Value of the surgical pancreatic duct anatomy and associated outcomes in pancreatic cancer.

INTRODUCTION: Pancreatic cancer recurrence following surgery is a significant challenge, and personalized surgical care is crucial. Topographical variations in pancreatic duct anatomy are frequent but often underestimated. This study aimed to investigate the potential importance of these variations in outcomes and patient survival after Whipple's procedures. METHODS: Data were collected from 105 patients with confirmed pancreatic head neoplasms who underwent surgery between 2008 and 2020. Radiological measurements of pancreatic duct location were performed, and statistical analysis was carried out using IBM SPSS. RESULTS: Inferior pancreatic duct topography was associated with an increased rate of metastatic spread and tumour recurrence. Additionally, inferior duct topography was associated with reduced overall and recurrence-free survival. Posterior pancreatic duct topography was associated with decreased incidence of perineural sheet infiltration and improved overall survival. DISCUSSION: These findings suggest that topographical diversity of pancreatic duct location can impact outcomes in Whipple's procedures. Intraoperative review of pancreatic duct location could help surgeons define areas of risk or safety and deliver a personalized surgical approach for patients with beneficial or deleterious anatomical profiles. This study provides valuable information to improve surgical management by identifying high-risk patients and delivering a personalized surgical approach with prognosis stratification.

Protective and Therapeutic Capacities of Lactic Acid Bacteria Postmetabolites against Koi Herpesvirus Infection In Vitro.

BACKGROUND: The accumulation of data on beneficial biological effects of probiotics and their metabolic products favors their potential use in the prevention and treatment of various malaises. METHODS: Nine postmetabolites from Lactic acid bacteria (LAB) of human or dairy origin and their antiviral activity were studied using the cytopathic effect inhibition test. The virucidal capacity, their influence on the adsorption stage of Koi herpes virus (KHV) and their preventive role against subsequent viral challenge on intact Common carp brain (CCB) cells were also determined by titration assay. Residual viral infectivity in postmetabolites-treated samples was compared to mock-treated controls and Δlgs were calculated. RESULTS: When administered during KHV replication, the microbial products isolated from Lactiplantibacillus plantarum showed remarkable activity with a selectivity index (SI) between 26.5 and 221.4, as those effects were dependent on the sample-virus incubation time. Postmetabolites from Lactobacillus gasseri and Lactiplantibacillus plantarum also demonstrated significant inhibition of KHV replication with SI of 24 and 16, respectively. The bioactive metabolites isolated from Limosilactobacillus fermentum had a minor effect on the viral replicative cycle. Compounds, produced during the fermentation by lactobacilli, grown on different nutritive media and collected at different time points, significantly inhibited extracellular KHV virions. All investigated postmetabolites remarkably blocked KHV attachment to the host cell (CCB), leading to a drop in viral titers by Δlg = 4.25-5.25, and exerted protective effects on CCB cells before they were subjected to viral infection. CONCLUSIONS: Our results open new horizons and promote LAB and their postbiotic products to be used in the prophylaxis and therapy of viral infections.

Anti-herpes virus activity of lactobacillus' postbiotics.

Background: Recently various lactic acid bacteria (LAB) and their post-metabolites have shown many positive effects on human and animal welfare. They appear to be beneficial in different disorders and pathological conditions, including in a broad-spectrum of infectious diseases. Aim: To estimate in vitro the anti-herpes simplex activity of 11 postbiotic samples (lysates or cell-free supernatants - CFS) produced during the fermentation of six candidate-probiotic Lactobacillus strains isolated from Bulgarian fermented milk products. Materials and methods: In vitro protocols for assessment of different LAB samples on the Herpes simplex virus type 1 (HSV-1) replication, adsorption and virucidal effects were applied using MDBK cells. Results: Four of the studied LAB samples expressed a statistically significant inhibition of the replication of HSV-1. The highest selective index (79.75) was calculated for the post-metabolites of Lactiplantibacillus plantarum, followed by a high molecular fraction of cell-derived fragments of Limosilactobacillus fermentum culture (S6) (SI = 34.63), CFS from late exponential L. plantarum (SI = 28.26) and neutralized CFS from L. fermentum (SI = 28.11). Pronounced virucidal activities of the postbiotics S1, S11 (L. fermentum), S3 (L. plantarum) and S6 (L. fermentum) were recorded, too. The inhibitory effect of the majority of the samples on the stage of adsorption of the virus to MDBK cells was remarkable. In addition, almost all of the postbiotics exerted a protective effect on healthy cells and significantly reduced viral yield at subsequent infection. Conclusion: Pre-selected Lactobacillus strains demonstrated strain-specific effects against HSV-1. These postbiotics influence different stages of viral infection in cell cultures and their promising characteristics are currently evaluated.

Recipient Hepatic Tumor-Associated Immunologic Infiltrates Predict Outcomes After Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND Transplantation of the liver entails a state of altered recipient immunologic competence. There are only scarce data concerning the impact of host immunologic factors on the outcome of liver transplant recipients in the context of hepatocellular carcinoma (HCC). MATERIAL AND METHODS Our study focused on evaluating the presence of tumor necrosis and frequency levels of angiopoietins and monocytes/macrophages subtypes in the host liver prior to liver transplantation (LTX) and their association with recurrence, graft rejection, survival, and clinical prognosis after LTX. Formation of tumor necrosis and tissue densities of angiopoietins and cellular immunologic infiltrates - CD68⁺ and CD163⁺ macrophages (TAMs) and TIE2-expressing monocytes (TEMs) - were quantified in recipient HCC specimens. The densities were then matched with clinicopathologic variables and patient survival after LTX (n=88). Some patients were treated prior to LTX by neoadjuvant transarterial chemoembolization (TACE, n=55). RESULTS Recipient hepatic infiltration with TEMs and CD68⁺ TAMs was associated with decreased 1-, 3-, and 5-year survival, as well as metastatic and recurrent HCC after LTX (all p<0.05). TEMs and infiltrating monocytes/macrophages were associated with angiopoietin expression, metastatic, and recurrent HCC (all p<0.05). Furthermore, hepatic angiopoietin-2 expression was associated with graft rejection after LTX (p<0.05). After TACE and LTX, formation of tumor necrosis was associated with an increased presence of monocytes/macrophages and a reduced incidence of recurrent HCC in the graft (all p<0.05). CONCLUSIONS Infiltrating monocytes/macrophages subsets and related angiopoietin axis are associated with worse survival, tumor recurrence, and clinical outcome after LTX for HCC.

Safety and feasibility of laparoscopic liver resection in patients with a history of abdominal surgeries.

BACKGROUND: Laparoscopic techniques have become the standard approach for most liver resections. Clinical studies providing conclusive evidence which patients benefit most from minimal-invasive surgery remain limited. METHODS: We retrospectively analyzed data of all consecutive cases of laparoscopic liver resection between 2015 and 2018 at our center. We compared patients with and without prior abdominal surgeries with respect to postoperative complications (Clavien-Dindo score), length of operation, length of ICU stay and length of hospitalization in univariate and multivariate analyses. RESULTS: Within the study period 319 patients underwent laparoscopic liver resections, 44% of which had a history of abdominal surgeries. Pre-operative characteristics were similar to patients without prior surgeries. Both groups showed comparable rates of post-operative complications (Clavien-Dindo score ≥3a; 12% in patients without vs. 16% with prior surgeries, p = 0,322). There were no significant differences in length of surgery or length of stay in the ICU or in the hospital. CONCLUSION: Our data suggest that history of prior abdominal surgery is not a risk factor for post-operative complications after laparoscopic liver resection. We conclude that prior abdominal surgery should not be considered a contra-indication for laparoscopic approach in liver resection.

Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis.

BACKGROUND: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC). METHODS: In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival. RESULTS: Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05). CONCLUSIONS: Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis-TEM-angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC.

Immunologic cellular characteristics of the tumour microenvironment of hepatocellular carcinoma drive patient outcomes.

BACKGROUND: Anti-tumour immune competence has an impact in hepatocarcinogenesis and success of anti-cancer therapies. Tumour-infiltrating lymphocytes (TILs) and monocytes/macrophages (TAMs) are proposed to have significance in cancer. However, there is only limited data concerning their impact on patient outcome and survival in hepatocellular carcinoma (HCC). METHODS: Frequencies of CD68+, CD163+ M2-polarized TAMs and TILs were measured in de novo HCC tumours in non-cirrhosis (n = 58) using immunohistology and correlated to patients' clinicopathological characteristics and survival rates. RESULTS: Patients with tumours marked by appearance of TILs and CD68+ TAMs showed an improved 1-, 3- and 5-year recurrence-free survival (all p ≤ 0.05). CD68+ TAMs were associated with reduced incidence of recurrent and multifocal disease. Conversely, CD163+ TAMs were associated with multifocal HCC and lymphangiosis carcinomatosa (all p ≤ 0.05). CONCLUSIONS: TILs and CD68+ TAMs are associated with multiple tumour characteristics and patient survival in HCC. However, there is only scarce data about the biology underlying their mechanistic involvement in human tumour progression. Thus, experimental data on functional links might help develop novel immunologic checkpoint inhibitor targets for liver cancer.

Power of computed-tomography-defined sarcopenia for prediction of morbidity after pancreaticoduodenectomy.

BACKGROUND: The goal of our study was to evaluate the current approach in prediction of postoperative major complications after pancreaticoduodenectomy (PD), especially symptomatic pancreatic fistula (POPF), using parameters derived from computed tomography (CT). METHODS: Patients after PD were prospectively collected in a database of the local department of surgery and all patients with CT scans available were assessed in this study. CT parameters were measured at the level of the intervertebral disc L3/L4 and consisted of the areas of the visceral adipose tissue (AVAT), the diameters of the pancreatic parenchyma (DPP) and the pancreatic duct (DPD), the areas of ventral abdominal wall muscle (AMVEN), psoas muscle (AMPSO), paraspinal muscle (AMSPI), total muscle (AMTOT), as well as the mean muscle attenuation (MA) and skeletal muscle index (SMI). Mann-Whitney-U Test for two independent samples and binary logistic regression were used for statistical analysis. RESULTS: One hundred thirty-nine patients (55 females, 84 males) were included. DPD was 2.9 mm (Range 0.7-10.7) on median and more narrow in patients with complications equal to or greater stadium IIIb (p < 0.04) and severe POPF (p < 0.01). DPP median value was 17 (6.9-37.9) mm and there was no significant difference regarding major complications or POPF. AVAT showed a median value of 127.5 (14.5-473.0) cm2 and was significantly larger in patients with POPF (p < 0.01), but not in cases of major complications (p < 0.06). AMPSO, AMSPI, AMVEN and AMTOT showed no significant differences between major complications and POPF. MA was both lower in groups with major complications (p < 0.01) and POPF (p < 0.01). SMI failed to differentiate between patients with or without major complications or POPF. CONCLUSION: Besides the known factors visceral obesity and narrowness of the pancreatic duct, the mean muscle attenuation can easily be examined on routine preoperative CT scans and seems to be promising parameter to predict postoperative complications and POPF.

Minimally Invasive Liver Surgery in Elderly Patients-A Single-Center Experience.

BACKGROUND: In recent years, laparoscopic liver resection has elicited growing attention as a safe procedure for various forms of hepatic resection. In the context of an aging population, this study aims to evaluate outcomes in elderly patients (>70 y) compared with younger patients (≤70 y). METHODS: All consecutive patients undergoing minimally invasive liver resections between December 2013 and January 2018 at the Department of Surgery, Charité-Universitätsmedizin Berlin, were included in this analysis. Patients' characteristics, such as body mass index, American Society of Anesthesiologists classification, as well as underlying liver disease and function, were examined and the perioperative outcomes of patients aged >70 y (group 1; G1) contrasted with patients aged ≤ 70 y (group 2; G2). RESULTS: Of 250 patients, 67 were >70 y old (G1) and 183 were ≤70 y old (G2). Patients in G1 were characterized by a higher body mass index (27.6 kg/m2versus 24.9 kg/m2; P = 0.004) and impaired physical states (American Society of Anesthesiologists score III/IV; 60% versus 37%; P = 0.002) when compared with group 2. G1 also exhibited higher rates of primary and secondary hepatic malignancies (G1: n = 62; 92.5%; G2: n = 115, 62.8%; P = 0.031) in addition to higher rates of cirrhosis (G1: n = 30, 44.8%; G2: n = 38, 20.8%; P = <0.001). The rate of major complications (Dindo-Clavien grade ≥ III) was similar between both groups (P = 0.58), with no differences regarding resection extent (P = 0.469). No difference was evident with regard to the median intensive care unit (median 1 versus 1 d; range, G1, 0-8 d, G2, 0-23 d; P = 0.1). However, we observed a significant longer hospital stay in G1 of 1 d (median 8 versus 9 d; G1 range: 4-35 d: G2 range: 4-59 d; P = 0.015). CONCLUSIONS: Minimally invasive liver resection is a feasible and safe procedure in elderly patients despite this age group exhibiting a higher rate of primary and secondary malignancy and cirrhosis, as well as an overall more severely compromised physical health when compared with patients under the age of 70 y. Therefore, it stands to reason that patients in poorer general health might particularly benefit from a minimally invasive approach.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Hilar en bloc resection for hilar cholangiocarcinoma in patients with limited liver capacities-preserving parts of liver segment 4.

BACKGROUND: A right trisectionectomy with portal vein resection represents the conventional approach for hilar cholangiocarcinoma. Here, we present a technical modification of hilar en bloc resection in order to increase the remnant volume by partially preserving liver segment 4. METHODS: The caudal parenchymal dissection line starts centrally between the left lateral and left medial segments. Cranially, the resection line switches to the right towards Cantlie's line and turns again upwards perpendicularly. Hence, segment 4a and subtotal segment 4b are partially preserved by this novel technique. The left hepatic duct is dissected at the segmental ramification and reconstruction is performed as a single hepaticojejunostomy. The feasibility of the novel parenchyma-sparing approach for hilar cholangiocarcinoma was proven in a case series and medical records were reviewed retrospectively. RESULTS: Ten patients (6 male, 4 female) underwent segment 4 partially preserving right trisectionectomy for hilar cholangiocarcinoma. Estimated future liver remnant volume was significantly increased (FLRV 38.3%), when compared to standard right trisectionectomy (FLRV 23.9%; p < 0.01). Three of 10 liver resections were associated with major surgical complications (≥IIIb; n = 3); categorized according to the Dindo-Clavien classification. No patient died due to complications associated with postoperatively impaired liver function. Tumor-free margins could be achieved in 8 patients while median overall survival and disease-free survival were 547 and 367 days, respectively. CONCLUSION: This novel parenchyma-sparing modification of hilar en bloc resection by partially preserving segment 4 allows to safely increase the remnant liver volume without neglecting principles of local radicality.

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 nanomolar sensing of nicotinamide adenine dinucleotide in human plasma using a cycling assay in albumin modified simulated body fluids.

Nicotinamide adenine dinucleotide (NAD), a prominent member of the pyridine nucleotide family, plays a pivotal role in cell-oxidation protection, DNA repair, cell signalling and central metabolic pathways, such as beta oxidation, glycolysis and the citric acid cycle. In particular, extracellular NAD+ has recently been demonstrated to moderate pathogenesis of multiple systemic diseases as well as aging. Herein we present an assaying method, that serves to quantify extracellular NAD+ in human heparinised plasma and exhibits a sensitivity ranging from the low micromolar into the low nanomolar domain. The assay achieves the quantification of extracellular NAD+ by means of a two-step enzymatic cycling reaction, based on alcohol dehydrogenase. An albumin modified revised simulated body fluid was employed as standard matrix in order to optimise enzymatic activity and enhance the linear behaviour and sensitivity of the method. In addition, we evaluated assay linearity, reproducibility and confirmed long-term storage stability of extracellular NAD+ in frozen human heparinised plasma. In summary, our findings pose a novel standardised method suitable for high throughput screenings of extracellular NAD+ levels in human heparinised plasma, paving the way for new clinical discovery studies.

Surgical therapy of chronic pancreatitis: clinical results and health-related quality of life.

INTRODUCTION: There are several well-established surgical procedures for the treatment of chronic pancreatitis (CP). The present study seeks to evaluate the perioperative and long-term outcome of these procedures. METHODS: All patients who had undergone pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR), and distal pancreatectomy (DP) for CP were retrospectively analyzed with regards to the perioperative outcome and long-term survival. Health-related quality of life (HRQoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: There were 145 patients available for analysis. Major complications (grade IIIb-V) occurred in 19 %, in-hospital mortality was 4.2 %, and 90-day mortality was 3 % with no differences between the different resection groups (all p > 0.05). Ten-year survival was 58 % and was highest in the DP group (100 %) but without statistical significance (p = 0.72). The response rate of the HRQoL assessment was 45 % (65 of 145). There was a significant improvement with regards to pain and HRQoL of all resection groups compared to the preoperative group (all p < 0.05). With respect to HRQoL and pain relief, the PD, DPPHR, and DP did not differ significantly. DISCUSSION: Surgical therapy of CP can be performed safely. The 3 different types of resection performed equally with regards to complications and HRQoL.

Mononuclear-cell-derived microparticles attenuate endothelial inflammation by transfer of miR-142-3p in a CD39 dependent manner.

Plasma microparticles (MP) bear functional active ectonucleotidases of the CD39 family with implications in vascular inflammation. MP appear to be able to fuse with cells and transfer genetic information. Here, we tested whether levels of different immunomodulatory microRNAs (miRs) in plasma MP are modulated by CD39 after experimental hepatectomy. We further investigated whether horizontal transfer of miR-142-3p between mononuclear (MNC) and endothelial cells via MP is regulated by purinergic signaling. Partial hepatectomy was performed in C57BL/6 wild type and Cd39 null mice. MP were collected via ultracentrifugation. MNC were stimulated with nucleotides and nucleosides, in vitro, and tested for miR-142-3p levels. Fusion of MNC-derived MP and endothelial cells with subsequent transfer of miR-142-3p was imaged by flow cytometry and confocal microscopy. Endothelial inflammation and apoptosis were quantified after transfection with miR-142-3p. Significantly lower miR-142-3p levels were observed in plasma MP of Cd39 null mice after partial hepatectomy, when compared to C57BL/6 wild types (p < 0.05). In contrast to extracellular nucleotides, anti-inflammatory adenosine significantly increased miR-142-3p levels in MNC-derived MP, in vitro (p < 0.05). MNC-derived MP are able to transfer miR-142-3p to endothelial cells by fusion. Transfection of endothelial cells with miR-142-3p decreased TNF-α levels (p < 0.05) and endothelial apoptosis (p < 0.05). MiR-142-3p levels in MNC-derived MP are modulated by nucleoside signaling and might reflect compensatory responses in vascular inflammation. Our data suggest the transfer of genetic information via shed MP as a putative mechanism of intercellular communication-with implications in organ regeneration.

Pancreaticoduodenectomy for periampullary cancer: does the tumour entity influence perioperative morbidity and long-term outcome?

BACKGROUND: Malignant tumours of the periampullary region include ductal adenocarcinoma of the pancreas (Pan-Ca), distal bile duct cancer (DBDC) and adenocarcinoma of the ampulla (Amp-Ca). The present retrospective clinical study was designed to evaluate the influence of tumour entity on postoperative complications and identify risk factors predicting survival and morbidity. METHODS: We retrospectively analysed data from all patients who underwent pancreatic resection for periampullary cancer with curative intent (R0 or R1). Demographic data, risk factors, perioperative complications and survival rates for the different subtypes were assessed. RESULTS: A total of 225 patients with periampullary cancer were identified: 124 (55.1%) had Pan-Ca, 55 (24.4%) had DBDC and 46 had (20.4%) Amp-Ca. Sixty-nine patients (30.7%) had major complications (grade IIIb-V). Patients with DBDC had significantly more grade C pancreatic fistulas. Univariate analysis revealed male gender, BMI >30, R1-status, and low-grade tumour differentiation as risk factors for major complications. Overall in-hospital-mortality was 6.7%. CONCLUSIONS: Further research will be needed to implement more individualized therapy.

Validity of the Iwate criteria for patients with hepatocellular carcinoma undergoing minimally invasive liver resection.

BACKGROUND: Recently proposed by the International Consensus Conference on Laparoscopic Liver Resection, the Iwate criteria (IC) can be used by surgeons to predict the operative difficulty of laparoscopic liver resection (LLR) and were validated in patients with hepatocellular carcinoma (HCC), the most common indication for LLR. METHODS: The IC comprise six preoperative factors that allow the grading of operative difficulty as low, intermediate, advanced, or expert. IC scores were validated in patients with HCC who underwent LLR (n = 77). RESULTS: The median operative time was 212 min (range 57-461 min). The difficulty of the resections was categorized as low in 9% (n = 7), intermediate in 38% (n = 29), advanced in 36% (n = 28), and expert in 15% (n = 12) of the patients. IC score was significantly linked to operative time, length of stay and liver function (P < 0.05). The rates of postoperative complications (Clavien-Dindo >II) for low, intermediate, advanced and expert were 0% (n = 0), 10% (n = 3), 3.5% (n = 1) and 50% (n = 6), respectively (P = 0.04). CONCLUSION: The IC can be used to preoperatively assess difficulty of LLR and to predict postoperative complications in HCC patients. Thus, the IC score may be useful to differentiate easy procedures from difficult procedures and is ideal to build an LLR curriculum for upcoming surgeons.

TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas.

INTRODUCTION: M2-polarized tumor-associated macrophages (TAMs) and TIE2-expressing monocytes (TEMs) are associated with angiogenesis and have been identified as a potential prognostic marker in several solid tumors, including hepatobiliary malignancies. However, little is known regarding their influence on tumor progression and patient survival in pancreatic ductal adenocarcinoma (PDAC). RESULTS: Patients with tumors characterized by the presence of CD163+ TAMs or TEMs in TCA or TIF, respectively, showed a significantly decreased 1-, 3- and 5-year overall and recurrence-free survival compared to patients without CD163+ TAMs or TEMs (all ρ < 0.05). Patients with TEMs in TCA showed a higher incidence of tumor recurrence (ρ < 0.05). Furthermore, the presence of CD163+ TAMs was associated with a higher tumor MVD (ρ < 0.05). CONCLUSIONS: Presence of M2-polarized TAMs and TEMs is associated with a decreased overall and recurrence-free survival of patients with PDAC. MATERIALS AND METHODS: The localization and density of CD163+ M2-polarized TAMs and TEMs were quantified in the tumor central area (TCA) and tumor-infiltrating front (TIF) in human PDAC tissue (n = 106) and correlated to clinicopathological characteristics, tumor recurrence rates and patient survival. In parallel, tumor microvascular density (MVD) and the density of angiopoietin-positive tumor cells were quantified. Statistical analysis was performed using SPSS software.

Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma.

BACKGROUND: Tumour angiogenesis is modulated on both an epigenetic and protein level and has potential implications for immune cell responses. However, the importance of related angiogenic biomarkers in cholangiocarcinoma (CCA) is unknown. This study assessed human CCA samples for the expression of angiogenesis-associated microRNAs, angiopoietins (Angs) and monocytes expressing the Ang-receptor, TIE2, with regards to prognostic significance after liver resection. METHODS: Angiogenic miRNAs were analysed in frozen samples of intrahepatic CCA (iCC; n = 43) and hilar CCA (HC; n = 45). Ang-1 and Ang-2, as well as TIE2-expressing monocytes (TEMs), were detected in paraffin-embedded iCC sections (n = 88). MiRNA expression and the abundance of TEMs and Angs were correlated with clinicopathological characteristics and survival. RESULTS: MiR-126 was downregulated in 76.7% of all CCA samples, with high relative expression associated with smaller tumours and reduced lymph node metastasis. High Ang-1 expression was associated with less lymphangiosis carcinomatosa and better histological grading (all p < 0.05). The absence of TEMs in iCC correlated with elevated CA19-9 levels. High relative miR-126 and low miR-128 levels were associated with improved survival in iCC and HC, respectively (all p < 0.05). High miR-126, low miR-128 and TEMs were independent prognostic factors for recurrence-free and overall survival (all p < 0.05). CONCLUSIONS: These results suggest that angiogenic miRNAs, Angs and TEMs are of prognostic value in CCA. In addition to the possible functional links between angiogenic miRNA expression profiles, Angs and immune-cell responses by TEMs, these data have clinical implications as novel diagnostic tools.

The value of microparticles in detecting acute rejection episodes after liver transplantation.

CONTEXT: Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet. OBJECTIVE: We analyzed the correlation of plasma microparticle levels (MP) with AR. MATERIALS AND METHODS: MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation. RESULTS: CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups. DISCUSSION AND CONCLUSION: MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.