BACKGROUND: Pancreaticoduodenectomy is associated with an incidence of postoperative complications of approximately 41%. One of the most severe complications is a postoperative pancreatic fistula. The exact cause of postoperative fistula development is still unknown, but it appears to be multifactorial. Proper perfusion of pancreatic remnant is essential for the healing of pancreaticojejunostomy. To date, there is no method to reliably evaluate the vascular supply of the remnant. One of the methods for the assessment of organ perfusion is the indocyanine green fluorescence. This study aims to determine if indocyanine green fluorescence is a reliable method to measure the perfusion of the post-resection pancreatic remnant. The secondary outcome is to determine if intraoperative evaluation of the vascular supply of the post-resection remnant may predict the increased risk of postoperative pancreatic fistula development. METHODS: This study is designed as a prospective, observational study. All consecutive patients undergoing open or robotic pancreaticoduodenectomies at our department during the 1st May 2024-31st December 2026 period will be enrolled. The exclusion criteria are an allergy to indocyanine green and refusal by the patient. The adequacy of the vascular supply of the post-resection pancreatic remnant will be intraoperatively evaluated using a fluorescence detector. Patients will be divided into two groups: Those with high risk of pancreatic fistula development and those with low risk. The incidence of pancreatic fistulas in both groups is to be compared. Postoperative data including morbidity, mortality, hospital stay, intensive care unit stay and postoperative fistula development will be collected. DISCUSSION: If an intraoperative assessment of the perfusion of post-resection pancreatic remnant using indocyanine green is proven to be a suitable method to estimate the increased risk of the pancreatic fistula, the list of the existing known risk factors could be expanded. In the most high-risk patients the modification of the surgical procedure could be considered. TRIAL REGISTRATION: Number: NCT06198400 ClinicalTrials.Gov. Date 08.01.2024.

• Klíčová slova
• ICG, Minimal invasive surgery, Pancreatic cancer, Pancreatic perfusion, Pancreatic surgery, Prospective study,
• MeSH
• fluorescence MeSH
• indokyanová zeleň * MeSH
• lidé MeSH
• pankreas krevní zásobení   chirurgie   MeSH
• pankreatická píštěl * etiologie   epidemiologie   MeSH
• pankreatoduodenektomie * škodlivé účinky   metody   MeSH
• pooperační komplikace * etiologie   diagnóza   MeSH
• pozorovací studie jako téma MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• indokyanová zeleň * MeSH

AIMS/HYPOTHESIS: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. METHODS: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2-L5 vertebrae). RESULTS: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = -0.434, p = 0.017), WHR (r = -0.411, p = 0.024), and VAT (r = -0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = -0.401, p = 0.028) and HOMA-IR (r = -0.376, p = 0.041). DISCUSSION/CONCLUSION: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

• Klíčová slova
• Blood perfusion, Obesity, Pancreas, Type 2 diabetes mellitus,
• MeSH
• diabetes mellitus 2. typu * MeSH
• index tělesné hmotnosti MeSH
• inzulin MeSH
• inzulinová rezistence * MeSH
• krevní glukóza MeSH
• lidé MeSH
• nitrobřišní tuk diagnostické zobrazování   patologie   MeSH
• obezita komplikace   MeSH
• pankreas patologie   MeSH
• perfuze MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inzulin MeSH
• krevní glukóza MeSH

BACKGROUND: Perfusion assessment of the pancreas is challenging and poorly evaluated. Pancreatic affection is a prevalent feature of cystic fibrosis (CF). Little is known about pancreatic perfusion in CF. We aimed to assess pancreatic perfusion by contrast-enhanced ultrasound (CEUS) analysed in the bolus-and-burst model and software. METHODS: We performed contrast enhanced ultrasound of the pancreas in 25 CF patients and 20 healthy controls. Perfusion data was analysed using a dedicated perfusion model providing the mean capillary transit-time (MTT), blood flow (BF) and blood-volume (BV). CF patients were divided according to exocrine function. RESULTS: The pancreas insufficient CF patients had longer MTT (p ≤ 0.002), lower BF (p < 0.001) and lower BV (p < 0.05) compared to the healthy controls and sufficient CF patients. Interrater analysis showed substantial agreement for the analysis of mean transit time. CONCLUSION: The bolus-and-burst method used on pancreatic CEUS-examinations demonstrates reduced perfusion in CF patients with pancreas affection. The perfusion model and software requires further optimization and standardization to be clinical applicable for the assessment of pancreatic perfusion.

• Klíčová slova
• Contrast enhanced ultrasound, Cystic fibrosis, Exocrine pancreatic function, Pancreas, Perfusion,
• MeSH
• cystická fibróza diagnostické zobrazování   MeSH
• dospělí MeSH
• kontrastní látky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• pankreas diagnostické zobrazování   MeSH
• perfuzní zobrazování metody   MeSH
• prospektivní studie MeSH
• senioři MeSH
• software MeSH
• studie případů a kontrol MeSH
• ultrasonografie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kontrastní látky MeSH

Instant Blood-Mediated Inflammatory Reaction (IBMIR) is a major cause of graft loss during pancreatic islet transplantation, leading to a low efficiency of this treatment method and significantly limiting its broader clinical use. Within the procedure, transplanted islets obstruct intrahepatic portal vein branches and consequently restrict blood supply of downstream lying liver tissue, resulting typically in ischemic necrosis. The extent of ischemic lesions is influenced by mechanical obstruction and inflammation, as well as subsequent recanalization and regeneration capacity of recipient liver tissue. Monitoring of immediate liver perfusion impairment, which is directly related to the intensity of post-transplant inflammation and thrombosis (IBMIR), is essential for improving therapeutic and preventive strategies to improve overall islet graft survival. In this study, we present a new experimental model enabling direct quantification of liver perfusion impairment after pancreatic islet transplantation using ligation of hepatic arteries followed by contrast-enhanced magnetic resonance imaging (MRI). The ligation of hepatic arteries prevents the contrast agent from circumventing the portal vein obstruction and enables to discriminate between well-perfused and non-perfused liver tissue. Here we demonstrate that the extent of liver ischemia reliably reflects the number of transplanted islets. This model represents a useful tool for in vivo monitoring of biological effect of IBMIR-alleviating interventions as well as other experiments related to liver ischemia. This technical paper introduces a novel technique and its first application in experimental animals.

• Klíčová slova
• IBMIR, MRI, Pancreatic islet transplantation, instant blood-mediated inflammatory reaction, liver ischemia, magnetic resonance imaging,
• MeSH
• embolie * komplikace   diagnóza   MeSH
• ischemie * diagnostické zobrazování   etiologie   MeSH
• játra * krevní zásobení   diagnostické zobrazování   patologie   MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční angiografie metody   MeSH
• přežívání štěpu MeSH
• reprodukovatelnost výsledků MeSH
• teoretické modely MeSH
• transplantace Langerhansových ostrůvků škodlivé účinky   MeSH
• vena portae * MeSH
• vylepšení obrazu metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) can be used for calculating organ perfusion. By combining bolus injection with burst replenishment, the actual mean transit time (MTT) can be estimated. Blood volume (BV) can be obtained by scaling the data to a vessel on the imaging plane. The study aim was to test interobserver agreement for repeated recordings using the same ultrasound scanner and agreement between results on two different scanner systems. MATERIALS AND METHODS: Ten patients under evaluation for exocrine pancreatic failure were included. Each patient was scanned two times on a GE Logiq E9 scanner, by two different observers, and once on a Philips IU22 scanner, after a bolus of 1.5 ml Sonovue. A 60-second recording of contrast enhancement was performed before the burst and the scan continued for another 30 s for reperfusion. We performed data analysis using MATLAB-based DCE-US software. An artery in the same depth as the region of interest (ROI) was used for scaling. The measurements were compared using the intraclass correlation coefficient (ICC) and Bland Altman plots. RESULTS: The interobserver agreement on the Logiq E9 for MTT (ICC=0.83, confidence interval (CI) 0.46-0.96) was excellent. There was poor agreement for MTT between the Logiq E9 and the IU22 (ICC=-0.084, CI -0.68-0.58). The interobserver agreement for blood volume measurements was excellent on the Logiq E9 (ICC=0.9286, CI 0.7250-0.98) and between scanners (ICC=0.86, CI=0.50-0.97). CONCLUSION: Interobserver agreement was excellent using the same scanner for both parameters and between scanners for BV, but the comparison between two scanners did not yield acceptable agreement for MTT. This was probably due to incomplete bursting of bubbles in some of the recordings on the IU22.

• Klíčová slova
• dynamic contrast-enhanced ultrasound, interobserver, pancreas, perfusion,
• Publikační typ
• časopisecké články MeSH

Infusing pancreatic islets into the portal vein currently represents the preferred approach for islet transplantation, despite considerable loss of islet mass almost immediately after implantation. Therefore, approaches that obviate direct intravascular placement are urgently needed. A promising candidate for extrahepatic placement is the omentum. We aimed to develop an extracellular matrix skeleton from the native pancreas that could provide a microenvironment for islet survival in an omental flap. To that end, we compared different decellularization approaches, including perfusion through the pancreatic duct, gastric artery, portal vein, and a novel method through the splenic vein. Decellularized skeletons were compared for size, residual DNA content, protein composition, histology, electron microscopy, and MR imaging after repopulation with isolated islets. Compared to the other approaches, pancreatic perfusion via the splenic vein provided smaller extracellular matrix skeletons, which facilitated transplantation into the omentum, without compromising other requirements, such as the complete depletion of cellular components and the preservation of pancreatic extracellular proteins. Repeated MR imaging of iron-oxide-labeled pancreatic islets showed that islets maintained their position in vivo for 49 days. Advanced environmental scanning electron microscopy demonstrated that islets remained integrated with the pancreatic skeleton. This novel approach represents a proof-of-concept for long-term transplantation experiments.

• Klíčová slova
• advanced environmental scanning electron microscopy, extracellular matrix skeletons, pancreas decellularization, splenic vein perfusion, transplantation into the omentum,
• Publikační typ
• časopisecké články MeSH

This paper presents a system for correcting motion influences in time-dependent 2D contrast-enhanced ultrasound (CEUS) images to assess tissue perfusion characteristics. The system consists of a semi-automatic frame selection method to find images with out-of-plane motion as well as a method for automatic motion compensation. Translational and non-rigid motion compensation is applied by introducing a temporal continuity assumption. A study consisting of 40 clinical datasets was conducted to compare the perfusion with simulated perfusion using pharmacokinetic modeling. Overall, the proposed approach decreased the mean average difference between the measured perfusion and the pharmacokinetic model estimation. It was non-inferior for three out of four patient cohorts to a manual approach and reduced the analysis time by 41% compared to manual processing.

• Klíčová slova
• CEUS, Contrast-enhanced ultrasound, Motion analysis, Motion compensation, Perfusion, Perfusion modeling, Registration, Ultrasonography,
• MeSH
• břicho diagnostické zobrazování   MeSH
• Crohnova nemoc diagnostické zobrazování   MeSH
• cystická fibróza diagnostické zobrazování   MeSH
• databáze faktografické * MeSH
• interpretace obrazu počítačem metody   MeSH
• kontrastní látky aplikace a dávkování   MeSH
• lidé MeSH
• pohyb těles MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kontrastní látky MeSH

We have recently developed a model of pancreatic islet transplantation into a decellularized pancreatic tail in rats. As the pancreatic skeletons completely lack endothelial cells, we investigated the effect of co-transplantation of mesenchymal stem cells and endothelial cells to promote revascularization. Decellularized matrix of the pancreatic tail was prepared by perfusion with Triton X-100, sodium dodecyl sulfate and DNase solution. Isolated pancreatic islets were infused into the skeletons via the splenic vein either alone, together with adipose tissue-derived mesenchymal stem cells (adMSCs), or with a combination of adMSCs and rat endothelial cells (rat ECs). Repopulated skeletons were transplanted into the subcutaneous tissue and explanted 9 days later for histological examination. Possible immunomodulatory effects of rat adMSCs on the survival of highly immunogenic green protein-expressing human ECs were also tested after their transplantation beneath the renal capsule. The immunomodulatory effects of adMSCs were also tested in vitro using the Invitrogen Click-iT EdU system. In the presence of adMSCs, the proliferation of splenocytes as a response to phytohaemagglutinin A was reduced by 47% (the stimulation index decreased from 1.7 to 0.9, P = 0.008) and the reaction to human ECs was reduced by 58% (the stimulation index decreased from 1.6 to 0.7, P = 0.03). Histological examination of the explanted skeletons seeded only with the islets showed their partial disintegration and only a rare presence of CD31-positive cells. However, skeletons seeded with a combination of islets and adMSCs showed preserved islet morphology and rich vascularity. In contrast, the addition of syngeneic rat ECs resulted in islet-cell necrosis with only few endothelial cells present. Live green fluorescence-positive endothelial cells transplanted either alone or with adMSCs were not detected beneath the renal capsule. Though the adMSCs significantly reduced in vitro proliferation stimulated by either phytohaemagglutinin A or by xenogeneic human ECs, in vivo co-transplanted adMSCs did not suppress the post-transplant immune response to xenogeneic ECs. Even in the syngeneic model, ECs co-transplantation did not lead to sufficient vascularization in the transplant area. In contrast, islet co-transplantation together with adMSCs successfully promoted the revascularization of extracellular matrix in the subcutaneous tissue.

• Klíčová slova
• Click-iT EdU, Mesenchymal stem cells, Pancreatic islets, Revascularization, Transplantation,
• MeSH
• decelularizovaná extracelulární matrix MeSH
• endoteliální buňky MeSH
• fyziologická neovaskularizace * MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• Langerhansovy ostrůvky * imunologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• pankreas MeSH
• transplantace Langerhansových ostrůvků * metody   MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• tuková tkáň * cytologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• decelularizovaná extracelulární matrix MeSH

Human islet transplantation seems to be a very promising clinical procedure for patients with type I diabetes mellitus. The aim of our study was to investigate the influence of in situ intravascular flushing with University of Wisconsin (UW) solution and intraductal collagenase injection at the time of pancreas procurement on the isolated islets and exocrine tissue injury. Our experiments indicated that in situ perfusion with the UW solution has a beneficial effect on pancreatic islets and intraductal distention results in an increase in the concentration of pancreatic enzymes released into the cold preservation solution during ischemic conditions. Cold ischemia reduced islet yield, but pancreas perfusion with the UW solution showed better ischemic tolerance of isolated islets during glucose static incubation. We conclude that intravascular pancreas flushing has a crucial effect on recovery and yield of pancreatic islets and protects against exocrine tissue injury.

• MeSH
• injekce MeSH
• kolagenasy aplikace a dávkování   MeSH
• krysa rodu Rattus MeSH
• Langerhansovy ostrůvky cytologie   účinky léků   fyziologie   MeSH
• odběr tkání a orgánů metody   MeSH
• peroxidace lipidů fyziologie   MeSH
• separace buněk metody   MeSH
• transplantace Langerhansových ostrůvků metody   MeSH
• uchovávání orgánů metody   MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• kolagenasy MeSH

BACKGROUND: Europe is currently the most active region in the field of pancreatic islet transplantation, and many of the leading groups are actually achieving similar good outcomes. Further collaborative advances in the field require the standardization of islet cell product isolation processes, and this work aimed to identify differences in the human pancreatic islet isolation processes within European countries. METHODS: A web-based questionnaire about critical steps, including donor selection, pancreas processing, pancreas perfusion and digestion, islet counting and culture, islet quality evaluation, microbiological evaluation, and release criteria of the product, was completed by isolation facilities participating at the Ninth International European Pancreas and Islet Transplant Association (EPITA) Workshop on Islet-Beta Cell Replacement in Milan. RESULTS: Eleven islet isolation facilities completed the questionnaire. The facilities reported 445 and 53 islet isolations per year over the last 3 years from deceased organ donors and pancreatectomized patients, respectively. This activity resulted in 120 and 40 infusions per year in allograft and autograft recipients, respectively. Differences among facilities emerged in donor selection (age, cold ischemia time, intensive care unit length, amylase concentration), pancreas procurement, isolation procedures (brand and concentration of collagenase, additive, maximum acceptable digestion time), quality evaluation, and release criteria for transplantation (glucose-stimulated insulin secretion tests, islet numbers, and purity). Moreover, even when a high concordance about the relevance of one parameter was evident, thresholds for the acceptance were different among facilities. CONCLUSIONS: The result highlighted the presence of a heterogeneity in the islet cell product process and product release criteria.

• MeSH
• časové faktory MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• kultivované buňky transplantace   MeSH
• Langerhansovy ostrůvky cytologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• odběr tkání a orgánů metody   normy   statistika a číselné údaje   MeSH
• perfuze metody   statistika a číselné údaje   MeSH
• počet buněk normy   statistika a číselné údaje   MeSH
• předškolní dítě MeSH
• primární buněčná kultura metody   normy   statistika a číselné údaje   MeSH
• průzkumy a dotazníky statistika a číselné údaje   MeSH
• senioři MeSH
• separace buněk metody   statistika a číselné údaje   MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• studená ischemie normy   statistika a číselné údaje   MeSH
• transplantace Langerhansových ostrůvků metody   normy   MeSH
• věkové faktory MeSH
• výběr dárců metody   normy   statistika a číselné údaje   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH