Search

Introduction Although sporadic non-ampullary duodenal adenomas (SNADA) are rare, with the risk of progression to cancer, they deserve therapy. Endoscopic therapy of SNADA is effective, but with the increased risk of complications, endotherapy should be performed in high-volume units. The results of endotherapy of SNADA in our unit are presented. Patients and methods A total of 97 patients with SNADA had endoscopic resection in 2005-2021 and control endoscopies between 3 and 24 months. Snare polypectomy, endoscopic mucosal resection (EMR), endoscopic band ligation (EBL) and endoloop were used (en bloc 37% and piecemeal 63%). In cases of residual/recurrent adenomas, endotherapy was repeated. Results The median size of the adenoma was 12 (5-60) mm and most polyps were sessile (25%) or flat (65%). Primary endotherapy eradicated adenomas in 57 (59%) cases. Residual and recurrence rates were 24% (n = 23) and 17% (n = 16) with successful endotherapy in 16 (70%) and 13 (81%) patients. Endotherapy was successful in 86 (89%) patients after a median (range) follow-up of 23 (1-166) months. Four out of 11 patients with failed endotherapy had surgery; seven patients were not fit for surgery. There were no disease-specific deaths or carcinoma. Eleven patients (11%) suffered from complications: perforation requiring surgery (n = 1), sepsis (n = 1), postprocedure bleeding (n = 7), cardiac arrest (n = 1) and coronary infarct (n = 1). The thirty-day mortality was zero. Colonoscopy was performed on 67 (69%) patients with neoplastic lesions in 33% patients during follow-up. Conclusions Endotherapy of SNADA is effective and safe. Repeat endotherapy in residual and recurrent adenomas is successful. Careful patient selection is mandatory.

BACKGROUND AND AIM This thesis includes two studies conducted in a paediatric and two studies conducted in an adult primary sclerosing cholangitis (PSC) population. The common denominator was endoscopic retrograde cholangiography (ERC) with brush cytology that was performed in all patients. The aims were to: i) identify the possible environmental risk factors (Study I) and report the long-term outcome (Study II) of paediatric-onset PSC, ii) compare ERC and magnetic resonance imaging with cholangiopancreatography (MRI-MRCP) in the evaluation of disease activity and severity of patients with PSC (Study III) and evaluate the role of ERC with brush cytology as screening for cholangiocarcinoma (CC) in patients with PSC (Study IV). MATERIAL AND METHODS PSC was diagnosed, followed-up (or both) in Helsinki University Hospital (HUH). Study I: 71 patients with a new diagnosis of paediatric-onset (age < 16 years) PSC, autoimmune hepatitis (AIH) or PSC-AIH (togheter autoimmune liver diseases or AILD) between 1985-2011. Two control groups were used: 1) 91 IBD patients matched for gender and age, collected from the IBD Population Registry at HUH and 2) 716 healthy subjects matched for gender, age and also place of birth at the time of AILD diagnosis, collected from the Population Registry Centre. A questionnaire of 22 items was administered. Study II: 41 patients with a new diagnosis of paediatric-onset PSC between 1993-2011. Study III: 48 patients with PSC who underwent ERC and MRI-MRCP within + 3 months for the diagnosis or the follow-up of the disease. Study IV: 261 patients with a new diagnosis of PSC (age > 18 years) between 1 January 2006 and 31 October 2011. All cholangiographic images were scored according to the modified Amsterdam PSC score. RESULTS Study I: In multivariate analysis, children ‘living with a cat in a block of flats’ had a higher risk (OR 3.6; 95% CI: 1.2-10.8) of having AILD than healthy controls, but not IBD controls. Study II: At the end of follow-up (9 years, range 2-20 years) all children were alive and no malignancy occurred. 29/33 (88%) were not transplanted; 26/29 (78%) were not cirrhotic and 3/29 (10%) were cirrhotic. 4/33 (12%) were transplanted after a median of 7.5 years; no PSC recurrence in the graft occurred. Study III: MRCP and ERC scores for IHBD were associated with alkaline phosphatase (p = 0.016 and p = 0.018, respectively) and CA19-9 level (p < 0.001 and p = 0.030, respectively); MRCP score for EHBD was also associated with CA19-9 level (p = 0.021). Finally, peribiliary enhancement detected on MRI correlated with cytology findings for both IHBD (Spearman’s rho = 0.322, SE: 0.095, p = 0.022) and EHBD (Spearman’s rho = 0.319, SE: 0.113, p = 0.025, respectively). Study IV: Most of the patients were asymptomatic (211/261; 80.8%) and had only mild changes on cholangiography (149/261; 57.1%) at time of first ERC. Follow-up was completed in 249/261 (95%). CC developed in 7 patients and biliary dysplasia in 8 patients; brush cytology was suspicious or malignant in 8 patients at time of PSC diagnosis. Advanced EHBD cholangiographic changes (HR: 1.7; 95% CI: 1.2-2.3) and alanine aminotransferase (HR: 14.2; 95% CI: 1.9-106.4) were associated with increased risk of biliary neoplasia. CONCLUSIONS An unidentified environmental risk factor (i.e., microbial) especially associated with cats may increase the risk of PSC in children. The clinical course and outcome of paediatric-onset PSC seems to be good until adulthood with a high survival rate, with no occurrence of malignancy and LT required in only a minority of patients. MRI-MRCP use in PSC follow-up seems to be low. In this respect, ERC with brush cytology is a good screening tool for detection of biliary dysplasia or neoplasia (or both) in patients with PSC. Advanced extrahepatic disease and alanine aminotransferase elevation may predict the occurrence of CC. TITLE IN FINNISH: Primaarinen sklerosoiva kolangiiitti lapsuudesta aikuisuuteen: riskitekijät, seuranta ja selviytyminen Common abstract in Finnish: Primaarinen sklerosoiva kolangiitti (PSC) on etiologialtaan tuntematon sappiteitä ahtauttava sairaus, joka voi johtaa maksakirroosiin tai sappitiesyöpään. Suurimmalla osalla PSC-potilaista on myös tulehduksellinen suolistosairaus (haavainen paksusuolentulehdus tai Crohnin tauti). Sappitiekarsinooman esiasteena pidetään sappitie-epiteelin dysplasiaa. Tässä väitöskirjatyössä tutkittiin sekä lapsi- että aikuispotilaita. Kaikille tutkituille potilaille oli tehty endoskooppinen retrogradinen kolangiografia (ERC) ja otettu harjairtosolunäyte sappiteistä. Väitöskirjatutkimuksen tavoitteina oli etsiä mahdollisia PSC:hen liittyviä ympäristötekijöitä, tutkia lapsipotilaiden selviytymistä pitkäaikaisseurannassa, vertailla ERC:tä ja magneettikolangiografiaa PSC:n aktiivisuuden seurannassa sekä arvioida ERC:n ja harjasolunäytteen merkitystä sappitiekarsinooman seulonnassa aikuisena PSC:hen sairastuneilla. Ensimmäisessä osatyössä selvitettiin kyselytutkimuksella PSC:n ympäristötekijöitä 71:ltä lapsena PSC:hen ja/tai autoimmuunihepatiittiin sairastuneelta. Mukana oli myös kaksi verrokkiryhmää. Tutkimuksessa todettiin, että mm. sisarusten lukumäärä, syntymäpaikka tai ruokailutottumukset eivät olleet yhteydessä sairastumisriskiin. Sen sijaan sairastumisriski oli 3.6-kertainen potilailla, jotka olivat asuneet rivitalossa ja joilla oli ollut kissa lemmikkinä. Toisessa osatyössä tutkittiin vuosina 1993-2011 PSC:hen sairastuneiden lasten selviytymistä pitkäaikaisseurannassa. Mukana oli 41 potilasta, joista 33 oli mukana lopullisessa analyysissä. Yhdeksällä prosentilla oli diagnoosivaiheessa maksakirroosi. Seurannan loppuvaiheessa kellään ei todettu sappitiekarsinoomaa, ja 36%:lla maksansisäisten sappiteiden PSC-muutokset olivat edenneet. Maksansiirto oli tehty 12%:lle. Kolmannessa osatyössä oli mukana 48 aikuispotilasta. Kaikille potilaille tehtiin sekä ERC että magneettikolangiografia ja todettiin, että näiden välinen korrelaatio sappitiemuutosten vaikeuden määrittämisessä oli vain kohtalainen. Kohonnut AFOS ja CA19-9 liittyivät maksan sisäisiin sappitiemuutoksiin sekä ERC:llä että magneettikolangiografialla tutkittuna. Harjasolunäytteen sytologinen löydös korreloi vain magneettikolangiografian löydöksiin. Neljännessä osatyössä tutkittiin 261 PSC:hen sairastunutta aikuispotilasta, joista suurin osa (81%) oli diagnoosivaiheessa oireettomia. ERC:ssä nähtävät sappitiemuutokset olivat lieviä 57%:lla. Seurannassa sappitiekarsinooma todettiin 7:llä potilaalla ja sappitiedysplasia 8:lla. Edenneet maksan ulkoisten sappiteiden muutokset, kohonnut ALAT, epäilyttävä sytologinen löydös ja kohonnut CEA assosioituivat sappitiekarsinooman ja dysplasian riskiin. Väitöskirjatyön johtopäätöksenä todettiin, että tuntematon ympäristötekijä (esim. kissoihin liittyvä mikrobi) voi lisätä PSC:n riskiä lapsilla. Lapsena alkaneella PSC:llä on kuitenkin hyvä ennuste ja maksansiirtoon päädytään harvoin. ERC:n ja magneettikolangiografian korrelaatio sappitiemuutosten arvioinnissa on vain kohtalainen. Magneettikolangiografian löydös korreloi sytologiseen löydökseen. ERC:n yhteydessä otettavaa harjasolunäytettä voidaan käyttää sappitiedysplasian tai karsinooman seulonnassa myös oireettomilla potilailla. Edenneet maksan ulkoisten sappiteiden PSC-muutokset ja kohonnut ALAT diagnoosivaiheessa liittyvät erityisen kohonneeseen sappitiekarsinooman riskiin.

BACKGROUND AND AIMS The natural history of paediatric onset PSC and PSC/AIH overlap syndrome is poorly known. Thus, this study was aimed at evaluating the clinical course and outcome of patients with a paediatric onset of disease. MATERIALS AND METHODS Between December 1993 and December 2011, thirty-five patients (median age at diagnosis 15 years), with confirmed PSC by cholangiography (ERC) and PSC/AIH by cholangiography and the modified score for AIH, were traced at Helsinki University Central Hospital. Clinical characteristics (symptoms and signs, associated diseases), diagnostic procedures (lab tests, liver biopsy, ERC) and long-term follow-up (mortality, liver transplantation, recurrence of the disease in the graft, malignancy) were reassessed until December 2013. RESULTS The original diagnosis was PSC in 22 children (63%) and PSC/AIH overlap syndrome in 13 (37%). At diagnosis most of the children had an insidious onset and most an associated IBD, being UC the most common form. Still, 4/35 (11%) had cirrhosis. Endoscopic retrograde cholangiography during follow-up was available for all of the patients and images showed a progression of intra-hepatic disease in 13/28 (46.4%) (p=0.0102). In the last follow-up (median 8 years), all patients were alive. Twenty-eight out of 35 patients (80%) and 13/35 patients (40%) were taken UDCA and immunosuppressive therapy, respectively; 3 patients were without treatment. Transaminases and GGT improved significantly. Four patients (11%) had undergone liver transplantation (after a median 7.5 years) and one was listed; and additional patient was transplanted because of Budd-Chiari syndrome. No difference in graft free survival was seen between patients with PSC and PSC/AIH. Three patients (two with PSC and one with PSC/AIH overlap syndrome) presented with cirrhosis. No malignancy occurred. CONCLUSION The clinical outcome of primary sclerosing cholangitis and overlap syndrome seems comparable including their progression to cirrhosis and requirement for liver transplantation. ?