Cost and clinical outcome of islet transplantation in Norway 2010-2015.

Islet transplantation is a minimally invasive ß-cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here, we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from January 2010 to June 2015. Patients were retrospectively divided into three groups. Thirteen patients received either one or two islet transplantation alone (ITA), while five patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan-Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation. An estimated 70% maintain at least partial graft function, defined as fasting C-peptide >0.1 nmol L-1 , and 47% maintain a HbA1c below 6.5% or 2 percent points lower than before ITA. For all groups combined, we estimate that 44% of the patients have a 50% reduction in insulin requirement 4 years after the initial islet transplantation. The average cost for an islet transplantation procedure was 347 297±60 588 NOK, or 35 424±6182 EUR, of which isolation expenses represent 34%. We hereby add to the common pool of growing experience with islet transplantation and also describe the cost of the treatment at our center.

Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial.

BACKGROUND: Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. METHODS: Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. FINDINGS: At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)--87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p<0·0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score ≥ 15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. INTERPRETATION: Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. FUNDING: Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital.

Graft function 1 year after pregnancy in an islet-transplanted patient.

Pancreatic islet transplantation is a treatment option for patients with type 1 diabetes (T1D), but pregnancy has generally not been advised for women after receiving an islet allograft. We hereby describe what is to our knowledge the first successful pregnancy and persistent graft function in a woman 4 years after her initial islet transplantation. A 37-year-old woman with brittle type 1 diabetes was transplanted with two separate islet graft infusions, eventually becoming insulin independent. Ten months after her second transplantation, her immunosuppression was switched from tacrolimus and sirolimus to tacrolimus, azathioprine, and prednisolone, due to her wish to become pregnant. She became pregnant one year later, and after 38 weeks of uncomplicated pregnancy, she gave birth to a healthy child by C-section. The current report suggests that pregnancy and childbirth can be accomplished after islet transplantation without loss of islet graft function.

Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial.

BACKGROUND: Conventional anticoagulant treatment for acute deep vein thrombosis (DVT) effectively prevents thrombus extension and recurrence, but does not dissolve the clot, and many patients develop post-thrombotic syndrome (PTS). We aimed to examine whether additional treatment with catheter-directed thrombolysis (CDT) using alteplase reduced development of PTS. METHODS: Participants in this open-label, randomised controlled trial were recruited from 20 hospitals in the Norwegian southeastern health region. Patients aged 18-75 years with a first-time iliofemoral DVT were included within 21 days from symptom onset. Patients were randomly assigned (1:1) by picking lowest number of sealed envelopes to conventional treatment alone or additional CDT. Randomisation was stratified for involvement of the pelvic veins with blocks of six. We assessed two co-primary outcomes: frequency of PTS as assessed by Villalta score at 24 months, and iliofemoral patency after 6 months. Analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00251771. FINDINGS: 209 patients were randomly assigned to treatment groups (108 control, 101 CDT). At completion of 24 months' follow-up, data for clinical status were available for 189 patients (90%; 99 control, 90 CDT). At 24 months, 37 (41·1%, 95% CI 31·5-51·4) patients allocated additional CDT presented with PTS compared with 55 (55·6%, 95% CI 45·7-65·0) in the control group (p=0·047). The difference in PTS corresponds to an absolute risk reduction of 14·4% (95% CI 0·2-27·9), and the number needed to treat was 7 (95% CI 4-502). Iliofemoral patency after 6 months was reported in 58 patients (65·9%, 95% CI 55·5-75·0) on CDT versus 45 (47·4%, 37·6-57·3) on control (p=0·012). 20 bleeding complications related to CDT included three major and five clinically relevant bleeds. INTERPRETATION: Additional CDT should be considered in patients with a high proximal DVT and low risk of bleeding. FUNDING: South-Eastern Norway Regional Health Authority; Research Council of Norway; University of Oslo; Oslo University Hospital.

[Portal vein embolization before surgery for liver tumours]. / Portveneembolisering før kirurgi av leversvulster.

BACKGROUND: Radical resection is the only long-term cure for malignant liver tumours. An important contraindication for surgery is that the liver remnant would be too small. Embolization of the portal vein in the tumour-bearing side of the liver may induce growth of the healthy part and thereby render liver resection possible. MATERIAL AND METHODS: 18 patients, aged 35 - 71 years, underwent portal vein embolization in the period 2002 - 2006. An interventional radiological percutaneous transhepatic technique was used. RESULTS: The liver remnant increased with 45 % (median), range 9 - 100 %, in all patients. Liver resection could be done and was performed in 10 patients. Due to tumour progression, resection could not be done in seven patients. One patient was excluded from surgery due to serious side effects of chemotherapy. Four-year survival for patients with metastases from colorectal cancer (n=9) was 58 %. INTERPRETATION: Portal vein embolization results in a substantial increase of liver volume. The technique effectively increases the number of patients eligible for liver surgery. It is possible for patients treated with this technique to obtain the same long-term survival as those primarily regarded to be operable. Advanced radiological technology is needed to exclude patients who would not profit from the procedure.

Catheter-directed Venous Thrombolysis in acute iliofemoral vein thrombosis--the CaVenT study: rationale and design of a multicenter, randomized, controlled, clinical trial (NCT00251771).

BACKGROUND: The conventional treatment of acute deep vein thrombosis (DVT) is anticoagulation and compression therapy, as recommended in the international guidelines. Anticoagulation prevents recurrent venous thrombosis, pulmonary embolism, and death. Compression therapy reduces the risk of developing long-term sequelae, that is, postthrombotic syndrome (PTS). Evaluation of systemic thrombolysis has shown effective thrombolysis and a likely reduction in PTS but at the cost of increased risk of bleeding complications. Catheter-directed thrombolysis (CDT) was introduced for rapid removal of thrombi and salvage of venous valves with less systemic thrombolytic effect, and is being offered to selected patients with iliofemoral DVT to prevent development of PTS. Case series have shown technical and thrombolytic success; however, no randomized studies have evaluated the long-term clinical effects of venous CDT. The aim of the CaVenT study is to investigate the role of adjunctive CDT by evaluating its clinical efficacy and safety compared with conventional treatment alone in patients with acute iliofemoral DVT. METHODS: The CaVenT study is an open, randomized, controlled, clinical trial. We plan to include 200 patients who will receive either CDT, in addition to conventional treatment, or conventional treatment alone. The primary outcome measures are patency at 6 months and prevalence of PTS at 2 years. CONCLUSION: Implementation of the CaVenT study will be a contribution toward evidence-based medicine in the treatment of acute proximal DVT of the leg. Any documentation of improved functional outcome will have a significant impact on clinical practice for this patient group and may lead to a modification of existing international guidelines.

Sirolimus-eluting versus bare-metal low-profile stent for renal artery treatment (GREAT Trial): angiographic follow-up after 6 months and clinical outcome up to 2 years.

PURPOSE: To evaluate the patency of sirolimus-eluting stents (SES) compared to bare-metal stents (BMS) in the treatment of atherosclerotic renal artery stenosis (RAS). METHODS: Between November 2001 to June 2003, 105 consecutive symptomatic patients (53 men; mean age 65.7 years) with RAS were treated with either a bare-metal (n=52) or a drug-eluting (n=53) low-profile Palmaz-Genesis peripheral stent at 11 centers in a prospective nonrandomized trial. The primary endpoint was the angiographic result at 6 months measured with quantitative vessel analysis by an independent core laboratory. Secondary endpoints were technical and procedural success, clinical patency [no target lesion revascularization (TLR)], blood pressure and antihypertensive drug use, worsening of renal function, and no major adverse events at 1, 6, 12, and 24 months. RESULTS: At 6 months, the overall in-stent diameter stenosis for BMS was 23.9%+/-22.9% versus 18.7%+/-15.6% for SES (p=0.39). The binary restenosis rate was 6.7% for SES versus 14.6% for the BMS (p=0.30). After 6 months and 1 year, TLR rate was 7.7% and 11.5%, respectively, in the BMS group versus 1.9% at both time points in the SES group (p=0.21). This rate remained stable up to the 2-year follow-up but did not reach significance due to the small sample. Even as early as 6 months, both types of stents significantly improved blood pressure and reduced antihypertensive medication compared to baseline (p<0.01). After 6 months, renal function worsened in 4.6% of the BMS patients and in 6.9% of the SES group. The rate of major adverse events was 23.7% for the BMS group and 26.8% for the SES at 2 years (p=0.80). CONCLUSION: The angiographic outcome at 6 months did not show a significant difference between BMS and SES. Renal artery stenting with both stents significantly improved blood pressure. Future studies with a larger patient population and longer angiographic follow-up are warranted to determine if there is a significant benefit of drug-eluting stents in treating ostial renal artery stenosis.

The feasibility of contrast-enhanced ultrasound during uterine artery embolization: a pilot study.

PURPOSE: To evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) during uterine artery embolization (UAE) in order to define the correct end-point of embolization with complete devascularization of all fibroids. METHODS: In this prospective study of 10 consecutive women undergoing UAE, CEUS was performed in the angiographic suite during embolization. When the angiographic end-point, defined as the "pruned-tree" appearance of the uterine arteries was reached, CEUS was performed while the angiographic catheters to both uterine arteries were kept in place. The decision whether or not to continue the embolization was based on the findings at CEUS. The results of CEUS were compared with those of contrast-enhanced magnetic resonance imaging (MRI) 1 day as well as 3 months following UAE. RESULTS: CEUS was successfully performed in all women. In 4 cases injection of particles was continued based on the findings at CEUS despite angiographically complete embolization. CEUS imaging at completion of UAE correlated well with the findings at MRI. CONCLUSION: The use of CEUS during UAE is feasible and may increase the quality of UAE.

Recurrent rupture of a hypogastric aneurysm caused by spontaneous recanalization of an Amplatzer vascular plug.

A patient with a ruptured hypogastric aneurysm was treated via an endovascular approach with coils in the outflow vessels and an Amplatzer vascular plug (AVP) in the main trunk. After 4 weeks, the patient was readmitted with a recurrence of rupture of the hypogastric aneurysm caused by recanalization of the AVP. Final occlusion of the hypogastric artery was achieved by placement of a stent-graft and additional coils. In consideration of this experience, it is recommended that additional coils or several AVPs be used and early contrast medium-enhanced computed tomography follow-up be performed.

Low-profile stent system for treatment of atherosclerotic renal artery stenosis: the GREAT trial.

PURPOSE: The Palmaz Genesis Peripheral Stainless Steel Balloon Expandable Stent in Renal Artery Treatment (GREAT) Trial was designed to assess the safety and performance of a low-profile stent for the treatment of obstructive renal artery disease by looking at 6-month renal artery patency uniformly analyzed by a Core Lab. MATERIALS AND METHODS: Fifty-two consecutive patients (mean age, 63.7 years) were successfully treated with the Palmaz Genesis Peripheral Stent (Cordis, Miami, FL) on the Slalom 0.018-inch Delivery System (Cordis Europe N.V., Oosteinde 8, NLO-9301 LJ Roden, The Netherlands) at 11 investigational centers. Patients with severe renal failure and > 8-mm renal artery were excluded. Primary endpoint was angiographic determination of in-stent percent diameter stenosis at 6 months. Fifty-one patients were treated with one stent, one patient was treated with two stents to cover the complete lesion. RESULTS: Mean percentage diameter stenosis before renal angioplasty was 68.2% +/- 12.0%. No stent implantation failure, displacement, need for additional stent implantation, or procedural complication was observed. Six-month angiography was performed in 41 of 52 patients (79%) resulting in a mean in-stent percent diameter stenosis or Quantitative Vessel analysis (QVA) at 6 months of 23.9%. The in-stent binary (percent diameter stenosis > 50%) restenosis rate at 6 months was 14.3%. No fatal events occurred up to 6 months after implantation. Major adverse events occurred in five patients: four patients (7.7%) required a revascularization and one patient (1.9%) experienced a cerebrovascular event, which regressed spontaneously. CONCLUSIONS: The Palmaz Genesis stent (Cordis) provides good results for renal artery stent placement, with an in-stent binary restenosis rate (percent diameter stenosis > 50%) at 6 months of 14.3% as determined with angiography.

[Interventional radiology in Norwegian hospitals]. / Intervensjonsradiologisk aktivitet ved norske sykehus.

BACKGROUND: In recent years, interventional radiology has gained in importance in patient treatment. In order to assess the impact of this trend, the executive committee of the Norwegian Society for Interventional Radiology made a registration of all interventional procedures in Norwegian hospitals in the year 2000. MATERIAL AND METHODS: Data were collected by a questionnaire sent to all Norwegian hospitals. Coronary interventions were not included. RESULTS: Forty-four out of 58 departments returned the questionnaire; 33 stated that they performed interventional procedures. A total of 18 135 procedures were performed in Norway in 2000; we present data on the distribution of types of procedures on different categories of hospitals. INTERPRETATION: A large number of interventional radiological procedures were performed in Norwegian hospitals in the year 2000, types of intervention that are considered very important in patient management in small hospitals, too.

Acceptable short-term results after endovascular repair of diseases of the thoracic aorta in high risk patients.

OBJECTIVE: To report our experience with endovascular stentgraft repair of diseases of the descending thoracic aorta in high risk patients. METHODS: Twenty-one procedures were performed in 20 patients (10 women), aged 22-81 years, for disease of the descending thoracic aorta with the Gore Excluder thoracic endoprosthesis (WL Gore) (n=11) and the Talent LPS Stent Graft System (Medtronic AVE) (n=10). All patients were considered high operative risk. Diagnoses included saccular aneurysm, aneurysm rupture, mycotic aneurysm, penetrating atherosclerotic ulcer, aortic dissection and aortitis. The access vessels were a tube graft of the (thoraco-) abdominal aorta (n=4), the common iliac (n=6) and the common femoral artery (n=11). Several patients needed major cardiovascular surgery for concomitant disease during the same stay. Computed tomography scan and chest X-ray was performed at 3 and 6 months and thereafter every sixth month postoperatively. RESULTS: Two patients died. One had a colon perforation 8 days postoperatively and died after 3.5 months, and the other with preoperative sepsis and a mycotic aneurysm died on day 11 from cardiac and renal failure. In one patient the stentgraft dislocated during release, and an additional stentgraft had to be implanted 1 week later to treat the proximal leak. In another patient the stentgraft could not be released from the introducer, and was pulled back to the aortic bifurcation and retrieved through laparotomy. Eighteen patients have been followed for 1-24 months, and no migration, wire fractures or endoleak have been seen. There were no neurologic complications. One patient treated for infected pseudoaneurysm had a chronic graft infection. CONCLUSION: In this small number of patients with high operative risk, short-term results of endovascular stentgraft repair of variable diseases of the descending aorta have been satisfactory. Stentgraft repair could be a valuable supplement to surgery for patients with complex multilevel or multiorgan disease.

[Endovascular stent-graft repair of abdominal aortic aneurysm]. / Endovaskulaer stentgraftbehandling av abdominale aortaaneurismer.

BACKGROUND: Endovascular stent-graft repair of abdominal aortic aneurysms was introduced in 1991. Long-term results from randomised studies are still not available. Aneurysm ruptures after stent-graft repair have been reported, and there has been a considerable need for redo procedures. MATERIAL AND RESULTS: At Rikshospitalet in Oslo, Norway, 26 stent-graft implantations for abdominal aortic aneurysms were performed during the years 1996-2000, two of which were primary technical failures immediately converted to open repair. During follow-up, two patients have died from unrelated causes after six and 12 months. Eight patients were converted to open repair 8-50 months (median 31) after implantation. Indications for conversion were migration (n = 4), increasing aneurysm diameter (n = 3) and rupture (n = 1). Of the 14 patients still under observation, six have had one or more endovascular interventions (a total of 10) for failing graft. INTERPRETATION: Continuous technology development has been used as an argument to postpone randomised studies, as improved results are expected with new generations of stent-grafts. There is a need for discussion of the strategy for the further use of endovascular repair of abdominal aortic aneurysm.