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Liver fibrosis progressing to cirrhosis is a major risk factor for liver cancer, impacting surgical treatment and survival. Our study focuses on the role of extracellular nicotinamide adenine dinucleotide (eNAD+) in liver fibrosis, analyzing liver disease patients undergoing surgery. Additionally, we explore NAD+'s therapeutic potential in a mouse model of extended liver resection and in vitro using 3D hepatocyte spheroids. eNAD+ correlated with aspartate transaminase (AST) and bilirubin after liver resection (AST: r = 0.2828, p = 0.0087; Bilirubin: r = 0.2584, p = 0.0176). Concordantly, post-hepatectomy liver failure (PHLF) was associated with higher eNAD+ peaks (n = 10; p = 0.0063). Post-operative eNAD+ levels decreased significantly (p < 0.05), but in advanced stages of liver fibrosis or cirrhosis, this decline not only diminished but actually showed a trend towards an increase. The expression of NAD+ biosynthesis rate-limiting enzymes, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase 3 (NMNAT3), were upregulated significantly in the liver tissue of patients with higher liver fibrosis stages (p < 0.0001). Finally, the administration of NAD+ in a 3D hepatocyte spheroid model rescued hepatocytes from TNFalpha-induced cell death and improved viability (p < 0.0001). In a mouse model of extended liver resection, NAD+ treatment significantly improved survival (p = 0.0158) and liver regeneration (p = 0.0186). Our findings reveal that eNAD+ was upregulated in PHLF, and rate-limiting enzymes of NAD+ biosynthesis demonstrated higher expressions under liver fibrosis. Further, eNAD+ administration improved survival after extended liver resection in mice and enhanced hepatocyte viability in vitro. These insights may offer a potential target for future therapies.
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Hepatectomia , Falência Hepática , NAD , NAD/metabolismo , Animais , Humanos , Camundongos , Falência Hepática/etiologia , Falência Hepática/metabolismo , Falência Hepática/patologia , Falência Hepática/cirurgia , Masculino , Hepatócitos/metabolismo , Pessoa de Meia-Idade , Feminino , Camundongos Endogâmicos C57BL , Cirrose Hepática/metabolismo , Cirrose Hepática/cirurgia , Modelos Animais de Doenças , IdosoRESUMO
Vascular surgery faces a critical demand for novel vascular grafts that are biocompatible and thromboresistant. This urgency particularly applies to bypass operations involving small caliber vessels. In the realm of tissue engineering, the development of fully vascularized organs holds great promise as a solution to organ shortage for transplantation. To achieve this, it is imperative to (re-)construct a biocompatible and non-thrombogenic vascular network within these organs. In this systematic review, we identify, classify and discuss basic principles and methods used to perform in vitro/ex vivo dynamic thrombogenicity testing of perfusable tissue engineered organs and tissues. We conducted a pre-registered systematic review of studies published in the last 23 years according to PRISMA-P Guidelines, comprising a systematic data extraction, in-depth analysis and risk of bias assessment of 116 included studies. We identified shaking (n=28), flow loop (n=17), ex vivo (arterio-venous shunt, n=33) and dynamic in vitro models (n=38) as main approaches for thrombogenicity assessment. This comprehensive review unveils a prevalent lack of standardization and serves as a valuable guide in the design of standardized experimental setups.
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BACKGROUND: Liver grafts are frequently declined due to high donor age or age mismatch with the recipient. To improve the outcome of marginal grafts, we aimed to characterize the performance of elderly vs. young liver grafts in a standardized rat model of normothermic ex vivo liver machine perfusion (NMP). METHODS: Livers from Sprague-Dawley rats aged 3 or 12 months were procured and perfused for 6 h using a rat NMP system or collected as a reference group (n = 6/group). Tissue, bile, and perfusate samples were used for biochemical, and proteomic analyses. RESULTS: All livers cleared lactate during perfusion and continued to produce bile after 6 h of perfusion (614 mg/h). Peak urea levels in 12-month-old animals were higher than in younger animals. Arterial and portal venous pressure, bile production and pH did not differ between groups. Proteomic analysis identified a total of 1477 proteins with oxidoreductase and catalytic activity dominating the gene ontology analysis. Proteins such as aldehyde dehydrogenase 1A1 and 2-Hydroxyacid oxidase 2 were significantly more present in livers of older age. CONCLUSIONS: Young and elderly liver grafts exhibited similar viability during NMP, though proteomic analyses indicated that older grafts are less resilient to oxidative stress. Our study is limited by the elderly animal age, which corresponds to mature but not elderly human age typically seen in marginal human livers. Nevertheless, reducing oxidative stress could be a promising therapeutic target in the future.
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Transplante de Fígado , Fígado , Perfusão , Proteômica , Ratos Sprague-Dawley , Animais , Fígado/metabolismo , Ratos , Perfusão/métodos , Transplante de Fígado/métodos , Proteômica/métodos , Masculino , Preservação de Órgãos/métodos , Humanos , Estresse Oxidativo , Envelhecimento/metabolismoRESUMO
Decellularized extracellular matrix (dECM) is an excellent natural source for 3D bioprinting materials due to its inherent cell compatibility. In vat photopolymerization, the use of dECM-based bioresins is just emerging, and extensive research is needed to fully exploit their potential. In this study, two distinct methacryloyl-functionalized, photocrosslinkable dECM-based bioresins were prepared from digested porcine liver dECM through functionalization with glycidyl methacrylate (GMA) or conventional methacrylic anhydride (MA) under mild conditions for systematic comparison. Although the chemical modifications did not significantly affect the structural integrity of the dECM proteins, mammalian cells encapsulated in the respective hydrogels performed differently in long-term culture. In either case, photocrosslinking during 3D (bio)printing resulted in transparent, highly swollen, and soft hydrogels with good shape fidelity, excellent biomimetic properties and tunable mechanical properties (~ 0.2-2.5 kPa). Interestingly, at a similar degree of functionalization (DOF ~ 81.5-83.5 %), the dECM-GMA resin showed faster photocrosslinking kinetics in photorheology resulting in lower final stiffness and faster enzymatic biodegradation compared to the dECM-MA gels, yet comparable network homogeneity as assessed via Brillouin imaging. While human hepatic HepaRG cells exhibited comparable cell viability directly after 3D bioprinting within both materials, cell proliferation and spreading were clearly enhanced in the softer dECM-GMA hydrogels at a comparable degree of crosslinking. These differences were attributed to the additional hydrophilicity introduced to dECM via methacryloylation through GMA compared to MA. Due to its excellent printability and cytocompatibility, the functional porcine liver dECM-GMA biomaterial enables the advanced biofabrication of soft 3D tissue analogs using vat photopolymerization-based bioprinting.
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Matriz Extracelular , Hidrogéis , Metacrilatos , Polimerização , Animais , Metacrilatos/química , Suínos , Hidrogéis/química , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Fígado , Humanos , Impressão Tridimensional , Processos Fotoquímicos , Bioimpressão/métodos , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Reagentes de Ligações Cruzadas/química , Compostos de Epóxi/químicaRESUMO
BACKGROUND: Acute necrotizing pancreatitis is still related to high morbidity and mortality rates. Minimal-invasive treatment options, such as endoscopic necrosectomy, may decrease peri-interventional morbidity and mortality. This study aims to compare the initial operative with endoscopic treatment on long-term parameters, such as endocrine and exocrine functionality, as well as mortality and recurrence rates. METHODS: We included 114 patients, of whom 69 were treated with initial endoscopy and 45 by initial surgery. Both groups were further assessed for peri-interventional and long-term parameters. RESULTS: In the post-interventional phase, patients in the group of initial surgical treatment (IST) showed significantly higher rates of renal insufficiency (p < 0.001) and dependency on invasive ventilation (p < 0.001). The in-house mortality was higher in the surgical group, with 22% vs. 10.1% in the group of patients following initial endoscopic treatment (IET; p = 0.077). In long-term follow-up, the overall mortality was 45% for IST and 31.3% for IET (p = 0.156). The overall in-hospital stay and intensive care unit (ICU) stay were significantly shorter after IET (p < 0.001). In long-term follow-up, the prevalence of endocrine insufficiency was 50% after IST and 61.7% after IET (p = 0.281). 57.1% of the patients following IST and 16.4% of the patients following IET had persistent exocrine insufficiency at that point (p = < 0.001). 8.9% of the IET and 27.6% of the IST patients showed recurrence of acute pancreatitis (p = 0.023) in the long-term phase. CONCLUSION: In our cohort, an endoscopic step-up approach led to a reduced in-hospital stay and peri-interventional morbidity. The endocrine function appeared comparable in both groups, whereas the exocrine insufficiency seemed to recover in the endoscopic group in the long-term phase. These findings advocate for a preference for endoscopic treatment of acute necrotizing pancreatitis whenever feasible.
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Pancreatite Necrosante Aguda , Humanos , Pancreatite Necrosante Aguda/cirurgia , Doença Aguda , Endoscopia , Pancreatectomia , Drenagem/efeitos adversos , Resultado do TratamentoRESUMO
INTRODUCTION: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). MATERIALS AND METHODS: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. RESULTS: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. CONCLUSION: In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Colorretais , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Hepatectomia/métodos , Colangiocarcinoma/cirurgia , Laparoscopia/métodos , Excisão de Linfonodo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/cirurgia , Sistema de Registros , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de PropensãoRESUMO
In the original publication [...].
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Solubilized, gel-forming decellularized extracellular matrix (dECM) is used in a wide range of basic and translational research and due to its inherent bioactivity can promote structural and functional tissue remodeling. The animal-derived protease pepsin has become the standard proteolytic enzyme for the solubilization of almost all types of collagen-based dECM. In this study, pepsin was compared with papain, α-amylase, and collagenase for their potential to solubilize porcine liver dECM. Maximum preservation of bioactive components and native dECM properties was used as a decisive criterion for further application of the enzymes, with emphasis on minimal destruction of the protein structure and maintained capacity for physical thermogelation at neutral pH. The solubilized dECM digests, and/or their physically gelled hydrogels were characterized for their rheological properties, gelation kinetics, GAG content, proteomic composition, and growth factor profile. This study highlights papain as a plant-derived enzyme that can serve as a cost-effective alternative to animal-derived pepsin for the efficient solubilization of dECM. The resulting homogeneous papain-digested dECM preserved its thermally triggered gelation properties similar to pepsin digests, and the corresponding dECM hydrogels demonstrated their enhanced bioadhesiveness in single-cell force spectroscopy experiments with fibroblasts. The viability and proliferation of human HepaRG cells on dECM gels were similar to those on pure rat tail collagen type I gels. Papain is not only highly effective and economically attractive for dECM solubilization but also particularly interesting when digesting human-tissue-derived dECM for regenerative applications, where animal-derived materials are to be avoided.
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Matriz Extracelular , Papaína , Ratos , Suínos , Humanos , Animais , Matriz Extracelular/química , Papaína/metabolismo , Matriz Extracelular Descelularizada , Pepsina A/análise , Pepsina A/metabolismo , Pepsina A/farmacologia , Proteômica , Hidrogéis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
To date, islet transplantation to treat type 1 diabetes mellitus remains unsuccessful in long-term follow-up, mainly due to failed engraftment and reconstruction of the islet niche. Alternative approaches, such as islet embedding structures (IESs) based on 3D printing have been developed. However, most of them have been implanted subcutaneously and only a few are intended for direct integration into the vascular system through anastomosis. In this study, we 3D printed a proof-of-concept IES using gelatin methacrylate biocompatible ink. This structure consisted of a branched vascular system surrounding both sides of a central cavity dedicated to islets of Langerhans. Furthermore, we designed a bioreactor optimized for these biological structures. This bioreactor allows seeding and perfusion experiments under sterile and physiological conditions. Preliminary experiments aimed to analyze if the vascular channel could successfully be seeded with mature endothelial cells and the central cavity with rat islets. Subsequently, the structures were used for a humanized model seeding human endothelial progenitor cells (huEPC) within the vascular architecture and human islets co-cultured with huEPC within the central cavity. The constructs were tested for hemocompatibility, suture strength, and anastomosability. The 3D printed IES appeared to be hemocompatible and anastomosable using an alternative cuff anastomosis in a simple ex vivo perfusion model. While rat islets alone could not successfully be embedded within the 3D printed structure for 3 days, human islets co-cultivated with huEPC successfully engrafted within the same time. This result emphasizes the importance of co-culture, nursing cells, and islet niche. In conclusion, we constructed a proof-of-concept 3D printed islet embedding device consisting of a vascular channel that is hemocompatible and perspectively anastomosable to clinical scale blood vessels. However, there are numerous limitations in this model that need to be overcome to transfer this technology to the bedside.
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Células Progenitoras Endoteliais , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Ratos , Humanos , Animais , Transplante das Ilhotas Pancreáticas/métodos , Técnicas de Cocultura , Impressão TridimensionalRESUMO
ABSTRACT: The mechanical traits of cancer include abnormally high solid stress as well as drastic and spatially heterogeneous changes in intrinsic mechanical tissue properties. Whereas solid stress elicits mechanosensory signals promoting tumor progression, mechanical heterogeneity is conducive to cell unjamming and metastatic spread. This reductionist view of tumorigenesis and malignant transformation provides a generalized framework for understanding the physical principles of tumor aggressiveness and harnessing them as novel in vivo imaging markers. Magnetic resonance elastography is an emerging imaging technology for depicting the viscoelastic properties of biological soft tissues and clinically characterizing tumors in terms of their biomechanical properties. This review article presents recent technical developments, basic results, and clinical applications of magnetic resonance elastography in patients with malignant tumors.
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Técnicas de Imagem por Elasticidade , Neoplasias , Humanos , Técnicas de Imagem por Elasticidade/métodos , Neoplasias/diagnóstico por imagemRESUMO
BACKGROUND: Anastomotic leakage and postoperative pancreatic fistula (POPF) may occur after pancreatic head resection, also in the setting of pancreato-gastric reconstruction. For adequate complication management, a variety of non-standardized treatments are available. Still, data on clinical evaluation of endoscopic methods remain scarce. Based on our interdisciplinary experience on endoscopic treatment of retro-gastric fluid collections after left-sided pancreatectomies, we developed an innovative endoscopic concept with internal peri-anastomotic stent placement for patients with anastomotic leakage and/or peri-anastomotic fluid collection. METHODS: Over the period of 6 years (2015-2020) we retrospectively evaluated 531 patients after pancreatic head resections at the Department of Surgery, Charité-Unversitätsmedizin Berlin. Of these, 403 received reconstruction via pancreatogastrostomy. We identified 110 patients (27.3%) with anastomotic leakage and/or peri-anastomotic fluid collection and could define four treatment groups which received either conservative treatment (C), percutaneous drainage (PD), endoscopic drainage (ED), and/or re-operation (OP). Patients were grouped in a step-up approach for descriptive analyses and in a stratified, decision-based algorithm for comparative analyses. The study's primary endpoints were hospitalization (length of hospital stay) and clinical success (treatment success rate, primary/secondary resolution). RESULTS: We characterized an institutional, post-operative cohort with heterogenous complication management following pancreato-gastric reconstruction. The majority of patients needed interventional treatments (n = 92, 83.6%). Of these, close to one-third (n = 32, 29.1%) were treated with endoscopy-guided, peri-anastomotic pigtail stents for internal drainage as either primary, secondary and/or tertiary treatment modality. Following a decision-based algorithm, we could discriminate superior primary-(77,8% vs 53.7%) and secondary success rates (85.7% vs 68.4%) as well as earlier primary resolutions (11.4 days, 95%CI (5.75-17.13) vs 37.4 days, 95%CI (27.2-47.5)] in patients receiving an endoscopic compared to percutaneous management. CONCLUSION: This study underscores the importance of endoscopy-guided approaches for adequate treatment of anastomotic leakage and/or peri-anastomotic fluid collections after pancreatoduodenectomy. We herein report a novel, interdisciplinary concept for internal drainage in the setting of pancreato-gastric reconstruction.
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Fístula Anastomótica , Pâncreas , Humanos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Endoscopia Gastrointestinal/métodos , Drenagem/métodos , Resultado do Tratamento , StentsRESUMO
Nicotinamide adenine dinucleotide (NAD+), a coenzyme for more than 500 enzymes, plays a central role in energy production, metabolism, cellular signaling, and DNA repair. Until recently, NAD+ was primarily considered to be an intracellular molecule (iNAD+), however, its extracellular species (eNAD+) has recently been discovered and has since been associated with a multitude of pathological conditions. Therefore, accurate quantification of eNAD+ in bodily fluids such as plasma is paramount to answer important research questions. In order to create a clinically meaningful and reliable quantitation method, we analyzed the relationship of cell lysis, routine clinical laboratory parameters, blood collection techniques, and pre-analytical processing steps with measured plasma eNAD+ concentrations. Initially, NAD+ levels were assessed both intracellularly and extracellularly. Intriguingly, the concentration of eNAD+ in plasma was found to be approximately 500 times lower than iNAD+ in peripheral blood mononuclear cells (0.253 ± 0.02 µM vs. 131.8 ± 27.4 µM, p = 0.007, respectively). This stark contrast suggests that cellular damage or cell lysis could potentially affect the levels of eNAD+ in plasma. However, systemic lactate dehydrogenase in patient plasma, a marker of cell damage, did not significantly correlate with eNAD+ (n = 33; r = -0.397; p = 0.102). Furthermore, eNAD+ was negatively correlated with increasing c-reactive protein (CRP, n = 33; r = -0.451; p = 0.020), while eNAD+ was positively correlated with increasing hemoglobin (n = 33; r = 0.482; p = 0.005). Next, variations in blood drawing, sample handling and pre-analytical processes were examined. Sample storage durations at 4°C (0-120 min), temperature (0° to 25°C), cannula sizes for blood collection and tourniquet times (0 - 120 s) had no statistically significant effect on eNAD+ (p > 0.05). On the other hand, prolonged centrifugation (> 5 min) and a faster braking mode of the centrifuge rotor (< 4 min) resulted in a significant decrease in eNAD+ levels (p < 0.05). Taken together, CRP and hemoglobin appeared to be mildly correlated with eNAD+ levels whereas cell damage was not correlated significantly to eNAD+ levels. The blood drawing trial did not show any influence on eNAD+, in contrast, the preanalytical steps need to be standardized for accurate eNAD+ measurement. This work paves the way towards robust eNAD+ measurements, for use in future clinical and translational research, and provides an optimized hands-on protocol for reliable eNAD+ quantification in plasma.
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(1) Background: Sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy is associated with unfavorable outcomes after partial hepatectomy for colorectal liver metastases (CLM). Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), may prevent SOS development. We investigated the impact of VEGF-inhibition on the development of SOS in a murine model. (2) Methods: Male wild-type and CD39-null mice received oxaliplatin, additional anti-VEGF (OxAV), or controls, and were sacrificed or subjected to major partial hepatectomy (MH). Specimen were used for histological analysis of SOS. Liver damage was assessed by plasma transaminases. The VEGF pathway was elucidated by quantitative PCR of liver tissue and protein analysis of plasma. (3) Results: Mice treated with oxaliplatin developed SOS. Concomitant anti-VEGF facilitated a reduced incidence of SOS, but not in CD39-null mice. SOS was associated with increased plasma VEGF-A and decreased hepatocyte growth factor (HGF). After OxAV treatment, VEGF-R2 was upregulated in wild-type but downregulated in CD39-null mice. Oxaliplatin alone was associated with higher liver damage after MH than in mice with concomitant VEGF-inhibition. (4) Conclusions: We established a murine model of oxaliplatin-induced SOS and provided novel evidence on the protective effect of VEGF-inhibition against the development of SOS that may be associated with changes in the pathway of VEGF and its receptor VEGF-R2.
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(1) Background: Perineural invasion (PNI) is a common characteristic of pancreatic ductal adenocarcinoma (PDAC) and is present in most resection margins. We hypothesized that curative pancreatic tumor resection with long-term survival could only be achieved in PNI-negative patients. (2) Material and Methods: A retrospective investigation of PDAC patients who underwent curative-intended surgery during the period 2008 to 2019 was performed at our institution. (3) Results: We identified 571 of 660 (86.5%) resected patients with well-annotated reports and complete datasets. Of those, 531 patients (93%) exhibited tumors with perineural invasion (Pn1), while 40 (7%) were negative for PNI (Pn0). The majority of patients in the Pn1 group presented advanced tumor stage and positive lymph node infiltration. Patients in the Pn0 group showed an improved disease-free and long-term survival compared to the Pn1 group (p < 0.001). Subgroup analysis of all R0-resected patients indicated improved long-term survival and disease-free survival of R0 Pn0 patients when compared to R0 Pn1 patients (p < 0.001). (4) Conclusion: Our study confirmed that Pn0 improves the long-term survival of PDAC-resected cancer patients. Furthermore, PNI significantly challenges the long-term survival of formally curative (R0) resected patients. We provide new insights into the dynamics of PNI in pancreatic cancer patients which are needed to define subgroups of patients for risk stratification and multimodal treatment strategies.
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BACKGROUND: Obesity in the recipient is linked to inferior transplant outcome. Consequently, access to kidney transplantation (KT) is often restricted by body mass index (BMI) thresholds. Bariatric surgery (BS) has been established as a superior treatment for obesity compared to conservative measures, but it is unclear whether it is beneficial for patients on the waiting list. METHODS: A national survey consisting of 16 questions was sent to all heads of German KT centers. Current situation of KT candidates with obesity and the status of BS were queried. RESULTS: Center response rate was 100%. Obesity in KT candidates was considered an important issue (96.1%; n = 49/51) and 68.6% (n = 35/51) of departments responded to use absolute BMI thresholds for KT waiting list access with ≥ 35 kg/m2 (45.1%; n = 23/51) as the most common threshold. BS was considered an appropriate weight loss therapy (92.2%; n = 47/51), in particular before KT (88.2%; n = 45/51). Sleeve gastrectomy was the most favored procedure (77.1%; n = 37/51). Twenty-one (41.2%) departments responded to evaluate KT candidates with obesity by default but only 11 (21.6%) had experience with ≥ n = 5 transplants after BS. Concerns against BS were malabsorption of immunosuppressive therapy (39.2%; n = 20/51), perioperative morbidity (17.6%; n = 9/51), and malnutrition (13.7%; n = 7/51). CONCLUSIONS: Obesity is potentially limiting access for KT. Despite commonly used BMI limits, only few German centers consider BS for obesity treatment in KT candidates by default. A national multicenter study is desired by nearly all heads of German transplant centers to prospectively assess the potentials, risks, and safety of BS in KT waitlisted patients.
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Cirurgia Bariátrica , Transplante de Rim , Obesidade Mórbida , Cirurgia Bariátrica/métodos , Índice de Massa Corporal , Alemanha/epidemiologia , Humanos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Robotic pancreatic surgery (RPS) is associated with high intraoperative costs compared to open pancreatic surgery (OPS). However, it remains unclear whether several advantages of RPS such as reduced surgical trauma and a shorter postoperative recovery time could lead to a reduction in total costs outweighing the intraoperative costs. The study aimed to compare patients undergoing OPS and RPS with regards to cost-effectiveness in a propensity score-matched (PSM) analysis. METHODS: Patients undergoing OPS and RPS between 2017 and 2019 were included in this monocentric, retrospective analysis. The controlling department provided financial data (costs and revenues, net loss/profit). A propensity score-matched analysis was performed or OPS and RPS (matching criteria: age, American society of anesthesiologists (ASA) score, gender, body mass index (BMI), and type of pancreatic resection) with a caliper 0.2. RESULTS: In total, 272 eligible OPS cases were identified, of which 252 met all inclusion criteria and were thus included in the further analysis. The RPS group contained 92 patients. The matched cohorts contained 41 patients in each group. Length of hospital stay (LOS) was significantly shorter in the RPS group (12 vs. 19 days, p = 0.003). Major postoperative morbidity (Dindo/Clavien ≥ 3a) and 90-day mortality did not differ significantly between OPS and RPS (p > 0.05). Intraoperative costs were significantly higher in the RPS group than in the OPS group (7334 vs. 5115, p < 0.001). This was, however, balanced by other financial categories. The overall cost-effectiveness tended to be better when comparing RPS to OPS (net profit-RPS: 57 vs. OPS: - 2894, p = 0.328). Binary logistic regression analysis revealed major postoperative complications, longer hospital stay, and ASA scores < 3 were linked to the risk of net loss (i.e., costs > revenue). CONCLUSIONS: Surgical outcomes of RPS were similar to those of OPS. Higher intraoperative costs of RPS are outweighed by advantages in other categories of cost-effectiveness such as decreased lengths of hospital stay.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Análise Custo-Benefício , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
BACKGROUND, OBJECTIVES: In recent years, ERAS treatment pathways have found their way into many surgical fields, as they reduce complications and accelerate postoperative recovery. For thoracic surgery, the first ERAS guidelines were published by the ERAS Society and the European Society of Thoracic Surgeons (ESTS) in 2019. We have now evaluated how ERAS-items are implemented in clinical practice by using an online survey. MATERIAL AND METHODS: An online survey was conducted from 12/5/2021 until 1/6/2021. The survey consisted of 22 questions focusing on the key elements of an ERAS program according to the published ERAS guidelines. Results were summarised, descriptively analysed and put into context with the current literature. RESULTS: Of 155 thoracic surgeons, 32 responded to the survey. In 28.1% (n = 9) of the hospitals, an ERAS core unit was established, and a database to record the ERAS items existed in 15.6% (n = 5). Only 3.1% (n = 1) kept an ERAS-diary preoperatively. A so-called Carboloading was conducted at 15.6% (n = 5) of surgeons. Standard PONV prophylaxis was administered to 59.4% (n = 19) of the patients. In most cases (84.4%, n = 29), a single drain was inserted into the pleural cavity during anatomic resections. In 3% (n = 1) of the centres two drains, in 12.5% (n = 4) no drainage was placed. The most commonly applied initial suction was -10 cmH2O (75%, n = 24). Suction ≤ 2 cmH2O was used by only two of those interviewed. Drainage removal took place in 50% (n = 16) of cases between the 1st or 2nd POD, in 34.4% of cases (n = 11) between the 3rd and 4th POD and in 9.4% (n = 3) the drain remained longer than the 4th POD. The first postoperative mobilisation took place in 71.9% (n = 23) of the centres on the day of the operation. CONCLUSIONS: The implementation of ERAS guidelines varies in Germany between centres. Certain perioperative processes are covered sufficiently, but the implementation of key features of ERAS is yet to be fully established in clinical practice. The first steps in this direction have already been taken and lay the foundation for cooperation across centres.
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Cirurgiões , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Alemanha , Humanos , Tempo de Internação , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Inquéritos e Questionários , Procedimentos Cirúrgicos Torácicos/efeitos adversosRESUMO
INTRODUCTION: In pediatric liver transplantation (pLT), hepatic artery thrombosis (HAT) is associated with inferior transplant outcome. Hepatic artery reconstruction (HAR) using an operating microscope (OM) is considered to reduce the incidence of HAT. METHODS: HAR using an OM was compared to a historic cohort using surgical loupes (SL) in pLT performed between 2009 and 2020. Primary endpoint was the occurrence of HAT. Secondary endpoints were 1-year patient and graft survival determined by Kaplan-Meier analysis and complications. Multivariate analysis was used to identify independent risk factors for HAT and adverse events. RESULTS: A total of 79 pLTs were performed [30 (38.0%) living donations; 49 (62.0%) postmortem donations] divided into 23 (29.1%) segment 2/3, 32 (40.5%) left lobe, 4 (5.1%) extended right lobe, and 20 (25.3%) full-size grafts. One-year patient and graft survival were both 95.2% in the OM group versus 86.2% and 77.8% in the SL group (p = .276 and p = .077). HAT rate was 0% in the OM group versus 24.1% in the SL group (p = .013). One-year patient and graft survival were 64.3% and 35.7% in patient with HAT, compared to 93.9% and 92.8% in patients with no HAT (both p < .001). Multivariate analysis revealed HAR with SL (p = .022) and deceased donor liver transplantation (DDLT) (p = .014) as independent risk factors for HAT. The occurrence of HAT was independently associated with the need for retransplantation (p < .001) and biliary leakage (p = .045). CONCLUSION: In pLT, the use of an OM is significantly associated to reduce HAT rate, biliary complications, and graft loss and outweighs the disadvantages of delayed arterial perfusion and prolonged warm ischemia time (WIT).
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Artéria Hepática/cirurgia , Transplante de Fígado , Trombose/prevenção & controle , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Procedimentos de Cirurgia Plástica , Fatores de Risco , Taxa de Sobrevida , Procedimentos Cirúrgicos VascularesRESUMO
INTRODUCTION: Establishing a sufficient pancreatico-enteric anastomosis remains one of the most important challenges in open single stage pancreatoduodenectomy as they are associated with persisting morbidity and mortality. Applicability on a robotic-assisted approach, however, even increases the requirements. With this analysis we introduce a dorsal-incision-only invagination type pancreatogastrostomy (dioPG) to the field of robotic assistance having been previously proven feasible in the field of open pancreatoduodenectomy and compare initial results to the open approach by means of morbidity and mortality. METHODS: An overall of 142 consecutive patients undergoing reconstruction via the novel dioPG, 38 of them in a robotic-assisted and 104 in an open approach, was identified and further reviewed for perioperative parameters, complications and mortality. RESULTS: We observed a comparable R0-resection rate (p = 0.448), overall complication rate (p = 0.52) and 30-day mortality (p = 0.71) in both groups. Rates of common complications, such as postoperative pancreatic fistula (p = 0.332), postoperative pancreatic hemorrhage (p = 0.242), insufficiency of pancreatogastrostomy (p = 0.103), insufficiency of hepaticojejunostomy (p = 0.445) and the re-operation rate (p = 0.103) were comparable. The procedure time for the open approach was significantly shorter compared to the robotic-assisted approach (p = 0.024). DISCUSSION: The provided anastomosis appeared applicable to a robotic-assisted setting resulting in comparable complication and mortality rates when compared to an open approach. Nevertheless, also in the field of robotic assistance establishing a predictable pancreatico-enteric anastomosis remains the most challenging aspect of modern single-stage pancreatoduodenectomy and requires expertise and experience.
Assuntos
Pancreaticoduodenectomia , Procedimentos Cirúrgicos Robóticos , Anastomose Cirúrgica/efeitos adversos , Humanos , Pâncreas/cirurgia , Fístula Pancreática/complicações , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Operatória/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
BACKGROUND: Since autologous veins are unavailable when needed in more than 20% of cases in vascular surgery, the production of personalized biological vascular grafts for implantation has become crucial. Surface modification of decellularized xenogeneic grafts with vascular cells to achieve physiological luminal coverage and eventually thromboresistance is an important prerequisite for implantation. However, ex vivo thrombogenicity testing remains a neglected area in the field of tissue engineering of vascular grafts due to a multifold of reasons. METHODS: After seeding decellularized bovine carotid arteries with human endothelial progenitor cells and umbilical cord-derived mesenchymal stem cells, luminal endothelial cell coverage (LECC) was correlated with glucose and lactate levels on the cell supernatant. Then a closed loop whole blood perfusion system was designed. Recellularized grafts with a LECC > 50% and decellularized vascular grafts were perfused with human whole blood for 2 h. Hemolysis and complete blood count evaluation was performed on an hourly basis, followed by histological and immunohistochemical analysis. RESULTS: While whole blood perfusion of decellularized grafts significantly reduced platelet counts, platelet depletion from blood resulting from binding to re-endothelialized grafts was insignificant (p = 0.7284). Moreover, macroscopic evaluation revealed thrombus formation only in the lumen of unseeded grafts and histological characterization revealed lack of CD41 positive platelets in recellularized grafts, thus confirming their thromboresistance. CONCLUSION: In the present study we were able to demonstrate the effect of surface modification of vascular grafts in their thromboresistance in an ex vivo whole blood perfusion system. To our knowledge, this is the first study to expose engineered vascular grafts to human whole blood, recirculating at high flow rates, immediately after seeding.