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.

L-Methionine inhibits growth of human pancreatic cancer cells.

We have previously shown that L-methionine inhibits proliferation of breast, prostate, and colon cancer cells. This study extends these findings to BXPC-3 (mutated p53) and HPAC (wild-type p53) pancreatic cancer cells and explores the reversibility of these effects. Cells were exposed to L-methionine (5 mg/ml) for 7 days or for 3 days, followed by 4 days of culture without L-methionine (recovery). Cell proliferation, apoptosis, and cell cycle effects were assessed by flow cytometry after staining for Ki-67 or annexin V/propidium iodide. Cell proliferation was reduced by 31-35% after 7 days of methionine exposure; the effect persisted in BXPC-3 and HPAC cells after 4 days of recovery. Methionine increased apoptosis by 40-75% in HPAC cells, but not in BXPC-3 cells. Continuous exposure to methionine caused accumulation of BXPC-3 cells in the S phase and HPAC cells in both the G0/G1 and S phases; however, after 4 days of recovery, these effects disappeared. In conclusion, L-methionine inhibits proliferation and interferes with the cell cycle of BXPC-3 and HPAC pancreatic cancer cells; the effects on apoptosis remarkably persisted after methionine withdrawal. Apoptosis was induced only in BXPC-3 cells. Some of the differences in the effects of methionine between cell lines may be related to disparate p53 status. These findings warrant further studies on the potential therapeutic benefit of L-methionine against pancreatic cancer.

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.

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.

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.

Redefining Statin Dosage Post-Gastric Bypass: Insights from a Population Pharmacokinetics-Pharmacodynamics Link Approach.

Roux-en-Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic-pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed-effect modeling approach. A parent-metabolite model with first-order absorption, 2-compartments for SV and 1-compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL-cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low-intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post-RYGB patients to maintain a comparable response to that of non-operated subjects. Moderate-intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non-statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post-RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non-statin drugs to attain equivalent responses and mitigate potential adverse events.

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.

Effect of Roux-En-Y Gastric Bypass in the Pharmacokinetics of (R)-Carvedilol and (S)-Carvedilol.

Roux-en-Y gastric bypass is one of the most common surgical treatments for obesity due to the effective long-term weight loss and remission of associated comorbidities. Carvedilol, a third-generation ß-blocker, is prescribed to treat cardiovascular diseases. This drug is a weak base with low and pH-dependent solubility and dissolution and high permeability. As the changes in the gastrointestinal tract anatomy and physiology after roux-en-Y gastric bypass can potentially affect drug pharmacokinetics, this study aimed to assess the effect of roux-en-Y gastric bypass on the pharmacokinetics of carvedilol enantiomers. Nonobese (n = 15, body mass index < 25 kg/m2 ), obese (n = 19, body mass index ≥ 30), and post-roux-en-Y gastric bypass subjects submitted to surgery for at least 6 months (n = 19) were investigated. All subjects were administered a single oral dose of 25-mg racemic carvedilol, and blood was sampled for up to 24 hours. Plasma concentrations of (R)- and (S)-carvedilol were determined by liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax ) and the area under the plasma concentration-time curve (AUC) of (R)-carvedilol were 2- to 3-fold higher than (S)-carvedilol in all groups. Obese subjects have shown reduced Cmax of (R)- and (S)-carvedilol without changing the AUC. Post-roux-en-Y gastric bypass subjects presented a 3.5-fold reduction in the Cmax of the active (S)-carvedilol and a 1.9 reduction in the AUC from time 0 to infinity compared to nonobese subjects. The time to reach Cmax of (S)-carvedilol increased 2.5-fold in post-roux-en-Y gastric bypass subjects compared to obese or nonobese. Although the ß-blockade response was not assessed, the reduced exposure to carvedilol in subjects post-roux-en-Y gastric bypass may be clinically relevant and require dose adjustment.

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.

Chemometric optimization of salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS for the analysis of carvedilol enantiomers in human plasma: Application to clinical pharmacokinetics.

Carvedilol is a commonly used antihypertensive whose oral absorption is limited by low solubility and significant first-pass metabolism. This work aimed to apply chemometrics for the optimization of a salting-out assisted liquid-liquid extraction (SALLE) combined with LC-MS/MS to analyze carvedilol enantiomers in plasma samples. Method development and validation were driven for application in pharmacokinetic studies. Parameters that influence the efficiency of SALLE were evaluated using a fractional factorial 24-1 design with 4 factors and a central composite design was used to evaluate the optimal extraction condition. Carvedilol enantiomers and the internal standard lidocaine were separated on an Astec® Chirobiotic® V column and a mixture of methanol:ethanol (90:10, v/v) with 0.02% diethylamine and 0.18% acetic acid as mobile phase. The positive ion mode on electrospray ionization was used to monitor the transitions of m/z 407 > 100 and 235 > 86 for carvedilol enantiomers and lidocaine, respectively. Acetonitrile and ammonium acetate solution were selected for sample preparation by SALLE. Surface graphs and the desirability test were used to define the optimized SALLE conditions which resulted in 93% recovery for both carvedilol enantiomers. The method was linear in the range of 0.5 to 100 ng/mL in plasma, with a lower limit of quantification of 0.5 ng/mL. Within-run and between-run precision (as the relative standard deviation) were all < 9.74% and accuracy (as relative error) did not exceed ± 10.30%. Residual effect and matrix effect were not observed. Carvedilol enantiomers were stable in plasma under the storage, preparation, and analysis conditions. The validated method was successfully applied to analyze carvedilol in plasma samples from patients previously submitted to a Roux-en-Y gastric bypass surgery treated with a single oral dose of 25 mg racemic-carvedilol. Higher plasma concentrations were observed for (R)-(+)-carvedilol when compared to (S)-(-)-carvedilol in two patients post-bariatric surgery.

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.

EPIDEMIOLOGICAL PROFILE OF PATIENTS WITH NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING SECONDARY TO PEPTIC DISEASE IN A TERTIARY REFERRAL BRAZILIAN HOSPITAL.

BACKGROUND: Non-variceal upper gastrointestinal bleeding (NVUGIB) secondary to peptic ulcer disease is a medical digestive emergency and could be one of the most serious adverse drug reactions. OBJECTIVE: To identify the frequency of diagnosis of NVUGIB secondary to peptic ulcer disease. METHODS: Prospective and epidemiological study conducted in a tertiary referral Brazilian hospital, from July 2016 to December 2019. Upper gastrointestinal endoscopies (UGE) reports were evaluated daily. The diagnosis of NVUGIB secondary to peptic ulcer disease was defined through endoscopic findings of peptic ulcer and erosive gastric lesions, and clinical symptoms. The frequency of diagnosis of NVUGIB secondary to peptic ulcer disease was estimated through the ratio between the number of patients diagnosed and the number of patients underwent UGE in the same period. RESULTS: A total of 2,779 endoscopic reports (2,503 patients) were evaluated, and 178 patients were eligible. The total frequency of diagnosis of NVUGIB secondary to peptic ulcer disease was 7.1%. The annual frequency of diagnosis between 2017 and 2019 ranged from 9.3% to 5.7%. Most patients were men (72.8%); self-declared white (71.8%); older people (56.7%); and, had no familiar or personal history of gastrointestinal diseases (60.1%). 90% of the patients had a peptic ulcer and melena (62.8%). Patients made chronic use of low-dose aspirin (29.3%), other antiplatelet agents (21.9%) and, oral anticoagulants (11.2%); and non-steroidal anti-inflammatories use in the week a prior to the onset of clinical symptoms (25.8%). CONCLUSION: Seven in every 100 patients admitted and underwent UGE in a tertiary hospital were diagnosed with NVUGIB secondary to peptic ulcer disease.

Clinical outcomes and costs of the use of fibrin sealant in pancreaticojejunal anastomosis after pancreaticoduodenectomy: a retrospective analysis study.

OBJECTIVES: The benefits of using a fibrin sealant to reinforce the pancreaticojejunal anastomosis are still contentious, a fact that justifies the study of its effects on clinical outcomes and costs of pancreaticoduodenectomy. METHODS: Study of 62 consecutive patients submitted to pancreaticoduodenectomy, divided into two groups of 31 patients each: GWS = group with sealant and GWOS = group without sealant that were compared according to demographic, clinical, laboratory aspects, the incidence of postoperative pancreatic fistula (POPF), according to the definition of the International Study Group on Pancreatic Fistula, updated in 2016, and its postoperative complications categorized according to the Clavien classification, as well as hospital costs evaluated by the absorption costing method (with the exception of those related to medications). RESULTS: The groups were homogeneous and there were no significant differences in the postoperative clinical course or in the indicators of hospital care between them. Hard texture of pancreatic tissue was the only protective factor against the development of POPF (RR = 0.29 (95%CI:0,12-0,68); p = 0.005). Moreover, hospital costs were higher in GWS than in GWOS (p < 0.0001). CONCLUSIONS: The use of fibrin sealant to reinforce pancreaticojejunal anastomosis did not improve the clinical and healthcare outcomes and, in addition, increased hospital costs.