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Background: Thoracic epidural analgesia (TEA) is not widely used for postoperative pain management in liver transplantation due to hepatic coagulopathy-related increased risk of inducing an epidural hematoma. However, an increasing number of patients are transplanted for other indications than the end-stage liver disease and without coagulopathy allowing insertion of an epidural catheter., Methods: This study is a retrospective observational single-center study of all adult patients undergoing first-time liver transplantation at Oslo University Hospital between January 1, 2008, and December 31, 2017. Data regarding patient characteristics were obtained from the Nordic liver transplant registry, medical records, and pain registration forms. Patients without coagulopathy (international normalized ratio <1.5 and platelets >100 × 10 9 /L) were eligible for TEA., Results: Out of 685 first-time liver transplantations in a 10-year period, 327 received TEA, and 358 did not. The median Model of End-stage Liver Disease score was lower in the TEA group than in the non-TEA-group (9 versus 17, P < 0.001), and fewer patients were hospitalized preoperatively (16 versus 127, P < 0.001). The median international normalized ratio (1.1 versus 1.6, P < 0.001) and platelet count (190 versus 78, P < 0.001) were different between the TEA and non-TEA groups. There were no serious complications related to insertion or removal of the TEA catheters. Patients in the TEA group had less pain with a mean numeric rating scale at postoperative days 0-5 of 1.4 versus 1.8 ( P = 0.008). Nearly 50% of the patients were prescribed opioids when discharged from hospital (non-TEA 154 versus TEA 158, P = 0.23), and there was no difference after 1 year ( P = 0.718)., Conclusions: Our report revealed very good pain control with both TEA and the non-TEA modality. TEA was without any serious complications like epidural hematoma or infection/abscess in selected liver transplant recipients without severe coagulopathy. Opioid prescription at hospital discharge and by 1-year follow-up did not differ between the groups., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

The purpose of this retrospective time-lapse data analysis from transferred preimplantation human embryos was to identify early morphokinetic cleavage variables that are related to implantation and live birth following in vitro fertilization (IVF). All embryos were monitored from fertilization check until embryo transfer for a minimum of 44 hours. The study was designed to assess the association between day 2 embryo morphokinetic variables with implantation and live birth based on Known Implantation Data (KID). The kinetic variables were subjected to quartile-based analysis. The predictive ability for implantation and live birth was studied using receiver operator characteristic (ROC) curves. Three morphokinetic variables, time to 2-cells (t2), duration of second cell cycle (cc2) below one threshold and cc2 above another threshold had the highest predictive value with regards to implantation and live birth following IVF treatment. The predictive pre-transfer information has little divergence between fetal heartbeat and live birth data and therefore, at least for early morphokinetic variables up to the four-cell stage (t4), conclusions and models based on fetal heartbeat data can be expected to be valid for live birth datasets as well. The three above mentioned variables (t2, cc2 below one threshold and cc2 above another threshold) may supplement morphological evaluation in embryo selection and thereby improve the outcome of in vitro fertilization treatments., Competing Interests: Co-author B.M. Petersen is the owner of BMP Analytics, an independent consultancy company. He therefore has no conflicting interests regarding the research presented in this manuscript. BMP has acted as freelance consultant for Vitrolife, as well as other enterprises within IVF and applied science in general. All other authors have no conflicts of interest to disclose.

Introduction: Assisted reproduction technologies are being rapidly developed and implementation of preimplantation genetic testing (PGT) has allowed patients with genetic disorders to initiate pregnancies while minimizing or eliminating the risk of transmitting these disorders to their offspring. Testing for numeric chromosomal anomalies has been proposed as a way to increase efficacy in assisted reproduction; however, this remains disputed. Legislation is lagging behind the rapid developments in this field., Material and Methods: We conducted a structured online survey of legislation and accessibility to preimplantation genetic testing in the Nordic countries to compare the regulation and uptake of this technique. The survey was designed and answered by the authors., Results: Key elements in the regulation of preimplantation testing for monogenic disorders and structural rearrangements are similar in the Nordic countries, although accessibility varies since only Denmark, Finland, and Sweden have national clinics offering treatment. In addition, Denmark and Finland have private clinics offering PGT. Regulation is the most stringent in Norway where a national board evaluates all couples seeking treatment. Treatment volumes vary between the Nordic countries, with Norway and Finland having lowest treatment numbers. Preimplantation genetic testing for aneuploidy in the embryo varies between the Nordic countries: Finland and Iceland allow this form of treatment, Denmark and Sweden offer it only in the form of a research protocol, and Norway does not allow it at all. Therefore the number of treatment cycles involving testing for embryo aneuploidy are lower in the Nordic countries than in other countries where this treatment option is more common., Conclusions: Science needs to inform politics regarding the rapidly evolving field of reproductive medicine and we recommend harmonization of legislation and accessibility between the Nordic countries., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Objective: We conducted a randomized, controlled, noninferiority trial to investigate if intravenous, multimodal, patient-controlled analgesia (IV-PCA) could be noninferior to multimodal thoracic epidural analgesia (TEA) in patients undergoing open liver surgery., Summary Background Data: The increasing use of minimally invasive techniques and fast track protocols have questioned the position of epidural analgesia as the optimal method of pain management after abdominal surgery., Methods: Patients operated with open liver resection between February 2012 and February 2016 were randomly assigned to receive either IV-PCA enhanced with ketorolac/diclofenac (IV-PCA, n = 66) or TEA (n = 77) within an enhanced recovery after surgery protocol. Noninferiority would be declared if the mean pain score on the numeric rating scale (NRS) for postoperative days (PODs) 0 to 5 in the IV-PCA group was no worse than the mean pain score in the TEA group by a margin of <1 point on an 11-point scale (0-10)., Results: The primary endpoint, mean NRS pain score was 1.7 in the IV-PCA group and 1.6 in the TEA group, establishing noninferiority. Pain scores were lower in the TEA group on PODs 0 and 1, but higher or equal on PODs 2 and 5. Postoperative hospital stay was significantly shorter for patients in the IV-PCA group (74 vs 104 h, P < 0.001). The total opioid consumption during the first 3 days was significantly lower in the IV-PCA group., Conclusions: IV-PCA was noninferior to TEA for the treatment of postoperative pain in patients undergoing open liver resection.

Background: Three-dimensional (3D) echocardiography with multiplanar reconstruction (MPR) is used clinically to quantify the mitral annulus. MPR images are, however, presented on a two-dimensional screen, calling into question their accuracy. An alternative to MPR is an autostereoscopic holographic display that enables in-depth visualization of 3D echocardiographic data without the need for special glasses. The aim of this study was to validate an autostereoscopic display using sonomicrometry as a gold standard., Methods: In 11 anesthetized open-chest pigs, sonomicrometric crystals were placed along the mitral annulus and near the left ventricular apex. High-fidelity catheters measured left atrial and ventricular pressures. Adjustments of pre- and afterload were done by constriction of the inferior vena cava and the ascending aorta, respectively. Three-dimensional epicardial echocardiography was obtained from an apical view and converted to the autostereoscopic display. A 3D virtual semitransparent annular surface (VSAS) was generated to measure commissure width (CW), septal-lateral length, area of the mitral annular surface, nonplanarity angle, and the annular height-to-commissure width ratio in mid-systole and late diastole., Results: Mitral annular measurements from the 3D VSAS derived from the 3D echocardiographic images and autostereoscopic display correlated well with sonomicrometry over a range of loading conditions: CW length (r = 0.98, P < .00001), septal-lateral length (r = 0.98, P < .00001), annular surface area (r = 0.93, P < .001), nonplanarity angle (r = 0.87, P < .001), and annular height-to-commissure width ratio (r = 0.85, P < .01). The 3D VSAS showed better agreement with the sonomicrometric measurements compared with MPR., Conclusions: Mitral annular measurements using 3D VSAS correlate well with sonomicrometry over a range of loading conditions and may represent a powerful tool for noninvasive quantification of mitral annular dynamics., (Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Though rare in cervical cancer patients, paraneoplastic syndrome usually presents with several endocrine and hormonal symptoms. Knowledge of the pathophysiology that underlies these abnormalities is beneficial to diagnosis and treatment. An interdisciplinary approach and test analysis prior to initiating specific treatment is recommended, though prognosis appears poor in advanced cases.

Objective: To perform the first randomized controlled trial to compare laparoscopic and open liver resection., Summary Background Data: Laparoscopic liver resection is increasingly used for the surgical treatment of liver tumors. However, high-level evidence to conclude that laparoscopic liver resection is superior to open liver resection is lacking., Methods: Explanatory, assessor-blinded, single center, randomized superiority trial recruiting patients from Oslo University Hospital, Oslo, Norway from February 2012 to January 2016. A total of 280 patients with resectable liver metastases from colorectal cancer were randomly assigned to undergo laparoscopic (n = 133) or open (n = 147) parenchyma-sparing liver resection. The primary outcome was postoperative complications within 30 days (Accordion grade 2 or higher). Secondary outcomes included cost-effectiveness, postoperative hospital stay, blood loss, operation time, and resection margins., Results: The postoperative complication rate was 19% in the laparoscopic-surgery group and 31% in the open-surgery group (12 percentage points difference [95% confidence interval 1.67-21.8; P = 0.021]). The postoperative hospital stay was shorter for laparoscopic surgery (53 vs 96 hours, P < 0.001), whereas there were no differences in blood loss, operation time, and resection margins. Mortality at 90 days did not differ significantly from the laparoscopic group (0 patients) to the open group (1 patient). In a 4-month perspective, the costs were equal, whereas patients in the laparoscopic-surgery group gained 0.011 quality-adjusted life years compared to patients in the open-surgery group (P = 0.001)., Conclusions: In patients undergoing parenchyma-sparing liver resection for colorectal metastases, laparoscopic surgery was associated with significantly less postoperative complications compared to open surgery. Laparoscopic resection was cost-effective compared to open resection with a 67% probability. The rate of free resection margins was the same in both groups. Our results support the continued implementation of laparoscopic liver resection.

Objective: The molecular adsorbent recirculating system (MARS) is used to purify blood from albumin-bound toxins in patients with liver failure. However, the application of MARS has not demonstrated improved survival in randomized clinical trials and the clinical utility has not been finally established. In our department, the use of MARS is now restricted to the most critically ill patients with acute or acute on chronic liver failure., Material and Methods: Since 2005, we have treated 69 patients (30 males/39 females with median age of 49 years ranging from 1 months to 70 years) listed for liver transplantation (LT) with MARS. Median model of end-stage liver disease score in patients older than 12 years of age (n = 56) was 33 (interquartile range 26-39). The flow rate was 35-40 mL/kg/h and treatment kits were changed every 8-12 h. The patients were treated for a median of 27 h (range 1-144 h)., Results: Fifty-six patients (81%) were transplanted. Nine died before they could be transplanted, and four patients recovered without transplantation. Forty-six (82%) of the transplanted patients were alive 30 days after transplantation. Ammonium decreased modestly from a median of 148 to 124 µM (p = 0.03) during MARS treatment. We detected worsening of coagulopathy with significant decreases in platelet count and fibrinogen concentrations, and increase in International Normalized Ratio. Phosphate and magnesium decreased significantly during MARS treatment., Conclusion: Continuous MARS therapy may bridge liver failure patients to LT under close observation and treatment of coagulopathy and electrolyte disturbances.

Objective: The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs)., Background: Patients with nonresectable CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated., Methods: In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy., Results: Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8-60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors., Conclusions: OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).

To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when < or = 5 follicles developed in a preceding cycle following a long agonist protocol with the use of > 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5 before expected start of menstruation and continued for 4-7 days. On cycle day 2-3 a starting dose of rFSH (300-400 IU/day) was given. At a leading follicle diameter of 14 mm, ganirelix administration was resumed until final oocyte maturation was induced with 10,000 IU hCG. GnRH antagonist only marginally affected the intercycle FSH rise; basal levels of FSH remained similar to those seen after 4 days of antagonist administration. The protocol effectively induced low LH levels and luteolysis, but daily administration of 350 IU rFSH (median) for 11 days only led to the collection of 3 oocytes in 49 oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release may improve the stimulation results in poor responders.

Background: In Norway, liver transplantation has been the treatment of choice for irreversible acute and chronic liver failure for 25 years. The aim of this article is to present a summary of the results obtained., Material and Methods: All liver transplants performed in Norway in the period 25.02.84-31.12.08 have been reviewed retrospectively with respect to patient and donor epidemiology, survival and recurrence., Results: 651 transplants have been performed in this period. The annual number of transplants increased gradually up to the year 2000 (31), and more steeply afterwards - to 79 in 2008. Also the number of organ donations has increased and reached 98 (20 pr. million inh.) in 2008. 5-year patient survival was 53 % in the period 1984-1994. In the period 2001-2008, 1-year survival was 90 % and 5-year survival was 83 %., Interpretation: The gradual improvement of results should be interpreted in light of improvements within transplant surgery, medicine and anaesthesiology and the increased local experience due to the increasing number of transplants performed. The transplant centre at Rikshospitalet has developed into being among the largest of its kind within the Nordic Countries and the results compare well with the best international data.