Histopathological Features of Time-Zero Kidney Biopsy Are Predictive Factors for Posttransplant Anemia.

INTRODUCTION: Posttransplant anemia (PTA) is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of PTA with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. METHODS: We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our center. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis (AH), vascular fibrous intimal thickening (CV), interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. RESULTS: The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and PTA in both time points, independently from estimated glomerular filtration rate. AH and interstitial fibrosis were identified as independent risk factors for anemia 6 months after transplantation. CONCLUSION: Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA.

Risk factors for non-melanoma skin cancer development in renal transplant recipients: a 40 year retrospective study in Croatia.

AIM: To determine the prevalence of non-melanoma skin cancer (NMSC) and disease-specific risk factors in renal transplant recipients (RTRs). METHODS: This retrospective cohort study enrolled 1232 RTRs (736 men) treated in University Hospital Center Zagreb over 40 years. The effect of sex, age at transplantation, geographic residence, dialysis vintage, and the type of immunosuppressive therapy on NMSC occurrence was investigated. RESULTS: The prevalence of NMSC was 6.81%. Overall, 60.7% of patients developed basal cell carcinoma (BCC) and 30.9% of patients developed cutaneous squamous cell carcinoma (cSCC). Only 8.3% developed both tumors. The BCC:cSCC ratio was 1.76:1. The risk for NMSC was 50% higher in men. Patients older than 50 years at transplantation were at greater risk for NMSC development. Residence in an area with higher ultraviolaet radiation (UV) exposure and dialysis vintage before transplantation did not influence NMSC development. Cyclosporine and azathioprine treatment conferred a greater risk for NMSC than tacrolimus or mycophenolate mofetil treatment. CONCLUSION: RTRs are at high risk for NMSC development. Sex, age at transplantation, and type of immunosuppressive therapy play a role in tumor development.

Emergency Ilio-femoral Bypass during Kidney Transplantation due to External Iliac Artery Dissection: Case Report.

Intraoperative iliac artery dissection during kidney transplantation is a rare but serious complication that requires prompt intervention. We present a case of right external iliac artery dissection during deceased donor kidney transplantation. A 57-year-old male patient underwent standard pretransplant evaluation and had no signs of either significant aortoiliac occlusive disease or peripheral arterial occlusive disease. Diabetic nephropathy, arterial hypertension and smoking were the underlying causes of the patient's end-stage renal disease. Transplantation was performed in the standard fashion. The kidney was positioned in the right iliac fossa and the venous end to-side anastomosis was performed first. A significant dissection of the right external iliac artery was found on arteriotomy. Immediate ilio-femoral bypass with a vascular prosthesis was performed. During two years of follow-up the kidney function is stable and there are no signs of lower limb vascular insufficiency.

Targeted prostate biopsy using a cognitive fusion of multiparametric magnetic resonance imaging and transrectal ultrasound in patients with previously negative systematic biopsies and non-suspicious digital rectal exam.

AIM: To compare cognitive fusion targeted and systematic prostate biopsy in patients with repeated negative systematic biopsy but persistent clinical suspicion for prostate cancer. METHODS: The study enrolled 63 patients with at least one previously negative systematic biopsy who underwent targeted prostate biopsy using multiparametric magnetic resonance imaging (mpMRI) and transrectal ultrasound (TRUS) in addition to standardized systematic biopsy from July 2016 to May 2018. Multiparametric MRI was performed with 3 Tesla device by uro-radiologists experienced in prostate cancer. Lesions with Prostate Imaging Reporting and Data System 3, 4, and 5 were considered suspicious. Targeted biopsies were performed with cognitive fusion of TRUS and mpMRI. RESULTS: Prostate cancer detection, using either targeted or systematic biopsy, was 60.32%. Targeted biopsies were positive in 52.38% and systematic biopsies in 47.62% of patients. The median highest percentage of cancer involvement per biopsy core was significantly higher in targeted cylinders. The biopsies obtained by using the two techniques did not significantly differ in Gleason score. CONCLUSION: Cognitive targeted prostate biopsy based on mpMRI presents a valuable addition to systematic biopsy in patients with repeated negative systematic biopsies but persistent clinical suspicion of prostate cancer.

THE PROSTATE CENTER: MULTIDISCIPLINARITY, ORGANIZATION OF DIAGNOSTIC WORK-UP AND TREATMENT OF PROSTATE CANCER.

The aim of this paper is to show the results of prostate cancer treatment in Prostate Center of Department of Urology at the University Hospital Center Zagreb. The answer to growing demands for prostate cancer treatment due to increasing incidence is the formation of specialized, multidisciplinary units/centers that deal mainly with prostate cancer. The need was recognized by European School of Oncology and European Association of Urology, who have proposed their concepts of validating such centers with the aim of promoting high-quality prostate cancer treatment. Following these trends, the Department of Urology at the University Hospital Center Zagreb has established the Prostate Center. This new unit offers specialized and individualized approach to workup, treatment and follow up for prostate cancer patients based on multidisciplinarity. The Prostate Center was also established as a platform for education and research.

SURGICAL TREATMENT OF HIGH-RISK PROSTATIC CARCINOMA AND OLIGOMETASTATIC DISEASE.

Prostate cancer is responsible for the largest number of cancer-related deaths in male population in many countries of the world. Aggressive forms of the disease are associated with an increased risk of local recurrence and death. Treatment of high-risk local prostate cancer most commonly involves radical prostatectomy (RP) or external beam radiation therapy (EBRT) combined with androgen deprivation therapy (ADT) with or without the addition of brachytherapy (BT). The use of surgery for high risk prostatic carcinoma (HRPC) is on the rise, because of its advantages including the possibility of cure with surgery alone without the risk of toxicities from prolonged ADT, accurate staging, and avoiding the influence of PSA originating from benign prostatic hyperplasia on future therapy. Oligometastatic prostate cancer may be considered as the last border of possibly curable disease. Radical prostatectomy in oligometastatic prostate cancer can significantly decrease the risk of local complications but only multimodal approach in selected group of patients may offer opportunities to eradicate tumor or delay its progression. Surgery for oligometastatic disease most commonly targets lymphatic disease with salvage pelvic lymph node dissection, whereas it rarely targets distant metastases. Further prospective, randomized studies are necessary to define the role and value of therapies in oligometastatic prostate cancer.

Therapeutic challenges in the mature patient.

With the tremendous increase in the proportion of seniors in the global population, geriatric health care has become of greater interest and concern. Increased emphasis on geriatric medicine, along with the growth in the development of age-related skin disorders, has led to particular attention for geriatric, dermatology and dermatopharmacology. An aging population has brought many therapeutic challenges that we need to recognize and overcome by applying geropharmacologic principles. The purpose of this paper is to inform dermatologists of the age-related changes in the pharmacokinetics of common dermatologic drugs, their various interactions potentially occurring in the elderly, and the principles and evidence-based strategies for detection, management, and prevention to improve medication adherence. By implementing these principles and strategies, we can ensure the best and the safest treatment to promote the desired therapeutic outcome and improved quality of life for this fragile subpopulation.

Penile cutaneous horn ten years after treatment of verrucous squamous cell carcinoma on penile glans: case report.

Penile cutaneous horn is a clinical term that describes protruding hyperkeratosis, usually conical in shape, located on penile glans. Penile localization of this lesion, predominantly located on sun-exposed areas, is very rare. The association with malignancy on the penis makes proper identification of these lesions essential. We present a 45-year-old man with a cutaneous horn, 25 mm in size, located on the basis of penile glans. The patient had a history of phimosis, pseudoepitheliomatous balanoposthitis, surgical excision of penile verrucous squamous cell carcinoma (SCC) and postoperative radiotherapy of carcinoma in situ on the same localization, ten years before. Complete surgical removal of the horn with separate excision of the margins and base was done. Pathologic examination revealed squamous hyperplasia with suspicion of carcinoma in situ. Additional negative p16(INK4a) immunohistochemical analysis confirmed benign proliferative lesion. DNA polymerase chain reaction for human papilloma virus infection was negative. These findings suggested sparing surgical procedure in our patient, without indication for partial penile amputation, but with mandatory follow-up. Our case confirmed the association of pseudoepitheliomatous balanoposthitis with verrucous SCC, as well as the possible influence of radiotherapy on the development of penile cutaneous horn. Additionally, we showed the important role p16(INK4a) immunohistochemical analysis in the differential diagnosis of alterations adjacent to invasive SCC of the penis.

[Evolution of arteriovenous fistula between renal artery and vein in renal allograft after percutaneous nephrostomy in a renal transplant recipient]. / Evolucija arteriovenske fistule renalne arterije i vene bubreznog alografta nakon perkutane nefrostomije u bolesnika s transplantiranim bubregom.

Percutaneous urologic intervention has been accepted as a standard method to identify the etiology of graft dysfunction, or for treatment of urinary obstruction. Although ultrasound-guided procedure is a relatively safe method, arteriovenous fistula (AVF) is an important complication that is sometimes encountered. In this report, we present a renal transplant patient in whom an AVF and renal vein pseudoaneurysm after percutaneous nephrostomy were diagnosed. Surgical approach was not indicated for preservation of renal function. A 50-year-old man was admitted with obstructive uropathy 11 months after cadaveric renal transplantation. Percutaneous nephrostomy was performed under ultrasound guidance. Doppler sonography and angiography revealed an AVF between the main renal artery for lower pole of the graft and renal vein, with formation of a venous pseudoaneurysm. Careful monitoring during the next 7 years after iatrogenic AVF and venous pseudoaneurysm formation resulted in preservation of renal graft function and improvement of the patient's quality of life. Radiological interventional procedure with vascular graft-stent placement was indicated because of rapid pseudoaneurysm enlargement and high risk of its rupture. Interventional endovascular graft-stent placement is a safe procedure for exclusion of renal allograft and AVF from circulation without indication for open surgery in high-risk transplanted patients. According to our opinion, radiological interventional or surgical procedure in transplanted patients with AVF and pseudoaneurysm should be considered as the treatment of choice only in patients who have clinical symptoms or rapid growth of AVF with a high risk of pseudoaneurysm rupture.

Transurethral incision/resection of the prostate (TUIP/TURP) in operative treatment of repeated bladder outlet obstruction early after kidney transplantation.

The aim of the study was to assess the incidence and etiology of repeated bladder outlet obstruction (BOO) after kidney transplantation and to analyze the results of transurethral incision of the prostate/transurethral resection of the prostate (TUIP/TURP) in the early period after kidney transplantation. The study included 24 male patients having undergone renal transplantation and early transurethral surgery for BOO in our institution between 2005 and 2011. TUIP or TURP was performed depending on the etiology of BOO. The indications for transurethral surgery were repeated urinary retention despite therapeutic attempts with alpha-receptor antagonists, or repeated residual urine with renal transplant dysfunction and/or consequent urinary tract infection. Preoperative assessment included past medical history, clinical examination, PSA, volume of residual urine estimated with ultrasound, and urinary culture. Among 345 male patients having undergone renal transplantation, repeated BOO was noted in 24 patients. TUIP was performed in 19 and TURP in five patients. The mean age of our patients was 52 (range, 33-73) years and the mean time on dialysis 7.43 years (range, 4 months to 25 years). The procedure was performed on the mean of day 16 (range, 14-29) after transplantation and urethral catheter was removed on the mean of day 3.3 (range, 2-9) after the procedure. The etiology of BOO was bladder neck contracture in nine and benign prostatic hyperplasia in 15 patients. In all patients, surgical procedures were performed without any complication. Restoration of urinary bladder function was complete in all patients. In conclusion, early transurethral treatment of repeated BOO is a safe procedure with excellent results following renal transplantation.

Head and neck malignancies in Croatian renal transplant recipients.

Renal transplantation is associated with increased incidence of cancer. We reviewed a large series of renal transplant recipients to determine the incidence and outcome of patients with malignant changes located at the head and neck. A total of 1232 renal transplant recipients have been followed at Department of Dialysis University Hospital Centre Zagreb from 1972 to 2009. Demographic data, localization and disease outcome were evaluated in patients who developed cancer. Twenty one patients (1.7%) developed 27 head and neck malignancies. The average time from transplantation to development of cancer was 56.8 months. The mean length of follow-up was 9.4+/-4.8 years. Eighteen malignancies were cutaneous in origin and 9 were noncutaneous. Of cutaneous malignancies, 88.9% were basal cell carcinoma; one patient had Merkell-cell carcinoma and one patient developed squamous cell carcinoma. Six cases of basocellular skin cancer were recorded in one fair-skin patient. Noncutaneous malignancies involved the oral cavity (2 cases of Kaposi's sarcoma and one pharyngeal cancer) and the thyroid gland in 3 patients each. Two patients had post-transplant lymphoproliferative disorder occurring at the head and neck. One patient had brain tumor. Radical surgery, radiation, and/or chemotherapy were necessary in 33.3% of patients. Immunosuppression was reduced in all patients, and 12 patients were switched from the calcineurin-based immunosuppression to sirolimus. They all have stable graft function. None of the patients died from cancer. Immunosuppression was ceased in one patient with Kaposi's sarcoma who returned to dialysis and died 10 years later from heart failure. An increased incidence of cancer occurring in the head and neck was recorded. Careful skin examination and oral examination is mandatory for discovering cancer before dissemination. Sirolimus is safe alternative to calcineurin-based immunosuppression in patients who developed head and neck malignancies.

Association of cyclooxygenase-2 immunoreactivity with tumor recurrence and disease progression in superficial urothelial bladder cancer.

AIMS AND BACKGROUND: The main characteristic of urothelial bladder cancer is a clear predisposition to recurrence and disease progression. The aim of this study was to assess the possible relationship between cyclooxygenase-2 (COX-2) immunoreactivity in superficial urothelial bladder carcinoma and tumor grade, stage, number of recurrences and clinical disease progression. METHODS: In this prospective study 70 consecutive patients who underwent transurethral resection for superficial urothelial bladder cancer were included. Tumor slides were immunohistochemically stained for COX-2, and COX-2 immunoreactivity in tumor and inflammatory stromal cells was categorized as negative or mildly, moderately or strongly positive. Patients were followed up for 2 years, and during this period the possible association of COX-2 immunoreactivity with tumor stage and grade, number of recurrences and progression of disease was evaluated. RESULTS: COX-2 immunoreactivity in tumor cells was found in 57 (81.4%) patients and did not correlate with tumor grade, stage of disease, number of recurrences, and progression of disease. COX-2 immunoreactivity in inflammatory cells was found in 16 of the 57 patients with COX-2 positive tumors, and was significantly related to the number of recurrences, time to appearance of the first recurrence, and disease progression. CONCLUSIONS: COX-2 immunoreactivity in inflammatory stromal cells adjacent to the COX-2-positive tumor might be useful in clinical practice for selection of patients with a high risk of tumor recurrence and disease progression.

Virilizing adrenal cancer and bail-out nephrectomy.

We report a rare case of virilizing adrenal cancer with tumorous invasion of the left renal vein in which a retroperitoneal adrenalectomy with bail-out nephrectomy was performed. A tumor thrombus infiltrated the wall of the left adrenal vein and extended into the left renal vein. Initially, a kidney sparing procedure with partial tangential excision of the involved renal vein wall was performed. After positive vein margins were confirmed with intraoperative histology, the indication for nephrectomy was made. To the authors' awareness, this is the first report of a virilizing adrenal cancer with a tumor thrombus infiltration of the renal vein and surgical tendency for kidney preservation.

Long-term outcome after surgical kidney revascularization for fibromuscular dysplasia and atherosclerotic renal artery stenosis.

PURPOSE: At a time of minimally invasive surgery in urology, the role of surgical kidney revascularization in the management of renal artery disease has changed during the last decade. Our experience with surgical kidney revascularization, and the long-term clinical outcomes of fibromuscular dysplasia (FMD) and atherosclerotic renal artery stenosis are reviewed. MATERIALS AND METHODS: The study group comprised 140 patients with renovascular hypertension, 72 with FMD and 68 with atherosclerotic renal artery disease, who underwent surgical revascularization between 1982 and 1999. The indications for surgical revascularization were the treatment of hypertension and the preservation of renal function in 17 patients with renal artery occlusion, 55 with ostial stenosis, 52 with branch stenosis, 6 with bilateral artery stenosis, 7 with solitary kidney renal artery stenosis and 3 with solitary kidney renal artery occlusion. RESULTS: Postoperative blood pressure and renal function were monitored for 1 to 17 years (mean 11.3). Long-term blood pressure control was observed in 93% of patients with FMD and in 71% of those with atherosclerosis. Improvement or stabilization of renal function was observed in 92% of patients with FMD and in 68% of those with atherosclerosis. The preoperative estimated glomerular filtration rate compared to postoperative was significantly increased in both groups. CONCLUSIONS: Surgical kidney revascularization is effective in secondary hypertension with a high long-term efficacy in the normalization of blood pressure and in the preservation of renal function, especially in patients with a solitary or 1 functional kidney.