Tacrolimus inhibits intimal hyperplasia in arterialised veins in rats.

OBJECTVES: We investigated whether tacrolimus (FK506) can inhibit neointimal formation in arterialised vein grafts in rats. METHODS: Lewis iliolumbar veins were implanted into the abdominal aorta of isogeneic rats. Animals in the treatment groups had daily intramuscular injections of tacrolimus at 0.2 mg/kg (group B) and 0.1 mg/kg (Group C), respectively. The control group A had no treatment. Light microscope evaluations of arterialised vein grafts were performed 30 days after operation. We determined the presence of endothelial cells, the thickness of intima and media, and the degree of infiltration by MHC class II positive, CD4 positive, and CD8 positive cells into the adventitia. RESULTS: The intimal thickness in group B (5.0±1.0 µm) was statistically lower (P < 0.05) when compared to group C (7.0±3.0 µm). The intimal thickness in untreated group A (12.7±7.0 µm) was statistically higher (P < 0.01) when compared to both treated groups B and C, respectively. The medial thickness and degree of adventitial infiltration by MHC class II positive, CD8 positive, and CD4 positive cells did not differ between groups. CONCLUSION: Treatment with tacrolimus (FK506) showed a dose dependant inhibition of neointimal hyperplasia in arterialised vein grafts in rats (Tab. 1, Fig. 3, Ref. 22).

[Intraarterial peroperative thrombolysis in therapy of the acute limb ischemia]. / Peroperacní intraarteriální trombolýza v terapii akutní koncetinové ischemie.

Acute limb ischemia is serious situation, jeopardizing limb salvage, causing embolization or thrombosis of the native arteries or vascular graft. Immediate surgical revascularization with balloon thromboembolectomy is indicated in patient with acute ischemia stage IIB of the Rutherford classification. Unfortunately, operative thromboembolectomy is frequently incomplete, with persistent thrombus remaining in the majority of patients. Residual thrombus compromises the clinical outcome, leading to poor revascularization and an increased risk of tissue loss. On depending of amount of the residual thrombus after surgical thromboembolectomy, we can choose one of the three options of intraoperative thrombolysis. This article summarized indication and technical realisation of intraoperative thrombolysis and describe cause report of the first patient treated with this method in our country. The combined use of intraoperative thrombolytics following mechanical thromboembolectomy is safe and efficacious method in patients with acute vascular occlusion.

[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.

[Liver transplantation in patients with portal vein thrombosis]. / Transplantace jater u pacientu s trombózou portální zíly.

AIM: The aim of the study was to perform a retrospective assessment in a group of patients with portal vein thromboses who underwent consecutive liver transplantation. MATERIAL AND METHODS: PVT was preoperatively diagnosed with ultrasound and CT portography. The follow up period was 1 to 6 years. Postoperative immunosuppressive medication was administered in combination with cyclosporin A, prednison and imuran upon initiation of the transplantation programme (8 patients). During the follow up period, the treatment protocol was replaced with FK 506, Cell Cept and prednisone. Liver biopsy was indicated when rejection was suspected. RESULTS: During 1996-2009, the team of authors performed a total of 740 liver transplantations in 303 female and 437 male subjects. The procedures included 703 primary procedures, 33 retransplantations and four second retransplantations. Out of the total, 57 recipients (7.7%) had portal vein obliteration. These subjects included 42 male and 15 females, their mean age was 52 (9-67) years. 62 liver transplantations were performed in these 57 patients. The following complications were recorded in the patient group: graft dysfunction in 10.5%, revisions for bleeding in 28%, hepatic artery thrombosis in 10.5%, portal vein rethrombosis in 1.8%, biliary complications in 17.5%, acute rejections in 19.3%. Perioperative mortality rate was 15.8%.The mean blood derivates requirement was 17.1 (0-425) erythrocyte transfusion units, 27.1 (0-132) frozen plasma transfusion units and 2.6 (0-20) thrombocyte transfusion units. CONCLUSION: The results of out retrospective study indicate that portal thrombosis is not a contraindication for liver transplantation. Current surgical techniques make liver transplantations in patients with complete splanchnic venous thrombosis possible.

[Early biliary complications following liver transplantation]. / Casné biliární komplikace po transplantaci jater.

INTRODUCTION: Biliary complications (BC) after liver transplantation (LTx) are serious problems with an incidence rate of 6-35%. There are two types of BC, early and late. Early BC is observed for 30 days post LTx or during the entire period of the patient's first hospital stay after LTx. The main causes of early BC are ischemia of the biliary tree (the bile duct of the transplanted liver is supplied only from the right hepatic artery descendingly; the supply from the gastroduodenal artery is lacking) as well as implementation of the biliary anastomosis surgical technique. Treatment of BC is administered by a surgeon, a gastroenterologist and a radiologist. AIM: To evaluate early biliary complications after LTx PATIENTS AND METHODS: We reviewed patients with early BC after LTx from 4/2004 - 12/2009. We defined early BC as a complication that is present during the first 30 days post LTx or during the entire period of the patient's first hospital stay after LTx. RESULTS: We performed 384 LTx during the above-mentioned period. We carried out reconstruction of the biliary tree in the form of a choledochocholedochostomy (CDD) in 312 cases and in the form of a choledochojejunostomy (CDJ) in 72 cases. Sixty-eight patients had early BC (17.7%), 25 patients experienced biliary leak (6.5%), 40 patients had anastomotic stenosis (10.4%) and 3 patients (0.8%) experienced both complications (biliary leak and stenosis). Most complications were eliminated by ERCP with a papilosfincterotomy, a balloon dilatation of stenosis, and a biliary stent implant with repeated stent replacements (45 cases in total- all patients with biliary stenosis). Twenty-two patients were reoperated on (16x CDJ, 3x re-CDD, 2x suture of aberrant bile duct, 1x suture common bile duct) and 1 patient was treated by percutaneous transhepatic bilary drainage (PTD). The mortality rate was zero. CONCLUSION: BC after LTx continue to pose a serious surgical problem. The treatment of choice when dealing with BC is ERCP, which has more than a 70% success rate. If ERCP or PTD are not successful, or when biliary peritonitis is present, we perform a reanastomosis of the bile duct. The combined effort of the surgeon, gastroenterologist and radiologist is the most important factor for successful treatment. The incidence of BC after LTx at IKEM is similar to that of treatment centers all over the world.

[First Czech and Slovak domino liver transplantation]. / První Cesko-Slovenská domino transplantace jater.

INTRODUCTION: The study introduces the first international, Czech and Slovak Domino Transplantation performed based on a tight cooperation between the Czech and Slovak transplant centres. MATERIAL AND METHODS: The donor of the cadaveric graft was a young Slovak man with Familial amyloidotic polyneuropathy. The livers of these patients are the predominant source of circulating transthyretin, and liver transplantation is the only treatment available for the disease. The graft was obtained from heart beating deceased donor with brain death. The domino graft was then transplanted to Czech sixty-three years old man with hepatocellular carcinoma and liver cirrhosis based on HCV. RESULTS: Both recipients had an uneventful immediate postoperative course with early graft function. The Czech patient faced early HCV recurrence in a graft which necessitated the reduction of immunosuppressives. CONCLUSION: The domino liver transplantation represents a suitable way for addressing graft shortage and reducing waiting list time. A well-organized cooperation between the two international centres is required to complete successful domino transplantation.

[Development of pancreas transplantation surgical techniques in IKEM]. / Vývoj chirurgické techniky transplantací pankreatu v IKEM.

A paper on the occasion of the fortieth anniversary of foundation of the Institute for Clinical and Experimental Medicine describes past, present and future trends in surgical technique of pancreas transplantation in the Czech Republic.

[Immunosuppression following venous allografts transplantations--the authors' experience]. / Imunosuprese po transplantaci zilních allograftu --nase zkusenosti.

AIM: Venous and arterial graft usage in vascular reconstructions was re-discovered in connection with organ transplantation development. Allografts are employed in many clinics, however, uniform opinion on the use of immunosuppression after the procedure of venous graft transfer from a cadaveric donor, is still lacking. MATERIAL AND METHODS: The authors present their own group of patients who underwent vascular reconstructions, and in whom allogenic vein was used. The majority of indications for bypass procedures resulted from critical limb ischemia. Immunosuppressive medication was administered during the vascular procedure and, over the past several years, it purely consisted of tacrolimus monotherapy. RESULTS: In the group of 101 patients, no serious complications due to adverse effects of immunosuppression therapy were recorded.

[Liver transplantations in children using reduced grafts]. / Transplantace jater u detí redukovaným stepem.

AIM: Liver transplantation is a life-saving procedure in patients with end stage liver disease. Five-year survival in patients indicated for transplantation based on standard indication criteria, has reached a rate over 80%. Shortage of suitable grafts remains the main problem in these procedures. While the situation in adult patients is relatively satisfactory, liver transplantations in children, mainly in the low-weight categories, remain a worldwide problem because of the absolute lack of suitable donors. In order to reduce mortality in the youngest patients on the waiting list, a concept of reduction of the adult graft for pediatric use was introduced in the early 1990s. Recent introduction of novel methods, such as split transplantations or transplantations between relatives, has resulted in lower mortality rates in the youngest recipients on the waiting lists. The author assesses a group of patients below 18 years of age, who underwent reduced liver graft transplantations in the Czech Republic. MATERIAL AND METHODS: From 1995 to 2009, a total of 43 patients below 18 years of age underwent transplantations, using 48 liver grafts. Further 17 children were sent abroad for transplantations, where a total of 23 liver grafts were used. Only patients who underwent transplantations using the liver grafts adjusted in IKEM were assessed in the patient group, i.e. 14 patients, resp. 16 liver grafts. Reduction was performed in 13 subjects. One subjects underwent transplantation between relatives and a liver split was used in two subjects. In the lowest weight category up to 10 kgs, 5 liver reductions were performed. OUTCOMES: Out of the total (n = 16), 4 grafts failed (2 were early postoperative failures, ie. within 2 postoperative days and 2 grafts failed in Month 5). The mean graft survival was 65 months. Within the youngest recipient age group (n = 5), no graft failure was recorded. The mean survival time is 26 months. CONCLUSION: Since 2007, the Czech Republic has been providing a program for all patients, including the lowest weight-category pediatric patients. To date data are satisfactory. No graft failure has been recorded in the category of the smallest (up to 10 kgs) pediatric patients.

Similar early complication rate in simultaneous pancreas and kidney recipients on tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus immunosuppressive regimens.

INTRODUCTION: We compared the incidence of severe complications among 123 consecutive simultaneous pancreas and kidney (SPK) recipients randomized for treatment either with tacrolimus plus mycophenolate mofetil (MMF) or tacrolimus plus sirolimus during their initial postoperative hospital stay. METHODS: Patients with type 1 diabetes mellitus (T1DM) and renal failure with no age limit who underwent SPK were randomly assigned to tacrolimus/sirolimus or tacrolimus/MMF immunosuppressive protocols. We analyzed the rate of adverse events that led to death, graft loss, operative revision, or prolonged hospital stay. RESULTS: From 2002 to 2009, 62 recipients were included in the MMF and 61 in the Rapamycin (Rapa) groups. More than 2/3 of recipients suffered from at least 1 complication: 74% MMF and 77 % Rapa group (P > .05). No patient died in the MMF and 3 in the Rapa group (P = .11). Pancreas graftectomy was performed in 13% of the MMF group and in 5% of the Rapa group (P = .20). Ten of 62 recipients in the MMF and 13/61 in the Rapa group required operative treatment of wound infections (P = .49). There were no differences in the rates of gastrointestinal bleeding (11% and 8%), kidney lymphocele (6% and 5%), ileus (1.6% both), pancreatic leak (1.6% both), or ureteral leak (0 and 3%) between the groups. CONCLUSION: We did not observe a difference in the rate of severe postoperative complications between groups. With the use of extraperitoneal placement of the pancreatic graft, fluid collections and wound infections remain the most frequent albeit curable postoperative complications.

[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.

The positive effect of immunosuppression on adaptation of venous allografts to arterialisation in rats.

OBJECTIVES AND DESIGN: We investigated whether immunosuppression was necessary for transplanted allogeneic veins to adapt to arterialisation. We used a transplant rat model with or without immunosuppression. MATERIAL AND METHODS: Iliolumbar veins from Lewis (LEW) or Brown-Norway (BN) rats were transplanted into the abdominal aorta of isogeneic (LEW to LEW; group A) or allogeneic (BN to LEW; groups B and C) rats. Group C had daily intramuscular injections of 0.2mgkg(-1) FK506. Light microscope evaluations of grafts were performed at 30 days following transplantation. We determined the presence of endothelial cells, the intensity of intimal proliferation and the degree of infiltration by Lewis major histocompatibility complex (MHC) class II positive, CD4-positive and CD8-positive cells into the adventitia. RESULTS: Groups A and C displayed similar results in intimal thickness (12.7+/-7.0microm vs. 15.0+/-8.4 mum, respectively) and degree of adventitial infiltration by MHC class II positive (16.6+/-7.5 vs. 14.6+/-6.2, respectively), CD8-positive (0.8+/-1.7 vs. 1.8+/-2.6, respectively) and CD4-positive (12.5+/-7.7 vs. 5.8+/-4.6, respectively) cells. In contrast, allogeneic rats without immunosuppression (group B) showed infiltration of host immunocompetent cells and destruction of the venous wall with no histological signs of arterialisation. CONCLUSION: Immunosuppressive therapy is necessary for venous allograft adaptation to arterialisation in rats.

Small bowel graft revascularization in experiment.

OBJECTIVES: The technical aspects of a procedure are most important for the outcome of the experiment. This study was designed to compare two techniques suitable for graft revascularization. METHODS: The first technique, where the animal is both donor and the recipient, consists of connecting the grafts' vascular anastomoses to the mesenteric vessel bed. In the second technique, one animal is the graft donor and the other is the recipient, with revascularization to the central vessel bed (subrenal inferior vena cava and aorta). Techniques of restoring digestive tract continuity and creation of diagnostic "chimney ileostomy" were identical in both groups. All experimental animals were monitored clinically regularly basis as per protocol (weight, temperature, stoma appearance, output and nature of stools). Blood and biopsy samples were obtained on days 0, 3, 5, 7, 10, 20, and 30. RESULTS: Overall, 43 transplant procedures were performed. The first group included 18 transplants and 66.7% animals had vascular complications. While in the second group (25 transplant procedures), vascular complication rate was only 12% (3 out of 25) perhaps due to technique modifications. CONCLUSION: Our experiment showed that both types of vascular anastomosis could be used in small bowel transplantation. Connecting the graft vessels to the aorta and inferior vena cava is technically simpler and safer because of fewer subsequent complications (Tab. 1, Fig. 4, Ref. 6). Full Text (Free, PDF) www.bmj.sk.

[Experimental small intestine transplantation]. / Transplantace tenkého streva v experimentu.

AIM: Transplantation of the small intestine is a standard treatment method in patients with small intestinal failures. The aim of this study was to master the surgical technique, optimalize immunosuppression regimes, diagnose acute cellular graft rejection based on cellular and humoral indicators. METHODS: The authors performed a total of 43 transplantation procedures in pigs. The first, surgical part of the experiment was aimed at mastering two principal methods of vascular anastomosis- firstly, connecting the graft with mesenteric vessels (Group n1 = 18) and secondly, connecting the graft with the aorta and the inferior vena cava (Group n2 = 25). The second part of the experiment included assessment of rejection changes in various immunosuppression regimes. Only animals who did not die because of a technical failure of the procedure or due to internal reasons (n = 24) were assessed. The study animals were assigned to four groups (A (n = 3)--autotransplantation, without immunosuppresion; B (n = 7) and C (n = 8)--allotransplantation with immunosuppression using tacrolimus, resp. in a combination with sirolimus; D (n = 6)--allotransplantation without immunosuppression. Rejection was diagnosed based on histological examination of the grafts@ biopsy samples. Plasmatic citruline was used as a non-invasive humoral indicator of the graft impairment. RESULTS: Procedural complications were observed in 12 (67%) study animals from the first group, and in 3 (12%) animals from the second group. In the assessment of rejection changes, the longest survival was observed with autotransplantations, the shortest survival period was shown with allotransplantations without immunosuppression. No significant survival differences were demonstrated between the both treated groups. (p < 0.05). Group C showed lower rates of cellular rejections, compared to Group B and D. CONCLUSION: During the experiment, the authors managed to master the graft collection, as well as the transplantation technique. Lower rates of surgical complications were observed when the graft was supplied by the central vascular system. No significant differencies were observed between the tacrolimus monoterapy regimen and the combination therapy with sirolimus. Histological examination is the golden standard for the cellular rejection diagnostics. Plasmatic citruline has no signifiance in the rejection assessment.

Aneurysmorrhaphy is an easy technique for arteriovenous fistula salvage.

The life-saving procedures for patients in chronic renal failure (CRF) are hemodialysis (HD) or successful kidney transplantation. HD requires a properly placed and functioning vascular access, most often obtained by creating an arteriovenous fistula (AVF). The long-term patency of AVFs is limited, in addition to other factors, by the development of intimal hyperplasia and the process results in venous wall thickening and progressive fistula occlusion. Another problem is limited patency, due to the development of pseudoaneurysm, which is associated with an increased risk of thrombosis, infection and bleeding, difficult cannulation for dialysis, pain and cosmetic defects. Treatment is focused on rapidly progressing pseudoaneurysms, which can predispose to rupture, technical problems during cannulation because of pseudoaneurysm size or a growing intraluminal thrombus. Most of these patients are scheduled for pseudoaneurysm removal and new fistula construction or, occasionally, an endovascular procedure involving stent graft implantation. This paper describes a simple and inexpensive technique of managing an AVF pseudoaneurysm, i.e. aneurysmorrhaphy. To offset the weakening of the venous wall by suture following aneurysmorrhaphy, an external polyethylene terephthalate (PET) prosthesis was implanted in the vein to prevent the development of intimal hyperplasia in the de novo created AVF.

[Dual kidney transplantation]. / Duální transplantace ledvin.

Despite the increasing demand for organs for transplantation, the number of cadaveric donors remains stable and waiting time for transplantation is gradually getting longer. In addition to the options of using kidneys from living donors and those of non heart-beating donors (NHBD), an alternative approach is transplantation of both kidneys from adult marginal donors who would otherwise be considered unsuitable for single-kidney donation. Dual kidney transplantation involves the use of both kidneys from a marginal donor for a single recipient without the recipient having to cope with the drawbacks of a limited number of functioning nephrons. Normally. these kidneys would be excluded from the transplantation program and remain unused. The submitted presentation provides information on donor and recipient selection criteria and describes the course of the first dual kidney transplantation in an adult recipient in the Czech Republic.

Aortoiliac reconstruction with allograft and kidney transplantation as a one-stage procedure: long term results.

OBJECTIVES: An increasing number of aortoiliac lesions and abdominal aortic aneurysms occur in renal failure patients waiting for renal transplantation. The aim of our study was to assess long term results of simultaneous renal transplantation and surgical repair of aortoiliac lesions with arterial allografts. DESIGN: A retrospective observational study. PATIENTS AND METHODS: From October 1997 to June 2007, we performed simultaneous aortoiliac reconstructions using fresh arterial allografts and kidney transplantation in 14 patients with chronic renal failure (men 9, women 5, mean age 53 years). The indication for vascular reconstruction was an asymptomatic abdominal aneurysm in 6 patients or aortoiliac stenosis/occlusion in 8 patients. The median follow up period for the cohort was 55.5 months (range from 1 to 116 months). RESULTS: Three patients died during the follow up period. In none of them there was an allograft (neither arterial nor renal) related death. No signs of arterial grafts infection or aneurysmal formation and no need for secondary intervention (angioplasty and/or thrombolysis) of any arterial reconstruction was observed during the follow up period in any patient. The renal grafts failed in three patients. CONCLUSIONS: Our experience suggests that it is possible and safe to use arterial allografts in the treatment of arterial occlusive disease or abdominal aortic aneurysm simultaneously with renal transplantation.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

[First experience with PTFE mesh prothesis in surgery of arteriovenous access]. / První zkusenosti s vyuzitím zevní pórované PTFE protézy v chirurgii arteriovenózních zkratu.

The authors present their initial experience with implantation of external porous PTFE prosthesis in transpositioning of the basilic vein in brachiocephalic fistules in 5 patients and in the management of radiocephalic fistules in 4 subjects during, operated from October 2006 to April 2007. Implantation of the external porous PTFE prosthesis in venous transpositions to form AVFs is aimed at prevention of pseudoaneurysms formation, as well as at prevention of development of intimal hyperplasias. The external prosthesis implantation is indicated in aneurysmoraphies, where the venous wall is weakened as a result of its suturing, which makes it predisposed for development of a new pseudoaneurysm.

[Surgical harvesting of small bowel intended for transplantation]. / Chirurgická technika odberu tenkého streva pro transplantaci.

The small intestine transplantations represent a logical alternative to final total parenteral nutrition in patients with chronic intestinal failures. It is considered a life- saving procedure in patients with intestinal failure, where standard treatment procedures cannot be further implemented. Perfect harvesting technique is very important for succesful clinical small bowel transplantation. The authors studied the surgical view of the small intestinal transplant harvesting and monitored differences in ischemic injuries to jejunum and ileum depending on duration of the cold ischemia time. The study is one of the inital works in the planned intestinal transplantation clinical programme.