Transfusions of packed red blood cells in surgery for liver cancer: predictor of impaired overall survival but not recurrence-free survival - impact of blood transfusions in liver surgery.

BACKGROUND: Liver surgery remains a cornerstone of potentially curative multimodal treatments for primary malignancies of the liver and hepatic metastases. Improving perioperative safety is a prerequisite in this context. Perioperative blood transfusions negatively influence postoperative recovery. This study aimed to identify risk factors for perioperative packed red blood cell (PRBC) transfusion and to elucidate its effect on postoperative outcomes. METHODS: This was an observational study of a prospective data collection. A monocentric, retrospective analysis of 1118 hepatectomies at the University Hospital Carl Gustav Carus between 2013 and 2020 was conducted to compare postoperative short- and long-term outcomes in patients undergoing curative intended liver resection of hepatic primary or secondary malignancies. The outcomes were compared between 356 patients (31.8%) who received PRBC transfusions during surgery or within 7 days after surgery and 762 patients (68.2%) who did not receive PRBC transfusions. RESULTS: Preoperative anemia could be observed in 45.0% of the whole cohort: 65.7% in the PRBC transfusion group and 35.3% in the nontransfused group. Postoperative complications were significantly more common in the PRBC transfusion group in association with prolonged lengths of hospital stay and increased 30-day mortality than in the nontransfused group. After adjustment for possible confounders, preexisting kidney failure, preoperative hemoglobin and albumin levels outside of the reference range, intraoperative plasma transfusions, and overall surgery time were recognized as negative predictors for perioperative PRBC transfusions. PRBC transfusion increased the risk of death by approximately 38.8% (hazard ratio, 1.388; 95% CI, 1.027-1.876; P = .033), whereas no influence on recurrence-free survival (RFS) was observed. CONCLUSION: PRBC transfusions were associated with postoperative morbidity and mortality after curative-intended surgery for liver cancers and represented an independent poor prognostic indicator for overall survival but not for RFS.

Comparative analysis of radiomics and deep-learning algorithms for survival prediction in hepatocellular carcinoma.

To examine the comparative robustness of computed tomography (CT)-based conventional radiomics and deep-learning convolutional neural networks (CNN) to predict overall survival (OS) in HCC patients. Retrospectively, 114 HCC patients with pretherapeutic CT of the liver were randomized into a development (n = 85) and a validation (n = 29) cohort, including patients of all tumor stages and several applied therapies. In addition to clinical parameters, image annotations of the liver parenchyma and of tumor findings on CT were available. Cox-regression based on radiomics features and CNN models were established and combined with clinical parameters to predict OS. Model performance was assessed using the concordance index (C-index). Log-rank tests were used to test model-based patient stratification into high/low-risk groups. The clinical Cox-regression model achieved the best validation performance for OS (C-index [95% confidence interval (CI)] 0.74 [0.57-0.86]) with a significant difference between the risk groups (p = 0.03). In image analysis, the CNN models (lowest C-index [CI] 0.63 [0.39-0.83]; highest C-index [CI] 0.71 [0.49-0.88]) were superior to the corresponding radiomics models (lowest C-index [CI] 0.51 [0.30-0.73]; highest C-index [CI] 0.66 [0.48-0.79]). A significant risk stratification was not possible (p > 0.05). Under clinical conditions, CNN-algorithms demonstrate superior prognostic potential to predict OS in HCC patients compared to conventional radiomics approaches and could therefore provide important information in the clinical setting, especially when clinical data is limited.

Preoperative IL-8 levels as prognostic indicators of overall survival: an extended follow-up in a prospective cohort with colorectal liver metastases.

INTRODUCTION: CRC with liver metastases is a major contributor to cancer-related mortality. Despite advancements in liver resection techniques, patient survival remains a concern due to high recurrence rates. This study seeks to uncover prognostic biomarkers that predict overall survival in patients undergoing curative hepatic resection for CRC liver metastases. METHODS: Prospectively collected serum samples from a cohort of 49 patients who received curative hepatic resection for CRC liver metastases were studied. The patients are part of a cohort, previously analyzed for perioperative complications (see methods). Various preoperative serum markers, clinical characteristics, and factors were analyzed. Univariate and multivariate Cox regression analyses were conducted to determine associations between these variables and disease-free survival as well as overall survival. RESULTS: For disease-free survival, univariate analysis highlighted the correlation between poor outcomes and advanced primary tumor stage, high ASA score, and synchronous liver metastases. Multivariate analysis identified nodal-positive primary tumors and synchronous metastases as independent risk factors for disease-free survival. Regarding overall survival, univariate analysis demonstrated significant links between poor survival and high preoperative IL-8 levels, elevated neutrophil-lymphocyte ratio (NLR), and presence of metastases in other organs. Multivariate analysis confirmed preoperative IL-8 and having three or more liver metastases as independent risk factors for overall survival. The impact of IL-8 on survival was particularly noteworthy, surpassing the influence of established clinical factors. CONCLUSION: This study establishes preoperative IL-8 levels as a potential prognostic biomarker for overall survival in patients undergoing curative liver resection for CRC liver metastases. This study underscores the importance of incorporating IL-8 and other biomarkers into clinical decision-making, facilitating improved patient stratification and tailored treatment approaches. Further research and validation studies are needed to solidify the clinical utility of IL-8 as a prognostic marker.

Interleukin-8 is superior to CRP for the prediction of severe complications in a prospective cohort of patients undergoing major liver resection.

INTRODUCTION: Early detection of severe complications may reduce morbidity and mortality in patients undergoing hepatic resection. Therefore, we prospectively evaluated a panel of inflammatory blood markers for their value in predicting postoperative complications in patients undergoing liver surgery. METHODS: A total of 139 patients undergoing liver resections (45 wedge resections, 49 minor resections, and 45 major resections) were prospectively enrolled between August 2017 and December 2018. Leukocytes, CRP, neutrophil-lymphocyte ratio (NLR), thrombocyte-lymphocyte ratio (TLR), bilirubin, INR, and interleukin-6 and -8 (IL-6 and IL-8) were measured in blood drawn preoperatively and on postoperative days 1, 4, and 7. IL-6 and IL-8 were measured using standardized immunoassays approved for in vitro diagnostic use in Germany. ROC curve analysis was used to determine predictive values for the occurrence of severe postoperative complications (CDC ≥ 3). RESULTS: For wedge and minor resections, leukocyte counts at day 7 (AUC 0.80 and 0.82, respectively), IL-6 at day 7 (AUC 0.74 and 0.73, respectively), and CRP change (∆CRP) at day 7 (AUC 0.72 and 0.71, respectively) were significant predictors of severe postoperative complications. IL-8 failed in patients undergoing wedge resections, but was a significant predictor of severe complications after minor resections on day 7 (AUC 0.79), had the best predictive value in all patients on days 1, 4, and 7 (AUC 0.72, 0.72, and 0.80, respectively), and was the only marker with a significant predictive value in patients undergoing major liver resections (AUC on day 1: 0.70, day 4: 0.86, and day 7: 0.92). No other marker, especially not CRP, was predictive of severe complications after major liver surgery. CONCLUSION: IL-8 is superior to CRP in predicting severe complications in patients undergoing major hepatic resection and should be evaluated as a biomarker for patients undergoing major liver surgery. This is the first paper demonstrating a feasible implementation of IL-8 analysis in a clinical setting.

Lymphoepithelial cyst mimicking malignant pancreatic signs: a case report.

BACKGROUND: A lymphoepithelial cyst of the pancreas is a rare benign lesion that is difficult to diagnose preoperatively and challenging in distinguishing from potentially malignant cystic pancreatic neoplasms. A diagnostic step-up approach is recommended to clarify the lesion's dignity and specify a treatment plan. CASE PRESENTATION: Here, we describe a case of a 51-year-old male European with a lymphoepithelial cyst of the pancreas mimicking malignant features in a mid-age male patient with abdominal pain and unintended weight loss. CONCLUSION: Patients with indeterminate cystic pancreatic lesions should be examined by a multidisciplinary diagnostic team in a step-up approach to clarify the lesion's entity. In the case of incidentally found lymphoepithelial cysts of the pancreas, a watchful waiting strategy might be clinically reasonable if the diagnosis is proven.

The role of local expression of hormone receptors in the genesis of idiopathic tracheal stenosis.

Background: Tracheal stenosis in adults is usually the result of mechanical injuries either from direct trauma, tracheotomy or intubation. Idiopathic stenosis in the cricotracheal section is a rare condition and occurs almost exclusively in females. Therefore, an influence of the female sexual hormones estrogen and progesterone has been assumed previously. Methods: Tracheal specimens of 27 patients who received tracheal resection for either idiopathic tracheal stenosis (ITS) (n=11) or posttraumatic tracheal stenosis (PTTS) (n=16) between 2008 and 2019 in our surgical department were included and retrospectively analyzed. Immunohistochemical staining of tracheal specimens concerning the hormone receptor status of progesterone and estrogen was performed. Results: While post-tracheotomy stenosis occurred in males (n=6) as well as in females (n=10), none of the patients with idiopathic stenosis were males. All of the idiopathic stenosis (n=11; 100%) showed a strong expression of the estrogen receptors (ERs) in the fibroblasts and expression of progesterone receptors (PRs) in fibroblasts in 8 of 11 (72.7%). In the post-tracheotomy patients, only 3/16 (18.8%) showed slight staining of PRs and 6/16 (37.5%) of ERs. Of those, only one male patient presented with expression of ERs and PRs and another male patient presented with isolated PRs. Oral intake of hormone compounds was seen in 11/27 (40.7%) patients: 7/11 (63.6%) in the ITS group and 4/16 (25%) in the PTTS (noteworthy that the PTTS group included 6 male patients). Conclusions: Although the number of patients is small, our results show that the expression of female sexual hormone receptors in the fibroblasts of the trachea is a persistent finding in ITS. Surgery provided good results with a favorable long-term outcome without recurrence of stenosis for ITS and PTTS. Further investigation with a special focus on hormones is needed to assist in the prevention of this rare disease.

Label-free multiphoton microscopy enables histopathological assessment of colorectal liver metastases and supports automated classification of neoplastic tissue.

As the state of resection margins is an important prognostic factor after extirpation of colorectal liver metastases, surgeons aim to obtain negative margins, sometimes elaborated by resections of the positive resection plane after intraoperative frozen sections. However, this is time consuming and results sometimes remain unclear during surgery. Label-free multimodal multiphoton microscopy (MPM) is an optical technique that retrieves morpho-chemical information avoiding all staining and that can potentially be performed in real-time. Here, we investigated colorectal liver metastases and hepatic tissue using a combination of three endogenous nonlinear signals, namely: coherent anti-Stokes Raman scattering (CARS) to visualize lipids, two-photon excited fluorescence (TPEF) to visualize cellular patterns, and second harmonic generation (SHG) to visualize collagen fibers. We acquired and analyzed over forty thousand MPM images of metastatic and normal liver tissue of 106 patients. The morphological information with biochemical specificity produced by MPM allowed discriminating normal liver from metastatic tissue and discerning the tumor borders on cryosections as well as formalin-fixed bulk tissue. Furthermore, automated tissue type classification with a correct rate close to 95% was possible using a simple approach based on discriminant analysis of texture parameters. Therefore, MPM has the potential to increase the precision of resection margins in hepatic surgery of metastases without prolonging surgical intervention.

Plasma extracellular vesicle messenger RNA profiling identifies prognostic EV signature for non-invasive risk stratification for survival prediction of patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one of the most dismal of all cancers and the median survival of PDAC patients is only 6-8 months after diagnosis. While decades of research effort have been focused on early diagnosis and understanding of molecular mechanisms, few clinically useful markers have been universally applied. To improve the treatment and management of PDAC, it is equally relevant to identify prognostic factors for optimal therapeutic decision-making and patient survival. Compelling evidence have suggested the potential use of extracellular vesicles (EVs) as non-invasive biomarkers for PDAC. The aim of this study was thus to identify non-invasive plasma-based EV biomarkers for the prediction of PDAC patient survival after surgery. METHODS: Plasma EVs were isolated from a total of 258 PDAC patients divided into three independent cohorts (discovery, training and validation). RNA sequencing was first employed to identify differentially-expressed EV mRNA candidates from the discovery cohort (n = 65) by DESeq2 tool. The candidates were tested in a training cohort (n = 91) by digital droplet polymerase chain reaction (ddPCR). Cox regression models and Kaplan-Meier analyses were used to build an EV signature which was subsequently validated on a multicenter cohort (n = 83) by ddPCR. RESULTS: Transcriptomic profiling of plasma EVs revealed differentially-expressed mRNAs between long-term and short-term PDAC survivors, which led to 10 of the top-ranked candidate EV mRNAs being tested on an independent training cohort with ddPCR. The results of ddPCR enabled an establishment of a novel prognostic EV mRNA signature consisting of PPP1R12A, SCN7A and SGCD for risk stratification of PDAC patients. Based on the EV mRNA signature, PDAC patients with high risk displayed reduced overall survival (OS) rates compared to those with low risk in the training cohort (p = 0.014), which was successfully validated on another independent cohort (p = 0.024). Interestingly, the combination of our signature and tumour stage yielded a superior prognostic performance (p = 0.008) over the signature (p = 0.022) or tumour stage (p = 0.016) alone. It is noteworthy that the EV mRNA signature was demonstrated to be an independent unfavourable predictor for PDAC prognosis. CONCLUSION: This study provides a novel and non-invasive prognostic EV mRNA signature for risk stratification and survival prediction of PDAC patients.

3D liver model-based surgical education improves preoperative decision-making and patient satisfaction-a randomized pilot trial.

OBJECTIVE: Hepatobiliary surgery bares obstacles to informed consent for the patients due to its complexity and related risk of postoperative complications. 3D visualization of the liver has been proven to facilitate comprehension of the spatial relationship between anatomical structures and to assist in clinical decision-making. Our objective is to utilize individual 3D-printed liver models to enhance patient satisfaction with surgical education in hepatobiliary surgery. DESIGN, SETTING: We conducted a prospective, randomized pilot study comparing 3D liver model-enhanced (3D-LiMo) surgical education against regular patient education during preoperative consultation at the department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany. PARTICIPANTS: Of 97 screened patients, undergoing hepatobiliary surgery, 40 patients were enrolled from July 2020 to January 2022. RESULTS: The study population (n = 40) was predominantly of male gender (62.5%) with a median age of 65.2 years and a high prevalence of preexisting diseases. Underlying disease, warranting hepatobiliary surgery, was malignancy in the majority of cases (97.5%). Patients in the 3D-LiMo group were more likely to feel very thoroughly educated and exhibited a higher level of satisfaction following surgical education than the control group (80 vs. 55%, n.s.; 90 vs. 65%, n.s.; respectively). Applying 3D models was also associated with enhanced understanding of the underlying disease with regard to amount (100% vs. 70%, p = 0.020) and location of liver masses (95 vs. 65%, p = 0.044). 3D-LiMo patients also demonstrated enhanced understanding of the surgical procedure (80 vs. 55%, n.s.), leading to better awareness for the occurrence of postoperative complications (88.9, vs. 68.4%, p = 0.052). Adverse event profiles were similar. CONCLUSION: In conclusion, individual 3D-printed liver models increase patient satisfaction with surgical education and facilitate patients' understanding of the surgical procedure as well as awareness of postoperative complications. Therefore, the study protocol is feasible to apply to an adequately powered, multicenter, randomized clinical trial with minor modifications.

Do certain surgical steps increase postoperative morbidity after cytoreductive surgery and HIPEC- a retrospective analysis.

INTRODUCTION: It has been shown that cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for patients suffering from peritoneal malignancies. Despite good results, there is an ongoing debate about this treatment due to perioperative morbidity. The aim of this study is to identify relevant risk factors for an unfavorable postoperative outcome after CRS and HIPEC. MATERIALS AND METHODS: A retrospective analysis of a prospectively recorded database of all patients undergoing CRS and HIPEC between 2013 and 2020 in the Department of Surgery of the University Hospital Dresden was performed with a special focus on certain surgical steps of multivisceral resection, one- or 2- stage CRS/HIPEC and underlying diagnosis as possible risk factors for worse postoperative course. RESULTS: N = 173 CRS and HIPEC procedures were performed for various diagnoses. Relevant postoperative morbidity was 24% and 30d-mortality 1.2%. Simultaneous liver resections, preoperative hypalbuminemia and 2-staged CRS/HIPEC were significant risk factors for a worse postoperative course in multivariable analysis. Assessment of the association of simultaneous anastomoses and morbidity and mortality was inconclusive. CONCLUSION: CRS and HIPEC is a safe treatment without relevant intraoperative morbidity and mortality and acceptable postoperative outcome. One-stage CRS/HIPEC should be preferred.

Case report: Incidentally discovered case of pheochromocytoma as a cause of long COVID-19 syndrome.

Pheochromocytomas (PCCs) are rare but potentially lethal tumors that arise from the adrenal medulla. The clinical suspicion and diagnosis of PCC can be challenging due to the non-specific nature of signs and symptoms. In many patients, infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could lead to long-term symptoms including fatigue, headaches, and cognitive dysfunction. Here, we present the case of a patient incidentally diagnosed with an adrenal mass that proved to be a PCC after imaging was performed due to persisting complaints after coronavirus disease 2019 (COVID-19) infection. A 37-year-old male patient was referred to our center because of a right-sided inhomogeneous adrenal mass, incidentally found during a computed tomographic scan of the thorax performed due to cough and dyspnea that persisted after COVID-19 infection. Other complaints that were present prior to COVID-19 infection included profuse sweating, dizziness, exhaustion with chronic fatigue, and concentration difficulties. The patient had no history of hypertension, his blood pressure was normal, and the 24-h ambulatory blood pressure monitoring confirmed normotension but with the absence of nocturnal dipping. Plasma normetanephrine was 5.7-fold above the upper limit (UL) of reference intervals (738 pg/ml, UL = 129 pg/ml), whereas plasma metanephrine and methoxytyramine were normal at 30 pg/ml (UL = 84 pg/ml) and <4 pg/ml (UL = 16 pg/ml), respectively. Preoperative preparation with phenoxybenzamine was initiated, and a 4-cm tumor was surgically resected. Profuse sweating as well as dizziness was resolved after adrenalectomy pointing toward PCC and not COVID-19-associated patient concerns. Altogether, this case illustrates the difficulties in recognizing the possibility of PCC due to the non-specific nature of signs and symptoms of the tumor, which in this case did not include hypertension and coincided with some of the symptoms of long COVID-19.

The use and future perspective of Artificial Intelligence-A survey among German surgeons.

Purpose: Clinical abundance of artificial intelligence has increased significantly in the last decade. This survey aims to provide an overview of the current state of knowledge and acceptance of AI applications among surgeons in Germany. Methods: A total of 357 surgeons from German university hospitals, academic teaching hospitals and private practices were contacted by e-mail and asked to participate in the anonymous survey. Results: A total of 147 physicians completed the survey. The majority of respondents (n = 85, 52.8%) stated that they were familiar with AI applications in medicine. Personal knowledge was self-rated as average (n = 67, 41.6%) or rudimentary (n = 60, 37.3%) by the majority of participants. On the basis of various application scenarios, it became apparent that the respondents have different demands on AI applications in the area of "diagnosis confirmation" as compared to the area of "therapy decision." For the latter category, the requirements in terms of the error level are significantly higher and more respondents view their application in medical practice rather critically. Accordingly, most of the participants hope that AI systems will primarily improve diagnosis confirmation, while they see their ethical and legal problems with regard to liability as the main obstacle to extensive clinical application. Conclusion: German surgeons are in principle positively disposed toward AI applications. However, many surgeons see a deficit in their own knowledge and in the implementation of AI applications in their own professional environment. Accordingly, medical education programs targeting both medical students and healthcare professionals should convey basic knowledge about the development and clinical implementation process of AI applications in different medical fields, including surgery.

[Predictors for Successful Liver Transplantation and Risk Factors]. / Prädiktoren für erfolgreiche Lebertransplantationen und Risikofaktoren.

Liver transplantation is the only curative treatment option for end stage liver disease. Moreover, oncological liver disease (hepatocellular carcinoma) is an important relevant indication for liver transplantation, together with acute liver failure.Since the first successful liver transplantation by Professor Thomas Starzl in 1967, liver transplantation has changed in many aspects. This concerns not only surgical, anaesthesiological and immunological improvements and further technical developments, but also altered patient characteristics. Patients undergoing liver transplantation are nowadays often more challenging, due to their age and relevant comorbidities.The number of liver transplantations is constantly rising. However, there are more patients in need of liver transplantation than donor grafts are available. Discrepancies between liver transplant candidates and organ supply can only partially be compensated by split liver transplantation and liver transplantation from living donors.To boost the pool of donor grafts, even marginal organs within the extended donor criteria (EDC) are being increasingly allocated. In some countries, even "donation after cardiac death (DCD) organs" are allocated as well.Marginal donor grafts are often associated with reduced graft and patient survival after liver transplantation. To improve the quality of poor liver grafts, innovations in organ conservation with development of new techniques as the machine perfusion techniques have been established in recent years.In summary, the constellation of risk factors of donor grafts as well as transplant recipients has become more challenging in recent decades. It is important to know the specific risk factors and predictors for liver transplantation, in order to obtain the best possible graft and patient survival after liver transplantation.This review gives an overview of predictors for liver transplantation, specific risk scores and indices for donor/recipient match as well as new technical devices in liver transplantation.

Oncological liver resection in elderly - A retrospective comparative study.

BACKGROUND: Due to demographic changes and higher life expectancy especially in industrial nations, the number of liver resections in patients ≥70 years is rising. It is known that older age is associated with higher postoperative morbidity and mortality after surgery under general anesthesia. The aim of this analysis is to compare the postoperative outcome after liver resections for malignancies in patients aged below and above 70 years. MATERIALS AND METHODS: A prospectively collected electronic database of 1034 liver resections between January 2013 and December 2019 was retrospectively analyzed. Comparative analysis of patients <70 and ≥ 70 years receiving liver resections for malignancies included 889 operations in 703 patients. Analysis of postoperative outcome and uni- and multivariate analyses of associated risk factors were performed. RESULTS: Median age of the whole cohort was 65 years (range 18-87 years). N = 582 liver resections (65.7%) were performed in patients <70 years with 42.8% major hepatectomies and n = 307 (34.3%) liver resections in patients ≥70 years with 50.5% major hepatectomies (p = 0.034). Relevant postoperative morbidity of the whole cohort was 27.9%. The 30-day mortality was 3.9% and re-operation rate 14.8%. Patients ≥70 years had significantly higher postoperative morbidity and mortality rates than patients <70 years. Major resections, longer operating time, need of intraoperative transfusions of blood products as well as biliodigestive anastomosis (BDA) and inferior vena cava (IVC) resection were independent risk factors for worse postoperative outcome. CONCLUSION: Liver resections in patients ≥70 years are associated with a worse postoperative course after. Parenchyma sparing resections should be preferred in those patients.

Novel Personalized Score Predicts Risk for Postoperative Biliary Leak in Liver Surgery-a Retrospective Database Analysis.

BACKGROUND: The number of liver resections is constantly rising over the last decades. Despite the reduction of overall mortality and morbidity in liver surgery, biliary leakage is still a relevant postoperative complication that can lead to a fatal postoperative course. Aim of this analysis is the identification of specific risk factors for postoperative biliary complications after liver resections and the development of a predictive biliary leakage risk score. METHODS: A single-center, retrospective analysis of 844 liver resections performed in the Department of Visceral, Thoracic and Vascular Surgery, Technische Universität Dresden, between 1/2013 and 12/2019 is conducted to identify risk factors for postoperative biliary leakage and a risk score for biliary leakage after hepatectomy is established based on multivariate regression. The score has been validated by an independent validation cohort consisting of 142 patients. RESULTS: Overall morbidity is 43.1% with 36% surgical complications and an overall mortality of 4.3%. Biliary leakage occurred in 15.8% of patients. A predictive score for postoperative biliary leakage based on age, major resection, pretreatment with FOLFOX/cetuximab and operating time is created. Patients are stratified to low (< 15%) and high (> 15%) risk with a sensitivity of 67.4% and a specificity of 70.7% in development cohort and a specificity of 68.2% and sensitivity of 75.8% in validation cohort. CONCLUSIONS: The presented score is robust and has been validated in an independent patient cohort. Depending on the calculated risk, prevention or early treatment can be initiated to avoid bile leakage and to improve postoperative course.

Extravesicular TIMP-1 is a non-invasive independent prognostic marker and potential therapeutic target in colorectal liver metastases.

Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1EV) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1EV-mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases.

Vascular surgery in liver resection.

Vascular surgery in liver resection is a standard part of liver transplantation, but is also used in oncological liver surgery. Malignant liver tumors with vascular involvement have a poor prognosis without resection. Surgery is currently the only treatment to provide long-term survival in advanced hepatic malignancy. Even though extended liver resections are increasingly performed, vascular involvement with need of vascular reconstruction is still considered a contraindication for surgery in many institutions. However, vascular resection and reconstruction in liver surgery-despite being complex procedures-are safely performed in specialized centers. The improvements of the postoperative results with reduced postoperative morbidity and mortality are a result of rising surgical and anesthesiological experience and advancements in multimodal treatment concepts with preconditioning measures regarding liver function and systemic treatment options. This review focuses on vascular surgery in oncological liver resections. Even though many surgical techniques were developed and are also used during liver transplantation, this special procedure is not particularly covered within this review article. We provide a summary of vascular reconstruction techniques in oncological liver surgery according to the literature and present also our own experience. We aim to outline the current advances and standards in extended surgical procedures for liver tumors with vascular involvement established in specialized centers, since curative resection improves long-term survival and shifts palliative concepts to curative therapy.

Radioembolization versus portal vein embolization for contralateral liver lobe hypertrophy: effect of cirrhosis.

PURPOSE: Preoperative hypertrophy induction of future liver remnant (FLR) reduces the risk of postoperative liver insufficiency after partial hepatectomy. One of the most commonly used methods to induce hypertrophy of FLR is portal vein embolization (PVE). Recent studies have shown that transarterial radioembolization (TARE) also induces hypertrophy of the contralateral liver lobe. The aim of our study was to evaluate contralateral hypertrophy after TARE versus after PVE taking into account the effect of cirrhosis. METHODS: Forty-nine patients undergoing PVE before hemihepatectomy and 24 patients with TARE as palliative treatment for liver malignancy were retrospectively included. Semi-automated volumetry of the FLR/contralateral liver lobe before and after intervention (20 to 65 days) was performed on CT or MRI, and the relative increase in volume was calculated. Cirrhosis was evaluated independently by two radiologists on CT/MRI, and interrater reliability was calculated. RESULTS: Hypertrophy after PVE was significantly more pronounced than after TARE (25.3% vs. 7.4%; p < 0.001). In the subgroup of patients without cirrhosis, the difference was also statistically significant (25.9% vs. 8.6%; p = 0.002), whereas in patients with cirrhosis, the difference was not statistically significant (18.2% vs. 7.4%; p = 0.212). After PVE, hypertrophy in patients without cirrhosis was more pronounced than in patients with cirrhosis (25.9% vs. 18.2%; p = 0.203), while after TARE, hypertrophy was comparable in patients with and without cirrhosis (7.4% vs. 8.6%; p = 0.928). CONCLUSION: TARE induces less pronounced hypertrophy of the FLR compared to PVE. Cirrhosis seems to be less of a limiting factor for hypertrophy after TARE, compared to PVE.

Evaluation of a novel navigation platform for laparoscopic liver surgery with organ deformation compensation using injected fiducials.

In laparoscopic liver resection, surgeons conventionally rely on anatomical landmarks detected through a laparoscope, preoperative volumetric images and laparoscopic ultrasound to compensate for the challenges of minimally invasive access. Image guidance using optical tracking and registration procedures is a promising tool, although often undermined by its inaccuracy. This study evaluates a novel surgical navigation solution that can compensate for liver deformations using an accurate and effective registration method. The proposed solution relies on a robotic C-arm to perform registration to preoperative CT/MRI image data and allows for intraoperative updates during resection using fluoroscopic images. Navigation is offered both as a 3D liver model with real-time instrument visualization, as well as an augmented reality overlay on the laparoscope camera view. Testing was conducted through a pre-clinical trial which included four porcine models. Accuracy of the navigation system was measured through two evaluation methods: liver surface fiducials reprojection and a comparison between planned and navigated resection margins. Target Registration Error with the fiducials evaluation shows that the accuracy in the vicinity of the lesion was 3.78±1.89 mm. Resection margin evaluations resulted in an overall median accuracy of 4.44 mm with a maximum error of 9.75 mm over the four subjects. The presented solution is accurate enough to be potentially clinically beneficial for surgical guidance in laparoscopic liver surgery.