Internal drainage for interdisciplinary management of anastomotic leakage after pancreaticogastrostomy.

BACKGROUND: Anastomotic leakage and postoperative pancreatic fistula (POPF) may occur after pancreatic head resection, also in the setting of pancreato-gastric reconstruction. For adequate complication management, a variety of non-standardized treatments are available. Still, data on clinical evaluation of endoscopic methods remain scarce. Based on our interdisciplinary experience on endoscopic treatment of retro-gastric fluid collections after left-sided pancreatectomies, we developed an innovative endoscopic concept with internal peri-anastomotic stent placement for patients with anastomotic leakage and/or peri-anastomotic fluid collection. METHODS: Over the period of 6 years (2015-2020) we retrospectively evaluated 531 patients after pancreatic head resections at the Department of Surgery, Charité-Unversitätsmedizin Berlin. Of these, 403 received reconstruction via pancreatogastrostomy. We identified 110 patients (27.3%) with anastomotic leakage and/or peri-anastomotic fluid collection and could define four treatment groups which received either conservative treatment (C), percutaneous drainage (PD), endoscopic drainage (ED), and/or re-operation (OP). Patients were grouped in a step-up approach for descriptive analyses and in a stratified, decision-based algorithm for comparative analyses. The study's primary endpoints were hospitalization (length of hospital stay) and clinical success (treatment success rate, primary/secondary resolution). RESULTS: We characterized an institutional, post-operative cohort with heterogenous complication management following pancreato-gastric reconstruction. The majority of patients needed interventional treatments (n = 92, 83.6%). Of these, close to one-third (n = 32, 29.1%) were treated with endoscopy-guided, peri-anastomotic pigtail stents for internal drainage as either primary, secondary and/or tertiary treatment modality. Following a decision-based algorithm, we could discriminate superior primary-(77,8% vs 53.7%) and secondary success rates (85.7% vs 68.4%) as well as earlier primary resolutions (11.4 days, 95%CI (5.75-17.13) vs 37.4 days, 95%CI (27.2-47.5)] in patients receiving an endoscopic compared to percutaneous management. CONCLUSION: This study underscores the importance of endoscopy-guided approaches for adequate treatment of anastomotic leakage and/or peri-anastomotic fluid collections after pancreatoduodenectomy. We herein report a novel, interdisciplinary concept for internal drainage in the setting of pancreato-gastric reconstruction.

Robotic vs. laparoscopic liver surgery: a single-center analysis of 600 consecutive patients in 6 years.

BACKGROUND: While laparoscopic liver surgery has become a standard procedure, experience with robotic liver surgery is still limited. The aim of this prospective study was to evaluate safety and feasibility of robotic liver surgery and compare outcomes with conventional laparoscopy. METHODS: We here report the results of a single-center, prospective, post-marketing observational study (DRKS00017229) investigating the safety and feasibility of robotic liver surgery. Baseline characteristics, surgical complexity (using the IWATE score), and postoperative outcomes were then compared to laparoscopic liver resections performed at our center between January 2015 and December 2020. A propensity score-based matching (PSM) was applied to control for selection bias. RESULTS: One hundred twenty nine robotic liver resections were performed using the da Vinci Xi surgical system (Intuitive) in this prospective study and were compared to 471 consecutive laparoscopic liver resections. After PSM, both groups comprised 129 cases with similar baseline characteristics and surgical complexity. There were no significant differences in intraoperative variables, such as need for red blood cell transfusion, duration of surgery, or conversion to open surgery. Postoperative complications were comparable after robotic and laparoscopic surgery (Clavien-Dindo ≥ 3a: 23% vs. 19%, p = 0.625); however, there were more bile leakages grade B-C in the robotic group (17% vs. 7%, p = 0.006). Length of stay and oncological short-term outcomes were comparable. CONCLUSIONS: We propose robotic liver resection as a safe and feasible alternative to established laparoscopic techniques. The object of future studies must be to define interventions where robotic techniques are superior to conventional laparoscopy.

Safety and feasibility of robotic liver resection after previous abdominal surgeries.

BACKGROUND: While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. METHODS: Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. RESULTS: Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. CONCLUSIONS: We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

Safety of intermittent Pringle maneuver during minimally invasive liver resection in patients with hepatocellular carcinoma with and without cirrhosis.

PURPOSE: The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. METHODS: In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis. Cases with use of IPM (IPM) and those without use of IPM (no IPM) were then compared regarding intraoperative and postoperative outcomes after propensity score matching (PSM) for surgical difficulty. RESULTS: One hundred fifty-one patients underwent liver resection for HCC at our center and met inclusion criteria. Of these, 73 patients (48%) received IPM with a median duration of 18 min (5-78). One hundred patients (66%) had confirmed liver cirrhosis. In multivariate analysis, patients with large tumors (≥ 3 cm) and difficult tumor locations (segments VII or VIII) were more likely to undergo IPM (OR 1.176, p = 0.043, and OR 3.243, p = 0.001, respectively). After PSM, there were no differences in intraoperative blood transfusion or postoperative complication rates between the IPM and no IPM groups. Neither did we observe any differences in the subgroup analysis for cirrhotic patients. Postoperative serum liver function tests were not affected by the use of IPM. CONCLUSIONS: Based on our findings, we conclude that the use of IPM in minimally invasive liver resection is safe and feasible for patients with HCC, including those with compensated liver cirrhosis.

Textbook outcome after major hepatectomy for perihilar cholangiocarcinoma - definitions and influencing factors.

PURPOSE: The concept of "textbook outcome" (TO) as composite quality measure depicting the ideal surgical has not yet been defined for patients undergoing major hepatectomy (MH) for perihilar cholangiocarcinoma (PHC). This study sought to propose a uniform definition through a systematic literature review as well as to identify patient- or procedure-related factors influencing TO. METHODS: In this retrospective study, we analyzed all patients undergoing MH for PHC at our department between January 2005 and August 2019. After conducting a systematic literature search, we defined TO as the absence of 90-day mortality and major complications, no hospital readmission within 90 days after discharge, and no prolonged hospital stay (<75. percentile). A binary logistic regression analysis was performed to identify factors influencing TO. RESULTS: Of 283 patients, TO was achieved in 67 (24%) patients. Multivariate analysis revealed that preoperative biliary drainage was associated with a decreased (OR= 0.405, 95% CI: 0.194-0.845, p=0.016) and left-sided-resection (OR= 1.899, 95% CI: 1.048-3.440, p=0.035) with increased odds for TO. Overall survival (OS) and DFS (disease-free survival) did not differ significantly between the outcome groups (OS: p=0.280, DFS: p=0.735). However, there was a trend towards better overall survival, especially in the late course with TO. CONCLUSION: Our analysis proposed a uniform definition of TO after MH for PHC. We identified left hepatectomy as an independent factor positively influencing TO. In patients where both right- and left-sided resections are feasible, this underlines the importance of a careful selection of patients who are scheduled for right hepatectomy.

Robotic versus open pancreatic surgery: a propensity score-matched cost-effectiveness analysis.

BACKGROUND: Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis. METHODS: Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2. RESULTS: In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334€ vs. 5115€, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit-RPS: 57€ vs. OPS: - 2894€, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue). CONCLUSIONS: Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.

Feasibility of robotic-assisted pancreatic resection in patients with previous minor abdominal surgeries: a single-center experience of the first three years.

BACKGROUND: Robotic-assisted pancreatic surgery is limited to specialized high-volume centers and selected patient cohorts. Especially for patients with a history of previous abdominal surgeries, the standard procedure remains open surgery due to the fear of complications caused by abdominal adhesions. METHODS: Clinical data of all consecutive patients undergoing robotic-assisted pancreatic surgery using the daVinci Xi system (Intuitive Surgical) at our center (Department of Surgery, Universitätsmedizin Berlin, Germany) were collected prospectively and further analyzed from October 2017 to October 2020. Prior abdominal surgeries were specified according to the surgical approach and localization. In univariate and multivariate analysis, baseline and perioperative parameters of patients with a history of prior abdominal surgeries (PS) were compared to those of patients with no history of prior abdominal surgeries (NPS). RESULTS: Out of 131 patients undergoing robotic-assisted pancreatic surgery, 62 (47%) had a history of abdominal surgery. Previous procedures included most often appendectomy (32%) followed by gynecological surgery (29%) and cholecystectomy (27%). 24% of PS had received multiple surgeries prior to the robotic-assisted pancreatic resections. Baseline characteristics and comorbidities were comparable between the groups. We did not detect differences in the duration of surgery (262 min), conversion rates (10%), and postoperative complications between NPS and PS. Postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), and in-house mortality showed no significant differences between the two groups. Multivariate analysis revealed male sex and high BMI as a potential predictive factor for severe postoperative complications. Other characteristics like the type of pancreatic resection, ASA, and underlying malignancy showed no difference in the multivariable analysis. CONCLUSIONS: We propose robotic-assisted pancreatic surgery to be safe and feasible for patients with a history of minor prior abdominal surgery. Hence, each patient should individually be evaluated for a minimally invasive approach regardless of a history of previous operations.

Right-sided resection with standard or selective portal vein resection in patients with perihilar cholangiocarcinoma: a propensity score analysis.

BACKGROUND: Standard portal vein resection (PVR) has been proposed to improve oncological outcomes in patients with perihilar cholangiocarcinoma (PHC), however it potentially introduces an increased risk of morbidity. The policy in Amsterdam UMC(AMC) is to resect the portal vein bifurcation selectively when involved, while in Charité-Universitätsmedizin Berlin, standard PVR is performed with right trisectionectomy. The objective of this study was to analyze postoperative outcomes and survival after standard or selective PVR for PHC. METHODS: A retrospective study was performed including PHC-patients undergoing right-sided resection in Amsterdam (2000-2018) and Berlin (2005-2015). Primary outcomes were 90-day mortality, severe morbidity (Clavien-Dindo≥3), and overall survival (OS). A propensity score comparison (1:1 ratio) was performed corrected for age/sex/ASA/jaundice/tumor diameter/N-stage/Bismuth-Corlette type-IV. RESULTS: A total of 251 patients who underwent right-sided resection for PHC were evaluated: 87 in the selective (Amsterdam) and 164 in the standard PVR-group (Berlin). Major differences in baseline characteristics were observed, with higher ASA and AJCC-stage in the standard PVR-group (Berlin). Severe morbidity and 90-day mortality were comparable before matching (selective/Amsterdam:68% and 19%, standard/Berlin:61% and 17%,p = 0.284 and p = 0.746, respectively). After propensity score matching, both short term outcomes and OS were comparable (selective/Amsterdam (n = 45) 33 months (95%CI:20-45), standard/Berlin (n = 45) 31 months (95%CI:24-38,p = 0.747)). CONCLUSION: In this combined cohort, standard PVR was not associated with increased severe morbidity or mortality. After propensity score matching, survival was comparable after selective (Amsterdam) and standard PVR (Berlin).

Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.

A tailored approach in lymph node-positive perihilar cholangiocarcinoma.

PURPOSE: Extended right hepatectomy is associated with wide surgical margins in PHC and often favored for oncological considerations. However, it remains uncertain whether established surgical principles also apply to the subgroup of node-positive patients. The aim of the present study was to define a tailored surgical approach for patients with perihilar cholangiocarcinoma (PHC) and lymph node metastases. METHODS: We reviewed the course of all consecutive patients undergoing major hepatectomy for PHC between 2005 and 2015 at the Department of Surgery, Charité - Universitätsmedizin Berlin. RESULTS: Two hundred and thirty-one patients underwent major hepatectomy for PHC with 1-, 3-, and 5-year overall (OS) and disease-free survival (DFS) rates of 72%, 48%, and 36%, and 60%, 22%, and 12%, respectively. In lymph node-positive patients (n = 109, 47%), extended left hepatectomy was associated with improved OS and DFS, respectively, when compared to extended right hepatectomy (p = 0.008 and p = 0.003). Interestingly, OS and DFS did not differ between R0 and R1 resections in those patients (both p = ns). Patients undergoing extended left hepatectomy were more likely to receive adjuvant chemotherapy (p = 0.022). This is of note as adjuvant chemotherapy, besides grading (p = 0.041), was the only independent prognostic factor in node-positive patients (p=0.002). CONCLUSION: Patients with node-positive PHC might benefit from less aggressive approaches being associated with lower morbidity and a higher chance for adjuvant chemotherapy. Lymph node sampling might help to guide patients to the appropriate surgical approach according to their lymph node status.

Robotic-assisted pancreatic surgery in the elderly patient: experiences from a high-volume centre.

BACKGROUND: Robotic-assisted pancreatic surgery (RPS) has fundamentally developed over the past few years. For subgroups, e.g. elderly patients, applicability and safety of RPS still needs to be defined. Given prognosticated demographic developments, we aim to assess the role of RPS based on preoperative, operative and postoperative parameters. METHODS: We included 129 patients undergoing RPS at our institution between 2017 and 2020. Eleven patients required conversion to open surgery and were excluded from further analysis. We divided patients into two groups; ≥ 70 years old (Group 1; n = 32) and < 70 years old (Group 2; n = 86) at time of resection. RESULTS: Most preoperative characteristics were similar in both groups. However, number of patients with previous abdominal surgery was significantly higher in patients ≥ 70 years old (78% vs 37%, p < 0.0001). Operative characteristics did not significantly differ between both groups. Although patients ≥ 70 years old stayed significantly longer at ICU (1.8 vs 0.9 days; p = 0.037), length of hospital stay and postoperative morbidity were equivalent between the groups. CONCLUSION: RPS is safe and feasible in elderly patients and shows non-inferiority when compared with younger patients. However, prospectively collected data is needed to define the role of RPS in elderly patients accurately. Trial registration Clinical Trial Register: Deutschen Register Klinischer Studien (DRKS; German Clinical Trials Register). Clinical Registration Number: DRKS00017229 (retrospectively registered, Date of Registration: 2019/07/19, Date of First Enrollment: 2017/10/18).

The ILLS Laparoscopic Liver Surgery Fellow Skills Curriculum.

INTRODUCTION: Laparoscopy is becoming the standard approach in liver surgery. As the degree of difficulty varies greatly from core skills to advanced procedures, strategies for teaching young surgeons need to be reconsidered. We here aimed to design a skills curriculum for LLR. METHODS: Using the nominal group technique, 22 substeps of LLR were identified by 61 hepatobiliary surgeons. The raters were asked to rate (1) the difficulty of substeps and (2) the minimum number of times that the substep must be performed for mastery of the technique. According to the frequency of defined substeps, being estimated on the basis of high volume center experiences (n = 222 LLR; 1/2017-12/2018), the center's training capacity and defined goals for a 2-year fellowship were calculated. RESULTS: Ten surgical substeps (45%) are routinely performed and can thus be taught sufficiently at centers carrying out ≥50 LLR in 2 years. As the mobilization of the right liver lobe and the dissection of the hepatic artery or portal vein is performed in only 27% and 28% of all LLR, respectively, sufficient training can only be provided at centers with ≥100 LLRs in 2 years. Mastery of complex parenchymal dissection (19%) and hilar lymphadenectomy (8%) can only be achieved in center performing ≥200 LLR in 2 years. CONCLUSION: We here suggest a stepwise approach for training of hepatobiliary fellows in LLR. Based on the estimated complexity of the substeps and the size of the center, not every substep can be learned within 2 years.

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.

TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells.

BACKGROUND: Monocytes are a major component of the tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC). However, the complex interactions between tumor cells and monocytes and their role in tumor invasion have not been fully established. METHODS: To specifically test the impact of interaction on invasive potential two PDAC cell lines PaTu8902 and CFPAC-1 were selected on their ability to form invasive adhesions, otherwise known as invadopodia and invade in a spheroid invasion assay. RESULTS: Interestingly when the PDAC cells were co-cultured with undifferentiated THP1 monocyte-like cells invadopodia formation was significantly suppressed. Moreover, conditioned media of THP1 cells (CM) was also able to suppress invadopodia formation. Further investigation revealed that both tissue inhibitor of metalloproteinase (TIMP) 1 and 2 were present in the CM. However, suppression of invadopodia formation was found that was specific to TIMP2 activity. CONCLUSIONS: Our findings indicate that TIMP2 levels in the tumour microenvironment may have prognostic value in patients with PDAC. Furthermore, activation of TIMP2 expressing monocytes in the primary tumour could present a potential therapeutic opportunity to suppress cell invasion in PDAC.

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.

Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice.

BACKGROUND: Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice. METHODS: Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process. Transgenic GFP-MSCs were administered i.p. 24 h after 70% hepatectomy in BALB/c nude mice, whereas control mice received phosphate-buffered saline. Mice were sacrificed 2, 3, and 5 d after partial hepatectomy. Blood and organs were harvested and metabolic alterations as well as liver regeneration subsequently assessed by liver function tests, multianalyte profiling immunoassays, histology, and immunostaining. RESULTS: Hepatocyte and sinusoidal endothelial cell proliferation were significantly increased after partial hepatectomy in mice receiving MSC compared to control mice (Hepatocyte postoperative day 3, P < 0.01; endothelial cell postoperative day 5, P < 0.05). Hepatocyte fat accumulation correlated inversely with hepatocyte proliferation (r2 = 0.4064, P < 0.01) 2 d after partial hepatectomy, with mice receiving MSC being protected from severe fat accumulation. No GFP-positive cells could be detected in the samples. Serum levels of IL-6, HGF, and IL-10 were significantly decreased at day 3 in mice receiving MSC when compared to control mice (P < 0.05). Relative body weight loss was significantly attenuated after partial hepatectomy in mice receiving MSC (2 d and 3 d, both P < 0.001) with a trend toward a faster relative restoration of liver weight, when compared to control mice. CONCLUSIONS: Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.

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.

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.

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.

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.