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.

Clinical Research in Renal Transplantation: A Bibliometric Perspective on a Half-century of Innovation and Progress.

BACKGROUND: Groundbreaking biomedical research has transformed renal transplantation (RT) into a widespread clinical procedure that represents the mainstay of treatment for end-stage kidney failure today. Here, we aimed to provide a comprehensive bibliometric perspective on the last half-century of innovation in clinical RT. METHODS: The Web of Science Core Collection was used for a comprehensive screening yielding 123 303 research items during a 50-y period (January 1973-October 2022). The final data set of the 200 most-cited articles was selected on the basis of a citation-based strategy aiming to minimize bias. RESULTS: Studies on clinical and immunological outcomes (n = 63 and 48), registry-based epi research (n = 38), and randomized controlled trials (n = 35) dominated the data set. Lead US authors have signed 110 of 200 articles. The overall level of evidence was high, with 84% of level1 and -2 reports. Highest numbers of these articles were published in New England Journal of Medicine , Transplantation , and American Journal of Transplantation. Increasing trend was observed in the number of female authors in the postmillennial era (26% versus 7%). CONCLUSIONS: This study highlights important trends in RT research of the past half-century. This bibliometric perspective identifies the most intensively researched areas and shift of research interests over time; however, it also describes important imbalances in distribution of academic prolificacy based on topic, geographical aspects, and gender.

Body composition is associated with postoperative complications in perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA. METHODS: All patients with pCCA who underwent curative-intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan-Meier analysis to evaluate oncological risk factors in the study cohort. RESULTS: BC was frequently altered in patients undergoing curative-intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien-Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no-sarcopenia, 21 months vs. 32 months, p = 0.048 log rank). CONCLUSIONS: BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.

Time to surgery is not an oncological risk factor in patients with cholangiocarcinoma undergoing curative-intent liver surgery.

Surgical resection is the only option to achieve long-term survival in cholangiocellular carcinoma (CCA). Due to limitations of health care systems and unforeseeable events, e.g., the COVID pandemic, the time from diagnosis to surgery (time-to-surgery (TTS)) has gained great interest in malignancies. Thus, we investigated whether TTS is associated with the oncological outcome in patients who underwent surgery for CCA. A cohort of 276 patients undergoing curative-intent surgery for intrahepatic and perihilar CCA excluding individuals with neoadjuvant therapy and perioperative mortality between 2010 and 2021 were eligible for analysis. Patients were grouped according to TTS (≤ 30; 31-60; 61-90; > 90 days) and compared by Kruskal-Wallis-analysis. Survival was compared using Kaplan-Meier analysis and characteristics associated with cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) using Cox regressions. The median CSS was 39 months (3-year-CSS = 52%, 5-year-CSS = 42%) and the median RFS 20 months (3-year-CSS = 38%, 5-year-CSS = 33%). In univariable Cox regressions, TTS was not associated with CSS (p = 0.971) or RFS (p = 0.855), respectively. A grouped analysis with respect to TTS (≤ 30 days, n = 106; 31-60 days, n = 134; 61-90 days, n = 44; > 90 days, n = 29) displayed a median CSS of 38, 33, 51 and 41 months and median RFS of 17, 22, 28 and 20 months (p = 0.971 log rank; p = 0.520 log rank). No statistical difference regarding oncological risk factors were observed between the groups. This study is the first comprehensive analysis of TTS in CCA patients. Within a representative European cohort, TTS was not associated with earlier tumor recurrence or reduced CCS.

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.

Osteopenia is associated with inferior survival in patients undergoing partial hepatectomy for hepatocellular carcinoma.

Osteopenia is known to be associated with clinical frailty which is linked to inferior outcomes in various clinical scenarios. However, the exact prognostic value of osteopenia in patients undergoing curative intent-surgery for hepatocellular carcinoma (HCC) is not completely understood. This retrospective study was conducted in a cohort of 151 patients who underwent partial hepatectomy for HCC in curative intent at a German university medical center (05/2008-12/2019). Preoperative computed tomography-based segmentation was used to assess osteopenia, and the prognostic impact of pathological changes in bone mineral density (BMD) on perioperative morbidity, mortality, and long-term oncological outcome was analyzed. Five-year overall survival of osteopenic patients was significantly worse compared to those with normal BMD (29% vs. 65%, p = 0.014). In line with this, the probability of disease-free survival at 5 years was significantly worse for patients with osteopenia (21% vs. 64%, p = 0.005). In our multivariable model, osteopenia was confirmed as an independent risk-factor for inferior overall survival (Hazard-ratio 7.743, p = 0.002). Concerning perioperative complications, osteopenic patients performed slightly worse, even though no statistical difference was detected (Clavien-Dindo ≥ 3b; 21% vs. 9%, p = 0.139). The present study confirms osteopenia as an independent risk-factor for inferior survival in patients undergoing partial hepatectomy for HCC in a European cohort. Further studies are warranted to validate these findings.

Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs.

INTRODUCTION: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. METHODS: We conducted an in vitro animal study by analyzing 21 lungs of New Zealand (n = 19) and Chinchilla Bastard (n = 2) rabbits (age, 11-18 weeks; weight, 2,400-3,600 g). Three groups, each comprising 7 animals, were evaluated. VIVO (VIVO-group) was compared with standard surgical lung parenchymal lesion closure with a polypropylene suture (Suture-group) and TachoSil® (TachoSil-group). We adopted a stable, pressure-controlled ventilation protocol. After explantation, a surgical incision 0.5-cm deep and 1.5-cm wide was made in the lungs using a customized template. Air leak was measured quantitatively (mL/min) using a respirator and visualized qualitatively by 2 observers who made independent judgments. Next, the leak was closed using VIVO, suture, or TachoSil® as specified by the manufacturer. Subsequently, positive end-expiratory pressure (PEEP) and inspiratory pressure were gradually increased until a maximum of 15 and 30 mbar were attained, respectively. RESULTS: At PEEPs of 8, 10, and 15 mbar, VIVO achieved complete sealing of the profound parenchymal defect in all (n = 7) lungs. After closure of the incision, we observed an air leak variation of 127 ± 114 mL/min (Suture-group), 31 ± 49 mL/min (VIVO-group), and 114 ± 134 mL/min (TachoSil-group). VIVO showed a significantly lower air leak than surgical sutures (p = 0.031) and TachoSil® (p = 0.046). CONCLUSION: VIVO offers sufficient closure of the lung parenchymal lesions. The novel adhesive enabled significantly better sealing with lower persistent air leakage than TachoSil® or surgical sutures. Further investigation using in vivo models is strongly encouraged to confirm our findings.

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.

Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury-An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies.

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular-pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.