A Circular RNA, Cholangiocarcinoma-Associated Circular RNA 1, Contributes to Cholangiocarcinoma Progression, Induces Angiogenesis, and Disrupts Vascular Endothelial Barriers.

BACKGROUND AND AIMS: Circular RNAs (circRNAs) and extracellular vesicles (EVs) are involved in various malignancies. We aimed to clarify the functions and mechanisms of dysregulated circRNAs in the cells and EVs of cholangiocarcinoma (CCA). APPROACH AND RESULTS: CircRNA microarray was used to identify circRNA expression profiles in CCA tissues and bile-derived EVs (BEVs). CCA-associated circRNA 1 (circ-CCAC1) expression was measured by quantitative real-time PCR. The clinical importance of circ-CCAC1 was analyzed by receiver operating characteristic curves, Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The functions of circ-CCAC1 and exosomal circ-CCAC1 were explored in CCA cells and human umbilical vein endothelial cells (HUVECs), respectively. Different animal models were used to verify the in vitro results. RNA sequencing, bioinformatics, RNA immunoprecipitation, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and luciferase reporter assays were used to determine the regulatory networks of circ-CCAC1 in CCA cells and HUVECs. Circ-CCAC1 levels were increased in cancerous bile-resident EVs and tissues. The diagnostic and prognostic values of circ-CCAC1 were identified in patients with CCA. For CCA cells, circ-CCAC1 increased cell progression by sponging miR-514a-5p to up-regulate Yin Yang 1 (YY1). Meanwhile, YY1 directly bound to the promoter of calcium modulating ligand to activate its transcription. Moreover, circ-CCAC1 from CCA-derived EVs was transferred to endothelial monolayer cells, disrupting endothelial barrier integrity and inducing angiogenesis. Mechanistically, circ-CCAC1 increased cell leakiness by sequestering enhancer of zeste homolog 2 in the cytoplasm, thus elevating SH3 domain-containing GRB2-like protein 2 expression to reduce the levels of intercellular junction proteins. In vivo studies further showed that increased circ-CCAC1 levels in circulating EVs and cells accelerated both CCA tumorigenesis and metastasis. CONCLUSIONS: Circ-CCAC1 plays a vital role in CCA tumorigenesis and metastasis and may be an important biomarker/therapeutic target for CCA.

The Challenges of Implementing Artificial Intelligence into Surgical Practice.

BACKGROUND: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD). METHODS: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted. RESULTS: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones. CONCLUSION: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Acute obstructive cholangitis due to fishbone in the common bile duct: a case report and review of the literature.

BACKGROUND: Choledocholithiasis is an endemic condition in the world. Although rare, foreign body migration with biliary complications needs to be considered in the differential diagnosis for patients presenting with typical symptoms even many years after cholecystectomy, EPCP, war-wound, foreign body ingestion or any other particular history before. It is of great clinical value as the present review may offer some help when dealing with choledocholithiasis caused by foreign bodies. CASE PRESENTATION: We reported a case of choledocholithiasis caused by fishbone from choledochoduodenal anastomosis regurgitation. Moreover, we showed up all the instances of choledocholithiasis caused by foreign bodies published until June 2018 and wrote the world's first literature review of foreign bodies in the bile duct of 144 cases. The findings from this case suggest that the migration of fishbone can cause various consequences, one of these, as we reported here, is as a core of gallstone and a cause of choledocholithiasis. CONCLUSION: The literature review declared the choledocholithiasis caused by foreign bodies prefer the wrinkly and mainly comes from three parts: postoperative complications, foreign body ingestion, and post-war complications such as bullet injury and shrapnel wound. The Jonckheere-Terpstra test indicated the ERCP was currently the treatment of choice. It is a very singular case of choledocholithiasis caused by fishbone, and the present review is the first one concerning choledocholithiasis caused by foreign bodies all over the world.

External Validation of Different Scoring Systems for Suspected Choledocholithiasis.

AIM OF THE STUDY: The diagnosis of choledocholithiasis is challenging. Previously published scoring systems designed to calculate the risk of choledocholithiasis were evaluated to appraise the diagnostic performance. PATIENTS AND METHODS: Data of patients who were admitted between 2013 and 2015 with the following characteristics were retrieved: bile stone-related symptoms and signs, and indication to laparoscopic cholecystectomy. To validate and appraise the performance of the 6 scoring systems, the acknowledged domains of each metrics were applied to the present cohort. Sensitivity, specificity, positive, negative predictive, Youden index, and receiver operating characteristic curve with the area under the curve (AUC) values of the scores were calculated. RESULTS: Two-hundred patients were analyzed. The highest sensitivity and specificity were obtained from the Menezes' (96.6%) and Telem's (99.3%) metrics respectively. The Telem's and Menezes' scores had the best positive (75.0%) and negative (96.4%) predictive values respectively. The best accuracy, as computed by the Youden index and AUC, was found for the Soltan's scoring system (0.628 and 0.88, respectively). CONCLUSION: The available scoring systems are precise only in identifying patients with a negligible risk of common bile duct stone, but overall insufficiently accurate to suggest the routine use in clinical practice.

Clinical Observation of the Efficacy of Endoscopic Retrograde Cholangiopancreatography on Elder Choledocholithiasis and Its Effects on the Levels of TNF-α, IL-1, and IL-6.

OBJECTIVE: We conducted this study to investigate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) on elder choledocholithiasis and its effects on the levels of TNF-α, IL-1, and IL-6. METHODS: Elder patients with choledocholithiasis were enrolled in this study, and according to the surgical methods, they were divided into the ERCP group and the surgical group. After treatment, we compared the efficacy of these two methods on patients, inflammatory responses indicated by the levels of TNF-α, IL-1, and IL-6, and the complications. RESULTS: No statistical significance was identified in the difference of the success rate in removal between the two groups (98% vs. 94%), but indicators of the ERCP group, including the surgical duration (28.5±12.8) min, remission duration of abdominal pain (1.2±0.2) d, recession time of jaundice (2.0±0.3) d, postoperative bedridden time (1.4±0.2) d, treatment time of the anti-infection (1.5±0.2) d, length of stay in hospital (6.5±0.3) d, levels of TNF-α (2.1±0.2) µg/L, IL-1 (6.3±0.8) µg/L, IL-6 (2.8±0.3) µg/L, and the incidence rate of complications (1.8%), were all significantly lower than those in the surgical group (p<0.05). CONCLUSION: In the treatment of choledocholithiasis, ERCP is excellent in controlling the trauma, accelerating the recovery duration, reducing the occurrence of complications and ameliorating the inflammatory responses. Thus, it is an ideal choice for choledocholithiasis.

Clinical Observation of the Efficacy of Endoscopic Retrograde Cholangiopancreatography on Elder Choledocholithiasis and Its Effects on the Levels of TNF-α, IL-1, and IL-6

SUMMARY OBJECTIVE: We conducted this study to investigate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP) on elder choledocholithiasis and its effects on the levels of TNF-α, IL-1, and IL-6. METHODS: Elder patients with choledocholithiasis were enrolled in this study, and according to the surgical methods, they were divided into the ERCP group and the surgical group. After treatment, we compared the efficacy of these two methods on patients, inflammatory responses indicated by the levels of TNF-α, IL-1, and IL-6, and the complications. RESULTS: No statistical significance was identified in the difference of the success rate in removal between the two groups (98% vs. 94%), but indicators of the ERCP group, including the surgical duration (28.5±12.8) min, remission duration of abdominal pain (1.2±0.2) d, recession time of jaundice (2.0±0.3) d, postoperative bedridden time (1.4±0.2) d, treatment time of the anti-infection (1.5±0.2) d, length of stay in hospital (6.5±0.3) d, levels of TNF-α (2.1±0.2) μg/L, IL-1 (6.3±0.8) μg/L, IL-6 (2.8±0.3) μg/L, and the incidence rate of complications (1.8%), were all significantly lower than those in the surgical group (p<0.05). CONCLUSION: In the treatment of choledocholithiasis, ERCP is excellent in controlling the trauma, accelerating the recovery duration, reducing the occurrence of complications and ameliorating the inflammatory responses. Thus, it is an ideal choice for choledocholithiasis.

RESUMO OBJETIVO: Realizamos este estudo para investigar a eficácia clínica da colangiopancreatografia retrógrada endoscópica (ERCP) na coledocolitíase idosa e seus efeitos nos níveis de TNF-α, IL-1 e IL-6. MÉTODOS: Pacientes idosos com coledocolitíase foram matriculados neste estudo. De acordo com os métodos cirúrgicos, eles foram divididos em grupo ERCP e grupo cirúrgico. Após o tratamento, comparamos a eficácia desses dois métodos em pacientes, respostas inflamatórias indicadas pelos níveis de TNF-α, IL-1 e IL-6 e as complicações. RESULTADOS: Não houve significância estatística na diferença da taxa de sucesso na remoção entre os dois grupos (98% versus 94%), mas indicadores do grupo ERCP, incluindo a duração cirúrgica (28,5 ± 12,8) min, duração da remissão da dor abdominal (1,2 ± 0,2) d, tempo de recessão de icterícia (2,0 ± 0,3) d, tempo pós-operatório (1,4 ± 0,2) d, tempo de tratamento da infecção (1,5 ± 0,2) d, duração da internação (6,5 ± 0,3) d, níveis de TNF-α (2,1 ± 0,2) μg / L, IL-1 (6,3 ± 0,8) μg / L, IL-6 (2,8 ± 0,3) μg / L e a taxa de incidência de complicações (1,8 %) foram todos significativamente inferiores aos do grupo cirúrgico (p<0,05). CONCLUSÃO: No tratamento da coledocolitíase, a ERCP é excelente no controle do trauma, acelerando a duração da recuperação, reduzindo a ocorrência de complicações e melhorando as respostas inflamatórias. Assim, é uma escolha ideal para a coledocolitíase.

Prospective validation of an initial cholecystectomy strategy for patients at intermediate-risk of common bile duct stone.

BACKGROUND AND AIMS: Initial cholecystectomy for patients at intermediate risk of common bile duct (CBD) stones (including increased liver function tests but bilirubin <4 mg/dL and no cholangitis) showed shorter length of stay and fewer CBD investigations without increased morbidity compared with sequential CBD endoscopic assessment and subsequent cholecystectomy in a randomized controlled trial. The objectives were to prospectively validate these results in daily clinical practice and discuss current guidelines. METHODS: Initial cholecystectomy has become the standard management strategy at Geneva University Hospitals since July 2013 for patients at intermediate risk of CBD stones admitted with acute gallstone-related conditions. Between July 2013 and December 2014, length of stay, number of CBD investigations, and number of adverse events were recorded for these patients and compared with the data of the patients in the randomized controlled trial. RESULTS: Data for 161 consecutive newly assessed patients at intermediate risk of CBD stones confirmed shorter length of stay (7.6 vs 9.8 days; P < .001), fewer CBD investigations (0.8 vs 1.4 investigations per patient; P < .001), and similar adverse event rates (5.6% vs 14%, P = .14 including all adverse events; 3.1% vs 8%, P = .22 including only grade ≥III adverse events, defined by endoscopic/surgical reintervention or intensive care unit admission) compared with the previously reported group of patients who underwent preoperative CBD investigations. CONCLUSIONS: These data confirm that initial cholecystectomy results in a shorter length of stay without increased morbidity among patients at intermediate risk of CBD stones compared with sequential CBD assessment and subsequent cholecystectomy. This approach may change current guidelines.

Use of Liver Function Tests as First-line Diagnostic Tools for Predicting Common Bile Duct Stones in Acute Cholecystitis Patients.

BACKGROUND: Prior studies have examined the use of liver function tests (LFT) for predicting the presence of common bile duct (CBD) stones in chronic cholecystitis (CC) patients. It is currently unclear whether LFT are also useful for predicting CBD stones in patients with acute cholecystitis (AC). METHODS: Of 1059 patients who visited an emergency room with gallbladder-related symptoms between March 2004 and December 2009, 854 patients were analyzed, and were divided into three groups (556 AC patients without CBD stones (AC - CBD), 98 AC patients with CBD stones (AC + CBD), and 200 CC patients without CBD stones). We compared the LFT values at admission and the changes in LFT values over time following admission among the three groups. RESULTS: The LFT values were significantly greater in the AC + CBD group than in the AC - CBD groups. Of all the LFT variables analyzed, γ-glutamyl transpeptidase was the most reliable variable for predicting the presence of CBD stones, with a sensitivity of 80.6 % and a specificity of 75.3 % at the cut-off level of 224 IU/L. The elevated LFT values decreased significantly from the start of the follow-up assessment to before cholecystectomy in the AC - CBD group, but were unchanged before stone removal in the AC + CBD group. CONCLUSION: The LFT values on initial admission and the changes in LFT values over time are reliable predictors of CBD stones in patients with AC.

An assessment of existing risk stratification guidelines for the evaluation of patients with suspected choledocholithiasis.

BACKGROUND: Prior studies have demonstrated that existing risk stratification guidelines for the evaluation of suspected choledocholithiasis lack accuracy, leading to the overutilization of endoscopic retrograde cholangiopancreatography (ERCP). The aim of our study was to evaluate the performance characteristics of published guidelines in predicting choledocholithiasis and to determine the impact of laboratory trends on diagnostic accuracy. METHODS: We identified patients with suspected choledocholithiasis hospitalized over a 5-year period (2009-2014) at a tertiary care academic medical center. Among eligible patients, we assessed the performance characteristics of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines predicting the presence of choledocholithiasis, confirmed by endoscopic ultrasound, magnetic resonance cholangiography, ERCP, or intra-operative cholangiography. We also evaluated whether a second set of liver function tests improved the accuracy of the guidelines. RESULTS: On presentation, 71 of the 173 eligible patients (41.4 %) met ASGE high-probability criteria for choledocholithiasis. Of these, only 39 (54.9 %) were found to have a choledocholithiasis on confirmatory testing. Conversely, of the 102 patients (58.6 %) who were classified as low or intermediate probability, 32 (31.4 %) had choledocholithiasis. Overall, the accuracy of the guidelines was 63 % (sensitivity 54.9 %; specificity 68.6 %). Incorporating a second set of laboratory tests did not improve accuracy (62.7 %), and a significant decline in liver function tests did not reliably predict spontaneous stone passage. CONCLUSIONS: Existing guidelines performed suboptimally for predicting choledocholithiasis in our patient population, similar to other validation studies. These findings further underscore the importance of developing alternate risk stratification tools for choledocholithiasis, aiming to minimize unnecessary diagnostic ERCP.

A scoring system for the prediction of choledocholithiasis: a prospective cohort study.

BACKGROUND: Techniques for diagnosing choledocholithiasis pose significant morbidity and mortality risks. OBJECTIVES: We aimed to develop and validate a clinical scoring system for predicting choledocholithiasis. DESIGN: Data from a prospectively maintained database of all patients with gallstones. SETTING: Patients were admitted to the general surgery department of a military hospital. PATIENTS AND METHODS: We enrolled consecutive patients with symptomatic gallstones, biliary pancreatitis, obstructive jaundice, or cholangitis, who subsequently underwent biochemical testing and ultrasonography. A predictive model was developed from a scoring system using their imaging and laboratory data. Endoscopic retrograde cholangiopancreatography (ERCP) or intraoperative cholangiography were used for confirmatory diagnoses. The predictive efficacy of the scoring system was validated using a retrospective cohort of 272 patients. MAIN OUTCOME MEASURES: Predictive accuracy of the scoring system. RESULTS: We enrolled 155 patients in the development group. The common bile duct diameter, alkaline phosphatase of >=200 IU, elevated bilirubin levels, alanine transaminase of >=220 IU, and male age of >=50 years were significantly associated with choledocholithiasis and were included in the scoring system. Ninety-six patients (35%) had scores of >=8 (high risk), 86 patients (32%) had scores of 4-7 (intermediate risk), and 27 patients (10%) had scores of 1-3 (low risk). In the validation cohort, the positive predictive value for a score of >=8 was 91.7%, and the scoring system had an area under the curve of 0.896. CONCLUSION: Scores of >=8 were strongly correlated with choledocholithiasis in the developmental and validation groups, which indicates that our scoring system may be useful for predicting the need for therapeutic ERCP. However, prospective validation in a large multicenter cohort is needed to fully understand the benefits of the system. LIMITATIONS: The retrospective validation cohort might have introduced selection and observational biases. The study may have been underpowered because of the sample size of the developmental cohort. The delay between admission and the time of ERCP theoretically may have increased the number of negative ERCP results, but our false negative rate for ERCP was consistent with the previously reported rates.

Predictor factors for choledocholithiasis.

BACKGROUND: The choledocolithiasis has an incidence of 8-20% in patients with cholecystolithiasis. The preoperative diagnosis guides the interventional treatment on the bile duct AIM: To evaluate the sensitivity and specificity of the laboratory markers and imaging studies for choledocholithiasis preoperatively. METHODS: The study comprised 254 patients divided into two groups: the control group (207 patients), patients without choledocholithiasis intraoperatively and cases group (47 patients), that enrolled the patients with choledocholithiasis intra-operatively. Were evaluated the laboratory markers, image exams and intra-operative diagnostic aspects. RESULTS: The sample was homogeneous for age and gender. It was observed that 47% of the cases the patients did not show comorbidities. Hospitalization showes in cases group acute pancreatitis in12.8%, jaundice in 30%, fever in 30% and pain in the right hypochondrium in 95%. By comparing them, was observed that fever and jaundice were the signs and symptoms with statistical significance. Patients with choledocholithiasis had transaminases, alkaline phosphatase, gamma-glutamyl transferase and higher bilirubin with statistical significance (p<0.001). In regard to imaging studies, ultrasound was fairly accurate for cholelithiasis and choledocholithiasis (p<0.001). CONCLUSION: Changes in canalicular and transaminase enzymes are suggestive for preoperative choledocholithiasis; GGT showed better sensitivity and alkaline phosphatase greater specificity; ultrasonography and nuclear magnetic resonance cholangiopancreatography showed high specificity.

Double-Duct Sign in the Clinical Context.

OBJECTIVES: Double-duct sign (combined dilatation of the common bile duct and pancreatic duct) is an infrequently encountered finding in cross-sectional radiological imaging of the pancreatobiliary system. This sign is commonly deemed to signify on ominous pathology and suggests the presence of pancreatic or biliary malignancy. METHODS: We aim to correlate double-duct sign discovered on magnetic resonance cholangiopancreatogram (MRCP) in the clinical context. We retrospectively analyzed MRCP database over a period of 4 years, January 2010 to December 2013. Follow-up information was available for a median of 27 months (range, 12-42 months) RESULTS: The commonest cause of double-duct sign was choledocholithiasis followed closely by pancreatobiliary malignancy. Patients with jaundice in the context of double-duct sign had a higher incidence of malignancy (48%). None of the anicteric patients were found to have malignancy (P = 0.002). CONCLUSIONS: In patients with MRCP evidence of double-duct sign, the absence of jaundice makes a malignant etiology unlikely. Conversely, in jaundiced patients, a malignant cause is much more likely. Figures from larger series are needed to support this conclusion.

Predictor factors for choledocholithiasis / Fatores preditores para coledocolitíase

BACKGROUND: The choledocolithiasis has an incidence of 8-20% in patients with cholecystolithiasis. The preoperative diagnosis guides the interventional treatment on the bile duct AIM: To evaluate the sensitivity and specificity of the laboratory markers and imaging studies for choledocholithiasis preoperatively. METHODS: The study comprised 254 patients divided into two groups: the control group (207 patients), patients without choledocholithiasis intraoperatively and cases group (47 patients), that enrolled the patients with choledocholithiasis intra-operatively. Were evaluated the laboratory markers, image exams and intra-operative diagnostic aspects. RESULTS: The sample was homogeneous for age and gender. It was observed that 47% of the cases the patients did not show comorbidities. Hospitalization showes in cases group acute pancreatitis in12.8%, jaundice in 30%, fever in 30% and pain in the right hypochondrium in 95%. By comparing them, was observed that fever and jaundice were the signs and symptoms with statistical significance. Patients with choledocholithiasis had transaminases, alkaline phosphatase, gamma-glutamyl transferase and higher bilirubin with statistical significance (p<0.001). In regard to imaging studies, ultrasound was fairly accurate for cholelithiasis and choledocholithiasis (p<0.001). CONCLUSION: Changes in canalicular and transaminase enzymes are suggestive for preoperative choledocholithiasis; GGT showed better sensitivity and alkaline phosphatase greater specificity; ultrasonography and nuclear magnetic resonance cholangiopancreatography showed high specificity. .

RACIONAL: A coledocolitíase tem incidência de 8-20% em pacientes com colecistolitíase. O diagnóstico pré-operatório orienta o tratamento intervencionista sobre a via biliar OBJETIVO: Avaliar a sensibilidade e especificidade dos marcadores laboratoriais e exames de imagem para coledocolitíase no pré-operatório. MÉTODO: Total de 254 pacientes foi dividido em dois grupos: grupo controle (207 pacientes) com os pacientes que não apresentaram coledocolitíase no intra-operatório e o grupo casos (47 pacientes), que foram os que apresentaram coledocolitíase no intra-operatório. Foram avaliados os marcadores laboratoriais, exames de imagem (ultrassonografia e colangiorresonância) e conclusão intra-operatória para diagnóstico. RESULTADOS: A amostra foi homogênea para sexo e idade. Foi observado que no grupo casos 47% dos pacientes não apresentaram comorbidades. Quanto ao motivo de internação observou-se no grupo casos que 12,8% apresentavam pancreatite aguda, 30% icterícia, 30% febre e 95% dor em hipocôndrio direito. Ao comparar os grupos observou-se que febre e icterícia foram o sinal e sintoma com relevância estatística. Os pacientes com coledocolitíase apresentaram transaminases, fosfatase alcalina, gama-glutamil transferase e bilirrubinas mais elevadas com significância estatística (p<0,001). Em relação aos exames de imagem, observou-se que a ultrassonografia demonstrou boa acurácia para colecistolitíase e coledocolitíase (p<0,001) . CONCLUSÃO: As alterações das enzimas canaliculares e transaminases são sugestivas para investigação pré-operatória de coledocolitíase, sendo que a GGT apresentou melhor sensibilidade e a fosfatase alcalina maior especificidade. A ultrassonografia e a colangioressonância nuclear magnética apresentaram alta especificidade. .

Regression tree for choledocholithiasis prediction.

OBJECTIVES: The aim of this study was to develop and compare the predictive accuracy of classification and regression tree (CART) analysis with logistic regression (LR) for predicting common bile duct stones (CBDS) in patients subjected to laparoscopic cholecystectomy. PATIENTS AND METHODS: We prospectively collected preoperative (demographic, biochemical, ultrasonographic) and intraoperative (intraoperative cholangiography, cystic duct diameter) data for 154 patients considered for elective laparoscopic cholecystectomy at the department of General Surgery at Gornji Milanovac from 2013 through 2014. Univariate and multivariate regression analyses were used to determine independent predictors of CBDS. The CART analysis was carried out using the predictors identified by LR analysis. Various measures for the assessment of risk prediction models were determined, such as predictive ability, accuracy, the area under the receiver operating characteristic curve, and clinical utility using decision curve analysis. RESULTS: The most decisive variable at the time of classification was the cystic duct diameter category, the alkaline phosphatase, and dangerous stones. The CART model was shown to have good discriminatory ability (93.9%). Accuracy was similar in both models, ranging from 92.9% in the CART model and 93.5% in the LR model. In decision curve analysis, the CART model outperformed the LR model. CONCLUSION: We developed a user-friendly risk model that can successfully predict the presence of choledocholithiasis in patients planned for elective cholecystectomy. However, before recommending its use in clinical practice, a larger and more complete database should be used to further clarify the differences between models in terms of prediction of the CBDS.

Predicting the likelihood of a persistent bile duct stone in patients with suspected choledocholithiasis: accuracy of existing guidelines and the impact of laboratory trends.

BACKGROUND: Existing guidelines aim to stratify the likelihood of choledocholithiasis to guide the use of ERCP versus a lower-risk diagnostic study such as EUS, MRCP, or intraoperative cholangiography. OBJECTIVE: To assess the performance of existing guidelines in predicting choledocholithiasis and to determine whether trends in laboratory parameters improve diagnostic accuracy. DESIGN: Retrospective cohort study. SETTING: Tertiary-care hospital. PATIENTS: Hospitalized patients presenting with suspected choledocholithiasis over a 6-year period. INTERVENTIONS: Assessment of the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, its component variables, and laboratory trends in predicting choledocholithiasis. MAIN OUTCOME MEASUREMENTS: The presence of choledocholithiasis confirmed by EUS, MRCP, or ERCP. RESULTS: A total of 179 (35.9%) of the 498 eligible patients met ASGE high-probability criteria for choledocholithiasis on initial presentation. Of those, 99 patients (56.3%) had a stone/sludge on subsequent confirmatory test. Of patients not meeting high-probability criteria on presentation, 111 (34.8%) had a stone/sludge. The overall accuracy of the guidelines in detecting choledocholithiasis was 62.1% (47.4% sensitivity, 73% specificity) based on data available at presentation. The accuracy was unchanged when incorporating the second set of liver chemistries obtained after admission (63.2%), suggesting that laboratory trends do not improve performance. LIMITATIONS: Retrospective study, inconsistent timing of the second set of biochemical markers. CONCLUSION: In our cohort of patients, existing choledocholithiasis guidelines lacked diagnostic accuracy, likely resulting in overuse of ERCP. Incorporation of laboratory trends did not improve performance. Additional research focused on risk stratification is necessary to meet the goal of eliminating unnecessary diagnostic ERCP.

Endosonography for Pancreatic Duct Dilatation without Definite Pathology on Ultrasonography.

BACKGROUND/AIMS: Main pancreatic duct dilatation raises concerns about the possibility of pancreatobiliary malignancy. We evaluated the etiologic yield of endosonography (EUS) for main pancreatic duct dilatation without definite pathology on Ultrasonography (US). METHODOLOGY: A retrospective review was conducted in 54 consecutive patients referred for EUS. RESULTS: No pathological finding (37.0%, 20/54), followed by periampullary cancer (35.2%, 19/54), was the most common finding. Elevated alkaline phosphatase (ALK-P) and marked common bile duct (CBD) dilatation (≥ 12 mm) were the predictors of malignancy (p < 0.05). Among the 37 subjects with available ALK-P and CBD diameter, the probability of malignancy was 84.6% (11/13) for both elevated ALK-P and marked CBD dilatation, 16.7% (1/6) for isolated elevated ALK-P, 18.2% (2/11) for isolated marked CBD dilatation, and none (0/7) was for subjects with neither elevated ALK-P nor marked CBD dilatation, respectively. The overall accuracy of EUS for periampullary carcinomas was 94.7% (18/19) and for choledocholithiasis was 100% (7/7), respectively. EUS had a 100.0% (20/20) sensitivity and a 97.1% (33/34) specificity in the diagnosis of no pathological obstruction. CONCLUSIONS: EUS is accurate for main pancreatic duct dilatation without definite pathology on US, and the presence of concomitant elevated ALK-P and CBD dilatation highly suggests malignancy.

Evaluation of concentrations of pro/anti-inflammatory cytokines after complication-free ECRP in cholangiocarcinoma.

BACKGROUND/AIMS: Variations in pro and anti-inflammatory cytokine levels occur commonly after ERCP procedure complications, such as in post-ERCP pancreatitis. Besides, the relationship between increased cytokine levels and multidrug resistance has been shown in cholangiocarcinoma patients. Our aim was to investigate the impact of cytokine level changes on treatment strategy after uncomplicated ERCP procedures in cholangiocarcinoma patients. MATERIALS AND METHODS: Of 75 patients enrolled in this study, 25 were cholangiocarcinoma, and 50 were choledocholithiasis patients. Levels of serum IL-1ß, IL-6, IL-8, IL-10, and TNF-α were evaluated 2 hours before and 12 hours after complication-free ERCP, and statistical analysis of the results was obtained; if p value<0.05, it was accepted as statistically significant. RESULTS: There was no statistically significant difference in the distribution of age (23-87 years; range: 59.8±16.6), gender (37 males vs 38 females), and levels of pre- and post-ERCP serum IL-1ß, IL-6, IL-8, IL-10, and TNF-α in both patient groups, despite the presence of some change in test means (p:0.179, 0.445, 0.522, 0.937, and 0.065, respectively). However, significantly decreased levels of TNF-α were observed in the benign group, when comparing pre- and post-ERCP period (p<0.05). CONCLUSION: Serum concentrations of IL-1ß, IL-6, IL-8, IL-10, and TNF-α evaluated after complication-free ERCP performed in patients with cholangiocarcinoma do not cause any change in treatment planning that would affect multidrug resistance.

Can red cell distribution width help to discriminate benign from malignant biliary obstruction? A retrospective single center analysis.

BACKGROUND/AIMS: Differentiation of benign obstructive jaundice from malignant obstructive jaundice still remains difficult, despite improvements in diagnostic modalities. The aim of this study is to evaluate the usefulness of red cell distribution width (RDW) in differentiating benign and malignant causes of obstructive jaundice. METHODOLOGY: One hundred and ninety four consecutive patients (101 malignant, 93 benign) with a history of obstructive jaundice were reviewed in the period between January 2008 and August 2009. Definition of biliary strictures was suggested by cholangiographic features and supported by brush cytology, fine needle aspiration (FNA) and the presence of mass or metastases by imaging and/or clinical followup. Patients were divided into two groups, benign and malignant, based on the discharge diagnosis. RESULTS: The receiver operating characteristic analysis showed that a RDW of 14.8% was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 72% and a specificity of 69% (AUC=0.755, 95% CI=0.649-0.810). RDW was increased (>14.8%) in 31.6% of benign cases and 68.4% of malignancies. Depressed RDW levels (<14.8%) were found in 72.9% of benign cases and 27.1% of malignancies, which was statistically significant (p<0.001). CONCLUSIONS: Our results show that RDW is useful in the differentiation of benign from malignant causes of biliary obstruction when using an optimized cut-off value. In patients in whom biliary obstruction is suspected, an elevated RDW value may be a reliable additional predictor for differentiating the underlying etiology of biliary obstruction.

Increased ACE in extrahepatic cholangiocarcinoma as a clue for activated RAS in biliary neoplasms.

AIM: Cholangiocarcinoma (CCA) is a primary neoplastic tumor of the epithelial lining of the biliary tree which carries a poor prognosis despite combined therapeutic strategies. Although the exact etiology remains obscure, it has been suggested that locally produced Angiotensin II (Ang II) in intrahepatic CCA tissues plays a key role in the proliferation and activation of CCA. In the present study, we aimed to analyze the relationship between the levels of circulating angiotensin converting enzyme (ACE), an important molecule of the renin-angiotensin system (RAS), and biliary disorders. PATIENTS AND METHODS: The study group comprised 19 extrahepatic cholangiocarcinoma (EHCC) (16 patients with hilar, three patients with distal CCA), and 15 choledocolithiasis (CL) patients, with 15 controls. Median age of EHCC, CL and healthy controls were 67 (48-82), 65 (29-87) and 56 (23-74) respectively. ACE was measured by monitoring the alteration in absorbance at 340 nm of the hydrolysis of furylacrylolylphenylalanylglycylglycine (FAPGG) to FAP and GG on an analyzer. The ACE activity in the sample was determined by comparing the sample reaction rate to that obtained with the ACE calibrator. RESULTS: Serum mean ACE levels were 56.6±27.4 U/L, 32.9±14.6 U/L and 28.6±10.6 U/L for patients with EHCC, CL and healthy controls, respectively. Serum ACE levels were significantly higher in patients with EHCC compared to CL and control groups. No significant differences with respect to ACE levels were observed between CL and control groups. CONCLUSION: Circulating ACE in the context of RAS might be associated with EHCC development by creating a local environment enriched with cytokines and other growth factors that may promote cholangiocyte turnover.