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.

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.

CLIF-C ACLF score is a better mortality predictor than MELD, MELD-Na and CTP in patients with Acute on chronic liver failure admitted to the ward.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a frequent syndrome associated with high mortality. The aims of the present study are: a) comparing the Chronic Liver Failure Consortium (CLIF-C) ACLF Model for End-Stage Liver Disease (MELD), MELD Sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores for prediction of short/medium term mortality; b) identifying ACLF prevalence in patients admitted to the ward; and c) comparing mortality between non-ACLF/ACLF. METHODS: Retrospective cohort study of 177 patients admitted to the Gastroenterology ward for acute decompensation of cirrhosis. RESULTS: We included 132 males. Alcohol was the cirrhosis cause/co-factor in 79.7% of cases. Infection was present in 40.7%. At admission, 19.8% of patients presented ACLF and 7.9% developed it during hospitalization (overall prevalence was 27.7%). ACLF grade 1 was diagnosed in 55.1% of the ACLF patients; grade 2, in 42.8%, and grade 3, in 2.0%. Infection (p < 0.001) and hepatic encephalopathy (p = 0.004) were more prevalent and C-reactive protein and leukocyte counts were higher in ACLF patients. ACLF 28 and 90-day mortality was 45.8% and 60.4%, respectively. The CLIF-C ACLF score was significantly superior to CTP, MELD, MELD-Na in predicting 28-day (AUROC 0.799 ± 0.078, 95% CI 0.637-0.891) and 90-day mortality (AUROC 0.828 ± 0.063, 95% CI 0.705-0.952). CONCLUSION: ACLF is highly prevalent in the ward. The new CLIF scores identify high mortality cirrhotic patients admitted to the ward and are better than their predecessors to predict ACLF patients' short/medium term mortality.

Gastric outlet obstruction: An unusual adverse event of percutaneous endoscopic gastrostomy.

Dear Editor, A 75-year-old woman living in a nursing home presented with a 24-hour history of abdominal cramping and vomiting. Medical history was remarkable for dementia and a percutaneous endoscopic gastrostomy (PEG) was performed 3 years earlier. The day before the admission the feeding tube was accidentally pulled out and a Foley catheter was placed in order to avoid stoma closure. On physical examination, there was extravasation of the gastric content through the stoma. The base of the "Y" of the Foley catheter was introduced in the gastric stoma and a pulling sensation was felt when it was mobilized. The remainder abdominal examination was unremarkable. On esophagogastroduodenoscopy the Foley catheter was identified passing the pylorus and pulling duodenal bulb towards the antrum (Figure 1). Advancing the scope through the duodenum, the Foley balloon impacted in the duodenal apex was identified. There was no mucosal injury so the balloon was deflated and the catheter removed. A 14 Fr. Bard PEG tube was latter placed to allow a reduction in the calibre of the stoma. Gastric outlet obstruction is an unusual adverse event of PEG tubes. In adults it is usually related to Foley catheters use as peristalsis can pull the balloon into the duodenum in the absence of an external bumper. A clinical picture of abdominal cramping, vomiting and resistance to the attempt of percutaneous reposition should raise the suspicion of gastrostomy tube migration through the pylorus. Foley catheters are easily available and some may use it to prevent gastrostomy closure after accidentally PEG tube extraction. We have performed more than 800 PEG and assisted several cases of gastric outlet obstruction and even stoma damage in this setting. This case emphasises the importance of receiving an early PEG tube with external bumper replacement to prevent this adverse event.

Critical Analysis of the Applicability of Small Bowel Capsule Endoscopy Performance Measures among 2 Portuguese Centers with Different Capsule Endoscopy Platforms.

Introduction: The European Society of Gastrointestinal Endoscopy (ESGE) identified the need to benchmark the quality of small bowel capsule endoscopy (SBCE) and produced a set of performance measures (PM). The aim of this study is to critically evaluate the accordance of the PM for SBCE in two Portuguese centers with different SBCE platforms. Methods: The authors conducted a cross-sectional analysis of consecutive SBCE performed in an 18-month period in 2 Portuguese centers that used two different SBCE platforms Mirocam® (IntroMedic, Seoul, South Korea) and PillCam® (Medtronic, Yokneam, Israel). A total of 10 PM (6 key, 4 minor) were evaluated and compared between the 2 centers. Results: A total of 493 SBCE were included. The minimum standard established by ESGE was reached in 3/6 key PM (complete visualization, lesion detection rate, and capsule retention rate), and none of the 4 minor PM. PM compliance significantly differed between the 2 centers: complete small bowel visualization 95.9 and 90% (p = 0.01), diagnostic yield 50.6 and 63% (p = 0.005), adequate small bowel cleansing level according to Brotz scale 69.54 and 84.6% (p ≤ 0.001), patients with high risk of capsule retention offered a patency capsule 4.2 and 73% (p ≤ 0.001), respectively. Conclusion: This study highlights and critically discusses technical and organizational issues that should be considered in defining more realistic PM thresholds, aiming to improve SBCE quality.

Introdução: A Sociedade Europeia de Endoscopia Digestiva (ESGE) identificou a necessidade de avaliar a qualidade da enteroscopia por videocápsula (EVC) e produziu um conjunto de medidas de desempenho (MD). O objetivo deste estudo é avaliar criticamente a concordância das medidas de desempenho de EVC em dois centros portugueses com diferentes plataformas de EVC. Métodos: Análise transversal de EVC consecutivas realizadas em 2 centros portugueses, com diferentes plataformas de EVC Mirocam® (IntroMedic, Seul, Coreia) e PillCam® (Medtronic, Yokneam, Israel), respetivamente. Um total de 10 medidas de desempenho (6 principais, 4 minor) foram avaliadas e comparadas entre os 2 centros. Resultados: Foram incluídas 493 EVC. O standard mínimo estabelecido pela ESGE foi alcançado em 3/6 MD principais (visualização completa, taxa de detecção de lesões e taxa de cápsula retida), e nenhum nas quatro MD minor. O cumprimento das MD diferiu significativamente entre os 2 centros: visualização completa do intestino delgado 95,9 e 90% (p = 0,01), taxa de deteção de lesões 50,6% e 63% (p = 0,005), adequada preparação do intestino delgado de acordo com a escala de Brotz 69,54 e 84,6% (p ≤ 0,001), doentes com alto risco de retenção da cápsula a quem foi oferecida cápsula de patência 4,2 e 73% (p ≤ 0,001), respectivamente. Introdução: Este estudo destaca e discute criticamente questões técnicas e organizacionais que devem ser consideradas na definição de limiares de MD mais realistas, com o objetivo de melhorar a qualidade da EVC.

HSV-1 hepatitis in an immunocompetent patient - Act before you know.

Herpes simplex virus type 1 (HSV-1) hepatitis is an unusual complication of HSV infection, which frequently results in acute liver failure. Even though the most affected individuals are immunosuppressed patients, around 25 % patients who present with HSV hepatitis are immunocompetent. We report a case of an anicteric febrile hepatitis in a 46-year-old immunocompetent women in which the early suspicion of HSV hepatitis allowed empirical treatment and later diagnosis confirmation by liver biopsy.

Risk stratification of colorectal polyps for predicting residual or recurring adenoma using the Size/Morphology/Site/Access score.

BACKGROUND AND AIMS: Endoscopic mucosal resection is an effective and safe procedure to manage large non-pedunculated colonic polyps for which residual/recurrent adenoma is the main drawback. Size/Morphology/Site/Access score determines polypectomy difficulty. We aimed to describe residual/recurrent adenoma rate according to Size/Morphology/Site/Access and to select the ize/Morphology/Site/Access cut-off to predict low residual/recurrent adenoma. METHODS: This was a retrospective cohort study of endoscopic mucosal resection for large non-pedunculated colonic polyps performed in a tertiary centre. RESULTS: Three hundred and sixteen procedures were included. The mean size of lesions was 34.5 ± 17.1 mm, 59.5% were sessile, 60.4% were in the right colon and in 17.7% (n = 56) the access was difficult. Of the lesions, 83.6% were Size/Morphology/Site/Access 3-4. Residual/recurrent adenoma at first and second follow-up was significantly lower in Size/Morphology/Site/Access 2 (1.9% and 0.0%, respectively) when compared to Size/Morphology/Site/Access 3 (18.2%, p = 0.004 and 6.7%, p = 0.049) and Size/Morphology/Site/Access 4 (30.8%, p < 0.001 and 22.7%, p = 0.030). The negative predictive value of Size/Morphology/Site/Access 2 for residual/recurrent adenoma at second follow-up was 86.1%. On multivariate analyses, Size/Morphology/Site/Access 3-4 predicted residual/recurrent adenoma at first (odds ratio 11.96, 95% confidence interval 1.57-91.13) and second follow-up (odds ratio 2.47, 95% confidence interval 1.51-4.22) and had higher cumulative incidence of residual/recurrent adenoma compared to Size/Morphology/Site/Access 2 (p ≤ 0.003). CONCLUSION: Use of the Size/Morphology/Site/Access score allows cases to be identified with a low risk of residual/recurrent adenoma.

Mid upper arm circumference and Powell-Tuck and Hennessy's equation correlate with body mass index and can be used sequentially in gastrostomy fed patients.

BACKGROUND & AIMS: Body Mass Index (BMI) is a simple and widespread method to assess undernutrition. However its use may be limited in bedridden patients. AIMS: 1) compare BMI, Mid Upper Arm Circumference (MUAC) and Powell-Tuck and Hennessy's regression equation for BMI (BMIPTH) in gastrostomy fed patients, 2) validate its correlation for sequential use and 3) select the best cut-off of MUAC and BMIPTH to predict risk of undernutrition. METHODS: Prospective study including adult patients who underwent endoscopic gastrostomy (PEG). BMI, MUAC and BMIPTH adjusted for sex and age were determined at the day of gastrostomy (0), first (1) and third (3) months of follow up. Correlations between BMI and MUAC and BMIPTH were calculated at all time-points using Spearman's test. MUAC's Area Under ROC (AUROC) to predict risk of undernutrition (BMI ≤ 18,5 kg/m2 in non-elderly (<65 years) and BMI ≤ 22,5 kg/m2 in elderly (≥65 years)) was calculated with DeLong method and Youden Index was used to select the best cut-off for this outcome. RESULTS: 405 PEG patients were included (69,9% males, median age 62,9 ± 15,3 years). Head and neck cancer and neurological disorders were the main indications for gastrostomy. BMI correlated moderately with BMIPTH0 (ρ = 0.646-0.694), MUAC0 (ρ = 0.669) and MUAC1 (ρ = 0.699). BMI correlated strongly with BMIPTH1 (ρ = 0.764-0.794), BMIPTH3 (ρ = 0.714-0.732) and MUAC3 (ρ = 0.725). MUAC and BMIPTH's accuracy was not significantly different to predict undernutrition neither in elderly (AUROC 0.835 ± 0.033 Vs. 0.836 ± 0.033 respectively, p = 0.319) nor in non-elderly patients (AUROC 0.857 ± 0.027 Vs. 0.888 ± 0.053 respectively, p = 0.256). MUAC <26 cm (positive predictive value (PPV) 83.5%) or BMIPTH <22 kg/m2 (PPV 83.5%) in elderly and MUAC <25 cm (PPV 90.7%) or BMIPTH <21 kg/m2 (PPV 91.7%) in non-elderly can accurately predict risk of undernutrition in PEG patients. CONCLUSIONS: MUAC and BMIPTH correlated with BMI not only at the day of PEG placement but also at the 1st and 3rd month of follow up and were equivalent to predict risk of undernutrition according to the new cut-offs defined for this population.

Idiopathic chylous ascites in a patient with HIV infection: response to total parenteral nutrition and octreotide therapy.

The authors describe a 47-year-old man infected with human immunodeficiency virus admitted for ascites and weight loss. Ascitic fluid analysis revealed chylous ascites (triglycerides 444 mg/dl) with negative microbiological tests. Neoplasia, cardiac disease and liver cirrhosis were excluded after an extensive diagnostic workout. Exploratory laparotomy with tissue sampling did not clarify ascites etiology. During hospital admission, patient status gradually deteriorated, severe malnutrition developed and ascites became refractory to diuretics. Total parenteral nutrition and octreotide therapy were started and maintained for 3 weeks with ascites resolution and no relapse after oral diet resumption. Chylous ascites is a rare entity with several causes that compromise intra-abdominal lymphatic drainage. This case illustrates the difficulty in establishing etiology in some patients and the effectiveness of total parenteral nutrition plus octreotide therapy in idiopathic chylous ascites in HIV-infected patients.

Pancreatoblastoma: an unusual diagnosis in an adult patient.

The authors describe a 31-year-old man admitted due to progressive weight loss, diarrhea and massive hepatomegaly. Laboratory data showed anemia (haemoglobin 11.7 g/dl), abnormal liver tests (total bilirubin 1.4 g/dl, aspartate aminotransferase 70 U/l, alanine aminotransferase 37 U/l and alkaline phosphatase 520 U/l). Abdominal ultrasound (US) displayed a large heterogeneous liver with a segment IV 25 mm nodule. Magnetic resonance revealed a 4 cm pancreatic tail mass and several liver nodules consistent with metastasis. The patient underwent an endoscopic ultrasound (EUS) with fine needle aspiration (FNA) from the pancreatic mass and liver metastasis with cytological evaluation consistent with a pancreatoblastoma, later confirmed through a percutaneous US-guided liver biopsy. During the inpatient period, liver function deteriorated and acute kidney injury developed. Severe progressive cachexia was observed. The patient was discharged on renal replacement therapy and palliative care. Death occurred 3 months after diagnosis. Pancreatoblastoma is an uncommon pancreatic malignant epithelial cancer of the pancreas, typically occurring in the paediatric population. Adult pancreatoblastoma is extremely rare, with about 40 cases reported in the literature and generally presenting a more aggressive biologic and clinical behaviour. Surgical resection is the treatment of choice, but most cases are detected in advanced stages. This case underlines the ability to establish a pancreatoblastoma cytology-based diagnosis with EUS-FNA, and confirms the associated poor outcome.

Modern role of clinical ultrasound in liver abscess and echinococcosis.

In the Western world, liver abscesses are predominantly of pyogenic origin and can present a wide range of ultrasonographic features, from a solid mass to a cystic cavity. Amoebic abscesses are endemic in tropical areas and typically round single lesions. Echinococcal cyst is diagnosed by ultrasound (US). Serology is particularly useful when pathognomonic US features are absent. Treatment is determined based on the WHO ultrasonographic classification, and puncture, aspiration, injection, re-aspiration (PAIR) is a US-guided therapeutic option. Hepatic alveolar echinococcosis presents on US as a pseudotumoral mass frequently with calcifications that may invade the biliary tree and portal and hepatic veins.

Adult Celiac Disease: The Importance of Extraintestinal Manifestations.

Celiac disease (CD) is a chronic immune-mediated enteropathy driven by gluten and affecting individuals of all ages. The diagnosis of CD in adulthood is emerging and patients often present with nonclassical extraintestinal manifestations. We report the case of a 53-year-old man presenting with neuromuscular symptoms, skin rash, inconspicuous chronic diarrhea, marked weight loss, and biochemical markers of malabsorption. A strong clinical suspicion led to the diagnosis of CD with clinical recovery after the initiation of a gluten-free diet. Clinical presentation with atypical symptoms in adult CD patients is the rule and not the exception. Most of the extraintestinal manifestations depend on background autoimmune phenomena and micronutrient malabsorption. A gluten-free diet re-establishes homeostasis and prevents long-term complications.

A Doença celíaca (DC) é uma enteropatia crónica imunomediada precipitada pela ingestão de glúten, afetando indivíduos de todas as faixas etárias. O diagnóstico de DC está a emergir, com os doentes a apresentarem-se frequentemente com manifestações extraintestinais não clássicas. Os autores descrevem o caso de um homem de 53 anos com sintomas neuromusculares, rash cutâneo, diarreia crónica não valorizada, marcada perda ponderal e evidência bioquímica e laboratorial de má absorção. O elevado nível de suspeição clínica conduziu ao diagnóstico de DC com recuperação clínica total após instituição de dieta sem glúten. A apresentação clínica da DC na idade adulta com sintomas atípicos é a regra e não a exceção. A maioria das manifestações extraintestinais está dependente de fenómenos de autoimunidade e má absorção de micronutrientes. A dieta sem glúten permite reestabelecer a homeostasia e prevenir complicações a longo prazo.

Catheter traction and gastric outlet obstruction: a repeated complication of using a Foley catheter for gastrostomy tube replacement.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a safe procedure and major morbidity is unusual. However, the number of PEG fed patients is increasing all over the world and complications may become more and more frequent. CASE REPORT: We describe a 73 years old woman with persistent vomit after replacement of the standard PEG tube with a Foley catheter. An upper GI endoscopy showed the catheter pulled into the duodenum causing gastric outlet obstruction. It was removed and replaced by a suitable standard PEG tube, allowing PEG feeding to be resumed. DISCUSSION: Previous reports pointed the risk of this complication, almost always associated with insertion of a Foley-type catheter. Replacement of PEG tubes should be performed by experienced teams using standard PEG tubes and the use of Foley-type catheters for this purpose should be banned from routine practice.

OUTCOME AND NUTRITIONAL ASSESSMENT OF CHRONIC LIVER DISEASE PATIENTS USING ANTHROPOMETRY AND SUBJECTIVE GLOBAL ASSESSMENT.

BACKGROUND:: Protein-calorie malnutrition is common in chronic liver disease (CLD) but adequate clinical tools for nutritional assessment are not defined. OBJECTIVE:: In CLD patients, it was aimed: 1. Characterize protein-calorie malnutrition; 2. Compare several clinical, anthropometric and functional tools; 3. Study the association malnutrition/CLD severity and malnutrition/outcome. METHODS:: Observational, prospective study. Consecutive CLD ambulatory/hospitalised patients were recruited from 01-03-2012 to 31-08-2012, studied according with age, gender, etiology, alcohol consumption and CLD severity defined by Child-Turcotte-Pugh. Nutritional assessment used subjective global assessment, anthropometry, namely body-mass index (BMI), triceps skinfold, mid upper arm circumference, mid arm muscular circumference and handgrip strength. Patients were followed during two years and survival data was recorded. RESULTS:: A total of 130 CLD patients (80 men), aged 22-89 years (mean 60 years) were included. Most suffered from alcoholic cirrhosis (45%). Hospitalised patients presented more severe disease ( P <0.001) and worst nutritional status defined by BMI ( P =0.002), mid upper arm circumference ( P <0.001), mid arm muscular circumference ( P <0.001), triceps skinfold ( P =0.07) and subjective global assessment ( P <0.001). A third presented deficient/low handgrip strength. Alcohol consumption ( P =0.03) and malnutrition detected by BMI ( P =0.03), mid upper arm circumference ( P =0.001), triceps skinfold ( P =0.06), mid arm muscular circumference ( P =0.02) and subjective global assessment ( P <0.001) were associated with CLD severity. From 25 patients deceased during follow-up, 17 patients were severely malnourished according with triceps skinfold. Malnutrition defined by triceps skinfold predicted mortality ( P <0.001). CONCLUSION:: Protein-calorie malnutrition is common in CLD patients and alcohol plays an important role. Triceps skinfold is the most efficient anthropometric parameter and is associated with mortality. Nutritional assessment should be considered mandatory in the routine care of CLD patients.