Deep, deep learning with BART.

PURPOSE: To develop a deep-learning-based image reconstruction framework for reproducible research in MRI. METHODS: The BART toolbox offers a rich set of implementations of calibration and reconstruction algorithms for parallel imaging and compressed sensing. In this work, BART was extended by a nonlinear operator framework that provides automatic differentiation to allow computation of gradients. Existing MRI-specific operators of BART, such as the nonuniform fast Fourier transform, are directly integrated into this framework and are complemented by common building blocks used in neural networks. To evaluate the use of the framework for advanced deep-learning-based reconstruction, two state-of-the-art unrolled reconstruction networks, namely the Variational Network and MoDL, were implemented. RESULTS: State-of-the-art deep image-reconstruction networks can be constructed and trained using BART's gradient-based optimization algorithms. The BART implementation achieves a similar performance in terms of training time and reconstruction quality compared to the original implementations based on TensorFlow. CONCLUSION: By integrating nonlinear operators and neural networks into BART, we provide a general framework for deep-learning-based reconstruction in MRI.

DNA damage alters nuclear mechanics through chromatin reorganization.

DNA double-strand breaks drive genomic instability. However, it remains unknown how these processes may affect the biomechanical properties of the nucleus and what role nuclear mechanics play in DNA damage and repair efficiency. Here, we have used Atomic Force Microscopy to investigate nuclear mechanical changes, arising from externally induced DNA damage. We found that nuclear stiffness is significantly reduced after cisplatin treatment, as a consequence of DNA damage signalling. This softening was linked to global chromatin decondensation, which improves molecular diffusion within the organelle. We propose that this can increase recruitment for repair factors. Interestingly, we also found that reduction of nuclear tension, through cytoskeletal relaxation, has a protective role to the cell and reduces accumulation of DNA damage. Overall, these changes protect against further genomic instability and promote DNA repair. We propose that these processes may underpin the development of drug resistance.

Selective Modification and Probing of the Electrocatalytic Activity of Step Sites.

Employing Pt(111) supported 2D Pt-core Au-shell model catalysts, we demonstrate that 2D core-shell surfaces prepared under ultrahigh vacuum (UHV) conditions constitute excellent model systems to determine the activity of step sites in electrocatalysis, especially because UHV-scanning tunneling microscopy (STM) enables control of the quality of narrow step modifications with high accuracy on such systems. As verified with STM, cyclic voltammetry (CV), and temperature-programmed desorption (TPD) measurements, this approach allows us (i) to increase the step density by homoepitaxial growth of monolayer high islands on the respective single crystal and (ii) to modify the step sites for adsorption of reactants by selective deposition of a guest metal. Herein, STM imaging in combination with electrochemical characterization provides a direct control to ascertain a selective modification of the entire steps. Comparing the electrocatalytic activity of 2D core-shell systems with and without the shell enables us to identify the activity of step sites for electrocatalytic reactions, as demonstrated for the bulk CO electro-oxidation.

S-adenosylmethionine and methylthioadenosine boost cellular productivities of antibody forming Chinese hamster ovary cells.

The improvement of cell specific productivities for the formation of therapeutic proteins is an important step towards intensified production processes. Among others, the induction of the desired production phenotype via proper media additives is a feasible solution provided that said compounds adequately trigger metabolic and regulatory programs inside the cells. In this study, S-(5'-adenosyl)- l-methionine (SAM) and 5'-deoxy-5'-(methylthio)adenosine (MTA) were found to stimulate cell specific productivities up to approx. 50% while keeping viable cell densities transiently high and partially arresting the cell cycle in an anti-IL-8-producing CHO-DP12 cell line. Noteworthy, MTA turned out to be the chemical degradation product of the methyl group donor SAM and is consumed by the cells.

Admixture, evolution, and variation in reproductive isolation in the Boechera puberula clade.

BACKGROUND: Hybridization is very common in plants, and the incorporation of new alleles into existing lineages (i.e. admixture) can blur species boundaries. However, admixture also has the potential to increase standing genetic variation. With new sequencing methods, we can now study admixture and reproductive isolation at a much finer scale than in the past. The genus Boechera is an extraordinary example of admixture, with over 400 hybrid derivates of varying ploidy levels. Yet, few studies have assessed admixture in this genus on a genomic scale. RESULTS: In this study, we used Genotyping-by-Sequencing (GBS) to clarify the evolution of the Boechera puberula clade, whose six members are scattered across the western United States. We further assessed patterns of admixture and reproductive isolation within the group, including two additional species (B. stricta and B. retrofracta) that are widespread across North America. Based on 14,815 common genetic variants, we found evidence for some cases of hybridization. We find evidence of both recent and more ancient admixture, and that levels of admixture vary across species. CONCLUSIONS: We present evidence for a monophyletic origin of the B. puberula group, and a split of B. puberula into two subspecies. Further, when inferring reproductive isolation on the basis of presence and absence of admixture, we found that the accumulation of reproductive isolation between species does not seem to occur linearly with time since divergence in this system. We discuss our results in the context of sexuality and asexuality in Boechera.

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality-Swiss Group for Clinical Cancer Research Protocol SAKK 40/00.

PURPOSE: This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers. METHODS: One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12-204). RESULTS: The following variations of median values or percentages between centers were found: length of bowel specimen 20-39 cm (25.8 cm), maximum height of mesocolon 6.5-12.5 cm (9.0 cm), number of examined lymph nodes 9-24 (16), distance to nearer bowel resection margin in colon cancer 4.8-12 cm (7 cm), and in rectal cancer 2-3 cm (2.5 cm), central ligation of major artery 40-97 % (71 %), blood loss 200-500 ml (300 ml), need for perioperative blood transfusion 5-40 % (19 %), tumor opened during mobilization 0-11 % (5 %), T4-tumors not en-bloc resected 0-33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0-8 % (4 %), no-touch isolation technique 36-86 % (67 %), abdominoperineal resection for rectal cancer 0-30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0-19 % (10 %), in-hospital mortality 0-6 % (2 %), anastomotic leak or intra-abdominal abscess 0-17 % (7 %), re-operation 0-17 % (8 %). CONCLUSION: In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

Water and CO (co-)adsorption on pseudomorphic Pt films on Ru(0001) - a low-temperature scanning tunneling microscopy study.

Coadsorption of CO and water under ultrahigh vacuum (UHV) conditions can be considered as a model system for the interaction of metal surfaces with CO in an aqueous electrochemical environment. Nevertheless, this has rarely been investigated, and in particular for catalytically relevant bimetallic systems, there is hardly any information available. Here we report results of a low-temperature scanning tunneling microscopy (STM) study on the adsorption and coadsorption of CO and water on a Ru(0001) surface covered with a pseudomorphic Pt film of 2 or 3 monolayers thickness. The role of kinetic effects introduced by the sequence of adsorption, either pre-adsorption of CO followed by water adsorption or pre-adsorption of water followed by CO adsorption, on the adlayer structure formation will be demonstrated and discussed. Furthermore, the data show a distinct influence of the thickness of the Pt film, reflecting changes in the chemistry of the Pt surface due to electronic interactions with the underlying Ru(0001) substrate ('vertical ligand effects'). Implications of the present findings on the interaction of CO with these bimetallic PtRu surfaces under electrochemical conditions will be discussed.

Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats.

Major hepatectomy or small-for-size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague-Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham-operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small-for-size liver transplantation.

Darbepoetin-α accelerates neovascularization and engraftment of extrahepatic colorectal metastases.

PURPOSE: Erythropoietin and its analogue darbepoetin (DPO)-α have been shown to improve liver function and regeneration after partial hepatectomy (Phx). However, previous experimental studies have also shown that DPO significantly enhances Phx-induced engraftment of colorectal liver metastases by increasing neovascularization and tumor cell proliferation. Therefore, the present study analyzed whether DPO affects engraftment and neovascularization of extrahepatic colorectal metastases after major hepatectomy. METHODS: Green fluorescent protein-transfected CT26.WT colorectal cancer cells were implanted into dorsal skinfold chambers of syngeneic BALB/c mice. Animals received a single dose of DPO (10 µg/kg body weight) at the day of tumor cell implantation (day 0). Phosphate-buffered saline-treated animals served as controls. To study whether the effect of DPO is influenced by Phx, additional animals with and without DPO treatment underwent 70% Phx at day 0. Tumor vascularization and growth as well as tumor cell migration, proliferation and apoptosis were studied repetitively over 14 days using intravital fluorescence microscopy, histology and immunohistochemistry. RESULTS: In nonhepatectomized animals, DPO significantly accelerated tumor cell engraftment and slightly enhanced tumor neovascularization. Tumor cell migration and host tissue infiltration were not affected by DPO. In hepatectomized animals, DPO slightly enhanced tumor growth and significantly accelerated tumor neovascularization, but did not affect tumor cell migration and infiltration. CONCLUSION: The present study indicates that DPO accelerates extrahepatic engraftment of colorectal cancer cells, most probably by stimulating the process of neovascularization.

Assessment of deep learning segmentation for real-time free-breathing cardiac magnetic resonance imaging at rest and under exercise stress.

In recent years, a variety of deep learning networks for cardiac MRI (CMR) segmentation have been developed and analyzed. However, nearly all of them are focused on cine CMR under breathold. In this work, accuracy of deep learning methods is assessed for volumetric analysis (via segmentation) of the left ventricle in real-time free-breathing CMR at rest and under exercise stress. Data from healthy volunteers (n = 15) for cine and real-time free-breathing CMR at rest and under exercise stress were analyzed retrospectively. Exercise stress was performed using an ergometer in the supine position. Segmentations of two deep learning methods, a commercially available technique (comDL) and an openly available network (nnU-Net), were compared to a reference model created via the manual correction of segmentations obtained with comDL. Segmentations of left ventricular endocardium (LV), left ventricular myocardium (MYO), and right ventricle (RV) are compared for both end-systolic and end-diastolic phases and analyzed with Dice's coefficient. The volumetric analysis includes the cardiac function parameters LV end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF), evaluated with respect to both absolute and relative differences. For cine CMR, nnU-Net and comDL achieve Dice's coefficients above 0.95 for LV and 0.9 for MYO, and RV. For real-time CMR, the accuracy of nnU-Net exceeds that of comDL overall. For real-time CMR at rest, nnU-Net achieves Dice's coefficients of 0.94 for LV, 0.89 for MYO, and 0.90 for RV and the mean absolute differences between nnU-Net and the reference are 2.9 mL for EDV, 3.5 mL for ESV, and 2.6% for EF. For real-time CMR under exercise stress, nnU-Net achieves Dice's coefficients of 0.92 for LV, 0.85 for MYO, and 0.83 for RV and the mean absolute differences between nnU-Net and reference are 11.4 mL for EDV, 2.9 mL for ESV, and 3.6% for EF. Deep learning methods designed or trained for cine CMR segmentation can perform well on real-time CMR. For real-time free-breathing CMR at rest, the performance of deep learning methods is comparable to inter-observer variability in cine CMR and is usable for fully automatic segmentation. For real-time CMR under exercise stress, the performance of nnU-Net could promise a higher degree of automation in the future.

Is surgical quality more important than radicality? Long-term outcomes of stage I-III colon cancer (SAKK 40/00).

BACKGROUND: To prospectively determine the influence of variations of surgical radicality and surgical quality on long-term outcome in patients with stage I-III colon cancer. METHODS: From a prospective multicenter cohort study including 1040 patients undergoing surgery for colorectal cancer from 09/2001 to 06/2005 in nine Swiss and one German hospital, 423 patients with stage I-III colon cancer were selected and analyzed. Surgeons and pathologists filled in standardized forms prospectively assessing items of oncosurgical radicality and quality. Patients had standardized follow-up according to national guidelines. RESULTS: Follow-up was median 6.2 years (range 0.3-10.4) showing a 5-year disease-free survival/overall survival of 83 %/87 % in stage I (n = 85), 69 %/77 % in stage II (n = 187), and 53 %/61 % in stage III (n = 151) colon cancer. Despite remarkable variations of oncosurgical radicality and quality, the multivariate model revealed that mainly quality items correlated significantly with disease-free survival (surgical tumor lesion HR 2.12, p = 0.036, perioperative blood transfusion HR 1.67, p = 0.018, emergency resection HR 1.74, p = 0.035) and overall survival (early venous ligation HR 0.66, p = 0.023, surgical tumor lesion HR 2.28, p = 0.027, perioperative blood transfusion HR1.79, p = 0.010, emergency resection HR 1.88, p = 0.026), while radicality parameters (length of specimen, distance of the tumor to nearest bowel resection site, number of lymph nodes, height of resected mesocolon and of central vascular dissection) did not. CONCLUSION: Surgical quality seems to have a stronger impact on oncologic long-term outcome in stage I - III colon cancer than surgical radicality.

Reperfusion of liver graft during transplantation: techniques used in transplant centres within Eurotransplant and meta-analysis of the literature.

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.

Hepatic arterial infusion but not systemic application of cetuximab in combination with oxaliplatin significantly reduces growth of CC531 colorectal rat liver metastases.

PURPOSE: Systemic chemotherapy still represents the gold standard in the treatment of irresectable colorectal liver metastases. Modern anticancer agents like the monoclonal antibody cetuximab have improved the outcome of patients in clinical studies. As hepatic arterial infusion (HAI) is capable to potentially increase the anticancer effect of cytostatics, we herein studied whether HAI of cetuximab (CE) as a single agent or in combination with oxaliplatin (OX) exerts increased anticancer effects compared to the systemic application (SYS) of the drugs. METHODS: WAG/Rij rats were randomized to eight groups and underwent 10 days after subcapsular hepatic tumor implantation either HAI or SYS of CE, OX, or the combination of both agents (CE + OX). Saline-treated animals served as controls. Tumor volume was measured at days 10 and 13 using three-dimensional ultrasound. On day 13, liver and tumor tissue was sampled for histological and immunohistochemical analysis. RESULTS: In controls, the tumor volume significantly increased from day 10 to 13. Application of OX alone via HAI or SYS did not inhibit tumor growth compared to controls. SYS of CE or CE + OX did also not reduce tumor growth. In contrast, HAI of CE and CE + OX significantly inhibited tumor growth. HAI of CE significantly reduced tumor vascularization as measured by the number of platelet endothelial cell adhesion molecule-1-positive cells and significantly increased the number of apoptotic tumor cells as measured by the cellular caspase-3 expression. CONCLUSION: HAI of CE and CE + OX reduces tumor growth of colorectal rat liver metastases involving the inhibition of angiogenesis and induction of tumor cell apoptosis.

Evolutionary history of an Alpine Archaeognath (Machilis pallida): Insights from different variant.

Reconstruction of species histories is a central aspect of evolutionary biology. Patterns of genetic variation within and among populations can be leveraged to elucidate evolutionary processes and demographic histories. However, interpreting genetic signatures and unraveling the contributing processes can be challenging, in particular for non-model organisms with complex reproductive modes and genome organization. One way forward is the combined consideration of patterns revealed by different molecular markers (nuclear vs. mitochondrial) and types of variants (common vs. rare) that differ in their age, mode, and rate of evolution. Here, we applied this approach to RNAseq data generated for Machilis pallida (Archaeognatha), an Alpine jumping bristletail considered parthenogenetic and triploid. We generated de novo transcriptome and mitochondrial assemblies to obtain high-density data to investigate patterns of mitochondrial and common and rare nuclear variation in 17 M. pallida individuals sampled from all known populations. We find that the different variant types capture distinct aspects of the evolutionary history and discuss the observed patterns in the context of parthenogenesis, polyploidy, and survival during glaciation. This study highlights the potential of different variant types to gain insights into evolutionary scenarios even from challenging but often available data and the suitability of M. pallida and the genus Machilis as a study system for the evolution of sexual strategies and polyploidization during environmental change. We also emphasize the need for further research which will be stimulated and facilitated by these newly generated resources and insights.

Darbepoetin-α promotes neovascularization and cell proliferation in established colorectal liver metastases.

BACKGROUND: The erythropoietin-analogue darbepoetin-α (DPO) improves liver function and regeneration after hepatectomy (Phx), however, also enhances Phx-induced tumor cell engraftment and neovascularization. Because it is unknown whether DPO also enhances the growth of established tumors, we herein studied the effect of DPO on established colorectal liver metastases after Phx. METHODS: CT26.WT cells were implanted into the liver of BALB/c mice. Five days after tumor establishment, animals underwent 50% Phx and received 10 µg/kgBW DPO or saline. Non-Phx animals with DPO or saline-treatment served as controls. Seven days after Phx tumors were analyzed regarding blood vessel formation, leukocyte adhesion, cell proliferation, apoptotic cell death, and growth using intravital fluorescence microscopy, histology, and immunohistochemistry. RESULTS: The growth of established colorectal liver metastases was slightly stimulated after DPO-treatment in hepatectomized and non-hepatectomized animals. However, tumor vessel formation and tumor cell proliferation were significantly enhanced after DPO-treatment in hepatectomized and non-hepatectomized mice compared with controls. Apoptotic cell death and leukocyte-endothelial cell interaction were significantly reduced after DPO-treatment. CONCLUSION: Our study indicates that DPO-treatment promotes neovascularization and cell proliferation in established colorectal liver metastases of hepatectomized and non-hepatectomized mice. DPO-application in patients with colorectal liver metastases might promote tumor progression and should therefore be avoided.

Evidence for tumor cell spread during local hepatic ablation of colorectal liver metastases.

INTRODUCTION: The aim of the present study was to analyze the impact of cryosurgery (CRYO) on liver metastases compared to other thermoablative techniques. In a rat liver metastases model, evidence for tumor cell spread was analyzed comparing CRYO, radiofrequency ablation (RFA), and laser-induced thermotherapy (LITT). METHODS: In an experimental study, we compared cell spillage in the washout of isolated perfused rat livers undergoing thermal ablation. Within the same model, CC531-GFP rat liver tumors were treated with CRYO, RFA, or LITT and the number of vital tumor cells within the perfusate was measured. Matrix metalloproteinases (MMP-2, MMP-9) were analyzed after in vivo ablation of rat colorectal liver metastases in the third experimental model. RESULTS: Our data showed pronounced washout of cells after CRYO with a higher amount of intravascular cells and cell detritus compared to RFA and LITT. Only the effluent fluid of cryosurgery-treated livers revealed GFP-stained tumor cells. MMP-2 and MMP-9 expression was significantly higher after cryosurgery than after RFA and LITT. CONCLUSION: When using thermoablative techniques, intravascular metastatic cell spillage is highest in CRYO, and increased expression of matrix metalloproteinases may further facilitate tumor cell spread. Therefore, RFA and LITT may be preferable whenever surgical resection of liver tumors is impossible.

Normative values in anorectal manometry using microtip technology: a cohort study in 172 subjects.

PURPOSE: The aims of this study were to obtain normative values in resting/squeeze pressure and surface electromyography (s-EMG) in anorectal manometry using microtip technology and to determine the relationship between objective measurable values, gender and age in a cohort with no anorectal disorders. METHODS: One hundred seventy-two white central European subjects (106 males/66 females) were recruited prior to left colonic or upper rectal surgery and studied by anorectal rapid pull-through manometry with a microtip transducer system and endoanal s-EMG using a bipolar plug electrode. s-EMG patterns were determined as plateau, peak and decrease by a blinded co-investigator. Objective measurable sphincter pressures and s-EMG values were correlated with gender, age and s-EMG patterns. RESULTS: Squeeze pressure, voluntary pressure as well as s-EMG amplitude and its area under the curve were significantly lower in women compared to men (p < 0.001 each), whereas resting pressure showed no gender differences. s-EMG patterns were strongly influenced by gender. Male patients showed significantly more plateau pattern whereas peak pattern was significantly more often in women. In both genders, the peak pattern was associated with significant higher squeeze pressures. In all measurements, we found considerable inter-individual variations being higher in elder patients. There was no manometric parameter correlating with age. CONCLUSIONS: Gender is the strongest factor influencing objective measurable manometric data for healthy men and women. There are significant gender differences concerning squeeze patterns. All manometric values should be interpreted in the context of gender and of methodology used. Large prospective cohort studies matched for gender are necessary to clarify the effect of ageing on anal sphincter strength.

Estimate or calculate? How surgeons rate volumes and surfaces.

PURPOSE: Surgeons frequently describe the shape of intraoperative findings using visual judgement and their own sense of proportion or describing these findings in comparison to commonly used or metaphoric subjects. The aim of the study was to analyse the reliability of surgeon's estimations of dimensions. METHODS: The study was performed in two phases. First, physicians had to estimate the metric proportions of four well-known objects. Second, surgeons were asked intraoperatively to estimate the liver resection surface after partial hepatectomy. The exact surface of the resection plane was measured using computed tomography-guided planimetry of the resection specimen. Physician's estimations and the exact measurements of the well-known objects and the liver resection surface were compared. Systematic error was defined by the natural logarithm of estimated/real size. RESULTS: We found a large individual discrepancy in estimating the metric proportions of commonly used objects and a tendency to underestimate both commonly used objects and liver resection surface. Experienced liver surgeons were more accurate in estimating liver resection surface compared with younger staff members. CONCLUSIONS: We found a large bias in estimating the dimension of both commonly used objects and the surface area of liver parenchyma transection. Obviously, estimating errors are more influenced by the individual subject who estimates than by the object itself. In clinical routine, surgeons should rely more on simple measuring devices than on their own sense of proportion. Education in how to estimate more correctly human liver resection surfaces can be achieved by ex vivo studies using porcine livers.

How to ensure the survival of the surgeon-scientist? The Homburg Program.

BACKGROUND: Academic surgery requires competence in research, teaching, and patient care. Because of the increasing complexity of both surgical research and clinical surgery, and additional skills necessary for adequate patient care, including economics, management, and organization, it becomes more and more difficult to provide an attractive education for surgeon-scientists. This has resulted in a dramatic decline in the number of surgeon-scientists in the past and alarms us to systematically restructure our research training system. DISCUSSION: We herein introduce a program involving the clinical departments of surgery, trauma surgery, and cardiac-thoracic surgery as well as a surgical research institution. The program allows the clinical departments to sharpen their overall research profile and facilitates the establishment of competent working groups, guaranteeing long-term research activities on a high scientific level. The program involves both surgical residents and medical students, who will represent our future generation of academic surgeons, ensuring the survival of the surgeon-scientist.

Parenchyma-preserving hepatic resection for colorectal liver metastases.

BACKGROUND: Hepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach. METHODS: Data from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan-Meier method. Correlations were calculated between clinical-pathological variables. RESULTS: One hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced. CONCLUSION: For colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches.