Updated guideline on the management of common bile duct stones (CBDS)

Common bile duct stones (CBDS) are estimated to be present in 10-20% of individuals with symptomatic gallstones. They can result in a number of health problems, including pain, jaundice, infection and acute pancreatitis. A variety of imaging modalities can be employed to identify the condition, while management of confirmed cases of CBDS may involve endoscopic retrograde cholangiopancreatography, surgery and radiological methods of stone extraction. Clinicians are therefore confronted with a number of potentially valid options to diagnose and treat individuals with suspected CBDS. The British Society of Gastroenterology first published a guideline on the management of CBDS in 2008. Since then a number of developments in management have occurred along with further systematic reviews of the available evidence. The following recommendations reflect these changes and provide updated guidance to healthcare professionals who are involved in the care of adult patients with suspected or proven CBDS. It is not a protocol and the recommendations contained within should not replace individual clinical judgement

Portal Hypertension

Portal hypertension is a clinical syndrome defined by a portal venous pressure gradient, exceeding 5 mm Hg. In this book the causes of its development and complications are described. Authors have presented personal experiences on conducting patients with various displays of portal hypertension. Moreover, the book presents modern data about molecular mechanisms of pathogenesis of portal hypertension in liver cirrhosis, the information about the original predictor of risk of bleeding from gastro-esophageal varices and new methods for their conservative treatment

Sappirakon hyvän- ja pahanlaatuisten sairauksien kirurginen hoito, komplikaatiot ja hoidon tulokset

Background: Laparoscopic cholecystectomy (LCC) is one of the most common surgical procedures. Surgery involves small, but noteworthy complication risks. Malignant changes in the pathology of the gallbladder are also rare. When gallbladder surgery is so common, this aspect of surgery can have an impact on a large portion of the population. Material and Methods: The Study I was a randomized controlled trial. We investigated whether 3D laparoscopic cholecystectomy would be faster and safer than a conventional laparoscopy in day surgery patients. The primary outcome was operation time. The Study II was a retrospective cohort study in which patients had been diagnosed with severe biliary injury (BDI). We studied the success of surgical treatment as well as the quality-of-life (QOL) of patients. The Studies III and IV addressed gallbladder cancer (GBC) in a retrospective study designs. Results: The Study I included 105 and 104 patients randomized to 3D and 2D LCC groups. The 3D system did not reduce the LCC operation time (3D vs 2D; 49.0 vs 48.0 min, p=0.703). The 3D technique did not either affect complications. The Study II included 52 patients with BDI and 53 patients without complications as controls. No difference in long-term (median 90 months) QOL was observed between groups. Three patients (5.8%) died from BDI. “Primary patency” was 71%. At one and five years, the “Actuarial primary patency rate” was 58% and 53%, respectively. Patency was achieved at 83% if the reconstructive surgery was primarily performed by a liver surgeon. In the Study III, GBC was rarely found (n = 10/2034; 0.5%) in the gallbladder, which was removed for benign reasons and no cancer was found in the macroscopically normal gallbladder. In the Study IV, we found 294 patients with GBC and revealed a low and slightly declining incidence of GBC in southern Finland. The proportion of patients who underwent curative surgery was 19%, and the five-year survival after curative-intent surgery was 57%. The five-year overall survival was 12% but without surgical or oncologic treatment 1.3%. Conclusions: Cholecystectomy is a common and safe procedure when the correct surgical technique and the possibility of anatomical variations are considered. The use of a 3D laparoscopy system does not improve the safety or efficacy. If a severe bile duct injury occurs, biliary reconstruction is recommended to be performed by a hepatobiliary surgeon. In a gallbladder sample removed for a benign reason, the use of selective histopathologic examination could save a substantial amount of health care resources. The prognosis of GBC is poor. Increasing the proportion of patients undergoing curative-intent resection and adjuvant therapy, as well as the use of neoadjuvant therapy, is likely to improve the prognosis of patients with GBC.Tausta: Laparoskooppinen sappirakonpoisto on yksi tavallisimmista toimenpiteistä. Leikkaukseen liittyy pieni, mutta huomionarvoinen komplikaatioriski. Harvinaisia ovat myös pahanlaatuiset muutokset sappirakon patologisessa tutkimuksessa. Kun sappirakon poistot ovat niin tavallisia, voi tällä kirurgian osa-alueella olla vaikutusta suureen väestön osaan. Materiaali ja menetelmät: Tämän väitöskirjan ensimmäinen osatyö oli satunnaistettu kontrolloitu tutkimus. Selvitimme siinä, olisiko 3D-laparoskooppinen sappirakonpoisto nopeampi ja turvallisempi kuin 2D-laparoskoopilla tehty toimenpide päiväkirurgisilla potilailla. Päävastemuuttuja oli leikkausaika. Toinen osatyö oli retrospektiivinen kohorttitutkimus, johon osallistuneilla potilailla oli todettu vakava sappitievaurio. Tutkimme kirurgisen hoidon onnistumista sekä potilaiden elämänlaatua. Kolmas ja neljäs osatyö käsittelivät sappirakon syöpää takautuvassa tutkimusasetelmassa. Tulokset: Osatyössä I, 105 ja 104 potilasta randomoitiin 3D- ja 2D-laparoskooppisiin sappirakonpoistoihin. 3D-järjestelmä ei nopeuttanut sappirakonpoiston leikkausaikaa (3D vs. 2D; 49,0 vs. 48,0 min, p = 0,703). Komplikaatioihin ei myöskään ollut vaikutusta. Osatyöhön II otettiin 52 sappitievaurion saanutta potilasta. Verrokkeina oli 53 potilasta ilman vauriota. Potilasryhmien välillä ei havaittu eroa pitkäaikaisessa (mediaani 90 kk) elämänlaadussa. Kolme potilasta (5,8 %) kuoli sappitievaurion vuoksi. ”Primary patency”, sappiteiden aukipysyvyyden aste, oli 71 %. Yhden ja viiden vuoden kohdalla ”Actuarial primary patency rate” oli 58 % ja 53 %. Avoimuus saavutettiin 83 %:lla, jos ensisijaisen korjausleikkauksen suoritti maksakirurgi. Osatyössä III sappirakon syöpä löytyi harvoin (n = 10/2034; 0,5 %) sappirakosta, joka poistettiin hyvänlaatuisista syistä eikä makroskooppisesti normaalista sappirakosta löytynyt syöpää. Osatyössä IV löysimme 294 syöpäpotilasta ja paljastimme matalan ja hieman laskevan sappirakon syövän ilmaantuvuuden Etelä-Suomessa. Kuratiivistavoitteisesti leikattujen leikkaukseen päätyneiden potilaiden osuus oli 19 %, ja kuratiivistavoitteisen leikkauksen jälkeen viiden vuoden eloonjääminen oli 57 %. Viiden vuoden kokonaiselossaoloaika on 12 %, mutta ilman kirurgisia tai onkologisia toimia 1,3 %. Johtopäätökset: Sappirakonpoisto on tavallinen ja turvallinen toimenpide, kun huomioidaan oikea kirurginen tekniikka ja anatomisten vaihtelujen mahdollisuus. 3D-laparoskopia ei paranna sappirakonpoiston turvallisuutta tai tehokkuutta. Vakavan sappitievaurion ilmaantuessa, maksakirurgin tulisi suorittaa korjaustoimenpide. Hyvänlaatuisesta syystä poistetussa sappirakkonäytteessä selektiivisen histopatologisen tutkimuksen käytöllä voitaisiin säästää huomattava määrä terveydenhuollon resursseja. Sappirakon syövän ennuste on huono. Lisäämällä kuratiivistavoitteisten leikkausten ja adjuvanttihoitoa saavien potilaiden määrää, sekä neoadjuvanttihoidon käyttöä, voitaisiin todennäköisesti parantaa sappirakon syöpäpotilaiden ennustetta

The Molecular Pathogenesis of Cholangiocarcinoma

Introduction: Cholangiocarcinoma (CC) is a malignancy of the biliary tract. It has a dismal prognosis and complete surgical resection offers the only chance of cure. The aim of this study was to identify prognostic DNA/microRNA signatures, and to identify key targets and pathways in CC to improve treatment. Methods: We performed a retrospective study to assess the role of surgery and adjuvant therapy on the survival outcomes of patients with CC based on the experience of two institutions. We investigated the molecular pathogenesis of CC assessing DNA copy number alterations and differential miRNA expression. We used array comparative genomic hybridization (CGH) (1Mb BAC array-CGH, and 180K Oligonucleotide array-CGH) on 71 UK and 24 Thai cases CC. We performed microRNA-arrays (Agilent Human miRNA slides V3) on 34 CC and 10 normal cholangiocyte samples. Results: Survival analysis showed a statistically significant difference in survival between those resected and those receiving medical management only. Thai CC cases exhibited a lower proportion of CNA compared to UK cases. A common UK alteration was seen at 17q12, the region encoding ErbB-2. The copy number gain at 17q12 was validated using CISH and IHC for ErbB-2 expression, revealing heterogeneous expression. Copy number gain of chromosome 8q24.21-24.3 was significantly related to survival. Median survival was 14.4 months vs 28.3 months with and without the gain (p = 0.016). Thirty-eight miRNAs showed significantly different expression, including several microRNAs implicated in other malignancies, with predicted gene targets including the p53 signaling pathway and the TGF-beta signaling pathway. We identified a 4-microRNA signature that correlated with overall survival. With a median survival of 15.7 months vs 35.6 months: p = 0.00016. Conclusion: This study illustrates the genetic variability of CC, highlights several potential therapeutic targets, and identified a DNA and miRNA signature that correlated with prognosis

The Molecular Pathogenesis of Cholangiocarcinoma

Introduction: Cholangiocarcinoma (CC) is a malignancy of the biliary tract. It has a dismal prognosis and complete surgical resection offers the only chance of cure. The aim of this study was to identify prognostic DNA/microRNA signatures, and to identify key targets and pathways in CC to improve treatment. Methods: We performed a retrospective study to assess the role of surgery and adjuvant therapy on the survival outcomes of patients with CC based on the experience of two institutions. We investigated the molecular pathogenesis of CC assessing DNA copy number alterations and differential miRNA expression. We used array comparative genomic hybridization (CGH) (1Mb BAC array-CGH, and 180K Oligonucleotide array-CGH) on 71 UK and 24 Thai cases CC. We performed microRNA-arrays (Agilent Human miRNA slides V3) on 34 CC and 10 normal cholangiocyte samples. Results: Survival analysis showed a statistically significant difference in survival between those resected and those receiving medical management only. Thai CC cases exhibited a lower proportion of CNA compared to UK cases. A common UK alteration was seen at 17q12, the region encoding ErbB-2. The copy number gain at 17q12 was validated using CISH and IHC for ErbB-2 expression, revealing heterogeneous expression. Copy number gain of chromosome 8q24.21-24.3 was significantly related to survival. Median survival was 14.4 months vs 28.3 months with and without the gain (p = 0.016). Thirty-eight miRNAs showed significantly different expression, including several microRNAs implicated in other malignancies, with predicted gene targets including the p53 signaling pathway and the TGF-beta signaling pathway. We identified a 4-microRNA signature that correlated with overall survival. With a median survival of 15.7 months vs 35.6 months: p = 0.00016. Conclusion: This study illustrates the genetic variability of CC, highlights several potential therapeutic targets, and identified a DNA and miRNA signature that correlated with prognosis