Finding Eden - alternative transplantation sites for pancreatic islets.

Pancreatic islets transplantation is an established treatment method for type 1 diabetic patients with the hypoglycemia unawareness syndrome in whom a therapy with modern technologies fails. Islet transplantation is most commonly done using an interventional radiology method: a tissue suspension of pancreatic islets is applied into a branch of the portal vein through a percutaneously installed catheter. Although being minimally invasive unlike pancreas organ transplant, this method is associated with many technical difficulties. Possible complications of the procedure include hemorrhage and portal vein thrombosis. Unlike their natural dispersed localization in exocrine pancreas, isolated pancreatic islets are exposed to hypoxia, toxins and immunosuppressive drugs in the liver parenchyma. Direct contact with the recipients blood causes an instant blood mediated inflammatory reaction (IBMIR) resulting in the death of more than half of the pancreatic islets shortly after their application. Therefore the size of the islet graft is often insufficient and a number of transplanted patients require administration of exogenous insulin. All of these are reasons for seeking an alternative transplantation site with more hospitable conditions for long-term islet survival. Various transplantation sites have been tested in experimental and clinical research. The advantages and disadvantages of some of them are summarized in this paper. Currently, transplantation into the greater omentum seems most promising, which has already been used in clinical practice at several institutions.

Deceased Donor Renal Transplantation Combined with Bilateral Nephrectomy in a Patient with Tuberous Sclerosis and Renal Failure.

INTRODUCTION: A 27-year-old female patient with known tuberous sclerosis complex (TSC), polycystic kidneys with multiple large bilateral angiomyolipomas, and failing renal functions with prehemodialysis values (urea: 19 mmol/L; creatinine: 317 µmol/L; CKD-EPI 0,27) was admitted to our department for pre-renal transplant evaluation. The patient was placed on the transplant waiting list as the living donor did not pass pretransplant workup and was subsequently contraindicated. Patient was placed on the "cadaverous kidney transplant waiting list". METHOD: Computed tomography angiography revealed symptomatic PSA in the right kidney angiomyolipoma (AML). The patient underwent urgent transarterial embolisation of the PSA's feeding vessel in the right kidney AML. Based on the "kidney transplant waiting list" order patient underwent a bilateral nephrectomy combined with transperitoneal renal allotransplantation of a cadaverous kidney graft through midline laparotomy, appendectomy, and cholecystectomy. RESULTS: Postoperative period was complicated by delayed graft function caused by acute tubular necrosis requiring postoperative hemodialysis. The patient was discharged on the 17th postoperative day with a good renal graft function. Patient's follow-up is currently 23 months with good graft function (urea: 9 mmol/L; creatinine: 100 µmol/L). CONCLUSION: Renal transplantation combined with radical nephrectomy provides a definitive treatment for TSC renal manifestations.

Transabdominal two-cavity approach for radical nephrectomy combined with inferior vena cava thrombectomy for malignant thrombus caused by renal cell carcinoma: a case series.

BACKGROUND: Advanced renal cell carcinoma in some cases causes malignant intravascular thrombus with the potential for growth into the inferior vena cava or even the right atrium. Renal cell carcinoma is accompanied by malignant intravascular thrombus in up to 10% of cases. We present an overview of three patients diagnosed as having renal cell carcinoma with malignant intravascular thrombus requiring radical nephrectomy combined with inferior vena cava thrombectomy. CASE PRESENTATION: Three patients diagnosed as having renal cell carcinoma were indicated for renal cell carcinoma combined with inferior vena cava thrombectomy between 2014 and 2017 at our department: a 69-year-old white Caucasian woman, a 74-year-old white Caucasian woman, and a 58-year-old white Caucasian woman. According to the Novick classification of inferior vena cava tumor thrombus, there was one infrahepatic (level II) and two supradiaphragmatic (level IV) malignant intravascular thrombi. The average age of these patients was 67 years (range 58-74 years). All patients underwent radical nephrectomy combined with inferior vena cava thrombectomy through transabdominal approach. In patients with level IV malignant intravascular thrombus, transesophageal echocardiogram was used to guide the placement of the inferior vena cava cross-clamp above the diaphragm. In one patient the pericardium was opened to place a cross-clamp above a tumor just below the right atrium. There were no postoperative mortalities to date with an average follow-up of 23 months (range 2-48 months). To date, no patient has demonstrated recurrent inferior vena cava malignant intravascular thrombus requiring secondary inferior vena cava thrombectomy or any other treatment. A comparison of estimated blood loss and transfusion rate was not significantly different in all three cases. CONCLUSION: Despite the technical complexity of the procedure, caval thrombectomy combined with radical nephrectomy currently represents the only radical treatment for renal cell carcinoma accompanied by malignant intravascular thrombus with good mid-term oncological outcomes.

Aorto-iliac endarterectomy: Old-fashioned or re-newed method?

INTRODUCTION: Aorto-iliac occlusive disease is best treated with endovascular angioplasty/stenting or surgical bypass, depending on disease severity. Aorto-iliac endarterectomy was frequently used until the 1980s. However, it can still be performed in cases of previous failure or contraindication of standard methods. The aim was a retrospective evaluation of a single-center case series of aorto-iliac endarterectomy. METHODS: Seven patients at mean age 60±8 years (5768 years) were treated by aorto-iliac endarterectomy between 2013 and 2018. Rutherford categories of leg ischemia were 2 (moderate claudication) 3x, 3 (severe claudication) 2x, 4 (rest pain) and 5 (toe gangrene). The reasons for endarterectomy approach were: late in-stent iliac occlusion in an oncology patient, failure or complication of previous endovascular treatment of short iliac stenosis 2×, high infection risk of prosthesis use in long iliac-femoral occlusion, and short iliac occlusions 3x. Two patients after previous organ transplant were on immunosuppression. RESULTS: Technical success rate was 100%. There was no peri-operative (30 days) death or amputation. Mean follow-up was 17 months (1.1 month3.3 year). One patient required additional tibial bypass 1 month after endarterectomy to heal foot gangrene. One patient developed symptomatic re-stenosis which was treated with iliac stenting 8 months after procedure. All patients clinically improved and recovered from leg ischemia. Two patients died of tumor with preserved limb 1.1 month and 3.1 years after procedure, respectively. Five remaining patients are asymptomatic with patent revascularization to date. CONCLUSION: Aorto-iliac endarterectomy is a vital alternative technique for revascularization in selected patients when other methods seem inappropriate. Key words: endarterectomy - peripheral arterial disease - iliac artery - abdominal aorta.

Gene expression changes in rat pancreas transplant model after long-term cold storage of the graft in perfluorohexyloctane.

BACKGROUND: Perfluorohexyloctane (PFH) is a promising storage solution that has been successfully used for pancreas preservation before islet isolation. This hyperoxygen carrier has been designed to prevent ischemic injury to the pancreas graft during cold storage. In our storage, we aimed to evaluate the impact of this solution on long-term cold storage in a rat whole pancreas transplantation model. METHOD: Brown-Norway rats were used for syngeneic heterotopic pancreas transplantation. The procured organs were cold-stored for 18 hours in preoxygenated PFH (PFH group; n = 8) or in the University of Wisconsin solution (UW group; n = 8), or were transplanted immediately in the control group (n = 8). Two hours after reperfusion, we obtained blood and pancreas tissue samples for biochemistry and gene analyses (real-time polymerase chain reaction). RESULTS: A significant difference between the UW and PFH group was observed in the tumor necrosis factor (TNF)ß and endothelin 1 genes, which was overexpressed more than twofold in the UW group. In the blood samples, the UW group compared with the PFH group showed significantly higher levels of pancreatic amylase and lipase (94.2 ± 25.2 vs 67.7 ± 13.4 µkat/L and 5.5 ± 2.8 vs 3 ± 0.7 µkat/L, respectively; P < .05). CONCLUSION: We found significantly lower expression levels of the endothelin 1 and TNFß genes and lower concentrations of pancreatic amylase and lipase in the PFH group. All these findings suggest lower rate of ischemic reperfusion injury in the PFH group. These findings may result in better post-transplant outcomes after long-term cold storage in PFH compared with the UW solution. Further research in this area is required.

Neoplasm incidence in simultaneous pancreas and kidney transplantation: a single-center analysis.

BACKGROUND: Long-term immunosuppression is associated with an increased rate of cancer. The aim of this study was to analyze the incidence of newly diagnosed tumors in simultaneous kidney and pancreas transplantation (SPKT). METHODS: We retrospectively analyzed the incidence of a neoplasm among 360 diabetic subjects who consecutively underwent SPKT from 1985 to August 2010 in a single institution. Data were retrieved from the institutional registry. We evaluated the nature of all newly diagnosed malignant tumors, including posttransplantation lymphoproliferative disease (PTLD), to compare Kaplan-Meier survival rates with those of patients free of a neoplasm. RESULTS: The median follow-up was 8 years; the overall 5-year patient survival was 84%. In 25 patients the tumors were malignant. Almost one-fourth of the cancers represented skin tumors (3 squamous cell and 4 basal cell carcinomas). PTLD was diagnosed in 5 recipients. The cumulative survival of patients with malignancies was significantly lower than that in recipients without cancer (8-year survival by 38% vs 70%; P < .001). The mean (±SD) time to diagnosis was 6 ± 3 years. Since 2004, the 12 recipients with malignancy who were switched to sirolimus at the time of diagnosis showed survivals that were not apparently better than those who remained on the established immunosuppression (46% vs 55%; P = .71). CONCLUSIONS: The risk of neoplasm development was similar to that reported by other centers. Recipients of SPKT show higher incidence of cancer, though their overall survival is still significantly better than in those usually remaining on dialysis.

[Simultaneous transplantation of the kidney and the islets of Langerhans]. / Simultánní transplantace ledviny a Langerhansových ostruvku.

Simultaneous kidney and islet transplantation is recent therapeutic alternative for diabetics with end-stage kidney disease, who are not acceptable for simultaneous pancreas-kidney transplantation. Islet transplantation has less complications but still worse long-term function compared to whole pancreas transplantation.

Perfluorocarbon improves post-transplant survival and early kidney function following prolonged cold ischemia.

BACKGROUND: The two-layer organ preservation method (TLM) based on oxygenated perfluorocarbon overlaid with University of Wisconsin (UW) solution has been successfully used in clinical islet and experimental heart and intestine transplantation. We tested whether this technique would prevent tissue damage and improve kidney function in a model of syngeneic kidney transplantation with prolonged ischemia time. METHODS: Kidneys were stored for 24 h either in UW solution (n = 16), with TLM (n = 16) or transplanted immediately (control group, n = 12). In half of the animals, survival was observed and in the other animals grafts were procured for semiquantitative histological scoring and TUNEL apoptosis assessment 24 h after transplantation. RESULTS: One-month survival rates in the UW, TLM and control groups were 12.5, 62.5 and 100%, respectively (UW vs. TLM, p < 0.01). Median creatinine levels 24 h after transplantation were 381, 299 and 121 microM, respectively (UW vs. TLM, p < 0.02). Histological scoring showed more severe tissue damage in the UW group than in the TLM group (p < 0.05). Apoptosis was more frequent in the UW group than in the TLM group (p < 0.05). CONCLUSION: We demonstrated for the first time that conservation with TLM significantly improves the outcome of kidney transplantation in a rat model and should therefore be further studied in larger animals.

[Clinical experience with cold-preservation of venous and arterial allografts. long-term outcomes]. / Klinické zkusenosti s pouzitím chladem konzervovaných zilních a tepenných allostepu: dlouhodobé výsledky.

INTRODUCTION: Venous and arterial allografts extend the possibilities of peripheral arterial disease as well as vascular prosthesis infections treatment. MATERIAL AND METHODS: Between 10/1997 and 1/2009 we used 112 allogeneic vessels (30 arteries, 82 veins) in 104 patients. Venous allografts were used for 82 reconstructions in 75 patients (M/F 41/34, aged 41-85 years, median 66 years) with critical limb ischemia and no suitable autogenous venous material. Arterial allografts were used in 9 patients (M/F 8/1, aged 56-77 years, median 63 years) with aortoiliac prosthetic infections or mycotic abdominal aortic aneurysms and in 20 transplanted patients (M/F 11/9, aged 32-67 years, median 56 years) with aortoiliac atherosclerotic disease. RESULTS: Patients survival rate after allovenous bypasses was 92% at 1 year and 78% at 3 years. Limb salvage rate was 67% at 1 year and 53% and 3 years. Secondary patency rate was 48% at 1 year and 27% at 3 years. Patient survival rate after alloarterial bypasses was 86% at 1 year and 69% at 3 years. No signs of arterial grafts aneurysmal formation and no need for secondary intervention of any arterial reconstruction was observed during the follow up period in any patient after alloarterial transplantation. CONCLUSIONS: Cold-stored venous and arterial allografts are suitable alternative conduits for limb salvage procedures, vascular prosthesis infections as well as for arterial reconstructions in transplanted patients.

Cold-stored venous allografts in the treatment of critical limb ischaemia.

OBJECTIVES: To assess the outcome of cold-stored venous allografts in critically ischemic limbs in patients with no ipsilateral autogenous greater saphenous vein. DESIGN: A non-randomised, retrospective, single-center study. METHODS: From September 2000 to June 2006, 46 cold-stored venous allografts obtained during multiorgan harvest were implanted into 44 critically ischaemic limbs of 43 patients. The indication for reconstructions was rest pain (24%) or tissue lost (76%). Sixty-seven percent of procedures were performed as secondary reconstructions, and 61% of veins were anastomosed to tibial or pedal arteries. Thirty-seven percent of patients received prednisone, and 46% tacrolimus as postoperative immunosuppressive therapy. Mean patient follow-up period was 13.3 months (range 1 week to 60 months). RESULTS: The secondary patency rate for the cohort was 83+/-5.6% at 1 month, 64+/-8.2% at 6 months, 57+/-10.0% at 12 months and 46+/-10.7% at 24 months. Limb salvage rate was 96+/-3.1% at 1 month, 78+/-6.9% at 6 months, 71+/-8.1% at 12 months and 50+/-11.8% at 24 months. CONCLUSION: Cold-stored venous allografts are an alternative conduit for limb salvage procedures when ipsilateral autogenous vein is unavailable.