Diagnostic Utility of Artificial Intelligence-assisted Transperineal Biopsy Planning in Prostate Cancer Suspected Men: A Prospective Cohort Study.

BACKGROUND AND OBJECTIVE: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone. METHODS: A total of 262 consecutive men scheduled for TPB at our referral centre were analysed. Reported PI-RADS lesions and an US Food and Drug Administration-cleared CAD tool were used for TPB planning. PI-RADS and CAD lesions were targeted on TPB, while four (interquartile range: 2-5) systematic biopsies were taken. The outcomes were the (1) proportion of csPCa (grade group ≥2) and (2) number of targeted lesions and false-positive rate. Performance was tested using free-response receiver operating characteristic curves and the exact Fisher-Yates test. KEY FINDINGS AND LIMITATIONS: Overall, csPCa was detected in 56% (146/262) of men, with sensitivity of 92% and 97% (p = 0.007) for PI-RADS- and CAD-directed TPB, respectively. In 4% (10/262), csPCa was detected solely by CAD-directed biopsies; in 8% (22/262), additional csPCa lesions were detected. However, the number of targeted lesions increased by 54% (518 vs 336) and the false-positive rate doubled (0.66 vs 1.39; p = 0.009). Limitations include biopsies only for men at clinical/radiological suspicion and no multidisciplinary review of MRI before biopsy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The tested CAD tool for TPB planning improves csPCa detection at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences. PATIENT SUMMARY: The computer-aided diagnosis tool tested for transperineal prostate biopsy planning improves the detection of clinically significant prostate cancer at the cost of an increased number of lesions sampled and false positives. This may enable more personalised biopsy planning depending on urological and patient preferences.

Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes.

Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes.

International Hepato-Pancreato-Billiary Association (IHPBA) registry study on COVID-19 infections in HPB surgery patients.

BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.

Computer-assisted intraoperative 3D-navigation for liver surgery: a prospective randomized-controlled pilot study.

Background: Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. Methods: This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. Results: The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. Conclusions: Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility.

Implementation of deep learning in liver pathology optimizes diagnosis of benign lesions and adenocarcinoma metastasis.

INTRODUCTION: Differentiation of histologically similar structures in the liver, including anatomical structures, benign bile duct lesions, or common types of liver metastases, can be challenging with conventional histological tissue sections alone. Accurate histopathological classification is paramount for the diagnosis and adequate treatment of the disease. Deep learning algorithms have been proposed for objective and consistent assessment of digital histopathological images. MATERIALS AND METHODS: In the present study, we trained and evaluated deep learning algorithms based on the EfficientNetV2 and ResNetRS architectures to discriminate between different histopathological classes. For the required dataset, specialized surgical pathologists annotated seven different histological classes, including different non-neoplastic anatomical structures, benign bile duct lesions, and liver metastases from colorectal and pancreatic adenocarcinoma in a large patient cohort. Annotation resulted in a total of 204.159 image patches, followed by discrimination analysis using our deep learning models. Model performance was evaluated on validation and test data using confusion matrices. RESULTS: Evaluation of the test set based on tiles and cases revealed overall highly satisfactory prediction capability of our algorithm for the different histological classes, resulting in a tile accuracy of 89% (38 413/43 059) and case accuracy of 94% (198/211). Importantly, the separation of metastasis versus benign lesions was certainly confident on case level, confirming the classification model performed with high diagnostic accuracy. Moreover, the whole curated raw data set is made publically available. CONCLUSIONS: Deep learning is a promising approach in surgical liver pathology supporting decision making in personalized medicine.

The Optimal Fluid Strategy Matters in Liver Surgery: A Retrospective Single Centre Analysis of 666 Consecutive Liver Resections.

As optimal intraoperative fluid management in liver surgery has not been established, we retrospectively analyzed our fluid strategy in a high-volume liver surgery center in 666 liver resections. Intraoperative fluid management was divided into very restrictive (<10 m kg-1 h-1) and normal (≥10 mL kg-1 h-1) groups for study group characterization. The primary endpoint was morbidity as assessed by the Clavien-Dindo (CD) score and the comprehensive complication index (CCI). Logistic regression models identified factors most predictive of postoperative morbidity. No association was found between postoperative morbidity and fluid management in the overall study population (p = 0.89). However, the normal fluid management group had shorter postoperative hospital stays (p = <0.001), shorter ICU stays (p = 0.035), and lower in-hospital mortality (p = 0.02). Elevated lactate levels (p < 0.001), duration (p < 0.001), and extent of surgery (p < 0.001) were the most predictive factors for postoperative morbidity. In the subgroup of major/extreme liver resection, very low total (p = 0.028) and normalized fluid balance (p = 0.025) (NFB) were associated with morbidity. Moreover, fluid management was not associated with morbidity in patients with normal lactate levels (<2.5 mmol/L). In conclusion, fluid management in liver surgery is multifaceted and must be applied judiciously as a therapeutic measure. While a restrictive strategy appears attractive, hypovolemia should be avoided.

Elderly Patients with Hepatocellular Carcinoma Benefit from Liver Transplantation as Much as Younger Ones.

Introduction: The literature on liver transplantation (LT) for cirrhosis-associated hepatocellular carcinoma (cirr-HCC) in elderly patients (≥65 years of age) is scarce. The aim of this study was therefore to analyze the outcome after LT for cirr-HCC in elderly patients in our single-center experience. Methods: All consecutive patients who underwent LT for cirr-HCC at our center were identified from our prospectively collected LT database and stratified into an elderly (≥65 years) and a younger (<65 years) cohort. Perioperative mortality as well as Kaplan-Meier estimations of overall (OS) and recurrence-free survival (RFS) were compared between age strata. A subgroup analysis was performed for patients with HCC only inside Milan criteria. For further oncological comparison, outcome in the subgroup of elderly LT recipients with HCC inside Milan was also compared to a group of elderly patients undergoing liver resection for cirr-HCC inside Milan extracted from our institutional liver resection database. Results: Out of 369 consecutive patients with cirr-HCC who underwent LT between 1998 and 2022 at our center, we identified 97 elderly (with a subgroup of 14 septuagenarians) and 272 younger LT patients. 5- and 10-year OS in elderly compared to younger LT patients was 63% and 52% versus 63% and 46% (p = 0.67), respectively, while 5- and 10-year RFS was 58% and 49% versus 58% and 44% (p = 0.69). 5-/10-year OS and RFS in 50 elderly LT recipients with HCC inside Milan were 68%/55% and 62%/54%, respectively, which compared to 46%/38% (p = 0.07) and 26%/14% (p < 0.0001) in elderly patients after liver resection for cirr-HCC inside Milan. Conclusion: Our results in almost 100 elderly patients after LT for cirr-HCC show that older age per se should not be considered a contraindication to LT and that selected elderly patients older than 65 and even 70 years benefit from LT as much as younger ones.

[Robotics in Liver Surgery - Tips and Tricks]. / Robotik in der Leberchirurgie ­ Tipps und Tricks.

Since minimally invasive liver surgery has proven benefits over open surgery, this technique should also be implemented more broadly in Germany. With the dramatic development in minimally invasive and robotic liver surgery, this approach has been established in recent years. Most recent analyses suggest lower complication rates, blood loss and hospital stay compared to open and laparoscopic liver surgery. In contrast to laparoscopic surgery, the technical setting of robotic liver surgery is widely independent of the type of resection. The laparoscopic and robotic technologies should be considered to be equal at the moment, although most recent analyses even suggest additional advantages of robotic over laparoscopic liver surgery. Moreover, robotics has a greater potential for technical refinements, including the inclusion of artificial intelligence and machine learning. Most steps can be transferred from open and laparoscopic liver surgery, but a dissection device such as the CUSA has not yet been developed. Consequently, different techniques have been reported for parenchymal transsection. Due to the special technical features of robotic surgery, intensive training programs should be used prior to the establishment of a robotic liver surgery program.

Microvascular invasion of hepatocellular carcinoma predicts microvascular invasion of its recurrence: potential implications for salvage liver transplantation?

Background: Microvascular invasion (MVI) can only be assessed on a full surgical specimen. We aimed at evaluating, whether the histology of the primary tumor is predictive of MVI in a hepatocellular carcinoma (HCC) recurrence. Methods: Patients, who underwent liver resection or orthotopic liver transplantation (OLT) for recurrent HCC from January 2001 until June 2018 were eligible for this retrospective analysis. Resected specimens were evaluated for HCC subtype/morphology, vessels encapsulating tumor clusters (VETC)-pattern and MVI. Dichotomous parameters were analyzed using χ2-test and ϕ-values, with P values <0.05 being considered significant. Results: Of 230 HCC recurrences, 37 (16.1%) underwent repeated liver resection (n=22) or OLT (n=15). Of these, 67.6% initially exceeded the Milan criteria. MVI correlated Milan criteria (P=0.005), tumor size (P=0.015) and VETC-pattern (P=0.034) in the primary specimen. The recurrences shared many features of the primary HCC such as tumor grade (P=0.002), VETC-pattern (P=0.035), and MVI (P=0.046). In recurrences, however, only the concordance with the Milan criteria correlated with MVI (P=0.018). No patient without MVI in the primary HCC revealed MVI on early recurrence (<2 years) (P=0.035). Conclusions: HCC recurrences share many biological features of the primary tumor. Moreover, early recurrences of MVI-negative HCC never revealed MVI. This finding offers novel concepts, e.g., patient selection for salvage OLT.

Numerical Investigation of the Particle Dynamics in a Rotorgranulator Depending on the Properties of the Coating Liquid.

In the pharmaceutical industry, the coating of particles is a widely used technique to obtain desired surface modifications of the final product, e.g., controlled release of the active agents. The production of round, coated particles is particularly important, which is why fluidized bed rotor granulators (FBRG) are often used for this process. In this work, Computational Fluid Dynamics (CFD) coupled with the Discrete Element Method (DEM) is used to investigate the wet particle dynamics, depending on the properties of the coating liquid in a FBRG. The DEM contact model was extended by liquid bridge model to account for capillary and viscous forces during wet contact of particles. The influence of the relative contact velocity on the maximum length of the liquid bridge is also considered in the model. Five different cases were compared, in which the particles were initially wetted, and the liquid loading as well as the surface tension and viscosity of the liquid were changed. The results show that increasing viscosity leads to a denser particle bed and a significant decrease in particle rotational velocities and particle motion in the poloidal plane of the FBRG. Reducing the liquid loading and surface tension results in increased particle movement.

Mixed Hepatocellular Cholangiocarcinoma: A Comparison of Survival between Mixed Tumors, Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma from a Single Center.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy, followed by intrahepatic cholangiocarcinoma (ICC). In addition, there is a mixed form for which only limited data are available. The aim of this study was to compare recurrence and survival of the mixed form within the cohorts of patients with HCC and ICC from a single center. METHODS: Between January 2008 and December 2020, all patients who underwent surgical exploration for ICC, HCC, or mixed hepatocellular cholangiocarcinoma (mHC-CC) were included in this retrospective analysis. The data were analyzed, focusing on preoperative and operative details, histological outcome, and tumor recurrence, as well as overall and recurrence-free survival. RESULTS: A total of 673 surgical explorations were performed, resulting in 202 resections for ICC, 344 for HCC (225 non-cirrhotic HCC, ncHCC; 119 cirrhotic HCC, cHCC), and 14 for mHC-CC. In addition, six patients underwent orthotopic liver transplant (OLT) in the belief of dealing with HCC. In 107 patients, tumors were irresectable (resection rate of 84%). Except for the cHCC group, major or even extended liver resections were required. Vascular or visceral extensions were performed regularly. Overall survival (OS) was highly variable, with a median OS of 17.6 months for ICC, 26 months for mHC-CC, 31.8 months for cHCC, and 37.2 months for ncHCC. Tumor recurrence was common, with a rate of 45% for mHC-CC, 48.9% for ncHCC, 60.4% for ICC, and 67.2% for cHCC. The median recurrence-free survival was 7.3 months for ICC, 14.4 months for cHCC, 16 months for mHC-CC, and 17 months for ncHCC. The patients who underwent OLT for mHC-CC showed a median OS of 57.5 and RFS of 56.5 months. CONCLUSIONS: mHC-CC has a comparable course and outcome to ICC. The cholangiocarcinoma component seems to be the dominant one and, therefore, may be responsible for the prognosis. 'Accidental' liver transplant for mHC-CC within the Milan criteria offers a good long-term outcome. This might be an option in countries with no or minor organ shortage.

IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8+ T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC. DESIGN: Infiltration of Tc17 cells in PDAC tissue was correlated with patient overall survival and tumour stage. Wild-type (WT) or Il17ra-/- quiescent pancreatic stellate cells (qPSC) were exposed to conditional media obtained from Tc17 cells (Tc17-CM); moreover, co-culture of Tc17-CM-induced inflammatory (i)CAF (Tc17-iCAF) with tumour cells was performed. IL-17A/F-, IL-17RA-, RAG1-deficient and Foxn1nu/nu mice were used to study the Tc17 role in subcutaneous and orthotopic PDAC mouse models. RESULTS: Increased abundance of Tc17 cells highly correlated with reduced survival and advanced tumour stage in PDAC. Tc17-CM induced iCAF differentiation as assessed by the expression of iCAF-associated genes via synergism of IL-17A and TNF. Accordingly, IL-17RA controlled the responsiveness of qPSC to Tc17-CM. Pancreatic tumour cells co-cultured with Tc17-iCAF displayed enhanced proliferation and increased expression of genes implicated in proliferation, metabolism and protection from apoptosis. Tc17-iCAF accelerated growth of mouse and human tumours in Rag1-/- and Foxn1nu/nu mice, respectively. Finally, Il17ra-expressed by fibroblasts was required for Tc17-driven tumour growth in vivo. CONCLUSIONS: We identified Tc17 as a novel protumourigenic CD8+ T-cell subtype in PDAC, which accelerated tumour growth via IL-17RA-dependent stroma modification. We described a crosstalk between three cell types, Tc17, fibroblasts and tumour cells, promoting PDAC progression, which resulted in poor prognosis for patients.

Potential role of the bitter taste receptor T2R14 in the prolonged survival and enhanced chemoresponsiveness induced by apigenin.

Bitter taste receptors (T2Rs) are G protein­coupled receptors originally detected in the gustatory system. More recently, T2Rs have been shown to be expressed in extra­oral cells eliciting non­gustatory functions. Emerging evidence has suggested a potential role for T2R signaling in diverse pathophysiological conditions, including cancer. -The aim of the present study was to evaluate the expression of T2R14 in pancreatic ductal adenocarcinoma (PDAC) and to assess its involvement in the anticancer effects induced by apigenin, a natural ligand of T2R14. For this purpose, T2R14 expression was explored in PDAC tumor tissue and tumor­derived cell lines. Using the cell lines expressing the highest levels of T2R14, its effects on chemoresponsiveness and migration upon activation with apigenin were investigated in vitro. To the best of our knowledge, the present study was the first to confirm the expression of the T2R family member T2R14 in PDAC. Patients with relatively high levels of T2R14 expression exhibited significantly prolonged overall survival compared with that of patients with low T2R14 expression. Furthermore, novel functions for apigenin were revealed; notably, apigenin was shown to elicit cytotoxic, anti­migratory and chemosensitizing effects to 5­fluoruracil (5­FU) and to 5­FU, leucovorin, irinotecan and oxaliplatin in pancreatic cancer cells. In conclusion, the present study extended the evidence for the anticancer effects of apigenin and strongly indicated the functional relevance of T2R14 in PDAC, even though their respective underlying pathways appear to be independent of each other.

[Liver Resections Can Be Safely Performed in Cirrhotic Patients after Careful Patient Selection]. / Leberresektionen können bei vorsichtiger Patientenselektion auch in Zirrhose sicher durchgeführt werden.

BACKGROUND: Hepatocellular Carcinoma (HCC) is the most frequent malignant primary liver tumour in a cirrhotic liver. Liver transplantation and resection are the only curative treatment options in compensated liver cirrhosis, but liver resections are associated with increased perioperative morbidity and mortality. PATIENTS: We identified 108 cirrhotic patients, who underwent liver resections at the University Hospital of Mainz between January 2008 and December 2019. During the same period, 185 liver resections were performed for HCC in non-cirrhotic livers. Furthermore, 167 liver resections served as control group, which were performed for colorectal liver metastases (CRLM) with comparable extent of resection to HCC in cirrhotic livers. Preoperatively, we assessed the Charlson Comorbidity Index (CCI), MELD and Child scores in addition to the general patient characteristics. Perioperative morbidity was graded according to the Clavien-Dindo classification. Resections of HCC in cirrhosis and liver metastases were additionally compared by a matched-pair analysis. RESULTS: The three groups were comparable in age. Preoperative liver function was best in patients with CRLM (p < 0.001). Resections for HCC in non-cirrhotic livers were more extended than in cirrhotic livers (p < 0.001). The overall morbidity (Clavien/Dindo stage III - IV) was higher after resections in cirrhotic livers than in CRLM resections (p = 0.026). Postoperative mortality was comparably low in all three groups (2.2%). Neither MELD nor Child score was predictive for postoperative morbidity or mortality (area under the curve: AUC < 0.6, each). Preoperative CCI was predictive for postoperative mortality (AUC = 0.78). CONCLUSIONS: Liver resections in cirrhotic livers are feasible after adequate patient selection and limitation of the extent of surgery. Comorbidities additionally increase the postoperative mortality in addition to impaired liver function and should therefore always be included into the preoperative assessment of patients undergoing liver surgery.

Hierarchical Coarse-Grained Strategy for Macromolecular Self-Assembly: Application to Hepatitis B Virus-Like Particles.

Macromolecular self-assembly is at the basis of many phenomena in material and life sciences that find diverse applications in technology. One example is the formation of virus-like particles (VLPs) that act as stable empty capsids used for drug delivery or vaccine fabrication. Similarly to the capsid of a virus, VLPs are protein assemblies, but their structural formation, stability, and properties are not fully understood, especially as a function of the protein modifications. In this work, we present a data-driven modeling approach for capturing macromolecular self-assembly on scales beyond traditional molecular dynamics (MD), while preserving the chemical specificity. Each macromolecule is abstracted as an anisotropic object and high-dimensional models are formulated to describe interactions between molecules and with the solvent. For this, data-driven protein-protein interaction potentials are derived using a Kriging-based strategy, built on high-throughput MD simulations. Semi-automatic supervised learning is employed in a high performance computing environment and the resulting specialized force-fields enable a significant speed-up to the micrometer and millisecond scale, while maintaining high intermolecular detail. The reported generic framework is applied for the first time to capture the formation of hepatitis B VLPs from the smallest building unit, i.e., the dimer of the core protein HBcAg. Assembly pathways and kinetics are analyzed and compared to the available experimental observations. We demonstrate that VLP self-assembly phenomena and dependencies are now possible to be simulated. The method developed can be used for the parameterization of other macromolecules, enabling a molecular understanding of processes impossible to be attained with other theoretical models.

Microscale Modeling of Frozen Particle Fluid Systems with a Bonded-Particle Model Method.

An inventive microscale simulation approach is applied to investigate the mechanics of frozen particle fluid systems (PFS). The simulation is based on the discrete element method (DEM) and bonded-particle model (BPM) approach. Discrete particles connected by solid bonds represent frozen agglomerates. Uniaxial compression experiments were performed to gather data for material modeling and further simulation model validation. Different typical mechanical behavior (brittle, ductile, dilatant) were reviewed regarding strain rates, saturation levels, and particle mechanical or surface properties. Among all these factors, strain rate significantly affects the mechanical behavior and properties of the agglomerates. A new solid bond model considering strain-dependent and time-dependent behavior is developed for describing the rheology of the frozen particle fluid systems. Without alternating Young's modulus and Poisson's ratio of the bond material, the developed solid model provides a suitable agreement with the experimental results regarding different strain rates.

Outcome after Resection for Hepatocellular Carcinoma in Noncirrhotic Liver-A Single Centre Study.

Liver cirrhosis is the most common risk factor for the development of hepatocellular carcinoma (HCC). However, 10 to 15% of all HCC arise in a non-cirrhotic liver. Few reliable data exist on outcome after liver resection in a non-cirrhotic liver. The aim of this single-centre study was to evaluate the outcome of resection for HCC in non-cirrhotic liver (NC-HCC) and to determine prognostic factors for overall (OS) and intrahepatic recurrence-free (RFS) survival. From 2008 to 2020, a total of 249 patients were enrolled in this retrospective study. Primary outcome was OS and RFS. Radiological and pathological findings, such as tumour size, number of nodules, Tumour-, Nodes-, Metastases- (TNM) classification and vascular invasion as well as extent of surgical resection and laboratory liver function were collected. Here, 249 patients underwent liver resection for NC-HCC. In this case, 50% of patients underwent major liver resection, perioperative mortality was 6.4%. Median OS was 35.4 months (range 1-151 months), median RFS was 10.5 months (range 1-128 moths). Tumour diameter greater than three centimetres, multifocal tumour disease, vascular invasion, preoperative low albumin and increased alpha-fetoprotein (AFP) values were associated with significantly worse OS. Our study shows that resection for NC-HCC is an acceptable treatment approach with comparatively good outcome even in extensive tumours.

[Liver Surgery 4.0 - Planning, Volumetry, Navigation and Virtual Reality]. / Leberchirurgie 4.0 - OP-Planung, Volumetrie, Navigation und Virtuelle Realität.

Due to the optimisation of conservative treatment, the improvement of imaging methods and the continuous development of surgical techniques, the borders of resectability in liver surgery have changed significantly in recent decades.Thanks to numerous technical developments, in particular three-dimensional segmentation, preoperative planning and orientation during the operation itself, can now be facilitated, especially in complex procedures.New technologies such as 3D printing as well as virtual and augmented reality offer additional display options for the patients' individual anatomy. Various intraoperative navigation options are intended to make preoperative planning available in the operating room in order to increase patient safety.This review article is intended to provide an overview of the current state of available technologies and an outlook into the operating theatre of the future.

Evaluation of systematic prostate biopsies when performing transperineal MRI/TRUS fusion biopsy with needle tracking-what is the additional value?

PURPOSE: To evaluate the additional value of systematic biopsies (SB) when performing transperineal MRI/TRUS fusion biopsies (MRI/TRUS TPBx) with needle tracking. METHODS: From January 2019 to March 2021 969 Patients after a MRI/TRUS TPBx were evaluated separately for target biopsies (TB) and systematic biopsies regarding PCa detection and PCa risk evaluation. Needle tracking in the axial sequences of multiparametric MRI was used to assess the localisation of the detected PCa in the biopsy cores related to the reported PI-RADS lesions. RESULTS: The overall cancer detection rate (CDR) for PCa and clinically significant (cs) PCa (ISUP ≥2) with the combination of TB and SB were 66 and 49%. TB detected 46% csPCa and SB 22% csPCa. SB identified 1.5% additional csPCa outside of the reported PI-RADS lesions. 16 patients (1.7%) showed a relevant upgrading from clinically insignificant PCa in TB to csPCa. In 736 patients with unilateral suspicious lesions on MRI, 145 patients (20%) were detected with contralateral PCa-positive SB. 238 patients (25%) showed PCa positive systematic biopsy cores outside of the described PI-RADS lesions. CONCLUSIONS: Needle tracking optimizes the 3D-localisation of cancer in the prostate. Our results show that the added value of SB with a reduced systematic biopsy scheme is low with regard to prostate cancer (PCa) detection and PCa risk evaluation. However, there is a relevant added value for localizing multifocal PCa in the primary diagnostic by a MRI/TRUS fusion biopsy of the prostate.

Stress Granules Determine the Development of Obesity-Associated Pancreatic Cancer.

Obesity is a global epidemic and a major predisposing factor for cancer. Increasing evidence shows that obesity-associated stress is a key driver of cancer risk and progression. Previous work has identified the phase-separation organelles, stress granules (SG), as mutant KRAS-dependent mediators of stress adaptation. However, the dependence of tumorigenesis on these organelles is unknown. Here, we establish a causal link between SGs and pancreatic ductal adenocarcinoma (PDAC). Importantly, we uncover that dependence on SGs is drastically heightened in obesity-associated PDAC. Furthermore, we identify a previously unknown regulator and component of SGs, namely, the serine/arginine protein kinase 2 (SRPK2), as a specific determinant of SG formation in obesity-associated PDAC. We show that SRPK2-mediated SG formation in obesity-associated PDAC is driven by hyperactivation of the IGF1/PI3K/mTOR/S6K1 pathway and that S6K1 inhibition selectively attenuates SGs and impairs obesity-associated PDAC development. SIGNIFICANCE: : We show that stress adaptation via the phase-separation organelles SGs mediates PDAC development. Moreover, preexisting stress conditions such as obesity are a driving force behind tumor SG dependence, and enhanced SG levels are key determinants and a chemopreventive target for obesity-associated PDAC. This article is highlighted in the In This Issue feature, p. 1825.