Renal cell carcinoma of 4 cm or less: an appraisal of its clinical presentation and contemporary surgical management.

OBJECTIVE: Greater availability and utilization of modern radiological imaging modalities have resulted in an increase in the incidental discovery of renal cell carcinoma. Such tumours tend to be smaller than their symptomatic counterparts and may potentially be adequately treated using nephron-sparing surgery. METHODS: A retrospective review of all patients who were diagnosed with renal cell carcinoma of 4 cm or less between January 1990 and December 2001 was conducted to review clinical presentation, surgical management and survival. RESULTS: The cohort comprised 102 patients who underwent surgery, of 402 patients diagnosed with renal cell carcinoma over the study period. Sixty-eight patients (67%) had tumours detected incidentally. Thirty patients (29%) were managed with partial nephrectomy and 72 (71%) with radical nephrectomy. The median tumour size was 3.0 cm (range, 1.5-4.0 cm). Overall, median follow-up was 60 months (range, 1-148 months). Overall 5-year survival for patients who underwent partial nephrectomy and radical nephrectomy was 96.6% and 85.8%, respectively. Cancer-specific 5-year survival was 100%. CONCLUSION: A significant proportion of patients had incidental diagnosis of small renal cell carcinoma. Local control may be achieved with either radical or partial nephrectomy, with excellent survival expected.

Diagnostic and prognostic value of bladder cancer-related transcript markers in urine.

PURPOSE: Since cytology as the current "gold standard" for noninvasive detection of bladder cancer (BCa) is characterized by a relatively low sensitivity, urinary transcript levels of survivin (SVV), Ki-67 and cytokeratin 20 (CK20) were evaluated as alternative or complementary biomarkers. Furthermore, their prognostic value was investigated. METHODS: Voided urine samples from 105 BCa patients and 156 controls were included. Total RNA was isolated from urine pellets and reverse-transcribed into cDNA. Expression levels of SVV, Ki-67 and CK20 were determined by quantitative PCR and normalized to the housekeeping gene TBP. Diagnostic performance of transcript markers and cytology was assessed by receiver operating characteristic (ROC) curve analyses. The prognostic value of the transcript markers was calculated by Cox proportional hazards models. RESULTS: ROC analyses resulted in AUC values between 0.71 (Ki-67) and 0.86 (CK20), indicating an appropriate diagnostic power. Using specifically defined cutoff values, the expression levels of the assessed biomarkers were significantly higher in urine specimens from BCa patients compared to control group (Mann-Whitney U test p < 0.001). Specificity ranged from 75% (SVV) to 84% (CK20) and sensitivity from 56% (Ki-67) to 87% (CK20). In combination with cytology, the sensitivity increased up to 97% (CK20). With regard to prognostic power, only SVV showed a significant, but not independent impact on the risk of recurrence (p = 0.008). CONCLUSIONS: Quantitative assessment of tumor-related transcript markers, particularly of CK20, may serve as a noninvasive method to identify patients with BCa. Moreover, SVV appears to be useful as a marker for a high risk of recurrence.

Penile cancer: current challenges.

Penile cancer remains a formidable challenge in many developing countries because of its high incidence and the advanced disease stage at diagnosis. For early penile cancer, surgery alone offers a high cure rate. Penile sparing therapies are proposed as alternative treatment options for select patients with the added advantages of preservation of body image and improved quality of life. The optimal management of lymph node disease remains controversial. The role of the sentinel lymph node biopsy, lymphatic mapping, prophylactic lymphadenectomy and the template for lymph node dissection are discussed. For advanced, metastatic penile cancer, more effective and less toxic chemotherapy is needed. This may be coupled with palliative surgery or radiotherapy for the primary tumor and inguinal disease.

Laparoscopic nephrectomy: new standard of care?

OBJECTIVE: The pace of implementation of a laparoscopic nephrectomy programme is affected by factors including surgical expertise, case load, learning curves and outcome audits. We report our experience in introducing a laparoscopic nephrectomy programme over a 3-year period. METHODS: From January 2001 to December 2003, 187 nephrectomies were performed (105 by conventional surgery, 82 by laparoscopy). Hand-assisted laparoscopy was used predominantly. The indications for surgery, factors affecting the approach and outcome parameters were studied. A cost comparison was made between patients with similar-sized renal tumours undergoing laparoscopic versus open surgery. RESULTS: Most operations were performed for malignancy in both the open (70%) and laparoscopic (67%) surgery groups. The laparoscopic approach was most commonly used in upper tract transitional cell cancers (TCCs; 70% of 30 patients) and benign pathologies (49% of 35 patients), followed by radical nephrectomies (34% of 99 patients) and donor nephrectomies (44% of 23 patients). There was a rapid rise in laparoscopic surgeries, from 30% in 2001 to 58% in 2002. The median hospital stay was 5.8 days in the laparoscopic group and 8.1 days in the open surgery group. The procedure cost for laparoscopic surgery was 4,943 dollars compared with 4,479 dollars for open surgery. However, due to a shorter hospital stay, the total hospital cost was slightly lower in the laparoscopic group (7,500 dollars versus 7,907 dollars). CONCLUSION: The laparoscopic approach for various renal pathologies was quickly established with a rapid increase in the number of laparoscopic procedures.

Does the introduction of a third examiner and global marking improve the generalisability of the surgical long case?

INTRODUCTION: Planning a high-stake clinical examination requires the evaluation of several psychometric and logistical variables. The authors conducted generalisability and decision studies to answer the following research questions in the context of the surgical long case: (1) Does the addition of a third examiner have any added benefit, vis-à-vis reliability, to the examination? (2) Is global marking more reliable than an itemised marking template? (3) What would be the impact on reliability if there was a reduction in the number of examinees that each panel of examiners is required to assess? METHODS: A third examiner and global marking were introduced. Separate generalisability and decision studies were carried out for both the two- and three-examiner models as well as for itemised and global scores. RESULTS: The introduction of a third examiner resulted in a modest gain of reliability by 0.05-0.07. Gain in reliability was higher when each candidate was allowed to undertake a higher number of clinical cases. Both the global and itemised scores provided equivalent reliability (generalisability coefficient 0.74-0.89). CONCLUSION: Our results showed that only a modest improvement in reliability of the surgical long case is achieved through the introduction of an additional examiner. Although the reliability of global scoring and the itemised marking template was comparable, the latter may provide opportunities for individualised feedback to examinees.

Differential expression of steroid 5alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer.

The biological role of steroid 5alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGFalpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 muM). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors.

Aurora-A expression, hormone receptor status and clinical outcome in hormone related cancers.

AIMS: We investigated the correlation between protein expression of Aurora-A with hormone receptor expression and clinicopathological parameters in ovarian, breast and prostate cancer. METHODS: Subcellular expression of Aurora-A, and androgen receptor (AR), oestrogen receptor (ER) and progesterone receptor (PR) expression, were examined by immunohistochemistry in human tissue microarrays of the three cancer types and by Western blot in cancer cell lines and selected patient tissues. RESULTS: Subgroups of all three cancer types exhibited both nuclear and cytoplasmic expression of Aurora-A. Nuclear presence of Aurora-A was observed in ER positive and negative breast cancer cell lines and tissues. Eighteen of the 126 (14%) tumour tissues that showed nuclear expression of Aurora-A were strongly associated with ER and PR positive breast tumours (p = 0.001). Cytoplasmic expression of AR and Aurora-A was strongly associated in prostate cancer tissues (45% versus 0, p = 0.015). Ovarian tumours (n = 45) with Aurora-A nuclear expression had decreased patient survival (mean survival, 29.5 versus 106.7 months; p < 0.0005) and showed a significant association with recurrence-free survival (mean survival 19.7 versus 95.9 months; p = 0.002). CONCLUSION: Association between nuclear Aurora-A with hormone receptors in breast cancer and with poor clinical outcome in ovarian cancer suggests the significance of active Aurora-A in disease initiation and progression.