Nobody needs "relative tumour sizes" to compare tumour growth curves.

Tumour growth curve experiments play an important role in experimental oncology and established methods exist for their unbiased interpretation. However, many authors till introduce systemic biases to their data by using the so-called "relative tumour size" transformation, inspite of wide awarance about the limitations of this latter method. With this communication and by using a fictive exaggeration of the problems connected with the application of this transformation we would like to appeal to both authors and reviewers likewise to ban this potential source of misinterpretation from the oncological literature.

A tool for self-dilatation of distal urethral strictures.

We propose the use of a catheter stopper with a smooth tip as a tool for the dilatation of distal urethral strictures. This allows for self-dilatation by the patient himself or by non-professionals involved in daily care at regular intervals. The method was successfully used in 2 patients.

[Molecular genetic and cell biology principles for the development of malignant tumors]. / Molekulargenetische und zellbiologische Grundlagen der Entstehung von malignen Tumoren.

The development of cancer is one of the most intensively studied areas of medical research resulting in an immense quantity of data. Therefore, the purpose of this article is to give an overview of the basic principles of cancer development. Key words such as multi-step carcinogenesis, cell cycle, protooncogene, tumor suppressor gene, DNA repair gene, apoptosis and telomeres are explained and described in examples. This paper aims to connect recent information of molecular and cellular biology in an overview of cancer origin and development.

[Colony stimulating factors in polychemotherapy of testicular tumors. A comparison between G-CSF and GM-CSF]. / Koloniestimulierende Faktoren bei der Polychemotherapie von Hodentumoren. Ein Vergleich zwischen G-CSF und GM-CSF.

Colony-stimulating factors (CSF) are frequently used in cases of cytostatic therapy of patients with testicular cancer assuming that they support hematopoietic recovery and, thus, shorten duration of neutropenia as well as reduce infections. Currently, G-CSF and GM-CSF are clinically used. In the present study efficacy and toxicity of these two drugs were investigated and compared in patients with testicular cancer treated by standard chemotherapy. Studying 83 chemotherapy cycles applied to 31 patients with advanced germ cell tumors the effectivity and the side effects of the two CSF were examined by questioning, clinical evaluation, and blood chemistry studies. G-CSF (480 micrograms subcutaneously (s.c.)) were used in 55 and GM-CSF (400 micrograms s.c.) in 28 chemotherapeutic cycles. The indications consisted in the treatment of leukocytopenia on the one hand and in the prophylaxis in subsequent cycles on the other hand. No difference between the two CSF could be found either with regard to postponement of the next cycle (G-CSF: 6.8 vs. GM-CSF: 7.3 days), or to the number of injections per cycle (G-CSF: 8 vs. GM-CSF: 12.5), or to the leukocyte (G-CSF: 2.1 vs. GM-CSF: 1.6 x 10(3)/microliter) or platelet nadir (G-CSF: 0.5 vs. GM-CSF: 0.5 x 10(5)/microliter; mean values of all cycles, respectively). Both CSF did not seem to influence the production of platelets. However, a difference between the two CSF was demonstrated with respect to the toxicity. Frequency (G-CSF: 38.5% vs. GM-CSF: 69.3%) as well as intensity of side effects causing a change of the drug (G-CSF: n = 1 vs. GM-CSF: n = 7) were lower in the case of G-CSF. In conclusion, these data demonstrate no difference was seen between G-CSF and GM-CSF with respect to the efficacy in patients with testicular cancer treated by standard chemotherapy. However, the use of G-CSF seems to be associated with lower toxicity.

[Lipoma of the adrenal gland. Case report and review of the literature]. / Lipom der Nebenniere. Fallbericht und Literaturübersicht.

Adrenal lipomas are extremely rarely occurring benign tumors being hormonally inactive. The patient described in this report underwent surgical excision of an adrenal lipoma because of the associated hypertension. The blood pressure decreased postoperatively to normal levels. This case report and the review of the literature consider diagnosis and therapy of the adrenal lipomas.

Localization and expression of adrenocorticotropic hormone receptor mRNA in normal and neoplastic human adrenal cortex.

The recent cloning of the ACTH receptor (ACTH-R) gene allows investigation of the tissue localization and relative abundance of ACTH-R mRNA in normal and neoplastic adrenal cortex. Using in situ hybridization (ISH) we studied the expression of ACTH-R mRNA in four adult adrenals of brain-dead patients, two cortisol-producing adenomas (CPA), three aldosterone-producing adenomas (APA), one non-functional adenoma (NFA), and three carcinomas. The results were compared with the mRNA expression of key steroidogenic enzymes and of the glucocorticoid receptor (GR) mRNA using Northern blotting. In adult adrenals, messenger RNA encoding ACTH-R was localized in all three zones of the adrenal cortex, in accordance with the stimulatory role of ACTH on mineralocorticoid, glucocorticoid and adrenal androgen secretion. In comparison, expression of side-chain cleavage enzyme (P450scc) showed a similar tissue distribution with mRNA abundance in all three zones, whereas 17-hydroxylase/17-20 lyase (P450c17) mRNA expression was only detected in the zona fasciculata and zona reticularis. All CPAs and APAs expressed significant levels of ACTH-R mRNA whereas an NFA showed low expression of ACTH-R mRNA. Two of three adrenocortical carcinomas expressed ACTH-R mRNA. Northern analysis using dot blot was employed to quantify ACTH-R and GR mRNA expression and confirmed the ISH data: ACTH-R mRNA expression was high in CPAs (275 and 195% vs 100 +/- 25% in adult adrenals), APAs (127, 200 and 221%) and two carcinomas (99 and 132%), but low in the NFA (7%) and in an androgen secreting carcinoma (16%). GR mRNA expression was high in the NFA (195%) and in two of three carcinomas (93, 188, 227%). We conclude that ACTH-R mRNA is upregulated in functional adenomas by yet unidentified mechanisms. The tissue distribution of ACTH-R and P450 enzyme mRNA expression is highly variable in neoplastic adrenals and does not allow a clear differentiation between benign and malignant tumors.

[Transvaginal closure of vesicovaginal fistulas]. / Transvaginaler Verschluss von vesikovaginalen Fisteln.

The surgical management of vesicovaginal fistulae (VVF) is a matter of controversy. This study deals with our experience with transvaginally treated patients suffering from VVF. Between 1966 and 1996, 64 patients with VVF were treated surgically. The VVF occurred in the course of hysterectomy in 54 patients, was due to radiotherapy in 7, was a result of obstetric complications in 2 patients, and occurred after colporrhaphy in 1 patient. In 60 of these 64 patients closure of the fistula was carried out transvaginally. Fourteen of these 60 patients (23%) had undergone prior surgical attempts to close the VVF (1 to 3 procedures). Transvaginal surgery was successful at first attempt in 55 of these 60 patients (92%). The other 5 patients were successfully treated by a second procedure (again transvaginal: n = 3; transabdominal: n = 2). In conclusion, the transvaginal approach to close VVF is of advantage, avoiding an abdominal incision and reducing postoperative morbidity. In the vast majority of the cases isolated VVF can be treated successfully by transvaginal repair.

Is the expression of multidrug resistance gene product a prognostic indicator for the clinical outcome of patients with renal cancer?

OBJECTIVE: To determine the significance of the expression of the multidrug resistance gene product (MDR-1) for the aggressiveness of renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 31 patients with clinically locally confined RCC treated with radical nephrectomy (mean age 64.1 years, range 41-78; mean follow-up 5.4 years, range 4.3-7.3). Their survival time and disease-free period were evaluated retrospectively. The expression of the MDR-1 gene product was determined immunohistochemically using the JSB-1 antibody in formalin-fixed paraffin-embedded tumour samples from these patients. The significance of this variable and tumour stage and malignancy grade was assessed for predicting the survival and disease-free period using Kaplan-Meier plots (log-rank test or Tarone's test) and the Cox multiple hazard regression analysis. RESULTS: In a univariate analysis, tumour stage (P < 0.002), malignancy grade (P < 0.007) and MDR-1 (P < 0.03) were significant prognostic variables for both survival and disease-free period. Lower MDR-1 expression was correlated with poorer prognosis. On multivariate analysis, MDR-1 and tumour stage were significant factors for predicting the disease-free period, whereas tumour stage and malignancy grade were the most relevant factors for survival time. Calculating prognostic indices based on the results of the Cox analysis, MDR-1 could replace malignancy grade, resulting in a better prediction of survival and disease-free period (P < 0.001 vs 0.0031, P < 0.001 vs 0.021, respectively). CONCLUSION: MDR-1, an established predictor for chemo-resistance, may also be a potent prognostic factor for outcome in patients with locally confined RCC. Moreover, MDR-1 expression seems to correlate with the differentiation of the RCC and thus its value as an objective measure of the degree of differentiation should be further explored.

[Radical prostatectomy as primary monotherapy in capsule penetrating prostatic carcinoma. 15 years outcome]. / Radikale Prostatektomie als primäre Monotherapie bei kapselüberschreitendem Prostatakarzinom. 15-Jahres-Ergebnisse.

Twenty-five patients with locally advanced prostate cancer (stage pT3pN0) underwent pelvic lymphadenectomy and radical prostatectomy and were followed up thereafter for at least 15 years. No hormonal treatment was given prior to tumor progression. Overall and disease-free 15-year survival rates were observed to be 44 and 24%, respectively. These data suggest that a cure from prostate cancer by radical prostatectomy can be expected in a quarter of patients with capsular penetration. From our results, no justification can be derived to exclude radical prostatectomy from the spectrum of treatment options for patients with capsular penetration of prostate cancer. More detailed analysis of the results depending on the local extent of the tumor and histological grade revealed distinct differences with respect to the risk of progression. Histological grade was the single most predictive parameter of progression. Out of all subgroups of patients with capsular penetration of prostate cancer, those with a poorly differentiated tumor showed the shortest progression-free interval after surgery, the highest level of overall progression and the largest proportion of tumor-related deaths. By contrast, the prognosis was only slightly influenced by the presence or absence of seminal vesicle involvement. The role of adjuvant treatment after radical prostatectomy for patients with stage pT3pN0 prostate cancer or for subgroups of them remains to be determined within the scope of prospective randomized trials.

[Immunochemotherapy of metastatic renal cell carcinoma with interleukin 2, interferon-alpha and 5-fluorouracil]. / Immunchemotherapie des metastasierten Nierenzellkarzinoms mit Interleukin-2, Interferon-alpha und 5-Fluorouracil.

Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) were both administered subcutaneously (SC) in combination with intravenously (IV) applied 5-fluorouracil (5-FU) for the treatment of patients with metastasized renal cell carcinoma (RCC). The therapy protocol consisted of a treatment cycle of 8 weeks, which could be carried out in an outpatient regimen. The IFN-alpha was given in each of the 8 weeks (6-9 MU/m2 once to three times weekly SC) combined sequentially with IL-2 (5-20 MU/m2 three times weekly SC for 4 weeks) and 5-FU (750 mg/m2 IV weekly for 4 weeks). Among the 30 consecutive patients treated, in 2 cases a complete, and in 9 cases a partial, remission was achieved in patients with mostly lung and skeletal metastases, with an overall objective response rate of 37%. Mean response duration was 8 months (range 3-18 months). A stable state of the disease lasting 3-18 months was observed in 10 cases. The side effects were only slight and corresponded to toxicity grade I (n = 2), grade II (n = 22) and grade III (n = 6), according to the WHO classification. In conclusion, this triple-drug biochemotherapy demonstrated significant clinical effectiveness comparable with that of an aggressive IL-2 treatment regimen (applied IV), but without its high toxicity.

Simultaneous occurrence of urothelial bladder carcinoma and primary retroperitoneal leiomyosarcoma.

A case of primary carcinoma of the urinary bladder associated with a primary retroperitoneal leiomyosarcoma is presented. Due to the lack of early symptoms, diagnosis of the retroperitoneal leiomyosarcoma was late and therefore the prognosis was poor. Twelve months after diagnosis the patient died not of the bladder tumor, but of the recurrent leiomyosarcoma.

Epidermal growth factor family and renal cell carcinoma: expression and prognostic impact.

OBJECTIVE: Expression and prognostic impact of some exponents of the epidermal growth factor (EGF) family in renal cell carcinoma (RCC) were examined. MATERIALS AND METHODS: EGF, transforming growth factor-alpha (TGF-alpha), EGF receptor (EGF-R), and c-erb B-2 were determined immunohistochemically in formalin-fixed paraffin-embedded tumor samples of 30 patients with locally confined RCCs. The prognostic significance of these growth factors and their receptors as well as of tumor stage and malignancy grade was examined with respect to survival and tumor recurrence by following up the fate of the patients after nephrectomy (mean follow-up time 5.2 years). RESULTS: The members of the EGF family and their receptors studied were expressed to a variable degree in all RCCs investigated. However, using log-rank tests in Kaplan-Meier plots only tumor stage (p < 0.0007) and malignancy grade (p < 0.007) but none of the growth factors or receptors studied (p > 0.05, respectively) exhibited prognostic significance with respect to both survival and disease-free period. On the contrary, there was a significant correlation between EGF and TGF-alpha (p < 0.001), EGF and EGF-R (p = 0.028), EGF-R and c-erb B-2 (p = 0.0009), and-inversely related-between TGF-alpha and tumor stage (p = 0.047) and between EGF-R and malignancy grade (p = 0.03). The coexpression of the factors studied also showed no prognostic relevance. CONCLUSION: The expression of these members of the EGF family seems not to bear evaluable prognostic information for clinical use in the case of RCC.

Cyclic interferon alpha treatment in metastatic renal cell carcinoma: results of a phase II study and review of the literature.

In a phase II clinical trial 23 patients with metastatic renal cell carcinoma were treated with a cyclic regimen of interferon alpha-2b (IFN-alpha). To these 23 patients IFN-alpha at a dose of 10 MU/m2 body surface was applied subcutaneously on 5 consecutive days every 4 weeks. In 12 out of these 23 patients tumor nephrectomy preceded this treatment. The mean follow-up period was 13.6 (range 2-36) months. No complete remission was achieved in any of the patients. One patient with lung metastases revealed a partial response for 19 months. Stable disease lasting 4 to > 36 (mean: 18.7) months was seen in 7 cases. Progressive disease was observed in 15 patients. Only slight side effects were noted, consisting of a maximum toxicity of grades II (n = 20) and III (n = 3) according to the WHO classification. Five out of 8 patients with partial responses or stable disease showed a long-lasting stabilization (> 12 months) of the disease with a good quality of life. In summary, in advanced renal cell carcinoma patients, the objective response rate of a cyclic treatment with IFN-alpha is rather low. However, a long-lasting stabilization of the disease including a good quality of life can be expected in a modest proportion of the patients.

Ureteroscopic treatment of ureteral stones: only an auxiliary measure of extracorporeal shockwave lithotripsy or a primary therapeutic option?

Both extracorporeal shockwave lithotripsy (ESWL) and ureteroscopy are well-established methods in stone treatment; however, the therapeutic procedure in ureteral calculi, especially in the distal third of the ureter, is still controversially discussed. The aim of the present study was to examine the role of ureteroscopy as an auxiliary measure after ESWL and its importance as an alternative therapeutic option in the treatment of distal ureteral stones. Between 1991 and 1994, 115 ureteroscopic procedures in 104 patients with ureteral stones or stone fragments were carried out at our institution. During the same period of time, 1,595 patients with ureteral calculi (in the proximal two thirds of the ureter: n = 956; in the distal third of the ureter: n = 639) were treated with a Dornier HM-3 lithotriptor. In 77 of those 104 patients treated by ureteroscopy, this procedure was indicated as an auxiliary measure after failure of ESWL including 34 out of the 639 patients (5.3%) with stones in the distal part of the ureter. The overall direct success rate during the ureteroscopic stone treatment (including 11 cases with a second procedure) in the proximal, middle and distal third of the ureter was 74, 81 and 92%, respectively. The success rate of primary ureteroscopic removal of distal-third ureteral stones alone was 100% in 27 of these 104 patients. After 3 months the overall stone-free rate of all patients treated with ureteroscopy was 94%. Ureteroscopy appears to be a safe and effective treatment modality, if used as an auxiliary measure after failure of ESWL as well as a primary treatment modality in the case of stones in the distal third of the ureter. On the other hand, ESWL alone is a noninvasive and also successful procedure in treating stones situated in the distal part of the ureter.

[Conservative therapy of blunt kidney injuries]. / Konservative Therapie des stumpfen Nierentraumas.

Forty-two patients with blunt renal injuries were treated between 1984 and 1994 at our institution. Twenty-nine patients revealed a contusion (grade I injury), 10 showed lacerations (grade II), 1 a severe fracture (grade III), and 2 presented pedicle injuries (grade IV). All 10 patients with incomplete renal injuries (grade II) were treated conservatively, i.e. without primary surgery. One of these 10 patients required surgical intervention 3 months after the trauma due to a urinary obstruction. Two of the ten patients with grade II injuries suffered late complications, namely a contracted kidney in one case and hypertension in the other. This means that of 10 patients with conservatively treated grade II renal trauma, a loss of the function of the affected kidney occurred in only one. In 9 patients complete function of the kidney could be preserved. In conclusion, conservative management of incomplete blunt renal injuries is an effective treatment option with few complications.

[Surgical treatment of metastases in renal cell carcinoma]. / Metastasenchirurgie beim Nierenzellkarzinom.

The aim of the present study was to investigate the efficacy of surgical excision of metastases in patients with renal cell carcinoma (RCC). Eighteen patients with metastatic RCC underwent resection of metastases between 1988 and 1994 (pulmonary: n = 6; skeletal: n = 6; cerebral: n = 3; local relapse: n = 3). Two patients suffered from synchronous appearance of metastases, whereas in 16 cases a metachronous occurrence was observed. In 12 out of a total of 18 patients metastases were completely resected. These patients survived longer than patients in whom metastases were incompletely resected (30 vs. 12 months). Six out of these 12 patients with a complete resection of metastases are presently free of disease for a mean duration of 24 months (10-34 months). The resection of lung metastases seems to be associated with longer survival times. In conclusion, surgical resection of metastases--solitary or single organ site--especially in the lung appears to be justified in patients with RCC. The surgical excision of skeletal metastases at least improves quality of life.

Prognostic relevance of the intrinsic growth deceleration of the first passage xenografts of human renal cell carcinomas.

BACKGROUND: Although successful xenotransplantation of human tumors in nude mice highly predicts prognosis, little is known regarding the biologic background of this correlation. In this study, the relationship between the macroscopic growth pattern of first-generation xenografts of human renal cell carcinomas in nude mice and prognosis was studied. METHODS: Macroscopic growth patterns of the first-generation xenografts of locally confined renal cell carcinomas were analyzed according to the best-fit Gompertz recursion formulas. RESULTS: The parameter "b" of the growth pattern, the measure of the intensity of growth deceleration as a function of tumor growth, strongly predicted prognosis after nephrectomy as a single factor; faster growth deceleration, i.e., lower b values, predicted better prognosis (mean follow-up, 5.2 years; P = 0.000008 for the disease free period and P = 0.000018 for overall survival). It is also the most significant single prognostic parameter among others (including staging and grading) according to a multivariate analysis. CONCLUSIONS: The parameter expressing the Gompertzian macroscopic growth deceleration of the first-generation xenografts of clinically locally confined renal cell carcinomas in nude mice explains the strong prognostic impact of xenotransplantation.