H. Wunderlich

Nephron sparing surgery for renal cell carcinoma 4 cm. or less in diameter: indicated or under treated?

PURPOSE Although radical nephrectomy is the standard treatment for localized unilateral renal cell carcinoma with a normal contralateral kidney, there is ongoing interest in the use of nephron sparing surgery or partial nephrectomy in such cases. The extent of radical surgery in such cases has also been reconsidered in view of the uncertainty regarding the malignant or benign nature. MATERIALS AND METHODS Of 14,793 autopsies in Jena from 1985 until 1995 there were 260 renal cell carcinomas. Of the 260 renal cell carcinomas the diameter was 40 mm. or less in 104. These 104 tumors were divided into group 1-20 mm. or less (33 cases), group 2-21 to 30 mm. (28) and group 3-31 to 40 mm. (43). RESULTS Grade 1 renal cell carcinomas decreased in frequency with increasing tumor diameter, while an opposite result was noted for grade 3. Lymph node and distant metastases were well correlated with tumor size. With an increase in tumor size the frequency of venous involvement increased as well. Significantly more multifocal malignant renal cell carcinomas were seen in tumors between 21 and 40 mm. compared to those 20 mm. or less in diameter. CONCLUSIONS The metastatic potential and biology of these small nodules are not yet known. To lower the risk of local recurrence the results of our study suggest that nephron sparing surgery might be advisable in patients with renal cell carcinoma 20 mm. or less in diameter.

Increase of renal cell carcinoma incidence in central Europe.

Objective: In recent years the incidence of renal cell carcinoma (RCC) diagnosis has increased about 15–20%. It remains to be established whether this increase of incidence is reality or not. The main aim of this study was to analyze the reason for the increase of incidence. Methods: In the present study, 23, 247 autopsies performed in the years 1985–1995 in the area of Jena (Germany) (14,793 autopsies) and Hradec Králové (Czech Republic) (8,454 autopsies) were analyzed. Results: In this autopsy series comprising 23,247 autopsies, the percentage of patients who died of RCC is 1.76% in Jena and 1.55% in Hradec Králové (200,000 inhabitants each). Over this time the incidence of RCC in autopsies has increased. Conclusion: In spite of the increased amount of incidentally found RCCs since beginning widespread use of ultrasonography, the percentage of clinically recognized RCCs in the total of all found RCCs in autopsies is nearly constant over the 11-year period in Jena and 10-year period in Hradec Králové. Thus, the increased number of radical nephrectomies is not only caused by widespread use of ultrasonography. The increasing trend of the incidence of RCC seems to be real.

Real Indications for Adrenalectomy in Renal Cell Carcinoma

Objectives: Adrenalectomy is a part of radical nephrectomy because of the surgical oncology principle of a ‘wide margin beyond the malignancy’ and due to concern over possible metastases to the ipsilateral adrenal gland, especially in upper pole tumors. But, neither the frequency, predisposing factors of the renal cell carcinoma nor mechanisms of involvement of the adrenal gland are well defined. We assessed the ipsilateral adrenal involvement in renal cell carcinoma to determine whether ipsilateral adrenalectomy during radical nephrectomy is essential. Material and Method: In a series of 15,347 autopsies in Jena from 1985 through 1996, 272 renal cell carcinoma with 24 adrenal metastases were found. In the same period 9 adrenal metastases were found in 639 radical nephrectomies. Contralateral and bilateral metastases were seen in 15 cases of the autopsy series and in 2 cases of the operative series. Results: The risk of adrenal metastases correlated with multifocal tumors, pleomorphic cell type, anaplastic growth pattern and tumors that were larger than 2.5 cm. Of the 24 renal cell carcinomas with adrenal metastases in the autopsy series, 23 had evidence of widespread disease and 22 had lymph node metastases. A preoperative abdominal computerized tomography was performed in all 9 patients of the operative series with renal cell carcinoma and adrenal involvement. The adrenal gland was considered abnormal in 8 of the 9 cases (88.9%). Only in 1 patient was the computerized tomography incorrectly interpreted as negative. Conclusion: We think adrenalectomy should only be performed if there is radiographic evidence of metastases in the adrenal gland or adrenal infiltration by a large upper-pole tumor is possible. Macroscopically normal adrenal glands should not be removed during tumor nephrectomy because the need and benefit of routine adrenalectomy are extremely limited.

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience.

An interesting group of papers in this section is headed by two papers on synchronous bilateral renal tumours, one from an international group of authors and one from Germany. The large series of patients are examined carefully by both groups, and the findings should be useful for all who are interested in this area.

Preoperative simulation of partial nephrectomy with three-dimensional computed tomography

Objective To evaluate prospectively the accuracy of computer‐aided three‐dimensional (3D) volume‐rendered computed tomography (CT) in determining the appropriate anatomical limits (tumour size, tumour location, multifocality and vascular supply) and as a potential tool in the preoperative simulation of nephron‐sparing surgery (NSS) in patients with small‐volume renal cell carcinoma (RCC).

Where Are the Limits of Elective Nephron– Sparing Surgery in Renal Cell Carcinoma?

Objectives: The indication for elective nephron–sparing surgery (NSS) in renal cell carcinoma (RCC) is still controversial. The presented study was performed to determine limitations for NSS regarding to multifocality and to characterize the biological importance of these small tumor lesions.Methods: In 372 patients who underwent radical nephrectomy for RCC consecutively, nephrectomy specimens were investigated by using 3–mm parenchyma sections regarding to local tumor spread and multifocality. To characterize multifocal tumors, we performed cytogenetic and molecular genetic investigations.Results: Serial sections of 372 nephrectomy specimens revealed a total of 92 multifocal tumors in 61 specimens (16.4%). The correlation between tumor size and multifocality is shown as follows: tumor diameter 1–20 mm: 12.5%; 21–30 mm: 23.4%; 31–40 mm: 10.2%; >40 mm: 16.7%. The mean diameter of the multifocal tumors was 8.8×9.1×6.1 mm and the mean distance to the primary tumor was 26.4 mm (5–84 mm). Using cytogenetic and moleculargenetic analysis, in nearly one third of all cases a concordance of chromosomal aberrations in primary and secondary tumors was found.Conclusions:Multifocality of renal cell carcinoma occurs independently from primary tumor size. The evidence of structural and/or numeric aberrations, found in additional tumor foci, obviously is an argument for their malignant potential. This findings have to be considered in preparation of nephron–sparing surgery for patients with renal cell carcinoma.

Multifocality in Renal Cell Carcinoma: A Bilateral Event?

Objectives: The major disadvantage of nephron-sparing surgery for renal cell carcinoma is the risk of local recurrence. This is most likely a manifestation of undetected small additional tumors in the renal remnant. To define more clearly the incidence and nature of unilateral and bilateral multifocal tumors, an autopsy study was undertaken. Materials and Methods: In a series of 14,793 autopsies from 1985 to 1995, 260 renal cell carcinomas were found. In all cases of renal cell carcinoma a search for small renal lesions was performed in the apparently normal-appearing portion of the kidneys. Every kidney was serially and systematically cut (5 mm) to probe for intraparenchymal lesions. Results: Of the 260 renal cell carcinomas 36 cases (13.85%) had multifocal malignant and/or benign nodules. The number of the additional nodules ranged from 2 to 18. 12% of the malignant multifocal carcinomas were limited to the ipsilateral kidney and 88% were bilateral. The average size of the multifocal renal lesions was 8.7 × 9.0 × 9.5 (range 3–23) mm. Renal cell carcinomas with low stage and good grading have a higher incidence of multifocal nodules. No significant difference was found with regard to metastasized and nonmetastasized renal cell carcinomas. In 38.1% of all chromophilic renal cell carcinomas additional nodules were found. Conclusions: Multifocality in renal cell carcinomas cannot be predicted reliably, although the papillary histological pattern, good grading and low staging seems to be associated with a higher incidence of multifocality. Nearly 90% of the multifocal nodules were bilateral.

Increased Transforming Growth Factor β1 Plasma Level in Patients with Renal Cell Carcinoma:A Tumor-Specific Marker?

Purpose: The most worrying problem with renal cell carcinoma (RCC) seems to be the prediction of metastases by means of tumor-specific markers. Therefore, much effort is committed to the development of new markers. Materials and Methods: The level of latent transforming growth factor β1 (TGF-β1) was measured in plasma samples by ELISA. These samples were collected from patients with RCC before they underwent radical nephrectomy, from patients 1 h after extracorporeal lithotripsy, from patients with pyelonephritis, and from healthy controls. Results: In all cases of RCC the levels of latent TGF-β1 in plasma were much higher (n = 20, 41.0 ± 13.9 ng/ml, range 19.3–78.1 ng/ml) than in healthy controls (n = 20, 3.8 ± 2.9 ng/ml, range 0.6–9.9 ng/ml, p < 0.0001). The TGF-β1 levels in plasma after extracorporeal lithotripsy (n = 20, 7.4 ± 4.64 ng/ml, range 2.9–21.7 ng/ml, p < 0.01) and in patients suffering from pyelonephritis (n = 20, 18.93 ± 14.2 ng/ml, range 4.2–46.7 ng/ml, p < 0.001) were also higher than in healthy controls. Conclusion: We conclude that increased levels of latent TGF-β1 are common in the plasma of RCC patients. The TGF-β1 plasma level in RCC was found to be significantly higher than in cases of inflammation. Thus, TGF-β1 is a possible tumor-prognostic marker in RCC.

Renal cell carcinoma in renal graft recipients and donors: incidence and consequence.

Introduction and Objectives: Numerous studies have reported an increasing incidence of small renal cell carcinoma (RCC). De novo RCC in a renal allograft is a rare event and has special implications in renal transplant recipients. The objective of this study was to retrospectively evaluate the incidence of RCC in renal graft recipients and donors and to determine a procedure in cases with newly detected small renal tumors at the time of kidney preparation before transplantation. Material andMethods: We mailed a questionnaire to 38 German transplant clinics and received answers from 27 centers. A total of 10,997 renal graft recipients were included in the period of 1990–1998. Results: In 30 kidneys (0.273%) RCC was detected at the time of preparation before transplantation. There were 23 male and 3 female donors. No bilateral RCC was described. The mean age of the donors with RCC was 50.9 years (range 37–72 years). The tumors had a mean size of 2.2 cm (range 0.4–6 cm). 67% of the patients had a renal tumor smaller than 20 mm. In 26/27 centers the decision to transplant relies on the result of the immediate section for microscopic examination. 16 patients (0.145%) developed RCC 3–12 years after renal transplantation (mean 7.4 years). The mean tumor size was 2.5 cm (range 2–2.8 cm). In 50% a grade 1 and in the other 50% a grade 2 carcinoma was found. Conclusions: Because of the RCC incidence in donor candidates we recommend an ultrasound screening of the native kidneys before renal explantation and an immediate preparation of the kidney surface especially in donors older than 45 years. In cases with small renal lesions we recommend an immediate section for microscopic examination before transplantation to prevent tumor implantation into an otherwise healthy patient. The frequency of RCCs after renal transplantation necessitates careful clinical and instrumental examinations in organ-transplanted recipients both before and at regular intervals after transplantation, including the patient’s kidneys.

A Study of Pelvic Floor Function Pre– and Postradical Prostatectomy Using Clinical Neurourological Investigations, Urodynamics and Electromyography

Objectives: Incontinence after radical prostatectomy is addressed to sphincter damage and/or bladder dysfunction. Taking into account a high cure rate of incontinence by pelvic floor biofeedback treatment, the search for further mechanisms of a complex physiological concept seems feasible.Methods: To characterize pelvic floor function, 18 patients were prospectively evaluated before and after radical prostatectomy by clinical neurourological tests, urodynamics and needle/surface electromyography (EMG).Results: In all patients (mean age 62 years) investigations were completed successfully. The outcomes of neurourological investigations (sacral reflexes, voluntary pelvic floor contraction and relaxation) and needle EMG showed no significant changes in the pre–/postoperative comparison. Only by using surface EMG polygraphy change of activation patterns during pelvic floor contraction (decreased mean and medium frequency) could be found.Conclusion: In patients without preexisting bladder dysfunction and with a basically normal operative and postoperative course, fine motoric changes of pelvic floor function are the main finding. This cannot be explained by a pure anatomical approach. Neurophysiological events, like a barrage of nociceptive information, caused by surgical dissection and an inflammatory reaction due to the healing process, contribute to altered processing within the central nervous system. The appreciation of these mechanisms, well studied in neuroscience and pain research, offers a better understanding of surgery–related short– and longterm morbidity after pelvic surgery, i.e., urinary incontinence and erectile dysfunction.