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OBJECTIVE: The goal of the current study was to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) in a high-volume center. BACKGROUND: Despite RPDs prospective advantages over OPD, current evidence comparing the 2 has been limited and has prompted further investigation. The aim of this study was to compare both approaches while including the learning curve phase for RPD. METHODS: A 1:1 propensity score-matched analysis of a prospective database of RPD with OPD (2017-2022) at a high-volume center was performed. The main outcomes were overall- and pancreas-specific complications. RESULTS: Of 375 patients who underwent PD (OPD n=276; RPD n=99), 180 were included in propensity score-matched analysis (90 per group). RPD was associated with less blood loss [500 (300-800) vs 750 (400-1000) mL; P =0.006] and more patients without a complication (50% vs 19%; P <0.001). Operative time was longer [453 (408-529) vs 306 (247-362) min; P <0.001]; in patients with ductal adenocarcinoma, fewer lymph nodes were harvested [24 (18-27) vs 33 (27-39); P <0.001] with RPD versus OPD. There were no significant differences for major complications (38% vs 47%; P =0.291), reoperation rate (14% vs 10%; P =0.495), postoperative pancreatic fistula (21% vs 23%; P =0.858), and patients with the textbook outcome (62% vs 55%; P =0.452). CONCLUSIONS: Including the learning phase, RPD can be safely implemented in high-volume settings and shows potential for improved perioperative outcomes versus OPD. Pancreas-specific morbidity was unaffected by the robotic approach. Randomized trials with specifically trained pancreatic surgeons and expanded indications for the robotic approach are needed.
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Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Pontuação de Propensão , Pâncreas/cirurgia , Complicações Pós-Operatórias/etiologia , Curva de Aprendizado , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Laparoscopia/efeitos adversosRESUMO
BACKGROUND: Recently, subclassification of pancreatoduodenectomy in 4 differing types has been reported, because additional major vascular and multivisceral resections have been shown to be associated with an increased risk of postoperative morbidity and mortality. OBJECTIVE: To classify distal pancreatectomy (DP) based on the extent of resection and technical difficulty and to evaluate postoperative outcomes with regards to this classification system. METHODS: All consecutive patients who had undergone DP between 2001 and 2020 in a high-volume pancreatic surgery center were included in this study. DPs were subclassified into 4 distinct categories reflecting the extent of resection and technical difficulty, including standard DP (type 1), DP with venous (type 2), multivisceral (type 3), or arterial resection (type 4). Patient characteristics, perioperative data, and postoperative outcomes were analyzed and compared among the 4 groups. RESULTS: A total of 2135 patients underwent DP. Standard DP was the most frequently performed procedure (64.8%). The overall 90-day mortality rate was 1.6%. Morbidity rates were higher in patients with additional vascular or multivisceral resections, and 90-day mortality gradually increased with the extent of resection from standard DP to DP with arterial resection (type 1: 0.7%; type 2: 1.3%; type 3: 3%; type 4: 8.7%; P <0.0001). Multivariable analysis confirmed the type of DP as an independent risk factor for 90-day mortality. CONCLUSIONS: Postoperative outcomes after DP depend on the extent of resection and correlate with the type of DP. The implementation of the 4-type classification system allows standardized reporting of surgical outcomes after DP improving comparability of future studies.
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Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Resultado do Tratamento , Fatores de Risco , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: Our investigation on in-hospital mortality after 4474 pancreatoduodenectomies aimed to identify time-dependent risks as well as windows of opportunity to rescue patients from complications. BACKGROUND: Pancreatoduodenectomy is generally considered a safe procedure with a 1-10% perioperative mortality based on complexity and surgical volume. Yet, patients are susceptible for life-threatening complications particularly with extended resections. Recognition of distinct vulnerabilities over time while patients recover is required to permit focused monitoring, sophisticated resource allocation, and greatest surgical safety. METHODS: Patients who deceased in-hospital after pancreatoduodenectomy between 2003-2021 were retrieved from the institutional pancreatectomy registry and analyzed in detail with respect to their postoperative course. RESULTS: Among 4474 pancreatoduodenectomies, 156 patients deceased in-hospital (3.5%). When assessing root causes of mortality, we observed 3 different clusters of complications which were postpancreatectomy-specific (47.4%), visceral vasculature-associated (25.6%), or cardiopulmonary in origin (23.7%). The median times of root cause onset in the 3 categories were postoperative day (POD) 9, POD 4.5 ( P =0.008) and POD 3 ( P <0.001), and medians of in-hospital mortality were POD 31, POD 18 ( P =0.009) and POD 8 ( P <0.001), respectively. Intervals between root cause onset and mortality varied with medians of 23 days, 11 days ( P =0.017), and 1 days ( P <0.001). The 3 categories were similarly distributed between different types of surgical complexity. CONCLUSION: Postpancreatectomy-specific complications prompt almost half of in-hospital mortalities after pancreatoduodenectomy, with rather long intervals for interventions to prevent failure to rescue. In contrast, visceral vasculature-related events and cardiopulmonary complications dominate early in-hospital mortalities with short intervals until mortality, demanding rigorous management of such events or preoperative conditioning. These data externally validate a previous high-volume initiative and highlight distinct windows of opportunity to optimize perioperative safety.
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OBJECTIVE: The aim of this study was to assess indications for and report outcomes of pancreatic surgery in pediatric patients. BACKGROUND: Indications for pancreatic surgery in children are rare and data on surgical outcomes after pediatric pancreatic surgery are scarce. METHODS: All children who underwent pancreatic surgery at a tertiary hospital specializing in pancreatic surgery between 2003 and 2022 were identified from a prospectively maintained database. Indications, surgical procedures, and perioperative as well as long-term outcomes were analyzed. RESULTS: In total, 73 children with a mean age of 12.8 years (range: 4 mo to 18 y) underwent pancreatic surgery during the observation period. Indications included chronic pancreatitis (n=35), pancreatic tumors (n=27), and pancreatic trauma (n=11). Distal pancreatectomy was the most frequently performed procedure (n=23), followed by pancreatoduodenectomy (n=19), duodenum-preserving pancreatic head resection (n=10), segmental pancreatic resection (n=7), total pancreatectomy (n=3), and others (n=11). Postoperative morbidity occurred in 25 patients (34.2%), including 7 cases (9.6%) with major complications (Clavien-Dindo≥III). There was no postoperative (90-d) mortality. The 5-year overall survival was 90.5%. The 5-year event-free survival of patients with chronic pancreatitis was 85.7%, and 69.0% for patients with pancreatic tumors. CONCLUSION: This is the largest single-center study on pediatric pancreatic surgery in a Western population. Pediatric pancreatic surgery can be performed safely. Centralization in pancreatic centers with high expertise in surgery of adult and pediatric patients is important as it both affords the benefits of pancreatic surgery experience and ensures that surgical management is adapted to the specific needs of children.
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Pancreatectomia , Pancreatopatias , Humanos , Criança , Pancreatectomia/métodos , Masculino , Adolescente , Feminino , Pré-Escolar , Lactente , Pancreatopatias/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Pancreaticoduodenectomia/métodosRESUMO
BACKGROUND: Patients with pancreatic cancer and obstructive jaundice routinely undergo endoscopic stent placement (ES). It is well known that ES causes bacterial contamination and infectious complications after pancreatic resection. OBJECTIVE: To compare short-term outcomes and survival in patients undergoing pancreatic head resection after preoperative ES vs preoperative surgical drainage (SD) via T-tube insertion. METHODS: Patients with obstructive jaundice who underwent SD or ES from 2016 to 2022 were identified from a prospective database. Outcome analyses included microbiological bile contamination, overall morbidity and assessment of the overall complication burden using the Comprehensive Complication Index (CCI). Overall survival was investigated by KaplanâMeier analysis. RESULTS: A total of 55 patients with SD were identified and matched with 110 ES patients. After the primary intervention, ES patients experienced more complications (ES: 17.3% vs. SD: 3.6%; P=0.013). The overall complication burden after pancreatic resection was higher in ES patients than in SD patients (CCI: 27.2 vs. 19.9; P=0.022). Additionally, bacterial contamination of the bile was more frequent in ES patients compared to SD individuals (94.3% vs. 7.1%; P<0.001) with similar bacteria in 83.3% of postoperative abdominal infections in ES patients. While overall survival did not differ between the two groups, patients with postinterventional complications after ES had an impaired survival compared to those without complications (11.3 mo vs. 20.4 mo; P=0.03). CONCLUSION: SD for obstructive jaundice in resectable pancreatic cancer is associated with a lower overall complication burden. Additionally, patients with complications after ES experience worse overall survival. These findings indicate to rethink our standards of treatment of obstructive jaundice in patients with pancreatic cancer.
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BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P Ë0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.
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Neoplasias Hepáticas , Regeneração Hepática , Humanos , Hepatectomia/efeitos adversos , Estudos de Coortes , Veia Porta/cirurgia , Fígado/cirurgia , Fígado/patologia , Neoplasias Hepáticas/secundário , Ligadura , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Diagnosis of adenocarcinoma in the liver is a frequent scenario in routine pathology and has a critical impact on clinical decision making. However, rendering a correct diagnosis can be challenging, and often requires the integration of clinical, radiologic, and immunohistochemical information. We present a deep learning model (HEPNET) to distinguish intrahepatic cholangiocarcinoma from colorectal liver metastasis, as the most frequent primary and secondary forms of liver adenocarcinoma, with clinical grade accuracy using H&E-stained whole-slide images. METHODS: HEPNET was trained on 714,589 image tiles from 456 patients who were randomly selected in a stratified manner from a pool of 571 patients who underwent surgical resection or biopsy at Heidelberg University Hospital. Model performance was evaluated on a hold-out internal test set comprising 115 patients and externally validated on 159 patients recruited at Mainz University Hospital. RESULTS: On the hold-out internal test set, HEPNET achieved an area under the receiver operating characteristic curve of 0.994 (95% CI, 0.989-1.000) and an accuracy of 96.522% (95% CI, 94.521%-98.694%) at the patient level. Validation on the external test set yielded an area under the receiver operating characteristic curve of 0.997 (95% CI, 0.995-1.000), corresponding to an accuracy of 98.113% (95% CI, 96.907%-100.000%). HEPNET surpassed the performance of 6 pathology experts with different levels of experience in a reader study of 50 patients (P = .0005), boosted the performance of resident pathologists to the level of senior pathologists, and reduced potential downstream analyses. CONCLUSIONS: We provided a ready-to-use tool with clinical grade performance that may facilitate routine pathology by rendering a definitive diagnosis and guiding ancillary testing. The incorporation of HEPNET into pathology laboratories may optimize the diagnostic workflow, complemented by test-related labor and cost savings.
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AIM: To evaluate the quantity and quality of randomized controlled trials (RCTs) in hepatobiliary surgery and for identifying gaps in current evidences. METHODS: A systematic search was conducted in MEDLINE (via PubMed), Web of Science, and Cochrane Controlled Register of Trials (CENTRAL) for RCTs of hepatobiliary surgery published from inception until the end of 2023. The quality of each study was assessed using the Cochrane risk-of-bias (RoB) tool. The associations between risk of bias and the region and publication date were also assessed. Evidence mapping was performed to identify research gaps in the field. RESULTS: The study included 1187 records. The number and proportion of published randomized controlled trials (RCTs) in hepatobiliary surgery increased over time, from 13 RCTs (.0005% of publications) in 1970-1979 to 201 RCTs (.003% of publications) in 2020-2023. There was a significant increase in the number of studies with a low risk of bias in RoB domains (p < .01). The proportion of RCTs with low risk of bias improved significantly after the introduction of CONSORT guidelines (p < .001). The evidence mapping revealed a significant research focus on major and minor hepatectomy and cholecystectomy. However, gaps were identified in liver cyst surgery and hepatobiliary vascular surgery. Additionally, there are gaps in the field of perioperative management and nutrition intervention. CONCLUSION: The quantity and quality of RCTs in hepatobiliary surgery have increased over time, but there is still room for improvement. We have identified gaps in current research that can be addressed in future studies.
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Hepatectomia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Colecistectomia , Procedimentos Cirúrgicos do Sistema BiliarRESUMO
Muscle-wasting and disease-related malnutrition are highly prevalent in patients with chronic liver diseases (CLD) as well as in liver transplant (LT) candidates. Alterations of body composition (BC) such as sarcopenia, myosteatosis and sarcopenic obesity and associated clinical frailty were tied to inferior clinical outcomes including hospital admissions, length of stay, complications, mortality and healthcare costs in various patient cohorts and clinical scenarios. In contrast to other inherent detrimental individual characteristics often observed in these complex patients, such as comorbidities or genetic risk, alterations of the skeletal muscle and malnutrition are considered as potentially modifiable risk factors with a major clinical impact. Even so, there is only limited high-level evidence to show how these pathologies should be addressed in the clinical setting. This review discusses the current state-of-the-art on the role of BC assessment in clinical outcomes in the setting of CLD and LT focusing mainly on sarcopenia and myosteatosis. We focus on the disease-related pathophysiology of BC alterations. Based on these, we address potential therapeutic interventions including nutritional regimens, physical activity, hormone and targeted therapies. In addition to summarizing existing knowledge, this review highlights novel trends, and future perspectives and identifies persisting challenges in addressing BC pathologies in a holistic way, aiming to improve outcomes and quality of life of patients with CLD awaiting or undergoing LT.
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Composição Corporal , Transplante de Fígado , Sarcopenia , Humanos , Sarcopenia/complicações , Transplante de Fígado/efeitos adversos , Fatores de Risco , Hepatopatias/complicações , Desnutrição/complicações , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologiaRESUMO
BACKGROUND: Image-guidance promises to make complex situations in liver interventions safer. Clinical success is limited by intraoperative organ motion due to ventilation and surgical manipulation. The aim was to assess influence of different ventilatory and operative states on liver motion in an experimental model. METHODS: Liver motion due to ventilation (expiration, middle, and full inspiration) and operative state (native, laparotomy, and pneumoperitoneum) was assessed in a live porcine model (n = 10). Computed tomography (CT)-scans were taken for each pig for each possible combination of factors. Liver motion was measured by the vectors between predefined landmarks along the hepatic vein tree between CT scans after image segmentation. RESULTS: Liver position changed significantly with ventilation. Peripheral regions of the liver showed significantly higher motion (maximal Euclidean motion 17.9 ± 2.7 mm) than central regions (maximal Euclidean motion 12.6 ± 2.1 mm, p < 0.001) across all operative states. The total average motion measured 11.6 ± 0.7 mm (p < 0.001). Between the operative states, the position of the liver changed the most from native state to pneumoperitoneum (14.6 ± 0.9 mm, p < 0.001). From native state to laparotomy comparatively, the displacement averaged 9.8 ± 1.2 mm (p < 0.001). With pneumoperitoneum, the breath-dependent liver motion was significantly reduced when compared to other modalities. Liver motion due to ventilation was 7.7 ± 0.6 mm during pneumoperitoneum, 13.9 ± 1.1 mm with laparotomy, and 13.5 ± 1.4 mm in the native state (p < 0.001 in all cases). CONCLUSIONS: Ventilation and application of pneumoperitoneum caused significant changes in liver position. Liver motion was reduced but clearly measurable during pneumoperitoneum. Intraoperative guidance/navigation systems should therefore account for ventilation and intraoperative changes of liver position and peripheral deformation.
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Movimentos dos Órgãos , Pneumoperitônio , Suínos , Animais , Pneumoperitônio/diagnóstico por imagem , Pneumoperitônio/etiologia , Laparotomia , Fígado/diagnóstico por imagem , Fígado/cirurgia , RespiraçãoRESUMO
OBJECTIVE: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. BACKGROUND: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. METHODS: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). RESULTS: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. CONCLUSIONS: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery.
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Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Realidade Virtual , Humanos , Tomografia Computadorizada por Raios X/métodos , Feminino , Masculino , Hepatectomia/métodos , Hepatectomia/educação , Adulto , Adulto Jovem , Tomada de Decisão Clínica , Interface Usuário-Computador , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
BACKGROUND: Current clinical guidelines recommend antifibrinolytic treatment for liver transplantation to reduce blood loss and transfusion utilization. However, the clinical relevance of fibrinolysis during liver transplantation is questionable, a benefit of tranexamic acid (TXA) in this context is not supported by sufficient evidence, and adverse effects are also conceivable. Therefore, we tested the hypothesis that use of TXA is associated with reduced blood loss. METHODS: We performed a retrospective cohort study on patients who underwent liver transplantation between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariable and multivariable linear regression analyses were used to determine the association between TXA administration and the primary end point intraoperative blood loss and the secondary end point intra- and postoperative red blood cell (RBC) transfusions. For further secondary outcome analyses, the time to the first occurrence of a composite end point of hepatic artery thrombosis, portal vein thrombosis, and thrombosis of the inferior vena cava were analyzed using a univariable and multivariable Cox proportional hazards model. RESULTS: Data from 779 transplantations were included in the final analysis. The median intraoperative blood loss was 3000 mL (1600-5500 mL). Intraoperative TXA administration occurred in 262 patients (33.6%) with an average dose of 1.4 ± 0.7 g and was not associated with intraoperative blood loss (regression coefficient B, -0.020 [-0.051 to 0.012], P = .226) or any of the secondary end points (intraoperative RBC transfusion; regression coefficient B, 0.023 [-0.006 to 0.053], P = .116), postoperative RBC transfusion (regression coefficient B, 0.007 [-0.032 to 0.046], P = .717), and occurrence of thrombosis (hazard ratio [HR], 1.110 [0.903-1.365], P = .321). CONCLUSIONS: Our data do not support the use of TXA during liver transplantation. Physicians should exercise caution and consider individual factors when deciding whether or not to administer TXA.
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PURPOSE: Infections are common complications in patients following liver transplantation (LTX). The early diagnosis and prognosis of these infections is an unmet medical need even when using routine biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT). Therefore, new approaches are necessary. METHODS: In a prospective, observational pilot study, we monitored 30 consecutive patients daily between days 0 and 13 following LTX using the 29-mRNA host classifier IMX-BVN-3b that determine the likelihood of bacterial infections and viral infections. True infection status was determined using clinical adjudication. Results were compared to the accuracy of CRP and PCT for patients with and without bacterial infection due to clinical adjudication. RESULTS: Clinical adjudication confirmed bacterial infections in 10 and fungal infections in 2 patients. 20 patients stayed non-infected until day 13 post-LTX. IMX-BVN-3b bacterial scores were increased directly following LTX and decreased until day four in all patients. Bacterial IMX-BVN-3b scores detected bacterial infections in 9 out of 10 patients. PCT concentrations did not differ between patients with or without bacterial, whereas CRP was elevated in all patients with significantly higher levels in patients with bacterial infections. CONCLUSION: The 29-mRNA host classifier IMX-BVN-3b identified bacterial infections in post-LTX patients and did so earlier than routine biomarkers. While our pilot study holds promise future studies will determine whether these classifiers may help to identify post-LTX infections earlier and improve patient management. CLINICAL TRIAL NOTATION: German Clinical Trials Register: DRKS00023236, Registered 07 October 2020, https://drks.de/search/en/trial/DRKS00023236.
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Infecções Bacterianas , Biomarcadores , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Biomarcadores/sangue , Idoso , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/sangue , RNA Mensageiro/genética , Adulto , Proteína C-Reativa/análise , Pró-Calcitonina/sangueRESUMO
BACKGROUND: We recently demonstrated that donor-derived modified immune cells (MICs)-PBMCs that acquire immunosuppressive properties after a brief treatment-induced specific immunosuppression against the allogeneic donor when administered before kidney transplantation. We found up to a 68-fold increase in CD19 + CD24 hi CD38 hi transitional B lymphocytes compared with transplanted controls. METHODS: Ten patients from a phase 1 clinical trial who had received MIC infusions before kidney transplantation were followed to post-transplant day 1080. RESULTS: Patients treated with MICs had a favorable clinical course, showing no donor-specific human leukocyte antigen antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and seven-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively ( P <0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiologic role of regulatory B lymphocytes in donor-specific unresponsiveness. CONCLUSIONS: These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population that when administered to recipients before transplantation, may exert a beneficial effect on kidney transplants. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1), NCT02560220.
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Linfócitos B Reguladores , Transplante de Rim , Humanos , Imunossupressores/uso terapêutico , Terapia de Imunossupressão , Tolerância Imunológica , TransplantadosRESUMO
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
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Biomarcadores Tumorais , Quimiocinas , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Prognóstico , Biomarcadores Tumorais/metabolismo , Quimiocinas/metabolismo , Receptores CXCR4/metabolismo , Intervalo Livre de DoençaRESUMO
OBJECTIVE: To evaluate the outcomes of pancreatic cancer [pancreatic ductal adenocarcinoma (PDAC)] surgery with concomitant portal vein resection (PVR), focusing on the PVR type according to the International Study Group of Pancreatic Surgery (ISGPS). BACKGROUND: Surgery offers the only chance for cure in PDAC. PVR is often performed for borderline or locally advanced tumors. METHODS: Consecutive patients with PDAC operated between January 2006 and January 2018 were included. Clinicopathologic characteristics and outcomes were analyzed and tested for survival prediction. RESULTS: Of 2265 PDAC resections, 1571 (69.4%) were standard resections and 694 (30.6%) were resections with PVR, including 149 (21.5%) tangential resections with venorrhaphy (ISGPS type 1), 21 (3.0%) resections with patch reconstruction (type 2), 491 (70.7%) end-to-end anastomoses (type 3), and 33 (4.8%) resections with graft interposition (type 4). The 90-day mortality rate was 2.6% after standard resection and 6.3% after resection with PVR ( P <0.0001). Postoperative portal vein thrombosis and pancreas-specific surgical complications most frequently occurred after PVR with graft interposition (21.2% and 48.5%, respectively). In multivariable analysis, age 70 years and above, ASA stages 3/4, increased preoperative serum carbohydrate antigen 19-9, neoadjuvant treatment, total pancreatectomy, PVR, higher UICC stage, and R+ resections were significant negative prognostic factors for overall survival. Radical R0 (>1 mm) resection resulted in 23.3 months of median survival. CONCLUSIONS: This is the largest single-center, comparative cohort study of PVR in PDAC surgery, showing that postoperative morbidity correlates with the reconstruction type. When radical resection is achieved, thrombosis risk is outweighed by beneficial overall survival times of nearly 2 years.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Trombose Venosa , Humanos , Idoso , Estudos de Coortes , Veia Porta/cirurgia , Veia Porta/patologia , Pancreatectomia/métodos , Pâncreas/cirurgia , Pancreaticoduodenectomia/métodos , Trombose Venosa/patologia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
OBJECTIVE: Evaluation of the outcome after resection for distal bile duct cancer (DBC) with focus on the impact of microscopic histopathological resection status R0 (>1 mm) versus R1 (≤1 mm) vs R1 (direct). SUMMARY BACKGROUND DATA: DBC is a rare disease for which oncologic resection offers the only chance of cure. METHODS: Prospectively collected data of consecutive patients undergoing pancreaticoduodenectomy for DBC were analyzed. Histopathological resection status was classified according to the Leeds protocol for pancreatic ductal adeno carcinoma (PDAC) (PDAC; R0 >1 mm margin clearance vs R1 ≤1 mm vs R1 direct margin involvement). RESULTS: A total of 196 patients underwent pancreaticoduodenectomy for DBC. Microscopic complete tumor clearance (R0>1 mm) was achieved in 113 patients (58%). Median overall survival (OS) of the entire cohort was 37 months (5- and 10-year OS rate: 40% and 31%, respectively). After R0 resection, median OS increased to 78 months with a 5-year OS rate of 52%. Negative prognostic factors were age >70 years ( P < 0.0001, hazard ratio (HR) 2.48), intraoperative blood loss >1000 mL ( P = 0.0009, HR 1.99), pN1 and pN2 status ( P = 0.0052 and P = 0.0006, HR 2.14 and 2.62, respectively) and American Society of Anesthesiologists score >II ( P = 0.0259, HR 1.61). CONCLUSIONS: This is the largest European single-center study of surgical treatment for DBC and the first to investigate the prognostic impact of the revised PDAC resection status definition in DBC. The results show that this definition is valid in DBC and that "true" R0 resection (>1 mm) is a key factor for excellent survival. In contrast to PDAC, there was no survival difference between R1 (≤1 mm) and R1 (direct).
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Idoso , Pancreaticoduodenectomia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Pancreatectomia/métodos , Prognóstico , Carcinoma Ductal Pancreático/cirurgia , Taxa de Sobrevida , Margens de Excisão , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
OBJECTIVE: To determine perioperative and oncologic outcomes after distal pancreatectomy with en bloc resection of the celiac axis (DP-CAR). BACKGROUND: DP-CAR can be used in a selective group of patients to resect locally advanced pancreatic cancer involving the celiac axis or common hepatic artery without arterial reconstruction by preserving retrograde blood flow via the gastroduodenal artery to the liver and stomach. METHODS: We analyzed all consecutive patients who had undergone DP-CAR between May 2003 and April 2022 at a tertiary hospital specialized in pancreatic surgery and present one of the largest single-center studies. RESULTS: A total of 71 patients underwent DP-CAR. Additional venous resection (VR) of the mesenterico-portal axis was performed in 31 patients (44%) and multivisceral resection (MVR) in 42 patients (59%). Margin-free (R0) resection was achieved in 40 patients (56%). The overall 90-day mortality rate was 8.4% for the entire patient cohort. After a cumulated experience of 16 cases, the 90-day mortality dropped to 3.6% in the following 55 patients. Extended procedures with (+) additional MVR with or without (+/-) VR resulted in higher major morbidity (Clavien-Dindo ≥IIIB; standard DP-CAR: 19%; DP-CAR + MVR +/- VR: 36%) and higher 90-day mortality (standard DP-CAR: 0%; DP-CAR + MVR +/- VR: 11%). Median overall survival after DP-CAR was 28 months. CONCLUSIONS: DP-CAR is a safe and effective procedure but requires experience. Frequently, surgical resection has to be extended with MVR and VR to accomplish tumor resection, which results in promising oncologic outcomes. However, extended resections were associated with increased morbidity and mortality.
Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Artéria Celíaca/cirurgia , Artéria Celíaca/patologia , Pâncreas/cirurgia , Estômago/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: The objective of this study was to identify the indications for and report the outcomes of completion pancreatectomy (CPLP) in the postoperative course after pancreatoduodenectomy (PD). BACKGROUND: CPLP may be considered or even inevitable for damage control after PD. METHODS: A prospectively maintained database of all patients undergoing PD between 2001 and 2019 was searched for patients who underwent CPLP in the postoperative course after PD. Baseline characteristics, perioperative details, and outcomes of CPLP patients were analyzed and specific indications for CPLP were identified. RESULTS: A total of 3953 consecutive patients underwent PD during the observation period. CPLP was performed in 120 patients (3%) after a median of 10 days following PD. The main indications for CPLP included postpancreatectomy acute necrotizing pancreatitis [n=47 (39%)] and postoperative pancreatic fistula complicated by hemorrhage [n=41 (34%)] or associated with uncontrollable leakage of the pancreatoenteric anastomosis [n=23 (19%)]. The overall 90-day mortality rate of all 3953 patients was 3.5% and 37% for patients undergoing CPLP. CONCLUSIONS: Our finding that only very few patients (3%) need CPLP suggests that conservative, interventional, and organ-preserving surgical measures are the mainstay of complication management after PD. Postpancreatectomy acute necrotizing pancreatitis, uncontrollable postoperative pancreatic fistula, and fistula-associated hemorrhage are highly dangerous and represent the main indications for CPLP after PD.
Assuntos
Pancreatectomia , Pancreatite Necrosante Aguda , Humanos , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreatite Necrosante Aguda/cirurgia , Pâncreas/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: To assesses the prevalence and severity of CAS in patients undergoing PD/total pancreatectomy and its association with major postoperative complications after PD. SUMMARY OF BACKGROUND DATA: CAS may increase the risk of ischemic complications after PD. However, the prevalence of CAS and its relevance to major morbidity remain unknown. METHODS: All patients with a preoperative computed tomography with arterial phase undergoing partial PD or TP between 2014 and 2017 were identified from a prospective database. CAS was assessed based on computed tomography and graded according to its severity: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). Postoperative complications were assessed and uni- and multivariable risk analyses were performed. RESULTS: Of 989 patients, 273 (27.5%) had CAS: 177 (17.9%) with grade A, 83 (8.4%) with grade B, and 13 (1.3%) with grade C. Postoperative morbidity and 90-day mortality occurred in 278 (28.1%) patients and 41 (4.1%) patients, respectively. CAS was associated with clinically relevant pancreatic fistula ( P =0.019), liver perfusion failure ( P =0.003), gastric ischemia ( P =0.001), clinically relevant biliary leakage ( P =0.006), and intensive care unit ( P =0.016) and hospital stay ( P =0.001). Multivariable analyses confirmed grade B and C CAS as independent risk factors for liver perfusion failure; in addition, grade C CAS was an independent risk factor for clinically relevant pancreatic fistula and gastric complications. CONCLUSIONS: CAS is common in patients undergoing PD. Higher grade of CAS is associated with an increased risk for clinically relevant complications, including liver perfusion failure and postoperative pancreatic fistula. Precise radiological assessment may help to identify CAS. Future studies should investigate measures to mitigate CAS-associated risks.