Sappitieatresia : hoidon tulokset ja oman maksan toiminta

Biliary atresia (BA) is a rare, devastating disease of infancy where a fibroinflammatory process destroys the bile ducts. BA is the most common indication for childhood liver transplantation (LT). BA treatment is started with a portoenterostomy (PE) operation and adjuvant medical therapy, and continued with LT if the PE fails. The aim of this study was to investigate the incidence of BA in Finland and to evaluate the outcomes of Finnish BA patients in the era of liver transplantation, with special emphasis on the effects of treatment centralization in 2005. The occurrence and predictors for esophageal varices, the relations between liver histology and clinical outcome variables evaluated, and noninvasive follow-up tools identified. BA patients born in Finland between 1987 and 2010 were identified from the national Register of Congenital Malformations and Children s Hospital database. All hospital records were reviewed for diagnosis confirmation, associated anomalies, treatment, follow-up data, LT, and outcome. Liver biopsies taken at PE and LT were reviewed together with follow-up biopsies. BA was diagnosed in 74 children. The incidence of BA was 1:19 900 live births. Anomalies associated with laterality disorders were observed in 17 (23%) patients. Births with BA were more common in autumn-winter than in spring-summer (p=0.013). After centralization, the clearance of jaundice rate improved significantly from 29% to 73%, p=0.001. This improvement translated into increased native liver survival: before centralization the native liver survival at four years was 21% and after centralization 73% (95% confidence interval, CI 54-91%), p<0.001. Importantly, overall survival improved significantly [50% vs. 86% (95% CI 74-98%), p=0.006]. Esophageal varices were equally common after failed (64%) and successful PE (53%). After failed PE varices bled more often and appeared significantly earlier, at eight months (4-23) vs. 19 months (4-165), p=0.004. Aspartate transferase to platelet ratio index APRI over 1.0 gave 91% sensitivity and 83% specificity for esophageal varices. A native liver biopsy taken from 23 patients at a median of 4.2 years after successful PE revealed cirrhosis in 12 (52%), and cholestasis in 4 (17%). BA incidence and the associated anomaly pattern were similar to other European and North American countries. The clear improvement in results observed after treatment centralization in 2005 supports centralizing BA treatment to designated multidisciplinary teams, despite the fact that annual caseload remained internationally low. Esophageal varices are common in BA. Endoscopic surveillance could be allocated to patients with elevated serum bilirubin levels or clinical signs of portal hypertension. APRI seems a useful tool for predicting varices.Sappitieatresia (biliary atresia) on harvinainen, vakava vastasyntyneillä esiintyvä maksasairaus, jossa sappitiet tuhoutuvat, sapen virtaus estyy ja kehittyy paheneva maksan toiminnan vajaus. Sappitieatresian oireita ovat pitkittynyt keltaisuus ja vaaleat ulosteet sekä veren korkea konjugoituneen bilirubiinin pitoisuus. Ensivaiheen hoito on mahdollisimman varhainen portoenterostomialeikkaus, jossa maksanulkoisten sappiteiden arpiset jäänteet korvataan ohutsuolella ompelemalla ohutsuoli maksaporttiin. Onnistunutkaan leikkaus ei kykene pysäyttämään maksan arpeutumista täysin. Mikäli sapen virtaus ei käynnisty tai onnistuneen portoenterostomian jälkeen kehittyy vaikeaan maksasairauteen liittyviä terveysongelmia, edetään maksansiirtoon. Suomessa sappitieatresian hoito keskitettiin vuonna 2005 Helsinkiin. Tutkimuksen tarkoituksena oli selvittää sappitieatresian esiintyvyys Suomessa ja tutkia sappitieatresiapotilaiden hoidon tuloksia ja erityisesti hoidon keskittämisen vaikutuksia. Lisäksi tutkittiin oman maksan toimintaa. Suomessa vuosina 1987-2010 syntyneet sappitieatresiapotilaat etsittiin Terveyden ja Hyvinvoinnin laitoksen Epämuodostumarekisteristä ja Lastenklinikan tietokannasta. Oikea diagnoosi varmistettiin ja kerättiin hoito- ja seurantatiedot. Sekä portoenterostomialeikkauksen yhteydessä että seurannan aikana otetut maksan koepalat arvioitiin systemaattisesti. Haussa löytyi 74 sappitieatresiapotilasta, ja ilmaantuvuus oli 1:19 900 elävänä syntynyttä lasta. Potilaista 57:llä oli ainoastaan sappitieatresia ja 17:lla oli muita rakennevikoja, kuten sydänvika, pernan poikkeava rakenne tai suoliston poikkeava kiertyminen. Sappitieatresialapsia syntyi hieman enemmän syksyllä ja talvella kuin keväällä ja kesällä. Hoidon keskittämisen jälkeen hoitotulokset paranivat oleellisesti: potilaiden osuus, joilta keltaisuus hälveni kokonaan, nousi 29% - 73%, ja neljän vuoden iässä omalla maksalla elävien osuus kasvoi 21% - 73%. Mikä tärkeintä, neljän vuoden iässä elossa olevien osuus nousi 50% - 86%. Ruokatorvikohjujen verenvuotoa esiintyi vain potilailla, joilla veren bilirubiinipitoisuus oli korkea. Seurantatutkimuksena 4,2 vuoden mediaani-iässä otetuissa maksan koepaloissa puolella potilaista oli kirroositasoinen maksavaurio. Sappitieatresian esiintyvyys oli samankaltainen kuin muissa Euroopan maissa ja Pohjois-Amerikassa. Hoidon keskittäminen on parantanut hoitotuloksia oleellisesti

The critical view of safety and bile duct injuries in laparoscopic cholecystectomy : a photo evaluation study on 1532 patients

Background: Laparoscopic cholecystectomy (LCC) carries a 0.3-1.8% risk of bile duct injury (BDI). This study investigated if intraoperative photo documentation of the critical view of safety (CVS) is related to lower rates of BDIs and postoperative complications in LCC. Methods: Surgeons were instructed to take photos of the view before clipping the cystic duct and artery. Two independent raters scored the photos 0-6 using predefined criteria for CVS. Mean scores of >= 4.5 were satisfactory. Results: The study consisted of 1532 patients undergoing LCC between April 2018 and October 2019. CVS was satisfactory in 354 (23.1%), unsatisfactory in 823 (53.7%), and photos were missing in 355 (23.2%) patients. Patients with satisfactory CVS had the lowest BDI rate compared with unsatisfactory CVS or missing photos (0.3% vs. 1.0% vs. 2.3%, p = 0.012). Four major BDIs (Strasberg D-E) occurred, but none in patients with satisfactory CVS. Patients with satisfactory CVS had the lowest postoperative complication rate compared with patients with unsatisfactory CVS or without photos (4.8% vs. 7.9 vs. 9.9%, p = 0.011). Of patients with acute cholecystitis, 15.7% had satisfactory CVS, whereas 26.8% without cholecystitis had satisfactory CVS (p < 0.001). Conclusion: Intraoperative photo documentation of satisfactory CVS is associated with lower rates of BDIs and complications.Peer reviewe

INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn (INCARO) : a multicentre, open-label, randomised controlled trial - study protocol

Introduction CT is the primary imaging option for acute abdominal pain in adults. Intravenous (IV) contrast media use improves CT quality but may cause post-contrast acute kidney injury (PC-AKI). Retrospective studies show no association between reduced baseline renal function and IV contrast CT, but, to our knowledge, no data from randomised controlled trials exist. Methods and analysis The INCARO (INtravenous Contrast computed tomography versus native computed tomography in patients with acute Abdomen and impaired Renal functiOn) trial is a multicentre, open-label, parallel group, superiority, individually randomised controlled trial comparing IV contrast-enhanced CT to native CT in patients requiring emergency abdominal or body CT with impaired renal function defined as an estimated glomerular filtration rate (eGFR) of 15 to 45 mL/min/1.73 m(2). The primary outcome is a composite of all-cause mortality or renal replacement therapy (RRT) within 90 days from CT. Secondary outcomes are AKI measured by KDIGO (The Kidney Disease: Improving Global Outcomes) criteria within 72 hours from CT, organ dysfunction defined by mSOFA (modified Sequential Organ Failure Assessment) criteria after 48 hours from CT, alive and hospital-free days within 90 days after CT, and time from imaging to definitive treatment. All-cause mortality, need for RRT and renal transplant in long-term follow-up are also measured. The calculated sample size is 994 patients. Patient recruitment is estimated to take 3 years. Ethics and dissemination The Ethics Committee of Helsinki University Hospital approved the study. The findings will be disseminated in peer-reviewed academic journals.Peer reviewe

Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia

Peer reviewe

Lääkärikouluttajan erityispätevyys on suuressa suosiossa

Lääkärikouluttajan erityispätevyyden saaneet kokevat hyötyneensä prosessista, vaikka pätevyyden tuoma arvostus ei näy työpaikalla. Teoreettisen pedagogisen koulutuksen saatavuus näyttää olevan pullonkaula

Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia

The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow-up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme-linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real-time reverse-transcription PCR. Liver expression of MMP-7 and cytokeratin-7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP-7 (29-fold, p <0.001), MMP-2 (3.1-fold, p <0.001), MMP-14 (1.7-fold, p 50.007), and TIMP-1 (1.8-fold, p <0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p <0.001) in relation to controls. BA patients had 6-fold higher serum levels of MMP-7 (p <0.001), which correlated positively with hepatic MMP-7 gene (r 50.548, p 50.007) and protein (r 50.532, p 50.007) expression. Patients showed a positive correlation between biliary MMP-7 expression and Metavir fibrosis stage (r 50.605, p 50.001) and portal fibrosis grade (r 50.606, p 50.001). Neither similarly increased MMP-7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure-associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered hepatic expression of MMP-7 in the progression of liver fibrosis after successful PE and introduce a potential therapeutic target to pharmacologically extend native liver survival by inhibiting MMP-7 hyperactivity. Serum MMP-7 may be a valuable postoperative prognostic tool in BA.Peer reviewe

Clinical practice selectively follows acute appendicitis guidelines

Peer reviewe

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) : introduction and methodology

Funding Information: The Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) project was conducted by the Clinical Urology and Epidemiology (CLUE) Working Group and supported by the Academy of Finland (309387, 340957), Sigrid Jusélius Foundation and Competitive Research Funding of the Helsinki University Hospital (TYH2019321; TYH2020248). The sponsors had no role in the analysis and interpretation of the data or the manuscript preparation, review, or approval. Funding Information: KMA received a research grant from Astra Zeneca, and is consultant for Gedeon Richter, and received reimbursement for attending a scientific meeting from GSK (Tesaro Bio). RMT received reimbursement for attending a scientific meeting from Olympus. LIL, GHG, YL, RC, ALL, VJS, IEJK, PJK, RJC, RLA, KA, KMA, IB-L, MHB, JLC, SC, PJG, HAG-P, FZG, HAG, LH, MLI-K, KMJ, PKK, NK, TPK, AJK, TK, HL, AKM, BTN, TPN, CN, SMO, SP, NP, CBBR, ARR, TS, RMT, RWMV, YW, YX, LY, JH, and KAOT have no financial conflicts of interest. GHG and RC were panel members of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery. KAOT was chair of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery and panel member of the American Society of Hematology (ASH) Guideline Panel on Prevention of Venous Thromboembolism (VTE) in Surgical Hospitalized Patients. Publisher Copyright: © 2021, The Author(s).Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119Peer reviewe

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology

Background: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries.Methods: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty.Discussion: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach.Systematic review registration: PROSPERO CRD42021234119</p

Poor performance of noninvasive predictors of esophageal varices during primary prophylaxis surveillance in biliary atresia

Objective: Our objective was to analyze performance of noninvasive markers for significant esophageal varices in relation to outcomes of endoscopic surveillance and primary prophylaxis in biliary atresia (BA). Methods: This was a prospective follow-up study of a national cohort of BA patients born between 1989 and 2017, including 72 consecutive patients who underwent variceal surveillance endoscopies. The risk for developing significant varices (grade >= 2) and variceal bleeding was compared between successful (postoperative total bilirubin Results: In total, 72 patients underwent 471 endoscopies during 427 follow-up years. Among 45 successful PE patients (63%), varices appeared later [at median age 1.6 (0.7-14) vs. 0.8 (0.4-1.9) years] and bled less often [7% vs. 41%, p b 0.001 for both] than after failed PE. Liver biochemistry, stiffness, and predictive scores showed poor accuracy for the presence of significant varices. After failed PE, lowered plasma albumin concentration predicted varices with an AUROC of 0.69 (95% CI 0.52-0.85, p = 0.030). After successful PE the varices prediction rule with AUROC 0.72 (95% CI 0.64-0.79) was the most accurate predictor. Individual predictors showed no meaningful changes between the two consecutive endoscopies leading to discovery of varices. Conclusion: Accurate targeting of endoscopies based on noninvasive predictors remains difficult during primary variceal prophylaxis protocol in BA. The differing prognoses after successful and failed PE should be considered in variceal surveillance and future studies. Type of study: Diagnostic/prognosis study. (c) 2020 Elsevier Inc. All rights reserved.Peer reviewe