The first 10 years of simultaneous pancreas-kidney transplantation in Finland.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program. METHODS: This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records. RESULTS: A total of 166 SPKs were performed (median 2 per year in the first 3 years, 17.5 per year for the following 4 years, and 23 per year for the past 3 years). Seven patients (4.1%) died with a functioning graft with a median 43 months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36 mmol/mol (SD 5.57) and creatinine was 107 µmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N = 28). No pancreas or kidney graft failure from thrombosis occurred. CONCLUSION: A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure.

Gamma-glutamyltransferase predicts macrovesicular liver graft steatosis - an analysis of discarded liver allografts in Finland.

OBJECTIVE: Liver-transplantation activity is limited by the shortage of grafts. Donor-liver macrovesicular steatosis predisposes to ischemia-reperfusion injury and is associated with reduced graft survival. The increasing prevalence of fatty-liver disease underlines the importance of identifying macrovesicular steatosis in potential donor livers. We analyzed liver grafts discarded for transplantation, and particularly the role of gamma-glutamyltransferase (GGT) in predicting graft steatosis. METHODS: One-hundred sixty rejected cadaveric-donor liver grafts were studied. Donor selection was based on clinical data, and macroscopic graft inspection. Discarded grafts were biopsied at procurement of non-liver organs. RESULTS: The most common reasons for discarding the graft were abnormal liver tests, ultrasound-verified steatosis and history of harmful alcohol use. GGT correlated moderately with macrovesicular steatosis (r = 0.52, p < 0.001), but poorly with microvesicular steatosis (r = 0.36, p < 0.001). Increased correlation between GGT and macrovesicular steatosis was observed among alcohol abusers (r = 0.67, p < 0.001). Area under the curve (AUC) of GGT for predicting >30% macrovesicular steatosis was 0.79 (95% CI 0.71-0.88), and for >60% steatosis, 0.79 (95% CI 0.68-0.90). The optimal GGT-cut off for detecting >30% and >60% macrovesicular steatosis were, respectively, 66 U/L (sensitivity 76% and specificity 68%) and 142 U/L (sensitivity 66% and specificity 83%). Among alcohol users, a GGT value >90 U/L showed 100% sensitivity for >60% macrovesicular steatosis. AUC for GGT in predicting fibrosis Stages 2-4 was 0.82 (95% CI 0.71-0.92, p < 0.001, optimal cut off 68, sensitivity 92%, specificity 61%). CONCLUSIONS: Abnormal liver values, steatosis and harmful alcohol use were the main reasons for discarding liver-graft offers in Finland. GGT proved useful in predicting moderate and severe liver graft macrovesicular steatosis.

Characteristics, management and outcomes of choledochal malformations in Finnish adult patients.

CONCLUSIONS: 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.

Timing of Organ Procurement From Brain-Dead Donors Associates With Short- and Long-Term Outcomes After Liver Transplantation.

Brain death-induced cytokine storm is thought to harm transplantable organs. However, longer procurement times have been associated with non-inferior or better outcomes in kidney, heart, and lung transplants, while optimal procurement time for liver allografts is unknown. Our aim was to analyze the association of time interval from brain death to organ procurement with liver allograft outcomes in two nationwide cohorts. The association of procurement interval with graft survival and short-term complications was analysed in multivariable models. Altogether 643 and 58,017 orthotopic liver transplantations from brain-dead donors were included from Finland between June 2004 and December 2017 and the US between January 2008 and August 2018, respectively. Median time from brain death to organ procurement was 10.5 h in Finland and 34.6 h in the US. Longer interval associated with better graft survival (non-linearly, p = 0.016) and less acute rejections (OR 0.935 95% CI 0.894-0.978) in the US cohort, and better early allograft function (p = 0.005; Beta -0.048 95% CI -0.085 -(-0.011)) in the Finnish cohort, in multivariable models adjusted with Donor Risk Index, recipient age, Model for End-Stage Liver Disease and indication for transplantation. Progressive liver injury after brain death is unlikely. Rushing to recover seems unnecessary; rest and repair might prove beneficial.

Genomic Characterization of Cholangiocarcinoma in Primary Sclerosing Cholangitis Reveals Therapeutic Opportunities.

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 as TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (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.

Gallbladder cancer epidemiology, treatment and survival in Southern Finland - a population-based study.

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.

Access of non-residents to transplantation of deceased donor organs: practices and strategies in the European setting.

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.

Long-term Morbidity of Choledochal Malformations in Children.

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.

Outcomes and quality of life after major bile duct injury in long-term follow-up.

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.

Pre- vs. postoperative initiation of thromboprophylaxis in liver surgery.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Initiating thromboprophylaxis preoperatively may reduce the incidence of postoperative VTE without affecting the incidence of posthepatectomy haemorrhage in patients undergoing liver resection.

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

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.

Predictors of insufficient recanalization and portal hypertensive complications after treatment of non-cirrhotic, non-malignant portal vein thrombosis - a population-based study.

OBJECTIVES: In acute portal vein thrombosis (PVT), a six-month anticoagulation treatment achieves complete recanalization in only 35%-45% of patients, but the predictors of poor treatment responses are unclear. We examined treatment outcomes in PVT and aimed to identify predictors of incomplete recanalization and portal hypertensive complications. MATERIALS AND METHODS: This retrospective study comprised patients diagnosed with PVT between 2006 and 2015. Key exclusion criteria were liver cirrhosis, malignancy, and age <18. RESULTS: The final cohort comprised 145 patients, of whom 132 (92%) were primarily treated with anticoagulation. The 5-year cumulative incidence of complete recanalization was 42% and of portal hypertensive complications, 31%. Independent predictors of insufficient recanalization were sub-acute or chronic thrombosis (hazard ratio (HR) 3.1, 95% CI 1.6-5.8), while acute pancreatitis was a protective factor (HR 0.3, 95% CI 0.2 - 0.7). Independent predictors of incident portal hypertensive complications were as cites at baseline (HR 3.3, 95% CI 1.7-6.7), sub-acute or chronic thrombosis (HR 2.9, 95% CI 1.6-5.3), extension of thrombosis to the splenic or mesenteric vein (HR 2.6, 95% CI 1.2-5.7), myeloproliferative disease (HR 3.0, 95% CI 1.4-6.5), and anemia (HR 2.1, 95% 1.1-3.9), while acute pancreatitis was a protective factor (HR 0.1, 95% CI 0.03-0.5). CONCLUSIONS: Etiology and age of thrombosis are associated with treatment responses in PVT. The presence of ascites at baseline, etiology, and extent of thrombosis, a non-acute thrombosis and anemia, are associated with the risk of portal hypertensive complications. Etiology and extent of thrombosis should be taken into account when determining the treatment (method) for PVT.

A randomized, controlled trial comparing the immunogenecity and safety of a 23-valent pneumococcal polysaccharide vaccination to a repeated dose 13-valent pneumococcal conjugate vaccination in kidney transplant recipients.

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.

L-Cysteine Containing Vitamin Supplement Which Prevents or Alleviates Alcohol-related Hangover Symptoms: Nausea, Headache, Stress and Anxiety.

AIMS: Alcohol-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. METHODS: Voluntary 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. RESULTS: The 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. CONCLUSIONS: L-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.

Incidence and long-term outcomes of surgically treated childhood hepatic malignancies in Finland.

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 1.1:106 . 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.

Cutavirus DNA in Malignant and Nonmalignant Skin of Cutaneous T-Cell Lymphoma and Organ Transplant Patients but Not of Healthy Adults.

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.

Transcatheter arterial embolization in hepatic tumor hemorrhage.

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, efficacy and feasibility of transcatheter arterial embolization (TAE) in the treatment of hepatic tumor hemorrhage. Methods: This retrospective study included all patients undergoing embolization attempt for hepatic tumor hemorrhage in the Helsinki University Hospital during 2004-2017. Electronic medical records provided the study data. Outcomes included the 30-day rebleeding, complication and mortality rates, need for blood transfusions, durations of intensive care unit and hospital admissions, estimates of overall survival, and analysis of factors associated with 30-day mortality. Results: During the study period, 49 patients underwent angiography for hepatic tumor hemorrhage. TAE was technically feasible in 45 patients (92%), and controlled the bleeding with the first attempt in 84%. The 30-day complication and mortality rates were 57 and 33%, respectively. Major complications occurred in 33% of patients. In-hospital mortality was higher among cirrhotic than non-cirrhotic patients (55 versus 7%, p < .001). Patients with bleeding hepatic metastases, but no cirrhosis, had an in-hospital mortality of 0% with no major complications. Patients with benign etiology had a good prognosis and no bleeding- or tumor-related mortality. Discussion: TAE is an effective method in controlling the bleeding in spontaneous hepatic hemorrhage. Underlying pathology determines the prognosis that is poor especially in cirrhotic patients with bleeding hepatocellular carcinoma.

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with squamous cell carcinoma in situ and actinic keratosis - a single-center cohort study.

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.

Liver trauma in a young woman.

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.

Donor-specific antibodies after pediatric liver transplantation: a cross-sectional study of 50 patients.

The role of donor-specific HLA antibodies (DSAs) after pediatric liver transplantation (LT) is inadequately established. We conducted a cross-sectional study on the prevalence of DSAs and their association with liver histology and biochemical variables after pediatric LT. Serum samples were drawn for HLA antibody analyses from 50 patients (76% of 66 eligible patients) operated on at age <18 years between 1987 and 2007 with a median of 10.0 (interquartile range 4.0-16.4) years after deceased donor LT. Mixed and single-antigen beads with Luminex were used for HLA antibody screening and detection. A mean fluorescence intensity (MFI) value of 1000 was used for positive cutoff. Twenty-six patients (52%; 95% confidence interval (CI) 39% to 65%) had DSAs. In 22 (85%) patients, DSAs were against class II HLA antigens with a mean (standard deviation) MFI of 13,481 (4727). The unadjusted prevalence ratio for portal inflammation in DSA-positive compared to DSA-negative patients (n = 47; 9/24 vs. 1/23) was 8.6 (95% CI 1.6 to 50.9). Laboratory values at the time of study were comparable between DSA-positive and DSA-negative patients. In conclusion, approximately half of patients studied had DSAs after pediatric LT. Portal inflammation was associated with DSA positivity although the wide confidence interval around the ratio estimate warrants cautious interpretation.