Osteoporosis and prostate cancer; a 24-month prospective observational study during androgen deprivation therapy.

Objective: To analyze the prevalence of osteoporosis during androgen deprivation therapy (A.D.T.). Background: Treatment and prognosis of prostate cancer necessitate management of long-term consequences of A.D.T., including accelerated bone loss resulting in osteoporosis; osteoporotic fractures are associated with excess morbidity and mortality. Patients and methods: Patients with prostate cancer awaiting initiation of A.D.T. were consecutively included from the daily clinic. They were followed every 6 months for 2 years. The study consisted of questionnaires, blood and urine samples and a D.X.A. scan every 6 months and yearly bone scintigraphy. A.D.T. was given as L.H.R.H. agonists, L.H.R.H. antagonists or orchiectomy. None of the patients had received prior A.D.T. or osteoporosis treatment. Results: A total of 105 individuals were included. The mean age was 70 years, median PSA level was 30.5 µg/L and median Gleason score was 7. During the study, the prevalence of osteoporosis rose from 10% at inclusion to 22% after the 2 years of follow-up and the prevalence of normal bone mineral density (B.M.D.) decreased from 32% to 8%. Osteoporotic fractures were prevalent; six patients had a clinical vertebral fracture and two patients had a hip fracture. One patient died after his hip fracture. Conclusion: After 2 years of A.D.T. the vast majority of prostate cancer patients will have osteoporosis or osteopenia. A rigorous observation strategy did not appear to prevent osteoporotic fractures. A new strategy to reduce A.D.T. induced osteoporotic fractures is mandatory.

Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers.

The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan® Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p < 0.001), disease specific survival (DSS) (HR = 6.21, p = 0.007) and progression free survival (PFS) (HR = 5.93, p = 0.005). High expression of SPP1 was associated to poor PFS (HR = 4.41, p = 0.04). DEFB1 was associated with a better PFS (HR = 0.24, p = 0.006). In multivariate analysis, CSNK2A1 was associated to a worse OS (HR = 3.56, p = 0.008) and PFS (HR = 3.84, p = 0.005), whereas SPP1 was an independent predictor of a worse PFS (HR = 3.46, p = 0.007) and DEFB1 of a better PFS (HR = 0.37, p = 0.027). These results show that with TaqMan®) Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cacer development.

[Diagnosis and treatment of symptomatic hydronephrosis in pregnancy]. / Diagnose og behandling af symptomgivende hydronefrose i graviditeten.

Hydronephrosis in pregnancy is common in the second and third trimester. Only a few cases are symptomatic, caused by a ureteric stone or by the pregnancy itself. The clinical dilemma is when to treat and when not to treat. We propose a multidisciplinary management based on renal ultrasonography to verify hydronephrosis and renography to diagnose obstructive hydronephrosis. Obstruction with a high intra-renal pressure must be treated to avoid kidney dysfunction. Patients with pyonephrosis need immediate treatment.

High expression of KCa3.1 in patients with clear cell renal carcinoma predicts high metastatic risk and poor survival.

BACKGROUND: Ca2+-activated K+ channels have been implicated in cancer cell growth, metastasis, and tumor angiogenesis. Here we hypothesized that high mRNA and protein expression of the intermediate-conductance Ca2+-activated K+ channel, KCa3.1, is a molecular marker of clear cell Renal Cell Carcinoma (ccRCC) and metastatic potential and survival. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed channel expression by qRT-PCR, immunohistochemistry, and patch-clamp in ccRCC and benign oncocytoma specimens, in primary ccRCC and oncocytoma cell lines, as well as in two ccRCC cell lines (Caki-1 and Caki-2). CcRCC specimens contained 12-fold higher mRNA levels of KCa3.1 than oncocytoma specimens. The large-conductance channel, KCa1.1, was 3-fold more highly expressed in ccRCC than in oncocytoma. KCa3.1 mRNA expression in ccRCC was 2-fold higher than in the healthy cortex of the same kidney. Disease specific survival trended towards reduction in the subgroup of high-KCa3.1-expressing tumors (p<0.08 vs. low-KCa3.1-expressing tumors). Progression-free survival (time to metastasis/recurrence) was reduced significantly in the subgroup of high-KCa3.1-expressing tumors (p<0.02, vs. low-KCa3.1-expressing tumors). Immunohistochemistry revealed high protein expression of KCa3.1 in tumor vessels of ccRCC and oncocytoma and in a subset of ccRCC cells. Oncocytoma cells were devoid of KCa3.1 protein. In a primary ccRCC cell line and Caki-1/2-ccRCC cells, we found KCa3.1-protein as well as TRAM-34-sensitive KCa3.1-currents in a subset of cells. Furthermore, Caki-1/2-ccRCC cells displayed functional Paxilline-sensitive KCa1.1 currents. Neither KCa3.1 nor KCa1.1 were found in a primary oncocytoma cell line. Yet KCa-blockers, like TRAM-34 (KCa3.1) and Paxilline (KCa1.1), had no appreciable effects on Caki-1 proliferation in-vitro. CONCLUSIONS/SIGNIFICANCE: Our study demonstrated expression of KCa3.1 in ccRCC but not in benign oncocytoma. Moreover, high KCa3.1-mRNA expression levels were indicative of low disease specific survival of ccRCC patients, short progression-free survival, and a high metastatic potential. Therefore, KCa3.1 is of prognostic value in ccRCC.

The epithelial sodium channel γ-subunit is processed proteolytically in human kidney.

The epithelial sodium channel (ENaC) of the kidney is necessary for extracellular volume homeostasis and normal arterial BP. Activity of ENaC is enhanced by proteolytic cleavage of the γ-subunit and putative release of a 43-amino acid inhibitory tract from the γ-subunit ectodomain. We hypothesized that proteolytic processing of γENaC occurs in the human kidney under physiologic conditions and that proteinuria contributes to aberrant proteolytic activation. Here, we used monoclonal antibodies (mAbs) with specificity to the human 43-mer inhibitory tract (N and C termini, mAbinhibit, and mAb4C11) and the neoepitope generated after proteolytic cleavage at the prostasin/kallikrein cleavage site (K181-V182 and mAbprostasin) to examine human nephrectomy specimens. By immunoblotting, kidney cortex homogenate from patients treated with angiotensin II type 1 receptor antagonists (n=6) or angiotensin-converting enzyme inhibitors (n=6) exhibited no significant difference in the amount of full-length or furin-cleaved γENaC or the furin-cleaved-to-full-length ratio of γENaC compared with homogenate from patients on no medication (n=5). Patients treated with diuretics (n=4) displayed higher abundance of full-length and furin-cleaved γENaC, with no significant change in the furin-cleaved-to-full-length γENaC ratio. In patients with proteinuria (n=6), the inhibitory tract was detected only in full-length γENaC by mAbinhibit. Prostasin/kallikrein-cleaved γENaC was detected consistently only in tissue from patients with proteinuria and observed in collecting ducts. In conclusion, human kidney γENaC is subject to proteolytic cleavage, yielding fragments compatible with furin cleavage, and proteinuria is associated with cleavage at the putative prostasin/kallikrein site and removal of the inhibitory tract within γENaC.

[Fistula as cause of cyclic haematuria in a woman].

We report a case of a 32-year-old female with a vesicouterine fistula (Youssef's syndrome). She had had a low segment caesarean section and subsequently developed cyclic haematuria and menorrhoea. There was a significant delay in diagnosis of the fistula because of problems with visualising the fistula. In this case the fistula was lastly diagnosed with magnetic resonance imaging (MRI), the patient was treated with hysterectomy (patient's wish) and the fistula tract was repaired succesfully. If investigation with ultrasonography, cystoscopy and computerised tomography at a highly specialised department is negative, we recommend that MRI should be performed.

[Urinary incontinence in the elderly].

Our objective was to look at urinary incontinence in the elderly, and what measures could be taken to help this group of people alleviate the problems they may have in regard to their incontinence. We have done this through the use of recent literature. Our desire is to help more patients achieve a higher quality of life as their incontinence problems diminish.

Incidental renal neoplasms: is there a need for routine screening? A Danish single-center epidemiological study.

On the basis of associations between tumor size, pathological stage, histological subtype and tumor grade in incidentally detected renal cell carcinoma vs symptomatic renal cell carcinoma, we discussed the need for a screening program of renal cell carcinoma in Denmark. We analyzed a consecutive series of 204 patients with renal tumors in 2011 and 2012. The tumors were classified according to detection mode: symptomatic and incidental and compared to pathological parameters. Eighty-nine patients (44%) were symptomatic, 113 (55%) were incidental. Information was not available in two patients. In the incidental group, the size (p<0.05), pathological stage (p<0.001), Fuhrman grading (p<0.0001) and Leibovich score (p<0.0001) were lower than in those causing symptoms. Significantly less in the incidental group had metastasis at follow-up (p<0.0001). Incidentally discovered RCC constitute a major part of kidney tumors. They have a more favorable prognosis than symptomatic tumors and seem to be discovered in an earlier phase. Needle core biopsy is an accurate technique for distinguishing between malignant and benign tumors and is recommendable for smaller incidental tumors. Screening may help detect RCC at an earlier stage.

Prostaglandin I2 and prostaglandin E2 modulate human intrarenal artery contractility through prostaglandin E2-EP4, prostacyclin-IP, and thromboxane A2-TP receptors.

Cyclooxygenase inhibitors decrease renal blood flow in settings with decreased effective circulating volume. The present study examined the hypothesis that prostaglandins, prostaglandin E2 (PGE2) and prostacyclin (PGI2), induce relaxation of human intrarenal arteries through PGE2-EP and PGI2-IP receptors. Intrarenal arteries were microdissected from human nephrectomy samples (n=53, median diameter ≈362 µm, 88% viable, 76% relaxed in response to acetylcholine). Rings were suspended in myographs to record force development. In vessels with K(+)-induced tension (EC70: -log [mol/L]=1.36±0.03), PGE2 and PGI2 induced concentration-dependent relaxation (-log EC50: PGE2=7.1±0.3 and PGI2=7.7). The response to PGE2 displayed endothelium dependence and desensitization. Relaxation by PGE2 was mimicked by an EP4 receptor agonist (CAY10598, EC50=6.7±0.2). The relaxation after PGI2 was abolished by an IP receptor antagonist (BR5064, 10(-8) mol/L). Pretreatment of quiescent arteries with PGE2 for 5 minutes (10(-6) mol/L) led to a significant right shift of the concentration-response to norepinephrine (EC50 from 6.6±0.1-5.9±0.1). In intrarenal arteries with K(+)-induced tone, PGE2 and PGI2 at 10(-5) mol/L elicited increased tension. This was abolished by thromboxane receptor (TP) antagonist (S18886, 10(-6) mol/L). A TP agonist (U46619, n=6) evoked tension (EC50=8.1±0.2) that was inhibited by S18886. Polymerase chain reaction and immunoblotting showed EP4, IP, and TP receptors in intrarenal arteries. In conclusion, PGE2 and PGI2 may protect renal perfusion by activating cognate IP and EP4 receptors associated with smooth muscle cells and endothelium in human intrarenal arteries and contribute to increased renal vascular resistance at high pathological concentrations mediated by noncognate TP receptor.

Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo.

Voltage-gated Ca(2+) (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Cav3.1(-/-) and Cav3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Cav3.1(-/-) and Cav3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Cav3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Cav3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Cav3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K(+) was observed in isolated afferent and efferent arterioles from Cav3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Cav3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Cav3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Cav3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Cav3.2 and Cav3.1, respectively, may account for the observed effects.

Osteoporosis and prostate cancer: a cross-sectional study of Danish men with prostate cancer before androgen deprivation therapy.

OBJECTIVE: The aim of this study was to analyse the prevalence of osteoporosis and risk factors of osteoporotic fractures before androgen deprivation in Danish men. Treatment and prognosis of prostate cancer necessitate management of long-term consequences of androgen deprivation therapy (ADT), including accelerated bone loss resulting in osteoporosis. Osteoporotic fractures are associated with excess morbidity and mortality. MATERIAL AND METHODS: Patients with prostate cancer awaiting initiation of ADT were consecutively included. Half of the patients had localized disease and were referred for curative intended radiation, and the remaining patients had disseminated disease. Blood samples were collected, a questionnaire was administered and a dual-energy X-ray absorptiometry (DXA) scan was performed before initiating ADT. The patients were included between January 2010 and March 2012. The study was approved by the local ethics committee. None of the patients had received prior androgen deprivation or osteoporosis treatment. RESULTS: In total, 105 individuals were included. The mean age of the participants was 70 years (range 53-91 years, SD 6.3). The median prostate-specific antigen level was 30.5 g/l (1-5714 g/l). The average Gleason score was 7.8 (range 5-10, SD 1.1). Fifty patients had localized prostate cancer and the other 55 patients had disseminated disease. The prevalence of osteoporosis was 10% and the prevalence of osteopenia was 58% before ADT. There was no significant difference between the two subgroups concerning osteoporosis. Smoking use was the only factor that was significantly associated with an increased prevalence of osteoporosis in the study population. CONCLUSION: Two-thirds of patients with prostate cancer awaiting ADT had osteoporosis or reduced bone mass. Further awareness regarding osteoporosis and bone health in prostate cancer is needed. It is suggested that patients with prostate cancer undergo a DXA scan before starting ADT.

Spine metastases in prostate cancer: comparison of technetium-99m-MDP whole-body bone scintigraphy, [(18) F]choline positron emission tomography(PET)/computed tomography (CT) and [(18) F]NaF PET/CT.

OBJECTIVE: To compare the diagnostic accuracy of the following imaging techniques in the detection of spine metastases, using magnetic resonance imaging (MRI) as a reference: whole-body bone scintigraphy (WBS) with technetium-99m-MDP, [18F]-sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) and [(18) F]-fluoromethylcholine (FCH) PET/CT. PATIENTS AND METHODS: The study entry criteria were biopsy-proven prostate cancer, a positive WBS consistent with bone metastases, and no history of androgen deprivation. Within 30 days of informed consent, trial scans were performed in random order. Scans were interpreted blindly for the purpose of a lesion-based analysis. The primary target variable was bone lesion (malignant/benign) and the 'gold standard' was MRI. RESULTS: A total of 50 men were recruited between May 2009 and March 2012. Their mean age was 73 years, their median PSA level was 84 ng/mL, and the mean Gleason score of the tumours was 7.7. A total of 46 patients underwent all four scans, while four missed one PET/CT scan. A total of 526 bone lesions were found in the 50 men: 363 malignant and 163 non-malignant according to MRI. Sensitivity, specificity, positive and negative predictive values and accuracy were: WBS: 51, 82, 86, 43 and 61%; NaF-PET/CT: 93, 54, 82, 78 and 81%; and FCH-PET/CT: 85, 91, 95, 75 and 87%, respectively. CONCLUSIONS: We found that FCH-PET/CT and NaF-PET/CT were superior to WBS with regard to detection of prostate cancer bone metastases within the spine. The present results call into question the use of WBS as the method of choice in patients with hormone-naïve prostate cancer.

Histological step sectioning of pelvic lymph nodes increases the number of identified lymph node metastases.

Pathological examinations of lymph nodes (LN) in prostate cancer patients are handled differently at various institutions. The objective of this study is to provide means to improve the guidelines by examining the impact of step sectioning on LN status in patients with intermediate and high-risk prostate cancer. Two hundred ten patients who awaited curative indented therapy were included. We first performed a standard pathological examination of the LN, followed by an extended pathological examination of the patients who were LN negative in the standard examination. The extended pathological examination included a 100-µm-deep haematoxylin and eosin (HE) section followed by a slide stained with cytokeratin AE1/AE3 and then by four HE sections at 0.5-mm intervals.The standard pathological examination detected 41 patients with LN metastasis. The remaining 169 patients had 1,185 HE sections made at the standard examination, whereas the extended examination gave additional 7,110 slides and detected 5 additional patients with LN metastasis. In all, 1,158 LN were removed. The additional LN metastases were smaller than the LN metastases found at the standard examination, mean 1.2 mm vs. 7.8 mm.Our results indicate that an extended pathological examination of LN will improve the staging of intermediate- and high-risk prostate cancer patients; however, we acknowledge that it is both costly and time consuming. We do not recommend the use of cytokeratin staining in routine staining because the immunohistochemistry did not reveal new or further information. A detailed guideline on how to handle the LN specimens at the pathological department is needed.

[18F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node staging of prostate cancer: a prospective study of 210 patients.

UNLABELLED: Study Type--Diagnostic (exploratory cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Staging of patients with prostate cancer is the cornerstone of treatment. However, after curative intended therapy a high portion of patients relapse with local and/or distant recurrence. Therefore, one may question whether surgical lymph node dissection (LND) is sufficiently reliable for staging of these patients. Several imaging methods for primary LN staging of patients with prostate cancer have been tested. Acceptable detection rates have not been achieved by CT or MRI or for that matter with PET/CT using the most common tracer fluoromethylcholine (FCH). Other more recent metabolic tracers like acetate and choline seem to be more sensitive for assessment of LNs in both primary staging and re-staging. However, previous studies were small. Therefore, we assessed the value of [(18) F]FCH PET/CT for primary LN staging in a prospective study of a larger sample and with a 'blinded' review. After a study period of 3 years and >200 included patients, we concluded that [(18) F]FCH PET/CT did not reach an optimal detection rate compared with LND, and, therefore, it cannot replace this procedure. However, we did detect several bone metastases with [(18) F]FCH PET/CT that the normal bone scans had missed, and this might be worth pursuing. OBJECTIVES: • To assess the value of [(18) F]fluoromethylcholine (FCH) positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging of prostate cancer. • To evaluate if FCH PET/CT can replace LN dissection (LND) for LN staging of prostate cancer, as about one-third of patients with prostate cancer who receive intended curative therapy will have recurrence, one reason being undetected LN involvement. PATIENTS AND METHODS: • From January 2008 to December 2010, 210 intermediate- or high-risk patients had a FCH PET/CT scan before regional LND. • After dissection, the result of histological examination of the LNs (gold standard) was compared with the result of FCH PET/CT obtained by 'blinded review'. • Sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of FCH PET/CT were measured for detection of LNe metastases. RESULTS: • Of the 210 patients, 76 (36.2%) were in the intermediate-risk group and 134 (63.8%) were in the high-risk group. A medium (range) of 5 (1-28) LNs were removed per patient. • Histological examination of removed LNs showed metastases in 41 patients. Sensitivity, specificity, PPV, and NPV of FCH PET/CT for patient-based LN staging were 73.2%, 87.6%, 58.8% and 93.1%, respectively. • Corresponding values for LN-based analyses were 56.2%, 94.0%, 40.2%, and 96.8%, respectively. • The mean diameter of the true positive LN metastases was significantly larger than that of the false negative LNs (10.3 vs 4.6 mm; P < 0.001). • In addition, FCH PET/CT detected a high focal bone uptake, consistent with bone metastases, in 18 patients, 12 of which had histologically benign LNs. CONCLUSIONS: • Due to a relatively low sensitivity and a correspondingly rather low PPV, FCH PET/CT is not ideal for primary LN staging in patients with prostate cancer. • However, FCH PET/CT does convey important additional information otherwise not recognised, especially for bone metastases.

Angiotensin AT1 receptor-associated protein Arap1 in the kidney vasculature is suppressed by angiotensin II.

Arap1 is a protein that interacts with angiotensin II type 1 (AT(1)) receptors and facilitates increased AT(1) receptor surface expression in vitro. In the present study, we assessed the tissue localization and regulation of Arap1 in vivo. Arap1 was found in various mouse organs, with the highest expression in the heart, kidney, aorta, and adrenal gland. Renal Arap1 protein was restricted to the vasculature and to glomerular mesangial cells and was absent from tubular epithelia. A similar localization was found in human kidneys. To test the hypothesis that angiotensin II may control renal Arap1 expression, mice were subjected to various conditions to alter the activity of the renin-angiotensin system. A high-salt diet (4% NaCl, 7 days) upregulated Arap1 expression in mice by 47% compared with controls (0.6% NaCl, P = 0.03). Renal artery stenosis (7 days) or water restriction (48 h) suppressed Arap1 levels compared with controls (-64 and -62% in the clipped and contralateral kidney, respectively; and -50% after water restriction, P < 0.01). Angiotensin II infusion (2 µg·kg(-1)·min(-1), 7 days) reduced Arap1 mRNA levels compared with vehicle by 29% (P < 0.01), whereas AT(1) antagonism (losartan, 30 mg·kg(-1)·day(-1), 7 days) enhanced Arap1 mRNA expression by 52% (P < 0.01); changes in mRNA were paralleled by Arap1 protein abundance. Experiments with hydralazine and epithelial nitric oxide synthase-/- mice further suggested that Arap1 expression changed in parallel with angiotensin II, rather than with blood pressure per se. Similar to in vivo, Arap1 mRNA and protein were suppressed by angiotensin II in a time- and dose-dependent manner in cultured mesangial cells. In summary, Arap1 is highly expressed in the renal vasculature, and its expression is suppressed by angiotensin II. Thus Arap1 may serve as a local modulator of vascular AT(1) receptor function in vivo.

Urinary tract cancer in patients with hereditary non-polyposis colorectal cancer.

OBJECTIVE: Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome, is characterized as a hereditary colorectal cancer with an increased risk of cancer elsewhere in the body. MATERIAL AND METHODS: In the Department of Urology at Odense University Hospital, screening for cancer in the urinary tract has been carried out on 20 patients with HNPCC since November 2001. Clinical records and pathology results were reviewed for all patients during the screening period. RESULTS: During screening two patients without urological symptoms were found to have cancer in the ureter. CONCLUSIONS: HNPCC patients with increased risk of urinary tract cancer should be referred for screening of the urinary tract. It is also important to discuss a rational strategy towards the screening of HNPCC patients for urinary tract cancer, and to initiate further investigation into this screening.

Tissue injury after lithium treatment in human and rat postnatal kidney involves glycogen synthase kinase-3ß-positive epithelium.

It was hypothesized that lithium causes accelerated and permanent injury to the postnatally developing kidney through entry into epithelial cells of the distal nephron and inhibition of glycogen synthase kinase-3ß (GSK-3ß). GSK-3ß immunoreactivity was associated with glomeruli, the thick ascending limb of Henle's loop, and collecting ducts in the developing and adult human and rat kidney. In rats, the abundance of inactive, phosphorylated GSK-3ß (pGSK-3ß) protein decreased during postnatal development. After feeding of dams with litters lithium [50 mmol Li/kg chow, postnatal (P) days 7-28], the offspring showed plasma lithium concentration of 1.0 mmol/l. Kidneys from lithium-treated rat pups exhibited dilated distal nephron segments with microcysts. Stereological analysis showed reduced cortex and outer medullary volumes. Lithium increased pGSK-3ß and the proliferation marker proliferating cell nuclear antigen (PCNA) protein abundances in the cortex and medulla. After lithium treatment, pGSK-3ß-immunopositive cells exhibited restricted distribution and were associated primarily with subsets of cells in dilated and microcystic segments of cortical collecting ducts. After 6 wk of lithium discontinuation, adult rats exhibited attenuated urine concentration capacity and diminished outer medullary volume. Histological sections of two nephrectomy samples and a biopsy from three long-term lithium-treated patients showed multiple cortical microcysts that originated from normally appearing tubules. Microcysts were lined by a cuboidal PCNA-, GSK-3ß-, and pGSK-3ß-immunopositive epithelium. The postnatal rat kidney may serve as an experimental model for the study of lithium-induced human kidney injury. The data are compatible with a causal relationship between epithelial entry of lithium into cells of the aldosterone-sensitive distal nephron, inactivation of GSK-3ß, proliferation, and microcysts.

[Prevention and treatment of osteoporosis during treatment of non-metastatic prostate cancer]. / Udredning og behandling af osteoporose hos patienter med prostatacancer uden knoglemetastaser.

The prevention of cancer treatment-induced bone loss in patients with prostate cancer due to gonadotropin-releasing hormone (GnRH)-agonist, GnRH-antagonist and orchidectomi therapy has a high priority. We present an algorithm for the prevention and treatment of osteoporosis during treatment of non-metastatic prostate cancer.

[Increased risk of cancer in the urinary tract in patients with hereditary colorectal cancer]. / Øget risiko for cancer i urinvejene hos patienter med arvelig tyktarmskræft.

During screening of 20 selected patients with hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome) carried out in the Department of Urology of Odense University Hospital from 2001 to 2010, two patients without urologic symptoms with cancer in the ureter were found. The purpose of the present case report is to underline the importance of referring those patients with HNPCC that have increased risk of urologic cancer to screening of the urinary tract. Furthermore, this paper seeks to point out the necessity of further investigation in the risk of urologic cancer in the different mutations causing HNPCC, as well as the effects of the different screening methods in order to find the optimal screening population and the optimal screening method.