Renal ischemia-reperfusion injury is one of the leading causes of acute renal failure, a condition which is associated with significant morbidity and mortality (1). Injury to the kidneys following ischemia and reperfusion is a clinical concern to a wide array of doctors involved in clinical medicine. Renal ischemia followed by reperfusion may be induced as a planned inevitable part of kidney transplantation, during repair of an aortic aneurism or during laparoscopic partial nephrectomy. However, it may also occur as a consequence of low blood pressure during sepsis or following severe bleeding. Methods that may protect the kidneys against ischemia reperfusion injury will thus have an impact not only to those involved in treatment of surgical patients. Although the only thing that can save an ischemic kidney from irreversible injury is the restoration of blood flow, there is evidence that reperfusion itself actually increases the cellular injury (2). The aim of this research project is to develop clinically applicable methods of protecting the kidney against ischemia-reperfusion injury, with special attention to the setting of clamping and unclamping the renal artery in vascular and urologic surgery.
1. Kelly KJ. Acute renal failure: much more than a kidney disease. Semin Nephrol 2006;26(2):105-113.
2. Weight SC, Bell PR, Nicholson ML. Renal ischaemia--reperfusion injury. Br J Surg 1996;83(2):162-170.
PhD candidate: Marius Roaldsen
Supervision: Erling Aarsæther
Research fellows: Tuva Johanne Arnesen, Ida Marie Simonsen Toldnes
Supervision: Thor Stenberg
In Norway, bladder cancer is the 5th most common cancer and contributes significantly to morbidity and mortality. Despite being such a common disease, bladder cancer is under-prioritized and understudied.
The vast majority of bladder cancers are non-muscle invasive and generally have a good prognosis, but as many as 50 to 70% of the patients experience recurrence and 10-20% progress to more aggressive muscle invasive bladder cancer. Due to the high recurrence rate, bladder cancer patients are frequently surveilled by cystoscopy after curative treatment. Cystoscopy is the gold standard for both diagnosis and surveillance of bladder cancer, but is invasive with suboptimal accuracy, and the frequent use makes bladder cancer one of the most expensive cancer types to manage for society. A non-invasive urinary test based on suitable biomarkers have the potential to replace parts of the cystoscopies and contribute to improved clinical management of bladder cancer. Indeed, such a non-invasive test has been requested for a long time, from both patients and urologists, and represents the clinical practice of tomorrow with clear benefits for the patients and the society.
We have recently developed a biomarker-based urine test for detection of bladder cancer, with promising initial results. A national multi-center clinical study aiming at demonstrating the clinical utility of this test was partly granted last year from the health regions. Here we apply for coverage of the remaining costs to fully fund the study.
Sponsor: Group Leader/professor Guro Elisabeth Lind, Oslo University Hospital
Local responsible researcher: Magnus Larsen
Primary radical prostatectomy versus primary radiotherapy for locally advanced prostate cancer: an open randomized clinical trial - The study is sponsored by the Scandinavian Prostate Cancer Group
This prospective, open randomized phase III surgical trial seeks to study whether radical prostatectomy (with or without the combination of external radiation) improves prostate-cancer specific survival in comparison with primary radiation treatment and hormonal treatment among patients diagnosed with locally advanced (T3) prostate cancer. Untreated or conservatively treated locally advanced prostate cancer is associated with high mortality. Modern curative treatment for advanced solid malign tumors include surgery and/or radiation plus attempted chemotherapy if available to achieve both local control and elimination of potential micro metastases. Whereas there is evidence that surgery can cure localized prostate cancer, there are no clinical trials of multi-modal treatment of locally advanced prostate cancer that includes surgical removal of the prostate.
One potential advantage of adding prostatectomy to the treatment of LAPC is that removing the prostate enables a full pathological assessment of the tumor characteristics and thus a better estimation of the risk of recurrence. Surgical treatment could thus reduce the numbers needed to treat with chemotherapy and radiation, and thus improve quality of life after treatment. In addition, evidence indicate that residual cancer in the prostate occurs in 25% after radiation treatment (56)and surgical removal of the prostate may improve survival beyond what can be achieved by radiation and ADT. On the other hand, patients treated with surgery, radiation and hormones will experience side effects of all three treatment modalities and might fare better if radiotherapy plus hormones can provide oncological control without prior surgery.
A randomized clinical trial comparing two multimodal treatment regimens of which one includes a radical prostatectomy is therefore warranted.
Prostate Cancer Active Surveillance Trigger Trial (PCASTT)
The Study is sponsored by the Scandinavian Prostate Cancer Group
A large proportion of men with prostate cancer are overdiagnosed and overtreated mainly due to PSA testing. Active surveillance (AS) aims to reduce these harms by recommending curative treatment only when and if signs of tumor progression occur. There are however a number of uncertainties in AS, the most important being when to initiate treatment. The investigators are therefore starting a large randomized multicenter trial testing the safety of a standardized active surveillance protocol with specified triggers for repeat biopsies and initiation of curative treatment. The standardized protocol is compared with current practice for active surveillance. The primary aim of the study is to reduce overtreatment and subsequent side effects, without increasing the risk of disease progression or prostate cancer mortality.
Immediate curative therapy (surgery/ radiatiotherapy) reduces the risk of progression and improves overall survival after 6-10 years in younger patients (<75 years) with non-metastatic, high risk prostate cancer. However, immediate curative therapy is essentially preventive and comes with the risk of overtreatment. Increasing life expectancy has raised the question if immediate curative therapy may also benefit the large patient group of older men (≥75yrs) that is usually treated conservatively and that has largely been excluded from previous randomized clinical trials. Many centers today opt to treat patients up to 80 yrs with immediate curative therapy. However, it is unclear if the survival benefit observed in younger patients can be achieved in older men. Despite increases in life expectancy, the life time of older men is limited. Furthermore, it is entirely unclear if immediate curative therapy helps to preserve long-term quality of life in older men or if it indeed causes more harm than benefit compared to a more conservative approach.
We therefore suggest a randomized, controlled, Scandinavian (SPCG) trial comparing immediate curative therapy of high-risk-non-metastatic prostate cancer to conservative, problem-directed management in patients 75 years or older (490 patients/ arm, total of 980 patients). We investigate if immediate curative treatment prolongs life and/ or improves health-related quality of life. The results of this study will have a major impact on national and international guidelines and demonstrate the feasibility of recruiting older patients to clinical trials.
Sponsor: Sven Løffeler/Scandinavian Prostate Cancer Group
Robot-assisted radical cystectomy (RARC) is today the surgical standard for muscle invasive bladder cancer at the University Hospital of North Norway (UNN). This surgical procedure has been the preferred method since 2018. Up until 2018, open radical cystectomy (ORC) was the gold standard procedure.
A common complication of urinary diversion is ureteroenteric stricture, which is associated with infectious complications, total or partial loss of kidney function and the need for additional surgical treatment. Benign ureteroenteric anastomotic strictures are reported to be caused by ischaemia and inflammation at the anastomotic region (Lobo N, et al 2016).
Extracorporeal anastomosis has previously ben recommended in RARC. However, intracorporeal anastomosis is the preferred choice at UNN. We believe Intracorporeal anastomosis provides better chances of reconstruction with a short ureter and most likely superior circulation of the distal end compared to an extracorporeal anastomosis. Our hypothesis is that patients undergoing RARC with intracorporeal anastomosis will develop less ureteroenteric anastomotic strictures.
Research fellow: Johannes Berre
Supervision: Erling Aarsæther and Marius Roaldsen