Effectiveness for Diagnosis of Malignancy of Bile Pyruvate Kinase M2 in Patients with Indeterminate Biliary Stricture.

BACKGROUND: Up to 70% of the cases of biliary strictures are cholangiocarcinoma. Cholangiocarcinoma has a late diagnosis and poor outcomes; therefore, effective biomarkers are needed for malignant lesions detection at earlier stages. AIM: The aim was to assess the diagnostic utility of bile pyruvate kinase M2 (PKM2) as a biomarker for the detection of malignant biliary strictures in patients with an indeterminate biliary stricture. MATERIALS AND METHODS: This is a prospective study to evaluate the diagnostic value of bile PKM2 for the diagnosis of malignant biliary strictures. Bile samples were collected during Endoscopic Retrograde Cholangio Pancreatography to quantify PKM2 levels and were used to compare their diagnostic value with biliary brush cytology, endoscopic ultrasound-guided fine needle biopsy, or clinical follow-up. RESULTS: Forty-six patients were recruited for the study; 19 patients with malignant strictures and 27 with benign biliary strictures. The bile PKM2 levels were elevated in patients with malignant biliary strictures [median 0.045 ng/mL (IQR 0.014 to 0.092)] compared with those with benign strictures [median 0.019 ng/mL (IQR 0.00 to 0.047)]. Bile PKM2 had a receiver-operating characteristic curve of 0.66 (0.49 to 0.83) with a cutoff value of bile PKM2 of 0.0017 ng/mL. The sensitivity and specificity of bile PKM2 for the diagnosis of cholangiocarcinoma were 89% and 26%; the positive and negative predictive values were 46% and 78%, respectively. CONCLUSION: In patients with indeterminate biliary strictures, bile PKM2 may be a potential biomarker for the diagnosis of malignancy.

Assessment of quality benchmarks in adenoma detection in Mexico.

Background and study aims Several Latin American countries, including Mexico, have reported an increase in colorectal cancer (CRC) mortality. The effectiveness of a colonoscopy in preventing CRC depends on the quality of the procedure, for which the adenoma detection rate (ADR) is one of the most trusted indicators. Awareness of ADR can improve the quality of colonoscopies through proper feedback and training of the specialists. The goal of this study was to estimate the ADR among Mexican endoscopists with experience in CRC screening and to compare it with previously reported data from this country. Methods We carried out a retrospective study to analyze ADR data in Mexico. The information was obtained from a group of certified endoscopists and compared with the former published data from Mexico. Results We found a current ADR of 24.6 % (95 %CI, 22.4 %-26.8 %) from 1,478 colonoscopies performed by eight endoscopists in two third-level private hospitals. The average ADR reported in previous publications was 15.2 % (95 %CI, 13.3 %-17.1 %). Statistical analysis showed differences between our results and those from previous studies (24.6 % vs. 15.2 %, P  < 0.001). Conclusions The actual ADR in Mexico is higher than previously reported. Previous low ADR values could be explained by poorly performed colonoscopies rather than by low adenoma and CRC incidence in our country.

Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study.

BACKGROUND: The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. METHODS: This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann-Whitney U non-parametric test. A p value < 0.05 was considered significant. RESULTS: A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05). CONCLUSION: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.

Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

Thrombosis of the Portal Venous System in Cirrhotic vs. Non-Cirrhotic Patients.

INTRODUCTION AND AIM: Thrombosis is a vascular disorder of the liver often associated with significant morbidity and mortality. Cirrhosis is a predisposing factor for portal venous system thrombosis. The aim of this study is to determine differences between cirrhotics and non-cirrhotics that develop thrombosis in portal venous system and to evaluate if cirrhosis severity is related to the development of portal venous system thrombosis. MATERIAL AND METHODS: We studied patients diagnosed with portal venous system thrombosis using contrast-enhanced computed tomography scan and doppler ultrasound at Medica Sur Hospital from 2012 to 2017. They were categorized into two groups; cirrhotics and non-cirrhotics. We assessed the hepatic function by Child-Pugh score and model for end-stage liver disease. RESULTS: 67 patients with portal venous system thrombosis (25 with non-cirrhotic liver and 42 with cirrhosis) were included. The mean age (± SD) was 65 ± 9.5 years in cirrhotic group and 57 ± 13.2 years (p = 0.009) in non-cirrhotic group. Comparing non-cirrhotics and cirrhotics, 8 non-cirrhotic patients showed evidence of extra-hepatic inflammatory conditions, while in the cirrhotic group no inflammatory conditions were found (p < 0.001). 27 (64.29%) cirrhotic patients had thrombosis in the portal vein, while only 9 cases (36%) were found in non-cirrhotics (p = 0.02). CONCLUSIONS: In cirrhotic patients, hepatocellular carcinoma and cirrhosis were the strongest risk factors to develop portal venous system thrombosis. In contrast, extrahepatic inflammatory conditions were main risk factors associated in non-cirrhotics. Moreover, the portal vein was the most frequent site of thrombosis in both groups.

Higher adenoma detection rate with the endocuff: a randomized trial.

Background and study aim Different techniques have been introduced to improve the endoscopist's view and enhance the detection of polyps. The endocuff is a polymer sleeve cap that is connected to the tip of the colonoscope in order to improve visualization of the mucosa during colonoscopy. The aim of the study was to compare adenoma detection rates (ADR) of endocuff-assisted colonoscopy and conventional colonoscopy. Patients and methods Patients 50 years or older were randomized into two groups: an endocuff-assisted colonoscopy group and a conventional colonoscopy group without the endocuff. Results A total of 337 patients were included: 174 in the endocuff group and 163 in the conventional group. The median age was 61 years (interquartile range 55 - 70 years), and 74 % were women. The ADR was higher in the endocuff group than in the conventional group (22.4 % vs. 13.5 %; P = 0.02). The mean number of adenomas was 0.30 (SD 0.25) in the endocuff group and 0.21 (SD 0.26) in the conventional group (P â€Š= 0.02). The rate of ileal intubation was lower in the endocuff group (73 % vs. 87 %; P < 0.001). No serious adverse events occurred with the use of the endocuff. Conclusions Endocuff colonoscopy achieved a greater ADR than conventional colonoscopy.Trial registered at ClinicalTrials.gov (NTC02387593).

Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma.

PURPOSE: To investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population. MATERIAL AND METHODS: We conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of in-patients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method. RESULTS: We reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis. DISCUSSION: We found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population.

The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD.

The Role of Epigenetics in the Progression of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease encompasses a spectrum of pathologies ranging from simple steatosis to non-alcoholic steatohepatitis. Patients with non-alcoholic steatohepatitis have increased risk of cirrhosis, liver failure and hepatocellular carcinoma. About 25% of subjects with simple steatosis progress to steatohepatitis; nowadays, the detailed pathological factors influencing the progression of non-alcoholic fatty liver disease remains unclear. It is proposed that genetic and environmental factors interact to determine the disease phenotype. Epigenetics could explain some relationships between genes and external influences. The epigenetic changes that have been related to non-alcoholic fatty liver disease are DNA methylation, onecarbon metabolism, histone modifications and the presence of micro-RNA. DNA methylation and micro-RNAs have been investigated in human samples, whereas histone modifications have only been studied until now in animal and cellular models. The aim of this study is to review the most relevant information about epigenetic changes in non-alcoholic steatohepatitis.

The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH. MATERIAL AND METHODS: Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRα, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot. RESULTS: Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRα did not show differences between groups. CONCLUSIONS: The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.

Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

Granulomatous hepatitis caused by Q fever: a differential diagnosis of fever of unknown origin.

The differential diagnosis of fever of unknown origin (FUO) includes infectious, neoplastic, rheumaticinflammatory and miscellaneous diseases. We report the case of a 35-year-old man with FUO caused by Q fever. A liver biopsy showed the characteristic fibrin-ring lipogranulomas compatible with Q fever. The serologic tests confirmed the diagnosis of acute infection by Coxiella burnetii. The therapeutic response was excellent. In conclusion, we described a patient with acute Q fever and granulomatous hepatitis.

[Relevance of nuclear medicine in the diagnosis and treatment of malignant paraganglioma]. / Relevancia de la medicina nuclear en el diagnóstico y tratamiento del paraganglioma maligno.

BACKGROUND: Paragangliomas are neoplasms of the chromaffin tissue characterized by the synthesis and/or secretion of catecholamines. Their treatment depends on the extension and functional characteristics of the tumor. In this pathology, the anatomic and functional diagnostic evaluations provided by nuclear medicine imaging studies have significant usefulness. CLINICAL CASE: A 34-year-old male was diagnosed with a paraganglioma at the level of the aortic bifurcation by means of laboratory tests, imaging studies and nuclear medicine studies. Nuclear medicine was carried out with a scintigraphy with a norepinephrine analog, radioactive meta-iodo-benzyl-guanidine (131I-MIBG), which demonstrates functionally and specifically the presence of neoplastic adrenergic tissue and extratumoral extension. In addition, a positron emission tomography coupled with computed tomography with a radioactive analog of glucose locates the extratumoral activity at bone level. Nuclear medicine studies allow the diagnosis of a malignant paraganglioma with presence of bone metastasis. The therapy includes surgical removal of the tumor and ablation of residual malignant tissue and metastatic lesions by radiotherapy with 131I-MIBG. Radiotherapeutic treatment was possible due to the capacity of the tumor to uptake and to concentrate the radioactive hormonal analog. CONCLUSIONS: In cases of paraganglioma, in addition to the localization of the tumor and the evaluation of biochemical alterations, it is indispensable to obtain anatomic and functional evaluation provided by nuclear medicine studies in order to achieve appropriate diagnoses and treatment.

Relevancia de la medicina nuclear en el diagnóstico y tratamiento del paraganglioma maligno / Relevance of nuclear medicine in the diagnosis and treatment of malignant paraganglioma

Introducción: Los paragangliomas son tumores del tejido cromafín caracterizados por la síntesis o secreción de catecolaminas, en los que el tratamiento depende de su extensión y características funcionales. Dentro de la evaluación diagnóstica anatómica y funcional de este padecimiento, los métodos de imagen de medicina nuclear sobresalen por su utilidad. Caso clínico: Paciente con paraganglioma a nivel de la bifurcación de la aorta en quien el diagnóstico se realizó por estudios de laboratorio, imagenología y medicina nuclear. Se llevó a cabo centelleografía con un análogo de norepinefrina, la metayodobencilguanidina marcada radiactivamente (131I-MIBG), que demostró funcional y específicamente la presencia de tejido adrenérgico neoplásico y su extensión extratumoral. Complementariamente se efectuó tomografía por emisión de positrones fusionada con tomografía computarizada, utilizando un análogo radiactivo de la glucosa que localizó la actividad extratumoral a nivel óseo. Los estudios de medicina nuclear permitieron concluir que se trataba de un paraganglioma maligno con metástasis óseas. El tratamiento incluyó resección quirúrgica del tumor y ablación del tejido tumoral residual y de los focos metastásicos con radioterapia interna mediante 131I-MIBG. El tratamiento radioterapéutico fue posible dada la capacidad del tumor y las metástasis de concentrar el análogo hormonal radiactivo. Conclusiones: Ante casos de paragangliomas, además de la localización del tumor y la evaluación de las alteraciones bioquímicas, es indispensable la evaluación funcional que brinda la medicina nuclear para la realización de un diagnóstico y tratamiento adecuados.

BACKGROUND: Paragangliomas are neoplasms of the chromaffin tissue characterized by the synthesis and/or secretion of catecholamines. Their treatment depends on the extension and functional characteristics of the tumor. In this pathology, the anatomic and functional diagnostic evaluations provided by nuclear medicine imaging studies have significant usefulness. CLINICAL CASE: A 34-year-old male was diagnosed with a paraganglioma at the level of the aortic bifurcation by means of laboratory tests, imaging studies and nuclear medicine studies. Nuclear medicine was carried out with a scintigraphy with a norepinephrine analog, radioactive meta-iodo-benzyl-guanidine (131I-MIBG), which demonstrates functionally and specifically the presence of neoplastic adrenergic tissue and extratumoral extension. In addition, a positron emission tomography coupled with computed tomography with a radioactive analog of glucose locates the extratumoral activity at bone level. Nuclear medicine studies allow the diagnosis of a malignant paraganglioma with presence of bone metastasis. The therapy includes surgical removal of the tumor and ablation of residual malignant tissue and metastatic lesions by radiotherapy with 131I-MIBG. Radiotherapeutic treatment was possible due to the capacity of the tumor to uptake and to concentrate the radioactive hormonal analog. CONCLUSIONS: In cases of paraganglioma, in addition to the localization of the tumor and the evaluation of biochemical alterations, it is indispensable to obtain anatomic and functional evaluation provided by nuclear medicine studies in order to achieve appropriate diagnoses and treatment.