Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings. MATERIALS AND METHODS: The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry. RESULTS: B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06). CONCLUSIONS: B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

[Prevention, early diagnosis and treatment of chemoextravasation. Practical management in the uro-oncological practice]. / Prävention, Früherkennung und Behandlung von Zytostatikaparavasaten. Praktisches Management in der uroonkologischen Praxis.

Extravasation of chemotherapeutic agents is a rare (1-6%) but potentially severe iatrogenic complication of systemic therapy. Depending on the cytotoxic agent, tissue damage and necrosis may occur, followed by a delay in administration of chemotherapy, prolonged hospitalization, impaired function, and the need for tissue excision. Therefore, optimal placement of the intravenous catheter is absolutely necessary to reduce the risk of extravasation. The aim of this report is to give urologists a practical and useful guide on how to prevent, diagnose, and treat this complication.

[Intravesical therapy in non-muscle-invasive bladder cancer: indications and practical considerations]. / Intravesikale Therapie beim nicht muskelinvasiven Urothelkarzinom der Harnblase : Indikation und praktisches Management.

Intravesical treatment with various agents is an accepted standard for treating patients with non-muscle-invasive bladder cancer; all guidelines recommend its use. Depending on the agent and the instillation schedule, a reduction in recurrence and a decrease in the progression rate can be achieved.However, many of the recommendations in the various guidelines are currently under debate. Early instillation with a chemotherapeutic agent is probably overtreatment in patients requiring further induction or maintenance therapy because it adds no further benefit. The economic aspects of early instillations are also being discussed. Recent studies question the ability of bacillus Calmette-Guérin (BCG) instillations to reduce the progression of non-muscle-invasive bladder cancer. Furthermore, the superiority of maintenance therapies compared with induction schedules is under debate.There is a great body of evidence that the effectiveness of intravesical chemotherapy can be increased by simple measures. Reduction of BCG side effects without compromising the oncological outcome is possible.

[Testosterone replacement therapy and prostate cancer. The current position 67 years after the Huggins myth]. / Testosteronsubstitution und Prostatakarzinom. Eine Standortbestimmung 67 Jahre nach dem Huggins-Mythos.

Hypogonadism is highly prevalent in the elderly and in men with prostate cancer. Symptoms of hypogonadism, such as depression, lack of libido, and decreased bone mineral density, can significantly impair quality of life. In addition, testosterone plays an important role in erectile preservation and in growth and function of the cavernosal and penile nerves. There are compelling data showing that testosterone replacement therapy (TRT) does not increase the risk of prostate cancer. The literature (four published studies) concerning men treated with TRT after definitive therapy for prostate cancer reports only one biochemical recurrence. Based on these data, physicians cannot really justify withholding TRT from symptomatic patients after they have been successful treated for prostate cancer. This review gives the practising urologist an overview of the latest literature and useful advice on this controversial topic.

Transrectal ultrasound as diagnostic tool for the detection of local recurrence following cystectomy and urinary diversion.

OBJECTIVE: Routine follow-up after cystectomy for bladder cancer detect patients with local recurrence late in the course of disease. We set out to determine the value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local failure. PATIENTS AND METHODS: Between 1986 and 2003, radical cystectomy for bladder cancer with orthotopic diversion was performed in 642 male patients. We identified all patients that simultaneously had transabdominal ultrasound, digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of local recurrence. RESULTS: Mean follow-up was 59.4 months. 83/642 patients (13%) had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%) the local recurrence was the first site of recurrence. 35/642 patients (5.5%) developed local failure with concomitant distant disease. 31/83 patients met the inclusion criteria. The median time between cystectomy and diagnosis of local recurrence was 13 months (2-51 months). Routine follow-up detected local recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in the lower extremities/pelvis, hematuria and urinary retention, respectively. Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients, respectively. CONCLUSIONS: TRUS is a highly sensitive tool in detecting local recurrence following cystectomy. It is easy to perform and inexpensive. We recommend TRUS in short intervals in all patients with high risk for local recurrence in order to detect cancer early.

[Role of androgen receptors in hormone-refractory prostate cancer: molecular basics and experimental therapy approaches]. / Die Rolle des Androgenrezeptors im hormonrefraktären Prostatakarzinom : Molekulare Grundlagen und experimentelle Therapieansätze.

The development of hormone-refractory prostate cancer cells is one of the major causes for the progression and high mortality rates in advanced prostate cancer (PCA). While the loss of the androgen receptor (AR) is the predominant mechanism for development of a hormone-insensitive disease in vitro, the first in vivo studies showed that the AR is still expressed or is even overexpressed in hormone-refractory PCA. In view of the increasing cases of PCA in the industrialized Western countries, a series of cell and molecular biological studies has led to the identification of various new factors and mechanisms that play a role during the development of hormone-refractory tumors. These findings should lead to the development of new therapeutic strategies.

[Ileal bladder substitute]. / Ileale Ersatzblasen.

The history of urinary diversion in general began in 1852 and started right away with continent diversion, i.e., ureterosigmoidostomy. Anastomosing an intestinal reservoir to the urethra was proposed by Tizzoni and Foggi in 1888. They replaced the bladder by an isoperistaltic ileal segment which was interposed between ureters and urethra in a female dog. In 1951 Couvelaire reactivated this idea of an ileal bladder substitute. Retrospectively many disappointing results of urinary diversion were often not caused by insufficient competence of the outlet mechanism, but because the intestinal reservoir maintained its peristaltic properties causing high pressure peaks. The decisive advance in ensuring continence, and thus an improvement in patient comfort, was achieved with the so-called low pressure reservoir. The main characteristics of this reservoir compared to those from intact intestinal segments are the larger diameter, the greater capacity with significantly low pressures, and the uncoordinated contraction of its wall. Transsection of the circular intestinal musculature when performing bladder augmentation had already been published by Rutkowski in 1899, Tasker in 1953, and Giertz in 1957. In 1969, Kock published the first results obtained with an ileal continent fecal reservoir in patients after total proctocolectomy. The significant advantages of interrupting the tubular structure of a reservoir obtained from intestine had been described much earlier. The need for reflux prevention is not the same as in ureterosigmoidostomy conduit or continent diversion. Reflux prevention in neobladders is even less important than in a normal bladder. When using nonrefluxing techniques, the risk of obstruction is at least twice that after direct anastomosis. Kidney function is not impaired by diversion if stenosis is recognized and managed. Patient health status is influenced more by underlying disease than by diversion. Orthotopic reconstruction has passed the test of time. In these patients life is similar to that in individuals with a native lower urinary tract. Until a better solution is devised orthotopic bladder reconstruction remains the best option for patients requiring cystectomy.

C4.4A as a candidate marker in the diagnosis of colorectal cancer.

C4.4A is a member of the Ly-6 family with restricted expression in non-transformed tissues. C4.4A expression in human cancer has rarely been evaluated. Thus, it became important to explore C4.4A protein expression in human tumour tissue to obtain an estimate on the frequency of expression and the correlation with tumour progression, the study focusing on colorectal cancer. The analysis of C4.4A in human tumour lines by western blot and immunoprecipitation using polyclonal rabbit antibodies that recognize different C4.4A epitopes revealed C4.4A oligomer and heavily glycosylated C4.4A isoform expression that, in some instances, inhibited antibody binding and interaction with the C4.4A ligand galectin-3. In addition, tumour cell lines released C4.4A by vesicle shedding and proteolytic cleavage. C4.4A was expressed in over 80% of primary colorectal cancer and liver metastasis with negligible expression in adjacent colonic mucosa, inflamed colonic tissue and liver. This compares well with EpCAM and CO-029 expression in over 90% of colorectal cancer. C4.4A expression was only observed in about 50% of pancreatic cancer and renal cell carcinoma. By de novo expression in colonic cancer tissue, we consider C4.4A as a candidate diagnostic marker in colorectal cancer, which possibly can be detected in body fluids.

[Systemic therapy approaches in patients with bone metastases of urogenital malignancies]. / Systemische Therapieansätze bei Knochenmetastasen urogenitaler Tumoren.

Bone metastases develop commonly in patients with a variety of urogenital malignancies and are a major cause of morbidity and diminished quality of life in a significant proportion of urogenital carcinoma patients. For example, bone metastases occur in approximately 80% of patients with hormone-refractory prostate cancer and in approximately 25% of patients with renal cell carcinoma. A sufficient and early therapy is crucial since adequate therapy can lead to significant improvements in pain control and function and maintain skeletal integrity. The effective treatment of bone metastases requires multidisciplinary cooperation between urologists, oncologists, surgeons, nuclear medicine physicians and radiation oncologists. Analgesic measures, bisphosphonates, radionuclides, radiation therapy as well as surgical procedures are available. This review will focus mainly on the role of analgetics, bisphosphonates, radionuclides and radiolabelled bisphosphonates in the treatment of bone metastases.

Clinical value of transrectal ultrasound in the diagnosis of suspected neoplasia in the small pelvis.

PURPOSE: In daily clinical practice, it is challenging to accurately diagnose suspected neoplasias in the small pelvis by minimal invasive means, and CT-guided biopsy is often limited in its feasibility. The aim of our study was to evaluate whether transrectal ultrasound (TRUS)-guided biopsy can verify suspected neoplasias in the small pelvis histologically. MATERIAL AND METHODS: The study population consisted of 12 patients who underwent biopsy of suspected malignancy in the pelvis by TRUS. All patients had clinical signs of an advanced tumour stage and in all cases, biopsy utilising computerised tomography (CT scan) had been unsuccessful despite of a documented lesion on CT scan or magnetic resonance imaging. For the TRUS guided biopsy, a commercially available 3-dimensional 7.5-MHz-probe was used (Combison 530 D, GENERAL ELECTRIC, Milwaukee, USA). The probe was armed with an 18 G biopsy gun. RESULTS: In all patients, the suspected lesion was easily detectable by TRUS, and tissue for verification of the malignant origin of the lesions could be collected under real-time TRUS with only 2 patients needing anaesthesia. The biopsy cores were of excellent quality and adequate for conclusive pathological diagnosis. 6 cases of lymph node metastases of a transitional cell carcinoma were detected. 1 case of extended node metastasis in prostate cancer, 1 paravesical manifestation of recurrent cervical cancer, 1 metastasis of a paravesically infiltrating colon cancer and 2 cases of paravesical metastases of a gastric cancer were also diagnosed. In one case, extragenital endometriosis could be diagnosed. CONCLUSION: Based on our experience it can be stated that TRUS-guided biopsy is a reliable diagnostic tool for verification of the neoplastic origin of suspected masses in the small pelvis. In all cases with a history of unsuccessful CT guided biopsy, sufficient tissue cores for conclusive histology could be collected with our technique, and surgical exploration could be avoided. This technique is minimally invasive, without radiation exposure, well tolerated under analgesia, time efficient and cheap.

[Ureteral stricture after extracorporeal shock wave lithotripsy. Case report and overview of the spectrum of rare side effects of modern ESWL treatment]. / Ureterstriktur nach extrakorporaler Stosswellenlithotripsie. Kasuistik und Ubersicht über das Spektrum seltener Nebenwirkungen der modernen ESWL-Therapie.

Extracorporeal shock wave lithotripsy (ESWL) is considered a very safe and noninvasive procedure for the treatment of urolithiasis. Achievements in the technical development of recent decades resulted in a continuous reduction of side effects. One of our patients, a woman with cystinuria, developed a temporary ureteral stricture after several sessions of ESWL. Encouraged by this observation we set out to explore--based on a MEDLINE literature search--published reports of more severe side effects observed in modern ESWL therapy. Besides hydronephrosis and renal colic the most common side effects were renal and perirenal hematomas in up to 4% in the larger series. Uncommon extrarenal complications are described mostly in case reports, which are also outlined in this report. The injury of visceral organs (liver, spleen, gut, pancreas) was published most frequently. A rupture or dissection of an abdominal aortic aneurysm as an outstanding serious complication was also reported several times. Taking obvious and well-known contraindications into consideration and carefully preparing the patients for the therapy (i.e., checking hemostasis, drug history), ESWL is a very safe procedure with a low risk of serious complications. Yet, postoperative clinical and ultrasound monitoring seems to be essential especially with respect to the increasing numbers of outpatient procedures.