0 em todos os doentes. Não se registaram complicações major. Todas as lesões foram eficazmente tratadas com a ressecção endoscópica e nenhum doente foi proposto para cirurgia. Nos doentes já submetidos a exames de vigilância (n = 6) não foram detetadas recorrências. CONCLUSÕES: A RET é uma técnica exequível e segura para a terapêutica de lesões coloretais. MENSAGENS CHAVE: A RET parece ser uma promissora ferramenta adicional para manejo de lesões colo-rectais difíceis de tratar.

KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound-Fine-Needle Aspiration in Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis.

To evaluate the diagnostic accuracy of KRAS mutation in pancreatic cystic fluid and compare it with carcinoembryonic antigen and cytology, we identified studies with cyst fluid obtained by endoscopic ultrasound prior to surgery. We classified cysts as malignant, premalignant, and benign. A random-effects model was used for quantitative meta-analysis. Pooled sensitivities, specificities, and summary receiver operating characteristic curve analysis were conducted. We analyzed 16 studies, with 3429 patients, including 731 referred for surgery. Carcinoembryonic antigen was better for clinically significant cysts (premalignant and malignant) with sensitivity = 0.58 (95% confidence interval [CI], 0.53-0.65), specificity = 0.9 (95% CI, 0.76-0.97), and area under the curve (AUC) = 0.69. Cytology performed better in malignant cysts, with sensitivity = 0.37 (95% CI, 0.27-0.48), specificity = 0.96 (95% CI, 0.93-0.98), and AUC = 0.78. Isolated, KRAS mutation failed the diagnosis of malignant and significant cysts, with sensitivities = 0.43 (95% CI, 0.34-0.43) and 0.46 (95% CI, 0.42-0.51), specificities = 0.62 (95% CI, 0.56-0.68) and 0.97 (95% CI, 0.92-0.99), and AUCs = 0.56 and 0.53, respectively. Carcinoembryonic antigen and cytology are more accurate than KRAS. Additional studies are lacking to recommend KRAS as a single diagnostic test.

Evaluation of fatigue in inflammatory bowel disease - a useful tool in daily practice.

Background: Fatigue is a common symptom reported in inflammatory bowel disease (IBD) patients. It can be severe and modify the self-perception of disease. Objective: To evaluate the contribution of clinical and demographic factors to the level of fatigue in IBD patients. Methods: Patients consecutively observed in an outpatient IBD clinic during a 9-month period were studied. Demographic and clinical data were collected. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A FACIT-F score <30 was considered as severe fatigue. Results: One hundred and five patients were evaluated. Of them, 57.1% had Crohn´s Disease (CD) and 42.9% had Ulcerative Colitis. Also 85.0% and 77.8% were in clinical remission, respectively. The mean FACIT-F score was 39.63 ± 9.67. Severe fatigue was observed in 17.1% of patients. Female gender and active CD were significantly associated with a severe level of fatigue (p = .05 and p = .04). There was no significant correlation between the level of fatigue (severe vs. non-severe) and type of IBD, hemoglobin, C-reactive protein, ferritin levels or previous surgeries. Patients under biological therapy had a significantly higher level of fatigue and a higher rate of previous hospitalizations (p = .02). Conclusions: Fatigue level is a simple and useful tool to evaluate the disease's impact in patients' life, and it should, therefore, be included in clinical practice. Biological therapy was associated to higher levels of fatigue. Future studies should evaluate the impact of therapy on the level of fatigue.

Cost-utility analysis of colonoscopy or faecal immunochemical test for population-based organised colorectal cancer screening.

Background: Organised programmes for colorectal cancer screening demand a high burden of medical and economic resources. The preferred methods are the faecal immunochemical test and primary colonoscopy. Objective: The purpose of this study was to perform an economic analysis and comparison between these tests in Europe. Methods: We used a Markov cost-utility analysis from a societal perspective comparing biennial faecal immunochemical test or colonoscopy every 10 years screening versus non-screening in Portugal. The population was screened, aged from 50-74 years, and efficacy was evaluated in quality-adjusted life years. For the base-case scenario, the faecal immunochemical test cost was €3 with 50% acceptance and colonoscopy cost was €397 with 38% acceptance. The threshold was set at €39,760/quality-adjusted life years and the primary outcome was the incremental cost-effectiveness ratio. Results: Screening by biennial faecal immunochemical test and primary colonoscopy every 10 years resulted in incremental utilities of 0.00151 quality-adjusted life years and 0.00185 quality-adjusted life years at additional costs of €4 and €191, respectively. The faecal immunochemical test was the most cost-effective option providing an incremental cost-effectiveness ratio of €2694/quality-adjusted life years versus €103,633/quality-adjusted life years for colonoscopy. Colonoscopy capacity would have to increase 1.3% for a faecal immunochemical test programme or 31% for colonoscopy. Conclusion: Biennial faecal immunochemical test screening is better than colonoscopy as it is cost-effective, allows more individuals to get screened, and provides a more rational use of the endoscopic capacity available.

Efficacy of Long-Term Oral Vitamin B12 Supplementation after Total Gastrectomy: Results from a Prospective Study.

BACKGROUND/OBJECTIVES: Vitamin B12 (VB12) deficiency is a common complication after total gastrectomy which may be associated with megaloblastic anemia and potentially irreversible neurologic symptoms. Intramuscular supplementation of VB12 has been considered the standard treatment, although it is associated with high costs and patient discomfort. PATIENTS/METHODS: We performed a prospective uncontrolled study (ACTRN12614000107628) in order to evaluate the clinical and laboratory efficacy of long-term oral VB12 supplementation in patients submitted to total gastrectomy. All patients received daily oral VB12 (1 mg/day) and were evaluated every 3 months (clinical and laboratory evaluation: hemoglobin, VB12, total iron, ferritin, and folate). RESULTS: A total of 26 patients were included with a mean age of 64 years (29-79). Patients were included with a mean period of 65 months (3-309) after total gastrectomy. At inclusion time, 17/26 patients were under intramuscular VB12, and 9 had not started supplementation yet. There were normal serum VB12 levels in 25/26 patients (mean VB12 serum levels: 657 pg/mL). The mean follow-up period was 20 (8.5-28) months. During follow-up, all patients had normal VB12 levels and there was no need for intramuscular supplementation. The patient with low VB12 levels had an increase to adequate levels, which remained stable. There were no differences with statistical significance among VB12 levels at 6 (867 pg/mL), 12 (1,008 pg/mL), 18 (1,018 pg/mL), and 24 (1,061 pg/mL) months. Iron and folate supplementation was necessary in 21 and 7 patients, respectively. CONCLUSIONS: Oral VB12 supplementation is effective and safe in patients who underwent total gastrectomy and should be considered the preferential form of supplementation.

INTRODUÇÃO: O défice de vitamina B12 (vitB12) ocorre de forma quase universal e precocemente após gastrectomia total (GT), podendo associar-se a anemia megaloblástica e alterações neurológicas potencialmente irreversíveis. A administração intramuscular de vitB12 é considerada a forma de suplementação adequada, sendo, contudo, desconfortável, dispendiosa e, atualmente, de acesso difícil. MÉTODOS/OBJETIVO: Estudo prospetivo, não controlado (ACTRN12614000107628), cujo objetivo principal foi avaliar a eficácia clínica e laboratorial a longo prazo da suplementação oral com vitB12 em doentes com GT. O objetivo secundário foi avaliar outros défices nutricionais (ferro e folatos). Os doentes foram medicados com vitB12 oral (1mg/dia) e sujeitos a avaliação clínica e laboratorial trimestral (hemoglobina, vitB12, ferro, ferritina e ácido fólico). SPSS 23 (Wilcoxon test). RESULTADOS: Incluídos 26 doentes (M-18; F-8), idade média 64 anos (29­79), com diagnósticos de adenocarcinoma (n = 25) e linfoma MALT (n = 1). Os doentes foram incluídos em média 65 meses (3­309) após GT. À data de inclusão, 17/25 doentes encontravam-se medicados com vitB12 intramuscular e 9 ainda não tinham iniciado suplementação, verificando-se níveis séricos adequados de vitB12 em 25/26 doentes (1/26 com níveis de vitB12 baixos por incumprimento da terap'utica intramuscular), sendo o valor médio de 657 pg/mL (136­1,642). Os doentes foram avaliados durante uma mediana de 23 meses (IQR 8,8). No follow-up todos os doentes apresentaram níveis normais de vitB12, não sendo necessária terap'utica intramuscular. O doente com vitB12 baixa registou um incremento para níveis adequados, que se mantiveram estáveis. Não houve diferenças com significado estatístico nos níveis de vitB12 aos 6 (867 pg/mL), 12 (1,008 pg/mL) e 24 (1,061 pg/mL) meses, embora com aumento progressivo dos mesmos. A suplementação com ferro e folatos foi necessária em 21 e 7 doentes, respetivamente. CONCLUSÃO: A suplementação oral de vitB12 é eficaz e segura em doentes com GT, pelo que esta deve ser considerada a forma preferencial de administração neste grupo de doentes.

Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis.

Centrosome abnormalities are a typical hallmark of human cancers. However, the origin and dynamics of such abnormalities in human cancer are not known. In this study, we examined centrosomes in Barrett's esophagus tumorigenesis, a well-characterized multistep pathway of progression, from the premalignant condition to the metastatic disease. This human cancer model allows the study of sequential steps of progression within the same patient and has representative cell lines from all stages of disease. Remarkably, centrosome amplification was detected as early as the premalignant condition and was significantly expanded in dysplasia. It was then present throughout malignant transformation both in adenocarcinoma and metastasis. The early expansion of centrosome amplification correlated with and was dependent on loss of function of the tumor suppressor p53 both through loss of wild-type expression and hotspot mutations. Our work shows that centrosome amplification in human tumorigenesis can occur before transformation, being repressed by p53. These findings suggest centrosome amplification in humans can contribute to tumor initiation and progression.