Development of a Model to Predict Liver Decompensation prior to Transarterial Chemoembolization Refractoriness in Patients with Intermediate-Stage Hepatocellular Carcinoma.

Introduction: Transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). For patients without an adequate response, current finding suggests that treatment with molecular target agents, approved for advanced stage, might present benefits. However, this requires a preserved liver function. This study aims to evaluate possible predictors of early deterioration of hepatic reserve, prior to TACE refractoriness, in a cohort of patients treated with TACE. Methods: Retrospective analysis of 99 patients with Child-Pugh class A and intermediate-stage HCC who underwent TACE as the first-line treatment. All patients were submitted to a biochemical and medical evaluation prior to initial TACE and every month afterward. Response to initial TACE was evaluated at 1 month. The time to Child-Pugh class deterioration before TACE refractoriness was assessed. Results: Ninety-nine patients were included. Objective response rate (ORR) to initial TACE was assessed as present in 59 (63.4%) and as absent in 34 (36.6%) patients. Liver decompensated before TACE refractoriness in 51 (51.5%) patients, and the median time to liver decompensation was 14 (IQR 8-20) months after first TACE. In multivariate analysis, beyond up-to-7 criteria (HR 2.4, p = 0.031), albumin <35 mg/dL (HR 3.5, p < 0.001) and absence of ORR (HR 2.4, p = 0.020) were associated with decreased overall survival free of liver decompensation. Moreover, beyond up-to-7 criteria, albumin <35 mg/dL and absence of ORR associated negatively with 6-month survival free of liver decompensation. Our model created using those variables was able to predict liver decompensation at 6 months with an AUROC of 0.701 (p = 0.02). Conclusions: The absence of ORR after initial TACE, beyond up-to-7 criteria and albumin <35 mg/dL, was a predictive factor for early liver decompensation before TACE refractoriness in our population. Such patients might benefit from treatment escalation to systemic therapy, in monotherapy or in combination with TACE.

Introdução: A quimioembolização transarterial (TACE) é o tratamento de primeira linha para doentes com carcinoma hepatocelular (HCC) em estadio intermédio. Em doentes sem resposta adequada, a evidência atual sugere que o tratamento com agentes de alvo molecular, aprovado para estágio avançado, pode apresentar benefícios. Porém, isso requer função hepática preservada. O objetivo deste estudo é avaliar possíveis preditores de deterioração precoce da reserva hepática, antes da refratariedade ao TACE, em uma coorte de doentes tratados com TACE. Métodos: Análise retrospectiva de noventa e nove doentes com Child-Pugh classe A e HCC em estadio intermédio que foram submetidos a TACE como tratamento de primeira linha. Todos os doentes foram submetidos a uma avaliação bioquímica e médica antes do TACE inicial e a cada mês após. A resposta ao TACE inicial foi avaliada em 1 mês. O tempo para a deterioração da classe Child-Pugh antes da refratariedade a TACE foi avaliado. Resultados: Noventa e nove doentes foram incluídos. A resposta radiológica objetiva (ORR) ao TACE inicial foi avaliada como presente em 59 (63.4%) e ausente em 34 (36.6%) doentes. Descompensação hepática ocorreu, antes da refratariedade a TACE, em 51 (51.5%) doentes e o tempo médio para a descompensação hepática foi de 14 (IQR 8­20) meses, após o primeiro TACE. Na análise multivariada, além dos critérios up-to-7 (HR 2,4, p = 0.031), albumina <35 mg/dL (HR 3,5, p < 0.001) e ausência de ORR (HR 2,4, p = 0.020) foram associados a diminuição da sobrevida livre de descompensação hepática. Além disso, a sobrevida de 6 meses livre de descompensação hepática apresentou associação, além dos critérios up-to-7 , albumina <35 mg/dL e ausência de ORR. Foi criado um modelo com essas variáveis, capaz de prever a descompensação hepática com AUROC de 0,701 (p = 0.02). Conclusões: A ausência de ORR após TACE inicial, além dos critérios up-to-7 e albumina <35 mg/dL foram fatores preditivos para descompensação hepática antes da refratariedade a TACE na nossa população. Esses doentes podem beneficiar do escalonamento do tratamento para a terapia sistêmica, em monoterapia ou em combinação com TACE.

Endoscopic Ultrasound Through-The-Needle Biopsy of Pancreatic Cysts: Toward Procedure Standardization.

BACKGROUND AND AIMS: EUS-guided through-the-needle microforceps biopsy (EUS-TTNB) was introduced as a new diagnostic tool to establish pancreatic cyst histotype and help to better risk stratify the patients. The aim of this study was to describe the technical success, diagnostic yield, and adverse events of through-the-needle biopsy and discuss the technique variations, focusing on future procedure standardization. METHODS: We performed a prospective single-center study including patients with presumed mucinous cysts harboring worrisome features or indeterminate cyst type on imaging, submitted to EUS-TTNB using Moray® microforceps between March 2018 and September 2021. Specimens were processed as a cell-block. RESULTS: We included 40 patients. Technical success was 97.5%. The diagnostic yield was 72.5% for TTNB whereas for cyst fluid cytology/analysis it was 27.5%. Moreover, without TTNB 5 mucinous lesions would not have been diagnosed. TTNB had a sensitivity of 76% and a specificity of 91%, while FNA cytology had a sensitivity and specificity of 35% and 91%, respectively. Moreover for IPMN lesions, subtyping was possible in 63% of cases. TTNB resulted in change in clinical management in 20% of patients. We registered three adverse events: 2 self-limited intracystic bleeding and 1 patient with abdominal pain not associated with pancreatitis. CONCLUSION: TTNB proved superior to cyst fluid analysis and cytology for the definition of cyst histotype and mucinous cyst diagnosis with acceptable risk profile. Further studies should explore the best steps for procedure standardization.

Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities.

BACKGROUND: Individuals within specific risk groups for pancreatic ductal adenocarcinoma (PDAC) [mucinous cystic lesions (MCLs), hereditary risk (HR), and new-late onset diabetes mellitus (NLOD)] represent an opportunity for early cancer detection. Endoscopic ultrasound (EUS) is a premium image modality for PDAC screening and precursor lesion characterization. While no specific biomarker is currently clinically available for this purpose, glypican-1 (GPC1) is overexpressed in the circulating exosomes (crExos) of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases. AIM: To evaluate the capacity of GPC1+ crExos to identify individuals at higher risk within these specific groups, all characterized by EUS. METHODS: This cross-sectional study with a prospective unicentric cohort included 88 subjects: 40 patients with MCL, 20 individuals with HR, and 20 patients with NLOD. A control group (CG) was submitted to EUS for other reasons than pancreatic pathology, with normal pancreas and absence of hereditary risk factors (n = 8). The inclusion period was between October 2016 and January 2019, and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João, Porto, Portugal. All patients provided written informed consent. EUS and blood tests for quantification of GPC1+ crExos by flow cytometry and carbohydrate antigen 19-9 (CA 19-9) levels by ELISA were performed in all subjects. EUS-guided tissue acquisition was done whenever necessary. For statistical analysis, SPSS® 27.0 (IBM Corp., Armonk, NY, United States) version was used. All graphs were created using GraphPad Prism 7.00 (GraphPad Software, San Diego, CA, United States). RESULTS: Half of MCLs harbored worrisome features (WF) or high-risk stigmata (HRS). Pancreatic abnormalities were detected by EUS in 10.0% and 35.0% in HR and NLOD individuals, respectively, all considered non-malignant and "harmless." Median levels of GPC1+ crExos were statistically different: MCL [99.4%, interquartile range (IQR): 94.9%-99.8%], HR (82.0%, IQR: 28.9%-98.2%), NLOD (12.6%, IQR: 5.2%-63.4%), and CG (16.2%, IQR: 6.6%-20.1%) (P < 0.0001). Median levels of CA 19-9 were within the normal range in all groups (standard clinical cut-off of 37 U/mL). Within HR, individuals with a positive history of cancer had higher median levels of GPC1+ crExos (97.9%; IQR: 61.7%-99.5%), compared to those without (59.7%; IQR: 26.3%-96.4%), despite no statistical significance (P = 0.21). Pancreatic cysts with WF/HRS were statistically associated with higher median levels of GPC1+ crExos (99.6%; IQR: 97.6%-99.8%) compared to those without (96.5%; IQR: 81.3%-99.5%) (P = 0.011), presenting an area under the receiver operating characteristic curve value of 0.723 (sensitivity 75.0% and specificity 67.7%, using a cut-off of 98.5%; P = 0.012). CONCLUSION: GPC1+ crExos may act as biomarker to support the diagnosis and stratification of PDAC precursor lesions, and in signaling individuals with genetic predisposition in the absence of EUS abnormalities.

Solid Pseudopapillary Neoplasm of the Pancreas: Unfolding an Intriguing Condition.

Pancreatic cancer is one of the most lethal malignant neoplasms, with a 1-year survival rate after diagnosis of 24%, and a 5-year survival rate of only 9%. While this illustrates the behavior of its main histologic type - ductal adenocarcinoma, there are other histologic subtypes of pancreatic cancer that can harbor excellent prognosis. Solid pseudopapillary neoplasm, described as a rare low-grade malignant neoplasm by the World Health Organization, is the best example of that, having an overall 5-year survival rate of about 97%. Not only the prognosis, but everything about this entity is unique: its histogenesis, epidemiology, presentation, imaging characteristics, cytology features, immunohistochemical profile, and treatment. This explains the urge to improve our understanding about this entity and thus our ability to accurately recognize and manage it. Having this in mind, this article aims to summarize the most relevant topics regarding this entity.

O cancro do pâncreas é uma das neoplasias malignas mais letais, com uma taxa de sobrevida 1 ano após o diagnóstico de 24% e 5 anos após o diagnóstico de apenas 9%. Estes dados espelham, contudo, o comportamento do subtipo histológico mais prevalente − o adenocarcinoma ductal. Porém, nem todas as neoplasias malignas do pâncreas são adenocarcinomas e nem todas estão a associadas a um prognóstico tão reservado. A Neoplasia Pseudopapilar Sólida do Pâncreas é o exemplo disso: descrita pela Organização Mundial da Saúde como uma neoplasia maligna de baixo grau, é um tumor raro associado a um excelente prognóstico, com uma taxa de sobrevida aos 5 anos de 97%. Mais que uma neoplasia com um prognostico peculiarmente favorável, é uma neoplasia única em todas as suas componentes: histogénese, epidemiologia, apresentação clínica, características imagiológicas, citológicas e imunohistoquímicas e no tratamento. Estas particularidades devem estar presentes e consolidadas no raciocínio clínico de qualquer médico, para que estas neoplasias sejam devidamente reconhecidas e tratadas. Neste sentido, foi realizado este artigo de revisão que visa sumariar os mais relevantes tópicos relacionados com esta entidade clínica.

Primary Myelofibrosis in the Prefibrotic Stage Presenting as Portal, Splenic, and Superior Mesenteric Vein Thrombosis: A Case Report and Review of the Literature.

Introduction: Myeloproliferative neoplasms are the most common cause of splanchnic vein thrombosis in the absence of cirrhosis or nearby malignancy. Case Presentation: A 31-year-old male presented to the emergency department with epigastric pain associated with mild thrombocytosis and elevated levels of aminotransferases, lactate dehydrogenase, and C-reactive protein. Contrast-enhanced abdominal computed tomography revealed splanchnic venous thrombosis that involved the portal, splenic, and superior mesenteric veins, without signs of chronic liver disease. Anticoagulation with warfarin was immediately started. Diagnostic work-up was remarkable for the presence of the JAK2 V617T mutation and hypercellular bone marrow, with increased myeloid cells and atypical megakaryocytes, consistent with primary myelofibrosis in a prefibrotic stage. No other hypercoagulable conditions were identified. Discussion: We present a rare case of primary myelofibrosis in the prefibrotic stage presenting as portal-splenic-superior mesenteric vein thrombosis. This demonstrates that extensive splanchnic vein thrombosis may be the onset manifestation of myeloproliferative neoplasms, even in early stages and in the absence of concomitant hypercoagulable conditions. The presence of the JAK2 mutation is an important prothrombotic risk factor that can, per se, contribute to large venous thrombosis.

Introdução: As neoplasias mieloproliferativas constituem a causa mais comum de trombose venosa esplâncnica na ausência de cirrose hepatica ou neoplasia regional. Descrição do caso: Um homem de 31 anos apresentou-se no Serviço de Urgência com dor epigástrica associada a trombocitose ligeira e elevação das transamínases, desidrogenase láctica e proteína C-reactiva. Em tomografia computorizada abdominal com contraste, foi identificada trombose venosa esplâncnica envolvendo a veia porta, esplénica e mesentérica superior, sem sinais de doença hepática crónica. Foi de imediato iniciada anticoagulação com varfarina. Da investigação etiológica, destaca-se a presença da mutação JAK2 V617F e medula óssea hiper-celular com aumento das contagens de células mielóides e megacariócitos atípicos, consistente com mielofibrose primária em estadio pré-fibrótico. Não se identificaram distúrbios pro-trombóticos concomitantes. Discussão: Apresenta-se um raro caso de trombose da veia porta, esplénica e mesentérica superior, demonstrando que as neoplasias mieloproliferativas podem apresentar-se sob a forma de trombose venosa esplâncnica extensa, mesmo em estadios precoces e na ausência de distúrbios protrombóticos concomitantes. A presença da mutação JAK2 é um importante factor de risco pro-trombótico que pode por si só contribuir para a formação de tromboses venosas extensas.

Use of suction during endoscopic ultrasound-guided fine needle biopsy of solid pancreatic lesions with a Franseen-tip needle: a pilot comparative trial.

Background and study aims The utility of suction during endoscopic ultrasound (EUS) fine-needle biopsy (FNB) using Franseen-tip needle remains unclear and has not been evaluated in randomized trials. We designed a randomized crossover trial to compare the diagnostic yield during EUS-FNB using a 22G Franseen-tip needle, with and without standard suction. Patients and methods Consecutive patients undergoing EUS-guided sampling of solid pancreatic lesions were recruited. A minimum of two passes were performed for each case: one with 20-mL syringe suction (S+) and another without (S-). The order of passes was randomized and the pathologist blinded. The endpoints were the diagnostic yield and the impact of blood contamination in the diagnosis. Results Fifty consecutive patients were enrolled. The overall diagnostic accuracy was 84 %. A diagnosis of malignancy was obtained in 70 samples: 36 in the S+group and 34 in the S-group. A statistically significant difference was seen in the diagnostic accuracy (S+: 78 % vs. S-: 72 %, P  < 0.01) and blood contamination (S+: 68 %; S-: 44 %, P  < 0.01). The sensitivity, specificity, negative likelihood ratio and positive likelihood ratio for S+vs. S-samples were 76.6 % vs. 73.9 %, 100 % vs. 100 % and 0.23 vs. 0.26, NA vs NA, respectively. A negative impact of blood contamination in the overall diagnostic yield wasn't seen, even in samples where suction was used (OR 0.36, P  = 0.15) Conclusions We found a higher diagnostic yield with the use of suction. It was associated with a higher degree of sample blood contamination that did not affect the diagnostic performance.

Development of an Online App to Predict Post-Endoscopic Retrograde Cholangiopancreatography Adverse Events Using a Single-Center Retrospective Cohort.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). AIM: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. METHODS: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. RESULTS: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). CONCLUSION: Our app may allow an optimization of the patients' care, by helping in the process of decision-making, not only regarding patient or endoscopist's selection but also definition of an adequate and tailored surveillance plan after the procedure.

Effectiveness and safety of obeticholic acid in a Southern European multicentre cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid.

BACKGROUND: Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. AIM: To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. METHODS: Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). RESULTS: One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). CONCLUSIONS: This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability.

Predictive Factors and Clinical Impact of Deep Remission in Celiac Disease.

INTRODUCTION: The ultimate indicator of adherence to a gluten-free diet is the demonstration of mucosal healing. However, the need for histological reassessment is subject to controversy among "experts". The aim of this study was to evaluate celiac patients who underwent histological reevaluation after starting a gluten-free diet in order to identify those with histological remission and associated factors. METHODS: This retrospective study included patients who agreed to a histological reassessment after apparent clinical and serological remission and reported at least 12 months of diet adherence. In all cases, informed consent was signed for upper endoscopy. RESULTS: A total of 69 patients were included. In 67.9% of cases, the diagnosis was made in the context of "classic" symptomatology, 17% had "nonclassical" presentation, and 15.1% were in latent phase. 69.2% of the diagnoses were initially suspected by serology. Endoscopically, 11.8% of the patients did not present suggestive features macroscopically, and a histological grade of Marsh IIIa-c was observed in 75.5% of all cases. The histological findings were normalized in 37.7%, which was associated with the presence of lower Marsh score values at diagnosis (p = 0.014) and lower DEXA T-score values (p = 0.038). A histological improvement was observed in 55 patients (≥2 grades in 37 cases), which was related to the initial transferrin saturation (p = 0.027) and with higher Marsh scores at diagnosis (p = 0.007). CONCLUSION: Even under a gluten-free diet, celiac histology normalization is difficult to obtain and appears to be independent of most clinical and serological findings at diagnosis. Patients with less severe histological levels at diagnosis reach remission more easily, but only represent the -minority of the population.

INTRODUÇÃO: O indicador final da adesão a uma dieta isenta de glúten é a demonstração da cicatrização da mucosa. No entanto, a necessidade de reavaliação histológica é um assunto controverso entre "experts." O objetivo deste estudo foi avaliar doentes celíacos submetidos a reavaliado histológica após o inicio da dieta isenta de glúten, a fim de identificar aqueles com remissão histológica e fatores associados. MÉTODOS: Estudo retrospectivo, incluindo doentes que concordaram com reavaliação histológica após aparente remissão clínica e serológica, com pelo menos doze meses de adesão relatada à dieta. Em todos os casos, o consentimento informado foi assinado para endoscopia digestiva alta. RESULTADOS: Um total de 69 doentes foram incluidos. Em 67.9% dos casos, o diagnóstico foi feito no contexto de sintomatologia clássica, 17% de apresentações não clássicas e 15.1 % em fase latente. A maioria (69.2%) dos diagnósticos foram inicial-mente suspeitos com base na serologia. Na endoscopia, 11.8% dos pacientes não apresentavam características macroscópicas sugestivas de doença celíaca, observandole um grau histológico de Marsh Illa-c em 75.5% dos casos. Os achados histológicos normalizaram em 37.7% dos doentes, o que foi associado à presença de menores valores de Marsh no momento do diagnóstico (p = 0.014) e menores valores no T-score da densitometria óssea (p = 0.038). Melhoria histológica foi observada em 55 doentes, em dois ou mais graus em 37 casos, o que se relacionou com a saturado inicial da transferrina (p = 0.027), e com maiores scores de Marsh no momento do diagnóstico (p = 0.007). CONCLUSÃO: Mesmo sob uma dieta isenta de glúten, a normalização da histologia na doença celíaca é difícil de obter e parece ser independente da maioria dos achados clínicos e serológicos no momento do diagnóstico. Doentes com níveis histológicos menos graves ao diagnóstico alcançam a remissão mais facilmente, mas representam apenas a minoria da populado.

Cholangiopancreatoscopy: Expanding the Diagnostic Indications of Endoscopic Retrograde Cholangiopancreatography.

Besides the adverse effects associated with endoscopic retrograde cholangiopancreatography (ERCP), indirect visualization of the biliopancreatic system through fluoroscopy has limited its diagnostic and therapeutic efficacy. Direct visualization through cholangiopancreatoscopy may overcome this limitation and allow the resolution of many dilemmas related to the diagnostic and therapeutic drawbacks of ERCP. Herein, we discuss the current indications of single-operator cholangioscopy (SOC) concerning the diagnostic interventions within the biliopancreatic system. The current role of SOC in the diagnosis of pancreatobiliary stenosis, primary sclerosing cholangitis, intraductal papillary mucinous neoplasm, and pre-surgical mapping of neoplastic lesions were reviewed. There is growing data in the literature supporting the early implementation of SOC in the diagnostic algorithm of pancreatobiliary diseases. In selected cases, this could prevent diagnostic delay and reduce the risks and costs related to repeated ERCPs. This potential characterizes SOC as safety and cost-effective.

Role of liver biopsy in the era of clinical prediction scores for "drug-induced liver injury" (DILI): experience of a tertiary referral hospital.

The clinical implications of the biopsy findings in cases of drug-induced liver injury (DILI) are not fully elucidated. The aim of this study was to evaluate the histopathological findings of cases diagnosed as DILI and to correlate them with clinical and biochemical findings (such as causality assessment algorithms). We searched our department database for all cases of liver biopsy with findings consistent with toxic liver disease and selected those with a clinical diagnosis of DILI. The causative relationships were established according to Roussel Uclaf Causality Assessment Method (RUCAM). A total of 53 cases of DILI were reviewed, most of them diagnosed in hospitalized patients (83%). The analytical toxicity profile was hepatocellular (R > 5) in 60% of the cases and cholestatic (R < 2) in 26.4% of cases. The group of drugs most implicated was the anti-microbials (18, 34%). The predominant histological patterns were "necroinflammation" (67.9%) and "cholestasis" (28.3%). The hepatocellular biochemical pattern was not associated with the presence of predominantly necroinflammatory findings in the biopsy (p = 0.44), and the biochemical cholestatic pattern was not associated with the presence of predominantly cholestatic findings in the biopsy (p = 0.51). This study supports that a better insight into the pathologic mechanisms associated with DILI should be based on liver biopsy due to the lack of a uniform correlation between clinical and biochemical patterns. Also, a liver biopsy may be used in those cases where clinical suspicion of DILI persists despite a low score on current causality assessment algorithms.

Particular aspects of gastroenterological disorders in chronic kidney disease and end-stage renal disease patients: a clinically focused review.

Besides renal disease, gastrointestinal (GI) disorders are frequently reported in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Related gastrointestinal symptoms tend to increase as the renal disease progresses. Also, in patients with ESRD, the modality of dialysis is related to particular forms of GI disorders.The kidney can interact with the digestive organs through functional endogenous systems such as the 'kidney-colon axis' and the 'kidney-liver axis'. Digestive diseases are one of the visible manifestations of the disturbance between hemostatic, hemodynamic and immunological balance in such patients.No clear management guidelines currently exist for many of the gastrointestinal problems that accompany renal failure. This review aims to describe the particular aspects of GI diseases present in CKD/ESRD. We focus our discussion in the specificities of epidemiology, diagnosis, and prognosis of such disorders between the different segments of the digestive system.

Exosomal glypican-1 for risk stratification of pancreatic cystic lesions: A case of pathological progression in the absence of any suspicious imaging finding.

The clinical management of patients with pancreatic cystic lesions is of utmost importance to identify those at high risk for pathological progression. Current recommendations are guided by clinical presentation and radiologic criteria, but the results fall short for a disease that the only curative option is surgical resection. There is an urgent need for the introduction of biomarkers that can help in risk assessment of such lesions. We report a case of a pancreatic cystic lesion without imagiological findings suggestive of advanced disease, and high levels of a circulating biomarker, glypican-1 (GPC-1), which parallel those of patients with pancreatic cancer. One year after, the patient revealed malignant progression at follow-up. Our report is unprecedented in the literature. It describes a clinical case in which a biomarker was positive for a patient that only showed progression one year after its detection. This clinical information goes beyond the current knowledge in the field because it shows that the introduction of liquid biopsy and biomarkers is a highly promising clinical tool for the non-invasive assessment of pancreatic cancer precursor lesions, ultimately increasing the rate of patients eligible for surgical resection.