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Abstract 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. [ABSTRACT FROM AUTHOR]

Abstract: Aim: The aim of this study was to characterize outcomes of children with severe intestinal motility disorders (IMD) requiring parenteral nutrition (PN). Methods: 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. Results: 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 (40cm) 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 5years, P <0.0001). Two (10%) patients developed end-stage liver disease. A total of 11 (55%) patients (5 CIPO and 6 aganglionosis) weaned off PN after 8.2years (1.8–17years), 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. Conclusions: 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. [Copyright &y& Elsevier]

Abstract: Emerging new techniques for liver resections set new requirements for the preoperative imaging and planning. Open surgery is a three-dimensional procedure and planning of the resection line may be difficult when basing on conventional two-dimensional CTs or MRIs, although all the information is there. With multidetector-row CT (MDCT), thin slices can be obtained with excellent temporal resolution, and precise three-dimensional (3D) models can be created. We regard 3D imaging technique useful in most liver resections. It improves the surgeon''s knowledge of liver anatomy and makes even more complicated liver resections safe. Better knowledge of three-dimensional appearances of liver structures may further improve the results of curative liver surgery. However, before becoming a routine clinical procedure, research and development are still needed. Also, careful testing and evaluation of the methods have to be performed. In the future, 3D models will probably play an important role in the preoperative planning of liver resections. [Copyright &y& Elsevier]

Abstract: Background: Cytomegalovirus (CMV) is a significant infectious agent after liver transplantation. To prevent CMV, most centres use prophylaxis for high-risk CMV-seronegative recipient/seropositive donor and many even for all seropositive recipients. However, pre-emptive therapy is commonly used for seropositive patients. Objectives: A prospective, long-term follow-up of CMV-seropositive adult liver-transplant patients under pre-emptive strategy was investigated. Study design: CMV-seropositive liver recipients were monitored for CMV by real-time quantitative plasma polymerase chain reaction (PCR) and received ganciclovir/valganciclovir pre-emptive therapy. The 161 patients with follow-up of >4 years were included in the study. Results: No CMV was detected in most cases 98/161 (61%), but 63/161 (39%) developed CMV-DNAaemia mean 49 days (7–183 days) after transplantation. Only 25/63 reactivations exceeded 5000copies/ml, which was considered as cut-off for the pre-emptive treatment by the method used (median 21,500, range 5100–813300copies/ml) and most were self-limiting, low-level DNAaemias (median 850, range 234–4000copies/ml). Thus, low-level temporal CMV viraemia occurred in 38/161 patients (23.5%) and only 25/161 (15.5%) demonstrated significant viral loads. Recurrent CMV appeared in one patient with low-level and in 11/25 with high-level DNAaemia, only 5/11 exceeding 5000copies/ml. CMV infections were successfully treated with ganciclovir/valganciclovir. Four patients with low and three with high DNAaemia have been retransplanted. Five patients with low and two with high DNAaemia have died subsequently. No patient or graft was lost due to CMV. Conclusions: Most CMV-seropositive liver recipients did not develop CMV reactivation, and if reactivations occurred, most were temporal, low-level DNAaemias. Significant CMV infections were successfully treated and recurrences were rare. [Copyright &y& Elsevier]

Background 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. Objectives A prospective long-term follow-up of CMV (D+/R−) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated. Study design 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 of >4 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. Results 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 1900–648950 cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (<1000 cps/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. Conclusions Primary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir. [ABSTRACT FROM AUTHOR]

Background/Aims: Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-α1-antitrypsin for cholangiocarcinoma and to compare them with CA19-9 and CEA. Methods: The study consisted of 84 patients with either PSC or cholangiocarcinoma or both referred for liver transplantation or other liver surgery. The serum concentrations were determined by time-resolved immunofluorometric assays. Results: Forty-six patients were transplanted due to PSC; in 3 of the explanted livers cholangiocarcinoma was found incidentally. All transplanted patients had severe biliary strictures together with cirrhosis or pre-cirrhosis. Twenty-nine of 38 patients with cholangiocarcinoma were candidates for intervention. In all, 8 patients had both PSC and cholangiocarcinoma. Receiver-operating characteristics curve analysis showed that serum trypsinogen-2 had the highest accuracy in differentiating between cholangiocarcinoma and PSC. The area under the curve (AUC) value was 0.804 for trypsinogen-2 and 0.613 for CA19-9. Serum trypsinogen-2 also showed the highest accuracy for differentiation between PSC and PSC with simultaneous cholangiocarcinoma with an AUC value of 0.759. Conclusions: Our results suggest that serum trypsinogen-2 is a most useful marker for diagnosing patients with cholangiocarcinoma, and it is superior to serum CA19-9 and CEA. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Solid organ transplant (SOT) patients are at significant risk for invasive pneumococcal disease. The optimal pneumococcal vaccination strategy for SOT patients is not known. 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). 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 (GMĆs) of antibodies for serotypes 6A, 7F and 23F, and the geometric mean titers (GMT́s) 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. 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. [ABSTRACT FROM AUTHOR]