Younger Age is an Independent Factor for Graft Weight Overestimation: Analysis of the Clinical Impact on Recipient Outcomes in 340 Japanese Living Liver Donors.

BACKGROUND: Accurate preoperative estimation of graft weight is essential for improving outcomes in living donor liver transplantation. METHODS: This retrospective study sought to identify factors associated with graft weight overestimation. From April 2006 to August 2015, 340 living donors were assigned to no-overestimate (n = 284) or overestimate (n = 56) groups. We defined graft weight overestimation as a discrepancy ≥15% between estimated graft volume and actual graft weight. Donor data were compared, and associated factors for graft weight overestimation were analyzed. Recipient outcomes were compared between the groups according to identified factors. RESULTS: Donors were significantly younger in the overestimate group than in the no-overestimate group (35.0 vs. 46.0 years; p < 0.001). Multivariate analysis identified donor age <45 years as an independent risk factor for graft weight overestimation (odds ratio 2.068; 95% confidence interval 1.114-3.839; p = 0.021). Among recipients with donors <45 years (n = 168), incidence of small-for-size dysfunction (SFSD) was significantly higher in the overestimate group than in the no-overestimate group (7/37 patients vs. 7/131 patients; p = 0.016); no significant difference was observed among recipients with donors ≥45 years (n = 172). First-year mortality was lower in SFSD recipients with donors <45 years (14.3 vs. 60.9%, p = 0.007). Among recipients with younger donors, graft survival was not significantly different between overestimate and no-overestimate groups. CONCLUSIONS: Younger donor age was an independent risk factor for graft weight overestimation leading to SFSD in recipients, but did not impair graft survival.

Pre-treatment estimation of future remnant liver function using gadoxetic acid MRI in patients with HCC.

BACKGROUND & AIMS: This study aimed to determine whether the predicted remnant liver function on dynamic hepatocyte-specific contrast media-enhanced magnetic resonance (DHCE-MR) imaging correlates with the results of the indocyanin green retention test (ICG R15) after hepatic resection or radiofrequency ablation (RFA). METHODS: This prospective multicenter study was approved by the Institutional Review Boards of each hospital. Informed consents were obtained from all. DHCE-MRI and ICG R15 were performed in 57 patients scheduled to undergo hepatectomy or RFA for hepatocellular carcinoma, once before treatment and repeated on post-treatment day 3. In nine donors and three recipients, DHCE-MRI and ICG R15 were performed only preoperatively. The predicted remnant liver function (HEFml) was estimated using the hepatic extraction fraction (HEF) multiplied by the remnant liver volume, and compared with post-treatment ICG R15. Intra-individual heterogeneity of HEF was assessed using pooled coefficients of variation (CV) among hepatic segments. Finally, development of post-treatment hepatic failure was assessed according to the 50-50 criteria on post-treatment day 5. RESULTS: Predicted remnant HEFml showed a negative correlation with post-treatment ICG R15 (r=-0.45, p=0.001), whereas liver volume did not (p>0.05). There were significant correlations between pre-treatment HEFml and pre-treatment ICG R15 (r=-0.33, p=0.006) and between post-treatment HEFml and post-treatment ICG R15 (r=-0.54, p<0.001). Pooled CV among segmental HEFs was 12.6%. No patients showed post-treatment liver failure on post-treatment day 5. CONCLUSIONS: DHCE-MRI using Gd-EOB-DTPA was able to provide both global and segmental liver function information, and post-treatment remnant liver function predicted on pre-treatment DHCE-MRI showed a significant negative correlation with post-treatment ICG R15. LAY SUMMARY: Post-treatment liver function could be predicted at pre-treatment DHCE-MRI. Liver function was heterogeneous among the liver segments. Liver anatomy, disease extent, and underlying liver function can be assessed in one DHCE-MRI examination. CLINICAL TRIAL NUMBER: ClinicalTrials.gov number, NCT01490203.

Intrahepatic Size Regulation in a Surgical Model: Liver Resection-Induced Liver Regeneration Counteracts the Local Atrophy following Simultaneous Portal Vein Ligation.

BACKGROUND/AIM: Liver size regulation is based on the balance between hepatic regeneration and atrophy. To achieve a better understanding of intrahepatic size regulation, we explored the size regulation of a portally deprived liver lobe on a liver subjected to concurrent portal vein ligation (PVL) and partial hepatectomy (PHx). MATERIALS AND METHODS: Using a surgical rat model consisting of right PVL (rPVL) plus 70% PHx, we evaluated the size regulation of liver lobes 1, 2, 3, and 7 days after the operation in terms of liver weight and hepatocyte proliferation. Portal hyperperfusion was confirmed by measuring portal flow. The portal vascular tree was visualized by injection of a contrast agent followed by CT imaging of explanted livers. Control groups consisted of 70% PHx, rPVL, and sham operation. RESULTS: The size of the ligated right lobe increased to 1.4-fold on postoperative day 7 when subjected to rPVL + 70% PHx. The right lobe increased to 3-fold when subjected to 70% PHx alone and decreased to 0.3-fold when subjected to rPVL only. The small but significant increase in liver weight after the combined procedure was accompanied by a low proliferative response. In contrast, hepatocyte proliferation was undetectable in the right lobe undergoing atrophy after PVL only. The caudate lobe in the rPVL + 70% PHx group increased to 4.6-fold, which is significantly more than in the other groups. This increase in liver weight was paralleled by persisting portal hyperperfusion and a prolonged proliferative phase of 3 days. CONCLUSIONS: A discontinued portal blood supply does not always result in atrophy of the ligated lobe. The concurrent regenerative stimulus induced by 70% PHx seemed to counteract the local atrophy after a simultaneously performed rPVL, leading to a low but prolonged regenerative response of the portally deprived liver lobe. This observation supports the conclusion that portal flow is not necessary for liver regeneration. The persisting portal hyperperfusion may be crucial for the specific kinetics of prolonged liver regeneration after rPVL + 70% PHx in the portally supplied caudate lobe. Both observations deserve more attention regarding the underlying mechanism in further studies.

Spatio-temporal simulation of first pass drug perfusion in the liver.

The liver is the central organ for detoxification of xenobiotics in the body. In pharmacokinetic modeling, hepatic metabolization capacity is typically quantified as hepatic clearance computed as degradation in well-stirred compartments. This is an accurate mechanistic description once a quasi-equilibrium between blood and surrounding tissue is established. However, this model structure cannot be used to simulate spatio-temporal distribution during the first instants after drug injection. In this paper, we introduce a new spatially resolved model to simulate first pass perfusion of compounds within the naive liver. The model is based on vascular structures obtained from computed tomography as well as physiologically based mass transfer descriptions obtained from pharmacokinetic modeling. The physiological architecture of hepatic tissue in our model is governed by both vascular geometry and the composition of the connecting hepatic tissue. In particular, we here consider locally distributed mass flow in liver tissue instead of considering well-stirred compartments. Experimentally, the model structure corresponds to an isolated perfused liver and provides an ideal platform to address first pass effects and questions of hepatic heterogeneity. The model was evaluated for three exemplary compounds covering key aspects of perfusion, distribution and metabolization within the liver. As pathophysiological states we considered the influence of steatosis and carbon tetrachloride-induced liver necrosis on total hepatic distribution and metabolic capacity. Notably, we found that our computational predictions are in qualitative agreement with previously published experimental data. The simulation results provide an unprecedented level of detail in compound concentration profiles during first pass perfusion, both spatio-temporally in liver tissue itself and temporally in the outflowing blood. We expect our model to be the foundation of further spatially resolved models of the liver in the future.

Suitability of DNN-based vessel segmentation for SIRT planning.

PURPOSE: The segmentation of the hepatic arteries (HA) is essential for state-of-the-art pre-interventional planning of selective internal radiation therapy (SIRT), a treatment option for malignant tumors in the liver. In SIRT a catheter is placed through the aorta into the tumor-feeding hepatic arteries, injecting small beads filled with radiation emitting material for local radioembolization. In this study, we evaluate the suitability of a deep neural network (DNN) based vessel segmentation for SIRT planning. METHODS: We applied our DNN-based HA segmentation on 36 contrast-enhanced computed tomography (CT) scans from the arterial contrast agent phase and rated its segmentation quality as well as the overall image quality. Additionally, we applied a traditional machine learning algorithm for HA segmentation as comparison to our deep learning (DL) approach. Moreover, we assessed by expert ratings whether the produced HA segmentations can be used for SIRT planning. RESULTS: The DL approach outperformed the traditional machine learning algorithm. The DL segmentation can be used for SIRT planning in [Formula: see text] of the cases, while the reference segmentations, which were manually created by experienced radiographers, are sufficient in [Formula: see text]. Seven DL cases cannot be used for SIRT planning while the corresponding reference segmentations are sufficient. However, there are two DL segmentations usable for SIRT, where the reference segmentations for the same cases were rated as insufficient. CONCLUSIONS: HA segmentation is a difficult and time-consuming task. DL-based methods have the potential to support and accelerate the pre-interventional planning of SIRT therapy.

A Clinical User Study Investigating the Benefits of Adaptive Volumetric Illumination Sampling.

Accurate and fast understanding of the patient's anatomy is crucial in surgical decision making and particularly important in visceral surgery. Sophisticated visualization techniques such as 3D Volume Rendering can aid the surgeon and potentially lead to a benefit for the patient. Recently, we proposed a novel volume rendering technique called Adaptive Volumetric Illumination Sampling (AVIS) that can generate realistic lighting in real-time, even for high resolution images and volumes but without introducing additional image noise. In order to evaluate this new technique, we conducted a randomized, three-period crossover study comparing AVIS to conventional Direct Volume Rendering (DVR) and Path Tracing (PT). CT datasets from 12 patients were evaluated by 10 visceral surgeons who were either senior physicians or experienced specialists. The time needed for answering clinically relevant questions as well as the correctness of the answers were analyzed for each visualization technique. In addition to that, the perceived workload during these tasks was assessed for each technique, respectively. The results of the study indicate that AVIS has an advantage in terms of both time efficiency and most aspects of the perceived workload, while the average correctness of the given answers was very similar for all three methods. In contrast to that, Path Tracing seems to show particularly high values for mental demand and frustration. We plan to repeat a similar study with a larger participant group to consolidate the results.

In Vitro Sensitivity of Neuroendocrine Neoplasms to an Armed Oncolytic Measles Vaccine Virus.

Neuroendocrine neoplasms represent a heterogenous group of rare tumors whose current therapeutic options show only limited efficacy. Oncolytic viruses exert their mode of action through (onco-)lysis of infected tumor cells and the induction of a systemic antitumoral immune response in a virus-induced inflammatory micromilieu. Here, we investigated the potential of our well-established second-generation suicide-gene armed oncolytic measles vaccine virus (MeV-SCD) in five human NEN cell lines. First, (i) expression of the MeV receptor CD46 and (ii) its correlation with primary infection rates were analyzed. Next, (iii) promising combination partners for MeV-SCD were tested by employing either the prodrug 5-fluorocytosine, which is converted into the chemotherapeutic compound 5-fluorouracil, or the mTOR-inhibitor everolimus. As a result, MeV-SCD was found to kill all NEN tumor cell lines efficiently in a dose-dependent manner. This oncolytic effect was further enhanced by exploiting the prodrug-converting system, which was found to be highly instrumental in overcoming the partial resistance found in a single NEN cell line. Furthermore, viral replication was unaffected by everolimus, which is a basic requirement for combined use in NEN patients. These data suggest that MeV-SCD has profound potential for patients with NEN, thus paving the way for early clinical trials.

Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic Virus Talimogene Laherparepvec with Small Molecule Inhibitors.

NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier case report, we could show that an oncolytic herpes simplex virus (T-VEC) is functional in NC patients. To identify further combination partners for T-VEC, we have investigated the anti-tumoral effects of T-VEC and five different small molecule inhibitors (SMIs) alone and in combination in human NC cell lines. Dual combinations were found to result in higher rates of tumor cell reductions when compared to the respective monotherapy as demonstrated by viability assays and real-time tumor cell growth monitoring. Interestingly, we found that the combination of T-VEC with SMIs resulted in both stronger and earlier reductions in the expression of c-Myc, a main driver of NC cell proliferation, when compared to T-VEC monotherapy. These results indicate the great potential of combinatorial therapies using oncolytic viruses and SMIs to control the highly aggressive behavior of NC cancers and probably will pave the way for innovative multimodal clinical studies in the near future.

Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations.

BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is often associated with a high risk of disease recurrence and subsequent graft loss after isolated renal transplantation. Evidence-based recommendations for a mutation-based management after renal transplantation in aHUS caused by a combined mutation with complement factor I (CFI) and membrane cofactor protein CD46 (MCP) are limited. CASE-DIAGNOSIS/TREATMENT: We describe a 9-year-old boy with a first manifestation of aHUS at the age of 9 months carrying combined heterozygous mutations in the CFI and MCP genes. At the age of 5 years, he underwent isolated cadaveric renal transplantation. Fresh frozen plasma was administered during and after transplantation, tapered and finally stopped after 3 years. CONCLUSIONS: During the 5-year follow-up after transplantation there have been no signs of aHUS recurrence and graft function has remained good. The combination of heterozygous MCP and CFI mutations with aHUS might have a positive impact on the post-transplant course, possibly predicting a lower risk of aHUS recurrence after an isolated cadaveric renal transplantation.

Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model.

Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models.

Boy with autosomal recessive polycystic kidney and autosomal dominant polycystic liver disease.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) shows a great phenotypic variability between patients, ranging from perinatal demise to mildly affected adults. Autosomal dominant polycystic liver disease (PCLD) does not manifest in childhood. CASE-DIAGNOSIS/TREATMENT: A boy was reported with the co-occurrence of ARPKD and PCLD. He presented at the age of 16 days with pyelonephritis and urosepsis. Subsequent investigations showed enlarged kidneys and hyperechogenic renal medulla and liver parenchyma. Genetic analysis revealed compound heterozygous mutations in the PKHD1 gene (p.Arg496X and p.Ser1862Leu). After his mother was diagnosed with PCLD, the finding of a liver cyst on ultrasound prompted analysis of the PRKCSH gene, revealing a missense mutation (p.Arg139His). At the most recent follow-up at 13 years of age, the patient's course and clinical examination was uneventful with normal renal and liver function without evidence of portal hypertension. CONCLUSIONS: The patient with ARPKD and PCLD has so far demonstrated a benign clinical outcome, consistent with the great phenotypic variability of ARPKD and, apart from the liver cyst, asymptomatic manifestation of PCLD in childhood. However, close long-term follow-up is mandatory.

Precise local resection for hepatocellular carcinoma based on tumor-surrounding vascular anatomy revealed by 3D analysis.

PURPOSES: Local resection for hepatocellular carcinoma (HCC) has been traditionally performed non-anatomically. The purpose of this study is to evaluate the feasibility of precise local resection of HCC according to the anatomy of tumor-surrounding vessels revealed by three-dimensional (3D) analysis technique. METHODS: The CT datasets of the livers of the patients with HCC were analyzed three-dimensionally. The tumor-bearing vessels were identified and virtually resected, and the depending parenchymal volume was calculated for definition of an optimal liver division plane. The actual local resections were then carried out according to the simulations. RESULTS: Precise local resection based on tumor-surrounding vascular anatomy was performed in 13 HCC patients. Both resection margin and volume were significantly correlated with those predicted by preoperative simulations. After precise local resection, neither ischemia nor congestion was observed in the remnant livers. All patients obtained adequate resection margins, without recurrences in the resection sites after a median follow-up time of 18 months. CONCLUSIONS: Local resection for HCC can be carried out precisely according to the anatomy of tumor-surrounding vessels when guided by a 3D analysis. This precise procedure will enhance both the accuracy and safety of traditional local resection.

Computer-assisted image-based risk analysis and planning in lung surgery - a review.

In this paper, we give an overview on current trends in computer-assisted image-based methods for risk analysis and planning in lung surgery and present our own developments with a focus on computed tomography (CT) based algorithms and applications. The methods combine heuristic, knowledge based image processing algorithms for segmentation, quantification and visualization based on CT images of the lung. Impact for lung surgery is discussed regarding risk assessment, quantitative assessment of resection strategies, and surgical guiding. In perspective, we discuss the role of deep-learning based AI methods for further improvements.

Improving automatic liver tumor segmentation in late-phase MRI using multi-model training and 3D convolutional neural networks.

Automatic liver tumor segmentation can facilitate the planning of liver interventions. For diagnosis of hepatocellular carcinoma, dynamic contrast-enhanced MRI (DCE-MRI) can yield a higher sensitivity than contrast-enhanced CT. However, most studies on automatic liver lesion segmentation have focused on CT. In this study, we present a deep learning-based approach for liver tumor segmentation in the late hepatocellular phase of DCE-MRI, using an anisotropic 3D U-Net architecture and a multi-model training strategy. The 3D architecture improves the segmentation performance compared to a previous study using a 2D U-Net (mean Dice 0.70 vs. 0.65). A further significant improvement is achieved by a multi-model training approach (0.74), which is close to the inter-rater agreement (0.78). A qualitative expert rating of the automatically generated contours confirms the benefit of the multi-model training strategy, with 66 % of contours rated as good or very good, compared to only 43 % when performing a single training. The lesion detection performance with a mean F1-score of 0.59 is inferior to human raters (0.76). Overall, this study shows that correctly detected liver lesions in late-phase DCE-MRI data can be automatically segmented with high accuracy, but the detection, in particular of smaller lesions, can still be improved.

Efficacy of Oncolytic Herpes Simplex Virus T-VEC Combined with BET Inhibitors as an Innovative Therapy Approach for NUT Carcinoma.

NUT carcinoma (NC) is an extremely aggressive tumor and current treatment regimens offer patients a median survival of six months only. This article reports on the first in vitro studies using immunovirotherapy as a promising therapy option for NC and its feasible combination with BET inhibitors (iBET). Using NC cell lines harboring the BRD4-NUT fusion protein, the cytotoxicity of oncolytic virus talimogene laherparepvec (T-VEC) and the iBET compounds BI894999 and GSK525762 were assessed in vitro in monotherapeutic and combinatorial approaches. Viral replication, marker gene expression, cell proliferation, and IFN-ß dependence of T-VEC efficiency were monitored. T-VEC efficiently infected and replicated in NC cell lines and showed strong cytotoxic effects. This implication could be enhanced by iBET treatment following viral infection. Viral replication was not impaired by iBET treatment. In addition, it was shown that pretreatment of NC cells with IFN-ß does impede the replication as well as the cytotoxicity of T-VEC. T-VEC was found to show great potential for patients suffering from NC. Of note, when applied in combination with iBETs, a reinforcing influence was observed, leading to an even stronger anti-tumor effect. These findings suggest combining virotherapy with diverse molecular therapeutics for the treatment of NC.

"Anatomical" versus "territorial" belonging of the middle hepatic vein: virtual imaging and clinical repercussions.

BACKGROUND: Venous drainage patterns are of vital importance in live donor liver transplantation. The purpose of this study was to delineate "anatomical-topographical" and "territorial-physiologic" patterns of the middle hepatic vein (MHV) in a 3-D liver model as determined by the Pringle line and its drainage volume of the right and left hemilivers. METHODS: One hundred thirty-seven consecutive live donor candidates were evaluated by 3-D CT reconstructions and virtual hepatectomies. Based on right (R) and left (L), anatomical (A) and territorial (T) belonging patterns of the MHV, each individual was assigned to one of four possible types: type I:A(R)-T(R); type II:A(L)-T(L); type III:A(R)-T(L); type IV:A(L)-T(R). Couinaud's anatomical MHV variants A-C were subsequently included in our combined anatomical/territorial MHV belonging classification. RESULTS: The MHV showed a significant predominance of right "anatomical" (59.1%) and left "territorial" belonging patterns (65.7%). The paradoxical combinations A(R)-T(L) (type III) and A(L)-T(R) (type IV) were encountered in 36.5% and 11.7% of cases, respectively. The constellations Couinaud's A-belonging type IV and Couinaud's C-belonging type IV were predictive of right hemiliver venous congestion. CONCLUSIONS: (1) Almost half of all livers in our series had paradoxical "anatomical"/"territorial" MHV belonging patterns that placed them at risk for right and left hepatectomies. (2) The proposed combined "anatomical"/"territorial" MHV belonging types (I-IV) provide useful preoperative information. (3) Combined types III and IV as well as Couinaud's A-IV, and Couinaud's C-IV should be considered particularly risky for venous congestion in right hemiliver grafts and in extended left hepatectomies.

In vivo validation of a therapy planning system for laser-induced thermotherapy (LITT) of liver malignancies.

PURPOSE: In situ ablation is increasingly being used for the treatment of liver malignancies. The application of these techniques is limited by the lack of a precise prediction of the destruction volume. This holds especially true in anatomically difficult situations, such as metastases in the vicinity of larger liver vessels. We developed a three-dimensional (3D) planning system for laser-induced thermotherapy (LITT) of liver tumors. The aim of the study was to validate the system for calculation of the destruction volume. METHODS: LITT (28 W, 20 min) was performed in close contact to major hepatic vessels in six pigs. After explantation of the liver, the coagulation area was documented. The liver and its vascular structures were segmented from a pre-interventional CT scan. Therapy planning was carried out including the cooling effect of adjacent liver vessels. The lesions in vivo and the simulated lesions were compared with a morphometric analysis. RESULTS: The volume of lesions in vivo was 6,568.3 ± 3,245.9 mm(3), which was not different to the simulation result of 6,935.2 ± 2,538.5 mm(3) (P = 0.937). The morphometric analysis showed a sensitivity of the system of 0.896 ± 0.093 (correct prediction of destructed tissue). The specificity was 0.858 ± 0.090 (correct prediction of vital tissue). CONCLUSIONS: A 3D computer planning system for the prediction of thermal lesions in LITT was developed. The calculation of the directional cooling effect of intrahepatic vessels is possible for the first time. The morphometric analysis showed a good correlation under clinical conditions. The pre-therapeutic calculation of the ablation zone might be a valuable tool for procedure planning.

Anisotropic 3D Multi-Stream CNN for Accurate Prostate Segmentation from Multi-Planar MRI.

BACKGROUND AND OBJECTIVE: Accurate and reliable segmentation of the prostate gland in MR images can support the clinical assessment of prostate cancer, as well as the planning and monitoring of focal and loco-regional therapeutic interventions. Despite the availability of multi-planar MR scans due to standardized protocols, the majority of segmentation approaches presented in the literature consider the axial scans only. In this work, we investigate whether a neural network processing anisotropic multi-planar images could work in the context of a semantic segmentation task, and if so, how this additional information would improve the segmentation quality. METHODS: We propose an anisotropic 3D multi-stream CNN architecture, which processes additional scan directions to produce a high-resolution isotropic prostate segmentation. We investigate two variants of our architecture, which work on two (dual-plane) and three (triple-plane) image orientations, respectively. The influence of additional information used by these models is evaluated by comparing them with a single-plane baseline processing only axial images. To realize a fair comparison, we employ a hyperparameter optimization strategy to select optimal configurations for the individual approaches. RESULTS: Training and evaluation on two datasets spanning multiple sites show statistical significant improvement over the plain axial segmentation (p<0.05 on the Dice similarity coefficient). The improvement can be observed especially at the base (0.898 single-plane vs. 0.906 triple-plane) and apex (0.888 single-plane vs. 0.901 dual-plane). CONCLUSION: This study indicates that models employing two or three scan directions are superior to plain axial segmentation. The knowledge of precise boundaries of the prostate is crucial for the conservation of risk structures. Thus, the proposed models have the potential to improve the outcome of prostate cancer diagnosis and therapies.

A fast and robust hepatocyte quantification algorithm including vein processing.

BACKGROUND: Quantification of different types of cells is often needed for analysis of histological images. In our project, we compute the relative number of proliferating hepatocytes for the evaluation of the regeneration process after partial hepatectomy in normal rat livers. RESULTS: Our presented automatic approach for hepatocyte (HC) quantification is suitable for the analysis of an entire digitized histological section given in form of a series of images. It is the main part of an automatic hepatocyte quantification tool that allows for the computation of the ratio between the number of proliferating HC-nuclei and the total number of all HC-nuclei for a series of images in one processing run. The processing pipeline allows us to obtain desired and valuable results for a wide range of images with different properties without additional parameter adjustment. Comparing the obtained segmentation results with a manually retrieved segmentation mask which is considered to be the ground truth, we achieve results with sensitivity above 90% and false positive fraction below 15%. CONCLUSIONS: The proposed automatic procedure gives results with high sensitivity and low false positive fraction and can be applied to process entire stained sections.

Case Report: Virtual and Interactive 3D Vascular Reconstruction Before Planned Pancreatic Head Resection and Complex Vascular Anatomy: A Bench-To-Bedside Transfer of New Visualization Techniques in Pancreatic Surgery.

Introduction: Bühler's anastomosis (or Bühler's arcade) is an embryonic relic and represents an arterio-arterial connection between the superior mesenteric artery and the celiac trunk. It can be found as a variety in 1-2% of patients. Case Presentation: We present a case of a patient with metatastatic squamous cell carcinoma of the lung. The patient was in stable disease for 4 years under palliative therapy (most recently second-line therapy with Nevolumab). In 2019, a locally advanced adenocarcinoma of the papilla vateri was diagnosed, additionally. The patient also underwent right hemicolectomy and patch plasty of the celiac trunk and superior mesenteric artery due to colonic ischemia and arteriosclerotic disease with 50-70% stenosis of the superior mesenteric artery several years ago. Due to a complex vascular prehistory, the standardized preoperative imaging was supplemented by two independent vascular reconstructions (a CT angiogram and a reconstruction based on the CT) for the planning of a pylorus-preserving pancreatic head resection and reconstruction according to Traverso-Longmire. In addition, a 3D print was produced. Both, the reconstruction based on the CT scan and the 3D print were created for off-label use as a part of a research project (VIVATOP: Versatile Immersive Virtual and Augmented Tangible OP). Discussion: In the standardized CT scan and in the clinical CT-angiography, there were no obvious surgically relevant anatomical variations. A Bühler anastomosis was detected in a digital, virtual and interactive 3D-reconstruction. In addition, in the 3D print of the abdominal site the anastomosis was seen as well. Intraoperatively, the presence of Bühler's anastomosis was confirmed. This information had a significant impact on the intraoperative approach. Retrospectively, the vessel variant could be surmised in the axial projection of the CT scan, if one knew what to look for. Conclusion: For the conduction of a safe surgical procedure, it is imperative that rare anatomical variations are known preoperatively. Increasing digitalization in surgical and perioperative preparation holds great potential for better planning and improved patient safety. Research and cooperation projects such as the VIVATOP project are instrumental for the development of new visualization techniques, which are able to enhance the understanding of complex anatomical relations.