Search results for: biliary atresia
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 46

Search results for: biliary atresia

46 MiR-200a/ZEB1 Pathway in Liver Fibrogenesis of Biliary Atresia

Authors: Hai-Ying Liu, Yi-Hao Chen, Shu-Yin Pang, Feng-Hua Wang, Xiao-Fang Peng, Li-Yuan Yang, Zheng-Rong Chen, Yi Chen, Bing Zhu

Abstract:

Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

Keywords: biliary atresia, liver fibrosis, MicroRNA, epithelial-mesenchymal transition, zinc finger E-box-binding homeobox 1

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45 Early Predictive Signs for Kasai Procedure Success

Authors: Medan Isaeva, Anna Degtyareva

Abstract:

Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

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44 A Case of Umbilical Arterial Atresia in the Third Trimester of Pregnancy

Authors: Caixiu Pu, Zhen Chen

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We present the rare case of umbilical arterial atresia, leading to a good outcome and provide clinical and pathological findings. A 27-year-old nulliparous first gravida with PGDM was found single umbilical artery(SUA) by routine ultrasound san at 30 weeeks of gestation. Fetal status was monitored weekly. A healthy male newborn was delivered by cesarean section at 39 weeks. The umbilical cord was overly twisted and no thrombus was found along the whole diseased vessel. The cause of umbilical arterial atresia was unclear, and the correct diagnosis was a challenge. Expected clinical management was recommended, in which sonographic diagnosis may play a very important part.

Keywords: pregnancy, single umbilical artery, umbilical arterial atresia, prenatal diagnosis

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43 Genomic Imprinting as a Possible Epigenetic Cause of Esophageal Atresia

Authors: M. Błoch, P. Karpiński, P. Gasperowicz, R. Płoski, A. Lebioda, P. Skiba, A. Rozensztrauch, D. Patkowski, R. Śmigiel

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Introduction: The cause of the isolated form of esophageal atresia has been yet unknown. Objectives: The primary objective of this study was to indicate epigenetic factors which may play an important role in the etiopathogenesis of esophageal atresia. Methods: We recruited a group of 6 pairs of twins, among whom one of the twins developed EA. The selection of such a group for testing allows for excluding external factors (e.g., infections, drugs, toxins) as the cause of the birth defect. The analyzes were performed with the use of genetic material isolated from the whole blood and esophagus tissue of a patient with EA. The reduced representation bisulphite sequencing (RRBS) technique was used to study the change in the genomic imprinting -a change in the expression of genes, which may be the epigenetic cause of EA. Results: In the course of the analyzes, significant hypomethylation and hypermethylation regions were identified. 65 genes with probably increased expression and 65 with decreased expression were selected. These genes have not been marked in literature as possibly pathogenic in esophageal atresia. However, their participation in the pathogenesis of esophageal atresia cannot be clearly excluded. Conclusion: We suggest a role of hypomethylation or hypermethylation of selected genes as one of the possible epigenetic factors in EA pathogenesis. The use of the RRBS technique in the search for the cause of EA is pioneer research; therefore, it seems necessary to extend the research group to new patients with EA. Acknowledgment: The work was supported by the National Science Centre, Poland, under research project 2016/21/N/NZ5/01927.

Keywords: esophageal atresia, epigenetics, embryonic development, surgery, genes expression, twins

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42 Incidence of Post Endoscopic Retrograde Cholangiopancreatography Biliary Ascariasis Diagnosed on Ultrasound

Authors: Shehzad Khan, Jehangir Khan, Shah Babar, Rashid Mahmood, Rizwan Khan, Sanya Hadi

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Ascaris lumbricoides are familiar with the roundworm that causes biliary infections in humans. Nevertheless, ascariasis is primarily found in the jejunum and transferred in numerous body parts with the intake of Ascaris lumbricoides present in food and water. These study methods were implemented at the Saidu Teaching Hospital Radiology Department from December 2021 to January 2023. This study includes the participants suffering from biliary ascariasis admitted or visited Saidu Teaching Hospital in that time frame. Clinical assessment of the participants was done based on the appearance of signs and symptoms present in them. The participant's laboratory test was done to determine the level of basic body parameters. After that ultrasonography was used to diagnose the presence and appearance of worms. Endoscopic retrograde cholangiopancreatography (ERCP) was used to extract worms from biliary channels, and the incidence of post-ERCP biliary ascariasis was accessed with ultrasonography. This study's results show the presence of numerous types of worms in the biliary channels of patients. Also, the level of body parameters, for instance, neutrophil, hemoglobin, and others, were compared at the time of admission and at the time of discharge from the hospital. Furthermore, the incidence of post-ERCP biliary ascariasis was reported as 4% in females, and 1% in males, respectively.

Keywords: Ascaris, biliary, ERCP, ultrasound

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41 MRCP as a Pre-Operative Tool for Predicting Variant Biliary Anatomy in Living Related Liver Donors

Authors: Awais Ahmed, Atif Rana, Haseeb Zia, Maham Jahangir, Rashed Nazir, Faisal Dar

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Purpose: Biliary complications represent the most common cause of morbidity in living related liver donor transplantation and detailed preoperative evaluation of biliary anatomic variants is crucial for safe patient selection and improved surgical outcomes. Purpose of this study is to determine the accuracy of preoperative MRCP in predicting biliary variations when compared to intraoperative cholangiography in living related liver donors. Materials and Methods: From 44 potential donors, 40 consecutive living related liver donors (13 females and 28 males) underwent donor hepatectomy at our centre from April 2012 to August 2013. MRCP and IOC of all patients were retrospectively reviewed separately by two radiologists and a transplant surgeon.MRCP was performed on 1.5 Tesla MR magnets using breath-hold heavily T2 weighted radial slab technique. One patient was excluded due to suboptimal MRCP. The accuracy of MRCP for variant biliary anatomy was calculated. Results: MRCP accurately predicted the biliary anatomy in 38 of 39 cases (97 %). Standard biliary anatomy was predicted by MRCP in 25 (64 %) donors (100% sensitivity). Variant biliary anatomy was noted in 14 (36 %) IOCs of which MRCP predicted precise anatomy of 13 variants (93 % sensitivity). The two most common variations were drainage of the RPSD into the LHD (50%) and the triple confluence of the RASD, RPSD and LHD (21%). Conclusion: MRCP is a sensitive imaging tool for precise pre-operative mapping of biliary variations which is critical to surgical decision making in living related liver transplantation.

Keywords: intraoperative cholangiogram, liver transplantation, living related donors, magnetic resonance cholangio-pancreaticogram (MRCP)

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40 A Case Report on Anesthetic Considerations in a Neonate with Isolated Oesophageal Atresia with Radiological Fallacy

Authors: T. Rakhi, Thrivikram Shenoy

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Esophageal atresia is a disorder of maldevelopment of esophagus with or without a connection to the trachea. Radiological reviews are needed in consultation with the pediatric surgeon and neonatologist and we report a rare case of esophageal atresia associated with atrial septal defect-patent ductus arteriosus complex. A 2-day old female baby born at term, weighing 3.010kg, admitted to the Neonatal Intensive Care Unit with respiratory distress and excessive oral secretions. On examination, continuous murmur and cyanosis were seen. Esophageal atresia was suspected, after a failed attempt to pass a nasogastric tube. Chest radiograph showed coiling of the nasogastric tube and absent gas shadow in the abdomen. Echocardiography confirmed Patent Ductus Arteriosus with Atrial Septal Defect not in failure and was diagnosed with esophageal atresia with suspected fistula posted for surgical repair. After preliminary management with oxygenation, suctioning in prone position and antibiotics, investigations revealed Hb 17gms serum biochemistry, coagulation profile and C-Reactive Protein Test normal. The baby was premedicated with 5mcg of fentanyl and 100 mcg of midazolam and a rapid awake laryngoscopy was done to rule out difficult airway followed by induction with o2 air, sevo and atracurium 2 mg. Placement of a 3.5 tube was uneventful at first attempt and after confirming bilateral air entry positioned in the lateral position for Right thoracotomy. A pulse oximeter, Echocardiogram, Non-invasive Blood Pressure, temperature and a precordial stethoscope in left axilla were essential monitors. During thoracotomy, both the ends of the esophagus and the fistula could not be located after thorough search suggesting an on table finding of type A esophageal atresia. The baby was repositioned for gastrostomy, and cervical esophagostomy ventilated overnight and extubated uneventful. Absent gas shadow was overlooked and the purpose of this presentation is to create an awareness between the neonatologist, pediatric surgeons and anesthesiologist regarding variation of typing of Tracheoesophageal fistula pre and intraoperatively. A need for imaging modalities warranted for a definitive diagnosis in the presence of a gasless stomach.

Keywords: anesthetic, atrial septal defects, esophageal atresia, patent ductus arteriosus, perioperative, chest x-ray

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39 A Comparison of Outcomes of Endoscopic Retrograde Cholangiopancreatography vs. Percutaneous Transhepatic Biliary Drainage in the Management of Obstructive Jaundice from Hepatobiliary Tuberculosis: The Philippine General Hospital Experience

Authors: Margaret Elaine J. Villamayor, Lobert A. Padua, Neil S. Bacaltos, Virgilio P. Bañez

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Significance: This study aimed to determine the prevalence of Hepatobiliary Tuberculosis (HBTB) with biliary obstruction and to compare the outcomes of ERCP versus PTBD in these patients. Methodology: This is a cross-sectional study involving patients from PGH who underwent biliary drainage from HBTB from January 2009 to June 2014. HBTB was defined as having evidence of TB (culture, smear, PCR, histology) or clinical diagnosis with the triad of jaundice, fever, and calcifications on imaging with other causes of jaundice excluded. The primary outcome was successful drainage and secondary outcomes were mean hospital stay and complications. Simple logistic regression was used to identify factors associated with success of drainage, z-test for two proportions to compare outcomes of ERCP versus PTBD and t-test to compare mean hospital stay post-procedure. Results: There were 441 patients who underwent ERCP and PTBD, 19 fulfilled the inclusion criteria. 11 underwent ERCP while 8 had PTBD. There were more successful cases in PTBD versus ERCP but this was not statistically significant (p-value 0.3615). Factors such as age, gender, location and nature of obstruction, vices, coexisting pulmonary or other extrapulmonary TB and presence of portal hypertension did not affect success rates in these patients. The PTBD group had longer mean hospital stay but this was not significant (p-value 0.1880). There were no complications reported in both groups. Conclusion: HBTB comprises 4.3% of the patients undergoing biliary drainage in PGH. Both ERCP and PTBD are equally safe and effective in the management of biliary obstruction from HBTB.

Keywords: cross-sectional, hepatobiliary tuberculosis, obstructive jaundice, endoscopic retrograde cholangiopancreatography, percutaneous transhepatic biliary drainage

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38 Management of Acute Biliary Pathology at Gozo General Hospital

Authors: Kristian Bugeja, Upeshala A. Jayawardena, Clarissa Fenech, Mark Zammit Vincenti

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Introduction: Biliary colic, acute cholecystitis, and gallstone pancreatitis are some of the most common surgical presentations at Gozo General Hospital (GGH). National Institute for Health and Care Excellence (NICE) guidelines advise that suitable patients with acute biliary problems should be offered a laparoscopic cholecystectomy within one week of diagnosis. There has traditionally been difficulty in achieving this mainly due to the reluctance of some surgeons to operate in the acute setting, limited, timely access to MRCP and ERCP, and organizational issues. Methodology: A retrospective study was performed involving all biliary pathology-related admissions to GGH during the two-year period of 2019 and 2020. Patients’ files and electronic case summary (ECS) were used for data collection, which included demographic data, primary diagnosis, co-morbidities, management, waiting time to surgery, length of stay, readmissions, and reason for readmissions. NICE clinical guidance 188 – Gallstone disease were used as the standard. Results: 51 patients were included in the study. The mean age was 58 years, and 35 (68.6%) were female. The main diagnoses on admission were biliary colic in 31 (60.8%), acute cholecystitis in 10 (19.6%). Others included gallstone pancreatitis in 3 (5.89%), chronic cholecystitis in 2 (3.92%), gall bladder malignancy in 4 (7.84%), and ascending cholangitis in 1 (1.97%). Management included laparoscopic cholecystectomy in 34 (66.7%); conservative in 8 (15.7%) and ERCP in 6 (11.7%). The mean waiting time for laparoscopic cholecystectomy for patients with acute cholecystitis was 74 days – range being between 3 and 146 days since the date of diagnosis. Only one patient who was diagnosed with acute cholecystitis and managed with laparoscopic cholecystectomy was done so within the 7-day time frame. Hospital re-admissions were reported in 5 patients (9.8%) due to vomiting (1), ascending cholangitis (1), and gallstone pancreatitis (3). Discussion: Guidelines were not met for patients presenting to Gozo General Hospital with acute biliary pathology. This resulted in 5 patients being re-admitted to hospital while waiting for definitive surgery. The local issues resulting in the delay to surgery need to be identified and steps are taken to facilitate the provision of urgent cholecystectomy for suitable patients.

Keywords: biliary colic, acute cholecystits, laparoscopic cholecystectomy, conservative management

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37 The Analysis of Acute Pancreatitis Patients in a University Hospital

Authors: Adnan Sahin, Ufuk Uylas, Ercument Pasaoglu, Tarik Caga, Enver Ihtiyar, Serdar Erkasap, Ersin Ates, Fatih Yasar

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Background: In this study, it was evaluated the demographic features, etiological factors and the management of acute pancreatitis. Methods: 106 patient hospitalized due to acute pancreatitis were retrospectively examined from 1 January 2015 to 31 December 2015 in Department of General Surgery of ESOGUMF. The data of gender, signs and symptoms, etiological factors, WBC, AST, ALT, Amilase, USG and CT findings treatment options ERCP, and complications, mortality rate were analysed. Results: The mean age of patients were 58.8 (53 men and 53 women). The causes of acute pancreatitis were as follows: gallbladder stone was 89, hyperlipidemia was 5 and idiopathic were 16 patients. Severe pancreatitis was developed in 16 patients in the biliary pancreatitis group and ERCP was performed. Cholecystectomy was performed to all biliary pancreatitis group patients after acute pancreatitis subside. The mean hospital stay period was 9.33 (2-37) day. Discussion and conclusion: Severe acute pancreatitis is a mortal disease. The most common etiological cause of acute pancreatitis is biliary origin. The first line treatment modality of acute pancreatitis is medical. Cholecystectomy should be planned to the all-biliary caused acute pancreatitis patients after the attack subside. ERCP is a useful treatment modality in the case of clinical worsening and suspicion of acute cholangitis. ERCP procedure used 16 patients in our series and these patients have a good morbidity and mean hospital period is lower than the others. We suppose that ERCP procedure should be planned selectively and conservatively.

Keywords: acute pancreatitis, ERCP, morbidity, treatment

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36 Two Cases of VACTERL Association in Pregnancy with Lymphocyte Therapy

Authors: Seyed Mazyar Mortazavi, Masod Memari, Hasan Ali Ahmadi, Zhaleh Abed

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Introduction: VACTERL association is a rare disorder with various congenital malformations. The aetiology remains unknown. Combination of at least three congenital anomalies of the following criteria is required for diagnosis: vertebral defects, anal atresia, cardiac anomalies, tracheo-esophageal fistula, renal anomalies, and limb defects. Case presentation: The first case was 1-day old male neonate with multiple congenital anomalies was bore from 28 years old mother. The mother had history of pregnancy with lymphocyte therapy. His anomalies included: defects in thoracic and lumbar vertebral, anal atresia, bilateral hydronephrosis, atrial septal defect, and lower limb abnormality. Other anomalies were cryptorchidism and nasal canal narrowing. The second case was born with 32 weeks gestational age from mother with history of pregnancy with lymphocyte therapy. He had thoracic vertebral defect, cardiac anomalies and renal defect. Conclusion: diagnosis based on clinical finding is VACTERL association. Early diagnosis is very important to investigation and treatment of other coexistence anomalies. VACTERL association in mothers with history of pregnancy with lymphocyte therapy has suggested possibly of relationship between VACTERL association and this method of pregnancy.

Keywords: anal atresia, tracheo-esophageal fistula, atrial septal defect, lymphocyte therapy

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35 Biomechanical Assessment of Esophageal Elongation

Authors: Marta Kozuń, Krystian Toczewski, Sylwester Gerus, Justyna Wolicka, Kamila Boberek, Jarosław Filipiak, Dariusz Patkowski

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Long gap esophageal atresia is a congenital defect and is a challenge for pediatric surgeons all over the world. There are different surgical techniques in use to treat atresia. One of them is esophageal elongation but the optimal suture placement technique to achieve maximum elongation with low-risk complications is still unknown. The aim of the study was to characterize the process of esophageal elongation from the biomechanical point of view. Esophagi of white Pekin Duck was used as a model based on the size of this animal which is similar to a newborn (2.5-4kg). The specimens were divided into two groups: the control group (CG) and the group with sutures (SG). The esophagi of the control group were mounted in the grips of the MTS Tytron 250 testing machine and tensile test until rupture was performed. The loading speed during the test was 10mm/min. Then the SG group was tested. Each esophagus was cut into two equal parts and that were fused together using surgical sutures. The distance between both esophagus parts was 20mm. Ten both ends were mounted on the same testing machine and the tensile test with the same parameters was conducted. For all specimens, force and elongation were recorded. The biomechanical properties, i.e., the maximal force and maximal elongation, were determined on the basis of force-elongation curves. The maximal elongation was determined at the point of maximal force. The force achieved with the suture group was 10.1N±1.9N and 50.3N±11.6N for the control group. The highest elongation was also obtained for the control group: 18mm±3mm vs. 13.5mm ±2.4mm for the suture group. The presented study expands the knowledge of elongation of esophagi. It is worth emphasizing that the duck esophagus differs from the esophagus of a newborn, i.e., its wall lacks striated muscle cells. This is why the parts of animal esophagi used in the research are may characterized by different biomechanical properties in comparison with newborn tissue.

Keywords: long gap atresia treatment, esophageal elongation, biomechanical properties, soft tissue

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34 Time to Pancreatic Surgery after Preoperative Biliary Drainage in Periampullary Cancers: A Systematic Review and Meta‑Analysis

Authors: Maatouk Mohamed, Nouira Mariem, Hamdi Kbir Gh, Mahjoubi M. F., Ben Moussa M.

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Background and aim: Preoperative biliary drainage (PBD) has been introduced to lower bilirubin levels and to control the negative effects of obstructive jaundice in patients with malignant obstructive jaundice undergoing pancreaticoduodenectomy (PD). The optimal time interval between PBD and PD is still not clear. Delaying surgery by 4 to 6 weeks is the commonly accepted practice. However, delayed PD has been shown to decrease the rate of resection and adversely affect the tumor grading and prognosis. Thus, the purpose of our systematic review and meta-analysis was to evaluate the optimal period for PBD prior to PD: short or prolonged in terms of postoperative morbidity and survival outcomes. Methods: Trials were searched in PubMed, Science Direct, Google Scholar, and Cochrane Library until November 2022. Studies using PBD in patients with malignant obstructive jaundice that compared short duration group (SDG) (surgery performed within 3-4 weeks) with prolonged duration group (PDG) (at least 3-4 weeks after PBD) were included in this study. The risk of bias was assessed using the Rob v2 and Robins-I tools. The priori protocol was published in PROSPERO (ID: CRD42022381405). Results: Seven studies comprising 1625 patients (SDG 870, PDG 882) were included. All studies were non-randomized, and only one was prospective. No significant differences were observed between the SDG and PDG in mortality (OR= 0.59; 95% CI [0.30, 1.17], p=0.13), major morbidity (Chi² = 30.28, p <0.00001; I² = 87%), pancreatic fistula (Chi² = 6.61, p = 0.25); I² = 24%), post pancreatectomy haemorrhage (OR= 1.16; 95% CI [0.67, 2.01], p=0.59), positive drainage culture (OR= 0.36; 95% CI [0.10, 1.32], p=0.12), septic complications (OR= 0.78; 95% CI [0.23, 2.72], p=0.70), wound infection (OR= 0.08, p=0.07), operative time (MD= 0.21; p=0.21). Conclusion: Early surgery within 3 or 4 weeks after biliary drainage is both safe and effective. Thus, it is reasonable to suggest early surgery following PBD for patients having resectable periampullary cancers.

Keywords: preoperative biliary drainage, pancreatic cancer, pancreatic surgery, complication

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33 Endoscopic Treatment of Patients with Large Bile Duct Stones

Authors: Yuri Teterin, Lomali Generdukaev, Dmitry Blagovestnov, Peter Yartcev

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Introduction: Under the definition "large biliary stones," we referred to stones over 1.5 cm, in which standard transpapillary litho extraction techniques were unsuccessful. Electrohydraulic and laser contact lithotripsy under SpyGlass control have been actively applied for the last decade in order to improve endoscopic treatment results. Aims and Methods: Between January 2019 and July 2022, the N.V. Sklifosovsky Research Institute of Emergency Care treated 706 patients diagnosed with choledocholithiasis who underwent biliary stones removed from the common bile duct. Of them, in 57 (8, 1%) patients, the use of a Dormia basket or Biliary stone extraction balloon was technically unsuccessful due to the size of the stones (more than 15 mm in diameter), which required their destruction. Mechanical lithotripsy was used in 35 patients, and electrohydraulic and laser lithotripsy under SpyGlass direct visualization system - in 26 patients. Results: The efficiency of mechanical lithotripsy was 72%. Complications in this group were observed in 2 patients. In both cases, on day one after lithotripsy, acute pancreatitis developed, which resolved on day three with conservative therapy (Clavin-Dindo type 2). The efficiency of contact lithotripsy was in 100% of patients. Complications were not observed in this group. Bilirubin level in this group normalized on the 3rd-4th day. Conclusion: Our study showed the efficacy and safety of electrohydraulic and laser lithotripsy under SpyGlass control in a well-defined group of patients with large bile duct stones.

Keywords: contact lithotripsy, choledocholithiasis, SpyGlass, cholangioscopy, laser, electrohydraulic system, ERCP

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32 First Occurrence of Histopathological Assessment in Gadoid Deep-Fish Phycis blennoides from the Southwestern Mediterranean Sea

Authors: Zakia Alioua, Amira Soumia, Zerouali-Khodja Fatiha

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In spite of a wide variety of contaminants such as heavy metals and organic compounds in addition to the importance of extended pollution, the deep-sea and its species are not in haven and being affected through contaminants exposure. This investigation is performed in order to provide data on the presence of pathological changes in the liver and gonads of the greater forkbeard. A total of 998 specimens of the teleost fish Phycis blennoides Brünnich, 1768 ranged from 5,7 to 62,7 cm in total length, were obtained from the commercial fisheries of Algerian ports. The sampling has been carried out monthly from December 2013 to June 2015 and from January to June 2016 caught by trawlers and longlines between 75 and 600 fathoms in the coast of Algeria. Individuals were sexed their gonads, and their livers were removed and processed for light microscopy and one case of atresia was identified. In whole, overall 0,002% of the specimens presented some degree of liver steatosis. For the gastric section, 442 selected stomachs contents were observed looking for parasitic infestation and enumerate 212 nematodes. A prospecting survey for metal contaminant was performed on the liver by atomic absorption spectrophotometry analysis.

Keywords: atresia, coast of Algeria, histopathology, nematode, Phycis blennoides, steatosis

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31 Autoimmune Diseases Associated with Primary Biliary Cirrhosis: A Retrospective Study of 51 Patients

Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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30 Duplicated Common Bile Duct: A Recipe for Injury

Authors: David Armany, Matthew Allaway, Preet Gosal, Senarath Edirimanne

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A potentially devastating complication of routine laparoscopic cholecystectomy includes iatrogenic bile duct injuries, which represent a stable incidence rate of 0.3% over the past three decades. Whilst related to several relative risks such as surgeon experience and patient factors (older age, male sex), misinterpretation of biliary tree anatomy remains the most common cause, accounting for 80% of iatrogenic Common Bile Duct injuries. Whilst extremely rare, a duplicate common bile duct anomaly remains a potential variation to encounter during biliary surgery, with 30 recognised cases in the worldwide literature, of which type Vb accounts for 4. We report the case of a rare type Vb variation encountered during intra-operative laparoscopic cholecystectomy and confirmed on cholangiogram. To our knowledge, this is the first documented Type Vb case encountered in an Australian population. Given these anomalies are asymptomatic and can perpetuate iatrogenic common bile duct injuries, awareness of all subtypes is crucial. Irrevocably, preoperative Magnetic Resonance Cholangiopancreatography can help recognise these anomalies before the operating theatre; however, their widespread adoption is limited by expensive and availability.

Keywords: duplicated common bile duct, type Vb, cholecystitis, MRCP, cholangiogram, iatrogenic CBD

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29 Investigating the Post-Liver Transplant Complications and Their Management in Children Referred to the Children’s Medical Center

Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

Abstract:

Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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28 Response of First Bachelor of Medicine, Bachelor of Surgery (MBBS) Students to Integrated Learning Program

Authors: Raveendranath Veeramani, Parkash Chand, H. Y. Suma, A. Umamageswari

Abstract:

Background and Aims: The aim of this study was to evaluate students’ perception of Integrated Learning Program[ILP]. Settings and Design: A questionnaire was used to survey and evaluate the perceptions of 1styear MBBS students at the Department of Anatomy at our medical college in India. Materials and Methods: The first MBBS Students of Anatomy were involved in the ILP on the Liver and extra hepatic biliary apparatus integrating the Departments of Anatomy, Biochemistry and Hepato-biliary Surgery. The evaluation of the ILP was done by two sets of short questionnaire that had ten items using the Likert five-point grading scale. The data involved both the students’ responses and their grading. Results: A majority of students felt that the ILP was better in as compared to the traditional lecture method of teaching.The integrated teaching method was better at fulfilling learning objectives (128 students, 83%), enabled better understanding (students, 94%), were more interesting (140 students, 90%), ensured that they could score better in exams (115 students, 77%) and involved greater interaction (100 students, 66%), as compared to traditional teaching methods. Most of the students (142 students, 95%) opined that more such sessions should be organized in the future. Conclusions: Responses from students show that the integrated learning session should be incorporated even at first phase of MBBS for selected topics so as to create interest in the medical sciences at the entry level and to make them understand the importance of basic science.

Keywords: integrated learning, students response, vertical integration, horizontal integration

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27 Growth and Bone Health in Children following Liver Transplantation

Authors: Faris Alkhalil, Rana Bitar, Amer Azaz, Hisham Natour, Noora Almeraikhi, Mohamad Miqdady

Abstract:

Background: Children with liver transplantation are achieving very good survival and so there is now a need to concentrate on achieving good health in these patients and preventing disease. Immunosuppressive medications have side effects that need to be monitored and if possible avoided. Glucocorticoids and calcineurin inhibitors are detrimental to bone and mineral homeostasis in addition steroids can also affect linear growth. Steroid sparing regimes in renal transplant children has shown to improve children’s height. Aim: We aim to review the growth and bone health of children post liver transplant by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) scan and assessing if there is a clear link between poor growth and impaired bone health and use of long term steroids. Subjects and Methods: This is a single centre retrospective Cohort study, we reviewed the medical notes of children (0-16 years) who underwent a liver transplantation between November 2000 to November 2016 and currently being followed at our centre. Results: 39 patients were identified (25 males and 14 females), the median transplant age was 2 years (range 9 months - 16 years), and the median follow up was 6 years. Four patients received a combined transplant, 2 kidney and liver transplant and 2 received a liver and small bowel transplant. The indications for transplant included, Biliary Atresia (31%), Acute Liver failure (18%), Progressive Familial Intrahepatic Cholestasis (15%), transplantable metabolic disease (10%), TPN related liver disease (8%), Primary Hyperoxaluria (5%), Hepatocellular carcinoma (3%) and other causes (10%). 36 patients (95%) were on a calcineurin inhibitor (34 patients were on Tacrolimus and 2 on Cyclosporin). The other three patients were on Sirolimus. Low dose long-term steroids was used in 21% of the patients. A considerable proportion of the patients had poor growth. 15% were below the 3rd centile for weight for age and 21% were below the 3rd centile for height for age. Most of our patients with poor growth were not on long term steroids. 49% of patients had a DEXA scan post transplantation. 21% of these children had low bone mineral density, one patient had met osteoporosis criteria with a vertebral fracture. Most of our patients with impaired bone health were not on long term steroids. 20% of the patients who did not undergo a DEXA scan developed long bone fractures and 50% of them were on long term steroid use which may suggest impaired bone health in these patients. Summary and Conclusion: The incidence of impaired bone health, although studied in limited number of patients; was high. Early recognition and treatment should be instituted to avoid fractures and improve bone health. Many of the patients were below the 3rd centile for weight and height however there was no clear relationship between steroid use and impaired bone health, reduced weight and reduced linear height.

Keywords: bone, growth, pediatric, liver, transplantation

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26 Congenital Malformations in Neonate Dogs in the Sao Paulo State University Veterinary Hospital, Botucatu, Sao Paulo, Brazil

Authors: Maria Lucia G. Lourenco, Keylla H. N. P. Pereira, Viviane Y. Hibaru, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

Abstract:

Congenital malformations are organ defects due to genetic or teratogenic causes, which can lead to high mortality in dog litters. This study assessed and described the congenital malformations in newborn dogs. The study included litters attend in the São Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil. One hundred seventy-eight litters and 803 newborns were evaluated. The occurrence of litters with malformations was 24.7%, and of newborns was 6.7%. Twenty-seven different malformations were registered: anasarca, anal atresia, cleft lip, cleft palate, duplicated right ribcage, equinovarus, exencephaly, gastroschisis, hydrocephaly, lissencephaly, macroglossia, microphthalmia, mitral valve dysplasia, omphalocele, eyelid agenesis, persistent urachus, polydactyly, pulmonary hypoplasia, pulmonary valve stenosis, rectovaginal fistula, agenesis of abdominal muscles, rib hypoplasia, scoliosis, segmental aplasia of the intestines, tricuspid valve dysplasia, unilateral kidney agenesis, and vaginal atresia. 68.7% of newborns died as a result of malformations. The pure breeds with the highest chances of manifesting malformations in contrast with mixed breeds were French Bulldog, Pug, English Bulldog, Rottweiler, German Spitz, Pinscher, Pitbull, Yorkshire Terrier, and Shih-Tzu. Significant values (P<0.05) occurred in races French Bulldogs and Pugs. The causes of congenital disabilities are possibly related to hereditary genetic factors considering that the highest incidence of malformations was observed among purebreds. There as one case of exposure to a teratogenic agent, but no other mothers were exposed to such agents during pregnancy. Two cases of consanguineal breeding between siblings were reported. The mortality rate was high. Genetic breeding programs for reproduction, avoiding consanguineous mating, care in choosing parents, and avoiding maternal exposure to teratogenic agents are of utmost importance in reducing dog malformations and consequent mortality.

Keywords: congenital defects, teratogenesis, canine neonatology, newborn puppy

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25 Diagnosis of Choledocholithiasis with Endosonography

Authors: A. Kachmazova, A. Shadiev, Y. Teterin, P. Yartcev

Abstract:

Introduction: Biliary calculi disease (LCS) still occupies the leading position among urgent diseases of the abdominal cavity, manifesting itself from asymptomatic course to life-threatening states. Nowadays arsenal of diagnostic methods for choledocholithiasis is quite wide: ultrasound, hepatobiliscintigraphy (HBSG), magnetic resonance imaging (MRI), endoscopic retrograde cholangiography (ERCP). Among them, transabdominal ultrasound (TA ultrasound) is the most accessible and routine diagnostic method. Nowadays ERCG is the "gold" standard in diagnosis and one-stage treatment of biliary tract obstruction. However, transpapillary techniques are accompanied by serious postoperative complications (postmanipulative pancreatitis (3-5%), endoscopic papillosphincterotomy bleeding (2%), cholangitis (1%)), the lethality being 0.4%. GBSG and MRI are also quite informative methods in the diagnosis of choledocholithiasis. Small size of concrements, their localization in intrapancreatic and retroduodenal part of common bile duct significantly reduces informativity of all diagnostic methods described above, that demands additional studying of this problem. Materials and Methods: 890 patients with the diagnosis of cholelithiasis (calculous cholecystitis) were admitted to the Sklifosovsky Scientific Research Institute of Hospital Medicine in the period from August, 2020 to June, 2021. Of them 115 people with mechanical jaundice caused by concrements in bile ducts. Results: Final EUS diagnosis was made in all patients (100,0%). In all patients in whom choledocholithiasis diagnosis was revealed or confirmed after EUS, ERCP was performed urgently (within two days from the moment of its detection) as the X-ray operation room was provided; it confirmed the presence of concrements. All stones were removed by lithoextraction using Dormia basket. The postoperative period in these patients had no complications. Conclusions: EUS is the most informative and safe diagnostic method, which allows to detect choledocholithiasis in patients with discrepancies between clinical-laboratory and instrumental methods of diagnosis in shortest time, that in its turn will help to decide promptly on the further tactics of patient treatment. We consider it reasonable to include EUS in the diagnostic algorithm for choledocholithiasis. Disclosure: Nothing to disclose.

Keywords: endoscopic ultrasonography, choledocholithiasis, common bile duct, concrement, ERCP

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24 Vagal Nerve Stimulator as a Treatment Approach in CHARGE Syndrome: A Case Report

Authors: Roya Vakili, Lekaa Elhajjmoussa, Barzin Omidi-Shal, Kim Blake

Abstract:

Objective: The purpose of this case report is to highlight the successful treatment of a patient with Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness, (CHARGE syndrome) using a vagal nerve stimulator (VNS). Background: This is the first documented case report, to the authors' best knowledge, for a patient with CHARGE syndrome, epilepsy, autism, and postural orthostatic tachycardia syndrome (POTS) that was successfully treated with an implanted VNS therapeutic device. Methodology: The study is a case report. Results: This is the case of a 24-year-old female patient with CHARGE syndrome (non-random association of anomalies Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) and several other comorbidities including refractory epilepsy, Patent Ductus Arteriosus (PDA) and POTS who had significant improvement of her symptoms after VNS implantation. She was a VNS candidate given her longstanding history of drug-resistant epilepsy and current disposition secondary to CHARGE syndrome. Prior to VNS implantation, she experienced three generalized seizures a year and daily POTS-related symptoms. She was having frequent lightheadedness and syncope spells due to a rapid heart rate and low blood pressure. The VNS device was set to detect a rapid heart rate and send appropriate stimulation anytime the heart rate exceeded 20% of the patient’s normal baseline. The VNS device demonstrated frequent elevated heart rates and concurrent VNS release every 8 minutes in addition to the programmed events. Following VNS installation, the patient became more active, alert, and communicative and was able to verbally communicate with words she was unable to say prior. Her GI symptoms also improved, as she was able to tolerate food better orally in addition to her G and J tube, likely another result of the vagal nerve stimulation. Additionally, the patient’s seizures and POTS-related cardiac events appeared to be well controlled. She had prolonged electroencephalogram (EEG) testing, showing no significant change in epileptiform activity. Improvements in the patient’s disposition are believed to be secondary to parasympathetic stimulation, adequate heart rate control, and GI stimulation, in addition to behavioral changes and other benefits via her implanted VNS. Conclusion: VNS showed promising results in improving the patient's quality of life and managing her diverse symptoms, including dysautonomia, POTs, gastrointestinal mobility, cognitive functioning as well seizure control.

Keywords: autism, POTs, CHARGE, VNS

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23 The Role of Glyceryl Trinitrate (GTN) in 99mTc-HIDA with Morphine Provocation Scan for the Investigation of Type III Sphincter of Oddi Dysfunction (SOD)

Authors: Ibrahim M Hassan, Lorna Que, Michael Rutland

Abstract:

Type I SOD is usually diagnosed by anatomical imaging such as ultrasound, CT and MRCP. However, the types II and III SOD yield negative results despite the presence of significant symptoms. In particular, the type III is difficult to diagnose due to the absence of significant biochemical or anatomical abnormalities. Nuclear Medicine can aid in this diagnostic dilemma by demonstrating functional changes in the bile flow. Low dose Morphine (0.04mg/Kg) stimulates the tone of the sphincter of Oddi (SO) and its usefulness has been shown in diagnosing SOD by causing a delay in bile flow when compared to a non morphine provoked - baseline scan. This work expands on that process by using sublingual GTN at 60 minutes post tracer and morphine injection to relax the SO and induce an improvement in bile outflow, and in some cases show immediate relief of morphine induced abdominal pain. The criteria for positive SOD are as follows: if during the first hour of the morphine provocation showed (1) delayed intrahepatic biliary ducts tracer accumulation; plus (2) delayed appearance but persistent retention of activity in the common bile duct, and (3) delayed bile flow into the duodenum. In addition, patients who required GTN within the first hour to relieve abdominal pain were regarded as highly supportive of the diagnosis. Retrospective analysis of 85 patients (pts) (78F and 6M) referred for suspected SOD (type III) who had been intensively investigated because of recurrent right upper quadrant or abdominal pain post cholecystectomy. 99mTc-HIDA scan with morphine-provocation is performed followed by GTN at 60 minutes post tracer injection and a further thirty minutes of dynamic imaging are acquired. 30 pts were negative. 55 pts were regarded as positive for SOD and 38/55 (60%) of these patients with an abnormal result were further evaluated with a baseline 99mTc-HIDA. As expected, all 38 pts showed better bile flow characteristics than during the morphine provocation. 20/55 (36%) patients were treated by ERCP sphincterotomy and the rest were managed conservatively by medical therapy. In all cases regarded as positive for SOD, the sublingual GTN at 60 minutes showed immediate improvement in bile flow. 11/55(20%) who developed severe post-morphine abdominal pain were relieved by GTN almost instantaneously. We propose that GTN is a useful agent in the diagnosis of SOD when performing 99mTc-HIDA scan and that the satisfactory response to the sublingual GTN could offer additional information in patients who have severe pain at the time the procedure or when presenting to the emergency unit because of biliary pain. And also in determining whether a trial of medical therapy may be used before considering surgery.

Keywords: GTN, HIDA, MORPHINE, SOD

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22 Adequate Nutritional Support and Monitoring in Post-Traumatic High Output Duodenal Fistula

Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal

Abstract:

Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.

Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma

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21 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

Abstract:

Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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20 Some Changes in Biochemical Parameters of Body and Hepato-Biliary System under the Influence of Hydrazine Derivatives

Authors: G. Y. Saspugayeva, R. R. Beysenova, M. R. Khanturin, E. T. Abseitov, K. B. Massenov

Abstract:

This research is devoted to the problems of rocket fuel and impact of its derivatives on environment and living things. Hydrazine derivatives are used in different spheres, in aero-space activity, medical practice, laboratory-diagnosis practice and etc. For Kazakhstan, which has the cosmodrome "Baikonur", the problem of environmental pollution by rocket fuel and its components is important issue. An unsymmetrical dimethylhydrazine is mostly used as rocket fuel for launch vehicles which has high toxicity to humans and animals referred to the World Health Organization. The question about influence of hydrazine derivatives on human organism and ways of detoxication is very actual and requires special approaches in solving these problems. In connection with this situation, we set the goal: study the negative influence of hydrazine derivatives-hydrazine sulphur, nitrosodimethylamine (NDMA), phenylhydrazine, isonicotinic acid hydrazide (IAH) on some biochemical parameters of blood, hepatobiliary system and correction of functional damages of organism with “Salsocollin” drugs.

Keywords: isonicotinic acid hydrazide (IAH), N-nitrosodimethylamine (NDMA), AlAT-alanine aminotransferase, AsAT-aspartate aminotransaminase

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19 Autoimmune Diseases Associated to Autoimmune Hepatitis: A Retrospective Study of 24 Tunisian Patients

Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

Abstract:

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. Concomitant autoimmune disorders have been described in 30–50% of patients with AIH. The aim of our study is to determine the prevalence and the type of autoimmune disorders associated with AIH. Material and Methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for AIH. The diagnosis of AHI was based on the criteria of the revised International AIH group scoring system (IAIHG). Results: Twenty-for patients (21 women and 3 men) followed for AIH were collected. The mean age was 39 years (17-65 years). Among these patients, 11 patients(45.8%) had at least one autoimmune disease associated to AIH. These diseases were Hashimoto's thyroiditis (n = 5), Gougerot Sjogren syndrome (n=5), Primary biliary cirrhosis (n=2), Primitive sclerosant Cholangitis (n=1), Addison disease (n = 1) and systemic sclerosis (n=1). Patients were treated with corticosteroids alone or with azathioprine associated to the specific treatment of associated diseases with complete remission of AIH in 90% of cases and clinical improvement of other diseases. Conclusion: In our study, the prevalence of autoimmune diseases in AIH patients was 45.8%. These diseases were dominated by autoimmune thyroiditis and Gougerot Sjogren syndrome. The investigation of autoimmune diseases in autoimmune hepatitis must be systematic because of their frequency and the importance of adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, autoimmune thyroiditis, gougerot sjogren syndrome

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18 The Admitting Hemogram as a Predictor for Severity and in-Hospital Mortality in Acute Pancreatitis

Authors: Florge Francis A. Sy

Abstract:

Acute pancreatitis (AP) is an inflammatory condition of the pancreas with local and systemic complications. Severe acute pancreatitis (SAP) has a higher mortality rate. Laboratory parameters like the neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), and mean platelet volume (MPV) have been associated with SAP but with conflicting results. This study aims to determine the predictive value of these parameters on the severity and in-hospital mortality of AP. This retrospective, cross-sectional study was done in a private hospital in Cebu City, Philippines. One-hundred five patients were classified according to severity based on the modified Marshall scoring. The admitting hemogram, including the NLR, RDW, and MPV, was obtained from the complete blood count (CBC). Cut-off values for severity and in-hospital mortality were derived from the ROC. Association between NLR, RDW, and MPV with SAP and mortality were determined with a p-value of < 0.05 considered significant. The mean age for AP was 47.6 years, with 50.5% being male. Most had an unknown cause (49.5%), followed by a biliary cause (37.1%). Of the 105 patients, 23 patients had SAP, and 4 died. Older age, longer in-hospital duration, congestive heart failure, elevated creatinine, urea nitrogen, and white blood cell count were seen in SAP. The NLR was associated with in-hospital mortality using a cut-off of > 10.6 (OR 1.133, 95% CI, p-value 0.003) with 100% sensitivity, 70.3% specificity, 11.76% PPV and 100% NPV (AUC 0.855). The NLR was not associated with SAP. The RDW and MPV were not associated with SAP and mortality. The admitting NLR is, therefore, an easily accessible parameter that can predict in-hospital mortality in acute pancreatitis. Although the present study did not show an association of NLR with SAP nor RDW and MPV with both SAP and mortality, further studies are suggested to establish their clinical value.

Keywords: acute pancreatitis, mean platelet volume, neutrophil-lymphocyte ratio, red cell distribution width

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17 Patient-Specific Design Optimization of Cardiovascular Grafts

Authors: Pegah Ebrahimi, Farshad Oveissi, Iman Manavi-Tehrani, Sina Naficy, David F. Fletcher, Fariba Dehghani, David S. Winlaw

Abstract:

Despite advances in modern surgery, congenital heart disease remains a medical challenge and a major cause of infant mortality. Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries in pulmonary valvar atresia. Current off-the-shelf options including human and adult products have limited biocompatibility and durability, and their fixed size necessitates multiple subsequent operations to upsize the conduit to match with patients’ growth over their lifetime. Non-physiological blood flow is another major problem, reducing the longevity of these prostheses. These limitations call for better designs that take into account the hemodynamical and anatomical characteristics of different patients. We have integrated tissue engineering techniques with modern medical imaging and image processing tools along with mathematical modeling to optimize the design of cardiovascular grafts in a patient-specific manner. Computational Fluid Dynamics (CFD) analysis is done according to models constructed from each individual patient’s data. This allows for improved geometrical design and achieving better hemodynamic performance. Tissue engineering strives to provide a material that grows with the patient and mimic the durability and elasticity of the native tissue. Simulations also give insight on the performance of the tissues produced in our lab and reduce the need for costly and time-consuming methods of evaluation of the grafts. We are also developing a methodology for the fabrication of the optimized designs.

Keywords: computational fluid dynamics, cardiovascular grafts, design optimization, tissue engineering

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