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HPB : the Official Journal of the... Jul 2024The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants...
Safety and performance of a synthetic sealant patch aimed to prevent postoperative pancreatic fistula after distal pancreatectomy (SHIELDS) - Prospective international multicenter phase II study.
OBJECTIVE
The incidence for clinically relevant postoperative pancreatic fistulas (CR-POPF) in distal pancreatectomy (DP) ranges up to 25%. None of the available sealants significantly reduce CR-POPF. A new biodegradable sealant patch was able to reduce POPF and to achieve bleeding control in a preclinical porcine DP model. The aim of this first-in-human study was to assess the safety and performance of the sealant patch.
METHODS
In this multicenter, single-arm study, 40 patients undergoing distal pancreatectomy were prospectively enrolled from 8 centers. Following surgical resection, the transection plane was closed according to the standard of care and manually covered with the sealant patch. As primary endpoint the incidence of CR-POPF up to 30-days postoperatively was evaluated. The secondary endpoints included the assessment of complications and device usability.
RESULTS
Among 40 patients after distal pancreatectomy, CR-POPF occurred in 7 (17.5%) up to postoperative day 30. No type C POPF was observed. There was no intraoperative bleeding observed after patch application.
CONCLUSION
The results of this international phase II study demonstrate promising results of a new sealant patch regarding the rate of CR-POPF. Randomized studies are now needed to confirm the superiority of the current patch as compared to the best current practice.
Topics: Humans; Pancreatic Fistula; Pancreatectomy; Prospective Studies; Female; Male; Middle Aged; Aged; Treatment Outcome; Adult; Time Factors; Aged, 80 and over
PubMed: 38653711
DOI: 10.1016/j.hpb.2024.03.002 -
Endokrynologia Polska 2024Despite advances in insulin delivery and glucose monitoring technology, prevention of the progression of secondary complications in patients with type 1 diabetes (T1DM)... (Review)
Review
Despite advances in insulin delivery and glucose monitoring technology, prevention of the progression of secondary complications in patients with type 1 diabetes (T1DM) remains a challenge. Beta cell replacement therapy in the form of islet or pancreas transplantation can restore long-term normoglycaemia with sustained periods of insulin independence among T1DM patients. However, the same genetic, behavioural, or gut microbiota-related factors that promoted autoimmunity and primary islet destruction may also affect the function of transplanted islets and the ultimate results of transplant procedures. In such cases, identifying genetic risk factors and modifying behavioural factors and those related to gut microbiota may be beneficial for the outcomes of transplant procedures. Herein, we review related literature to the identified current gap in knowledge to be addressed in future clinical trials.
Topics: Humans; Diabetes Mellitus, Type 1; Islets of Langerhans Transplantation; Gastrointestinal Microbiome; Risk Factors; Pancreas Transplantation; Diet
PubMed: 38646984
DOI: 10.5603/ep.98903 -
Cell Transplantation 2024Calcineurin inhibitors (CNIs) are critical in preventing rejection posttransplantation but pose an increased risk of post-transplant diabetes (PTD). Recent studies show...
Calcineurin inhibitors (CNIs) are critical in preventing rejection posttransplantation but pose an increased risk of post-transplant diabetes (PTD). Recent studies show that late conversion from CNIs to belatacept, a costimulation blocker, improves HbA1c in kidney transplant recipients with PTD or diabetes. This study investigates whether the observed effects on PTD stem solely from CNI withdrawal or if belatacept influences PTD independently. The study assessed the impact of tacrolimus and belatacept on insulin secretion in MIN6 cells (a beta cell line) and rat islets. Tacrolimus and belatacept were administered to the cells and islets, followed by assessments of cell viability and insulin secretion. Tacrolimus impaired insulin secretion without affecting cell viability, while belatacept showed no detrimental effects on either parameter. These findings support clinical observations of improved HbA1c upon switching from tacrolimus to belatacept. Belatacept holds promise in islet or pancreas transplantation, particularly in patients with unstable diabetes. Successful cases of islet transplantation treated with belatacept without severe hypoglycemia highlight its potential in managing PTD. Further research is needed to fully understand the metabolic changes accompanying the transition from CNIs to belatacept. Preserving insulin secretion emerges as a promising avenue for investigation in this context.
Topics: Tacrolimus; Abatacept; Animals; Rats; Insulin; Immunosuppressive Agents; Humans; Male; Insulin Secretion; Mice; Islets of Langerhans Transplantation; Cell Line; Cell Survival; Diabetes Mellitus; Islets of Langerhans
PubMed: 38646716
DOI: 10.1177/09636897241246577 -
BioRxiv : the Preprint Server For... Apr 2024Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen...
Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2 islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2.5) T cells. In mice transplanted with HLA-A2 islets, A2-CAR Tregs reduced BDC2.5 T cell engraftment, proliferation and cytokine production, and protected mice from diabetes. Tolerance to islets was systemic, including protection of the HLA-A2 endogenous pancreas. In tolerant mice, a significant proportion of BDC2.5 T cells gained FOXP3 expression suggesting that long-term tolerance is maintained by Treg generation. Thus, A2-CAR Tregs mediate linked suppression and infectious tolerance and have potential therapeutic use to simultaneously control both allo- and autoimmunity in islet transplantation.
PubMed: 38645184
DOI: 10.1101/2024.04.06.588414 -
BMJ Open Apr 2024Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to...
Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.
BACKGROUND
Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising.
METHODS
The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints.
DISCUSSION
Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial.
ETHICS AND DISSEMINATION
The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives.
TRIAL REGISTRATION NUMBER
DRKS00027474.
Topics: Humans; Pancreatectomy; Ultrasonics; Pilot Projects; Pancreas; Pancreatic Fistula; Postoperative Complications; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38637127
DOI: 10.1136/bmjopen-2023-082024 -
Avicenna Journal of Medical... 2024
PubMed: 38618507
DOI: 10.18502/ajmb.v16i2.14854 -
Transplantation Direct May 2024Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor...
BACKGROUND
Pancreas transplant volumes are limited because of poor utilization of "extended criteria grafts." Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model.
METHODS
The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients. Control grafts were subjected to cold storage (CS) in a University of Wisconsin solution for 21 to 24 h (n = 6), whereas the test group received an additional 3 h NEVP after CS of 21 h (n = 5).
RESULTS
The 3-d survival was 60% in the NEVP arm versus 0% in the control arm ( = 0.008; log rank). Graft parenchyma was 60% to 70% preserved in the NEVP arm at necropsy on gross appearance. In addition, the islet function was well preserved, and both the pancreas (including the islets) and the duodenal morphology were maintained histologically. The intravenous glucose tolerance test on the day of euthanasia was in the normoglycemic range for 80% of cases in the NEVP arm.
CONCLUSIONS
Optimization of pancreas grafts exposed to extended CS with NEVP seems promising at rescuing and reanimating these grafts for transplantation, resulting in significantly improved survival in a porcine pancreas transplant model.
PubMed: 38617463
DOI: 10.1097/TXD.0000000000001620 -
Transplant International : Official... 2024A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the... (Clinical Trial)
Clinical Trial Observational Study
A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (β-cell Tx; = 51) to control T1D patients ( = 272). Fear of coronavirus infection was higher in those with β-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, < 0.001). A previous β-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with β-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), = 0.038). Fewer patients with β-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with β-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205).
Topics: Female; Humans; Male; Anxiety; Blood Glucose; Blood Glucose Self-Monitoring; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Glycemic Control; Insulin-Secreting Cells; Islets of Langerhans Transplantation; Pandemics; Public Health
PubMed: 38601276
DOI: 10.3389/ti.2024.12278 -
Journal of Diabetes Apr 2024Although pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin-dependent diabetes, a shortage of donors is a major... (Review)
Review
Although pancreas and islet cell transplantation are the only ways to prevent the late complications of insulin-dependent diabetes, a shortage of donors is a major obstacle to tissue and organ transplantation. Stem cell therapy is an effective treatment for diabetes and other pancreatic-related diseases, which can be achieved by inducing their differentiation into insulin-secreting cells. The liver is considered an ideal source of pancreatic cells due to its similar developmental origin and strong regenerative ability as the pancreas. This article reviews the traditional and emerging strategies using hepatocytes for pancreatic regenerative medicine and evaluates their advantages and challenges. Gene reprogramming and chemical reprogramming technologies are traditional strategies with potential to improve the efficiency and specificity of cell reprogramming and promote the transformation of hepatocytes into islet cells. At the same time, organoid technology, as an emerging strategy, has received extensive attention. Biomaterials provide a three-dimensional culture microenvironment for cells, which helps improve cell survival and differentiation efficiency. In addition, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology has brought new opportunities and challenges to the development of organoid technology.
Topics: Humans; CRISPR-Cas Systems; Regenerative Medicine; Pancreas; Diabetes Mellitus, Type 1; Hepatocytes
PubMed: 38599852
DOI: 10.1111/1753-0407.13545 -
Journal of Clinical Medicine Feb 2024CA 19-9 is a commonly assessed tumor marker, considered characteristic of pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers; however, the positive...
BACKGROUND
CA 19-9 is a commonly assessed tumor marker, considered characteristic of pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers; however, the positive predictive value of CA 19.9 is too low, and the usage of CA 19.9 as a screening tool in the healthy population remains controversial.
METHODS
The presented case illustrates a reversed diagnosis of highly elevated serum CA 19-9 levels in a 54-year-old female complaining of pain in the epigastric region, shortly after COVID-19 vaccination. Laboratory tests showed a significantly elevated level of the CA 19-9 marker (>12,000 U/mL, reference value: <37 U/mL) with normal pancreatic enzyme activity. The patient underwent imaging examination, which showed no abnormalities, except for increased pancreatic dimension and areas of fluid signal in the pancreas in magnetic resonance imaging (MRI), which may correspond to autoimmune pancreatitis (AIP). The patient remains asymptomatic with a recommendation for a follow-up MRI in 12 months.
RESULTS
A literature review conducted revealed multi-causal CA 19-9 increases above 1000 U/mL, including non-cancerous diseases of the lung, pancreas, liver, ovary, kidney, and others. The median concentration of CA 19-9 regardless of the cause of disease was 2810 U/mL (IQR ± 6895). The median CA 19-9 values in men and women were 3500 (IQR ± 10,050) and 2455 (IQR ± 3927), respectively, and differ significantly between the compared groups ( < 0.05). There was no difference between CA 19-9 values and the categorized cause of the increase.
CONCLUSIONS
Conducting differential diagnosis, it should not be forgotten that most international guidelines recommend the use of CA 19-9 only in conjunction with pathology of pancreas in radiological imaging; however, even such a combination can point the diagnostic pathway in the wrong direction. A highly elevated CA 19-9 level, typically associated with PDAC, may be the result of benign disease including AIP related to COVID-19 vaccination.
PubMed: 38592088
DOI: 10.3390/jcm13051263