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Aim: We aimed to assess management, comorbidities, biliary histopathology and outcomes of choledochal malformations (CM) in adults. Methods: All adult CM patients managed during 1987–2021 at the Helsinki University Hospital were retrospectively reviewed. Results: Of the 39 patients (females 79%) identified, 19 (49%) underwent surgery, 5 (13%) therapeutic ERCP with papillotomy for type 3 CM and 15 (38%) were managed conservatively. Twenty-five (66%) patients had ≥1 comorbidity, and five (13%) patients had associated inflammatory bowel disease (IBD); ulcerative colitis (n = 3) and Crohn’s disease (n = 2). Most surgically treated patients underwent hepaticojejunostomy (n = 13) or pancreaticoduodenectomy (n = 3) and they were younger at presentation than other patients [29 (21 – 48) vs. 59 (41 – 71), p = 0.001]. Three patients (23%) suffered from pancreatitis following diagnostic ERCP. Early surgical complications occurred in six (32%) patients, including one anastomotic leakage. Biliary epithelial dysplasia was found in three (15%) patients in resected specimens, while no neoplastic changes were observed. Nine patients (47%) had long-term postoperative complications, cholangitis (n = 5) and anastomotic stricture (n = 3) being the most common ones. No evidence of malignant change was observed after median follow-up of 2.3 (0.60 − 4.5) years included all patient cohorts. Conservatively managed patients remained symptomless with unprogressive biliary tract imaging findings and normal liver biochemistry values during follow-up. Nearly half of operated patients developed long-term postoperative complications. A novel association between CMs and IBD was observed. Although no hepatobiliary malignancies regardless of treatment modality were encountered, the number of patients and length of follow-up remained limited.

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.

OBJECTIVE The aim of the study was to assess long-term morbidity in children operated for choledochal malformation (CM) by relating clinical complications to liver histopathology, follow-up imaging, liver stiffness, and biochemistry. METHODS A single-center retrospective follow-up study including all CM patients (n = 55, 71% girls) treated during 1976 to 2018 was performed. Mann-Whitney U test and Spearman rank correlation were used for statistical analyses. RESULTS During median follow-up of 5.8 (interquartile range, 2.5-12) years, 1 patient was lost to follow-up whereas all survived. Intraoperative liver biopsies showed fibrosis in 32%, and patients with Metavir stage ≥2 were younger at surgery (0.36 [0.11-1.9] vs 3.8 [0.72-10.5] years, P = 0.024) than those without fibrosis. Overall, 21% had long-term complications including cholangitis in 9 (>2 episodes in 5) patients, anastomotic stricture in 2 referred patients and adhesive volvulus or hepatocellular carcinoma in 1 each. Anastomotic strictures were successfully managed nonoperatively and hepatocellular carcinoma with thermoablation. In postoperative magnetic resonance cholangiography (MRCP) performed 6.4 (3.6-16) years after hepaticojejunostomy, diameters of both main intrahepatic ducts had decreased significantly to 3.0 (2.5-3.5) mm (P = 0.0001) but a distal cyst stump was remaining in 30% with a length of 6.0 (4.0-20) mm that associated with operation age (r = 0.71, P = 0.015) and fusiform CM type. Follow-up ultrasound revealed mild dilation of intrahepatic bile ducts in 6.3% and mildly to moderately elevated liver biochemistry in 23%, and liver stiffness (>7 kPa) in 22%. CONCLUSIONS Whilst cholangitis was the most common postoperative problem, individual patients experienced other more significant complications and one quarter of patients showed evidence of underlying liver dysfunction.

Background and objective: Acute mesenteric ischemia (AMI) has a high mortality rate due to the development of bowel necrosis. Patients are often ruled outside active care if a large proportion of small bowel is necrotic. With the development of treatment for short bowel syndrome (SBS) and intestinal transplantation methods, long-term survival is possible even after extensive small bowel resections. This study aims to assess the incidence of SBS and potentially suitable candidates for intestinal transplantation among patients treated for AMI. Methods: This population-based retrospective study comprised patients aged less than 70 years and diagnosed with AMI between January 2006 and October 2020 in Helsinki and Uusimaa health care district, Finland. Results: Altogether, AMI was diagnosed in 711 patients, of whom 133 (19%) were aged below 70. An intervention was performed in 110 (83%) patients. Of these 133 patients, 16 (12%) were ruled outside active treatment due to extensive small bowel necrosis at exploratory laparotomy, of whom 6 (5%) were potentially suitable for intestinal transplantation. Two patients were considered as potential candidates for intestinal transplantation at bowel resection but died of AMI. Nine (7%) patients needed parenteral nutrition after resection, and two of them (2%) developed SBS. Only one patient needed long-term parenteral nutrition after hospital discharge. This patient remained dependent on parenteral nutrition but died before evaluation of intestinal transplantation could be carried out while the other patient was able to return to enteral nutrition. Conclusions: A small number of patients with AMI below 70 years of age are potentially eligible for intestinal transplantation.

The access of non-resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non-residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non-residents. Two countries never allow non-residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non-resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life-threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non-residents to DDWL should be clearly defined at national level.

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.

Objective: Spontaneous hepatic tumor hemorrhage is a rare but challenging emergency especially among cirrhotic patients with poor hepatic function. This study aimed at analyzing the safety,...

Background: Perihilar cholangiocarcinoma and distal cholangiocarcinoma arise from the same tissue but require different surgical treatment methods. It remains unclear whether these cholangiocarcinoma types have different outcomes, prognostic factors, and/or recurrence patterns. Methods: This retrospective study evaluated patients who underwent curative-intent resection for perihilar cholangiocarcinoma or distal cholangiocarcinoma at a tertiary academic hospital during 2000–2015. Survival and prognostic factors were identified using Kaplan–Meier and Cox regression analyses. Results: The 90-day mortality rates were 0% for perihilar cholangiocarcinoma (36 patients) and 4% for distal cholangiocarcinoma (47 patients). There were no significant differences between perihilar cholangiocarcinoma or distal cholangiocarcinoma in median overall survival (30.9 vs 40.4 months) or median disease-free survival (14.2 vs 21.4 months). Among perihilar cholangiocarcinoma patients, age > 65 years was an independent predictor of poorer overall survival (hazard ratio: 2.45, 95% confidence interval: 1.07–5.64), while requiring bile duct re-resection was an independent predictor of disease-free survival (hazard ratio: 2.76, 95% confidence interval: 1.01–7.51). Among distal cholangiocarcinoma patients, a pN1 category independently predicted poorer overall survival (hazard ratio: 3.40, 95% confidence interval: 1.14–10.11), while preoperative CA19-9 levels >30 U/mL (hazard ratio: 2.51, 95% confidence interval: 1.09–5.79) and pN1 category (hazard ratio: 2.51, 95% confidence interval: 1.09–5.79) predicted a shorter disease-free survival. Local recurrence was more common with perihilar cholangiocarcinoma (50% of recurrences), while multiple synchronous sites were more common for distal cholangiocarcinoma (41% of recurrences). Conclusion: Perihilar cholangiocarcinoma and distal cholangiocarcinoma patients have similar survival outcomes. However, local control appears to be more prognostic for perihilar cholangiocarcinoma patients, while positive lymph nodes are critical prognostic factor for distal cholangiocarcinoma patients.

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.

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 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.

Background Solid organ transplant (SOT) patients are at significant risk for invasive pneumococcal disease. The optimal pneumococcal vaccination strategy for SOT patients is not known. Methods The potential adult liver transplant recipients were randomised into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before the transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before the transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, e.g. before and after the second PCV13 (visits V3,V4). Results Out of 47 patients, 19 (PCV13 arm) and 17 (PPV23 arm) received a liver transplant and all these patients completed the study (36/47, 76,6%). Each vaccine schedule elicited a good immune response. At V2, the geometric mean concentrations (GMCs) of antibodies for serotypes 6A, 7F and 23F, and the geometric mean titers (GMTs) of OPA for serotypes 4, 6A, 6B and 23F were significantly higher for PCV13, but the proportions of patients reaching OPA cut-off ≥ 8 or ELISA cut-off ≥ 1.0 µg/ml did not differ between the arms. At V3 the antibody concentrations and the OPA had declined to baseline in both arms. The second PCV13 vaccination elicited an immune response. There was no difference in adverse events. No vaccine-related allograft rejection was detected. Conclusions The immunogenicity of PPV23 and PCV13 was comparable in this patient material, but the seroresponses waned after transplantation. The second dose of PCV13 restored the immune responses and was well tolerated.

Introduction Recently new standards for reporting outcomes of bile duct injury (BDI) have been proposed. It is unclear how these treatment outcomes are reflected in quality of life (QOL). The aim of this study was to report outcomes and QOL after repair of major BDI and compare repairs by hepatobiliary surgeon to repairs by non-hepatobiliary surgeons. Methods This was a retrospective study of patients treated for major (Strasberg E-type) BDI after cholecystectomy at a tertiary hepatobiliary center. Outcomes were assessed using Cho-Strasberg proposed standards. QOL was assessed using Short Form Health Survey (SF-36) and the gastrointestinal QOL-index (GIQLI). Patients undergoing uneventful cholecystectomy matched by age, urgency, and duration of follow-up were used as controls. Results Fifty-two patients with major BDI treated between 2000 and 2016 were included (42% male, median age 53 years). Thirty-seven (71%) patients attained primary patency (29 (83%) if primarily operated by a hepatobiliary surgeon). Actuarial primary patency rate (grade A result) at 1, 3, and 5 years was 58%, 56%, and 53% in the whole cohort, and 83%, 80%, and 80% in patients primary treated by a hepatobiliary surgeon, respectively. At 3-year follow-up 6 (11.5%) patients obtained grade B, 10 (19.2%) grade C, and 7 (13.5%) grade D result. QOL was similar in patients with BDI and controls (median SF-36 physical component 51.7 and 53.6, p = 1.0, mental component 53.3 and 53.4, p = 1.0, GIQLI 109.0 and 123.0, p = 0.174, respectively) at median 90 (IQR 70–116) months from cholecystectomy. QOL was similar regardless of outcome grade. Conclusion First attempt to repair a severe BDI should be undertaken by a hepatobiliary surgeon. However, long-term QOL is not affected even by severe BDI, and QOL is not associated with the grade of the outcome.

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.

OBJECTIVE: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial). SUMMARY AND BACKGROUND DATA: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data. PATIENTS AND METHODS: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence. RESULTS: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245). CONCLUSIONS: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients. CLINICAL TRIAL REGISTRATION: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862. ispartof: ANNALS OF SURGERY vol:272 issue:5 pages:855-862 ispartof: location:United States status: published

Background The risk of invasive pneumococcal disease is significant among solid organ transplant (SOT) recipients. The optimal pneumococcal vaccination strategy for SOT patients is not known. Methods The potential kidney transplant recipients in dialysis were randomized into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, for example, before and after the second PCV13 (visits V3,V4). Results Out of 133 participants, 48 (PCV13 arm) and 46 (PPV23 arm) received a kidney transplant, and 37 + 37 in both arms completed the study. After the first vaccination, the geometric mean concentrations (GMCs) in the PCV13 arm were significantly higher for 9/13 serotypes and the OPA geometric mean titers (GMTs) were significantly higher for 4/13 serotypes. At V3, the antibody levels had declined but OPA remained significantly higher for 7/13 (PCV13) vs 4/13 (PPV23) serotypes. At V4, the GMCs for 9/13 serotypes and the GMTs for 12/13 serotypes were significantly higher in the PCV13 arm. The GMCs but not GMTs were lower than at V2. There was no difference in adverse effects. No vaccine-related allograft rejection was detected. Conclusions The immunogenicity of PCV13 was better in dialysis patients, and revaccination with PCV13 was immunogenic and safe.

ObjectiveIschaemia/reperfusion-injury degrades endothelial glycocalyx. Graft glycocalyx degradation was studied in human liver transplantation.MethodsTo assess changes within the graft, blood was drawn from portal and hepatic veins in addition to systemic samples in 10 patients. Plasma syndecan-1, heparan sulfate and chondroitin sulfate, were measured with enzyme-linked immunosorbent assay.ResultsDuring reperfusion, syndecan-1 levels were higher in graft caval effluent [3118 (934-6141) ng/ml, P = 0.005] than in portal venous blood [101 (75-121) ng/ml], indicating syndecan-1 release from the graft. Concomitantly, heparan sulfate levels were lower in graft caval effluent [96 (32-129) ng/ml, P = 0.037] than in portal venous blood [112 (98-128) ng/ml], indicating heparan sulfate uptake within the graft. Chondroitin sulfate levels were equal in portal and hepatic venous blood. After reperfusion arterial syndecan-1 levels increased 17-fold (P < 0.001) and heparan sulfate decreased to a third (P < 0.001) towards the end of surgery.ConclusionSyndecan-1 washout from the liver indicates extensive glycocalyx degradation within the graft during reperfusion. Surprisingly, heparan sulfate was taken up by the graft during reperfusion. Corroborating previous experimental reports, this suggests that endogenous heparan sulfate might be utilized within the graft in the repair of damaged glycocalyx.

Background Three new parvoviruses of Protoparvovirus genus, bufavirus (BuV), tusavirus (TuV), and cutavirus (CuV), have recently been discovered in diarrheal stools. CuV was further detected in a proportion of cutaneous T-cell lymphoma (CTCL)/mycosis fungoides skin samples and in one melanoma. Patients and methods With novel multiplex quantitative polymerase chain reaction and antibody assays, we studied 3 patient groups for BuV, TuV, and CuV DNA and immunoglobulin G (IgG): CTCL patients, immunosuppressed solid-organ transplant recipients, and immunocompetent healthy adults. Results CuV DNA was detected in skin biopsies of 4/25 (16.0%) CTCL and 4/136 (2.9%) transplant patients but not in any of 159 skin samples of 98 healthy adults. The dermal CuV-DNA prevalence was significantly higher in CTCL patients than in the other subjects. CuV DNA was further detected in healthy skin of 4 organ transplant recipients, 2 of whom also had CuV-positive skin carcinomas. One CTCL patient harbored CuV DNA in both malignant (CTCL, melanoma) and nonmalignant skin and sentinel lymph nodes but not in his prostate. The CuV IgG seroprevalences were among CTCL patients 9.5% (4/42), transplant recipients 6.5% (8/124), and healthy adults 3.8% (3/78). BuV and TuV DNAs were absent and antibodies infrequent in all cohorts. Parvoviral antibodies were shown to persist for ≥20 years and dermal CuV DNA for 4 years. All 3 CuV-DNA-positive patients, with both biopsies and sera available, were CuV-IgG positive. Conclusion Our results suggest that dermal CuV DNA carriage is associated with CTCL. Any putative roles of CuV in the carcinogenesis must be determined in forthcoming studies.

Aim: We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases. Methods & patients: The Helsinki VCA program initially required the fulfillment of legal, hospital, financial, and ethical requirements. Thereafter, the assembling of a multidisciplinary team commenced. A team of Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The protocol involves collaboration with the Solid Organ Transplant (SOT) team, transplant immunology, immunosuppression, microbiology, psychiatric evaluation, well-defined VCA indications and informed consent. Between 2011 and 2017 two patients were selected for transplantation. Both patients had a severe composite facial deformity involving the maxilla and mandible following earlier ballistic injury. Results: Patient 1 was a 35 year-old male who underwent successful near total face transplantation in February 2016 and at 30 months he has a good aesthetic outcome with symmetrical restoration of the central face and good sensory and symmetrical motor functional outcomes. Patient 2 was a 58 year-old male who underwent full face transplantation in March 2018 and at 5 months he has recovered without major problems. Conclusion: A successful facial VCA program requires a well-prepared research protocol, experts from multiple specialties and careful patient selection. The establishment of the Helsinki VCA program required long and thorough planning and resulted in the first two Nordic face transplantation cases. This protocol now forms the platform (as a proof of concept) for other types of vascularized composite allotransplantations. (C) 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Teema : syntymä

Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC occurs more frequently than expected in immunosuppressed subjects, especially in organ transplant recipients. The current literature comprises reports of 79 organ transplant recipients with MCC. The risk of MCC in organ transplant recipients is increased up to 66-182-fold compared with the general population. In addition to the increased risk of developing MCC, immunosuppressed individuals have poorer MCC-specific survival. The aim of this review article is to familiarize organ transplant doctors with this unique and clinically challenging skin cancer, and to provide recent data on the diagnosis and current treatment recommendations for an immunosuppressed population.

To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV), and Lyon IARC polyomavirus (LIPyV) were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant versus benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.

Key Clinical Message In an intestinal transplant patient under triple immunosuppression therapy with tacrolimus levels >10 ng/L, a 2‐day oral immunoglobulin therapy given as treatment for chronic norovirus infection was temporally closely associated with the development of severe steroid‐resistant acute graft rejection, thus suggesting that oral immunoglobulin might be able to promote a rejection response.

AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage liver disease (MELD) score. We aimed to summarize key outcome measures and developments for the activity up to December 2013.MATERIALS AND METHODS: The registry is integrated with the operational waiting-list and liver allocation system of Scandiatransplant (www.scandiatransplant.org) and accounted at the end of 2013 for 6019 patients out of whom 5198 were transplanted. Data for recipient and donor characteristics and relevant end-points retransplantation and death are manually curated on an annual basis to allow for statistical analysis and the annual report.RESULTS: Primary sclerosing cholangitis, acute hepatic failure, alcoholic liver disease, primary biliary cirrhosis and hepatocellular carcinoma are the five most frequent diagnoses (accounting for 15.3%, 10.8%, 10.6%, 9.3% and 9.0% of all transplants, respectively). Median waiting time for non-urgent liver transplantation during the last 10-year period was 39 days. Outcome has improved over time, and for patients transplanted during 2004-2013, overall one-, five- and 10-year survival rates were 91%, 80% and 71%, respectively. In an intention-to-treat analysis, corresponding numbers during the same time period were 87%, 75% and 66%, respectively.CONCLUSION: The liver transplant program in the Nordic countries provides comparable outcomes to programs with a MELD-based donor liver allocation system. Unique features comprise the diagnostic spectrum, waiting times and the availability of an integrated waiting list and transplant registry (NLTR).

A young woman fell off a horse, leaving her right flank contused by a hoof. This resulted in a severe liver trauma that seemed to require surgical treatment. After fluid resuscitation and five units of red blood cells the patient's status, however, stabilized upon entering the operating room. The operation was avoided, but intensive care follow-up was continued for six days. The patient made a complete recovery. Conservative treatment of liver trauma is successful in 90% of mild and almost 70% in severe traumas.

AIM To investigate markers for high-grade dysplasia for the optimal timing of liver transplantation in patients with primary sclerosing cholangitis (PSC). METHODS Earlier data support a dysplasia-carcinoma sequence, even low-to high-grade dysplasia, in PSC-associated cholangiocarcinoma (CCA). Surveillance using endoscopic retrograde cholangiography (ERC) and brush cytology aims to detect cases of biliary dysplasia, and liver transplantation is an option in cases with suspicion of malignancy in brushing. This study investigated markers to identify patients with high-grade biliary dysplasia for optimal timing in early liver transplantation. Patients undergoing surveillance using ERC and brush cytology during 2008-2014 and who were diagnosed with biliary dysplasia in explanted liver or CCA until February 2016 were included in the study. Demographic data, cholangiography findings, laboratory values, cytological morphology and DNA ploidy were analysed. RESULTS Thirty PSC patients had biliary neoplasia in the explanted liver during the study period. Sixteen of these patients had low-grade dysplasia, 10 patients had high-grade dysplasia, and 4 patients had CCA. Fifteen PSC patients diagnosed with CCA were not transplanted. Patients with low-grade dysplasia were younger. Alkaline phosphatase or carcinoembryonic antigen values did not differ between groups during surveillance, but carbohydrate antigen 19-9 was higher in CCA patients. No difference in PSC duration, ERC scores, suspicious cytology, or ploidy analysis was found between groups. No difference was observed between fibrosis stage in explanted livers. Low-and high-grade dysplasia could not be differentiated before liver transplantation based on liver enzymes, tumour markers, ERC scores, brush cytology or DNA ploidy. CONCLUSION Repeated suspicion of neoplasia in brush cytology should be an indication for evaluations of liver transplantation prior to the development of CCA.

Patients with mutations in the POLG1 gene encoding mitochondrial DNA polymerase gamma have an increased risk of valproate-induced liver failure. POLG1 mutations are common, and these patients often suffer from intractable seizures. The role of liver transplantation in the treatment of patients with mitochondrial diseases has been controversial. We studied valproate-induced liver failure associated with POLG1 mutations and the prognosis for these patients after liver transplantation. POLG1 was analyzed in blood DNA, mitochondrial DNA (mtDNA) was quantified in liver samples, and clinical data were collected. Five patients with valproate-induced liver failure associated with POLG1 mutations were retrospectively identified. Three patients were previously suspected to have Wilson's disease. Four patients with homozygous p.W748S and p.E1143G mutations had mtDNA depletion in the liver. One of these patients died before anticipated transplantation; the other 3 patients with liver transplantation have survived 4 to 19 years. Two patients have presented with occasional epileptic seizures, and 1 patient has been seizure-free for 11 years. One patient with a heterozygous p.Q1236H mutation (but without mtDNA depletion in the liver) died suddenly 2 years after liver transplantation. In conclusion, the POLG1 mutation status and the age at presentation of valproate-induced liver failure can affect the prognosis after liver transplantation. A heterozygous POLG1 p.Q1236H mutation was related to valproate-induced liver failure without mtDNA depletion, whereas patients homozygous for POLG1 p.W748S and p.E1143G mutations had mtDNA depletion. An analysis of the POLG1 gene should be performed for all patients with suspected mitochondrial disease before the introduction of valproate therapy, and treatment with valproic acid should be avoided in these patients. Liver Transpl 20:1402–1412, 2014. © 2014 AASLD.

Half of adult liver transplantation (LT) recipients develop metabolic syndrome, but the prevalence after childhood LT remains unknown. We conducted a national cross-sectional study of all living patients who had undergone LT between 1987 and 2007 at an age less than 18 years. We gathered information on blood pressure, body composition, serum lipids, glucose metabolism, and histological liver fat content. The diagnostic criteria for metabolic syndrome of the American Heart Association and the International Diabetes Federation were used. After a median post-LT follow-up time of 12 years, half of all patients had no components of metabolic syndrome. The prevalence of overweight/obesity was 20%, and the prevalence of hypertension was 24%. Serum triglycerides were high in 9%, and high-density lipoprotein levels were low in 23%. Fasting glucose levels were impaired in 14%, but none had diabetes. Altogether, 9 patients (14%) had metabolic syndrome. Moderate liver steatosis found in protocol liver biopsy samples was associated with the accumulation of metabolic syndrome features (P = 0.01). No significant associations were found between immunosuppressive medications and metabolic syndrome. In conclusion, the prevalence of metabolic syndrome after childhood LT is similar to the prevalence in the general population of the same age. Guidelines for the general population, therefore, seem valid for the prevention and treatment of metabolic syndrome after pediatric LT as well. Liver Transpl 20:1185–1192, 2014. © 2014 AASLD.

Kidney outcomes in early post-liver transplantation (LT) are crucial for long-term prognosis, but difficult to predict. Among 203 adult LT patients, we studied the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) measured pre-LT for predicting acute kidney injury (AKI), kidney-replacement therapy within three months, and kidney dysfunction at three months post-LT. Glomerular filtration rate (GFR) was estimated by creatinine-based and cystatin C-based equations. Highest NGAL levels were among patients on pre-LT kidney-replacement therapy, whereas NGAL exceeded 200 μg/L in only three (2%) patients with pre-LT GFR60 mL/min. Pre-LT NGAL260 μg/L predicted GFR60 mL/min at three months post-LT (OR 17.8, 95% CI 2.1-153) independently of 19 other variables reflecting recipient characteristics, liver and kidney function, perioperative hemodynamic stress, and immunosuppression. Of 81 patients with pre-LT GFR60 mL/min, 48% had GFR60 mL/min at three months, and an NGAL level260 μg/L predicted this outcome with 90% specificity and 46% sensitivity. NGAL failed to predict post-LT AKI or need for temporary kidney-replacement therapy. In conclusion, NGAL independently predicted irreversibility of pre-LT kidney dysfunction and could thus help in optimizing patient care and in the decision to perform combined liver-kidney transplantation. Pre-LT NGAL was not useful in patients with preserved pre-LT kidney function or in predicting post-LT AKI.

Hepatic artery thrombosis (HAT) after liver transplantation (LT) increases patient morbidity and mortality. Early HAT is considered to occur within the first month after LT, whereas late HAT occurs after the first month. Few studies have addressed late HAT after LT, especially in pediatric patients. Between 1987 and 2007, 99 patients (age

Cytomegalovirus (CMV) can cause severe infections in transplanted patients. To prevent CMV infection, most liver centers use prophylaxis for CMV-seronegative recipients receiving an organ from a seropositive donor (D+/R-). Valganciclovir is mostly given for 3-6 months after transplantation. However, the patients may develop primary CMV infection after the cessation of prophylaxis and late-onset CMV disease may occur.A prospective long-term follow-up of CMV (D+/R-) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated.Of 154 consecutive adult liver recipients transplanted from 2006 to 2009, 20 (13%) were CMV D+/R- and received antiviral prophylaxis up to 3 months after transplantation. After excluding the recipients with incomplete prophylaxis or monitoring, 13 (D+/R-) patients with follow-up of4 years after the 3-month period of valganciclovir prophylaxis were included in the study.The patients were monitored for CMV by real-time quantitative plasma PCR.No break-through CMV infections were recorded during the prophylaxis period. After cessation of valganciclovir prophylaxis 12/13 (90%) patients demonstrated CMV-DNAemia following a post transplantation mean interval of 165 days (range 95-320). Ten patients with high viral loads (peak viral load mean 81,510, range 1900-648950cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (1000cps/ml) were asymptomatic and not treated. No intragraft infection was seen, but one patient developed gastrointestinal CMV infection verified from ileum biopsy. During long-term follow-up, 3 patients demonstrated low-level viral replication, but no symptomatic recurrences occurred. One patient died of bacterial sepsis, but no patient or graft was lost due to CMV.Primary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir.

Prediction of prognosis in hepatocellular carcinoma (HCC) is difficult. The aim of this study was to evaluate the prognostic value of serum MMP-8, -9, -13, and TIMP-1 in patients with HCC.Pre-treatment serum samples from 134 patients with HCC were retrospectively analyzed. The serum concentration of MMP-8 was analyzed with immunofluorometric assay (IFMA), and those of MMP-9, MMP-13, and TIMP-1 were determined by enzyme-linked immunosorbent assays (ELISA). Clinical data were retrieved from patient records and survival data obtained from Statistics Finland.The overall cumulative disease-specific survival was 69% at 1 year, 50% at 2 years, and 33% at 5 years. Kaplan-Meier overall survival analysis showed that patients with low concentrations of serum MMP-8 or TIMP-1 had a statistically significantly better overall survival than patients with high concentrations of serum MMP-8 or TIMP-1 (P=0.013 and P=0.003). Interestingly, the overall survival in patients with high MMP-9/TIMP-1 ratio was statistically significantly better than in those patients with low MMP-9/TIMP-1 ratio (P=0.004).Our results suggest that serum MMP-8, TIMP-1, and the ratio of MMP-9/TIMP-1 might be useful adjuncts as predictors of prognosis in patients with HCC.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer death worldwide. The aim of this study was to evaluate the prognostic value of serum tumor-associated trypsin inhibitor (TATI) and the free β subunit of human chorionic gonadotropin (hCGβ) in patients with HCC.The serum concentrations of TATI and hCGβ were determined by time-resolved immunofluorometric assays (IFMA) in pretreatment serum samples from 144 patients with HCC. Clinical data were retrieved from patient records and survival data obtained from Statistics Finland.The overall cumulative disease-specific survival was 69% at 1 year, 50% at 2 years and 33% at 5 years. Disease-specific median survival time was 26 months. The overall survival in patients with low serum concentrations of TATI or hCGβ was statistically significantly better than in patients with elevated concentrations (p = 0.003 and 0.003, respectively). In multivariate analysis, both serum TATI and serum hCGβ were independent prognostic markers.The results imply that elevated serum concentrations of TATI and hCGβ are predictors of adverse prognosis in patients with HCC and appear to be useful adjuncts in predicting prognosis in patients with HCC.

Background Chronic calcineurin inhibitor (CNI) nephrotoxicity is associated with histologic kidney lesions, but the contribution of maintenance-dose CNI use to the decline over time in glomerular filtration rate (GFR) post liver transplantation (OLT) remains unclear. Methods We studied annual changes in estimated GFR >1 year posttransplant among 105 CNI-treated adult OLT patients with a GFR of 60–100 mL/min at 1 year during a mean follow-up of 7 years (20 years in 20 patients). Results The annual GFR decline >1 year posttransplant was 0.2 mL/min per year (SD 3.8). This decline rate was unaffected by the decade of OLT, follow-up period, or GFR at 1 year, and showed no correlation with CNI blood levels. Of the 13 (12%) patients with a GFR deterioration >3 mL/min per year, 77% presented with hypertension, diabetes, and/or dyslipidemia. The decline in GFR >1 year post-OLT did not exceed the decline of 0.5–0.8 mL/min per year reported in the general population. Declines faster than 3 mL/min per year, which occurred no more frequently among patients than in the general population, seemed attributable to coexistent vascular risk factors. Conclusions Among OLT patients with preserved renal function at 1 year posttransplant, our findings challenge the clinical impact of chronic progressive CNI nephrotoxicity and highlight the importance of a tight control of blood pressures, glucose and lipid levels, and other modifiable risk factors in order to preserve long-term renal function.

Controversy remains about the role of protocol liver biopsy for symptom-free recipients and about the long-term use of low-dose steroids after pediatric liver transplantation (LT). We conducted a national cross-sectional study of pediatric recipients who underwent LT between 1987 and 2007. Liver biopsy samples were taken from 54 patients (82% of survivors) after a median posttransplant follow-up of 11 years, and they were reviewed by 2 pathologists blinded to the clinical data. Biopsy samples from 18 patients (33%) showed nearly normal histology with no inflammation, fibrosis, or steatosis. Portal inflammation was detected in 14 samples (26%), showed no correlation with anti-nuclear antibodies, and was less frequent in the 35 patients whose immunosuppression included steroids (14% versus 47% of patients not using steroids, P = 0.008). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 16 were stage 1, 3 were stage 2, and 2 were stage 3. The fibrosis stage correlated negatively with serum prealbumin levels (r = -0.364, P = 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r = 0.529, P < 0.001) and portal inflammation (r = 0.350, P = 0.01). Microvesicular steatosis was found in 23 biopsy samples (43% of patients in 5%-80% of hepatocytes), and it correlated with the body mass index (r = 0.458, P < 0.001) but not with steroid use. The age of the allograft (donor age plus follow-up time) correlated with higher serum gamma-glutamyltransferase (r = 0.472, P < 0.001) and conjugated bilirubin levels (r = 0.420, P = 0.002) as well as chronic cholestasis (r = 0.299, P = 0.03). The biopsy findings led to treatment changes in 10 patients (19%), whereas only 1 complication (subcapsular hematoma) was encountered. In conclusion, continuing low-dose steroids indefinitely after pediatric LT may have a positive effect on the long-term histological state of the liver graft. Allograft aging may lead to chronic cholestasis and thus contribute to the development of liver fibrosis.

The aim of this study was to characterize outcomes of children with severe intestinal motility disorders (IMD) requiring parenteral nutrition (PN).Twenty consecutive children with primary IMD requiring long-term PN between 1984 and 2010 were included. Median (interquartile range) follow-up was 13.1 (5.2-20.1) years. Treatment, PN dependence, growth, nutritional status, liver function, and survival were assessed.Underlying etiology included chronic intestinal pseudo obstruction (CIPO; n=8) and Hirschsprung disease with extensive aganglionosis (n=12). CIPO and aganglionosis patients had 100 (86-100%) and 29 (19-40%) of age-adjusted small bowel length remaining, respectively. In order to facilitate enteral tolerance and avoid PN-associated liver disease, short aganglionic segment (40 cm) was left in situ in four of five cases, with aganglionosis extending to duodenojejunal flexure combined with Ziegler myectomy-myotomy in two. Six of seven children with aganglionosis extending into mid small intestine underwent staged jejunoanal pull-through. Feeding/venting gastrostomies (n=13) or jejunostomies were commonly employed. Probability of PN dependence owing to IMD was markedly increased in relation to short bowel syndrome (70 versus 19% at 5 years, P0.0001). Two (10%) patients developed end-stage liver disease. A total of 11 (55%) patients (5 CIPO and 6 aganglionosis) weaned off PN after 8.2 years (1.8-17 years), including two patients after intestinal transplantation (ITx). Two children died before ITx-era giving overall survival of 90%. Survivors had well-preserved liver function, growth, and nutritional status.Despite high PN dependence, long-term survival is achievable in the majority of children with IMD requiring PN. A wide repertory of surgical options including ITx is required for optimal outcomes.