Rerouting cardiovascular management following gastric bypass surgery: Dose optimization of carvedilol using population-based analysis.

AIMS: A population-based pharmacokinetic (PK) modeling approach (PopPK) was used to investigate the impact of Roux-en-Y gastric bypass (RYGB) on the PK of (R)- and (S)-carvedilol. We aimed to optimize carvedilol dosing for these patients utilizing a pharmacokinetic/pharmacodynamic (PK/PD) link model. METHODS: PopPK models were developed utilizing data from 52 subjects, including nonobese, obese, and post- RYGB patients who received rac- carvedilol orally. Covariate analysis included anthropometric and laboratory data, history of RYGB surgery, CYP2D6 and CYP3A4 in vivo activity, and relative intestinal abundance of major drug- metabolizing enzymes and transporters. A direct effect inhibitory Emax pharmacodynamic model was linked to the PK model of (S)- carvedilol to simulate the changes in exercise- induced heart rate. RESULTS: A 2-compartmental model with linear elimination and parallel first-order absorptions best described (S)-carvedilol PK. RYGB led to a twofold reduction in relative oral bioavailability compared to nonoperated subjects, along with delayed absorption of both enantiomers. The intestinal ABCC2 mRNA expression increases the time to reach the maximum plasma concentration. The reduced exposure (AUC) of (S)-carvedilol post-RYGB corresponded to a 33% decrease in the predicted area under the effect curve (AUEC) for the 24-hour ß-blocker response. Simulation results suggested that a 50-mg daily dose in post-RYGB patients achieved comparable AUC and AUEC to 25-mg dose in nonoperated subjects. CONCLUSION: Integrated PK/PD modeling indicated that standard dosage regimens for nonoperated subjects do not provide equivalent ß-blocking activity in RYGB patients. This study highlights the importance of personalized dosing strategies to attain desired therapeutic outcomes in this patient cohort.

Pure Cut or Endocut for Biliary Sphincterotomy? A Multicenter Randomized Clinical Trial.

INTRODUCTION: Adverse events (AE) after endoscopic retrograde cholangiopancreatography (ERCP) are not uncommon and post-ERCP acute pancreatitis (PEP) is the most important one. Thermal injury from biliary sphincterotomy may play an important role and trigger PEP or bleeding. Therefore, this study evaluated the outcomes of 2 electric current modes used during biliary sphincterotomy. METHODS: From October 2019 to August 2021, consecutive patients with native papilla undergoing ERCP with biliary sphincterotomy were randomized to either the pure cut or endocut after cannulation. The primary outcome was PEP incidence. Secondary outcomes included intraprocedural and delayed bleeding, infection, and perforation. RESULTS: A total of 550 patients were randomized (272 pure cut and 278 endocut). The overall PEP rate was 4.0% and significantly higher in the endocut group (5.8% vs 2.2%, P = 0.034). Univariate analysis revealed >5 attempts ( P = 0.004) and endocut mode ( P = 0.034) as risk factors for PEP. Multivariate analysis revealed >5 attempts ( P = 0.005) and a trend for endocut mode as risk factors for PEP ( P = 0.052). Intraprocedural bleeding occurred more often with pure cut ( P = 0.018), but all cases were controlled endoscopically during the ERCP. Delayed bleeding was more frequent with endocut ( P = 0.047). There was no difference in perforation ( P = 1.0) or infection ( P = 0.4999) between the groups. DISCUSSION: Endocut mode may increase thermal injury leading to higher rates of PEP and delayed bleeding, whereas pure cut is associated with increased intraprocedural bleeding without clinical repercussion. The electric current mode is not related to perforation or infection. Further RCT assessing the impact of electric current on AE with overlapping preventive measures such as rectal nonsteroidal anti-inflammatory drugs and hyperhydration are needed. The study was submitted to the Brazilian Clinical Trials Platform ( http://www.ensaiosclinicos.gov.br ) under the registry number RBR-5d27tn.

Adverse events and mortality: comparative analysis between diagnostic and interventional endoscopic ultrasound.

BACKGROUND AND AIMS: Escalating an indication of EUS for diagnosis and treatment justifies the evaluation of the conditions associated with the adverse events (AE) and related deaths. The aim is to evaluate and compare the incidence of AE and deaths after diagnostic-EUS (D-EUS) and interventional-EUS (I-EUS). METHODS: This retrospective study included patients undergoing D-EUS and I-EUS, in two centers for 28 years (03/1992 to 12/2019). Were noted parameters such as: age, gender, indication of EUS, modality, time of occurrence and severity of AE, type of treatment imposed and whether there was death. Descriptive analysis was performed using means, standard deviation and frequencies of the variables of interest. RESULTS: 13,196 procedures performed, 9843 D-EUS and 3353 I-EUS. Thirty-seven (0.3%) had AE with six deaths (0.04%). The overall rate of AE for D-EUS and I-EUS was 0.08% and 0.86%, respectively (p > .05). Three deaths (0.03%) occurred after D-EUS and three (0.09%) after I-EUS. AE were immediate and early in 70% and 30%, respectively, with no late complications. Perforation was detected immediately in 80% and early in 20%, being more frequent after D-EUS than I-EUS. Acute pancreatitis occurred immediately in 70% and early in 30%. The AE were mild, moderate, and severe in 35.1%, 27%, and 37.8%, respectively. Overall, D-EUS presented the majority of AE as severe (87.5%), while I-EUS presented mild AE in most cases (41.4%), followed by severe complications (24.1%). CONCLUSIONS: Despite the low incidence of AE and mortality after EUS, the occurrence of severe complications, especially perforation in D-EUS, may support the review of therapeutic protocols, aiming to ensure that a quality and safety process is implemented in the practice of EUS.

A rare case of recurrent acute pancreatitis after EUS-FNA in a patient withpancreatic intraepithelial neoplasia type 2.

Pancreatic intraepithelial neoplasia (PanIN) is considered a pre-malignant lesion difficult to identify by imaging methods. EUSFNA is an effective technique to obtain material for histopathological study of pancreatic cystic tumors, but it is not free of adverse events. We report a case of a 56 years old patient, with chronic abdominal pain (early 1994). MRI showed pancreatic cystic images. The etiologic diagnosis was doubtful and EUS-FNA was performed. Immediately after a FNA, patient had an episode of acute pancreatitis, requiring hospitalization. During one year after FNA he had five episodes of AP. A new EUS suspected of PanIN, which was confirmed by surgery. After surgery the patient is well and has no more episodes of AP. Although the risk of AP, EUS-FNA should be performed to determine the best treatment for these patients with chronic abdominal pain who have cystic changes of pancreatic gland.

Impact of endoscopic ultrasound-guided fine-needle aspiration on incidental pancreatic cysts. A prospective study.

OBJECTIVE: Widespread use of imaging procedures has promoted a higher identification of incidental pancreatic cysts (IPCs). However, little is known as to whether endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could change the management strategy of patients having IPCs. This study has aimed to evaluate the management impact of EUS-FNA on IPCs. MATERIAL AND METHODS: Patients with pancreatic cysts (PCs) who were referred to EUS-FNA were recruited prospectively. The referring physicians were questioned about the management strategy for these patients before and after EUS-FNA. The impact of EUS-FNA on management was then evaluated. RESULTS: A total of 302 PC patients were recruited. Of these, 159 (52.6%) patients had asymptomatic IPCs. The average size was 2.3 cm (range: 0.2-7.1 cm), and 110 patients having smaller than 3 cm sized cysts. Lesions were located in the pancreatic head in 96 (61%) cases, and most patients (94%) had only a single cyst. The final diagnoses, obtained by EUS-FNA (91) and surgery (68), were 93 (58%) benign lesions, 36 (23%) cysts with malignant potential, 14 (9%) noninvasive malignancies, 10 (6%) malignant precursor lesions (PanIN), and 6 (4%) invasive malignancies. Management strategy changed significantly after EUS-FNA in 114 (71.7%) patients: 43% of the cases were referred to surgery, 44% of the patients were discharged from surveillance, and 13% of the cases were given further periodical imaging tests. CONCLUSION: EUS-FNA has a management impact in almost 72% of IPCs, with a major influence on the management strategy, either discharge rather than surgical resection or surgery rather than additional follow up.

The Frequency of Anatomical Variants of the Bile Ducts: A Review Based on a Single Classification as Support for Cholangiographic Examinations.

Complications arising from hepatobiliary surgery can have adverse effects on both the quality of life and the survival of patients. Magnetic resonance cholangiography (MRC) techniques are highly effective at revealing anatomical variants of the bile ducts and thus play a vital role in minimizing the occurrence of complications. The aims of this review are threefold: to ascertain the classifications utilized for categorizing anatomical variants of the bile ducts, to present the reported results on the prevalence of these anatomical variants, and to explore the diagnostic modalities employed to visualize these anatomical variants and associated complications during surgical procedures. A review of the literature was carried out using the Cochrane Library database and the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Google Scholar platforms. We conducted a comprehensive review of relevant studies to categorize the different anatomical variants according to the Huang classification. According to the Huang classification, our study showed type A1, 60.44%; type A2, 11.76%; type A3, 11.73%; type A4, 5.47%; type A5, 0.26%; and type B, which was identified in insignificant numbers (0.16%) or does not appear; additionally, variants that do not fit into the Huang classification have also been identified (10.18%). The Huang classification serves as an invaluable presurgical guide, aiding in the strategic planning of biliary interventions and effectively reducing the risk of iatrogenic complications, morbidity, mortality, and postoperative length of stay. MRC is still considered the noninvasive gold standard method for evaluating the bile ducts and their anatomical variations.

Extrahepatic cholestasis associated with paracoccidioidomycosis: Challenges in the differential diagnosis of biliopancreatic neoplasia.

BACKGROUND: Paracoccidioidomycosis (PCM) may involve the hepatic pedicle and peripancreatic lymph nodes, cause damage to the bile duct and manifest, exceptionally, in combination with extrahepatic cholestasis (EHC), making investigation and treatment challenging. AIM: To investigate the management of patients with visceral PCM admitted with EHC. METHODS: All patients diagnosed with PCM treated in a public, tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated. Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical, laboratory, and imaging findings, resources used for etiological diagnosis, treatment results, and prognosis. Statistical analyses were performed using the linear mixed-effects model (random and fixed effects), which was adjusted using the PROC MIXED procedure of the SAS® 9.0 software, and Fisher's exact test. RESULTS: Of 1645 patients diagnosed with PCM, 40 (2.4%) had EHC. Of these, 20 (50.0%) lived in the rural area and 29 (72.5%) were men, with a mean age of 27.1 years (3-65 years). Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients (40.0%), and a mass in the head of the pancreas was observed in 8 (20.0%). The etiological diagnosis was made by tissue collection during surgery in 4 cases (10.0%) and by endoscopic methods in 3 cases (7.5%). Twenty-seven patients (67.5%) received drug treatment alone (Group 1), whereas 13 (32.5%) underwent endoscopic and/or surgical procedures in combination with drug treatment (Group 2). EHC was significantly reduced in both groups (40.7% in Group 1, with a mean time of 3 months; and 38.4% in Group 2, with a mean time of 7.5 months), with no statistically significant difference between them. EHC recurrence rates, associated mainly with treatment nonadherence, were similar in both groups: 37% in Group 1 and 15.4% in Group 2. The mortality rate was 18.5% in Group 1 and 23% in Group 2, with survival estimates of 71.3% and 72.5%, respectively, with no statistically significant difference. CONCLUSION: Although PCM-related EHC is rare, it needs to be included in the differential diagnosis of malignancies, as timely treatment can prevent hepatic and extrahepatic sequelae.

The Safety and Cost Analysis of Outpatient Laparoendoscopy in the Treatment of Cholecystocholedocholithiasis: A Retrospective Study.

INTRODUCTION: The advantages of single-stage treatment of cholecystocholedocholithiasis are well established, but the conditions for carrying out treatment on an outpatient basis require a review of concepts and practices of medical corporations. OBJECTIVE: To evaluate the practice of treating cholecystocholedocholithiasis by laparoendoscopy on an outpatient basis with cost analysis. METHOD: A retrospective study was conducted on patients with cholecystocholedocholithiasis treated by combined laparoscopic cholecystectomy and endoscopic choledocholithotomy from January 2015 to January 2019. After collecting data from physical and digital medical records, the patients were divided into two groups-AR (n = 42)-ambulatory regimen and HR (n = 28)-hospitalization regimen-which were compared in terms of demographic, clinical and treatment variables and their results, as well as in terms of costs. RESULTS: The mean age of the AR group was lower than that of the HR group and the physical status of the AR patients was better when assessed according to the American Society of Anesthesiologists (ASA) (p = 0.01). There was no difference between groups regarding the risk of choledocholithiasis (p = 0.99). For the AR group, the length of stay was shorter: 11.29 h × 65.21 h (p = 0.02), as was the incidence of postoperative complications assessed by applying the Clavien-Dindo classification: 3 (7.1%) × 11 (39.2%) (p < 0.01). The total mean costs were higher for the HR group (USD 2489.93) than the AR group (USD 1650.98) (p = 0.02). CONCLUSION: Outpatient treatment of cholecystocholedocholithiasis by laparoendoscopy is safe and viable for most cases, has a lower cost and can support the reorientation of training and practice of hepatobiliary surgeons.

Atypical phosphatase DUSP11 inhibition promotes nc886 expression and potentiates gemcitabine-mediated cell death through NF-kB modulation.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers among all solid tumors. First-line treatment relies on gemcitabine (Gem) and despite treatment improvements, refractoriness remains a universal challenge. Attempts to decipher how feedback-loops control signaling pathways towards drug resistance have gained attention in recent years, particularly focused on the role of phosphatases. In this study, a CRISPR/Cas9-based phenotypic screen was performed to identify members from the dual-specificity phosphatases (DUSP) family potentially acting on Gem response in PDAC cells. The approach revealed the atypical RNA phosphatase DUSP11 as a potential target, whose inhibition creates vulnerability of PDAC cells to Gem. DUSP11 genetic inhibition impaired cell survival and promoted apoptosis, synergistically enhancing Gem cytotoxicity. In silico transcriptome analysis of RNA-seq data from PDAC human samples identified NF-ĸB signaling pathway highly correlated with DUSP11 upregulation. Consistently, Gem-induced NF-ĸB phosphorylation was blocked upon DUSP11 inhibition in vitro. Mechanistically, we found that DUSP11 directly impacts nc886 expression and modulates PKR-NF-ĸB signaling cascade after Gem exposure in PDAC cells resulting in resistance to Gem-induced cell death. In conclusion, this study provides new insights on DUSP11 role in RNA biology and Gem response in PDAC cells.

Clinical usefulness of tissue acquisition of pancreatic cystic lesions using an endoscopic ultrasound-guided needle for histological analysis.

Background and study aims There are rare data on the usefulness of endosonography-guided tissue acquisition (EUS-TA) in patients with pancreatic cystic lesions (PCLs). This study aimed to determine the accuracy of EUS-TA with ProCore 20G (PC20) for differentiating between mucinous neoplasia (MN) and non-MNs (n-MN) and identifying malignant PCLs, as well as its adverse events (AEs) in patients with PCLs without a classificatory diagnosis by imaging exams. Patients and methods In this observational, retrospective, single-center study, all patients with PCL who underwent EUS-TA due to diagnostic doubts in imaging studies were consecutively recruited from June 2017 to December 2021. The outcomes were to determine the diagnostic accuracy of EUS-TA with PC20 for differentiating between MN and n-MN, identifying malignant PCLs, and the AEs. Results Herein, 145 patients underwent EUS-TA, with 83 women (57.2%) and a mean age of 62.2 years. The mean size was 2.3 cm, with 81 patients (77.9%) having a PCL < 3.0 cm. The final diagnosis was made by EUS-TA (n = 81), surgery (n = 58), and follow-up (n = 6). The sensitivity, specificity, positive and negative predictive values, and accuracy for differentiating between MNs and n-MNs and identifying malignant PCLs were 92.6%, 98.4%, 98.7%, 91.3%, and 95.2% (kappa=0.9), and 92%, 99.2%, 95.8%, 98.3%, and 97.9% (kappa = 0.93), respectively. The AE rate was 2.7%, with no deaths in this cohort. Conclusions EUS-TA with PC20 has high accuracy and technical success with a low AE rate for PCL diagnosis.

mRNA Expression and Methylation of the RAD51, ATM, ATR, BRCA1, and BRCA2 Genes in Gastric Adenocarcinoma.

Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers. Objective and design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm. Methods: We evaluated mRNA expression and methylation of RAD51, ATM, ATR, BRCA1, and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features. Results: RAD51, ATR, BRCA1, BRCA2, and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR (P = .027), BRCA1 (P < .001), and BRCA2 (P < .001); ATR with BRCA1 (P = .007), and ATM (P = .001); BRCA1 with BRCA2 (P = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P = .010) and death (1.664 vs 0.929, P = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P = .032), and no significant correlation for the other markers. Conclusions: Our results suggest RAD51, BRCA1, and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR, can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.

Accuracy of endoscopic ultrasound-guided fine-needle aspiration in the suspicion of pancreatic metastases.

BACKGROUND: Metastases to the pancreas are rare, and usually mistaken for primary pancreatic cancers. This study aimed to describe the histology results of solid pancreatic tumours obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosis of metastases to the pancreas. METHODS: In a retrospective review, patients with pancreatic solid tumours and history of previous extrapancreatic cancer underwent EUS-FNA from January/1997 to December/2010. Most patients were followed-up until death and some of them were still alive at the end of the study. The performance of EUS-FNA for diagnosis of pancreatic metastases was analyzed. Symptoms, time frame between primary tumour diagnosis and the finding of metastases, and survival after diagnosis were also analyzed. RESULTS: 37 patients underwent EUS-FNA for probable pancreas metastases. Most cases (65%) presented with symptoms, especially upper abdominal pain (46%). Median time between detection of the first tumour and the finding of pancreatic metastases was 36 months. Metastases were confirmed in 32 (1.6%) cases, 30 of them by EUS-FNA, and 2 by surgery. Other 5 cases were non-metastatic. Most metastases were from lymphoma, colon, lung, and kidney. Twelve (32%) patients were submitted to surgery. Median survival after diagnosis of pancreatic metastases was 9 months, with no difference of survival between surgical and non-surgical cases. Sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA with histology analysis of the specimens for diagnosis of pancreatic metastases were, respectively, 93.8%, 60%, 93.8%, 60% and 89%. CONCLUSION: EUS-FNA with histology of the specimens is a sensitive and accurate method for definitive diagnosis of metastatic disease in patients with a previous history of extrapancreatic malignancies.

Endosonography-Guided Tissue Acquisition for Diagnosis of Squamous Carcinoma of the Pancreas: A Report of Three Cases.

While approximately 85% of neoplasms are ductal pancreatic adenocarcinomas (DPA), adenosquamous pancreatic carcinoma (APC) is a rare subtype of pancreatic cancer that exhibits aggressive behavior and poor prognosis. The authors report three cases of primary APC diagnosed through endoscopic ultrasound-guided tissue acquisition (EUS-TA) using the new ProCore 20G needle, which had been developed to improve fine-needle aspiration results by providing more tissue for histopathology. Given its ability for microcore retrieval, pancreatic stroma examination, and excellent histopathology results, EUS-TA has exhibited exceptional diagnostic yield among patients with solid pancreatic lesions. All three APC cases presented herein had been accurately diagnosed using immunohistochemistry after microcore acquisition.

Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma.

Since the incidence of gastric adenocarcinoma (GA) is high in populations living at high altitudes, we evaluated the influence of altitude on the expression of HIF-1 and survival of Ecuadorian GA patients. METHOD: 155 GA cases were studied: 56 from coastal (GAC) and 99 from mountainous regions (GAM), and 74 non-GA controls (25 coast and 49 mountain). The expression of HIF-1/HER2 was analyzed by immunohistochemistry. Analyses were performed using Fisher's exact and Breslow-Day tests for homogeneity and Kaplan-Meier curves and restricted median survival time ΔRMST. RESULTS: HIF-1 was overexpressed in normal/inflamed gastric mucosa, especially in mountainous non-GA patients (p = 0.001). There was no difference between GAC and GAM in terms of age/gender, HIF-1/HER2 expression, stage/tumor location. Median survival at 120 months was significantly higher among GAC, with a difference (ΔRMST) of 43.7 months (95% CI 29.5, 57.8) (p < 0.001) and those with positive HIF-1 expression: ΔRMST 26.6 months (95% CI 11.0, 42.1) (p < 0.001). Positive HIF-1 expression was associated with better GAM survival, with ΔRMST 33.6 months (95% CI 14.2, 52.9) (p < 0.001). CONCLUSION: Despite the limitations of this retrospective study, GA patients in the coastal region and those who expressed HIF-1 exhibited a better prognosis, but this factor was associated with better survival only in the mountain region.

Prognostic Value of the Immunohistochemical Expression of RAD51 and BRCA2 in Gastric Adenocarcinoma.

Current scientific literature lacks data on the prognostic value of the expression of RAD51 and BRCA2 in gastric adenocarcinoma. Therefore, we aimed to evaluate those and other homologous recombination-related proteins (ATM, ATR, BRCA1, CHK2, γH2AX, p53) in gastric cancer, assessing their correlation with clinical prognosis. Paraffin-embedded samples were obtained from surgical specimens collected in total or subtotal gastrectomy procedures. Between 2008 and 2017, 121 patients with advanced gastric adenocarcinoma underwent surgical resection and were included in this study. Negativity for nuclear RAD51 correlated with vascular invasion, lymph node metastasis, larger tumor size, and lower overall survival and disease-free survival in univariate analysis. However, nuclear RAD51-negative cases presented better response rates to adjuvant therapy than the positive ones. Nuclear ATR negativity correlated with larger tumor size and a higher histological grade. Positivity for ATM was associated with more prolonged disease-free survival. Positivity for nuclear BRCA2 correlated with lower overall survival and diffuse histological type, whereas its high expression was associated with vascular invasion. Nevertheless, tumors positive for nuclear BRCA2 were more frequently low grade in the intestinal histological type. Our findings indicate that RAD51 and BRCA2 are valuable immunohistochemical prognostic markers in gastric adenocarcinoma.

Influence of biliary drainage on the repair of hepatic lesions in biliary fibrosis.

BACKGROUND: Bilioduodenal (BD) and biliojejunal (BJ) derivation induce enterobiliary reflux and bile stasis. Decompression of the excluded loop of the Roux-en-Y (BJD) was proposed to minimize these effects. The aim of this study was to compare the influence of these three modalities of biliary bypass on hepatic lesion repair in rats with secondary biliary fibrosis. MATERIALS AND METHODS: Rats with 15 d of biliary obstruction underwent BD, BJ, and BJD drainage and were compared with a group submitted to simulated operation (SO) and biliary obstruction (CBO). The serum values of total and fractional bilirubin, alkaline phosphatase (ALP), and aminotransferases (AST and ALT), as well as hepatobiliointestinal excretion determined with (99m)Tc-Disida, were used for comparison. In addition, we used morphometric analyses to estimate the mass of the hepatocytes, bile ducts, and liver fibrosis. We also counted hepatic stellate cells (SC). RESULTS: For each of the three modalities of biliary drainage, there were significant reductions in bilirubin, AST, ALP, and the number of SCs. The recovery of the estimated mass of all histologic components occurred only after BJ and BJD; in the BD group, the estimated hepatocyte mass was reduced compared with the SO group. The residual hepatic radioactivity of (99m)Tc-Disida was greater in the BJD group than in the SO group. CONCLUSIONS: The interposition of the jejunal loop between the biliary tree and the intestine may slow hepatobiliary clearance of radioactivity, even though it provides the resolution of cholestasis and is effective in recovering from hepatic lesions.

The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis.

Diagnosis and treatment of pancreatic ductal adenocarcinoma (PA) remains a challenge in clinical practice. The aim of this study was to assess the role of microRNAs (miRNAs-21, -23a, -100, -107, -181c, -210) in plasma and tissue as possible biomarkers in the diagnosis of PA. Samples of plasma (PAp-n = 13), pancreatic tumors (PAt-n = 18), peritumoral regions (PPT-n = 9) were collected from patients during the surgical procedure. The control group consisted of samples from patients submitted to pancreatic surgery for trauma or cadaveric organs (PC-n = 7) and healthy volunteers donated blood (PCp-n = 6). The expression profile of microRNAs was measured in all groups using RT-PCR, serum CA19-9 levels were determined in PA and PC. In tissue samples, there was a difference in the expression of miRNAs-21, -210 (p < 0.05) across the PAt, PC and PPT groups. The PAp showed overexpression of miRNAs-181c, -210 (p < 0.05) when compared to PCp. The combination of miRNAs-21, -210 tissue expression and serum CA19-9 showed 100% accuracy in the diagnosis of PA, as well as miR-181c expression in the plasma (PApxPCp). The expression of microRNAs in plasma proved to be a promising tool for a noninvasive detection test for PA, as well as further studies will evaluate the utility of microRNAs expression as biomarkers for prognostic and response to therapy in PA.

Analysis of risk factors associated with acute pancreatitis after endoscopic papillectomy.

Acute pancreatitis (AP) is a common adverse event (AE) of endoscopic papillectomy (EP). Prophylactic plastic pancreatic stent (PPS) placement appears to prevent AP. We evaluated factors associated with post-EP AP by a retrospective analysis of patients with tumors of the duodenal papilla who underwent EP from January 2008 to November 2016 at 2 tertiary care centers. Clinical, laboratory, endoscopic ultrasound parameters, and PPS placement were evaluated. Seventy-two patients underwent EP (37 men), with mean age of 60.3 (31-88) years. Mean main pancreatic duct (MPD) diameter was 0.44 (0.18-1.8) cm. Mean tumor size was 1.8 (0.5-9.6) cm. Tumors were staged as uT1N0, uT2N0, and uT1N1 in 87.5%, 11.1%, and 1.4%. Thirty-eight AEs occurred in 33 (45.8%) patients, with no mortality. Total bilirubin, tumor size, MPD diameter, and PPS placement had odds ratios (ORs) of 0.82, 0.14, 0.00, and 6.43 for AP. Multivariate analysis (PPS placement × MPD diameter) showed ORs of 4.62 (95%CI, 1.03-21.32; p = 0.049) and 0.000 (95%CI, 0.00-0.74; p = 0.042) for AP. In conclusion, patients with jaundice, large tumors, and dilated MPD seem less likely to have post-EP AP. PPS placement was associated with a higher risk of AP, which may question its use.

Photodynamic therapy of extrahepatic cholangiocarcinoma using digital cholangioscopy.

BACKGROUND: Photodynamic therapy (PDT) of an extrahepatic cholangiocarcinoma using a digital cholangioscopy to deliver the laser. BACKGROUND: Cholangiocarcinoma is an aggressive neoplasm that usually requires palliative biliary drainage. Photodynamic therapy (PDT) has been described as a successful adjunct treatment to malignant biliary obstruction. AIM: To describe the use of digital cholangioscope to help provide laser light during biliary PDT session using locally developed light source. METHOD: Patient receives intravenous photosensitizer 24 h before the procedure. It starts with a regular duodenoscopy. After identification of the major papilla and retrograde cannulation, the digital cholangioscope is introduced into the common bile duct. Then, the cholangioscopic examination helps to identify the neoplastic stricture. Under direct visualization lighting catheter is advanced through the cholangioscope. Repositioning is recommended every centimeter to cover all strictured area. At the end of the procedure, a final cholangioscopy assesses the bile duct for the immediate result and adverse events. RESULT: This procedure was applied in one 82-year-old male due to obstructive jaundice in the last two months. EUS and ERCP revealed a severe dilation of the common bile duct associated with choledocholithiasis. Besides, was revealed dilation of hepatic duct up to a well-circumscribed hypoechoic solid mass measuring 1.8x2 cm compressing the common hepatic duct. The mass was deemed unresectable and the patient was referred for palliative treatment with PDT. He remained asymptomatic for three months. He perished due to complications 15 months after the PDT session. CONCLUSION: Digital cholangioscopy-guided biliary PDT is feasible and seems safe and effective as an adjunct modality in the palliation of extrahepatic cholangiocarcinoma.