Z. Varga

Extended Pelvic Lymphadenectomy In Patients Undergoing Radical Prostatectomy: High Incidence Of Lymph Node Metastasis

PURPOSE Lymphadenectomy for prostate cancer is limited to obturator and external iliac lymph nodes, although the internal lymph nodes represent the primary landing zone of lymphatic drainage. We performed anatomically adequate extended pelvic lymphadenectomy to assess the incidence of lymph node metastasis in cases of clinically localized prostate cancer. MATERIALS AND METHODS A total of 103 consecutive patients underwent extended pelvic lymphadenectomy at radical retropubic prostatectomy comprising 9 selective fields, namely the external iliac, internal iliac, obturator and common iliac lymph nodes bilaterally, and the presacral lymph nodes. Histopathological findings were compared with serum prostate specific antigen (PSA), histopathological stage, preoperative biopsy and postoperative prostatectomy Gleason score. Extended pelvic lymphadenectomy was compared with radical retropubic prostatectomy and standard lymphadenectomy in 100 consecutive patients in terms of complications, the number of lymph nodes dissected and operative time. RESULTS There were no significant differences in age, preoperative PSA or mean biopsy Gleason score in patients who underwent extended pelvic and standard lymphadenectomy. Metastases were diagnosed in 27 of the 103 patients (26.2%) who underwent the extended procedure. A mean of 28 lymph nodes (range 21 to 42) were dissected. Metastases were identified in the internal iliac and presacral regions despite negative obturator lymph nodes. Of the 27 patients 1 to 3 lymph nodes involved with metastasis were detected in 15, 9 and 1, respectively. In 26 of the 27 patients (95.8%) with lymph node metastasis PSA was greater than 10.5 ng./ml. and preoperative biopsy Gleason sum was 7 or greater. A low risk of 2% for lymph node disease was noted in patients with serum PSA less than 10.5 ng./ml. and biopsy Gleason sum less than 7. There were no significant differences in regard to intraoperative and postoperative complications, lymphocele formation or blood loss in the 2 groups. CONCLUSIONS Extended pelvic lymphadenectomy is associated with a high rate of lymph node metastasis outside of the fields of standard lymphadenectomy in cases of clinically localized prostate cancer. Lymphadenectomy including the internal iliac lymph nodes should be performed in all patients with prostate cancer who are at high risk for lymph node involvement, as indicated by PSA greater than 10.5 ng./ml. and biopsy Gleason sum 7 or greater. In the low risk group pelvic lymphadenectomy can be omitted.

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients.

Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.

Bilateral fine-needle administered local anaesthetic nerve block for pain control during TRUS-guided multi-core prostate biopsy: a prospective randomised trial.

INTRODUCTION Transrectal multi-core biopsies of the prostate can cause substantial discomfort with the need for high dose systemic analgesics. In a prospective randomised trial we investigated the efficacy of fine-needle administered local anaesthesia for bilateral prostatic nerve block prior to transrectal ultrasound (TRUS) guided prostate biopsy. MATERIALS AND METHODS One hundred and eight men suspected of having cancer of the prostate were randomised to receive TRUS-guided bilateral prostate nerve block prior to biopsy or not, when having no history of previous prostate biopsies (groups I and II, n=68). In group III (n=40) all patients with history of previous biopsies exclusively received local anaesthesia injection. Patients routinely underwent a 10-core biopsy regimen. For repeat biopsy 12 cores were taken. The consented patients documented pain on a visual analogue pain score. RESULTS In the randomised groups I and II average pain score was 1.85 with versus 3.29 without periprostatic nerve block (p<0.0001). In group III the difference in pain stated for the present biopsy with local anaesthesia nerve block in comparison to the pain experienced with the previous biopsy solely under transrectal lidocaine gel was even higher (1.71 versus 4.59; p<0.0001). Pain relief was independent of the number of biopsy cores sampled. Overall cancer detection rate was 46% (50/108). CONCLUSION Bilateral local anaesthesia nerve block prior to multi-core TRUS-guided prostate biopsy significantly reduces pain independent of the number of cores taken.

Individual Positioning: A Comparative Study of Adjuvant Breast Radiotherapy in the Prone Versus Supine Position

PURPOSE To study breast radiotherapy in the prone vs. supine positions through dosimetry and clinical implementation. METHODS AND MATERIALS Conformal radiotherapy plans in 61 patients requiring only breast irradiation were developed for both the prone and supine positions. After evaluation of the of the first 20 plan pairs, the patients were irradiated in the prone or supine position in a randomized fashion. These cases were analyzed for repositioning accuracy and skin reactions related to treatment position and patient characteristics. RESULTS The planning target volume covered with 47.5-53.5 Gy in the prone vs. the supine position was 85.1% +/- 4.2% vs. 89.2 +/- 2.2%, respectively (p < 0.0001). Radiation exposure of the ipsilateral lung, expressed in terms of the mean lung dose and the V(20Gy), was dramatically lower in the prone vs. supine position (p < 0.0001), but the doses to the heart did not differ. There was no difference in the need to correct positioning during radiotherapy, but the extent of displacement was significantly higher in the prone vs. supine position (p = 0.021). The repositioning accuracy in the prone position exhibited an improvement over time and did not depend on any patient-related parameters. Significantly more radiodermatitis of Grade 1-2 developed following prone vs. supine irradiation (p = 0.025). CONCLUSIONS Conformal breast radiotherapy is feasible in the prone position. Its primary advantage is the substantially lower radiation dose to the ipsilateral lung. The higher dose inhomogeneity and increased rate of Grade 1-2 skin toxicity, however, may be of concern.

Metastatic non-clear cell renal cell carcinoma: current therapeutic options.

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.

Nephron-sparing surgery for Renal angiomyolipoma

INTRODUCTION Renal angiomyolipoma (RAML) is a benign tumor composed of varying amounts of mature adipose tissue, smooth muscle and thick-walled blood vessels. RAML tend to grow over time requiring active intervention due to serious associated complications, such as hemorrhage and pain. Although RAML is an ideal tumor for organ preservation, data concerning efficacy of nephron-sparing surgery (NSS) are sparse. The aim of the study was to evaluate the efficacy of NSS in RAML with regard to renal function, tumor recurrence and surgical feasibility. PATIENTS AND METHODS Charts of patients with pathologically confirmed RAML were reviewed and data recorded: tumor size, associated symptoms, intraoperative blood loss, serum creatinine, follow-up data with regard to tumor recurrence and long-term renal function. A total of 28 patients were identified with RAML who underwent NSS because of tumor size > 4 cm, pain and/or to rule out malignancy due to radiographic features of uncertain interpretation. RESULTS The median follow-up of all patients is 58 (3-114) months; median age was 55.6 (34-78) years, 24 patients were women, 4 patients were men. None of the patients developed a local recurrence. Median size of enucleated tumors was 5.5 (2.5-15) cm; indication for NSS was symptomatic tumor with hemorrhage in 4 patients (16%), prophylaxis of hemorrhage in 5 patients (20%) and radiographic features suspicious for malignancy in 16 patients (64%). In those cases, unenhanced and enhanced CT scans exhibit a hyperdense and a hypodense lesion as compared to the adjacent normal renal cortex, respectively. There were no intraoperative complications, median blood loss was 320 (50-1200) ml, none of the patients required blood transfusions. Post-operative course was uneventful in 26 patients (96%), 2 patients (7.1%) developed a urinary fistula managed by an endoluminal stent. Pre-operative serum creatinine was 0.9 (0.7-1.3) mg/dl, post-operative creatinine was 1.23 (0.7-1.5) mg/dl and serum creatinine at last follow-up was 0.95 (0.7-1.2) mg/dl. CONCLUSIONS NSS can be performed with a high success rate in RAML when surgical management is indicated. Long-term follow-up reveals no local tumor recurrences and stable renal function even in patients with a solitary kidney.

Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer.

To evaluate and compare the value of several markers of bone turnover in different stages of prostate cancer, as bone metastases are a common feature in this disease, and for assessing bone metastases both bone formation and bone resorption markers are diagnostic.

Second-line strategies for metastatic renal cell carcinoma: classics and novel approaches

Objectives: Renal cell carcinoma is an aggressive malignancy with a high propensity for both early and metachronous regional and distant metastasis. While surgical resection is the mainstay of therapy for patients with localized disease, the prognosis for patients with distant metastasis is poor with a 5-year survival rate of less than 10%. Response rates to first-line immunotherapy or immunochemotherapy range from 10–35%; responses achieved are predominantly partial remissions of short duration. Until today, there is no standard therapeutic procedure for the growing number of patients who relapse following first-line therapy and desire further active treatment. Materials and Methods: This article reviews classic and recent publications about second- and third-line approaches, their potential efficacy and toxicity. Results: Several novel approaches have raised well-founded hope. Especially the application of monoclonal antibodies targeting VEGF signalling as well as different receptor tyrosine kinase inhibitors have the potential to change the face of second-line treatment of patients with metastatic RCC. Both groups of agents are focused in current phase III trials, either as mono- and/or combination therapy. Conclusions: Until today, second-line treatment of patients with metastatic RCC progressing under therapy with biological response modifiers remains an unresolved issue. The results of ongoing clinical trials evaluating novel targeted approaches can be expected with suspense.

Clinical experience with a new ultrasonic and LithoClast combination for percutaneous litholapaxy.

Objective  To assess a new lithotripter for intracorporal lithotripsy, which combines the mechanically driven pneumatic LithoClast™ (Electro‐Medical Systems, Nyon, Switzerland) and a new ultrasonic device (Electro‐Medical Systems), for use in percutaneous nephrolitholapaxy (PNL).

High frequency of serum DNA alterations in renal cell carcinoma detected by fluorescent microsatellite analysis.

To date there are no reliable serological markers for renal cell carcinoma (RCC). We applied fluorescent microsatellite analysis (MSA) to detect serum DNA alterations in patients with RCC. Fresh tumour, peripheral blood and serum specimens from 60 consecutive patients treated for malignant renal tumours (n= 53 RCC and n= 7 non‐RCC) were prospectively collected. After DNA extraction, we performed MSA with a total of 9 markers from the chromosomal regions 3p, 5q, 7p, 7q, 9p, 13q, 17p and 17q to identify tumour specific serum DNA alterations in Group I (n= 53 RCC); 11 additional markers were used in the first 23 RCCs (Group II) in order to increase sensitivity; and 20 healthy controls were investigated with 10 markers. Besides the histomorphological diagnosis the RCCs were genetically stratified according to the “Heidelberg Classification” of renal tumours. Detection of allelic imbalance and loss of heterozygosity (LOH) was carried out on an automated laser sequencer. In Group I we identified serum DNA alterations in 74% (39/53) of cases. When applying 20 markers, the sensitivity was elevated to 87% (20/23) in Group II. Investigating 20 healthy controls with 10 markers, the method rendered 85% specificity. The highest incidence of alterations was detected for chromosomal regions 3p and 5q. The presence of serum DNA alteration was not associated with tumour nuclear grade but exhibited a trend towards advanced stages (p = 0,044). In RCC, the microsatellite analysis has a high sensitivity in the detection of serum DNA alterations when a sufficient number of markers from various chromosomal regions are used. Advanced tumours tend to express serum DNA alterations more frequently.