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Abstract Objective Hilar cholangiocarcinoma is the fourth most common gastrointestinal malignancy. CA19-9 and CEA are helpful devices in the management of gastrointestinal malignancies and belong to clinical routine in surgical oncology. But the validity of these parameters in terms of tumor extension and prognosis of bile duct malignancies still remains unclear. Methods From 1998 to 2008, we obtained preoperative CA19-9 and CEA serum levels in 136 patients with hilar cholangiocarcinoma. We correlated tumor stage, resectability rate and survival with preoperative CA 19-9 and CEA serum levels. Results CA19-9 (UICC I: 253 ± 561 U/ml; UICC II: 742 ± 1572 U/ml; UICC III: 906 ± 1708 U/ml; UICC IV: 1707 ± 3053 U/ml) and CEA levels (UICC I: 2.9 ± 3.8 U/ml; UICC II: 4.6 ± 6.5 U/ml; UICC III: 18.1 ± 29.6 U/ml; UICC IV: 22.7 ± 53.9 U/ml) increase significantly with rising tumor stage. Patients with pre operative serum levels of CA19-9 (> 1000 U/ml) and CEA (> 14.4 ng/ml) showed a significant poorer resectability rate and survival than patients with lower CA19-9 and CEA serum levels respectively. Conclusion CA19-9 and CEA serum levels are associated with the tumor stage. If preoperatively obtained CA19-9 and CEA serum levels are highly elevated patients have an even worse survival and the frequency of irresectability is significantly higher.

Background. Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion. This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge. [ABSTRACT FROM AUTHOR]

Hand-sewn and stapled intestinal anastomoses are both daily performed routine procedures by surgeons. Yet, differences in micro perfusion of these two surgical techniques and their impact on surgical outcomes are still insufficiently understood. Only recently, hyperspectral imaging (HSI) has been established as a non-invasive, contact-free, real-time assessment tool for tissue oxygenation and micro-perfusion. Hence, objective of this study was HSI assessment of different intestinal anastomotic techniques and analysis of patients’ clinical outcome.

Abstract: Producing active polymer optical fibers (POFs) is a key step towards new applications such as fluorescent fiber solar concentrators (FFSCs), sensors, contactless coupling devices, or fiber integrated light sources and lasers. Therefore, integration of fluorescent nanoparticles into the polymer matrix is necessary and becomes accessible via in situ polymerization. For optical applications, the polymer has to fulfill various requirements such as chemical and physical stability, optical transparency in the application-relevant spectral region as well as a good synthetic accessibility. A common material for these is poly(methyl methacrylate) (PMMA). The β-phase NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNP) were synthesized from the rare earth salts via thermal decomposition method in high-boiling point solvent 1-octadecene and capping agent oleic acid. Current results show hazy samples of the polymer with integrated nanoparticles made from monomer solution of methyl methacrylate. However, further optical tuning such as increasing the transparency of the bulk samples by changing the monomer solution to non-polar n-butyl methacrylate (nButMA) or cyclohexyl methacrylate (CHMA) or further optimization of the UCNP shell could lead to more suitable polymer bulk samples. [ABSTRACT FROM AUTHOR]

Background: Antiplatelet therapy is common in patients on the waiting list for kidney transplantation. Objective: To evaluate the incidence of post-operative bleeding in patients with antiplatelet therapy undergoing kidney transplantation and analyze the impact on the outcome. Methods: We studied all patients with concomitant antiplatelet therapy undergoing kidney transplantation in our center from January 2007 to June 2012. Data were collected by chart review. Univariate and multivariate logistic regression and Cox proportional hazard model were used to identify risk factors for the long-term outcome. Results: Of 744 kidney transplant recipients during the study period, 161 received oral antiplatelet therapy and were included in the study. One-third of the patients demonstrated signs of bleeding, half of which requiring surgical treatment. Coronary artery disease, deceased donor kidney transplantation, and dual antiplatelet medication were independent risk factors for post-operative bleeding. One-year allograft survival was significantly better in the non-bleeding group (91.4% vs 75.9%, p=0.023). Multivariable analysis found that post-operative bleeding, recipient age, and biopsy-proven rejection were independent risk factors for graft survival. Recipient age and biopsy-proven rejection were also identified as independent risk factors for patient survival. Conclusion: This analysis indicated a high risk for post-operative bleeding in renal transplant patients under antiplatelet therapy. The associated negative effect on allograft survival underscored the need to reduce any risk factors for post-operative bleeding. [ABSTRACT FROM AUTHOR]

Women represent the majority of medical students in several countries. In any surgical specialty and above all in surgical leadership positions, women still remain disproportionally underrepresented. The objective of this study was to investigate female surgeons’ career advancement and satisfaction with training. A standardized questionnaire was devised and sent out via the web-based survey tool SurveyMonkey® to female surgeons in the German federal state of North Rhine-Westphalia. A total of 125 completed questionnaires were analyzed (response rate 40.8%). Female surgeons are at least largely (76%) satisfied with their surgical training. Increased time (>5 h/week) as the principal surgeon in the operating room significantly stimulates the satisfaction with the surgical training (86% vs. 68%, p = 0.0384). At the participants’ current workplace, the heads of departments are predominantly male surgeons (91%). Respondents not satisfied with their surgical training prefer a female head of department more frequently (24% vs. 2%, p = 0.0085). The majority of the respondents themselves aspire to become a consultant surgeon (56%), while only 12% intend to become a head of a department. Female surgeons aiming at leadership positions work overtime (≥50 h/week) significantly more frequently (81% vs. 57%, p = 0.0041). Favoritism of male colleagues is perceived by 34%. Respondents who do not perceive any preferential treatment are significantly more satisfied with their surgical training (88% vs. 57%, p = 0.0004). In conclusion, female surgeons seem positive about their career choice, once in the surgical profession, and aptly fill upcoming positions. Women interested in surgery are likely to pursue a surgical career despite the alleged workload, demonstrating the importance of professional self-fulfillment among female surgeons.

Bacterial biofilms can pose a serious health risk to humans and are less susceptible to antibiotics and disinfection than planktonic bacteria. Here, a novel method for biofilm eradication based on antimicrobial photodynamic therapy utilizing a nanoparticle in conjunction with a BODIPY derivative as photosensitizer was developed. Reactive oxygen species are generated upon illumination with visible light and lead to a strong, controllable and persistent eradication of both planktonic bacteria and biofilms. One of the biggest challenges in biofilm eradication is the penetration of the antimicrobial agent into the biofilm and its matrix. A biocompatible hydrophilic nanoparticle was utilized as a delivery system for the hydrophobic BODIPY dye and enabled its accumulation within the biofilm. This key feature of delivering the antimicrobial agent to the site of action where it is activated resulted in effective eradication of all tested biofilms. Here, 3 bacterial species that commonly form clinically relevant pathogenic biofilms were selected: Escherichia coli , Staphylococcus aureus and Streptococcus mutans . The development of this antimicrobial photodynamic therapy tool for biofilm eradication takes a promising step towards new methods for the much needed treatment of pathogenic biofilms., Competing Interests: SR is an employee of a company producing and marketing substances for diagnostic imaging. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kromer, Schwibbert, Radunz, Thiele, Laux, Luch and Tschiche.)

Limited treatment options in patients with intrahepatic cholangiocarcinoma (iCCA) demand the introduction of new, catheter-based treatment options. Especially, 90 Y radioembolization may expand therapeutic abilities beyond surgery or chemotherapy. Therefore, the purpose of this study was to identify factors associated with an improved median overall survival (mOS) in iCCA patients receiving radioembolization in a retrospective study at 5 major tertiary-care centers. Methods: In total, 138 radioembolizations in 128 patients with iCCA (female, 47.7%; male, 52.3%; mean age ± SD, 61.1 ± 13.4 y) were analyzed. Clinical data, imaging characteristics, and radioembolization reports, as well as data from RECIST, version 1.1, analysis performed 3, 6, and 12 mo after radioembolization, were collected. mOS was compared among different subgroups using Kaplan-Meier curves and the log-rank test. Results: Radioembolization was performed as first-line treatment in 25.4%, as second-line treatment in 38.4%, and as salvage treatment in 36.2%. In patients receiving first-line, second-line, and salvage radioembolization, the disease control rate was 68.6%, 52.8%, and 54.0% after 3 mo; 31.4%, 15.1%, and 12.0% after 6 mo; and 17.1%, 5.7%, and 6.0% after 1 y, respectively. In patients receiving radioembolization as first-line, second-line, and salvage treatment, mOS was 12.0 mo (95% CI, 7.6-23.4 mo), 11.8 mo (95% CI, 9.1-16.6 mo), and 8.4 mo (95% CI, 6.3-12.7 mo), respectively. No significant differences among the 3 groups were observed ( P = 0.15). Hepatic tumor burden did not significantly influence mOS ( P = 0.12). Conclusion: Especially in advanced iCCA, second-line and salvage radioembolization may be important treatment options. In addition to ongoing studies investigating the role of radioembolization as first-line treatment, the role of radioembolization in the later treatment stages of the disease demands further attention., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

(1) Background: Patient sex is associated with differential outcome of many procedures although the exact mechanisms remain unknown. Especially in transplant surgery, surgeon-patient sex-concordance is rarely present for female patients and outcome may be negatively affected. (2) Methods: In this single-center retrospective cohort study, recipient, donor, and surgeon sex were evaluated and short- and long-term outcome was analyzed with regards to sex and sex-concordance of patients, donors, and surgeons. (3) Results: We included 425 recipients in our study; 50.1% of organ donors, 32.7% of recipients, and 13.9% of surgeons were female. Recipient-donor sex concordance was present in 82.7% of female recipients and in 65.7% of male recipients ( p = 0.0002). Recipient-surgeon sex concordance was present in 11.5% of female recipients and in 85.0% of male recipients ( p < 0.0001). Five-year patient survival was comparable between female and male recipients (70.0% vs. 73.3%, p = 0.3978). Five-year patient survival of female recipients treated by female surgeons was improved without reaching significance (81.3% vs. 68.4%, p = 0.3621). (4) Conclusions: Female recipients and female surgeons are underrepresented in liver transplant surgery. Societal factors influencing outcome of female patients suffering from end-stage organ failure need to be further examined and acted upon to possibly improve the outcome of female liver transplant recipients.

Introduction: Gemcitabine and cisplatin is the standard first-line systemic treatment in patients with advanced cholangiocarcinoma (CCA). However, a substantial number of patients do not qualify for cisplatin due to comorbidities or poor performance status. The phase II pilot study NACHO evaluated the efficacy of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) given on days 1, 8, and 15 every 4 weeks as first-line therapy in patients with advanced CCA ineligible for cisplatin-based chemotherapy., Methods: Patients with any comorbidity precluding cisplatin therapy, such as renal impairment, impaired hearing, increased risk or history for thromboembolic events, intolerance of extensive hydration, or significant cardiovascular disease were eligible. Primary endpoint was overall response rate (ORR) per RECIST 1.1. Secondary endpoints were progression-free survival (PFS), overall survival (OS), safety, and patient reported outcome., Results: From December 2016 to July 2017, 10 patients were prospectively enrolled and treated. The ORR with nab-paclitaxel/gemcitabine was 50%, the disease control rate (DCR) was 90%. Median PFS was 5.7 months (95% CI: 5.3-6.1), and median OS was 7.8 months (95% CI: 5.4-10.2). In total, 13 SAEs were documented without any new safety signals. There were 14 grade 3-4 treatment-related adverse events (TRAEs) in 10 patients of the ITT population. Exploratory subgroup analyses including known prognostic markers were performed., Conclusions: The NACHO trial supports safety and efficacy of nab-paclitaxel and gemcitabine in patients with advanced CCA ineligible for cisplatin-based therapy and should be further evaluated in a larger prospective trial., (© 2023 S. Karger AG, Basel.)

Purpose: Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP., Methods: Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA., Results: Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted., Conclusion: Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table., (© 2022. The Author(s).)

Normothermic machine perfusion (NMP) is nowadays frequently utilized in liver transplantation. Despite commonly accepted viability assessment criteria, such as perfusate lactate and perfusate pH, there is a lack of predictive organ evaluation strategies to ensure graft viability. Hyperspectral imaging (HSI)-as an optical imaging modality increasingly applied in the biomedical field-might provide additional useful data regarding allograft viability and performance of liver grafts during NMP., Methods: Twenty-five deceased donor liver allografts were included in the study. During NMP, graft viability was assessed conventionally and by means of HSI. Images of liver parenchyma were acquired at 1, 2, and 4 h of NMP, and subsequently analyzed using a specialized HSI acquisition software to compute oxygen saturation, tissue hemoglobin index, near-infrared perfusion index, and tissue water index. To analyze the association between HSI parameters and perfusate lactate as well as perfusate pH, we performed simple linear regression analysis., Results: Perfusate lactate at 1, 2, and 4 h NMP was 1.5 [0.3-8.1], 0.9 [0.3-2.8], and 0.9 [0.1-2.2] mmol/L. Perfusate pH at 1, 2, and 4 h NMP was 7.329 [7.013-7.510], 7.318 [7.081-7.472], and 7.265 [6.967-7.462], respectively. Oxygen saturation predicted perfusate lactate at 1 and 2 h NMP (R 2 = 0.1577, P = 0.0493; R 2 = 0.1831, P = 0.0329; respectively). Tissue hemoglobin index predicted perfusate lactate at 1, 2, and 4 h NMP (R 2 = 0.1916, P = 0.0286; R 2 = 0.2900, P = 0.0055; R 2 = 0.2453, P = 0.0139; respectively)., Conclusions: HSI may serve as a noninvasive tool for viability assessment during NMP. Further evaluation and validation of HSI parameters are warranted in larger sample sizes., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5−28.5] vs. 11.3 [5.4−24.1], p < 0.0001). The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts (arterial flow 22.50 [18.00−48.00] vs. 51.83 [25.50−92.67] ml/min, p = 0.0256; organ resistance 123.33 [57.67−165.50] vs. 51.33 [28.17−111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08−7.64] vs. 1.67 [0.90−6.56], p < 0.0001) and at 1 year post transplant (1.80 [1.09−7.95] vs. 1.59 [0.87−7.40], p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome.

Introduction: In liver transplantation (LT), steatosis is commonly judged to be a risk factor for graft dysfunction, and quantitative assessment of hepatic steatosis remains crucial. Liver biopsy as the gold standard for evaluation of hepatic steatosis has certain drawbacks, that is, invasiveness, and intra- and inter-observer variability. A non-invasive, quantitative modality could replace liver biopsy and eliminate these disadvantages, but has not yet been evaluated in human LT., Methods: We performed a pilot study to evaluate the feasibility and accuracy of hyperspectral imaging (HSI) in the assessment of hepatic steatosis of human liver allografts for transplantation. Thirteen deceased donor liver allografts were included in the study. The degree of steatosis was assessed by means of conventional liver biopsy as well as HSI, performed at the end of back-table preparation, during normothermic machine perfusion (NMP), and after reperfusion in the recipient., Results: Organ donors were 51 [30-83] years old, and 61.5% were male. Donor body mass index was 24.2 [16.5-38.0] kg/m 2 . The tissue lipid index (TLI) generated by HSI at the end of back-table preparation correlated significantly with the histopathologically assessed degree of overall hepatic steatosis (R2 = .9085, P < .0001); this was based on a correlation of TLI and microvesicular steatosis (R2 = .8120; P < .0001). There is also a linear relationship between the histopathologically assessed degree of overall steatosis and TLI during NMP (R2 = .5646; P = .0031) as well as TLI after reperfusion (R2 = .6562; P = .0008)., Conclusion: HSI may safely be applied for accurate assessment of hepatic steatosis in human liver grafts. Certainly, TLI needs further assessment and validation in larger sample sizes., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment., Methods: We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival., Results: Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death., Conclusions: Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies., (© 2022. The Author(s).)

Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of the liver, and data on patient outcome after surgical treatment are scarce. The aim of this study was to evaluate postoperative morbidity and overall survival (OS) of patients who underwent hepatectomy for PHA. This is a bicentric retrospective analysis of all consecutive patients who underwent liver resection in curative intent for PHA between 2012 and 2019 at the University Hospital of Muenster and the University Hospital of Bern. Nine patients (five female, four male) were included from both centers. Median age was 72 years (44-82). Most lesions (77.8%) were larger than 5 cm, and mean size of the biggest lesion was 9.4 ± 4.5 cm. Major hepatectomy was performed in four (44.4%), and radical resection (R0) was achieved in six (66.7%) patients. Postoperative complication rate was 88.8%, including 44.4% higher than 3a in the Clavien-Dindo classification. OS survival rates at 1, 2, and 3 years were 44.4%, 22.2%, and 12.5%, respectively, and median OS was 5 months. OS was significantly better after radical resection (R0: 15 months vs. R1: 0 months, p = 0.04), whereas presentation with tumor rupture at diagnosis was associated with the worst OS (0 months vs. 15 months, p = 0.005). Disease recurrence occurred in three patients (33.3%) between three and seven months after surgery. Radical resection remains the only potentially curative treatment option for PHA. However, postoperative morbidity is high, and the overall prognosis remains poor. Multimodal therapy options and management strategies are urgently needed and could improve the prognosis of patients suffering from PHA in the future.

The aim of our study was to evaluate hyperspectral imaging (HSI) as a rapid, non-ionizing technique for the assessment of organ quality and the prediction of delayed graft function (DGF) in kidney transplantation after static cold storage (SCS, n = 20), as well as hypothermic machine perfusion (HMP, n = 18). HSI assessment of the kidney parenchyma was performed during organ preservation and at 10 and 30 min after reperfusion using the TIVITA ® Tissue System (Diaspective Vision GmbH, Am Salzhaff, Germany), calculating oxygen saturation (StO 2 ), near-infrared perfusion index (NIR), tissue haemoglobin index (THI), and tissue water index (TWI). Recipient and donor characteristics were comparable between organ preservation groups. Cold ischemic time was significantly longer in the HMP group (14.1 h [3.6-23.1] vs. 8.7h [2.2-17.0], p = 0.002). The overall presence of DGF was comparable between groups (HMP group n = 10 (55.6%), SCS group n = 10 (50.0%)). Prediction of DGF was possible in SCS and HMP kidneys; StO 2 at 10 (50.00 [17.75-76.25] vs. 63.17 [27.00-77.75]%, p = 0.0467) and 30 min (57.63 [18.25-78.25] vs. 65.38 [21.25-83.33]%, p = 0.0323) after reperfusion, as well as NIR at 10 (41.75 [1.0-58.00] vs. 48.63 [12.25-69.50], p = 0.0137) and 30 min (49.63 [8.50-66.75] vs. 55.80 [14.75-73.25], p = 0.0261) after reperfusion were significantly lower in DGF kidneys, independent of the organ preservation method. In conclusion, HSI is a reliable method for intraoperative assessment of renal microperfusion, applicable after organ preservation through SCS and HMP, and predicts the development of DGF.

Surgery has become well established for patients with colorectal and neuroendocrine liver metastases. However, the value of this procedure in non-colorectal and non-neuroendocrine metastases (NCRNNELMs) remains unclear. We analyzed the outcomes of patients that underwent liver surgery for NCRNNELMs and for colorectal liver metastases (CRLMs) between 2012 and 2017 at our institution. Prognostic factors of overall and recurrence-free survival were analyzed, and a comparison of survival between two groups was performed. Seventy-three patients (30 NCRNNELM and 43 CRLM) were included in this study. Although the mean age, extrahepatic metastases, and rate of reoperation were significantly different between the groups, recurrence-free survival was comparable. The 5-year overall survival rates were 38% for NCRNNELM and 55% for CRLM. In univariate analysis, a patient age of ≥60 years, endodermal origin of the primary tumor, and major complications were negative prognostic factors. Resection for NCRNNELM showed comparable results to resection for CRLM. Age, the embryological origin of the primary tumor, and the number of metastases might be the criteria for patient selection.

Purpose: Bariatric surgery is on the rise worldwide. With the desired weight loss after bariatric surgery, patients frequently develop massive skin flaps resulting in the need of abdominoplasty. In these patients, this surgical technique is frequently associated with perioperative complications. Strategies to minimize complications are sought after. The objective of our study was to compare two different dissection techniques and their impact on postoperative outcome., Methods: We included 66 patients in our study who underwent abdominoplasty after massive weight loss following bariatric surgery. In group 1, abdominoplasty was performed using the conventional technique of diathermia (n = 20). In group 2, abdominoplasty was performed using LigaSure Impact™ (n = 46). The duration of the surgical procedure and perioperative complications were recorded as primary endpoints. Secondary endpoints were length of hospital stay and assessment of additional risk factors., Results: Baseline characteristics were comparable between groups. The duration of surgery was significantly shorter in group 2. Postoperative complications were significantly less frequent in group 2 (p = 0.0035). Additional risk factors, e.g., smoking and diabetes mellitus, were not associated with increased rates of perioperative complications., Conclusions: The choice of technical device for dissection in abdominoplasty alone will not guarantee minimized complication rates. Yet, the utilization of LigaSure Impact™ in refined surgical techniques may facilitate reduced rates of complications, especially wound infections, and a shortened duration of surgery., (© 2021. The Author(s).)

We report on the temperature- and structural-dependent optical properties and photophysics of a set of boron dipyrromethene (BODIPY) dyes with different substitution patterns of their meso-aryl subunit. Single-crystal X-ray diffraction analysis of the compounds enabled a classification of the dyes into a sterically hindered and a unhindered group. The steric hindrance refers to a blocked rotational motion of the aryl subunit around the bond connecting this moiety to the meso-position of the BODIPY core. The energy barriers related to this rotation were simulated by DFT calculations. As follows from the relatively low rotational barrier calculated to about 17 kcal/mol, a free rotation is only possible for sterically unhindered compounds. Rotational barriers of more than 40 kcal/mol determined for the sterically hindered compounds suggest an effective freezing of the rotational motion in these molecules. With the aid of temperature-dependent spectroscopic measurements, we could show that the ability to rotate directly affects the optical properties of our set of BODIPY dyes. This accounts for the strong temperature dependence of the fluorescence of the sterically unhindered compounds which show a drastic decrease in fluorescence quantum yield and a significant shortening in fluorescence lifetime upon heating. The optical properties of the sterically hindered compounds, however, are barely affected by temperature. Our results suggest a nonradiative deactivation of the first excited singlet state of the sterically unhindered compounds caused by a conical intersection of the potential energy surfaces of the ground and first excited state which is accessible by rotation of the meso-subunit. This is in good agreement with previously reported deactivation mechanisms. In addition, our results suggest the presence of a second nonradiative depopulation pathway of the first excited singlet state which is particularly relevant for the sterically hindered compounds.

Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired damage. This encouraged us to exploit the more acidic pH of cancerous tissue and design pH-controllable singlet oxygen-generating boron-dipyrromethene (BODIPY) dyes. A pH sensitivity of the dyes is achieved by the introduction of an electronically decoupled, photoinduced electron transfer (PET)-capable subunit in meso-position of the BODIPY core. To favor triplet-state formation as required for singlet oxygen generation, iodine substituents were introduced at the chromophore core. The resulting pH-controlled singlet oxygen-generating dyes with p K a values in the physiological range were subsequently assessed regarding their potential as pH-controlled PS for PDT. Using HeLa cells, we could successfully demonstrate markedly different pH-dependent cytotoxicities upon illumination.

We present the design and fabrication of pH responsive ratiometric dual component sensor systems based on multicolor emissive upconversion nanoparticles (UCNP) and pH sensitive BODIPY dyes with tunable p K a values embedded into a polymeric hydrogel matrix. The use of NIR excitable NaYF 4 :Yb 3+ ,Tm 3+ UCNPs enables background free read-out. Furthermore, the spectrally matching optical properties of the UCNPs and the dyes allow the UCNPs to serve as excitation light source for the analyte-responsive BODIPY as well as intrinsic reference. The blue upconversion luminescence (UCL) of NaYF 4 :Yb 3+ ,Tm 3+ UCNPs excited at 980 nm, that overlaps with the absorption of the pH-sensitive fluorophore, provides reabsorption based excitation of the dye, the spectrally distinguishable green fluorescence of which is switched ON upon protonation, preventing photoinduced electron transfer (PET) within the dye moiety, and the pH-inert red UCL act as reference. The intensities ratios of the dye's fluorescence and the analyte-inert red Tm 3+ UCL correlate directly with pH, which was successfully utilized for monitoring time-dependent pH changes of a suspension of quiescent E. coli metabolizing d-glucose.

Background: Locoregional bridging treatments are commonly applied in patients with hepatocellular carcinoma (HCC) prior to liver transplantation to prevent tumor progression during waiting time. It remains unknown whether pre-transplant radioembolization treatment may increase the prevalence of hepatic artery and biliary complications post-transplant., Methods: We performed a retrospective review of 173 consecutive patients with HCC who underwent liver transplantation at our transplant center between January 2007 and December 2016., Results: Radioembolization bridging treatment was applied in 42 patients while 131 patients received other or no forms of bridging treatment. The overall prevalence of intra-operative and early post-operative hepatic artery complications was 9.5% in the radioembolization group and 9.2% in the control group (P = 1.000). Biliary complications were significantly less frequent in the radioembolization group (4.8% vs 17.6%, P = .0442). In multivariable analysis, radioembolization was not significantly associated with an increased risk of arterial complications. Considering biliary complications, radioembolization bridging treatment was the only factor significantly associated with decreased odds (OR 0.187 (0.039, 0.892), P = .036)., Conclusions: Radioembolization is not associated with higher odds of hepatic artery complications following liver transplantation. There may even be a protective effect regarding biliary complications. Radioembolization as a bridge to transplantation may effectively be applied without compromising successful liver transplantation., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The demand for transplantable organs exceeds donor organ supply. Transplantation of organs from donors with a history of malignancy remains controversial and the transmission of cancer in liver transplant recipients has not been sufficiently examined., Methods: From 2002 until 2017, 83 livers from donors with a history of malignancy were transplanted at the University Hospital Essen, Germany. Donor and recipient data, type of malignancy, tumor-free interval at organ procurement, and follow-up data were analyzed., Results: Nine different tumor sites (central nervous system [n = 27], genitourinary [n = 24], breast [n = 10], skin [n = 8], colorectal [n = 5], lung [n = 3], hemato-oncological [n = 3], thyroid [n = 2], and larynx [n = 1]) were detected in 83 donors. The majority (58%) of donors had tumor-free intervals of less than 5 years versus 19% of 6 to 10 years versus 23% over 10 years. The risk of tumor transmission from donors was assessed as low in 44 (53%), intermediate in 28 (34%), and high in 11 (13%) cases. During median follow-up of 19.9 (0-155) months, none of the recipients developed donor-transmitted malignancy., Conclusions: Liver transplantation with organs from donors with a medical history of malignancy is feasible, and the risk of donor-transmitted malignancy appears to be low in this single-center analysis. A careful selection of donors remains mandatory and can expand the donor pool., Competing Interests: The authors declare no funding or conflicts of interest.

BACKGROUND Bridging treatments are employed in liver transplant waitlist patients with hepatocellular carcinoma (HCC) because of the risk of tumor progression during the waiting time. Radioembolization is mostly employed in the control of large or multifocal HCCs when other locoregional treatment modalities cannot be applied because of the number or size of lesions. The purpose of this study was to evaluate our experience with the use of radioembolization as a bridge to transplantation and its effect on tumor recurrence and survival after liver transplantation. MATERIAL AND METHODS A retrospective review of 40 consecutive patients with HCC who underwent liver transplantation after radioembolization bridging treatment between January 2007 and December 2015 at the University Hospital Essen, Germany, was performed. Patients' characteristics, alpha-fetoprotein (AFP) levels, pathologic tumor response, tumor recurrence rate, and survival rates were examined through chart review. RESULTS Histopathological examination of the explanted liver specimen revealed complete tumor necrosis in 17 specimens, partial necrosis in 18 specimens, and no significant necrosis in five specimens. Median overall survival was 46 months. Nine patients developed recurrent HCC. Median time from liver transplantation to diagnosis of tumor recurrence was 15 months. There was a trend towards a lower risk of tumor recurrence for patients with complete necrosis on explant specimens. Patients with tumor recurrence demonstrated statistically significantly higher pre- and post-treatment AFP levels (p=0.0234 and p=0.0236) and statistically significantly more frequently microvascular invasion (p=0.0163). CONCLUSIONS Histopathological assessment of explanted livers revealed at least partial necrosis in 87.5% of patients. Patients with successful bridging treatment, i.e. complete necrosis of explant specimens, demonstrate a trend towards a lower risk of tumor recurrence.

Purpose: Women represent up to 60 % of students entering the medical profession in many countries in the world. However, the proportion of women to men is not accordingly balanced among surgical residents and especially in leadership positions in surgery. Therefore, we investigated the career goals as well as family and lifestyle priorities of female surgeons in German liver transplant centers., Methods: A standardized questionnaire was developed using the web-based survey tool SurveyMonkey®. Questionnaires were distributed electronically to 180 female surgeons in 24 German liver transplant centers. A total of 81 completed questionnaires were analyzed., Results: Female surgeons in German liver transplant centers are eager to assume leadership positions and do not wish to follow traditional role models. After finishing training, most female surgeons plan to continue working at a university hospital. About 80 % of the respondents intend to continue working full time and wish to combine career and family., Conclusions: This is the first survey on career intentions of female surgeons in Germany. In the face of gender changes in the medical profession, we were able to demonstrate that female surgeons are willing to fill leadership positions. Individual and institutional creative modifications are necessary if the advancement of women in surgery is to be promoted.

Background: International data on training, work, and lifestyle of transplant physicians and surgeons are scarce. Such data might help in development of uniform education paths and provide insights for young clinicians interested in this field. This study aimed at the evaluation of these data in all transplant-associated medical disciplines., Methods: A survey on professional and academic training, workload, and lifestyle was generated. The questionnaire was distributed to all members of the German Transplant Association (DTG), utilizing the tool SurveyMonkey(®) ., Results: A total of 127 members of the DTG responded (male/female 66.1%/33.9%, 45.8±10.3 years). The majority had been working in transplant medicine for more than 10 years (61.9%). Fifteen respondents (11.8%) obtained an official European certification (European Union of Medical Specialists). A total of 57 (48.3%) respondents worked full time on research during training. The research focus was clinical for most respondents (n=72, 61.5%). An average working time of 62±1.5 h/wk was reported. Fifty-eight percent of all respondents complained of inadequate remuneration and 50% reported inadequate acknowledgment of their professional performance., Conclusion: This is the first study reporting characteristics of training, work, and lifestyle in an interdisciplinary cohort of German transplant physicians and surgeons. Enormous efforts in clinical and research work were reported, associated with high rates of professional and financial dissatisfaction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Infections are a major cause for morbidity and mortality in liver transplant recipients. So far there has been no study systematically investigating the correlation between the MELD (Model for End-Stage Liver Disease) scoring system and complications caused by infections. The aim of the present retrospective study was to evaluate the impact of the pretransplant MELD score on incidence and mortality of pneumonia and septicemia in liver transplant recipients., Material and Methods: The clinical courses of 201 liver transplant recipients between 12/2006 and 3/2009 were recorded and analyzed on the basis of chart review. Patients were stratified into three groups (pretransplant MELD score: group I 6-20, group II ≥ 21-30, group III ≥ 31-40) and compared in terms of incidence of infection and survival., Results: The mean pretransplant MELD score was 22 ± 12. There were 81 patients in group I, 65 patients in group II, and 55 patients in group III. There was no difference in incidence of infections between the MELD groups. However, septicemia-associated mortality was significantly higher in group III., Conclusions: A high MELD score is not associated with higher incidence of infections but it is associated with a significantly higher mortality in the case of septicemia. Prevention of infections is of utmost importance, especially in liver transplant recipients with high MELD scores.

Two pairs of divalent and tetravalent porphyrin building blocks carrying the complementary supramolecular crown ether/secondary ammonium ion binding motif have been synthesized and their derived pseudorotaxanes have been studied by a combination of NMR spectroscopy in solution and ESI mass spectrometry in the gas phase. By simple mixing of the components the formation of discrete dimeric and trimeric (metallo)porphyrin complexes predominates, in accordance to binding stoichiometry, while the amount of alternative structures can be neglected. Our results illustrate the power of multivalency to program the multicomponent self-assembly of specific entities into discrete functional nanostructures.

Background: One of the main reasons for organ shortage is insufficient education on organ donation. Knowledgeable medical students could share the information with friends and families resulting in a positive attitude to organ donation of the general public., Methods: During six consecutive years (2009 to 2014), we conducted a voluntary, anonymous educational intervention study on organ donation among fourth year medical students in the course of the main surgery lecture at the University of Essen, Germany., Results: Questionnaires of 383 students were analyzed. Prior to the specific lecture on organ donation, 64% of the students carried a signed organ donor card with the intention to donate. Further information regarding organ donation was required by 37% of the students. The request for further information was statistically significantly higher among students without a donor card compared to organ donor card carriers (P < 0.0001). After the lecture, the number of students requiring further information decreased statistically significantly to 19% (P < 0.0001)., Conclusions: Already a 45-minute lecture for fourth year medical students significantly decreases their request for further information on organ donation and improves their attitude to organ donation. Continued training on organ donation will help medical students to become disseminators for this important topic in our society.

Background: Organ shortage remains a major challenge in transplantation medicine. The aim of this study was to analyze the public's willingness to donate organs and to observe whether increased knowledge about organ donation has an effect on the attitude toward organ donation. The study in particular tested the efficacy of using electronic communication as a means to distribute information., Methods: In 2011, an Email invitation to participate in a survey was sent to the employees of the University Duisburg-Essen. The survey consisted of a two-piece questionnaire with an informational intervention on organ donation between the questionnaires. The technical design ensured that interviewees remained anonymous and could participate only once., Results: In total, 1,818 interviewees completed the questionnaire. Of the respondents, 42% were organ-donor card holders (which was consistent among genders and age groups), whereas 87% of the interviewees would support an organ donation for themselves. Of the interviewees who did not possess an organ-donor card, 67% were positively inclined toward holding one in future after reading the interventional information., Conclusions: The considerable improvement in attitude toward carrying an organ-donor card after reading the information illustrates the effectiveness of distributing concise information on organ donation. To increase the willingness to donate organs, it is of great importance to inform the public and facilitate the documentation of a decision to donate. The present study has proven the use of Email communication to be an important asset to this process.

It has been demonstrated that intraoperative radiotherapy is a therapeutic option for patients suffering from perihilar cholangiocarcinoma. Aim of our study was to investigate vascular and nerve damages after irradiation of the liver hilum in a pig model. Twenty-four pigs underwent central bile duct resection followed by biliodigestive anastomosis. Nine pigs underwent this surgical procedure alone (group 1). Ten pigs were treated with additional intraoperative radiation therapy (IORT) of 20Gy to the liver hilum (group 2). And five pigs received operation and IORT with 40Gy to the area of anastomosis (group 3). Six weeks after operation and treatment the animals were sacrificed and histopathological examination was performed. Histology showed no vascular or nerve damage in non-irradiated perihilar tissue. Significant changes of nerve structures occurred, as well as vascular damage in large and even more in small hilar arteries in the irradiated neighboring liver tissue. In detail for small hilar arteries: intima proliferation (p ≤ .0001), endothelial swelling (p ≤ .0001), fibrinoid arterial wall necrosis (p ≤ .0001), and arterial thrombosis (p = .0079) were detected. Venous vessels did not show significant dose dependant cell damage. Overall, 20Gy as a single dose application during operation showed similar damage to vessels and nerves compared to 40Gy. A radiation dosage of 20Gy seems to be sufficient to induce necrosis due to vascular and nerve damage in potential malignant liver tissue with acceptable damage to surrounding tissue. Perineural invaded tumor cells might be diminished due to IORT.

Background: Miscellaneous clinical classifications of liver function after liver transplantation are rested upon elevation of transaminases which represent damaging of hepatocytes and with it of the liver., Case Report: We report the case of a 35-year-old man suffering from hepatocellular carcinoma in the setting of alcoholic liver cirrhosis. The patient underwent liver transplantation and developed an extreme peak of transaminases due to prolonged cold ischemia time and additional extended donor criteria. On the first postoperative day the laboratory results showed peak transaminases as follows: AST 17577 U/l and ALT 9884 U/l. Frequent ultrasound revealed no signs of vascular complications. In spite of the dramatically elevated transaminases the liver showed a good primary function and the patient was cardiopulmonary stable. The entire postoperative course was uneventful. We discharged the patient after three weeks in a very good general state of health, with normal laboratory values., Conclusions: Exclusive extreme elevation of transaminases after liver transplantation combined with adequate liver synthesis does not always require re-transplantation, if situation of the patient is stable. Nevertheless re-transplantation should be reconsidered in any case of clinical deterioration of the patient.

Invasive aspergillosis is recognized as one of the most significant opportunistic infections after liver transplantation. Diagnosis of invasive aspergillosis in transplant recipients has been proven to be challenging, and optimal approach to the treatment of invasive aspergillosis is still controversial. We here present an unusual case of Aspergillus tracheobronchitis in the setting of liver transplantation. A 47-year-old female patient with persistent dry cough after liver transplantation developed respiratory insufficiency and was readmitted to the intensive care unit 55 days after liver transplantation. A CT scan revealed subtotal tracheal stenosis; bronchoscopy was performed, and extended white mucus coverings causative of the tracheal stenosis were removed. Microbiological assessment isolated Aspergillus fumigatus. The diagnosis was obstructive Aspergillus tracheobronchitis. The patient was started on a treatment of voriconazole 200 mg orally twice daily, adjusted to a trough level of 1-4 mg/L. For further airway management, a tracheal stent had to be implanted. The patient is alive and well 28 months after liver transplantation. Invasive aspergillosis should be considered a possible etiology in liver transplant patients presenting with unspecific symptoms such as persistent dry cough. Optimal strategies for improved and early diagnosis as well as prophylaxis need to be defined.

Background: The seventh edition of the TNM classification separates extrahepatic bile duct tumors into perihilar and distal tumors and further changes the definition of the TNM classification. The impact of the seventh edition on stage-based prognostic prediction for patients with perihilar cholangiocarcinoma was evaluated., Methods: Between January 1998 and March 2010, 223 consecutive patients with perihilar cholangiocarcinoma underwent surgery at the West German Cancer Center. Median survival times were calculated for the 195 evaluable patients (excluding those with in-hospital mortality) after separate classification by both sixth and seventh editions., Results: Median overall survival was increased in patients classified using the seventh compared with the sixth edition (UICC I: 56.5 vs 23.75 months; II: 45.9 vs 31.6 months; III: 21.3 vs. 8.76 months; IV: 7.03 vs 5.93 months). The T category of the seventh edition did not alter median survival times of T1 (54.07 months) and T4 (7.83 months) cases, but median survival was prolonged for T2 patients (29.4 vs 31.6 months), and shortened for T3 patients (19.43 vs 11.8 months) staged using the seventh edition. According to Cox proportional hazards regression analysis, patient survival was better predicted by the seventh edition UICC stage and pT categories (p=0.0014 and p=0.0396, respectively), than the corresponding sixth edition categories (p=0.4376 and p=0.0926, respectively)., Conclusions: The UICC seventh edition TNM classification for perihilar cholangiocarcinoma improves separation of patients with intermediate stage tumors compared with the sixth edition. The prognostic value of the UICC staging system has been strengthened by the introduction of the seventh edition.