S. Pahernik

Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels

Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A‐Mel‐3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double‐fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome‐induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3‐fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.

Nephron Sparing Surgery for Renal Cell Carcinoma With Normal Contralateral Kidney: 25 Years of Experience

PURPOSE We report the long-term results of our consecutive series of 504 patients who underwent NSS for cancer suspicious, solid renal tumors in the presence of a normal opposite kidney at our institution since 1979. MATERIALS AND METHODS A total of 715 patients underwent NSS since 1969, including 504 for an elective indication, that is with a normal opposite kidney. Of these patients 381 (75.6%) had RCC, 123 (24.4%) had cancer suspicious benign lesions, including 53 (10.5%) with oncocytoma, 33 (6.5%) with angiomyo(lipo)ma, 23 (4.6%) with a complicated cyst and 13 (2.8%) with other benign lesions. Of the 381 patients with RCC 283 (74.3%) had clear cell, 68 (17.8%) had papillary and 30 (7.9%) had chromophobic RCC. Mean tumor diameter was 3.0 cm (range 0.5 to 11.0). Mean followup was 6.77 years (range 0.2 to 24.1). The oncological outcome was studied, including pathological features associated with tumor progression. RESULTS Estimated cancer specific survival rates at 5 and 10 years were 98.5% and 96.7%, respectively. Estimated survival rates free of distant metastasis at 5 and 10 years were 97.5% and 95.1%, respectively. Nine patients with localized RCC experienced local recurrence after NSS. Estimated survival rates free of local recurrence at 5 and 10 years were 98.3% and 95.7%, respectively. CONCLUSIONS The long-term results of our series support the concept of organ sparing surgery for RCC in the presence of a normal opposite kidney with excellent long-term survival and a low tumor recurrence rate.

Cellular damage to human hepatocytes through repeated application of 5-aminolevulinic acid

BACKGROUND/AIMS 5-Aminolevulinic acid (ALA), a precursor of porphyrins is used for photodynamic diagnosis and therapy within topical or systemic applications. A potential toxic effect on the human liver is of major interest and therefore we investigated the impact of a repeated application of ALA without illumination on cultures of human hepatocytes. METHODS After ALA treatment of hepatocytes in vitro the porphyrin synthesis, albumin secretion, liver-specific enzyme release, and malondialdehyde levels were determined. In order to reduce levels of reactive oxygen substances, mannitol and the antioxidant enzymes superoxide dismutase and catalase were supplemented. RESULTS Porphyrin biosynthesis by human hepatocytes in vitro was repeatedly stimulated by ALA (0.001-1.0 mM), which was indicated by an accumulation of protoporphyrin IX. A repetitive treatment (up to four times) of hepatocytes with ALA resulted in an impairment of the hepatic function and viability, depending on the ALA concentration (0.1-1.0 mM) and frequency of application (2-3 times). This was also accompanied by increased malondialdehyde levels indicating enhanced lipid peroxidation. Only superoxide dismutase was able to reduce cellular damage and prevent specific function. CONCLUSIONS Repeated, not single, ALA treatment without illumination may cause deleterious effects to the liver, which are mediated by oxygen radicals and inhibited by an antioxidant.

Long-Term Followup of the Intussuscepted Ileal Nipple and the In Situ, Submucosally Embedded Appendix as Continence Mechanisms of Continent Urinary Diversion With the Cutaneous Ileocecal Pouch (Mainz Pouch I)

PURPOSE We analyzed stoma related complications and continence rates in patients who underwent continent urinary diversion with the cutaneous ileocecal pouch (Mainz pouch I). We compared the intussuscepted ileal nipple and in situ, submucosally embedded appendix as continence mechanisms. MATERIALS AND METHODS A total of 401 patients were included in a retrospective followup study. Continence mechanisms were the intussuscepted ileal nipple in 205 patients and the in situ, submucosally embedded appendix in 196. RESULTS A total of 144 patients (36%) required intervention for a stomal complication. Of patients who received an intussuscepted ileal nipple 34 (17%) had stomal stenosis at a mean time to first stenosis of 43.8 months, 41 (20%) had stones at a mean interval to the first stone of 62.8 months, 12 underwent reoperation for stomal incontinence, including 1 because of nipple necrosis, and 82% were completely continent. Of patients who received an in situ, submucosally embedded appendix 63 (32%) had stomal stenosis at a mean time to first stenosis of 31.4 months, 20 (10%) had stones at a mean interval to the first stone of 47.5 months, 3 underwent reoperation for stomal incontinence, 4 had appendiceal necrosis and 92% were completely continent. CONCLUSIONS Of stomal complications 63% were treated endoscopically. The higher rate of stomal stenosis with the appendiceal stoma is most likely due to the smaller diameter of the appendix. The higher rate of stone formation in patients with the intussuscepted ileal nipple is related to metal staples. Continence rates of the 2 outlets are good with somewhat larger amounts of mucous secretion from the larger stoma of the intussuscepted ileal nipple.

Rectosigmoid Pouch (Mainz Pouch II) in Children

PURPOSE Continent anal urinary diversion is a therapeutic option in bladder exstrophy. We report our long-term results with the rectosigmoid pouch (Mainz pouch II), a modification of the classic ureterosigmoidostomy. MATERIALS AND METHODS A total of 38 children with a mean age of 5 years (range 0.5 to 17) underwent a Mainz pouch II procedure between 1991 and 2004. Most patients (33) had bladder exstrophy or incontinent epispadias. In 14 children (37%) urinary diversion was performed after failed primary reconstruction. In 6 children conversion was performed from an incontinent type of urinary diversion. Renal function, continence and metabolic changes were analyzed. A total of 35 children were followed for a mean of 112 months (range 5 to 147). RESULTS All children were continent during the daytime but 3 (8.6%) suffered from nighttime incontinence requiring pads. With respect to the upper urinary tract, 6 children (15.8%) had development of pyelonephritis, mostly with stenosis of the ureterointestinal anastomosis. Reimplantation of the ureter was required in 10 of 69 RU (14.5%), of which 7 (10.1%) were due to ureterointestinal stenosis and 3 (4.3%) were due to reflux. Serum creatinine was within normal limits in all children. During followup acid-base balance was monitored, and early alkali supplementation was initiated in 24 of 35 children (69%) when the base excess was less than -2.5 mmol/l. One child had development of clinical acidosis requiring hospitalization. After followup of more than 10 years annual rectosigmoidoscopy was performed in 16 children/young adults without pathological findings. CONCLUSIONS The Mainz pouch II procedure for children with genitourinary anomalies promises excellent continence rates. However, periodic followup studies are important to check the upper urinary tract and prevent metabolic acidosis. Due to the risk of malignancy at the ureterointestinal anastomosis, endoscopy should be performed annually beginning at postoperative year 10. The Mainz pouch II procedure is safe in the long term. Without stoma, appliance or catheterization this type of continent urinary diversion is specifically suitable for children.

Bilateral synchronous sporadic renal cell carcinoma: surgical management, oncological and functional outcomes

To analyse the functional and oncological outcomes of surgical treatment of bilateral synchronous sporadic renal cell carcinoma (RCC).

Long-term follow-up of submucosal tunnel and serosa-lined extramural tunnel ureter implantation in ileocaecal continent cutaneous urinary diversion (Mainz pouch I)

Authors from Mainz, Germany present the long‐term follow‐up of submucosal tunnel and serosa‐lined extramural tunnel ureter implantation in the ileocaecal continent cutaneous urinary diversion first described in that department, called the Mainz‐Pouch I.

Renal tumour surgery in elderly patients.

To analyse morbidity, renal function and oncological outcome in patients aged ≥80 years who had surgery for renal tumours, as in the elderly such surgery is controversial in relation to life‐expectancy and other causes of death.

Diabetes mellitus und Blasenfunktion

ZusammenfassungSteigende Prävalenz und zunehmende Patientenlebenserwartung haben beim Diabetes mellitus trotz oder gerade wegen modernster medizinischer Behandlungsmethoden zu einer Häufung urologisch relevanter Spätkomplikationen geführt. Die Prävalenz der diabetischen Zystopathie (herabgesetztes Blasenfüllungsgefühl, hohe Blasenkapazität und Blasenentleerungsstörungen) liegt bei nicht insulinpflichtigen Diabetikern bei 25% und bei insulinpflichtigen bei 48%. Ursachen sind die diabetogene autonome und peripher-somatische Polyneuropathie mit beeinträchtigter Blasensensibilität sowie Blasenhypokontraktilität infolge einer Überdehnungsmyopathie des Detrusors. Aufgrund ihrer Symptomarmut erfordert die Verhütung schwerwiegender Folgezustände der diabetischen Zystopathie (Reflux, rezidivierende Harnwegsinfekte, Urolithiasis, Pyelonephritis) die volle urologische Aufmerksamkeit und den frühzeitigen und wiederholten Einsatz urodynamischer Diagnostik. Komorbiditäten können zu einer Vielfalt urodynamischer Befunde führen. Die Therapie ist in der Regel konservativ (Miktionstraining, Einmalkatheterismus, ggf. Pharmakotherapie) und sollte nur interdisziplinär erfolgen, da unerkannte Komplikationen fachfremder Organsysteme langfristig größere volkswirtschaftliche Belastungen verursachen als die präventive Hinzuziehung anderer Fachrichtungen.AbstractIncreasing prevalence of diabetes mellitus and rising patient life expectancy are causing an accumulation of urologic late complications—despite or due to steadily improving medical health care. The prevalence of diabetic cystopathy (impaired bladder sensation, increased bladder capacity, sometimes accompanied by voiding difficulties and residual urine) is 25% in non-insulin-dependent diabetics and 48% in insulin-dependent diabetics. Autonomic and peripheral neuropathy lead to detrusor hyposensitivity, and chronic overstretching of the bladder causes myogenic detrusor hypocontractility. Since diabetic cystopathy often develops insidiously and asymptomatically, prevention of secondary complications such as recurrent urinary tract infections, vesicorenal reflux, nephrolithiasis, and pyelonephritis requires the urologist’s full attention as well as early and repeated urodynamic diagnostics. Comorbidities can lead to a variety of urodynamic findings. Therapeutic options are generally conservative (timed voiding, micturition training, CIC, pharmacotherapy) and should be part of an integrated interdisciplinary health care approach since undiscovered complications involving non-urologic organ systems create a higher long-term socioeconomic burden than preventive support provided by other specialists.

Bevorzugte Behandlungsoptionen des lokalisierten Prostatakarzinoms von deutschen Urologen und Radioonkologen bei eigener Erkrankung

INTRODUCTION We evaluated the currently preferred primary treatment options among German urologists and radio-oncologists if personally diagnosed with localized prostate cancer, taking into consideration the different prognostic risk groups. MATERIALS AND METHODS A questionnaire was mailed to 3,217 urologists and 598 radio-oncologists. They were asked to choose their preferred primary treatment option if they were personally diagnosed with prostate cancer, taking into consideration the different prognostic risk groups: low risk [Gleason score < or =6, prostate-specific antigen (PSA) < or =10 microg/l, T1c], intermediate risk (Gleason score 7, PSA 11-19 microg/l, T2), and high risk (Gleason score > or =8, PSA> or =20 microg/l, T3). Surgical options were further subdivided according to technique (retropubic, laparoscopic, perineal). RESULTS The questionnaire return rate was 49% for urologists and 41% for radio-oncologists. The mean age was 48 years (28-86) for urologists and 47 years (29-68) for radio-oncologists. Primary surgical treatment was selected by 62% of urologists for low-risk prostate cancer, 90% for intermediate-risk prostate cancer, and 77% for high-risk prostate cancer. Radiotherapy as a primary treatment option was elected by 71% of radio-oncologists for low-risk prostate cancer, 84% for intermediate-risk prostate cancer, and 89% for high-risk prostate cancer. Retropubic, laparoscopic, and perineal prostatectomy would be chosen by 61%, 28%, and 10% of urologists, respectively, for low-risk prostate cancer; by 70%, 24%, and 6%, respectively, for intermediate-risk prostate cancer, and by 80%, 15%, and 5%, respectively for high-risk prostate cancer. CONCLUSION Urologists prefer surgery and radio-oncologists radiotherapy for primary treatment of prostate cancer, irrespective of the prognostic risk group. Particularly for high-risk prostate cancer, the majority of radiooncologists would still choose radiotherapy as a primary treatment option. In the age of minimally invasive surgery, radical retropubic prostatectomy is still the preferred surgical treatment option among urologists for any prognostic risk group.