BackgroundWe investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC).MethodsIn a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor–free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor–free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint.ResultsRecurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874).ConclusionsSirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

BackgroundThe potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.Methods/DesignThe study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.DiscussionIf our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.Trial RegisterTrial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36)

The presented method provides accurate and reproducible p(tc)O(2) values under changing microcirculatory conditions. The lack of oxygen consumption during measurement allows both a more realistic estimation of p(tc)O(2) than compared with the gold standard and permanent use in regions with critical oxygen supply.

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Background Preoperative ultrasound (US)-guided perforator mapping has immensely simplified perforator flap planning. It may be executed by the microsurgeon. Device settings and selection of ultrasound modes are of utmost significance for detection of low-flow microvessels. The following study evaluates different US modes. Methods A prospective complete data acquisition was performed from July 2018 to June 2019 in a subset of patients who underwent US-guided flap planning. Multifrequency linear transducers were used applying five US modes. Brightness (B)-mode, color flow (CF), power Doppler (PD), pulse wave (PW), and B-flow modes were evaluated regarding applicability by microsurgeons. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were chosen to evaluate flow characteristics. US results were correlated to intraoperative findings. Results A total number of eight patients (six males and two females) undergoing anterolateral thigh (ALT) or superficial circumflex iliac artery perforator (SCIP) flap surgery received an extensive standardized US-guided perforator characterization. Qualitative evaluation was performed in B-mode, color-coded duplex sonography (CCDS), PD, and B-flow mode. Quantitative assessment was executed using PW-mode and CCDS measuring the microvessels' diameter (mm) and flow characteristics (PSV, EDV, and RI). CCDS provided a mean diameter of 1.93 mm (range: 1.2–2.8 ± 0.51), a mean systolic peak of 16.9 cm/s (range: 9.9–33.4 ± 7.79), and mean RI of 0.71 (range: 0.55–0.87 ± 0.09) for lower limb perforators. All perforators located with US were verified by intraoperative findings. An optimized, time-effective US mapping algorithm was derived. Qualitative parameters may be evaluated with B-mode, CF, or B-flow. Smallest microvessels may be assessed in PD-mode. Lowering pulse-repetition frequency (PRF)/scale is mandatory to image low-flow microvessels as perforators. Quantitative information may be obtained using PW-mode and the distance-measuring tool in CF-mode. Image and video materials are provided. Conclusion CCDS proved to be a powerful tool for preoperative perforator characterization when using a structured approach and mapping algorithm. Different techniques may be applied for specific visualizations and performed by the microsurgeon.

Compressed Sensing (CS) is a relatively new approach to signal acquisition which has as its goal to minimize the number of measurements needed of the signal in order to guarantee that it is captured to a prescribed accuracy. It is natural to inquire whether this new subject has a role to play in Electron Microscopy (EM). In this paper, we shall describe the foundations of Compressed Sensing and then examine which parts of this new theory may be useful in EM.

6 7 9 THURSDAY Supplement to Transplantation July 27, 2008, Volume 86 Number 2SHCC, and no mortality occurred during the follow-up (mean, 35 ± 8.5 months; range 26-45 months). In conclusion, the incidence of HCC in cirrhotic patients who underwent liver transplant is similar to that of other studies in literature. The incidentally found HCC showed less invasive pathological features and a better prognosis than preoperatively detected HCC. The recurrence of hepatocellular carcinoma (HCC) after transplantation is main limitation of liver transplantation. Therefore the several selection criteria for liver transplantation in HCC patients are established. The objective of this study was to verify the clinical validity of selection criteria by pretransplant radiologic imaging study. recipients (49 whole liver transplant and 20 partial liver transplant) were enrolled this study. We analyzed the posttransplant survival and recurrence rate by radiologic selection criteria and other clinical factors. Grouping by pre-transplant criteria for liver transplantation, 16 recipients (23.2%) were above Milan criteria and 7 recipients (10.1%) were above the UCSF (University of California, San Francisco) criteria. According to combined categories, nine recipients (13.0%) were grouped as above Milan/ below UCSF group. The recipients who met Milan criteria (below Milan) and UCSF criteria (below UCSF) showed 85.8% and 82.7% of 1-year survival rate respectively, which was comparable to that of non-HCC (91.6%) without signifi cance (p=0.767 in below Milan, p=0.2604 in below UCSF). During post-transplant followup period (1-52 months, 14.8 ± 12.0 months), 16 recurrences (23.2%) were diagnosed. There was a signifi cant difference in the 1-year recurrence-free survival rate according to the selection criteria, recipients who satisfi ed the Milan criteria was 78.6% and of those that did not meet these criteria was 22.7% (p<0.0001), with regard to the UCSF criteria, 72.0% and 14.2%, respectively (p<0.0001). According to combined grouping, 1-year recurrencefree survival rate was 25.4% in above Milan/below UCSF group. There was signifi cant difference among each groups (overall p<0.0001) (Figure) which was confi rmed in multivariate survival analysis. The application of the UCSF criteria by pre-transplant radiologic fi ndings as patient selection criteria for liver transplantation is limited.

SUMMARYThe concept of fully adaptive multiscale ÿnite volume methods has been developed to increase spatial resolution and to reduce computational costs of numerical simulations. Here grid adaptation is performed by means of a multiscale analysis based on biorthogonal wavelets. In order to update the solution in time we use a local time stepping strategy that has been recently developed for hyperbolic conservation laws.The adaptive multiresolution scheme is now applied to two-dimensional shallow water equations with source terms. The e ciency of the scheme is demonstrated on several problems with a general geometry, including circular damp breaks, oblique hydraulic jump, supercritical channel ows encountering sudden change in cross-section, and, ÿnally, the bore wave and its interactions.