Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.

Kidney surgery often includes organ ischaemia with a risk of acute kidney injury. The present study tested if treatment with the combined angiotensin II-angiotensin II receptor type 1 and neprilysin blocker Entresto (LCZ696, sacubitril/valsartan) protects filtration barrier and kidney function after ischaemia and partial nephrectomy (PN) in pigs. Single kidney glomerular filtration rate (GFR) by technetium-99m diethylene-triamine-pentaacetate clearance was validated (n = 6). Next, four groups of pigs were followed for 15 days (n = 24) after PN (one-third right kidney, 60 min ischaemia) + Entresto (49/51 mg/day; n = 8), PN + vehicle (n = 8), sham + Entresto (49/51 mg/day; n = 4) and sham + vehicle (n = 4). GFR, diuresis and urinary albumin were measured at baseline and from each kidney after 15 days. The sum of single-kidney GFR (right 25 ± 6 mL/min, left 31 ± 7 mL/min) accounted for the total GFR (56 ± 14 mL/min). Entresto had no effect on baseline blood pressure, p-creatinine, mid-regional pro-atrial natriuretic peptide (MR-proANP), heart rate and diuresis. After 15 days, Entresto increased GFR in the uninjured kidney (+23 ± 6 mL/min, P < .05) and reduced albuminuria from both kidneys. In the sham group, plasma MR-proANP was not altered by Entresto; it increased to similar levels 2 h after surgery with and without Entresto. Fractional sodium excretion increased with Entresto. Kidney histology and kidney injury molecule-1 in cortex tissue were not different. In conclusion, Entresto protects the filtration barrier and increases the functional adaptive response of the uninjured kidney.

Protection of kidney function and tissue integrity by pharmacologic use of natriuretic peptides and neprilysin inhibitors.

With variable potencies atrial-, brain-type and c-type natriuretic peptides (NP)s, best documented for ANP and its analogues, promote sodium and water excretion, renal blood flow, lipolysis, lower blood pressure, and suppress renin and aldosterone secretion through interaction predominantly with cGMP-coupled NPR-A receptor. Infusion of especially ANP and its analogues up to 50 ng/kg/min in patients with high risk of acute kidney injury (cardiac vascular bypass surgery, intraabdominal surgery, direct kidney surgery) protects kidney function (GFR, plasma flow, medullary flow, albuminuria, renal replacement therapy, tissue injury) at short term and also long term and likely additively with the diuretic furosemide. This documents a pharmacologic potential for the pathway. Neprilysin (NEP, neutral endopeptidase) degrades NPs, in particular ANP, and angiotensin II. The drug LCZ696, a mixture of the neprilysin inhibitor sacubitril and the ANGII-AT1 receptor blocker valsartan, was FDA approved in 2015 and marketed as Entresto®. In preclinical studies of kidney injury, LCZ696 and NPs lowered plasma creatinine, countered hypoxia and oxidative stress, suppressed proinflammatory cytokines, and inhibited fibrosis. Few randomized clinical studies exist and were designed with primary cardiac outcomes. The studies showed that LCZ696/entresto stabilized and improved glomerular filtration rate in patients with chronic kidney disease. LCZ696 is safe to use concerning kidney function and stabilizes or increases GFR. In perspective, combined AT1 and neprilysin inhibition is a promising approach for long-term renal protection in addition to AT1 receptor blockers in acute kidney injury and chronic kidney disease.

Shared care in prostate cancer: a three-year follow-up.

OBJECTIVE: The aim of this study was to investigate 3 year follow-up in patients with stable prostate cancer (PCa) managed in a shared care program by general practitioners (GPs) in collaboration with urological departments. PCa patients who have undergone curative treatment or endocrine therapy require long-term follow-up. Until recently, follow-up has primarily been managed by urologists at hospital-based outpatient clinics. However, new organizational strategies are needed to meet the needs of the growing number of elderly, comorbid cancer patients. These new organizational strategies target patients, GPs and specialists as joint stakeholders in the care and management of PCa. MATERIALS AND METHODS: In this 3 year follow-up to a Danish shared care PCa trial, 530 patients, out of a total of 2585 patients, were outsourced to the GPs. Strict evaluation criteria were selected to assess compliance according to individually agreed follow-up and re-referral plans for patients and GPs, respectively. RESULTS: This study included 426 (80.4%) out of the 530 PCa patients. Among these, 196 patients had initially undergone curative-intended treatment, whereas 230 patients underwent non-curative treatment. Ninety-one deaths occurred during the study period. Among the 425 patients who were alive, 335 (78.8%) gave consent for their medical records to be accessed. Overall, patient compliance was successfully met in 390 (91.5%) of the cases, while GP compliance was successfully met in 393 (92.3%) of the cases. CONCLUSION: The shared care regimen for patient follow-up between the departments of urology and the local GPs had a high rate of patient and GP compliance.

Shared care is a model for patients with stable prostate cancer.

INTRODUCTION: Patients with prostate cancer (PC) have so far been followed in specialised hospital departments after diagnosis and initiation of treatment. The main obstacles associated with the transfer of this activity to general practice include lack of experience and uncertainty as to whether general practitioners (GPs) can handle follow-up. MATERIAL AND METHODS: A Steering Committee was established in collaboration with health-care professionals to devise a strategy for a shared care model. An action plan was designed that included 1) the development of a shared care model for follow-up and treatment, 2) implementation of the shared care model in cooperation between the parties involved, 3) design of procedures for re-referral, and 4) evaluation of effect, change processes and contextual factors. RESULTS: A total of 2,585 patients with PC were included in the study: 1,172 had disseminated disease, 754 had no recurrence after curative treatment, 244 who had been treated with a curative intent were being treated for relapse, 186 underwent watchful waiting, 135 underwent active surveillance, while other scenarios applied in the remaining 94 cases. A total of 530 patients were transferred to follow-up with a GP and 2,055 were not transferred to their GP. The main reason why patients were considered not suitable for transfer to primary health care was the patients' own desire (33%), followed by clinical or biochemical disease progression (33%). The evaluation found that 96% of the patients were very comfortable with the permanent or temporary closure of the hospital course. CONCLUSION: The project focused on factors that are essential for the successful transfer of responsibility for long-term follow-up of patients with prostate cancer. Patient transfer succeeded with high initial patient satisfaction. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Samarium-153 treatment of bone pain in patients with metastatic prostate cancer.

INTRODUCTION: Painful bone metastases are common in advanced prostate cancer. We report the clinical outcome after administration of Samarium-153 ((153)Sm), an emitter of beta-particles that concentrates in the areas of enhanced osteoblastic activity. METHODS: Twenty-two patients (median age 73 years) with metastatic, hormone-refractory prostate cancer received a single bolus infusion of (153)Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region, and most had inadequate pain relief to narcotic analgesics. Bone specific pain, analgesic score according to WHO, ECOG performance status, and blood count were evaluated before and up to 28 weeks after treatment. RESULTS: Median follow-up was six weeks (mean 14 weeks). Eleven patients died within the 28 week observation period (ten from terminal disease), and four patients had their observation period truncated. Median pain score was 56.3%, 50.0%, and 50.0% of baseline values at week 4 (n = 20), 16 (n = 10), and 28 (n = 7), respectively. A reduction of baseline pain score by 50% or more was observed in 50%, 70% and 71% of patients at week 4, 16, and 28, respectively. Hematological toxicity was mild and reversible in most cases. CONCLUSION: Administration of (153)Sm to prostate cancer patients with painful bone metastases offered clinical relevant pain relief with tolerable hematological toxicity.

Bisphosphonate (zoledronic acid)-induced osteonecrosis of the jaw.

OBJECTIVE: The use of bisphosphonates (zoledronic acid) in the treatment of metastatic bone disease has been raised during recent years. The purpose of this treatment is mainly to reduce skeletal-related events, e.g. pain and pathological fractures. The aim of this study was to report the incidence of bisphosphonate-related osteonecrosis of the jaw (ONJ). MATERIAL AND METHODS: All patients treated with bisphosphonates during a 5-year period (2003-2007) were reviewed. RESULTS: Fifty-three patients, median age 69 years (range 56-81 years) were treated with bisphosphonates during the period. Fifty-one patients had hormone-refractory metastatic prostate cancer and two women had metastatic renal cell carcinoma. During this 5-year period, 686 treatments with bisphosphonates were administrated. The average treatment duration was 14 months (range 1-40 months) with administration of 4 mg of bisphosphonates every 4 weeks. Two cases of ONJ were registered. In the first case, the patient developed spontaneous osteonecrosis, whereas the second patient developed symptoms after a dental procedure. Since the initiation of a routine maxillofacial examination before treatment with bisphosphonates, no ONJ has been seen. CONCLUSION: ONJ is a rare but a very serious complication in relation to treatment with bisphosphonates. To decrease the incidence of ONJ, a maxillofacial examination could be performed in all patients before treatment with bisphosphonates.

[Acute cardiac failure in pheochromocytoma]. / Faeokromocytom debuterende som akut hjerteinsufficiens.

Pheochromocytoma (P) is an endocrine catecholamine-secreting tumor. Classical symptoms like hypertension, attacks of sweating, palpitations, headache and palor are related to catecholamine discharge. We provide a case of P in a 71 year-old man presenting with acute cardiac failure, severe reduction in left ventricular function and elevated myocardial enzymes. No coronary stenoses were found. The myocardium regained nearly normal systolic function in one and a half month. A renal P was laparoscopically removed. We discuss the pathophysiology of catecholamine cardiomyopathy.

[Urachal adenocarcinoma]. / Adenokarcinom i urachus.

We report a case of a mucin-producing adenocarcinoma in an urachal lesion. Other histological subtypes of this rare condition are mentioned. Treatment modalities for adenocarcinomas in an urachal lesion include en bloc total or partial cystectomy with excision of the urachus and umbilectomy or local resection with surveillance in highly selected cases. We discuss the reported results from these treatment modalities.

[Diagnosis, evaluation and follow-up of patients with prostatic cancer]. / Diagnose, udredning og opfølgning af patienter med prostatacancer.

The current diagnostic modalities for diagnosing and evaluating prostate cancer are described. DRE, PSA and TRUS are the three major cornerstones of the diagnostic approach and further evaluation includes bone scans. Lymphnode status can be evaluated only by lymphadenectomy, but is only of interest when curative treatment is considered. Follow-up after both curative intended treatment and hormonal treatment for advanced disease includes regular clinical checkups and evaluation of PSA status. Specific examinations may be considered depending on the symptoms and findings.

[Development of an Internet search strategy to identify new medical technologies in prostate cancer]. / Udvikling af en internetsøgestrategi til identifikation af ny medicinsk teknologi inden for prostatacancer.

INTRODUCTION: Technological change is rapid in medicine. The Internet is becoming more and more important as a source of keeping abreast of technological change, but tools to aid clinicians in finding relevant information on the Internet are lacking. The objective of this project was to develop an Internet search strategy to identify new technologies for the treatment of localised prostate cancer. MATERIALS AND METHODS: Web sites were found by means of a literature search and by searching specific Internet sources. Inclusion and exclusion criteria were developed based on literature and applied to a variety of potentially relevant sites. An initial strategy was developed, technologies identified, and the novelty and relevance were assessed by urologists in the team. This information was used to adjust the strategy. 6 general urologists assessed the efficiency of the strategy. Their input was used to define a final listing of sites. RESULTS: The strategy consists of 10 sites which should be visited in the following order: YahooHealth, DoctorsGuide, The National Electronic Library for Medicines, CancerPage, Medscape, MedlinePlus, HealthAndAge, CancerConsultants, EurekAlert, Oncolink. Links to the exact sites are provided at www.ugeskriftet.dk. CONCLUSION: This study resulted in an Internet search strategy to identify new medical technologies for a well-defined indication. The methods used may be useful in order to develop similar strategies in other clinical areas in urology or other specialties.

[Radical prostatectomies for localized prostate cancer performed in center satellite collaboration--is it possible?]. / Radikal prostatektomi for lokaliseret prostatacancer udført i center-satellit-samarbejde--kan man det?

INTRODUCTION: In an effort to comply with the increasing demand for surgery for localized prostate cancer a center satellite collaboration was established between a university department and two local urological departments. The purpose of the present study was to evaluate open radical prostatectomies performed by this collaboration. MATERIALS AND METHODS: The centre satellite collaboration included preoperative evaluation and treatment at local hospitals and evaluation of operative results by audit every 6 months. RESULTS: 104 patients were operated during the study period. 4 patients were excluded due to findings of carcinoma in lymph nodes examined by frozen section. This study describes the first 100 radical prostatectomies. Median operating time was 85 minutes (60-175) and median hospitalization was 6 days (5-23). 18 patients received blood transfusions in relation to surgery. Perioperative mortality was 0. Histological examination of prostatectomy specimens revealed that 70 patients had a localised prostate cancer (organ confined tumour) and were considered cured for their cancer. Few patients had full urinary control (no pads) at 6 weeks control, and at 12 months control 49 of 50 controlled patients were considered continent. Potency was a major problem. 22% of the 50 patients evaluated after 12 months had PSA recurrence and almost all were given adjuvant hormonal treatment. CONCLUSIONS: Radical prostatectomy performed in collaboration between a university department and local urological departments as described is beneficial to both patients and the departments involved. Postoperative results matching larger departments can be achieved.

Peritoneal dialysis catheter placement: is laparoscopy an option?

UNLABELLED: Peritoneal dialysis (CAPD) is the preferred and gentlest type of dialysis in patients with end-stage renal disease (ESRD). One of the most frequent complications following peritoneal dialysis catheter (P-catheter) placement is malfunction owing to displacement, which frequently entails major problems for the patient, including reoperation and the risk of having to switch to haemodialysis. Consequently, to ensure optimal P-catheter function and reduce patient morbidity, it is essential to develop and assess new surgical techniques for dialysis catheter placement. The objective of this survey is to describe and assess a laparoscopic-assisted procedure for P-catheter placement. MATERIAL AND METHODS: Survey of laparoscopic-assisted P-catheter placements performed during a one-year period. The study describes the operative procedure, catheter function and complications. Furthermore, a comparison with open surgery performed in the period is made. RESULTS: One of nine P-catheters inserted using laparoscopic-assisted surgery under general anaesthesia was displaced while four of 13 P-catheters inserted using traditional open surgery under local anaesthesia were displaced. The five displaced catheters were subsequently fixed laparoscopically under general anaesthesia. CONCLUSION: Laparoscopic P-catheter placement is uncomplicated, quick and reduces P-catheter displacement frequency. Drawbacks include costly equipment and the need for general anaesthesia. Future follow-up will reveal whether laparoscopically placed P-catheters yield longer-lasting and better-functioning catheters than traditionally placed P-catheters.

[Outcome of open and laparoscopic nephrectomies in a county hospital--centralization]. / Abne og laparoskopiske nefrektomier ved en amtsurologisk afdeling--centralisering?

INTRODUCTION: The results of conventional open and laparoscopic nephrectomy in a six-year period from a county hospital are presented. MATERIALS AND METHODS: In the period June 1st 1995 to June 2nd 2005, a total of 123 nephrectomies were performed. One hundred and five patients had cancer of whom 85 were operated (46 by laparoscopy and 39 by open surgery). Thirty-eight patients were operated due to a benign disease e.g. non-functional kidney, stone disease etc. RESULTS: There were 105 patients (54 men, 51 women) with cancer and 85 were operated. The hospital stay was seven days (2-29) for open surgery. The need for transfusion was 0 units (0-8 units). In 55% of the cases the operation was performed by a senior registrar. Crude survival was 60%. Overall mortality was 1.6% (2 patients). CONCLUSION: It is concluded that nephrectomy, both conventional open and laparoscopical, can safely be performed at a county hospital in terms of surgery, hospital stay, morbidity and mortality. If it is technically feasible one should offer the patient laparoscopic treatment. The operation has a high educational value for surgeons in urological training.

[Laparoscopy-assisted cryoablation of small kidney tumours]. / Laparoskopisk assisteret kryobehandling af nyretumorer.

INTRODUCTION: During the last 10 years, the number of incidentally found renal tumours has increased from 60 to 75%. Treatment modalities for these small tumours include nefron sparing surgery performed as partial nefrectomy, RFA (radio frequency ablation) or cryoablation. The purpose of this study is to present the first Danish experiences with laparoscopic assisted cryoablation of small kidney tumours. MATERIALS AND METHODS: During a period of 11 months, seven patients were treated with the procedure. All tumours were renal cell carcinomas verified on biopsy. The cryoablation (Oncura) was performed using the SeedNet system. The cryo-ablation was performed using 1.47 mm needles placed in the tumour. Ablation used Argon for freezing and Helium for thawing under high pressure (300 bar). RESULTS: A total of seven patients (median age 77 years (47-83)) were included in the study. The average operating time was 2 hours and 5 minutes. We experienced no complications during surgery and all patients were discharged the day after surgery. All patients were followed with blood samples, x-ray of the thorax and contrast CT of the abdomen. All tumours were found to be well treated, but one demonstrated slight contrast enhancement in the tumour region on control CT. CONCLUSION: Our initial experiences with laparoscopic assisted cryoablation of small kidney tumours show that this treatment modality is safe and effective. However, longer follow-up is needed for this procedure.

[Testicular torsion after previous fixation of the testis]. / Torsio testis efter tidligere testisfiksation.

Testicular torsion (TT) is caused by rotation of the testis. If not treated acutely, TT causes ischaemic necrosis. As the anatomic variations responsible for the torsion are likely to be bilateral, the opposite testis should also be fixed. We report on a case where a patient was admitted to hospital with clinical signs of TT. Two years earlier the patient had undergone fixation of the testis in an operation for TT on the opposite side. Patients with clinical signs of TT should be explored even if both testis have previously been fixed.