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.

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.

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.

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.

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.

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.

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.

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.

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.

Endoscopic Ultrasound-Guided Fine-Needle Aspiration Microhistology in Asymptomatic and Symptomatic Pancreatic Cystic Lesions.

OBJECTIVE: This study aimed to analyze the usefulness of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) microhistology to detect malignancy in pancreatic cystic lesions (PCLs). METHODS: Patients with PCLs were identified and submitted to EUS-FNA from January 2010 to January 2017. The percentage of samples suitable for diagnostic classification by microhistology and the positive and negative likelihood ratios to detect malignancy in asymptomatic (APC) and symptomatic (SPC) PCLs were determined. RESULTS: Endoscopic ultrasound-guided fine-needle aspiration was performed in 510 patients. The resulting material was processed by microhistology and useful for diagnosis in 432 (84.2%). Clinical characteristics of APC (341) and SPC (169) revealed that APC patients were younger (P = 0.004) and had smaller PCLs (23 vs 35 mm; P < 0.001). In APC, we found more preneoplastic (38.7% vs 30.2%; P = 0.0016) and a lower number of malignant PCLs (8.2% vs 24.3%; P < 0.001). In APC and SPC, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of microhistology to detect malignancy were 71.4%, 99.7%, 95.2%, 97.5%, and 97.4% (k = 0.80) and 58.5%, 96.9%, 85.7%, 87.9%, and 87.6%, respectively. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration was technically feasible. Microhistology was especially useful to detect neoplastic or malignant PCLs in APC patients.

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 / Terapia fotodinâmica em colangiocarcinoma extra-hepático utilizando colangioscopia digital

ABSTRACT 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.

RESUMO Racional: Colangiocarcinoma é neoplasia agressiva que geralmente exige drenagem biliar paliativa. A terapia fotodinâmica (TFD) tem sido descrita como tratamento adjunto bem-sucedido para tratar obstrução biliar maligna. Objetivo: Descrever o emprego do colangioscópio digital para ajudar a fornecer luz de laser durante sessão de TFD biliar usando fonte de luz desenvolvida localmente. Método: Paciente recebe fotossensibilizador intravenoso 24 h antes do procedimento que começa com duodenoscopia regular. Após a identificação da papila principal e da canulação retrógrada, o colangioscópio digital é introduzido no ducto biliar comum. Em seguida, o exame colangioscópico ajuda a identificar a estenose neoplásica. Sob visualização direta, o cateter de iluminação avança através do colangioscópio. Reposicionamento é feito a cada centímetro. Ao final colangioscopia avalia o ducto biliar quanto ao resultado imediato e a eventos adversos. Resultado: Este procedimento foi aplicado em um homem de 82 anos devido à icterícia obstrutiva nos últimos dois meses. EUS e CPRE revelaram dilatação grave do ducto biliar comum associada à coledocolitíase. Além disso, havia dilatação do ducto hepático até massa sólida hipoecóica bem circunscrita, medindo 1,8x2 cm, comprimindo o ducto hepático comum. Ela foi considerada irressecável e paciente encaminhado para tratamento paliativo com TFD que permaneceu assintomático por três meses. Morreu devido a complicações 15 meses após a sessão de TFD. Conclusão: A TFD biliar guiada por colangioscopia digital é viável e parece segura e eficaz como modalidade auxiliar na paliação de colangiocarcinoma extra-hepático.

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.

A rare case of recurrent acute pancreatitis after EUS-FNA in a patient with pancreatic intraepithelial neoplasia type 2 / Un raro caso de pancreatitis aguda recurrente después de EUS-FNA en un paciente con neoplasia intraepitelial tipo 2

Pancreatic intraepithelial neoplasia (PanIN) is considered a pre-malignant lesion difficult to identify by imaging methods. EUS- FNA 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.

La neoplasia intraepithelial pancreática (PanIN) es considerada una lesión premaligna con dificultad diagnostica mediante métodos imagenlógicos. La EUS-FNA es una técnica efectiva para obtener material para el estudio histopatológico de tumores quísticos pancreáticos, pero no está libre de efectos adversos. Nosotros reportamos un caso de un paciente de 56 años de edad, con dolor abdominal cronico (desde 1994). En la resonancia abdominal se observó un quiste pancreático. El diagnostico etiológico fue dudoso y EUS-FNA fue realizada, después de la cual el paciente presento un cuadro de pancreatitis, requiriendo hospitalización. Durante el periodo de un año posterior a la FNA, éste presento cinco episodios de pancreatitis aguda. Un nuevo estudio ecoendoscopico dio la sospecha de PanIN, la cual se confirmó con la realización de la cirugía. Después de la cirugía quedo asintomático y sin presentar nuevos episodios de pancreatitis aguda hasta el momento. Aunque exista riego de pancreatitis aguda, la EUS-FNA debe realizarse para determinar el mejor tratamiento para pacientes con dolor abdominal crónico que tienen cambios quísticos de la glándula pancreática.

Impact of Ethnicity on Somatic Mutation Rates of Pancreatic Adenocarcinoma.

BACKGROUND/AIM: Ethnicity has an effect on survival in patients with pancreatic adenocarcinoma (PDAC), which may be reflected in the rate of somatic driver mutations. The Brazilian population represents au extensive interethnic admixture and little is known about the spectrum and rates of somatic driver mutations in Brazilian PDAC cases. MATERIALS AND METHODS: Direct sequencing of six genes in 23 PDAC cases was performed and the ancestry of patients was determined using a validated panel of ancestry-informative insertion/deletion DNA polymorphisms. RESULTS: KRAS proto-oncogene (KRAS) was the most commonly mutated gene (60%). A novel putatively pathogenic mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (c.2948T>A; p.M983K) was identified. Mutations in epidermal growth factor receptor (EGFR) (4%), PIK3CA (4%), cyclin-dependent kinase inhibitor 2A (CDKN2A) (4%) and TP53 (8%) were noted, in rates that are less frequent than those reported for other populations. Mutations of B-Raf proto-oncogene, serine/threonine kinase (BRAF) were not present. All individuals with high African ancestral component (allelic frequency, >0.45) exhibited KRAS mutations. CONCLUSION: Our results highlight the importance of the effect of ethnicity on somatic mutations in Brazilian patients with PDAC.

Different options of endosonography-guided biliary drainage after endoscopic retrograde cholangio-pancreatography failure.

AIM: To investigate the success rates of endosonography (EUS)-guided biliary drainage (EUS-BD) techniques after endoscopic retrograde cholangiopancreatography (ERCP) failure for management of biliary obstruction. METHODS: From Feb/2010 to Dec/2016, ERCP was performed in 3538 patients, 24 of whom (0.68%) suffered failure to cannulate the biliary tree. All of these patients were initially submitted to EUS-guided rendez-vous (EUS-RV) by means of a transhepatic approach. In case of failure, the next approach was an EUS-guided anterograde stent insertion (EUS-ASI) or an EUS-guided hepaticogastrostomy (EUS-HG). If a transhepatic approach was not possible or a guidewire could not be passed through the papilla, EUS-guided choledochoduodenostomy (EUS-CD) was performed. RESULTS: Patients were submitted to EUS-RV (7), EUS-ASI (5), EUS-HG (6), and EUS-CD (6). Success rates did not differ among the various EUS-BD techniques. Overall, technical and clinical success rates were 83.3% and 75%, respectively. Technical success for each technique was, 71.4%, 100%, 83.3%, and 83.3%, respectively (P = 0.81). Complications occurred in 3 (12.5%) patients. All of these cases were managed conservatively, but one patient died after rescue percutaneous transhepatic biliary drainage (PTBD). CONCLUSION: The choice of a particular EUS-BD technique should be based on patient's anatomy and on whether the guidewire could be passed through the duodenal papilla.

Influence of Roux-en-Y Gastric Bypass on the Hepatocellular Function and Bile Flow of Obese Patients Assessed by Scintigraphy with DISIDA.

BACKGROUND: Obesity is associated with nonalcoholic fatty liver disease (NAFLD), which is improved by bariatric surgery. Hepatobiliary scintigraphy with 99m.-Tc diisopropylacetanilido iminodiacetic acid (99mTc-DISIDA) has proved to be highly effective for the assessment of bile flow, representing an indirect measurement of hepatocyte and cholangiocyte function. The objective of this study was to assess the effects of Roux-en-Y gastric bypass (RYGB) on bile flow in obese subjects by hepatobiliary scintigraphy. This study was conducted in a public university hospital in Brazil. METHODS: Twenty obese patients and five nonobese patients (with no hepatic or biliary disease) were studied. The obese patients were submitted to anthropometric evaluation and biochemical exams when they arrived at the service, during the immediate preoperative period and 3, 6, and 12 months after surgery. They were also submitted to abdominal ultrasound and hepatobiliary scintigraphy with 99mTc-DISIDA during the preoperative period and 12 months after RYGB. Tmax (time of maximum marker uptake) and T1/2 (half time between peak uptake and disappearance of the marker) were determined and compared between obese patients and controls, before and after surgery. The results were compared to those obtained with an intraoperative liver biopsy. RESULTS: A weight loss of 12.2 ± 4.3 % was observed during preparation for surgery, and a loss of 30.4 ± 5.6 % was observed 1 year after RYGB. Ultrasound hepatic analysis revealed some degree of NAFLD in the operated patients. Obese patients showed a prolonged T1/2 compared to control, with a reduction to normal levels after RYGB. CONCLUSIONS: We concluded that NAFLD compromises bile excretion, a process that can be reversed by treatment with RYGB.

Personalized medicine in gastric cancer: Where are we and where are we going?

Despite improvements in adjuvant therapies for gastric cancer in recent years, the disease is characterized by high recurrence rates and a dismal prognosis. The major improvement in the treatment of recurrent or metastatic gastric cancer in recent years has been the incorporation of trastuzumab, a monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization, after the demonstrated predictive value of the overexpression and/or amplification of this receptor. Beyond HER2, other genetic abnormalities have been identified, and these mutations may be targetable by tyrosine kinase inhibitors or monoclonal antibodies. The demonstration of four distinct molecular subtypes of gastric cancer by the Cancer Genome Atlas study highlight the enormous heterogeneity of the disease and its complex interplay between genetic and epigenetic alterations and provide a roadmap to implement genome-guided personalized therapy in gastric cancer. In the present review, we aim to discuss, from a clinical point of view, the genomic landscape of gastric cancer described in recent studies, the therapeutic insights derived from these findings, and the clinical trials that have been conducted and those in progress that take into account tailored therapies for gastric cancer.