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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.

Prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) with knowledge of explant data is important for guiding post-LT surveillance and treatment. The RETREAT score was recently introduced for this purpose, but has not been validated outside the USA. In a retrospective single-center study of 169 consecutive patients undergoing LT in Gothenburg, through 2000-2017 (mean age 57 years, 80% men), there were 34 HCC recurrences during a median 4.6-year follow-up. The 5-year cumulative incidence of HCC recurrence was 0% with RETREAT scores of 0-1 (18%), 11-22% with scores of 2-4 (58%), and 65% with scores of 5-8 (24%). The C-statistic, as a measure of discrimination for prediction of HCC recurrence was 0.762, 0.664, 0.616, and 0.717, for the RETREAT score, Milan criteria, UCSF criteria, and post-MORAL criteria. The RETREAT score had no significant impact on patient survival after HCC recurrence (HR 1.00, P = 0.97). In conclusion, the RETREAT score provided valid predictions of post-LT HCC recurrence in a European setting, with the ability to discriminate between high, intermediate, and low risk for HCC recurrence in a clinically important way. Prognosis after recurrence did not differ according to the RETREAT score in our study.

Background Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from adjuvant therapy. We recently identified and functionally characterized a previously unknown protein that we called ASTROPRINCIN (APCN) due to its abundance in astrocytes. APCN, also annotated as FAM171A1, is found in trophoblasts of early placenta. We demonstrated that high expression levels of APCN in cancer cells induced motility and ability of invasive growth in semisolid medium. Methods We screened by immunohistochemistry a tissue microarray material from the tumors of 429 CC patients with clinical follow-up in a test series and 255 CC patients in a validation series. Results We showed that low or absent APCN expression correlates with a favorable prognosis while high APCN expression was a sign of an adverse outcome. Cox uni- and multivariable analysis revealed that elevated tumor expression of APCN constitutes a robust marker of poor prognosis independent of stage, grade, patient’s age, or gender. Conclusion Our findings demonstrate that APCN is a novel independent prognostic marker in CC and could potentially select patients for more intense postoperative adjuvant treatment and follow-up.

Thromboprophylaxis protocols in liver surgery vary greatly worldwide. Due to limited research, there is no consensus whether the administration of thromboprophylaxis should be initiated pre- or postoperatively.Patients undergoing liver resection in Helsinki University Hospital between 2014 and 2017 were reviewed retrospectively. Initiation of thromboprophylaxis was changed in the institution in the beginning of 2016 from postoperative to preoperative. Patients were classified into two groups for analyses: thromboprophylaxis initiated preoperatively (Preop-group) or postoperatively (Postop-group). The incidences of VTE and haemorrhage within 30 days of surgery were compared between these groups. Patients with permanent anticoagulation were excluded.A total of 512 patients were included to the study (Preop, n = 253, Postop, n = 259). The incidence of VTE was significantly lower in the Preop-group compared to the Postop-group (3 (1.2%) vs. 25 (9.7%), P =.0001), mainly due to a lower incidence of pulmonary embolisms in the Preop-group (3 (1.2%) vs. 24 (9.3%), P .0001). The rates of posthepatectomy haemorrhage within 30 days of surgery were similar (Preop 38 (15.0%) vs. Postop 36 (13.9%), p = .719).Initiating thromboprophylaxis preoperatively may reduce the incidence of postoperative VTE without affecting the incidence of posthepatectomy haemorrhage in patients undergoing liver resection.

Recurrent attacks of acute intermittent porphyria (AIP) result in poor quality of life and significant risks of morbidity and mortality. Liver transplantation (LT) offers a cure, but published data on outcomes after LT are limited. We assessed the pretransplant characteristics, complications, and outcomes for patients with AIP who received a transplant. Data were collected retrospectively from the European Liver Transplant Registry and from questionnaires sent to identified transplant and porphyria centers. We studied 38 patients who received transplants in 12 countries from 2002 to 2019. Median age at LT was 37 years (range, 18-58), and 34 (89%) of the patients were women. A total of 9 patients died during follow-up, and 2 patients were retransplanted. The 1-year and 5-year overall survival rates were 92% and 82%, which are comparable with other metabolic diseases transplanted during the same period. Advanced pretransplant neurological impairment was associated with increased mortality. The 5-year survival rate was 94% among 19 patients with moderate or no neuropathy at LT and 83% among 10 patients with severe neuropathy (P = 0.04). Pretransplant renal impairment was common. A total of 19 (51%) patients had a GFR < 60 mL/minute. Although few patients improved their renal function after LT, neurological impairments improved, and no worsening of neurological symptoms was recorded. No patient had AIP attacks after LT, except for a patient who received an auxiliary graft. LT is a curative treatment option for patients with recurrent attacks of AIP. Severe neuropathy and impaired renal function are common and increase the risk for poor outcomes. If other treatment options fail, an evaluation for LT should be performed early. ispartof: LIVER TRANSPLANTATION vol:27 issue:4 pages:491-501 ispartof: location:United States status: published

Background Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0–1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0–1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007–2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007–2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0–146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

Background: The population-based Finnish Cancer Registry (FCR) is an important resource for research and healthcare politics in Finland. The aim of this study was to validate the accuracy of the colorectal cancer (CRC) data within the FCR. Material and methods: FCR data are based on independent cancer report forms (CRFs) from both clinicians and pathologists. Data from patients diagnosed with CRC during a randomized, population-based CRC screening program between 2004 and 2012 were extracted from the FCR and compared to data extracted from the original clinical patient records of these individuals by two gastrointestinal surgeons. The study focused on tumour characteristics and primary treatment. Accuracy was measured by calculating Cohen's kappa coefficient (kappa), which considers the possibility of agreement by chance. Results: Altogether, 1475 patients were studied. kappa was 0.74 for stage, 0.87 for tumour location (right/left), 0.78 for a more detailed location, 0.72 for tumour histology, 0.46 for surgical removal of the primary tumour, and 0.43 for chemotherapy. Among those who underwent surgery, the radicality of surgical treatment had a kappa of 0.24. In total, 173 (12%) patients were lacking a CRF from a clinician. Conclusion: The FCR data had good accuracy regarding tumour characteristics, but poor accuracy in treatment information. The main reason for this suboptimal accuracy was missing CRFs from treating clinicians. Awareness of these findings is crucial when research and decision making is based on FCR data. Measures have since been taken to improve the completeness of FCR recording.

BACKGROUND: Hypertriglyceridemia is the third most common cause of acute pancreatitis (AP). It has been shown that hypertriglyceridemia aggravates the severity and related complications of AP; however, detailed analyses of large cohorts are contradictory. Our aim was to investigate the dose-dependent effect of hypertriglyceridemia on AP. METHODS: AP patients over 18 years old who underwent triglyceride measurement within the initial three days were included into our cohort analysis from a prospective international, multicenter AP registry operated by the Hungarian Pancreatic Study Group. Data on 716 AP cases were analyzed. Six groups were created based on the highest triglyceride level (

Background and objectives Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era. Design, setting, participants, & measurements The Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch). Results Cold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ?65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found. Conclusions We were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.

In kidney transplant recipients (KTRs), BK polyomavirus (BKPyV) replication may progress to polyomavirus-associated nephropathy (PVAN). In this retrospective study, we assessed the chemokine CXCL10 in urine and blood samples consecutively acquired from 85 KTRs who displayed different stages of BKPyV replication and eventually developed PVAN. In parallel to progression toward PVAN, CXCL10 gradually increased in blood and urine, from baseline (prior to virus replication) to BKPyV DNAuria (median increase in blood: 42.15 pg/ml, P = 0.0156), from mere DNAuria to low- and high-level BKPyV DNAemia (median increase: 52.60 and 87.26 pg/ml, P = 0.0010 and P = 0.0002, respectively) and peaked with histologically confirmed PVAN (median increase: 145.00 pg/ml, P

Background. Long cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome. Materials and Methods. Pretransplant histocompatibility tests were modernized at our laboratory in 2015, leading to significant decrease of time consumed for these enabling earlier surgery. The effects of this on kidney transplant CIT, DGF, and other clinical outcomes were studied. The study population consisted of 896 consecutive deceased donor kidney recipients, of which 442 patients received a transplant with the old crossmatch and 454 received a transplant with the new crossmatch. Results. CIT shortened from mean 20 hours 6 minutes to 15 hours 52 minutes (P

Background & Aims Gut-derived endotoxemia has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We analyzed whether endotoxemia is associated with incident advanced liver disease in the general population. Methods Serum lipopolysaccharide (LPS) was measured in 6,727 (3,455 male and 3,272 female, mean age 53.4 ± 10.9 years, mean body mass index 27.2 ± 4.5) individuals participating in the Finnish population-based health examination survey FINRISK 1997. Data were linked with electronic health registers for incident advanced liver disease (hospitalization, cancer or death related to liver disease). During a mean follow-up of 16.3 ± 3.8 years (109,282 person-years), 86 liver events occurred. Univariate and multivariate Cox regression, and Kaplan-Meier analyses were performed. Results Serum LPS predicted incident advanced liver disease with a hazard ratio per 1 SD of 1.41 (95% CI 1.24–1.59; p ≪0.001) when adjusted for age, sex, gamma-glutamyltransferase, metabolic syndrome, alcohol use, patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M, waist-hip ratio and type 2 diabetes. This association remained robustly significant in additional multivariate analyses with various levels of adjustment. The association was accentuated among carriers of the PNPLA3 risk variant. The population attributable fraction of the highest LPS tertile for liver events was 29.7%. However, LPS was not associated with all-cause mortality. Conclusion Serum LPS is associated with hospitalization, cancer or death related to liver disease in the general population, with the highest tertile potentially accounting for 30% of the risk of liver disease. Lay summary Lipopolysaccharide, a gut-derived bacterial endotoxin, has been implicated in the development of chronic liver disease, but its relevance at the population level remains unclear. We found that serum lipopolysaccharide levels were associated with incident advanced liver disease in the general population, with the highest tertile accounting for up to 30% of the risk of hospitalization, cancer or death related to liver disease., Graphical abstract Unlabelled Image, Highlights • Serum LPS was associated with incident advanced liver disease in the general population. • LPS was associated with liver-related risk of hospitalization, cancer or death. • The highest LPS tertile may account for up to 30% of the risk of incident liver disease. • The risk of liver disease was accentuated among carriers of the PNPLA3 I143M. • Serum LPS was not associated with all-cause mortality.

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.

Background Resection of colorectal cancer (CRC) metastases provides good survival but is probably underused in real-world practice. Methods A prospective Finnish nationwide study enrolled treatable metastatic CRC patients. The intervention was the assessment of resectability upfront and twice during first-line therapy by the multidisciplinary team (MDT) at Helsinki tertiary referral centre. The primary outcome was resection rates and survival. Findings In 2012–2018, 1086 patients were included. Median follow-up was 58 months. Multiple metastatic sites were present in 500 (46%) patients at baseline and in 820 (76%) during disease trajectory. In MDT assessments, 447 (41%) were classified as resectable, 310 (29%) upfront and 137 (18%) after conversion therapy. Six-hundred and ninety curative intent resections or local ablative therapies (LAT) were performed in 399 patients (89% of 447 resectable). Multiple metastasectomies for multisite or later developing metastases were performed in 148 (37%) patients. Overall, 414 liver, 112 lung, 57 peritoneal, and 107 other metastasectomies were performed. Median OS was 80•4 months in R0/1-resected (HR 0•15; CI95% 0•12–0•19), 39•1 months in R2-resected/LAT (0•39; 0•29–0•53) patients, and 20•8 months in patients treated with “systemic therapy alone” (reference), with 5-year OS rates of 66%, 40%, and 6%, respectively. Interpretation Repeated centralized MDT assessment in real-world metastatic CRC patients generates high resectability (41%) and resection rates (37%) with impressive survival, even when multisite metastases are present or develop later. Funding The funders had no role in the study design, analysis, and interpretation of the data or writing of this report. Tiivistelmä Tausta Kolorektaalisyövän etäpesäkkeiden leikkaushoitoa käytetään todennäköisesti liian vähän tosielämän hoidoissa. Menetelmät RAXO on maanlaajuinen suomalainen tosielämän prospektiivinen interventiotutkimus, joka rekrytoi lääkehoitokuntoisia, levinnyttä suolistosyöpää sairastavia potilaita. Tutkimuksessa arvioitiin keskitetysti etäpesäkkeiden leikattavuutta levinneen syövän toteamisvaiheessa ja kahdesti ensilinjan hoidon aikana Helsingin yliopistollisen sairaalan moniammatillisessa hoitokokouksessa. Tulokset Vuosina 2012-2018 tutkimukseen otettiin 1086 potilasta. Mediaaniseuranta-aika oli 58 kuukautta. Usean elimen etäpesäkkeet todettiin 500:lla (46 %) levinneen syövän toteamisvaiheessa ja 820:lla (76 %) seurannan aikana. Moniammatillisessa arvioinnissa 447 luokiteltiin leikattavaksi 310 (29%) toteamisvaiheessa ja 137 (18%) konversiohoidon jälkeen. Kuusisataayhdeksänkymmentä etäpesäkekirurgista ja/tai paikallishoitotoimenpidettä tehtiin 399 potilaalle (89 % 447:sta), joista parantavalla tavoitteella R0/1-resektio 326 potilaalle ja R2-resektio ja/tai paikallistoimenpide 73:lle. Useita toimenpiteitä tehtiin 148 (37%) potilaalle useamman elimen etäpesäkkeiden tai uusien etäpesäkekohtien ilmentymisen takia. Kaiken kaikkiaan tehtiin 414 maksa-, 112 keuhko-, 57 peritoneaalikarsinoosi- ja 107 muuta toimenpidettä. Mediaanielinaika oli 80,4 kuukautta R0/1-resekoiduilla potilailla (HR 0,15; 95 % luottamusväli 0,12–0,19), 39,1 kuukautta R2-resekoiduilla/paikallishoidetuilla (0,39; 0,29–0,53), ja 20,8 kuukautta vain lääkehoitoa saaneilla (referenssi), ja vastaavat viiden vuoden elossaololuvut olivat 66%, 40% ja 6%. Merkitys Keskitetyllä, toistetulla moniammatillisella toiminnalla saavutetaan korkea arvio etäpesäkkeiden leikattavuudesta (41%). Etäpesäkkeiden leikkaus- ja/tai paikallishoito toteutuu 37 prosentilla erinomaisin tuloksin silloinkin, kun syöpä on levinnyt useaan elimeen sairauden toteamisvaiheessa tai sen aikana Tuki Tutkimuksen tukijat eivät osallistuneet tutkimussuunnitelman kirjoittamiseen, datan analysointiin tai tulkintaan, eivätkä tämän raportin kirjoittamiseen. Abstrakt Bakgrund Resektion av kolorektalcancermetastaser ger god överlevnad, men används troligen suboptimalt i normal praktik. Metod RAXO-studien är en prospektiv finsk studie som inkluderade behandlingsbara patienter med spridd kolorektalcancer. Studiens intervention utvärderade möjligheten till metastasoperation vid centraliserad multidisciplinär konferens (MDK) på Helsingfors universitetssjukhus vid behandlingsinitiering och två gånger under första linjens behandling. Det primära syftet var att undersöka resekabilitet och resektioner, samt överlevnad. Fynd 1086 patienter inkluderades 2012-2018. Medianuppföljningstiden var 58 månader. Multipel metastasering sågs hos 500 (46%) av patienterna vid metastasdiagnostidpunkten och hos 820 (76%) under uppföljningen. I MDK-utvärderingen klassificerades 447 (41%) som operabla, varav 310 (29%) vid metastastasdiagnos och 137 (18%) efter konversionsbehandling. Sexhundranittio åtgärder gjordes hos 399 patienter (89% av de 447 operabla), med R0/1-resektion hos 326 och R2-resektion eller lokalbehandling hos 73. Flera åtgärder gjordes hos 148 (37%) patienter med multipla metastasorgan eller nya metastaslokaler under uppföljningen; totalt 414 lever-, 112 lung-, 57 peritoneal-, och 107 andra åtgärder. Medianöverlevnaden var 80,4 månader hos R0/1-opererade (HR 0,15; 95% konfidensintervall 0,12–0,19), 39,1 månader hos R2-opererade/lokalbehandlade (0,39; 0,29–0,53) och 20,8 månader hos ”enbart systembehandlade” (referens), och femårsöverlevnaden var 66%, 40% och 6% i respektive grupp. Betydelse Upprepad centraliserad MDK-utvärdering vid spridd kolorektalcancer visar att 41% av metastaserna någon gång bedöms som resekabla och att operation och/eller lokalbehandling är möjlig i 37% av fallen. Imponerande överlevnad ses även i fall med multipla metastaslokaler vid diagnostillfället eller under uppföljningen. Finansiering Finansiärerna hade ingen roll i utformningen av denna studie, i dataanalys, tolkning av data eller i skrivandet av denna forskningsrapport. publishedVersion

Background Longer duration from symptom onset is associated with increased risk of perforation in appendicitis. In previous studies, in-hospital delay to surgery has had conflicting effects on perforation rates. Although preoperative antibiotics have been shown to reduce postoperative infections, there are no data showing that administration of antibiotics while waiting for surgery has any benefits. The aims of this study are to evaluate the role of both in-hospital delay to surgery and antibiotic treatment while waiting for surgery on the rate of appendiceal perforation. Methods This prospective, open-label, randomized, controlled non-inferiority trial compares the in-hospital delay to surgery of less than 8 hours versus less than 24 hours in adult patients with predicted uncomplicated acute appendicitis. Additionally, participants are randomized either to receive or not to receive antibiotics while waiting for surgery. The primary study endpoint is the rate of perforated appendicitis discovered during appendicectomy. The aim is to randomize 1800 patients, that is estimated to give a power of 90 per cent (χ2) for the non-inferiority margin of 5 percentage points for both layers (urgency and preoperative antibiotic). Secondary endpoints include length of hospital stay, 30-day complications graded using Clavien–Dindo classification, preoperative pain, conversion rate, histopathological diagnosis and Sunshine Appendicitis Grading System classification. Discussion There are no previous randomized controlled studies for either in-hospital delay or preoperative antibiotic treatment. The trial will yield new level 1 evidence. EU Clinical Trials Register, EudraCT Number: 2019–002348-26; registration number: NCT04378868 (http://www.clinicaltrials.gov), Study protocol for a randomized non-inferiority trial (PERFECT). The aims of this study are to evaluate the role of in-hospital delay to surgery and antibiotic treatment whilst waiting for surgery on the rate of appendiceal perforation.

Supplemental digital content is available in the text., BACKGROUND Acute mesenteric ischemia (AMI) is a disease with high mortality and requires a multidisciplinary approach for effective management. A pathway and care bundle were developed and implemented with the objective to reduce mortality. The aim of this retrospective comparative study was to analyze the effects of the pathway on patient management and outcome. METHODS All consecutive patients operated in a secondary and tertiary referral center because of occlusive arterial AMI were identified between 2014 and April 2020. The pathway aimed to increase overall awareness, and hasten and improve diagnostics and management. Patients treated before implementation of the pathway (pregroup, years 2014–2017) were compared with patients treated using the pathway (postgroup, May 2018 to April 2020). Univariate and multivariate analyses were used to compare the groups. RESULTS There were 78 patients in the pregroup and 67 patients in the postgroup with comparable baseline characteristics and disease acuity. The postgroup was more often diagnosed with contrast-enhanced computed tomography (58 [74%] vs. 63 [94%], p = 0.001) and had shorter mean in-hospital delay to operating room (7 hours [interquartile range, 3.5–12.5] vs. 3 hours [interquartile range, 2–11], p = 0.023). Revascularization was done more often in the postgroup (53 [68%] vs. 56 [84%], p = 0.030) especially using endovascular treatment (26 [33%] vs. 43 [64%], p < 0.001). Thirty-day mortality was lower in the postgroup (23 [51%] vs. 17 [25%], p = 0.001). Being managed in the postgroup remained as a protective factor (odds ratio, 0.32; 95% confidence interval, 0.14–0.75; p = 0.008) for 30-day mortality in the multivariate analysis. CONCLUSION Implementing a pathway and care bundle resulted in enhanced regional and in-hospital awareness of AMI, more appropriate computed tomography imaging, shorter in-hospital delays, increased number of revascularizations, and, hence, lower mortality. LEVEL OF EVIDENCE Therapeutic/Care Management, level IV.

BACKGROUND & AIMS While several anthropometric measures predict liver disease, the waist-hip ratio (WHR) has shown superiority in previous studies. We analysed independent and joint associations of waist circumference (WC) and hip circumference (HC) with liver disease and liver-related risk factors. METHODS Cross-sectional study (n = 6619) and longitudinal cohort (n = 40 923) comprised individuals from Health 2000 and FINRISK 1992-2012 studies. Prevalent and viral liver diseases were excluded. Longitudinal cohort was linked with national healthcare registers for severe incident liver disease. Linear regression and Cox proportional hazards models were used to analyse anthropometric, lifestyle, metabolic and bioimpedance-related parameters; liver enzymes; and 59 liver-related genetic risk variants. RESULTS WC and HC showed independent and opposite associations with both liver enzymes and incident liver disease among men (HR for liver disease: WC, 1.07, 95% CI 1.03-1.11; HC, 0.96, 95% CI 0.92-0.99; P-range .04 to

Introduction Gallbladder cancer (GBC) is a rare malignancy in Western population with poor prognosis. This study aimed to investigate the trends in GBC incidence, treatment pattern, and survival in Finland. Methods Patients diagnosed with primary GBC in a geographically defined area (Southern Finland Regional Cancer Center) during 2006-2017 were identified. Results Final cohort included 270 patients with GBC. The incidence was 1.32/100,000 persons, and it decreased 6.8 cases per million personyears during the study period. One hundred fifty-one (56%) patients were diagnosed at Stage IV. Fifty-one patients (19%) underwent curative-intent resection with 96% R0-resection rate. The median overall survival was 7.1 months and 5-year overall survival 11.6% for all patients, and 67.7 months and 56.8% after curative-intent resection, respectively. No improvement was noted over time in overall survival in patients with GBC, or in subgroups of different stages of GBC. Conclusions The incidence of GBC is slightly decreasing in Southern Finland, but survival has not improved over time.

Supplemental Digital Content is available in the text., Background. Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3–4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T). Methods. DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15–0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis). Results. Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients. Conclusions. In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant.

The incidence and medical costs of acute pancreatitis (AP) are on the rise, and severe cases still have a 30% mortality rate. We aimed to evaluate hypoalbuminemia as a risk factor and the prognostic value of human serum albumin in AP. Data from 2461 patients were extracted from the international, prospective, multicentre AP registry operated by the Hungarian Pancreatic Study Group. Data from patients with albumin measurement in the first 48 h (n = 1149) and anytime during hospitalization (n = 1272) were analysed. Multivariate binary logistic regression and Receiver Operator Characteristic curve analysis were used. The prevalence of hypoalbuminemia (

Background Previous research on parastomal hernia repair following ileal conduit urinary diversion is limited. This nationwide cohort study aims to present the results of keyhole and Sugarbaker techniques in parastomal hernia repair in the setting of ileal conduit urinary diversion. Method All patients in this cohort underwent primary elective parastomal hernia repair following ileal conduit urinary diversion in four university hospitals and one central hospital in Finland in 2007–2017. Retrospective clinical data were collected from patient registries to compare keyhole and Sugarbaker parastomal hernia repair techniques. The primary outcome was parastomal hernia recurrence during the follow-up from primary surgery to the last confirmed follow-up date of the patient. The secondary outcomes were reoperations during the follow-up and complication rate at 30 days’ follow-up. Results The results of 28 hernioplasties were evaluated. The overall parastomal hernia recurrence rate was 18%, the re-operation rate was 14%, and the complication rate was 14% during the median follow-up time of 30 (21–64) months. Recurrence rates were 22% (4/18) after keyhole repair and 10% (1/10) after Sugarbaker repair. Re-operation rates referred to keyhole repair were 22% and Sugarbaker repair 0% during follow-up. The majority of reoperations were indicated by recurrence. Complication rates were 17% after keyhole and 10% after Sugarbaker repair during the 30 days’ follow-up. Conclusion The results of parastomal hernia repair in the setting of ileal conduits are below optimal in this nationwide cohort comparing keyhole to Sugarbaker repair in elective parastomal hernia repair. Nonetheless, the Sugarbaker technique should be further studied to confirm the encouraging results of this cohort in terms of recurrence.

Introduction Pain is the most common symptom in acute pancreatitis (AP) and is among the diagnostic criteria. Therefore, we aimed to characterize acute abdominal pain in AP. Methods The Hungarian Pancreatic Study Group prospectively collected multicentre clinical data on 1435 adult AP patients between 2012 and 2017. Pain was characterized by its intensity (mild or intense), duration prior to admission (hours), localization (nine regions of the abdomen) and type (sharp, dull or cramping). Results 97.3% of patients (n = 1394) had pain on admission. Of the initial population with acute abdominal pain, 727 patients answered questions about pain intensity, 1148 about pain type, 1134 about pain localization and 1202 about pain duration. Pain was mostly intense (70%, n = 511/727), characterized by cramping (61%, n = 705/1148), mostly starting less than 24 h prior to admission (56.7%, n = 682/1202). Interestingly, 50.9% of the patients (n = 577/1134) had atypical pain, which means pain other than epigastric or belt-like upper abdominal pain. We observed a higher proportion of peripancreatic fluid collection (19.5% vs. 11.0%; p = 0.009) and oedematous pancreas (8.4% vs. 3.1%; p = 0.016) with intense pain. Sharp pain was associated with AP severity (OR = 2.481 95% CI: 1.550-3.969) and increased mortality (OR = 2.263, 95% CI: 1.199-4.059) compared to other types. Longstanding pain (>72 h) on admission was not associated with outcomes. Pain characteristics showed little association with the patient's baseline characteristics. Conclusion A comprehensive patient interview should include questions about pain characteristics, including pain type. Patients with sharp and intense pain might need special monitoring and tailored pain management. Significance Acute abdominal pain is the leading presenting symptom in acute pancreatitis; however, we currently lack specific guidelines for pain assessment and management. In our cohort analysis, intense and sharp pain on admission was associated with higher odds for severe AP and several systemic and local complications. Therefore, a comprehensive patient interview should include questions about pain characteristics and patients with intense and sharp pain might need closer monitoring.

Background Simultaneous pancreas-kidney transplantation (SPK) carries a high risk of major postoperative complications, but knowledge on early warning signs and surrogate markers for postoperative complications is scarce. Aims Our aim was to analyze the complication-predictive value of different laboratory tests in pancreas transplantation. Materials & Methods All SPKs in Finland between January 2010 and February 2020 were retrospectively analyzed. Levels of first three-day plasma amylase, drain fluid amylase, C-reactive protein, C-peptide, plasma trypsinogen, and white blood cell count were assessed for their performance predicting cumulative postoperative complications (assessed using the Comprehensive Complication Index) within 90 days from transplantation by using ROC analyses. Results Of the 164 SPK patients included, 39 suffered at least one complication requiring laparotomy. First-day plasma amylase had the best value in predicting complications based on its high AUC value and easy clinical applicability, with an optimum cutoff of six times the upper normal limit. Negative predictive values (NPVs) and positive predictive values of this cutoff were 0.81 and 0.71 for any relaparotomy, and 0.91 and 0.71 for the Comprehensive Complication Index >47.7 (which equals the morbidity of two relaparotomies), respectively. Conclusion In conclusion, first-day plasma amylase could be able to detect patients at risk of complications after SPK.

Background and Aim Liver disease is traditionally categorized as alcoholic and non-alcoholic. We studied various risk factors predictive of advanced non-viral liver disease in general population and analyzed the interaction between these factors and alcohol consumption. Methods Persons without underlying liver disease who participated in the Health2000 or FINRISK studies 1992-2012 comprised a cohort of 41 260 individuals. Pattern of alcohol consumption and metabolic, lifestyle-related, and anthropometric parameters were analyzed with Cox regression analysis using severe liver disease hospitalization, cancer, or death as end-point. Viral liver diseases were excluded. Results A total of 355 liver events occurred during the mean 12.4-year follow-up (511 789 person-years). In the multivariate model, age (hazard ratio [HR] 1.03, P = 0.0083 for men; HR 1.04, P = 0.0198 for women), waist-to-hip ratio (WHR) (HR 1.52, P = 0.0006 for men; HR 1.58, P = 0.0167 for women), patatin-like phospholipase-containing domain 3 mutations (HR 1.9, P = 0.024 for men; HR 2.7, P = 0.0109 for women), and weekly binge drinking (HR 2.4, P = 0.0024 for men; HR 7.4, P

BACKGROUND Kidney transplantation is reported to save costs compared to maintenance dialysis. We analyzed the current actual costs of kidney transplantation compared to dialysis, and analyzed risk factors for higher costs after transplantation. MATERIAL AND METHODS Altogether, 338 kidney transplant recipients between 2009 and 2014 were included in this study. All individual-level cost data from specialized health care and data from all reimbursed medication and travel costs were acquired from official records. Cost data were compared before and after transplantation within the same patients starting from dialysis initiation and continued until the end of follow-up at the end of 2015. RESULTS Total annual costs were median 53 275 EUR per patient in dialysis, 59 583 EUR for the first post-transplantation year (P

Background: Pretransplant dialysis modality may affect outcome after simultaneous pancreas-kidney transplantation (SPKT), and it has been suspected that peritoneal dialysis (PD) is associated with more postoperative complications compared to hemodialysis (HD). The aim of this study was to evaluate whether pretransplant dialysis modality affects the risk for postoperative complications in SPKT recipients. Material/ Methods: This was a retrospective longitudinal cohort study of all patients undergoing SPKT from 2010 to 2017, during which 99 simultaneous pancreas-kidney transplantations were performed. Three pre-emptive transplantations were excluded. Patient groups receiving PD (n=59) or HD (n=37) were similar regarding baseline characteristics. All complications occurring during the first 3 months after transplantation, as well as patient and graft survival, were analyzed. Results: There were no significant differences in postoperative complications between groups, with similar rates of intraabdominal infections (8% in HD vs. 10% in PD), pancreatitis (16% in HD vs. 17% in PD), gastrointestinal bleedings (22% in HD vs. 10% in PD), and relaparotomies (27% in HD vs. 24% in PD). None of the patients had venous graft thrombosis. Past peritonitis was not associated with increased risk for postoperative complications in PD patients. Patient and graft survival were similar between PD and HD groups. Conclusions: Peritoneal dialysis is not a risk factor for postoperative complications after SPKT.

Background The prognostic role of what a surgeon observes in the abdomen of patients with complicated intra-abdominal infection (cIAI) is largely unknown. The aim of this prospective study was to systemically analyze components of the intra-abdominal view (IAV) and their association to severe complicated intra-abdominal sepsis (SCIAS) or mortality. Methods The study cohort consisted of adult patients with cIAI. The operating surgeon filled a paper form describing the intra-abdominal view. Demographics, operative details, and preoperative physiological status were collected. Descriptive, univariate, and multivariate statistical analyses were performed, and a new score was developed based on regression coefficients. The primary outcome was a composite outcome of SCIAS or 30-day mortality, in which SCIAS was defined as organ dysfunctions requiring intensive care unit admission. Results A total of 283 patients were analyzed. The primary outcome was encountered in 71 (25%) patients. In the IAV, independent risk factors for the primary outcome were fecal or bile as exudate (odds ratio (OR) 1.98, 95% confidence interval 1.05–3.73), diffuse peritonitis (OR 2.15, 1.02–4.55), diffuse substantial redness of the peritoneum (OR 5.73, 2.12–15.44), and a non-appendiceal source of cIAI (OR 11.20, 4.11–30.54). Based on these factors, an IAV score was developed and its performance analyzed. The area under the receiver operating characteristic for the IAV score was 0.81. The IAV score also correlated significantly with several outcomes and organ dysfunctions. Conclusions The extent of peritonitis, diffuse substantial redness of the peritoneum, type of exudate, and source of infection associate independently with SCIAS or mortality. A high IAV score associates with mortality and organ dysfunctions, yet it needs further external validation. Combining components of IAV into comprehensive scoring systems for cIAI patients may provide additional value compared to the current scoring systems. Trial registration The study protocol was retrospectively registered on April 4, 2016, right after the first enrolled patient at Clinicaltrials.gov database (NCT02726932). Electronic supplementary material The online version of this article (10.1186/s13017-019-0232-7) contains supplementary material, which is available to authorized users.

OBJECTIVE To examine time trends in mortality rates and causes of death in patients with type 1 diabetes and end-stage renal disease on dialysis and after kidney transplantation. RESEARCH DESIGN AND METHODS In a nationwide retrospective cohort analysis, all patients with type 1 diabetes in Finland who received a kidney transplant alone were compared with patients who remained on dialysis. The main outcome was patient survival after starting dialysis. The cohort was divided into dialysis, functioning kidney transplant, and dialysis after transplant loss. Causes of death were retrieved and standardized mortality ratios calculated. RESULTS We studied 2,383 patients. Patients survived a median of 15.9 years after a successful transplant, 11.2 years if transplant function was lost, and 2.9 years if they remained on chronic dialysis. Standardized mortality ratio decreased in all subgroups during the past four decades: from 2005 onwards, it was 3.9 in patients receiving a kidney transplant, 11.5 in patients with graft loss, and 32.5 in patients on dialysis. The most common cause of death in all patients was ischemic heart disease (45%) followed by infection (18%), which was more common in patients on dialysis. CONCLUSIONS Kidney transplantation is the treatment of choice for patients with type 1 diabetes and end-stage renal disease because it substantially reduces the excess death risk when compared with dialysis. Even when kidney graft function is lost, the excess death risk is still considerably lower. Although overall mortality has decreased over the years, premature death due to ischemic heart disease remains high.

Introduction: The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. Methods: Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- and postoperative serum concentrations of MMP-8, MMP-9, and MPO were determined using a time-resolved immunofluorometric assay or commercially available enzyme-linked immunosorbent assay kits. Clinical data were retrieved from patient records and the Central Statistical Office of Finland. Associations with disease-free survival (DFS) and overall survival (OS) were estimated using Cox regression analysis and the Kaplan-Meier method. Results: High expression of MMP-9 in colorectal tumor tissue was associated with better DFS (p = 0.010), and high preoperative MPO in serum with improved DFS and OS (p < 0.001 and p = 0.014, respectively). The prognostic significance varied according to gender, age, and the synchronicity of liver metastases. Conclusion: Low preoperative MPO in serum might identify patients at high risk of recurrence and death after resection of colorectal liver metastases. Elevated preoperative MPO and high expression of MMP-9 in colorectal tumor tissue indicate an improved prognosis. The use of these biomarkers should be adjusted according to clinical characteristics.

Cytomegalovirus continues to be a concern after transplantation despite prophylaxis regimens. Our aim was to analyse post-prophylaxis primary cytomegalovirus infections among kidney transplant recipients after 6-month valganciclovir prophylaxis and to determine the usefulness of surveillance after prophylaxis. Data from all cytomegalovirus D+/R- kidney transplant recipients from January 2004 to October 2018 at our center who received 6-month prophylaxis with valganciclovir were retrospectively analysed (N = 481). Detailed analyses were performed for 136 patients who were monitored every 2-4 weeks for DNAemia after the discontinuation of prophylaxis. Post-prophylaxis primary cytomegalovirus infection occurred in 182/481 (38%) patients median 264 days after transplantation (IQR: 226-367) and median 84 days after the end of prophylaxis (IQR: 46-187). In 49% patients, cytomegalovirus infection occurred over 3 months after the end of prophylaxis. Cytomegalovirus infection was not associated with lower patient or graft survival and no independent risk factors for infection were found. From patients monitored closely, 71/136 (52%) patients developed post-prophylaxis primary cytomegalovirus infection. Altogether, 52/136 (38%) patients were diagnosed with probable post-prophylaxis cytomegalovirus disease and 19/136 (14%) patients had asymptomatic CMV infection. Recurrent infection occurred in 38/71 (39%) patients. The incidence of post-prophylaxis primary cytomegalovirus infection among D+/R- kidney transplant recipients remains high despite 6-month prophylaxis. Surveillance after prophylaxis was challenging as a considerable portion of the infections occurred late and already symptomatic.

Background In retrospective series, mechanical and oral antibiotic bowel preparation (MOABP) has been reported to reduce surgical-site infections (SSIs) after colectomy compared with no bowel preparation (NBP). Method This was a subgroup analysis of a multicentre randomized trial that included patients scheduled for elective colectomy. The MOABP group underwent mechanical bowel preparation, and took 2 g neomycin and 2 g metronidazole orally during the day before surgery. The NBP group did not undergo bowel preparation. Patients were categorized according to the side of resection (right versus left colectomy), and these subgroups compared for postoperative outcomes. Results Among 217 patients undergoing right colectomy (106 in MOABP and 111 in NBP group), SSI was detected in seven (7 per cent) and 10 (9 per cent) patients (odds ratio (OR) 0.71, 95 per cent c.i. 0.26 to 1.95; P = 0.510), anastomotic dehiscence in two (2 per cent) and two (2 per cent) patients (OR 1.05, 0.15 to 7.58; P = 1.000), and the mean(s.d.) Comprehensive Complication Index (CCI) score was 9.4(12.9) and 10.5(18.0) (mean difference –1.09; 95 per cent c.i. –5.29 to 3.11; P = 0.608) in the MOABP and NBP groups respectively. Among 164 patients undergoing left colectomy (84 in MOABP and 80 in NBP group), SSI was detected in five (6 per cent) and eight (10 per cent) patients (OR 0.57, 0.18 to 1.82; P = 0.338), anastomotic dehiscence in four (5 per cent) and five (6 per cent) patients (OR 0.75, 0.19 to 2.90; P = 0.742), and the CCI score was 10.2(13.1) and 6.5(11.0) (mean difference 3.68, –0.06 to 7.42; P = 0.053) in the MOABP and NBP groups respectively. Conclusions MOABP did not decrease the rate of SSI or complications in patients undergoing either right or left colectomy compared with NBP., Mechanical preparation in colorectal surgery

Background Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan–Meier estimates of overall survival (OS). Results In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. Conclusions Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup., Highlights • Colorectal liver metastases respond to systemic therapy by shrinking but also by morphological and metabolic changes. • Advanced MRI technologies (DWI and 1H-MRS) might provide more detailed insight into cancer treatment-induced changes. • We compare changes seen in MRI with histology. • Reduction of ADC during chemotherapy was associated with improved survival after liver resection.

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.

Background The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to elucidate the outcome of the liver-first approach and to identify patients who benefit at most from this approach. Methods Patients with synchronous CRLM included in the LiverMetSurvey registry between 2000 and 2017 were considered. Three strategies were analyzed, i.e. liver-first approach, colorectal resection followed by liver resection (primary-first), and simultaneous resection, and three groups of patients were analyzed, i.e. solitary metastasis, multiple unilobar CRLM, and multiple bilobar CRLM. In each group, patients from the three strategy groups were matched by propensity score analysis. Results Overall, 7360 patients were analyzed: 4415 primary-first, 552 liver-first, and 2393 simultaneous resections. Compared with the other groups, the liver-first group had more rectal tumors (58.0% vs. 31.2%) and higher hepatic tumor burden (more than three CRLMs: 34.8% vs. 24.0%; size > 50 mm: 35.6% vs. 22.8%; p < 0.001). In patients with solitary and multiple unilobar CRLM, survival was similar regardless of treatment strategy, whereas in patients with multiple bilobar metastases, the liver-first approach was an independent positive prognostic factor, both in unmatched patients (3-year survival 65.9% vs. primary-first 60.4%: hazard ratio [HR] 1.321, p = 0.031; vs. simultaneous resections 54.4%: HR 1.624, p < 0.001) and after propensity score matching (vs. primary-first: HR 1.667, p = 0.017; vs. simultaneous resections: HR 2.278, p = 0.003). Conclusion In patients with synchronous CRLM, the surgical strategy should be decided according to the hepatic tumor burden. In the presence of multiple bilobar CRLM, the liver-first approach is associated with longer survival than the alternative approaches and should be evaluated as standard.

The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations. Funding Agencies|Mary and Georg Ehrnrooth Foundation; Medicinska Understodsforeningen Liv och Halsa; Finska Lakaresallskapet; Finnish Foundation for Cardiovascular Research; National Institute of Diabetes, Digestive and Kidney DiseasesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [K08DK115883]; Innovation Fund Denmark; European UnionEuropean Commission [668031]; Novo Nordisk FoundationNovo Nordisk Foundation [NNF15OC0016692]; Region of Southern Denmark [K2017--4579]; Center for Innovative Medicine [20180889]

Background We aim to shed light on long-term subjective outcomes after re-operations for failed fundoplication. Methods 1809 patients were operated on for hiatal hernia and/or gastroesophageal reflux disease (GERD) at the Helsinki University Hospital between 2000 and 2017. 111 (6%) of these had undergone a re-operation for a failed antireflux operation. Overall, HRQoL was assessed in 89 patients at the latest follow-up using the generic 15D© instrument. The results were compared to a sample of the general population, weighted to reflect the age and gender distribution of patients. Disease-specific HRQoL was assessed using the GERD-HRQoL questionnaire. We studied variation in the overall HRQoL with respect to disease-specific HRQoL and known patients' parameters using univariate and multivariable linear regression models. Results The median postoperative follow-up period was 9.3 years. All patients were operated on laparoscopically (6% conversion rate), and 87% were satisfied with the re-operation. Postoperative complications were minimal (5%). Twelve patients (11%) underwent a second re-operation. The median GERD-HRQoL score was nine. In multivariable analysis, four variables were independently associated with the 15D score, suggesting a decrease in the 15D score with increasing GERD-HRQoL score, increasing Charlson Comorbidity Index (CCI) and the presence of chronic pain syndrome (CPS) and depression. Conclusion Re-do LF is a safe procedure in experienced hands and may offer acceptable long-term alleviation in patients with recurring symptoms after antireflux surgery. Decreased HRQoL in the long run is related to recurring GERD and co-morbidities.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2–3.4). The AER of any cancer was 1560 cases (95% CI: 1468–1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778–901), non-Hodgkin lymphoma (145, 95% CI: 119–174), lung cancer (126, 95% CI: 98.2–149), and kidney cancer (122, 95% CI: 98.0–149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6–8.6%) and 16.8% (95% CI: 16.0–17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance. publishedVersion

IntroductionRemote ischaemic preconditioning (RIPC) using a non-invasive pneumatic tourniquet is a potential method for reducing ischaemia-reperfusion injury. RIPC has been extensively studied in animal models and cardiac surgery, but scarcely in solid organ transplantation. RIPC could be an inexpensive and simple method to improve function of transplanted organs. Accordingly, we aim to study whether RIPC performed in brain-dead organ donors improves function and longevity of transplanted organs.Methods and analysesRIPTRANS is a multicentre, sham-controlled, parallel group, randomised superiority trial comparing RIPC intervention versus sham-intervention in brain-dead organ donors scheduled to donate at least one kidney. Recipients of the organs (kidney, liver, pancreas, heart, lungs) from a randomised donor will be included provided that they give written informed consent. The RIPC intervention is performed by inflating a thigh tourniquet to 300 mm Hg 4 times for 5 min. The intervention is done two times: first right after the declaration of brain death and second immediately before transferring the donor to the operating theatre. The sham group receives the tourniquet, but it is not inflated. The primary endpoint is delayed graft function (DGF) in kidney allografts. Secondary endpoints include short-term functional outcomes of transplanted organs, rejections and graft survival in various time points up to 20 years. We aim to show that RIPC reduces the incidence of DGF from 25% to 15%. According to this, the sample size is set to 500 kidney transplant recipients.Ethics and disseminationThis study has been approved by Helsinki University Hospital Ethics Committee and Helsinki University Hospital’s Institutional Review Board. The study protocol was be presented at the European Society of Organ Transplantation congress in Copenhagen 14−15 September 2019. The study results will be submitted to an international peer-reviewed scientific journal for publication.Trial registration numberNCT03855722.

AimsAlcohol-related hangover symptoms: nausea, headache, stress and anxiety cause globally considerable amount of health problems and economic losses. Many of these harmful effects are produced by alcohol and its metabolite, acetaldehyde, which also is a common ingredient in alcohol beverages. The aim of the present study is to investigate the effect of the amino acid L-cysteine on the alcohol/acetaldehyde related aftereffects.MethodsVoluntary healthy participants were recruited through advertisements. Volunteers had to have experience of hangover and/or headache. The hangover study was randomized, double-blind and placebo-controlled. Nineteen males randomly swallowed placebo and L-cysteine tablets. The alcohol dose was 1.5 g/kg, which was consumed during 3 h.ResultsThe primary results based on correlational analysis showed that L-cysteine prevents or alleviates hangover, nausea, headache, stress and anxiety. For hangover, nausea and headache the results were apparent with the L-cysteine dose of 1200 mg and for stress and anxiety already with the dose of 600 mg.ConclusionsL-cysteine would reduce the need of drinking the next day with no or less hangover symptoms: nausea, headache, stress and anxiety. Altogether, these effects of L-cysteine are unique and seem to have a future in preventing or alleviating these harmful symptoms as well as reducing the risk of alcohol addiction.

Background and Aims Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) may exceed 20%, and BTC is currently the leading cause of death in patients with PSC. To open new avenues for management, we aimed to delineate clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). Approach and Results We analyzed formalin-fixed, paraffin-embedded tumor tissue from 186 patients with PSC-BTC from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations, and copy number variations, along with histomorphological and immunohistochemical characterization. Regardless of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, such asTP53(35.5%),KRAS(28.0%),CDKN2A(14.5%), andSMAD4(11.3%), as well as potentially druggable mutations (e.g.,HER2/ERBB2). We found a high frequency of nontypical/nonductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%). Conclusions Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC shows a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.

Background There are limited data about the use and clinical value of JC polyomavirus (JCPyV) DNA detection in various clinical indications. Methods We reviewed the clinical records of 410 patients from whom cerebrospinal fluid (CSF), plasma, urine, or tissue samples had been collected for JCPyV DNA polymerase chain reaction (PCR) between 2012 and 2018. Results JCPyV DNA was analyzed in 224 plasma, 190 CSF-, 32 urine and 10 tissue samples. 240 patients had a history of hematopoietic stem cell or solid organ transplantation, 159 had nephrological disease, 90 had hematologic malignancies, 58 had neurological disease, 37 had infectious disease and 23 had AIDS/HIV as underlying disease. Six patients had no underlying disease. The main reasons to take CSF or plasma samples were neurological symptoms of unknown etiology. Most urine samples were taken to monitor kidney transplantation patients. JCPyV DNA PCR contributed to the diagnosis of progressive multifocal leukoencephalopathy in eight patients (2.0 %), of which seven had hematologic malignancy as an underlying disease. Conclusions JCPyV PCR is most informative among immunosuppressed patients with neurologic symptoms. CSF and brain biopsy are useful when there is clinical suspicion of PML, whereas plasma samples are not useful. The value of plasma samples is a matter of dispute in the screening of JCPyV-associated nephropathy, as BK polyomavirus is the causative agent in most polyomavirus-associated nephropathy cases. JCPyV detection is valuable in case the patient has past, current or planned treatment with immunosuppressive drugs.

Fatty liver disease is the most common liver disease in the world. It is characterized by a buildup of excess fat in the liver that can lead to cirrhosis and liver failure. The link between fatty liver disease and gut microbiome has been known for at least 80 years. However, this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample in Finland. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥ 60, indicates likely liver steatosis) and low FLI (< 60) in our validation set, consisting of 30% of the data not used in model training, with an average AUC of 0.75. In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Pathway analysis of representative genomes of the FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of e.g., ethanol fermentation pathways. Through modeling the fatty liver index, our results provide with high resolution associations between gut microbiota composition and fatty liver in a large representative population cohort and support the role of endogenous ethanol producers in the development of fatty liver.

Background and objectives Transplant centers in Europe aim to minimize the time from brain death to organ procurement (procurement delay), but evidence to justify this is scarce. In the United States, procurement times are significantly longer. Our objective was to analyze how procurement delay associates with kidney allograft outcomes. Design, setting, participants, & measurements Kidney transplantations from brain-dead donors were retrospectively analyzed from the Finnish Kidney Transplant Registry and the Scientific Registry of Transplant Recipients in the United States. Multivariable models were adjusted with donor and recipient characteristics, and the relationship between procurement delay and outcomes was modeled with cubic spline functions. Results In total, 2388 and 101,474 kidney transplantations in Finland and the United States were included, respectively. The median procurement delay was 9.8 hours (interquartile range, 7.8-12.4) in Finland and 34.8 hours (interquartile range, 26.3-46.3) in the United States. A nonlinear association was observed between procurement delay and the risk of delayed graft function, with highest risk seen in short and very long procurement delays. In multivariable models, the lowest risk of delayed graft function was associated with procurement delay between 20 and 50 hours. In multivariable models, longer procurement delay was linearly associated with lower risk of graft loss (hazard ratio, 0.90/1 h longer; 95% confidence interval, 0.88 to 0.92; P Conclusions Longer procurement delay was associated with noninferior or even better kidney allograft outcomes.

The etiology and prognosis of acute liver failure (ALF) remains unknown in a significant proportion of cases. Signs of autoimmunity may be present, but no consistent pattern has been observed. We aimed to analyze if pretransplant immunological findings, human leukocyte antigen (HLA) haplotypes, and clinical features among patients with an unknown etiology differ from those of autoimmune or other known etiologies. We also analyzed whether such signs impact posttransplant biopsy findings or complications. All adult ALF patients undergoing liver transplantation (LT) in Finland during 1987-2015 were followed to 2016. Data were collected from the LT registry, pathology database, and patient records. A total of 124 patients were included in the analysis. Study subgroups were acute autoimmune hepatitis (AIH; n = 25), known non-AIH etiology (n = 54), and unknown etiology (n = 45). The unknown etiology group differed from the known non-AIH group with regard to the following pretransplant autoimmunity-associated features: positive perinuclear anti-neutrophil cytoplasmic antibodies (36% versus 8%; P = 0.02) and higher mean immunoglobulin A (IgA; 3.2 ± 1.7 versus 2.1 ± 1.4, P = 0.006) and immunoglobulin G (IgG; 12.7 ± 4.3 versus 8.5 ± 3.6, P = 0.001). AIH-associated HLA haplotypes B8, DR3, and B8DR3 were more common in the AIH group (40%, 44%, and 36%, respectively) and in the unknown group (29%, 33%, and 29%, respectively) than in the known non-AIH group (11%, 17%, and 11%, respectively) or in the Finnish general population (17%, 18%, and 8%, respectively). However, these findings had no association with protocol biopsies, extrahepatic autoimmune diseases, or survival. Patients with ≥ 1 rejection episode had higher pretransplant IgA (3.7 ± 2.3 versus 2.6 ± 1.2; P = 0.02) and IgG (16.4 ± 10.2 versus 12.4 ± 6.8; P = 0.03) than those without rejections. Autoimmunity-associated pretransplant laboratory findings and HLA haplotypes were common in ALF of unknown etiology, but they showed minimal predictive value for posttransplant biopsy findings, clinical complications, or survival.

Importance Both hydrocortisone and pasireotide have been shown in randomized clinical trials to be effective in reducing postoperative complications of pancreatic surgery, but to date no randomized clinical trial has evaluated the effectiveness of pasireotide compared with hydrocortisone. Objective To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy. Design, Setting, and Participants A noninferiority, parallel-group, individually randomized clinical trial was conducted at a single academic center between May 19, 2016, and December 17, 2018. Outcome collectors and analyzers were blinded. A total of 281 patients undergoing partial pancreatectomy were assessed for inclusion. Patients younger than 18 years, those allergic to hydrocortisone or pasireotide, patients undergoing pancreaticoduodenectomy with hard pancreas or dilated pancreatic duct, and patients not eventually undergoing partial pancreatectomy were excluded. Modified intention-to-treat analysis was used in determination of the results. Interventions Treatment included pasireotide, 900 μg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days. Main Outcomes and Measures The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points. Results Of the 281 patients (mean [SD] age, 63.8 years) assessed for eligibility, 168 patients (mean [SD] age, 63.6 years) were randomized and 126 were included in the modified intention-to-treat analyses. Sixty-three patients received pasireotide (35 men [56%]; median [interquartile range] age, 64 [56-70] years) and 63 patients received hydrocortisone (25 men [40%]; median [interquartile range] age, 67 [56-73] years). The mean (SD) CCI score was 23.94 (17.06) in the pasireotide group and 30.11 (20.47) in the hydrocortisone group (mean difference, –6.16; 2-sided 90% CI, –11.73 to –0.60), indicating that hydrocortisone was not noninferior. Postoperative pancreatic fistula was detected in 34 patients (54%) in the pasireotide group and 39 patients (62%) in the hydrocortisone group (odds ratio, 1.39; 95% CI, 0.68-2.82;P = .37). One patient in the pasireotide group and 2 patients in the hydrocortisone group died within 30 days. In subgroup analyses of patients undergoing distal pancreatectomy, the CCI score was a mean of 10.3 points lower (mean [SD], 16.03 [11.94] vs 26.28 [21.76]; 2-sided 95% CI, −19.34 to −2.12;P = .03) and postoperative pancreatic fistula rate was lower (37% vs 67%;P = .02) in the pasireotide group compared with the hydrocortisone group. Conclusions and Relevance In this study, hydrocortisone was not noninferior compared with pasireotide in patients undergoing partial pancreatectomy. Pasireotide may be more effective than hydrocortisone in patients undergoing distal pancreatectomy. Trial Registration ClinicalTrials.gov identifier:NCT02775227; EudraCT identifier:2016-000212-16

Background and Aims The effects of alcohol use in nonalcoholic fatty liver disease are unclear. We investigated the impact of alcohol use in fatty liver disease on incident liver, cardiovascular, and malignant disease, as well as death. Approach and Results Our study comprised 8,345 persons with hepatic steatosis (fatty liver index >60) who participated in health-examination surveys (FINRISK 1992-2012 or Health 2000), with available data on baseline alcohol intake. Main exclusions were baseline clinical liver disease, viral hepatitis, ethanol intake >50 g/day, and current abstainers. Data were linked with national registers for hospital admissions, malignancies, and death regarding liver, cardiovascular, and malignant disease, as well as all-cause death. Adjustment were for multiple confounders. Alcohol consumption showed a dose-dependent risk increase for incident advanced liver disease and malignancies. Consuming 10-19 g/day of alcohol in general or 0-9 g/day as nonwine beverages doubled the risk for advanced liver disease compared to lifetime abstainers. In contrast, alcohol intake up to 49 g/day was associated with a 22%-40% reduction of incident cardiovascular disease (CVD). We observed a J-shaped association between alcohol intake and all-cause death with a maximal risk reduction of 21% (95% confidence interval, 5%-34%) at alcohol intake of 0-9 g/day compared to lifetime abstainers. However, these benefits on CVD and mortality were only observed in never smokers. Alcohol intake >30 g/day yielded increased risk estimates for mortality compared to lifetime abstainers. In a subpopulation with longitudinal data, alcohol intake remained stable over time in >80% of subjects. Conclusions Even low alcohol intake in fatty liver disease is associated with increased risks for advanced liver disease and cancer. Low to moderate alcohol use is associated with reduced mortality and CVD risk but only among never smokers.

Aim To analyse incidence, treatment and outcomes of paediatric liver malignancies in Finland during 1987-2017. Methods Medical records and national cancer registry data of 47 children with liver malignancies were reviewed. Survival was calculated with the Kaplan-Meier method. Results During follow-up, liver malignancy incidence remained stable at 1.1:10(6). Altogether, 42 patients with hepatoblastoma (n = 24), hepatocellular carcinoma (n = 11) and undifferentiated embryonal sarcoma (n = 7) underwent surgery at median age 4.6 (interquartile range, 2.0-9.6) years and were followed up for 13 (7.0-19) years. Cumulative 5-year survival was 86% for hepatoblastoma, 41% for hepatocellular carcinoma and 67% for undifferentiated embryonal sarcoma. Five-year survival was decreased among hepatoblastoma patients aged >= 2.4 years (73% versus 100%, P = .040), with PRETreatment EXTent of disease IV (PRETEXT, 60% vs 100%, P = .004), and with recurrent disease (67% vs 88%, P = .029). Recurrent/residual disease associated with decreased 5-year survival in hepatocellular carcinoma (0% vs 83%, P = .028). Survival was similar among 19 transplanted and 23 resected patients. In total, 14 deaths occurred either for the underlying malignancy (n = 8), adverse effects of chemotherapy (n = 5) or unrelated reasons (n = 1). Conclusion Outcomes for PRETEXT I-III hepatoblastoma and un-metastasized hepatocellular carcinoma were encouraging. Adverse effects of chemotherapy significantly contributed to mortality.

Importance: Diverticulitis has a tendency to recur and affect quality of life. Objective: To assess whether sigmoid resection is superior to conservative treatment in improving quality of life of patients with recurrent, complicated, or persistent painful diverticulitis. Design, Setting, and Participants: This open-label randomized clinical trial assessed for eligibility 128 patients with recurrent, complicated, or persistent painful diverticulitis in 6 Finnish hospitals from September 29, 2014, to October 10, 2018. Exclusion criteria included age younger than 18 years or older than 75 years; lack of (virtual) colonoscopy or sigmoidoscopy data within 2 years, or presence of cancer, contraindication to laparoscopy, or fistula. Outcomes were assessed using intention-to-treat analysis. A prespecified interim analysis was undertaken when 66 patients had been randomized and their 6-month follow-up was assessable. Data were analyzed from June 2018 to May 2020. Interventions: Laparoscopic sigmoid resection or conservative treatment. Main Outcomes and Measures: The primary outcome was difference in Gastrointestinal Quality of Life Index (GIQLI) score between randomization and 6 months. Results: Of 128 patients assessed for eligibility, 90 were randomized (28 male [31%]; mean [SD] age, 54.11 [11.9] years; 62 female [69%]; mean [SD] age, 57.13 [7.6] years). A total of 72 patients were included in analyses for the primary outcome (37 in the surgery group and 35 in the conservative treatment group), and 85 were included in analyses for clinical outcomes (41 in the surgery group and 44 in the conservative treatment group). The difference between GIQLI score at randomization and 6 months was a mean of 11.96 points higher in the surgery group than in the conservative treatment group (mean [SD] of 11.76 [15.89] points vs −0.2 [19.07] points; difference, 11.96; 95% CI, 3.72–20.19; P = .005). Four patients (10%) in the surgery group and no patients in the conservative treatment group experienced major complications (Clavien-Dindo grade III or higher). There were 2 patients (5%) in the surgery group and 12 patients (31%) in the conservative treatment group who had new episodes of diverticulitis within 6 months. Conclusions and Relevance: In this randomized clinical trial, elective laparoscopic sigmoid resection improved quality of life in patients with recurrent, complicated, or persistent painful diverticulitis but carried a 10% risk of major complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02174926.

Background: There is a wide variety of disease severity in patients with complicated intraabdominal infection (cIAI). The prognostic role of intraabdominal view (IAV) was recently studied, and an IAV score was introduced. The aim of this study was to analyze the associations between the preoperative levels of eight relevant circulating cytokines and IAV components, the IAV score, as well as outcome. Materials and methods: This was a single-center prospective study. The study cohort consisted of operatively managed adult patients with a cIAI. Preoperative plasma levels of eight cytokines were determined. The operating surgeon filled a form describing IAV. Outcomes analyzed were 30-day mortality and the development of organ dysfunctions requiring intensive care unit admission. Results: A total of 131 patients with cIAI were analyzed, 30-day mortality was 9.9% (n = 13), and 28 (21.4%) patients had postoperative organ dysfunctions. All components of IAV, the IAV score, and outcomes were associated with various cytokine levels. Interleukin-8 was the most competent marker associating with all the variables assessed in this study: diffuse peritonitis (P