Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. In the last decade, non-invasive liquid biopsies have transformed the field of clinical oncology, showcasing the potential of various liquid-biopsy derived analytes, including extracellular vesicles (EVs), to diagnose and monitor HCC progression and metastatic spreading, serving as promising novel biomarkers. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Serum EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). EVs of R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to EVs of NR-HCC patients (p = 0.0033). EVs of NMLD-group showed significantly higher expressions of CD41b than EVs of HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in EVs of the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs could play a role as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence. Further, more in-depth analysis of the specific EV markers are needed to corroborate their potential role as diagnostic and therapeutic targets for HCC.

Proteomic analysis of decellularized mice liver and kidney extracellular matrices.

BACKGROUND: The extracellular matrix (ECM) is a three-dimensional network of proteins that encases and supports cells within a tissue and promotes physiological and pathological cellular differentiation and functionality. Understanding the complex composition of the ECM is essential to decrypt physiological processes as well as pathogenesis. In this context, the method of decellularization is a useful technique to eliminate cellular components from tissues while preserving the majority of the structural and functional integrity of the ECM. RESULTS: In this study, we employed a bottom-up proteomic approach to elucidate the intricate network of proteins in the decellularized extracellular matrices of murine liver and kidney tissues. This approach involved the use of a novel, perfusion-based decellularization protocol to generate acellular whole organ scaffolds. Proteomic analysis of decellularized mice liver and kidney ECM scaffolds revealed tissue-specific differences in matrisome composition, while we found a predominantly stable composition of the core matrisome, consisting of collagens, glycoproteins, and proteoglycans. Liver matrisome analysis revealed unique proteins such as collagen type VI alpha-6, fibrillin-2 or biglycan. In the kidney, specific ECM-regulators such as cathepsin z were detected. CONCLUSION: The identification of distinct proteomic signatures provides insights into how different matrisome compositions might influence the biological properties of distinct tissues. This experimental workflow will help to further elucidate the proteomic landscape of decellularized extracellular matrix scaffolds of mice in order to decipher complex cell-matrix interactions and their contribution to a tissue-specific microenvironment.

Multi-organ Radiomics-Based Prediction of Future Remnant Liver Hypertrophy Following Portal Vein Embolization.

BACKGROUND: Portal vein embolization (PVE) is used to induce remnant liver hypertrophy prior to major hepatectomy. The purpose of this study was to evaluate the predictive value of baseline computed tomography (CT) data for future remnant liver (FRL) hypertrophy after PVE. METHODS: In this retrospective study, all consecutive patients undergoing right-sided PVE with or without hepatic vein embolization between 2018 and 2021 were included. CT volumetry was performed before and after PVE to assess standardized FRL volume (sFRLV). Radiomic features were extracted from baseline CT after segmenting liver (without tumor), spleen and bone marrow. For selecting features that allow classification of response (hypertrophy ≥ 1.33), a stepwise dimension reduction was performed. Logistic regression models were fitted and selected features were tested for their predictive value. Decision curve analysis was performed on the test dataset. RESULTS: A total of 53 patients with liver tumor were included in this study. sFRLV increased significantly after PVE, with a mean hypertrophy of FRL of 1.5 ± 0.3-fold. sFRLV hypertrophy ≥ 1.33 was reached in 35 (66%) patients. Three independent radiomic features, i.e. liver-, spleen- and bone marrow-associated, differentiated well between responders and non-responders. A logistic regression model revealed the highest accuracy (area under the curve 0.875) for the prediction of response, with sensitivity of 1.0 and specificity of 0.5. Decision curve analysis revealed a positive net benefit when applying the model. CONCLUSIONS: This proof-of-concept study provides first evidence of a potential predictive value of baseline multi-organ radiomics CT data for FRL hypertrophy after PVE.

Clinical impact of a celiac axis stenosis in patients undergoing hepatobiliary surgery.

BACKGROUND: Celiac axis stenosis (CAS) often is an incidental finding in terms of diagnostic for hepatobiliary surgery since most cases remain asymptomatic. It remains unclear whether CAS is a risk factor for postoperative complications after hepatobiliary surgery. Therefore, the aim of this study was to evaluate the impact of an asymptomatic CAS on the postoperative morbidity and survival of patients undergoing hepatobiliary surgery. METHODS: We retrospectively analyzed CT scans and clinicopathological data of 250 consecutive patients undergoing hepatobiliary surgery between 2011 and 2018 in our tertiary center. We compared the postoperative course between patients with and without an incidental CAS as well as their overall survival. RESULTS: CAS was caused by atherosclerotic stenosis in 16 (64%) patients, by ligamentous stenosis in 4 (16%) and by combined conditions in 5 cases (20%). Mean age of patients in the CAS group was significantly higher in comparison to patients of the non-CAS group (71.0 vs. 59.1 years, p < 0.001). Major hepatectomy was conducted in 40% of the CAS patients and 19.6% of non-CAS patients, respectively (p = 0.036). Interestingly, no statistically significant differences in postoperative morbidity (40 vs. 46.2%, p = 0.673) or in overall survival between the groups (41.3 vs. 51.9 months, p = 0.611) were observed. CONCLUSION: Our analysis found no correlation between an asymptomatic celiac axis stenosis and postoperative complications or overall survival after hepatobiliary surgery. Which impact the incidental CAS may have in highly complex cases remains unclear. Further studies are needed to identify patients who benefit from CAS treatment before hepatobiliary surgery.

Robotic-Assisted Esophagectomy Leads to Significant Reduction in Postoperative Acute Pain: A Retrospective Clinical Trial.

BACKGROUND: Robot-assisted minimally invasive esophagectomy (RAMIE) shows promising results regarding postoperative complications in patients with esophageal cancer. To date, no data are available regarding postoperative analgesic consumption. The aim of this work is to evaluate analgesic consumption after esophagectomy. METHODS: A total of 274 Ivor Lewis esophageal resections performed sequentially from January 2012 to December 2020 were evaluated. RAMIE cases (n = 51) were compared with the hybrid technique (laparoscopic abdominal phase followed by open thoracotomy, n = 59) and open abdominothoracic esophagectomy (OTE) (n = 164). Data were collected retrospectively. The primary endpoint was the overall postoperative morphine consumption, which represents a reliable indirect measurement of pain. Pain levels recorded on the first, third, and fifth postoperative days were assessed as secondary endpoints. RESULTS: A total of 274 patients were included. The postoperative opioid consumption rate for patients who underwent RAMIE (quartiles: 0.14, 0.23, 0.36 mg morphine milligram equivalents (MME)/kg body weight (bw)/day) was significantly lower than in the open group (0.19, 0.33, 0.58 mg MME/kg bw/day, p = 0.016). The overall postoperative opioid consumption for patients who underwent RAMIE was significantly lower (2.45, 3.63, 7.20 mg MME/kg bw/day; morphine milligram equivalents per kilogram body weight) compared with the open (4.85, 8.59, 14.63 MME/kg bw/day, p < 0.0001) and hybrid (4.13, 6.84, 11.36 MME/kg bw/day, p = 0.008) groups. Patients who underwent RAMIE reported lower pain scores compared with the open group on the fifth postoperative day, both at rest (p = 0.004) and while performing activities (p < 0.001). CONCLUSIONS: This study shows that patients who underwent RAMIE experienced similar postoperative pain while requiring significantly lower amounts of opioids compared with patients who underwent open and hybrid surgery. Further studies are required to verify the results.

Liver Resection for Primary Hepatic Angiosarcoma: Bicentric Analysis of a Challenging Entity.

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of the liver, and data on patient outcome after surgical treatment are scarce. The aim of this study was to evaluate postoperative morbidity and overall survival (OS) of patients who underwent hepatectomy for PHA. This is a bicentric retrospective analysis of all consecutive patients who underwent liver resection in curative intent for PHA between 2012 and 2019 at the University Hospital of Muenster and the University Hospital of Bern. Nine patients (five female, four male) were included from both centers. Median age was 72 years (44-82). Most lesions (77.8%) were larger than 5 cm, and mean size of the biggest lesion was 9.4 ± 4.5 cm. Major hepatectomy was performed in four (44.4%), and radical resection (R0) was achieved in six (66.7%) patients. Postoperative complication rate was 88.8%, including 44.4% higher than 3a in the Clavien-Dindo classification. OS survival rates at 1, 2, and 3 years were 44.4%, 22.2%, and 12.5%, respectively, and median OS was 5 months. OS was significantly better after radical resection (R0: 15 months vs. R1: 0 months, p = 0.04), whereas presentation with tumor rupture at diagnosis was associated with the worst OS (0 months vs. 15 months, p = 0.005). Disease recurrence occurred in three patients (33.3%) between three and seven months after surgery. Radical resection remains the only potentially curative treatment option for PHA. However, postoperative morbidity is high, and the overall prognosis remains poor. Multimodal therapy options and management strategies are urgently needed and could improve the prognosis of patients suffering from PHA in the future.

Hyperspectral imaging for quantitative assessment of hepatic steatosis in human liver allografts.

INTRODUCTION: In liver transplantation (LT), steatosis is commonly judged to be a risk factor for graft dysfunction, and quantitative assessment of hepatic steatosis remains crucial. Liver biopsy as the gold standard for evaluation of hepatic steatosis has certain drawbacks, that is, invasiveness, and intra- and inter-observer variability. A non-invasive, quantitative modality could replace liver biopsy and eliminate these disadvantages, but has not yet been evaluated in human LT. METHODS: We performed a pilot study to evaluate the feasibility and accuracy of hyperspectral imaging (HSI) in the assessment of hepatic steatosis of human liver allografts for transplantation. Thirteen deceased donor liver allografts were included in the study. The degree of steatosis was assessed by means of conventional liver biopsy as well as HSI, performed at the end of back-table preparation, during normothermic machine perfusion (NMP), and after reperfusion in the recipient. RESULTS: Organ donors were 51 [30-83] years old, and 61.5% were male. Donor body mass index was 24.2 [16.5-38.0] kg/m2 . The tissue lipid index (TLI) generated by HSI at the end of back-table preparation correlated significantly with the histopathologically assessed degree of overall hepatic steatosis (R2 = .9085, P < .0001); this was based on a correlation of TLI and microvesicular steatosis (R2 = .8120; P < .0001). There is also a linear relationship between the histopathologically assessed degree of overall steatosis and TLI during NMP (R2 = .5646; P = .0031) as well as TLI after reperfusion (R2 = .6562; P = .0008). CONCLUSION: HSI may safely be applied for accurate assessment of hepatic steatosis in human liver grafts. Certainly, TLI needs further assessment and validation in larger sample sizes.

Surgery for Liver Metastasis of Non-Colorectal and Non-Neuroendocrine Tumors.

Surgery has become well established for patients with colorectal and neuroendocrine liver metastases. However, the value of this procedure in non-colorectal and non-neuroendocrine metastases (NCRNNELMs) remains unclear. We analyzed the outcomes of patients that underwent liver surgery for NCRNNELMs and for colorectal liver metastases (CRLMs) between 2012 and 2017 at our institution. Prognostic factors of overall and recurrence-free survival were analyzed, and a comparison of survival between two groups was performed. Seventy-three patients (30 NCRNNELM and 43 CRLM) were included in this study. Although the mean age, extrahepatic metastases, and rate of reoperation were significantly different between the groups, recurrence-free survival was comparable. The 5-year overall survival rates were 38% for NCRNNELM and 55% for CRLM. In univariate analysis, a patient age of ≥60 years, endodermal origin of the primary tumor, and major complications were negative prognostic factors. Resection for NCRNNELM showed comparable results to resection for CRLM. Age, the embryological origin of the primary tumor, and the number of metastases might be the criteria for patient selection.

[Influence of molecular pathology on oncological surgery of liver and bile duct tumors]. / Einfluss der Molekularpathologie auf die onkologische Chirurgie von Leber- und Gallengangstumoren.

BACKGROUND: Molecular pathology is increasingly being used to guide treatment in oncology. Approximately 25% of all hepatocellular carcinomas (HCC) and 50% of cholangiocarcinomas (CCA) present with known cancer-relevant mutations; however, the impact of the mutations on the treatment of these tumors is not yet sufficiently understood. PURPOSE: To evaluate the current literature on molecular pathological advances in HCC/CCA and the potential impact on oncological surgery. MATERIAL AND METHODS: A comprehensive search of the available literature on currently known molecular biomarkers in HCC/CCA was performed in PubMed and clinitrials.gov. Following review, the potential impact of these biomarkers on oncological surgery was analyzed and is discussed. CONCLUSION: Molecular pathological investigations can be used to support the classification of tumors and to determine the dignity of HCC/CCA. Predictive molecular biomarkers are not yet established in routine diagnostics but can be used to individualize advanced oncological treatment.

In vitro recellularization of decellularized bovine carotid arteries using human endothelial colony forming cells.

BACKGROUND: Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients. Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology. RESULTS: Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful. CONCLUSION: Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.

Totally implantable venous access port insertion via open Seldinger approach of the internal jugular vein-a retrospective risk stratification of 500 consecutive patients.

PURPOSE: Modern oncological treatment algorithms require a central venous device in form of a totally implantable venous access port (TIVAP). While most commonly used techniques are surgical cutdown of the cephalic vein or percutaneous puncture of the subclavian vein, there are a relevant number of patients in which an additional strategy is needed. The aim of the current study is to present a surgical technique for TIVAP implantation via an open Seldinger approach of the internal jugular vein and to characterize risk factors, associated with primary failure as well as short- (< 30 days) and long-term (> 30 days) complications. METHODS: A total of 500 patients were included and followed up for 12 months. Demographic and intraoperative data and short- as well as long-term complications were extracted. Primary endpoint was TIVAP removal due to complication. Logistic regression analysis was used to analyze associated risk factors. RESULTS: Surgery was primarily successful in all cases, while success was defined as functional (positive aspiration and infusion test) TIVAP which was implanted via open Seldinger approach of the jugular vein at the intended site. TIVAP removal due to complications during the 1st year occurred in 28 cases (5.6%) while a total of 4 (0.8%) intraoperative complications were noted. Rates for short- and long-term complications were 0.8% and 6.6%, respectively. CONCLUSION: While the presented technique requires relatively long procedure times, it is a safe and reliable method for TIVAP implantation. Our results might help to further introduce the presented technique as a secondary approach in modern TIVAP surgery.

Portal and hepatic vein embolization prior to major hepatectomy.

PURPOSE: To analyze safety and effectiveness of simultaneous portal and hepatic vein embolization (PHVE) or sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE) for future remnant liver (FRL) hypertrophy prior to major hepatic surgery. METHODS: Patients undergoing PVE, PHVE or HVE at our tertiary care center between 2018 and 2020 were retrospectively included. FRLV, standardized FRLV (sFRLV) and sFRLV growth rate per day were assessed via volumetry, as well as laboratory parameters. RESULTS: 36 patients (f = 15, m = 21; median 64.5 y) were included, 16 patients received PHVE and 20 patients PVE, of which 4 received sequential HVE. Significant increase of FRLV was achieved with both PVE and PHVE compared to baseline (p < 0.0001). sFRLV growth rate did not significantly differ following PHVE (2.2 ±â€Š1.2 %/d) or PVE (2.2 ±â€Š1.7 %/d, p = 0.94). Left portal vein thrombosis (LPVT) was observed after PHVE in 6 patients and in 1 patient after PVE. Sequential HVE showed a considerably high growth rate of 1.42 ±â€Š0.45 %/d after PVE. CONCLUSION: PHVE effectively induces FRL hypertrophy but yields comparable sFRLV to PVE. Sequential HVE further induces hypertrophy after insufficient growth due to PVE. Considering a potentially higher rate of LPVT after PHVE, PVE might be preferred in patients with moderate baseline sFRLV, with optional sequential HVE in non-sufficient responders.

Robotic Liver Surgery - Current Standards and Future Perspectives.

BACKGROUND: Robotic liver surgery is emerging as the future of minimal invasive surgery. The robotic surgical system offers a stable camera platform, elimination of physiologic tremor, augmented surgical dexterity as well as improved ergonomics because of a seated operating position. Due to the theoretical advantages of the robotic assisted system, complex liver surgery might be an especially interesting indication for a robotic approach since it demands delicate tissue dissection, precise intracorporeal suturing as well as difficult parenchymal transection with subsequent need for meticulous hemostasis and biliostasis. MATERIAL AND METHODS: An analysis of English and German literature on open, laparoscopic and robotic liver surgery was performed and this review provides a general overview of the existing literature along with current standards and aims to specifically point out future directions of robotic liver surgery. RESULTS: Robotic liver surgery is safe and feasible compared to open and laparoscopic surgery, with improved short-term postoperative outcomes and at least non-inferior oncological outcomes. CONCLUSION: In complex cases including major hepatectomies, extended hepatectomies with biliary reconstruction and difficult segmentectomies of the posterior-superior segments, robotic surgery appears to emerge as a reasonable alternative to open surgery rather than being an alternative to laparoscopic procedures.

Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts.

The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted.

Laparoscopic Resection for Adenocarcinoma of the Stomach or Gastroesophageal Junction Improves Postoperative Outcomes: a Propensity Score Matching Analysis.

BACKGROUND: Minimally invasive resection for upper gastrointestinal tumors has been associated with favorable results. However, the role of laparoscopic surgery (LS) in the multimodal treatment of patients with advanced adenocarcinoma of the stomach or gastroesophageal junction needs further investigation. METHODS: Clinicopathological data of patients who underwent gastrectomy between 2005 and 2017 were assessed. Outcomes of patients undergoing LS were compared with those of patients treated with a conventional open resection (OR) using a 1:1 propensity score matching analysis. RESULTS: Curative resection for adenocarcinoma of the stomach or gastroesophageal junction was performed in 417 patients during the study period. Beginning in June 2014, the majority of patients underwent LS (n = 72) and they were matched with 72 patients who were treated with an OR. The majority of patients treated with LS (89%) had advanced cancer (UICC stages II and III) and 82% of them received neoadjuvant chemotherapy. LS was significantly associated with a higher number of harvested lymph nodes (26 (9-62) vs. 21 (4-46), P = .007), a lower 90-day major complication rate (13 vs. 26%, P = .035), and a lower length of hospital stay (14 vs. 16 days, P = .001). After a median follow-up time of 32 months, 1-year overall survival rate was higher after LS than after OR (93 vs. 74%, P = .126); however, results did not reach statistical significance. CONCLUSION: LS for adenocarcinoma of the stomach or gastroesophageal junction is feasible and significantly reduces major postoperative morbidity resulting in a reduced length of hospital stay. Therefore, LS should be preferably considered for the curative treatment of patients with these malignancies.

The role of hepatectomy for synchronous liver metastases from pancreatic adenocarcinoma.

BACKGROUND: The role of hepatectomy for patients with liver metastases from ductal adenocarcinoma of the pancreas (PLM) remains controversial. Therefore, the aim of our study was to examine the postoperative morbidity, mortality, and long-term survivals after liver resection for synchronous PLM. METHODS: Clinicopathological data of patients who underwent hepatectomy for PLM between 1993 and 2015 were assessed. Major endpoint of this study was to identify predictors of overall survival (OS). RESULTS: During the study period, 76 patients underwent resection for pancreatic cancer and concomitant hepatectomy for synchronous PLM. Pancreatoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 67%, 25%, and 8% of the patients, respectively. The median PLM size was 1 (1-13) cm and 36% of patients had multiple PLM. The majority of patients (96%) underwent a minor liver resection. After a median follow-up time of 130 months, 1-, 3-, and 5-year OS rates were 41%, 13%, and 7%, respectively. Postoperative morbidity and mortality rates were 50% and 5%, respectively. Preoperative and postoperative chemotherapy was administered to 5% and 72% of patients, respectively. In univariate analysis, type of pancreatic procedure (P = .020), resection and reconstruction of the superior mesenteric artery (P = .016), T4 stage (P = .086), R1 margin status at liver resection (P = .001), lymph node metastases (P = .016), poorly differentiated cancer (G3) (P = .037), no preoperative chemotherapy (P = .013), and no postoperative chemotherapy (P = .005) were significantly associated with worse OS. In the multivariate analysis, poorly differentiated cancer (G3) (hazard ratio [HR] = 1.87; 95% confidence interval [CI] = 1.08-3.24; P = .026), R1 margin status at liver resection (HR = 4.97; 95% CI = 1.46-16.86; P = .010), no preoperative chemotherapy (HR = 4.07; 95% CI = 1.40-11.83; P = .010), and no postoperative chemotherapy (HR = 1.88; 95% CI = 1.06-3.29; P = .030) independently predicted worse OS. CONCLUSIONS: Liver resection for PLM is feasible and safe and may be recommended within the framework of an individualized cancer therapy. Multimodal treatment strategy including perioperative chemotherapy and hepatectomy may provide prolonged survival in selected patients with metastatic pancreatic cancer.

Minimal-invasive versus open hepatectomy for hepatocellular carcinoma: Comparison of postoperative outcomes and long-term survivals using propensity score matching analysis.

BACKGROUND: Minimal-invasive hepatectomy (MIH) has been increasingly performed for benign and malignant liver lesions with most promising results. However, the role of MIH for the treatment of patients with hepatocellular carcinoma (HCC) needs further investigation. METHODS: Clinicopathological data of patients who underwent liver resection for HCC between 2005 and 2016 were assessed. Postoperative outcomes und long-term survivals of patients following MIH were compared with those of patients undergoing conventional open hepatectomy (OH) after 1:1 propensity score matching. RESULTS: During the study period, 407 patients underwent liver resection for HCC with curative intent. Fifty-six patients underwent MIH and were compared with a matched cohort of 56 patients who underwent OH. The rate of patients with fibrosis/cirrhosis (82% vs. 86%, p = 0.959), multiple lesions (32% vs. 32%, p = 1.00), tumor size >30 mm (61% vs. 55%, p = 0.566), and major resection (16% vs. 16%, p = 1.00) was comparable between the two groups (MIH vs. OH). MIH was associated with lower 90-day complication rate (32% vs. 54%, p = 0.022), lower postoperative major complication rate (14% vs. 30%, p = 0.041), lower liver failure rate (0% vs. 7%, p = 0.042), lower 90-day mortality rate (0 vs. 7%, p = 0.042), and shorter length of hospital stay (9 vs. 12 days, p = 0.009) compared to OH. After a median follow-up time of 51 months, MIH and OH showed comparable 5-year overall survival (54% vs. 41%, p = 0.151), and 5-year disease-free survival rates (50% vs. 38%, p = 0.956). CONCLUSIONS: MIH for HCC is associated with lower postoperative morbidity and mortality and shorter length of hospital stay, resulting in oncologic outcomes similar to those achieved with the established OH. Our findings suggest that MIH should be considered as the preferred method for the treatment of curatively resectable HCC.

The Predictive Value of the Maximal Liver Function Capacity Test for the Isolation of Primary Human Hepatocytes.

The need for primary human hepatocytes is constantly growing for basic research, as well as for therapeutic applications. However, the isolation outcome strongly depends on the quality of liver tissue, and we are still lacking a preoperative test that allows the prediction of the hepatocyte isolation outcome. In this study, we evaluated the "maximal liver function capacity test" (LiMAx) as predictive test for the quantitative and qualitative outcome of hepatocyte isolation. This test is already used in clinical routine to measure preoperative and to predict postoperative liver function. The patient's preoperative mean LiMAx was obtained from the patient records, and preoperative computed tomography and magnetic resonance images were used to calculate the whole liver volume to adjust the mean LiMAx. The outcome parameters of the hepatocyte isolation procedures were analyzed in correlation with the adjusted mean LiMAx. Primary human hepatocytes were isolated from partial hepatectomies (n = 64). From these 64 hepatectomies we included 48 to our study and correlated their isolation outcome parameters with volume corrected LiMAx values. From a total of 11 hepatocyte isolation procedures, metabolic parameters (albumin, urea, and aspartate aminotransferase or AST) were assessed during the hepatocyte cultivation period of 5 days. The volume adjusted mean LiMAx showed a significant positive correlation with the total cell yield (p = 0.049; r = 0.242; n = 48). The correlations of volume adjusted LiMAx values with viable cell yield and cell viability did not reach statistical significance. To create a more homogenous study group regarding tumor entities, subgroup analyses were performed. A subgroup analysis of isolations from patients with colorectal metastasis revealed a significant correlation between volume adjusted mean LiMAx and total cell yield (p = 0.012; r = 0.488; n = 21) and viable cell yield (p = 0.034; r = 0.405; n = 21), whereas a subgroup analysis of isolations of patients with carcinoma of the biliary tree showed significant correlations of volume adjusted mean LiMAx with cell viability (r = 0.387; p = 0.046; n = 20) and lacked significant correlations with total cell yield (r = -0.060; p = 0.401; n = 20) and viable cell yield (r = 0.012; p = 0.480; n = 20). The volume-adjusted mean LiMAx did not show a significant correlation with any of the metabolic parameters. In conclusion, the LiMAx test might be a useful tool to predict the quantitative outcome of hepatocyte isolation, as long as underlying liver disease is taken into consideration.