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Abdominal Radiology (New York) May 2024Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective... (Review)
Review
Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications.
PubMed: 38806704
DOI: 10.1007/s00261-024-04368-8 -
The Annals of Pharmacotherapy May 2024Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV...
BACKGROUND
Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies.
OBJECTIVE
The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min.
METHODS
This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant.
RESULTS
Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease.
CONCLUSION AND RELEVANCE
Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.
PubMed: 38801191
DOI: 10.1177/10600280241255110 -
Journal of Diabetes Research 2024Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients...
Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1 (SDF-1)), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes.
Topics: Animals; Islets of Langerhans Transplantation; Diabetes Mellitus, Experimental; Myoblasts, Skeletal; Mice; Male; Insulin; Neovascularization, Physiologic; Hepatocyte Growth Factor; Mice, Inbred C57BL; Vascular Endothelial Growth Factor A; Islets of Langerhans; Chemokine CXCL12; Blood Glucose; Diabetes Mellitus, Type 1; Signal Transduction; Insulin Secretion; Cell Differentiation
PubMed: 38800586
DOI: 10.1155/2024/5574968 -
European Journal of Surgical Oncology :... Jul 2024Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging... (Observational Study)
Observational Study
INTRODUCTION
Distal Cholangiocarcinoma (dCCA) represents a challenge in hepatobiliary oncology, that requires nuanced post-resection prognostic modeling. Conventional staging criteria may oversimplify dCCA complexities, prompting the exploration of novel prognostic factors and methodologies, including machine learning algorithms. This study aims to develop a machine learning predictive model for recurrence after resected dCCA.
MATERIAL AND METHODS
This retrospective multicentric observational study included patients with dCCA from 13 international centers who underwent curative pancreaticoduodenectomy (PD). A LASSO-regularized Cox regression model was used to feature selection, examine the path of the coefficient and create a model to predict recurrence. Internal and external validation and model performance were assessed using the C-index score. Additionally, a web application was developed to enhance the clinical use of the algorithm.
RESULTS
Among 654 patients, LNR (Lymph Node Ratio) 15, neural invasion, N stage, surgical radicality, and differentiation grade emerged as significant predictors of disease-free survival (DFS). The model showed the best discrimination capacity with a C-index value of 0.8 (CI 95 %, 0.77%-0.86 %) and highlighted LNR15 as the most influential factor. Internal and external validations showed the model's robustness and discriminative ability with an Area Under the Curve of 92.4 % (95 % CI, 88.2%-94.4 %) and 91.5 % (95 % CI, 88.4%-93.5 %), respectively. The predictive model is available at https://imim.shinyapps.io/LassoCholangioca/.
CONCLUSIONS
This study pioneers the integration of machine learning into prognostic modeling for dCCA, yielding a robust predictive model for DFS following PD. The tool can provide information to both patients and healthcare providers, enhancing tailored treatments and follow-up.
Topics: Humans; Cholangiocarcinoma; Bile Duct Neoplasms; Male; Female; Machine Learning; Retrospective Studies; Middle Aged; Neoplasm Recurrence, Local; Pancreaticoduodenectomy; Artificial Intelligence; Aged; Disease-Free Survival; Neoplasm Staging; Prognosis
PubMed: 38795677
DOI: 10.1016/j.ejso.2024.108375 -
Clinical Transplantation May 2024Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite...
Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI: .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications.
Topics: Humans; Female; Male; Pancreas Transplantation; Retrospective Studies; Kidney Transplantation; Adult; Postoperative Complications; Follow-Up Studies; Risk Factors; Kidney Failure, Chronic; Graft Survival; Prognosis; Diabetes Mellitus, Type 1; Graft Rejection; Middle Aged; Reoperation; Kidney Function Tests; Survival Rate; Glomerular Filtration Rate
PubMed: 38775413
DOI: 10.1111/ctr.15339 -
Diabetes Care Jun 2024
Topics: Humans; Intensive Care Units; Blood Glucose; Vital Signs; Monitoring, Physiologic; Continuous Glucose Monitoring
PubMed: 38768336
DOI: 10.2337/dci24-0020 -
HPB : the Official Journal of the... Apr 2024There is a lack of data on the impact of donor liver function tests (LFTs) on pancreas transplantation outcomes. Understanding their contribution could expand the donor...
BACKGROUND
There is a lack of data on the impact of donor liver function tests (LFTs) on pancreas transplantation outcomes. Understanding their contribution could expand the donor pool.
METHODS
Using the UNOS database, data from January 2010-2022 was retrospectively analyzed. Multivariable cox regressions were performed to evaluate the association between LFTs (AST, ALT and total bilirubin levels), graft failure and mortality up to three years post-transplant.
RESULTS
9138 pancreas transplants were completed. Multivariate analysis showed no association between donor AST values > 500 U/L and increased rates of graft failure (p = 0.826) or mortality (p = 0.836). Similar findings were noted for donor ALT values > 500 U/L (p = 0.522 and p = 0.997, respectively). There was no correlation with graft failure (p = 0.322) or mortality (p = 0.423) for total bilirubin levels >3 mg/dL.
CONCLUSION
LFTs in the deceased pancreas donor did not increase risk of graft failure or mortality following pancreas transplantation. Elevated LFTs should not serve as absolute contraindications to transplant.
PubMed: 38763805
DOI: 10.1016/j.hpb.2024.04.012 -
Transplantation Direct Jun 2024For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined...
BACKGROUND
For patients with complicated type 1 diabetes having, for example, hypoglycemia unawareness and end-stage renal disease because of diabetic nephropathy, combined pancreas and kidney transplantation (PKT) is the therapy of choice. However, the shortage of available grafts and complex impact of risk factors call for individualized, impartial predictions of PKT and pancreas transplantation (PT) outcomes to support physicians in graft acceptance decisions.
METHODS
Based on a large European cohort with 3060 PKT and PT performed between 2006 and 2021, the 3 primary patient outcomes time to patient mortality, pancreas graft loss, and kidney graft loss were visualized using Kaplan-Meier survival curves. Multivariable Cox proportional hazards models were developed for 5- and 10-y prediction of outcomes based on 26 risk factors.
RESULTS
Risk factors associated with increased mortality included previous kidney transplants, rescue allocations, longer waiting times, and simultaneous transplants of other organs. Increased pancreas graft loss was positively associated with higher recipient body mass index and donor age and negatively associated with simultaneous transplants of kidneys and other organs. Donor age was also associated with increased kidney graft losses. The multivariable Cox models reported median C-index values were 63% for patient mortality, 62% for pancreas loss, and 55% for kidney loss.
CONCLUSIONS
This study provides an online risk tool at https://riskcalc.org/ptop for individual 5- and 10-y post-PKT and PT patient outcomes based on parameters available at the time of graft offer to support critical organ acceptance decisions and encourage external validation in independent populations.
PubMed: 38757051
DOI: 10.1097/TXD.0000000000001632 -
ACS Pharmacology & Translational Science May 2024Type 1 diabetes (T1D) is characterized by insufficient insulin secretion due to β-cell loss. Despite exogenous insulin administration being a lifesaving treatment, many...
Type 1 diabetes (T1D) is characterized by insufficient insulin secretion due to β-cell loss. Despite exogenous insulin administration being a lifesaving treatment, many patients still experience severe glycemic lability. For these patients, a β-cell replacement strategy through pancreas or pancreatic islet transplantation is the most physiological approach. However, donors' scarcity and the need for lifelong immunosuppressive therapy pose some challenges. This study proposes an innovative biomimetic pancreas, comprising β- and α-cells differentiated from human induced pluripotent stem cells (hiPSCs) embedded in a biofunctional matrix with glucose-responsive nanoparticles (NPs) encapsulating a glucagon-like peptide 1 (GLP-1) analogue, which aims to enhance the glucose responsiveness of differentiated β-cells. Herein, glucose-sensitive pH-responsive NPs encapsulating exenatide or semaglutide showed an average size of 145 nm, with 40% association efficiency for exenatide-loaded NPs and 55% for semaglutide-loaded NPs. Both peptides maintained their secondary structure after in vitro release and showed a similar effect on INS-1E cells' insulin secretion. hiPSCs were differentiated into β- and α-cells, and insulin-positive cells were obtained (82%), despite low glucose responsiveness, as well as glucagon-positive cells (17.5%). The transplantation of the developed system in diabetic mice showed promising outcomes since there was an increase in the survival rate of those animals. Moreover, diabetic mice transplanted with cells and exenatide showed a decrease in their glucose levels. Overall, the biomimetic pancreas developed in this work showed improvements in diabetic mice survival rate, paving the way for new cellular therapies for T1D that explore the synergy of nanomedicines and stem cell-based approaches.
PubMed: 38751616
DOI: 10.1021/acsptsci.4c00173 -
Transplantation Proceedings May 2024A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified...
BACKGROUND
A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation.
METHODS
First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz.
RESULTS
No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly.
CONCLUSION
Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.
Topics: Humans; Cystic Fibrosis; Pancreas Transplantation; Female; Liver Transplantation; Young Adult; Diabetes Mellitus, Type 1; Exocrine Pancreatic Insufficiency; Treatment Outcome
PubMed: 38749862
DOI: 10.1016/j.transproceed.2024.03.034