No abstract

No abstract

Isolated upper pole access is indicated in a select group of patients with complex stones. Upper calyceal and staghorn stones are more commonly managed by upper pole access, which is associated with a higher complication rate and longer hospital stay as well as a lower stone-free rate due to procedure complexity.

Docetaxel has shown promise for the treatment of hormone-refractory prostate cancer and has become the standard of care. The flare phenomenon is a known entity in androgen-deprivation therapy of advanced prostate cancer and it has also been described in palliative chemotherapy of hormone-refractory prostate cancer. The aim of this study was to evaluate the clinical impact of a prostate-specific antigen flare phenomenon in docetaxel-treated hormone-refractory prostate cancer patients. From December 2002 to August 2005, we treated 44 patients with hormone-refractory prostate cancer applying docetaxel-based regimens. Prostate-specific antigen levels were determined before therapy and weekly thereafter. Patients were divided into three groups: response (group 1), progression (group 2) and flare (group 3). Flare was defined as initially rising prostate-specific antigen under therapy, dropping thereafter to values below baseline. The groups were compared for overall survival by Kaplan-Meier analysis. We observed a prostate-specific antigen flare phenomenon in eight (18%) of 44 evaluable patients; 24 (54.5%) patients were primary responders and 12 (27.3%) experienced progressive disease. In group 3, prostate-specific antigen levels rose to 107-180% from baseline and then dropped to 21-68%. Kaplan-Meier analysis showed significantly better overall median survival for groups 1 (18 months, P=0.0005) and 3 (19 months, P=0.006) than for group 2 (7 months). Survival in groups 1 and 3 was comparable. Grade 3 and 4 toxicity was below 5% and equally distributed between the 3 groups. In our limited patient cohort, prostate-specific antigen flare phenomenon does not seem to be a clinically relevant issue in terms of overall survival. Thus, an initial rise of prostate-specific antigen under docetaxel therapy in hormone-refractory prostate cancer does not indicate therapeutic failure and should not lead to early withdrawal from therapy in the absence of clinical signs of progression.

PurposeGenome-wide analyses revealed basal and luminal subtypes of urothelial carcinomas of the bladder. It is unknown if this subtyping can also be applied to upper tract urothelial carcinomas.Materials and methodsTumor samples from 222 patients with upper tract urothelial carcinomas who were treated with radical nephroureterectomy were analyzed for the expression of seven basal/luminal immunohistochemical markers (CK5, EGFR, CD44, CK20, p63, GATA3, FOXA1).ResultsHierarchical clustering revealed a basal-like subtype (enrichment of CK5, EGFR and CD44) in 23.9% and a luminal-like subtype (enrichment of CK20, GATA3, p63 and FOXA1) in 13.1% of the patients. In 60.8%, little to no markers were expressed, whereas markers of both subtypes were expressed in 2.2%. By using CK5 and CK20 as surrogate markers for the basal and luminal subtypes, we defined four subtypes of upper tract urothelial carcinomas: (i) exclusively CK20 positive and CK5 negative (CK20+/CK5-), (ii) exclusively CK5 positive and CK20 negative (CK20-/ CK5+), (iii) both markers positive (CK20+/CK5+) and (iv) both markers negative (CK20-/CK5-). A receiver-operator analysis provided the optimal cut-off values for this discrimination. An immunoreactive score >1 for CK5 and >6 for CK20 were defined as positive. In multivariate Cox’s regression analysis, the CK20+/CK5- subtype was an independent negative prognostic marker with a 3.83-fold increased risk of cancer-specific death (p = 0.02) compared to the other three subtypes.ConclusionsImmunohistochemical subgrouping of upper tract urothelial carcinomas by analyzing CK5 and CK20 expression can be performed in a routine setting and can identify tumors with a significantly worse cancer-specific survival prognosis.

There are no reliable serologic tumor markers for transitional cell carcinoma (TCC) of the urinary bladder and noninvasive urine investigations are inadequate. We used fluorescent microsatellite analysis (MSA) to detect serum DNA and urine-sediment DNA alterations in patients with bladder cancer and prospectively collected fresh tumor, peripheral blood, serum and spontaneous urine specimens from 39 consecutive patients treated for TCC of the bladder to obtain the corresponding DNA. Urinary bladder cancer accounts for approximately 3% of all newly diagnosed malignancies in Western countries. In contrast to most other tumors, bladder carcinoma offers the opportunity of noninvasive diagnosis via urinary cytology. Yet a reliable serologic tumor marker is not available. Follow-up for bladder carcinoma is demanding and time consuming, as most bladder cancers at diagnosis grow superficially and will recur in 70% of cases within 2 years of primary treatment. 1 The intensive follow-up for transitional cell carcinoma (TCC) of the bladder still relies on invasive diagnostic measures such as cystoscopy and bladder washings for urine cytology. Cytology has a low sensitivity in the diagnosis of well-differentiated papillary tumors. A reliable serologic marker and a highly sensitive urinary investigation could reduce the requirement and frequency of invasive procedures during follow-up.In recent studies molecular techniques have proved applicable for the detection of smallest amounts of free circulating tumor DNA in serum and plasma of cancer patients. 2,3 Using microsatellite analysis (MSA) Goessl et al. 3 identified plasma DNA alterations in 63% of patients with renal cell carcinoma. In recent studies MSA was also used to detect tumor-specific DNA alterations in urine sediment samples of patients with TCC of the urinary bladder. 4,5 In a pilot study Steiner et al. 4 achieved a sensitivity of 90% for the urinary cancer diagnosis with radiolabeled microsatellite markers. In contrast to cytology, this method is independent of tumor histomorphologic features, and thus offers high sensitivity in well-differentiated tumors. This molecular genetic assay, not previously looked at in TCC, could reliably identify tumor-specific alterations in the serum of patients and its use in follow-up after radical surgical therapy could lead to early tumor recurrence identification. In the case of superficial bladder cancers, MSA may be helpful in diagnosing local recurrence without the need for invasive measures dependent on morphologic tumor features. We therefore used MSA with 17 highly polymorphic fluorescently labeled microsatellite markers from the chromosomal regions 5q, 8p, 9p, 9q, 13q, 14q, 17p, 17q and 20q to detect serum DNA and sediment-DNA alterations from spontaneous urine samples of 39 consecutive patients treated for TCC of the urinary bladder, to evaluate the sensitivity of the method in the serologic and urinary diagnosis of bladder TCC. MATERIAL AND METHODS Tumor, blood and urine samplingIn 1999, we prospectively collected preo...

No abstract

Non‐clear cell (ncc) renal cell carcinoma (RCC) accounts for ≈25% of all patients with metastatic RCC. It is refractory to standard immuno(chemo)therapy and, to date, no specific trials have been reported to evaluate the efficacy of novel targeted drugs in the different subtypes of metastatic nccRCC. We review all available data from subgroup analyses of the global sorafenib and sunitinib expanded access programmes, current phase‐III trials, and smaller multi‐ and single‐centre studies focusing on the activity of targeted agents in these specific and rare RCC subtypes. Both sorafenib and sunitinib have significant activity in metastatic nccRCC, but the efficacy of each agent seems to vary between different nccRCC forms. Preliminary clinical data for temsirolimus appear to be promising but more extensive and long‐term data are awaited. With the advent of novel therapeutic options, specific controlled multicentre trials are urgently needed to define their exact value and efficacy for treating the historically resistant nccRCC forms. The medium‐term aim should be to tailor the most advantageous therapy for each patient with respect to his/her individual RCC subtype and physical condition.