Preoperative hypoalbuminaemia in liver surgery: an observational study at a university medical centre.

OBJECTIVES: Preoperative hypoalbuminaemia is associated with adverse outcome, including increased postoperative mortality in cardiovascular surgery, neurosurgery, trauma and orthopaedic surgery. However, much less is known about the association between preoperative serum albumin and clinical outcomes after liver surgery. In this study, we sought to determine whether hypoalbuminaemia before partial hepatectomy is associated with a worse postoperative outcome. DESIGN: Observational study. SETTING: University Medical Centre in Germany. PARTICIPANTS: We analysed 154 patients enrolled in the perioperative PHYsostigmine prophylaxis for liver resection patients at risk for DELIrium and postOperative cognitive dysfunction (PHYDELIO) trial with a preoperative serum albumin assessment. Hypoalbuminaemia was defined as serum albumin <35 g/L. Subgroups classified as hypoalbuminaemia and non-hypoalbuminaemia consisted of 32 (20.8%) and 122 (79.2%) patients, respectively. OUTCOME MEASURES: The outcome parameters of interest were postoperative complications according to Clavien (moderate: I, II; major: ≥III), length of intensive care unit (ICU) stay, length of hospital stay and survival rates 1 year after surgery. RESULTS: Preoperative hypoalbuminaemia was associated with the occurrence of major postoperative complications (OR 3.051 (95% CI 1.197 to 7.775); p=0.019) after adjusting for age, sex, randomisation, American Society of Anesthesiologists physical status, preoperative diagnosis and Child-Pugh class. Both ICU and hospital lengths of stay were significantly prolonged in patients with preoperative hypoalbuminaemia (OR 2.573 (95% CI 1.015 to 6.524); p=0.047 and OR 1.296 (95% CI 0.254 to 3.009); p=0.012, respectively). One-year survival was comparable between patients with and without hypoalbuminaemia. CONCLUSIONS: We found that low serum albumin before surgery was associated with a worse short-term outcome after partial hepatectomy, which strengthens the prognostic value of serum albumin in the setting of liver surgery. TRIAL REGISTRATION NUMBERS: ISRCTN18978802 and EudraCT 2008-007237-47.

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis. METHODS: This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451. FINDINGS: 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0·28 [95% CI 0·06-1·24; p=0·087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths. INTERPRETATION: In patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised. FUNDING: Novo Nordisk A/S.

The Clinical Importance of Preoperative Rectal Swabs in Patients after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Background: Surgical site infections are among the most common healthcare-associated infections, especially in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this retrospective study was to examine postoperative infectious complications according to preoperative screening findings of nasal and rectal swabs. Methods: Two hundred four consecutive patients received nasal and rectal swab examination for multidrug-resistant (MDR) bacteria within 30 days before the operation in patients where CRS and HIPEC were planned. Inclusion criteria were as follows: confirmed peritoneal metastases (histologically and/or cytologically); age under 85 years; adequate renal, liver, and bone marrow function; no sign of infection preoperatively; resectable disease; and CRS and HIPEC procedure. If surgical site infection occurred, the microbial spectrum of the site was assessed. One hundred twenty-one patients (63 female [52.1%] and 58 male [47.9%]) met the criteria and were further analyzed retrospectively. Statistical correlations between postoperative complications and risk factors were investigated by univariate and multivariate analysis. Results: Postoperative complications in total were observed in 57 patients (47.1%) with major complications (Clavien-Dindo grades 3-4) in 15 patients (12.4%) and infectious complications in 37 (30.6%) patients. The overall prevalence of nasal MRSA carriage was 3.28%, and the overall prevalence of rectal MDR bacteria carriage was 10.7%. In propensity score analysis, colonized patients compared to noncolonized patients showed increased total complications (CD1-5, p = 0.025), infectious complications (p = 0.028), surgical site infections (p = 0.022) as well as pneumonia (p = 0.016). Multivariate analysis showed that in addition to preoperative rectal colonization, American Society of Anesthesiologists score was a risk factor for postoperative complications. Conclusions: Preoperative 3-MRGN and vancomycin-resistant enterococcus colonization were associated with increased complications and surgical site infections. Special antimicrobial treatment pathways are necessary for these patients to reduce postoperative complications due to colonization.

Hepatic artery reconstruction using an operating microscope in pediatric liver transplantation-Is it worth the effort?

INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).

Thoracic Surgery in the COVID-19 Pandemic: A Novel Approach to Reach Guideline Consensus.

The COVID-19 pandemic challenges international and national healthcare systems. In the field of thoracic surgery, procedures may be deferred due to mandatory constraints of the access to diagnostics, staff and follow-up facilities. There is a lack of prospective data on the management of benign and malignant thoracic conditions in the pandemic. Therefore, we derived recommendations from 14 thoracic societies to address key questions on the topic of COVID-19 in the field of thoracic surgery. Respective recommendations were extracted and the degree of consensus among different organizations was calculated. A high degree of consensus was found to temporarily suspend non-critical elective procedures or procedures for benign conditions and to prioritize patients with symptomatic or advanced cancer. Prior to hospitalization, patients should be screened for respiratory symptoms indicating possible COVID-19 infection and most societies recommended to screen all patients for COVID-19 prior to admission. There was a weak consensus on the usage of serology tests and CT scans for COVID-19 diagnostics. Nearly all societies suggested to postpone elective procedures in patients with suspected or confirmed COVID-19 and recommended constant reevaluation of these patients. Additionally, we summarized recommendations focusing on precautions in the theater and the management of chest drains. This study provides a novel approach to informed guidance for thoracic surgeons during the COVID-19 pandemic in the absence of scientific evidence-based data.

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer]. / Zytoreduktive Chirurgie und hypertherme intraperitoneale Chemotherapie beim Magenkarzinom.

BACKGROUND: Gastric cancer with peritoneal metastases is associated with an extremely poor prognosis. Developed multimodal treatment concepts, which include a combination of perioperative systemic treatment and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), show promising results with respect to improvement of the long-term survival. METHODS: This article contains a review of the literature of published studies on the topic of gastric cancer and peritoneal metastasis. RESULTS: The prognosis of patients with gastric cancer peritoneal carcinomatosis shows an extremely limited median survival of 7 months under palliative second-line systemic treatment. The median survival time increased to 12 months with cytoreductive surgery and in combination with HIPEC showed a positive effect on survival in individual studies. EXPERT OPINION: Treatment recommendations for patients with peritoneal metastases of gastric cancer should be carried out by experts in surgical reference centers.

[COVID-19 Pandemic in Germany: The Current Situation in Thoracic Surgery]. / COVID-19-Pandemie in Deutschland: Die aktuelle Lage in der Thoraxchirurgie.

BACKGROUND: The new COVID-19 pandemic has an impact on routine thoracic surgery. Various concepts and recommendations are being pursued to protect patients and hospital staff. However, the implementation of these recommendations may depend on the existing infrastructure, local conditions and in-house procedural instructions. MATERIAL AND METHOD: Between 11th May and 26th May 2020, an anonymous online survey on the topic of COVID-19 was conducted among thoracic surgeons in Germany. The survey consisted of 16 questions on the local COVID-19 case numbers, protective measures, procedural instructions and treatment concepts. The results were summarised, descriptively analysed and discussed. RESULTS: The response rate of 42.6% (n = 66), included replies from 23 (34.8%) specialised hospitals, 18 (27.3%) maximum care hospitals and 14 (21.2%) university clinics. COVID-19-positive patients were treated in 65 (99%) clinics and 37.9% of the clinics also performed surgery on COVID-19-positive patients. Nasopharyngeal swabs were the main instrument for COVID-19 patient testing (in 95.4% of the clinics). Test results influenced decisions on treatment in 71.2% of the clinics. In 59.1% of clinics, safety equipment was supplemented with FFP2 masks and eye protection during thoracic surgeries due to the COVID-19 pandemic. DISCUSSION: Almost all thoracic surgeons reported that they had treated patients with COVID-19 and half of them also had performed surgery on COVID-19-positive patients. The applied procedural instructions as well as the effects of COVID-19 on treatment decisions and patient-doctor contact differed between the reporting clinics.

Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

Outcomes of Liver Resections after Liver Transplantation at a High-Volume Hepatobiliary Center.

Although more than one million liver transplantations have been carried out worldwide, the literature on liver resections in transplanted livers is scarce. We herein report a total number of fourteen patients, who underwent liver resection after liver transplantation (LT) between September 2004 and 2017. Hepatocellular carcinomas and biliary tree pathologies were the predominant indications for liver resection (n = 5 each); other indications were abscesses (n = 2), post-transplant lymphoproliferative disease (n = 1) and one benign tumor. Liver resection was performed at a median of 120 months (interquartile range (IQR): 56.5-199.25) after LT with a preoperative Model for End-Stage Liver Disease (MELD) score of 11 (IQR: 6.75-21). Severe complications greater than Clavien-Dindo Grade III occurred in 5 out of 14 patients (36%). We compared liver resection patients, who had a treatment option of retransplantation (ReLT), with actual ReLTs (excluding early graft failure or rejection, n = 44). Bearing in mind that late ReLT was carried out at a median of 117 months after first transplantation and a median of MELD of 32 (IQR: 17.5-37); three-year survival following liver resection after LT was similar to late ReLT (50.0% vs. 59.1%; p = 0.733). Compared to ReLT, liver resection after LT is a rare surgical procedure with significantly shorter hospital (mean 25, IQR: 8.75-49; p = 0.034) and ICU stays (mean 2, IQR: 1-8; p < 0.001), acceptable complications and survival rates.

Epidural Anesthesia in Liver Surgery-A Propensity Score-Matched Analysis.

OBJECTIVE: To assess the effects of epidural anesthesia (EA) on patients who underwent liver resection. DESIGN: Secondary analysis of a prospective randomized controlled trial. SETTING: This single-center study was conducted at an academic medical center. METHODS: A subset of 110 1:1 propensity score-matched patients who underwent liver resection with and without EA were analyzed. Outcome measures were pain intensity ≥5 on a numeric rating scale (NRS) at rest and during movement on postoperative days 1-5, analyzed with logistic mixed-effects models, and postoperative complications according to the Clavien-Dindo classification, length of hospital stay (LOS), and one-year survival. One-year survival in the matched cohorts was compared using a frailty model. RESULTS: EA patients were less likely to experience NRS ≥5 at rest (odds ratio = 0.06, 95% confidence interval [CI] = 0.01 to 0.28, P < 0.001). These findings were independent of age, sex, Charlson comorbidity index, baseline NRS, and surgical approach (open vs laparoscopic). The number and severity of postoperative complications and LOS were comparable between groups (P = 0.258, P > 0.999, and P = 0.467, respectively). Reduced mortality rates were seen in the EA group one year after surgery (9.1% vs 30.9%, hazard ratio = 0.32, 95% CI = 0.11 to 0.90, P = 0.031). No EA-related adverse events occurred. Earlier recovery of bowel function was seen in EA patients. CONCLUSIONS: Patients with EA had better postoperative pain control and required fewer systemic opioids. Postoperative complications and LOS did not differ, although one-year survival was significantly improved in patients with EA. EA applied in liver surgery was effective and safe.

Future liver remnant function as a predictor of postoperative morbidity following liver resection for hepatocellular carcinoma - A risk factor analysis.

BACKGROUND: Advances in anaesthesia and surgical technique have considerably reduced mortality in hepatocellular carcinoma (HCC) patients undergoing liver resection. However, extended resections in patients with liver cirrhosis still represent a challenge. The aim of this study was to investigate the predictive value of volume/function analysis for the prediction of morbidity in HCC patients following liver resection. METHODS: Between 2001 and 2014, a total of 261 patients who underwent open hepatectomy for HCC were enrolled in this study. Future liver remnant volume (FLRV) and future liver remnant function (FLRF) based on LiMAx testing were obtained retrospectively. Uni- and multivariable analyses were performed to identify predictors for postoperative ascites, post-hepatectomy haemorrhage (PHH), and wound healing disorders (WHD) within the total cohort and in a subgroup of cirrhotic patients. RESULTS: The most commonly observed complication was ascites (57.1%), followed by liver failure (25.3%), PHH (19.5%), and WHD (19.2%). FLRF was a major predictor of postoperative ascites (AUC 0.776; OR 0.987, p = 0.001), PHH (AUC 0.717; OR 0.984, p = 0.001), and WHD (AUC 0.660; OR 0.994, p = 0.032) in total cohort. Multivariable analysis of the cirrhosis subgroup showed FLRF to be an independent predictor of ascites (AUC 0.814; OR 0.989, p = 0.021), PHH (AUC 0.677; OR 0.991, p = 0.040), and WHD (AUC 0.615; OR 0.989, p = 0.033). CONCLUSIONS: FLRF is a major predictor of postoperative ascites, haemorrhage, and wound healing disorders in cirrhotic and non-cirrhotic patients whereas FLRV failed to show significant correlations. Preoperative calculation of FLRF may augment surgical decision-making in high-risk patients and thereby improve perioperative outcome.

Perioperative Pleural Drainage in Liver Transplantation: A Retrospective Analysis from a High-Volume Liver Transplant Center.

BACKGROUND Pleural effusions represent a common complication after liver transplantation (LT) and chest drain (CD) placement is frequently necessary. MATERIAL AND METHODS In this retrospective cohort study, adult LT recipients between 2009 and 2016 were analyzed for pleural effusion formation and its treatment within the first 10 postoperative days. The aim of the study was to compare different settings of CD placement with regard to intervention-related complications. RESULTS Overall, 597 patients met the inclusion criteria, of which 361 patients (60.5%) received at least 1 CD within the study period. Patients with a MELD >25 were more frequently affected (75.7% versus 56.0%, P<0.001). Typically, CDs were placed in the intensive care unit (ICU) (66.8%) or in the operating room (14.1% during LT, 11.5% in the context of reoperations). In total, 97.0% of the patients received a right-sided CD, presumably caused by local irritations. Approximately one-third (35.4%) of ICU-patients required pre-interventional optimization of coagulation. Of the 361 patients receiving a CD, 15 patients (4.2%) suffered a post-interventional hemorrhage and 6 patients (1.4%) had a pneumothorax requiring further treatment. Less complications were observed when the CD was performed in the operating room compared to the ICU: 1 out 127 patients (0.8%) versus 20 out of 332 patients (6.0%); P=0.016. CONCLUSIONS CD placement occurring in the operating room was associated with fewer complications in contrast to placement occurring in the ICU. Planned CD placement in the course of surgery might be favorable in high-risk patients.

The role of Pressurized IntraPeritoneal Aerosol Chemotherapy in the management of gastric cancer: A systematic review.

BACKGROUND: The quest to cure or to contain the disease in cancer patients leads to new strategies and techniques being added to the armamentarium of oncologists. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a recently described surgical technique which is being evaluated at many centers for the management of peritoneal metastasis (PM). The present study is a systematic review to evaluate the current role of PIPAC in the management of gastric cancer associated PM. METHODS: A systematic search was conducted in Pubmed and EMBASE database using relevant keywords and confirming to the PRISMA guidelines to identify the articles describing the role of PIPAC in gastric cancer associated PM. All the studies which were published prior to July 1, 2018 in English literature and reported the role of PIPAC in gastric cancer associated PM were included in the systematic review. RESULTS: The search yielded 79 articles; there were ten published studies which have reported the use of PIPAC in gastric cancer associated PM. A total of 129 patients with gastric cancer associated PM were treated in the studies. Only two studies had an exclusive cohort of gastric cancer patients while eight other studies had a heterogeneous population with a small proportion of gastric cancer patients. There was only one study highlighting the role of PIPAC in neoadjuvant setting to downgrade the peritoneal carcinomatosis index. All the studies revealed that PIPAC is feasible and has minimal perioperative morbidity, even after repeated applications. CONCLUSION: There is a scarcity of English literature related to the role of PIPAC in gastric cancer associated PM. PIPAC is a safe and well-tolerated procedure which has the potential to contain spreading PM. Further studies are warranted to better define the role of PIPAC in gastric cancer associated PM.

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis.

Dynamic liver function assessment by the [13C]methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic cytochrome P-450 (CYP) 1A2 activity. One proven strategy for preoperative risk assessment in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver, and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery. The CYP1A2 activity analysis of neoplastic lesions and adjacent nontumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in nontumor tissues (35.5, 15.9-54.4 µU/mg) compared with hepatocellular adenomas (7.35, 1.2-32.5 µU/mg), hepatocellular carcinomas (0.18, 0.0-2.0 µU/mg), or colorectal liver metastasis (0.17, 0.0-2.1 µU/mg). In nontumor liver tissue, a gradual decline in CYP1A2 activity with exacerbating fibrosis was observed. The CYP1A2 activity differences were also reflected in CYP1A2 protein signals in the assessed hepatic tissues. Volume-function analysis showed a minimal deviation compared with the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), whereas a difference of 11.9% was observed for hepatocellular adenomas. These findings are important for a refined preoperative volume-function analysis and improved surgical risk assessment in hepatocellular adenoma cases with low LiMAx values. NEW & NOTEWORTHY The cytochrome P-450 (CYP) 1A2-dependent maximal liver function capacity test reflects the overall functional capacity of the liver. To which extent hepatocellular tumors harbor CYP1A2 activity and thus contribute to the maximal liver function capacity test outcome is unknown. We here show that hepatocellular adenomas but not hepatocellular carcinomas or colorectal liver metastasis contain significant residual CYP1A2 activity. These findings are important for an improved preoperative volume-function analysis and an accurate surgical risk assessment in hepatocellular adenoma cases.

The predictive value of future liver remnant function after liver resection for HCC in noncirrhotic and cirrhotic patients.

BACKGROUND: Surgical procedures in patients with underlying liver disease are still burdened by a high rate of postoperative morbidity, especially posthepatectomy liver failure (PHLF), ranging from 1.2 to 33.8%. The aim of this study was to investigate the prognostic value of volume/function analysis for the prediction of hepatectomy-related morbidity in patients with hepatocellular carcinoma. METHODS: Clinicopathological data were analysed in 261 patients who underwent liver resection for HCC between 2001 and 2014. Future liver remnant volume (FLRV) and future liver remnant function (FLRF) based on LiMAx test were obtained retrospectively. A subgroup analysis for high-risk patients with impaired liver function was conducted. Univariate and multivariate regression analysis was performed to identify risk factors for major complications, defined by Dindo ≥ IIIb and PHLF grade ≥ B. RESULTS: In the total cohort, FLRF was independently associated with major complications. FLRV, resected liver volume, and FLRF were independent risk factors for PHLF. In a subgroup analysis of high-risk patients, FLRF was identified as the only independent risk factor for major complications and PHLF development. DISCUSSION: These results suggest the superior value of FLRF to FLRV in predicting postoperative complications as well as PHLF in patients with chronic liver disease.

Prospective Assessment of Liver Function by an Enzymatic Liver Function Test to Estimate Short-Term Survival in Patients with Liver Cirrhosis.

BACKGROUND: MELD attempts to objectively predict the risk of mortality of patients with liver cirrhosis and is commonly used to prioritize organ allocation. Despite the usefulness of the MELD, updated metrics could further improve the accuracy of estimates of survival. AIMS: To assess and compare the prognostic ability of an enzymatic 13C-based liver function test (LiMAx) and distinct markers of liver function to predict 3-month mortality of patients with chronic liver failure. METHODS: We prospectively investigated liver function of 268 chronic liver failure patients without hepatocellular carcinoma. Primary study endpoint was liver-related death within 3 months of follow-up. Prognostic values were calculated using Cox proportional hazards and logistic regression analysis. RESULTS: The Cox proportional hazard model indicated that LiMAx (p < 0.001) and serum creatinine values (p < 0.001) were the significant parameters independently associated with the risk of liver failure-related death. Logistic regression analysis revealed LiMAx and serum creatinine to be independent predictors of mortality. Areas under the receiver-operating characteristic curves for MELD (0.86 [0.80-0.92]) and for a combined score of LiMAx and serum creatinine (0.83 [0.76-0.90]) were comparable. CONCLUSIONS: Apart from serum creatinine levels, enzymatic liver function measured by LiMAx was found to be an independent predictor of short-term mortality risk in patients with liver cirrhosis. A risk score combining both determinants allows reliable prediction of short-term prognosis considering actual organ function. Trial Registration Number (German Clinical Trials Register) # DRKS00000614.

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.

Liver Transplantation and Liver Resection for Cirrhotic Patients with Hepatocellular Carcinoma: Comparison of Long-Term Survivals.

BACKGROUND: Both liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively. METHODS: Clinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods. RESULTS: In total, 364 and 141 patients underwent LT and LR for HCC in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59 underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P < .0001), but not mortality (3 vs. 1%, P = .165), was higher after LR than after LT for HCC within MC. In the period 1989-2004, overall survival (OS) was significantly higher in patients who underwent LT compared to LR for HCC within MC (5-year OS: 77 vs. 36%, P < .0001). Interestingly, in the more recent period 2005-2011, OS was comparable between LT and LR for HCC within MC (5-year OS: 73 vs. 61%, P = .07). CONCLUSION: We have noted an improvement of outcomes among patients selected for partial hepatectomy in recent years that were comparable to stable results after LT in cirrhotic patients with HCC. Whether those improvements are due to advances in liver surgery, optimized perioperative managament for patients with liver cirrhosis, and the development of modern multimodal treatment strategies for the recurrent lesions appears plausible.