Background
Hemostasis is a central issue in laparoscopic surgery. Ultrasonic scissors and bipolar clamps are commonly used, with known advantages with each technique.
Methods
The prototype of new ...surgical scissors, delivering ultrasonically generated frictional heat energy and bipolar heat energy simultaneously (THUNDERBEAT
®
TB), was compared to ultrasonic scissors (Harmonic ACE
®
HA) and an advanced bipolar device (LigaSure
®
LS) using a pig model. As safety parameters, temperature profiles after single activation and after a defined cut were determined. As efficacy parameters, seal failures and the maximum burst pressure (BP) were measured after in vivo sealing of vessels of various types and diameters (categories 2–4 and 5–7 mm). Moreover, the vertical width of the tissue seal was measured on serial histological slices of selected arteries. The cutting speed was measured during division of isolated arteries and during dissection of a defined length of compound tissue (10 cm of mesentery). Burst-pressure measurement and histological analysis were performed by investigators blinded to the used sealing device.
Results
Using the TB, the burst pressure in larger arteries was significantly higher (734 ± 64 mmHg) than that of the HA (453 ± 50 mmHg). No differences in the rate of seal failures were observed. The cutting speed of the TB was significantly higher than that of all other devices. Safety evaluation revealed temperatures below 100 °C in the bipolar device. The maximum temperature of the HA and the TB was significantly higher. No relevant differences were observed between the HA and the TB.
Conclusions
The ultrasonic and bipolar technique of the TB has the potential to surpass the dissection speed of ultrasonic devices with the sealing efficacy of bipolar clamps. However, heat production that is comparable to conventional ultrasonic scissors should be minded for clinical use.
De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our ...institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow‐up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow‐up. The median follow‐up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3‐81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio HR, 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A–treated compared with tacrolimus‐treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow‐up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404–1414 2017 AASLD.
Patients after LT due to combined HBV/HDV infection are considered to be high-risk patients for recurrence of hepatitis B and D. To date, life-long prophylaxis with hepatitis B immunoglobulin (HBIG) ...and replication control with nucleos(t)ide analogs (NA) remains standard. We examined the course of 36 patients that underwent liver transplantation from 1989 to 2020 for combined HBV/HDV-associated end-stage liver disease in this retrospective study. Seventeen patients eventually discontinued HBIG therapy for various reasons. Their graft function, histopathological findings from routine liver biopsies and overall survival were compared with those that received an unaltered NA-based standard regimen combined with HBIG. The median follow-up was 204 and 227 months, respectively. The recurrence of HBV was 25% and did not differ between the groups of standard reinfection prophylaxis NA/HBIG (21.1%) and HBIG discontinuation (29.4%); (
= 0.56). No significant differences were found regarding the clinical course or histopathological aspects of liver tissue damage (inflammation, fibrosis, steatosis) between these two groups. Overall, and adjusted survival did not differ between the groups. Discontinuation of HBIG in stable patients after LT for combined HBV/HDV did not lead to impaired overall survival or higher recurrence rate of HBV/HDV infection in this long-term follow-up. Therefore, the recommendation of the duration of HBG administration must be questioned. The earliest time of discontinuation remains unclear.
As COVID-19 remains an issue in transplantation medicine, a successful vaccination can prevent infections and life-threatening courses. The probability of poor immune response in liver transplant ...recipients gained attention and insecurity among those patients, leading us to investigate the humoral immune response alongside the influence of underlying diseases and immunosuppressive regimen on seroconversion rates. We included 118 patients undergoing anti-spike-protein-IgG testing at least 21 days after completed SARS-CoV-2 vaccination. Ninety-seven patients also underwent anti-spike-protein-IgA testing. The influence of baseline demographics, immunosuppressive regimen and underlying disease on seroconversion was analyzed, and 92 of 118 patients (78.0%) developed anti-spike-protein-IgG antibodies. Patients with a history of alcoholic liver disease before transplantation showed significantly lower seroconversion rates (
= 0.006). Immunosuppression also significantly influenced antibody development (
< 0.001). Patients run on a mycophenolate mofetil (MMF)-based regimen were more likely not to develop antibodies compared to patients run on a non-MMF regimen (
< 0.001). All patients weaned off immunosuppression were seropositive. The seroconversion rate of 78.0% in our cohort of liver transplant recipients is promising. The identification of alcohol-induced cirrhosis as underlying disease and MMF for immunosuppression as risk factors for seronegativity may serve to identify vaccination non-responder after liver transplantation.
The development of liver graft disease is partially determined by individual genetic background. Interleukin 28B (IL28B) is strongly suspected to be involved in susceptibility for hepatitis C virus ...(HCV) infection, inflammation, and antiviral treatment response before and after liver transplantation (LT). Currently, the role of IL28B polymorphism (rs12979860) in the development of hepatocellular carcinoma (HCC) is unclear, and only limited data are available on the course of HCV recurrence.
One hundred sixty-seven HCV-positive patients after LT were genotyped for IL28B (C→T; rs12979860). Sixty-one patients with histologically confirmed HCC in the explanted liver were compared with 106 patients without HCC regarding IL28B genotypes. Among patients with HCC, IL28B genotypes were correlated with tumor histology and pretransplant α-fetoprotein (AFP) levels. Furthermore, the role of IL28B polymorphism was evaluated regarding interferon-based treatment success and fibrosis progression after LT.
The prevalence of HCC in explanted livers was significantly higher among patients with TT genotype, suggesting a protective role of the C allele in HCC development (P=0.041). Median AFP level was closely to significance higher in the presence of T allele (P=0.052). Significant differences in IL28B genotype distribution were detected between AFP-negative and AFP-positive HCCs (<15 μg/L vs. >15 μg/L; P=0.008). Although no impact could be observed regarding acute cellular rejection (P=0.940), T allele was significantly associated with antiviral therapy failure (P=0.028) and faster development of advanced fibrosis (P=0.017) after LT.
IL28B polymorphism seems to be involved in the development of HCV-induced HCC and in the course of HCV recurrence after LT. T allele may be regarded as a genetic risk factor for HCV-related carcinogenesis, posttransplant fibrosis progression, and antiviral therapy failure.
Background and Objectives: Development of hepatitis-B is considered a serious complication after liver transplantation. HBV de novo infection is a rather rare phenomenon, however it deserves ...attention in the era of donor organ shortage. The aim of the present analysis was to examine its course in liver transplant patients. Materials and Methods: Prevalence of de novo HBV-infections was extracted from our local transplant data base. Analysis focused on the moment of HBV-detection and on the long-term follow-up in terms of biochemical and histological changes over 30 years. Results: 46 patients were identified with the diagnosis of de novo hepatitis B. Median time from liver transplantation to diagnosis was 397 days (7–5505). 39 patients received antiviral therapy. No fibrosis progression could be detected, whereas the grade of inflammation significantly lessened from the moment of HBV detection to the end of histological follow-up over a median of 4344 days (range 123–9490). Patients with a poor virological control demonstrated a significantly poorer overall survival. Conclusions: De novo hepatitis B in liver transplant patients is a condition that can be controlled very well without significant fibrosis progression or graft loss if recognized on time within a regular transplant follow-up schedule.
Background and objectives Budd-Chiari syndrome (BCS) refers to a complete thrombotic obstruction of the venous hepatic outflow tract due to various etiologies and constitutes a rare indication for ...ortothopic liver transplantation (LT). Few studies investigated long-term outcomes after LT for BCS. The aim of this study was to examine potential risk factors for late mortality and to evaluate long-term outcomes after LT for BCS. Materials and methods: 46 patients received an LT for BCS between 1989 and 2019 at the transplant center of the Charité-Universitätsmedizin Berlin. We analyzed potential effects of disease etiology, vascular events, rejection, and immunosuppression on long-term survival after transplantation using Kaplan-Meier curves and Cox logistic regression. Results: Of the 46 patients, 70% were female and 30% were male. Median age at the time of transplantation was 36 years. A total of 41 vascular events, including 26 thrombotic and 17 hemorrhagic incidents, occurred. The 1 year, the 5 year, the 10 year, and the 20 year survival rates were 87%, 83%, 76%, and 60%, respectively. By comparison, survival rates of the liver transplant cohort across all other indications at our center were slightly inferior with 85%, 75%, 65%, and 46%, respectively. In the study population, patients with myeloproliferative disorders showed worse outcomes compared to patients with other causes of BCS. Conclusion: Liver transplantation for BCS showed excellent results, even superior to those for other indications. Vascular events (i.e., thrombotic or hemorrhagic complications) did not have any prognostic value for overall mortality. Patients with myeloproliferative disorders seem to have a disadvantage in survival.
Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of ...great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown.
All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed.
Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0-203.0), with the majority presenting early after transplantation (63.0%, <2 years). Median survival after rHCC diagnosis was 10.6 months (0.3-228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (
= 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months).
Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.
Background and Objectives: After liver transplantation (LT), long-term immunosuppression (IS) is essential. IS is associated with de novo malignancies, and the incidence of colorectal cancer (CRC) is ...increased in LT patients. We assessed course of disease in patients with de novo CRC after LT with focus of IS and impact on survival in a retrospective, single-center study. Materials and Methods: All patients diagnosed with CRC after LT between 1988 and 2019 were included. The management of IS regimen following diagnosis and the oncological treatment approach were analyzed: Kaplan−Meier analysis as well as univariate and multivariate analysis were performed. Results: A total of 33 out of 2744 patients were diagnosed with CRC after LT. Two groups were identified: patients with restrictive IS management undergoing dose reduction (RIM group, n = 20) and those with unaltered regimen (maintenance group, n = 13). The groups did not differ in clinical and oncological characteristics. Statistically significant improved survival was found in Kaplan−Meier analysis for patients in the RIM group with 83.46 (8.4−193.1) months in RIM and 24.8 (0.5−298.9) months in the maintenance group (log rank = 0.02) and showed a trend in multivariate cox regression (p = 0.054, HR = 14.3, CI = 0.96−213.67). Conclusions: Immunosuppressive therapy should be reduced further in patients suffering from CRC after LT in an individualized manner to enable optimal oncological therapy and enable improved survival.
Body composition alterations are frequent in patients with cancer or chronic liver disease, but their prognostic value remains unclear in many cancer entities.
We investigated the impact of disease ...aetiology and body composition after surgery for intrahepatic cholangiocarcinoma (iCCA), a rare and understudied cancer entity in European and North American cohorts.
Computer tomography-based assessment of body composition at the level of the third lumbar vertebra was performed in 173 patients undergoing curative-intent liver resection for iCCA at the Department of Surgery, Charité - Universitätsmedizin Berlin. Muscle mass and -composition as well as subcutaneous and visceral adipose tissue quantity were determined semi-automatically. (Secondary) sarcopenia, sarcopenic obesity, myosteatosis, visceral and subcutaneous obesity were correlated to clinicopathological data.
Sarcopenia was associated with post-operative morbidity (intraoperative transfusions p = 0.027, Clavien-Dindo ≥ IIIb complications p = 0.030, post-operative comprehensive complication index, CCI p < 0.001). Inferior overall survival was noted in patients with myosteatosis (33 vs. 23 months, p = 0.020). Fifty-eight patients (34%) had metabolic (dysfunction)-associated fatty liver disease (MAFLD) and had a significantly higher incidence of sarcopenic (p = 0.006), visceral (p < 0.001) and subcutaneous obesity (p < 0.001). Patients with MAFLD had longer time-to-recurrence (median: 38 vs. 12 months, p = 0.025, log-rank test). Multivariable cox regression analysis confirmed only clinical, and not body, composition parameters (age > 65, fresh frozen plasma transfusions) as independently prognostic for overall survival.
This study evidenced a high prevalence of MAFLD in iCCA, suggesting its potential contribution to disease aetiology. Alterations of muscle mass and adipose tissue were more frequent in patients with MAFLD.
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