The Influence of Hepatic Steatosis and Fibrosis on Postoperative Outcomes After Major Liver Resection of Perihilar Cholangiocarcinoma.

BACKGROUND: Surgical resection for perihilar cholangiocarcinoma (pCCA) is associated with high operative risks. Impaired liver regeneration in patients with pre-existing liver disease may contribute to posthepatectomy liver failure (PHLF) and postoperative mortality. This study aimed to determine the incidence of hepatic steatosis and fibrosis and their association with PHLF and 90-day postoperative mortality in pCCA patients. METHODS: Patients who underwent a major liver resection for pCCA were included in the study between 2000 and 2021 from three tertiary referral hospitals. Histopathologic assessment of hepatic steatosis and fibrosis was performed. The primary outcomes were PHLF and 90-day mortality. RESULTS: Of the 401 included patients, steatosis was absent in 334 patients (83.3%), mild in 58 patients (14.5%) and moderate to severe in 9 patients (2.2%). There was no fibrosis in 92 patients (23.1%), periportal fibrosis in 150 patients (37.6%), septal fibrosis in 123 patients (30.8%), and biliary cirrhosis in 34 patients (8.5%). Steatosis (≥ 5%) was not associated with PHLF (odds ratio [OR] 1.36; 95% confidence interval [CI] 0.69-2.68) or 90-day mortality (OR 1.22; 95% CI 0.62-2.39). Neither was fibrosis (i.e., periportal, septal, or biliary cirrhosis) associated with PHLF (OR 0.76; 95% CI 0.41-1.41) or 90-day mortality (OR 0.60; 95% CI 0.33-1.06). The independent risk factors for PHLF were preoperative cholangitis (OR 2.38; 95% CI 1. 36-4.17) and future liver remnant smaller than 40% (OR 2.40; 95% CI 1.31-4.38). The independent risk factors for 90-day mortality were age of 65 years or older (OR 2.40; 95% CI 1.36-4.23) and preoperative cholangitis (OR 2.25; 95% CI 1.30-3.87). CONCLUSION: In this study, no association could be demonstrated between hepatic steatosis or fibrosis and postoperative outcomes after resection of pCCA.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Laparoscopic Living donor liver transplantation in irresectable intrahepatic cholangiocarcinoma in primary sclerosing cholangitis associated liver cirrhosis.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor and usually associated with a poor oncological prognosis. The current gold standard is the surgical resection of the tumor with subsequent adjuvant therapy. However, in case of irresectability e.g. in case of liver cirrhosis, a palliative treatment regime is conducted.This report demonstrates the case of an irresectable iCCA in liver cirrhosis due to primary sclerosing cholangitis (PSC) treated by living-donor liver transplantation (LDLT) facilitated by minimal invasive donor hepatectomy. No postoperative complications were observed in the donor and the donor was released on the 6th postoperative day. Further, after a follow-up of 1.5 years, no disease recurrence was detected in the recipient.According to the recent international literature, liver transplantation can be evaluated in case of small solitary iCCA (< 3 cm) in cirrhosis. Less evidence is provided for transplantation in advanced tumors which are surgically not resectable due to advanced liver disease or infiltration of major vessels, however some reports display adequate long-term survival after strict patient selection. The selection criteria comprise the absence of distant metastases and locoregional lymph node metastases as well as partial remission or stable disease after neoadjuvant chemotherapy. Due to no established graft allocation for iCCA in Germany, LDLT is currently the best option to realize transplantation in these patients. Developments in the last decade indicate that LDLT should preferentially be performed in minimal invasive manner (laparoscopic or robotic) as this approach is associated with less overall complications and a shorter hospitalization. The presented case illustrates the possibilities of modern surgery and the introduction of transplant oncology in the modern therapy of patients combining systemic therapy, surgical resection and transplantation to achieve optimal long-term results in patients which were initially indicated for palliative treatment.

Living-Donor Liver Transplantation for a Large Hepatocellular Carcinoma in a Genetically Identical Twin Sister.

Hepatocellular carcinoma (HCC) is, to date, the most common malignant tumor of the liver and is commonly staged with the Milan criteria. While deceased-donor liver transplantations (DDLT) are reserved for patients within the Milan criteria, living-donor liver transplantation (LDLT) might be a curative option for patients outside the Milan criteria. We here report a case of a 32-year-old woman who developed a giant, unresectable HCC out of a hepatocellular adenoma (HCA) after a pregnancy. The genetically identical twin sister donated her left hemi-liver after ethical approval and preoperative screening. No long-term immunosuppressive therapy was necessary, and after more than eight years, both are in perfect health and the recipient gave birth to a second child. This case shows that in certain situations large HCCs outside the standard criteria can be cured by LT. Careful evaluation of both donor and recipient should be performed for indications like this to assure optimal clinical outcome.

Survival after combined resection and ablation is not inferior to that after resection alone, in patients with four or more colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. METHODS: This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010-2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. RESULTS: Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan-Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. CONCLUSION: For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease.

Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection.

PURPOSE: Given limitations of the health care systems in case of unforeseeable events, e.g., the COVID pandemic as well as trends in prehabilitation, time from diagnosis to surgery (time to surgery, (TTS)) has become a research issue in malignancies. Thus, we investigated whether TTS is associated with oncological outcome in HCC patients undergoing surgery. METHODS: A monocentric cohort of 217 patients undergoing liver resection for HCC between 2009 and 2021 was analyzed. Individuals were grouped according to TTS and compared regarding clinical characteristics. Overall survival (OS) and recurrence-free survival (RFS) was compared using Kaplan-Meier analysis and investigated by univariate and multivariable Cox regressions. RESULTS: TTS was not associated with OS (p=0.126) or RFS (p=0.761) of the study cohort in univariate analysis. In multivariable analysis age (p=0.028), ASA (p=0.027), INR (0.016), number of HCC nodules (p=0.026), microvascular invasion (MVI; p<0.001), and postoperative complications (p<0.001) were associated with OS and INR (p=0.005), and number of HCC nodules (p<0.001) and MVI (p<0.001) were associated with RFS. A comparative analysis of TTS subgroups was conducted (group 1, ≤30 days, n=55; group 2, 31-60 days, n=79; group 3, 61-90 days, n=45; group 4, >90 days, n=38). Here, the median OS were 62, 41, 38, and 40 months (p=0.602 log rank) and median RFS were 21, 26, 26, and 25 months (p=0.994 log rank). No statistical difference regarding oncological risk factors were observed between these groups. CONCLUSION: TTS is not associated with earlier tumor recurrence or reduced overall survival in surgically treated HCC patients.

Clinical determinants of hospital mortality in liver failure: a comprehensive analysis of 62,717 patients.

BACKGROUND: Liver failure (LF) is characterised by a loss of the synthetic and metabolic liver function and is associated with a high mortality. Large-scale data on recent developments and hospital mortality of LF in Germany are missing. A systematic analysis and careful interpretation of these datasets could help to optimise outcomes of LF. METHODS: We used standardised hospital discharge data of the Federal Statistical Office to evaluate current trends, hospital mortality and factors associated with an unfavourable course of LF in Germany between 2010 and 2019. RESULTS: A total of 62,717 hospitalised LF cases were identified. Annual LF frequency decreased from 6716 (2010) to 5855 (2019) cases and was higher among males (60.51%). Hospital mortality was 38.08% and significantly declined over the observation period. Mortality significantly correlated with patients' age and was highest among individuals with (sub)acute LF (47.5%). Multivariate regression analyses revealed pulmonary (ORARDS: 2.76, ORmechanical ventilation: 6.46) and renal complications (ORacute kidney failure: 2.04, ORhepatorenal syndrome: 2.92) and sepsis (OR: 1.92) as factors for increased mortality. Liver transplantation reduced mortality in patients with (sub)acute LF. Hospital mortality significantly decreased with the annual LF case volume and ranged from 47.46% to 29.87% in low- or high-case-volume hospitals, respectively. CONCLUSIONS: Although incidence rates and hospital mortality of LF in Germany have constantly decreased, hospital mortality has remained at a very high level. We identified a number of variables associated with increased mortality that could help to improve framework conditions for the treatment of LF in the future.

Value of prognostic scoring systems in the era of multimodal therapy for recurrent colorectal liver metastases.

BACKGROUND: Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS: Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION: The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.

Nestin as a diagnostic and prognostic marker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND & AIMS: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer (PLC) associated with a poor prognosis. Given the challenges in its identification and its clinical implications, biomarkers are critically needed. We aimed to investigate the diagnostic and prognostic value of the immunohistochemical expression of Nestin, a progenitor cell marker, in a large multicentric series of PLCs. METHODS: We collected 461 cHCC-CCA samples from 32 different clinical centers. Control cases included 368 hepatocellular carcinomas (HCCs) and 221 intrahepatic cholangiocarcinomas (iCCAs). Nestin immunohistochemistry was performed on whole tumor sections. Diagnostic and prognostic performances of Nestin expression were determined using receiver-operating characteristic curves and Cox regression modeling. RESULTS: Nestin was able to distinguish cHCC-CCA from HCC with AUCs of 0.85 and 0.86 on surgical and biopsy samples, respectively. Performance was lower for the distinction of cHCC-CCA from iCCA (AUCs of 0.59 and 0.60). Nestin, however, showed a high prognostic value, allowing identification of the subset of cHCC-CCA ("Nestin High", >30% neoplastic cells with positive staining) associated with the worst clinical outcome (shorter disease-free and overall survival) after surgical resection and liver transplantation, as well as when assessment was performed on biopsies. CONCLUSION: We show in different clinical settings that Nestin has diagnostic value and that it is a useful biomarker to identify the subset of cHCC-CCA associated with the worst clinical outcome. Nestin immunohistochemistry may be used to refine risk stratification and improve treatment allocation for patients with this highly aggressive malignancy. LAY SUMMARY: There are different types of primary liver cancers (i.e. cancers that originate in the liver). Accurately identifying a specific subtype of primary liver cancer (and determining its associated prognosis) is important as it can have a major impact on treatment allocation. Herein, we show that a protein called Nestin could be used to refine risk stratification and improve treatment allocation for patients with combined hepatocellular carcinoma, a rare but highly aggressive subtype of primary liver cancer.

The role of re-resection in recurrent hepatocellular carcinoma.

PURPOSE: While liver resection is a well-established treatment for primary HCC, surgical treatment for recurrent HCC (rHCC) remains the topic of an ongoing debate. Thus, we investigated perioperative and long-term outcome in patients undergoing re-resection for rHCC in comparative analysis to patients with primary HCC treated by resection. METHODS: A monocentric cohort of 212 patients undergoing curative-intent liver resection for HCC between 2010 and 2020 in a large German hepatobiliary center were eligible for analysis. Patients with primary HCC (n = 189) were compared to individuals with rHCC (n = 23) regarding perioperative results by statistical group comparisons and oncological outcome using Kaplan-Meier analysis. RESULTS: Comparative analysis showed no statistical difference between the resection and re-resection group in terms of age (p = 0.204), gender (p = 0.180), ASA category (p = 0.346) as well as main preoperative tumor characteristics, liver function parameters, operative variables, and postoperative complications (p = 0.851). The perioperative morbidity (Clavien-Dindo ≥ 3a) and mortality were 21.7% (5/23) and 8.7% (2/23) in rHCC, while 25.4% (48/189) and 5.8% (11/189) in primary HCC, respectively (p = 0.851). The median overall survival (OS) and recurrence-free survival (RFS) in the resection group were 40 months and 26 months, while median OS and RFS were 41 months and 29 months in the re-resection group, respectively (p = 0.933; p = 0.607; log rank). CONCLUSION: Re-resection is technically feasible and safe in patients with rHCC. Further, comparative analysis displayed similar oncological outcome in patients with primary and rHCC treated by liver resection. Re-resection should therefore be considered in European patients diagnosed with rHCC.

Elevated Serum Levels of CCL23 Are Associated with Poor Outcome after Resection of Biliary Tract Cancer.

Background: Surgical tumor resection is the only potentially curative treatment option for patients with biliary tract cancer (BTC). However, 5-year survival rates are still below 50% mainly due to tumor recurrence. The preoperative identification of ideal surgical candidates has remained a major challenge and easily accessible algorithms including parameters of the individual tumor biology are missing. Chemokine (C-C motif) ligand 23 (CCl23) has been associated with tumor progression in hepatocellular carcinoma (HCC), but its role in the context of BTC is largely unknown. Here, we evaluated circulating levels of CCL23 as potential diagnostic and prognostic biomarker in patients with resectable BTC. Methods: CCl23 serum levels were analyzed by multiplex immunoassay in a cohort of 119 BTC patients receiving surgical tumor resection as well as 50 healthy control samples and 11 patients with primary sclerosing cholangitis (PSC). Results: Baseline serum CCL23 levels were significantly elevated in BTC patients compared to PSC patients as well as healthy controls. CCL23 increased the diagnostic sensitivity and specificity of established tumor markers including CA19-9 and correlated with patients' age and makers of systemic inflammation. Elevated preoperative CCL23 levels were associated with a significantly impaired postoperative outcome. BTC patients with a preoperative CCL23 level above the optimal prognostic cut-off value of 702.4 pg/ml showed a median OS of only 110 days compared to 501 days for patients with low initial CCL23 levels. The prognostic value of circulating CCL23 was confirmed in Cox-regression analysis. Conclusion: Serum levels of CCL23 are elevated in patients with BTC, and high preoperative CCL23 levels were associated with an impaired postoperative survival. CCL23 serum levels could help to identify the ideal surgical candidates for BTC resection in the future.

Perioperative and long-term outcome of en-bloc arterial resection in pancreatic surgery.

BACKGROUND: Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival. RESULTS: Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively. CONCLUSION: In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.

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.

Clinical value and limitations of the preoperative C-reactive-protein-to-albumin ratio in predicting post-operative morbidity and mortality after deceased-donor liver transplantation: a retrospective single-centre study.

Liver transplantation is still associated with a high risk of severe complications and post-operative mortality. This study examines the predictive value of the preoperative C-reactive-protein-to-albumin ratio (CAR) regarding perioperative morbidity and mortality in deceased-donor liver transplantation (DDLT) recipients. In total, 390 DDLT recipients between 05/2010 and 03/2020 were eligible. Predictive abilities of CAR were examined through receiver operating characteristic curve (ROC) analyses. Groups were compared using parametric and non-parametric tests as appropriate. Independent risk factors for morbidity and mortality were identified using uni- and multivariable logistic regression analyses. A good predictive ability for CAR was shown regarding perioperative morbidity (comprehensive complication index ≥75, Clavien-Dindo score ≥4a) and 12-month mortality, with an ideal cut-off of CAR = 26%. Patients with CAR>26% had significantly higher median CCI scores (60 vs. 43, P < 0.001), longer intensive care unit (ICU, 5 vs. 4 days, P < 0.001) and hospital (28 vs. 21 days, P < 0.001) stays and higher 12-month mortality rates (20% vs 6%, P < 0.001). Multivariable analyses identified CAR>26%, pre-OLT inpatient hospitalization (including ICU) and post-operative red blood cell transfusions as independent predictors of severe cumulative morbidity (CCI≥75). Preoperative CAR might be a reliable additional tool to predict perioperative morbidity and mortality in DDLT recipients.

Prognostic evaluation of HCC patients undergoing surgical resection: an analysis of 8 different staging systems.

PURPOSE: No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. METHODS: Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ2 (homogeneity), linear trend (LT) χ2 (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. RESULTS: Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32-46 months) and median RFS was 26 months (95% CI: 16-34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ2 30.08, LT χ2 13.90, AIC 455.27) and CLIP (LR χ2 28.65, LT χ2 18.95, AIC 460.07) being the best performing staging systems. CONCLUSIONS: ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.

Incisional hernia repair by synthetic mesh prosthesis in patients with inflammatory bowel disease: a comparative analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a high-life time risk undergoing abdominal surgery and are prone to develop incisional hernias (IH) in the postoperative course. Therefore, we investigated the role of IBD as perioperative risk factor in open ventral hernia repair (OVHR) as well as the impact of IBD on hernia recurrence during postoperative follow-up. METHODS: The postoperative course of 223 patients (Non-IBD (n = 199) and IBD (n = 34)) who underwent OVHR were compared by means of extensive group comparisons and binary logistic regressions. Hernia recurrence was investigated in the IBD group according to the Kaplan-Meier method and risk factors for recurrence determined by Cox regressions. RESULTS: General complications (≥ Clavien-Dindo I) occurred in 30.9% (72/233) and major complications (≥ Clavien-Dindo IIIb) in 7.7% (18/233) of the overall cohort with IBD being the single independent risk-factor for major complications (OR = 4.2, p = 0.007). Further, IBD patients displayed a recurrence rate of 26.5% (9/34) after a median follow-up of 36 months. Multivariable analysis revealed higher rates of recurrence in patients with ulcerative colitis (UC, 8/15, HR = 11.7) compared to patients with Crohn's disease (CD, 1/19, HR = 1.0, p = 0.021). CONCLUSION: IBD is a significant risk factor for major postoperative morbidity after OVHR. In addition, individuals with IBD show high rates of hernia recurrence over time with UC patients being more prone to recurrence than patients with CD.

Operative Time, Age, and Serum Albumin Predict Surgical Morbidity After Laparoscopic Liver Surgery.

Background. Laparoscopic liver resection (LLR) has emerged as a considerable alternative to conventional liver surgery. However, the increasing complexity of liver resection raises the incidence of postoperative complications. The aim of this study was to identify risk factors for postoperative morbidity in a monocentric cohort of patients undergoing LLR. Methods. All consecutive patients who underwent LLR between 2015 and 2019 at our institution were analyzed for associations between complications with demographics and clinical and operative characteristics by multivariable logistic regression analyses. Results. Our cohort comprised 156 patients who underwent LLR with a mean age of 60.0 ± 14.4 years. General complications and major perioperative morbidity were observed in 19.9% and 9.6% of the patients, respectively. Multivariable analysis identified age>65 years (HR = 2.56; P = .028) and operation time>180 minutes (HR = 4.44; P = .001) as significant predictors of general complications (Clavien ≥1), while albumin<4.3 g/dl (HR = 3.66; P = .033) and also operative time (HR = 23.72; P = .003) were identified as predictors of major postoperative morbidity (Clavien ≥3). Conclusion. Surgical morbidity is based on patient- (age and preoperative albumin) and procedure-related (operative time) characteristics. Careful patient selection is key to improve postoperative outcomes after LLR.

Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma.

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients' prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. METHODS: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. RESULTS: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. CONCLUSION: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.

Insufficient future liver remnant and preoperative cholangitis predict perioperative outcome in perihilar cholangiocarcinoma.

BACKGROUND: Major liver resection has evolved as the mainstay of treatment for patients with perihilar cholangiocarcinoma (pCCA). Here we assessed the suitability of preoperative future liver remnant (FLR) measurement to predict perioperative complications, since surgical morbidity and mortality are high compared to other malignancies. METHODS: Between 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. The associations of surgical complications with FLR and clinico-pathological characteristics were assessed using logistic regression analyses. Different methods of FLR assessment, the calculated-FLR (cFLR; ratio of FLR to total liver volume), standardized FLR (sFLR; ratio of FLR to liver volume estimated by body surface area) and FLR to bodyweight ratio (FLR/BW) were tested for validity. RESULTS: Multivariable analysis identified preoperative cholangitis (Exp(B) = 0.236; p = 0.030) as the single significant predictor of postoperative mortality and cFLR (Exp(B) = 0.009, p = 0.004) as the single significant predictor of major postoperative morbidity (Clavien-Dindo ≥ 3b). Based on these findings we designed a futility criterion (cFLR<40% OR preoperative cholangitis) predicting in-house mortality. CONCLUSIONS: In patients with pCCA, the preoperative FLR<40% as well as preoperative cholangitis are two risk factors to independently predict perioperative morbidity and mortality. The cFLR should be the preferred method of liver volumetry.

The prognostic role of tumor-associated unilateral portal vein occlusion in perihilar cholangiocarcinoma.

BACKGROUND: While a certain degree of tumor infiltration of the portal vein is common in patients with perihilar cholangiocarcinoma (pCCA) scheduled for surgery, complete tumor-associated portal vein occlusion (PVO) is less frequently observed. Here, we analyzed the impact of PVO on perioperative and oncological outcomes in pCCA patients. METHODS: Between 2010 and 2019, 127 patients with pCCA underwent surgery in curative intent at our department of which 17.3% (22/127) presented with PVO. Extensive group comparisons were conducted and the association of cancer-specific (CSS) and disease-free survival (DFS) with PVO and other clinico-pathological characteristics were assessed using Cox regression models. RESULTS: Patients without PVO showed a median CSS of 65 months (3-year-CSS = 64%, 5-year-CSS = 53%) compared to 31 months (3-year-CSS = 43%, 5-year-CSS = 17%) in patients with PVO (p = 0.025 log rank). Patients with PVO did also display significant perioperative mortality (22.7%, 5/22) compared to patients without PVO (14.3%, 15/105, p = 0.323). Further, PVO (CSS: HR = 5.25, p = 0.001; DFS: HR = 5.53, p = 0.001) was identified as independent predictors of oncological outcome. CONCLUSIONS: PVO has been identified as an important prognostic marker playing a role in inferior oncological outcome in patients with pCCA. As PVO is also associated with notable perioperative mortality, surgical therapy should be considered carefully in pCCA patients.