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.

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.

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.

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.

Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.

OBJECTIVE: Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals. RESEARCH DESIGN AND METHODS: The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA(1c) 7.3%, and BMI 32 kg/m(2)). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma C-peptide concentrations were measured at baseline and after 4 weeks of treatment. RESULTS: Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA(1c) levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA(1c) levels) than the same total dose of repaglinide divided into morning and evening mealtime doses. CONCLUSIONS: These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.

[Distribution of colonic surgery among surgeons in the city of Copenhagen]. / Fordeling af colonkirurgi på operatører i hovedstadsområdet.

INTRODUCTION: The outcome of some surgical procedures is related to the surgeon's experience. We examined how much experience surgeons in 12 hospitals in the region of Copenhagen gained in colon surgery in 1999. MATERIAL AND METHODS: The Ministry of Health identified the number of colon patients operated on in the region of Copenhagen in 1999. The departments were asked to validate the lists of patients and to fill in a questionnaire describing the surgeon's experience in that year. RESULTS: Eleven of 12 departments answered the questionnaire (92%). One hundred and two senior surgeons operated on 674 patients. Forty of the surgeons operated on one to four patients in 1999, and only five performed 15 or more operations. More than 50% of the surgical procedures were carried out by surgeons who performed fewer than 10 colon operations in 1999. Most of the low-volume surgeons' operations were performed during calls. DISCUSSION: Colon surgery in the region of Copenhagen was performed by a large number of surgeons in many hospitals in 1999. Hospital volume was not associated with surgeon volume.

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.

[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.

[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.

[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.

[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.