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Biosensors & Bioelectronics Oct 2024The quest to reduce kidney transplant rejection has emphasized the urgent requirement for the development of non-invasive, precise diagnostic technologies. These...
The quest to reduce kidney transplant rejection has emphasized the urgent requirement for the development of non-invasive, precise diagnostic technologies. These technologies aim to detect antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR), which are asymptomatic and pose a risk of potential kidney damage. The protocols for managing rejection caused by ABMR and TCMR differ, and diagnosis has traditionally relied on invasive biopsy procedures. Therefore, a convergence system using a nano-sensing chip, Raman spectroscopy, and AI technology was introduced to facilitate diagnosis using serum samples obtained from patients with no major abnormality, ABMR, and TCMR after kidney transplantation. Tissue biopsy and Banff score analysis were performed across the groups for validation, and 5 μL of serum obtained at the same time was added onto the Au-ZnO nanorod-based Surface-Enhanced Raman Scattering sensing chip to obtain Raman spectroscopy signals. The accuracy of machine learning algorithms for principal component-linear discriminant analysis and principal component-partial least squares discriminant analysis was 93.53% and 98.82%, respectively. The collagen (an indicative of kidney injury), creatinine, and amino acid-derived signals (markers of kidney function) contributed to this accuracy; however, the high accuracy was primarily due to the ability of the system to analyze a broad spectrum of various biomarkers.
Topics: Kidney Transplantation; Humans; Spectrum Analysis, Raman; Graft Rejection; Machine Learning; Biosensing Techniques; Nanotubes; Male; Gold; Biomarkers; Middle Aged; Female; Adult
PubMed: 38924813
DOI: 10.1016/j.bios.2024.116523 -
International Journal of Cancer Jun 2024Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in...
Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.
PubMed: 38924078
DOI: 10.1002/ijc.35046 -
Transplant International : Official... 2024In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their...
In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.
Topics: Humans; Netherlands; Male; Female; Tissue and Organ Procurement; Pancreas Transplantation; Kidney Transplantation; Retrospective Studies; Liver Transplantation; Graft Survival; Middle Aged; Adult; Risk Factors; Tissue Donors
PubMed: 38919904
DOI: 10.3389/ti.2024.12989 -
Annals of Surgery Jun 2024To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past five decades.
OBJECTIVE
To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past five decades.
BACKGROUND
The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care.
METHODS
A single-center retrospective review of 2,500 pancreas transplants performed over >50 years in bivariate and multivariable models. Transplants were divided into six eras; outcomes are presented for the entire cohort and by era.
RESULTS
All measures of patient and graft survival improved progressively through the six transplant eras. The overall death censored (DC) pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year DC pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time.
CONCLUSIONS
Pancreas outcomes have significantly improved over time via sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.
PubMed: 38916985
DOI: 10.1097/SLA.0000000000006415 -
Journal of Visualized Experiments : JoVE Jun 2024Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet...
Pancreatic islet transplantation is an emerging treatment for type I diabetes; however, it is limited by donor matching and availability. Porcine islet xenotransplantation offers a promising alternative to allotransplantation, with the potential for large-scale production of on-demand, functional islets. The yield and viability of isolated islets is highly susceptible to the quality of the donor pancreas and the method of procurement, particularly the duration of warm-ischemia time. To improve organ preservation and subsequent islet yield and viability, we have developed a protocol for surgical perfusion and resection of the porcine pancreas. This protocol employs direct infrarenal aortic cannulation and organ perfusion to both minimize warm-ischemia time and simplify the procedure for operators who do not have extensive surgical expertise. Subsequent arterial perfusion of the pancreas via the aorta flushes stagnant blood from the microvasculature, thereby reducing thrombosis and oxidative damage to the tissue. This manuscript provides a detailed protocol for surgical perfusion and resection of the porcine pancreas, followed by islet isolation and purification.
Topics: Animals; Swine; Islets of Langerhans; Islets of Langerhans Transplantation; Perfusion; Pancreas; Transplantation, Heterologous
PubMed: 38912778
DOI: 10.3791/66350 -
Transplantation Direct Jul 2024Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to...
BACKGROUND
Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors.
METHODS
ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed.
RESULTS
Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; = 0.021). The IEQ ( < 0.001) and percent trapped ( < 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity ( = 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively ( = 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30-0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; = 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%-7%) (MAiD = 6.3% versus DCD-III = 6.1%; = 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; = 0.229) did not differ.
CONCLUSIONS
ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.
PubMed: 38911274
DOI: 10.1097/TXD.0000000000001667 -
Pancreas Jun 2024
PubMed: 38904670
DOI: 10.1097/MPA.0000000000002382 -
Trials Jun 2024Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy,...
Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.
BACKGROUND
Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial.
METHODS
This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment.
DISCUSSION
The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained.
TRIAL REGISTRATION
Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Pancreatectomy; Time Factors; Quality of Life; Prospective Studies; Multicenter Studies as Topic; Treatment Outcome; Predictive Value of Tests; Netherlands; United Kingdom; Research Design; Early Detection of Cancer
PubMed: 38902836
DOI: 10.1186/s13063-024-08223-5 -
Abdominal Radiology (New York) Jun 2024Pancreas transplantation is a complex surgical procedure performed to restore normoglycemia in patients with type 1 diabetes and includes whole/segmental organ... (Review)
Review
Pancreas transplantation is a complex surgical procedure performed to restore normoglycemia in patients with type 1 diabetes and includes whole/segmental organ transplant and islet cell transplantation (ICT). In the United States, simultaneous pancreas-kidney transplant (SPK) is most commonly performed due to the higher occurrence of end-stage renal disease in diabetic patients. Understanding the surgical technique and postoperative anatomy is imperative for effective and accurate surveillance following transplantation. Imaging plays an essential role in patients with pancreatic transplants and is often used to evaluate viability, vascular and parenchymal anatomy, and identify potential complications. Imaging techniques such as ultrasound, color and spectral Doppler, computed tomography (CT), magnetic resonance imaging (MRI), and angiography have a complementary role in the postoperative evaluation following a pancreas transplant. The common complications after a whole organ pancreas transplant include vascular thrombosis, graft rejection, pancreatitis, and infections. Complications can be classified into vascular (partial or complete venous thrombosis, arterial thrombosis, stenosis or pseudoaneurysm), parenchymal (pancreatitis, graft rejection), and bowel-related or miscellaneous causes (bowel obstruction, anastomotic leak, and peripancreatic fluid collections). Islet cell transplantation is an innovative therapy for patients with type 1 diabetes. It involves isolating insulin-producing islet cells from donor pancreas and transplanting into recipients, to provide long-term insulin independence or significantly reduce insulin requirements. In recent years, isolation techniques, immunosuppressive regimens, and post-transplant monitoring advancements have propelled ICT as a viable therapeutic option. This comprehensive review aims to provide insights into the current state-of-the-art imaging techniques discussing both normal and abnormal features following pancreas transplantation.
PubMed: 38900315
DOI: 10.1007/s00261-024-04383-9 -
Kidney International Reports Jun 2024
PubMed: 38899215
DOI: 10.1016/j.ekir.2024.04.009