Risk of biochemical recurrence in patients with a positive surgical margin after radical prostatectomy.

INTRODUCTION: Serum prostate specific antigen (PSA) is an irreplaceable marker in the detection and follow-up of patients with prostate cancer. In our analysis we addressed factors that could indicate the likelihood of biochemical recurrence (BCR) early after radical prostatectomy. We mainly focused on the positive surgical margin (R1). METHODS: Retrospective evaluation and analysis of the database of patients with prostate cancer after radical prostatectomy from 2001 to 2019. In total 1529 patients were enrolled in the study. The median follow-up was 48 months. The age of the patients ranged from 49 to 76 years. We used pre-operative PSA values, and the monitoring of the dynamics of 3rd generation PSA progression (detection limit 0.003 ng/ml) at month 1 and month 3 after surgery and then in 3-month intervals. We monitored the surgical margin positivity (R0 negative, R1 positive) and the Gleason score (GS) based on histological samples and we analysed the relationship to biochemical recurrence of the disease. RESULTS: The pre-operative PSA value did not show a direct relationship to the R1 risk. Patient values in the groups R1 and R0 differed only by 1.159 ng/ml (p=NS). The 3rd generation PSA value at month 1 after surgery was 50.82% higher in R1 patients (p>0.001). 50% of patients with R1 (29.5% patients of the total) did develop BCR during the follow-up period, while in patients with R0 (70.5% patients of the total) this proportion was 30% (p>0.001). Among those with GS 67, 47% developed BCR. The GS 810 group relapsed in 75% of the cases (p>0.001). CONCLUSION: According to our analysis 33% of the patients reached the stage of biochemical recurrence. We demonstrated a direct dependency between the risk of recurrence and the final Gleason score. The presence of R1 should not be viewed as a direct indication for adjuvant radiotherapy.

Transformation by oncogenes encoding protein kinases induces the metastatic phenotype.

Oncogenes encoding serine/threonine or tyrosine kinases were introduced into the established rodent fibroblast cell line NIH 3T3 and tested for tumorigenic and metastatic behavior in T cell-deficient nude mice. Transforming oncogenes of the ras family were capable of converting fibroblast cell lines to fully metastatic tumors. Cell lines transformed by the kinase oncogenes mos, raf, src, fes, and fms formed experimental metastases and (in some cases) these genes were more efficient at metastatic conversion than a mutant ras gene. In contrast, cells transformed by either of two nuclear oncogenes, myc or p53, were tumorigenic when injected subcutaneously but were virtually nonmetastatic after intravenous injection. These data demonstrate that, in addition to ras, a structurally divergent group of kinase oncogenes can induce the metastatic phenotype.

Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH 3T3 cells.

Using three independent approaches, we studied the effects of H-ras on metastasis formation. Analysis of five in vitro-ras-transfected 10T1/2 clones with either flat or refractile morphologies revealed a relationship between metastatic potential, H-ras expression, and anchorage-independent growth. Four metastatic variants derived from a poorly metastatic, low-H-ras-expressing line all expressed high levels of H-ras RNA and grew efficiently in soft agar. Activation of H-ras expression in the metastatic tumors had occurred through amplification and rearrangement of H-ras sequences. In addition, preinduction of p21 synthesis in NIH 3T3 line 433, which contains v-H-ras under transcriptional control of the glucocorticoid-sensitive mouse mammary tumor virus long terminal repeat, significantly increased metastatic efficiency. Glucocorticoid treatment of normal or pEJ-transformed NIH 3T3 cells did not affect metastatic potential. These data reveal a direct relationship between ras expression and metastasis formation and suggest that metastatic and transformed phenotypes may be coregulated in ras-transformed 10T1/2 and NIH 3T3 cells.

Sulcus nervi dorsalis penis: site of origin of Alcock's syndrome in bicycle riders?

This article introduces a hypothesis that the pudendal nerve compression syndrome, also known as the Alcock's syndrome in long-time duration bicycle riders might be caused by an irritation of the dorsal nerve of penis in a groove on the inferior ramus and the anterior surface of pubis, previously described by authors as the sulcus nervi dorsalis penis. Alcock's syndrome in bicycle riders has been characterized as a prolonged glans and penile insensitivity, genital numbness and an erectile dysfunction. Although no anorectal pain or disturbance of the bulbocavernosus reflex has been reported in these patients, we assume it cannot be caused by a compression of the pudendal nerve in pudendal (Alcock's) canal, hence by a compression of the dorsal nerve of penis in the sulcus nervi dorsalis penis. In future, if clinical studies confirm our hypothesis, it might be more sophisticated to evaluate this syndrome apart from the Alcock's syndrome and term it the dorsal nerve compression syndrome rather than the Alcock's syndrome.

Sulcus nervi dorsalis penis/clitoridis: its reliability as a character for sex determination of isolated human pubic bones.

This study describes a distinct groove on the caudal and ventral surfaces of the pubic bone termed the "sulcus nervi dorsalis penis/clitoridis" and assesses its usefulness as a character for sex determination of isolated pubic bones. Analysis of 168 male and 118 female pubic bones showed that the presence of a sulcus was a non-random event. A sulcus was present in 72% of male pubic bones and 83% of female pubic bones examined (Czech population). Seven characters (including three of the sulcus) were measured in a sample of an 86 isolated pelvises grouped according to the gender. A step-wise discriminant function analysis was performed on this dataset to assess whether a combination of these characters could be used for gender identification of isolated pubic bones. A bivariate plot using Mahalanobis distances showed distinct differences in male and female pubic bones. The width of the sulcus and the craniocaudal length of the pubic symphysis significantly described most of the variations observed between male and female pelvises. A post hoc analysis of the reliability of the technique showed that stepwise discriminant function correctly identified 83% of male and 86% of female known-sex pelves. Thus discriminant function analysis of the sulcus and pubic bones can reliably be used to determine sex in human osseal remnants.

[Sulcus nervi dorsalis penis/clitoridis: clinical and forensic aspects]. / Sulcus nervi dorsalis penis/clitoridis: klinické a forenzní aspekty.

Sulcus nervi dorsalis penis/clitoridis is a groove on inferior ramus of pubis and ventral surface of the body of pubis, where dorsal nerve of penis in male and dorsal nerve and artery of clitoris in female run. Close relation of the dorsal nerve of penis/clitoris and pubis, represented by the course of sulcus nervi dorsalis penis/clitoridis has a major impact in surgical disciplines. Exact preparation of the dorsal nerve of penis is crucial in correct performance of conversion of genitalia in patients with transsexualism, in reconstruction of posterior urethra, in hypospadia, during performance of penile blockade during circumcision and in revascularization surgery of erectile dysfunction. The role of sulcus nervi dorsalis penis in the Alcock's syndrome is discussed. Similarly, it is advisable to take care of the dorsal nerve of clitoris inside sulcus nervi dorsalis clitoridis during reduction clitoridoplasty in patients with adrenogenital syndrome and during the insertion of transobturator vaginal tape. Injury of dorsal nerve of penis/clitoridis leads to hypestesia or anestesia of glans penis/clitoridis. The injury of dorsal artery of clitoris leads to hematoma. It is possible to use sulcus nervi dorsalis penis/clitoridis in sexing of isolated pubis from antropological or forensic purposes. Lateral border of sulcus nervi dorsalis penis/clitoridis corresponds to vertical ridge and lateral border of sulcus nervi dorsalis clitoridis to ventral arc--two parameters, which are part of the Phenice's method for sexing of isolated pubis.

Natural killer cell regulation of implantation and early lung growth of H-ras-transformed 10T1/2 fibroblasts in mice.

We examined the relative role of the natural killer (NK) cell and H-ras gene in controlling metastasis formation using a novel assay for quantitating viable tumor cells entering and surviving in the lung for up to 13 days following i.v. tumor inoculation. This assay utilized the resistance to G418 sulfate conferred by transfection of the neoR gene into 10T1/2 fibroblasts along with activated H-ras. We had previously shown that the metastatic efficiency of T-24-H-ras-transformed 10T1/2 fibroblasts correlated with H-ras expression at the RNA level. In this paper we show that the NK cell could recognize H-ras-transformed fibroblasts in vivo and control experimental metastasis formation using NK-suppressed and -activated syngeneic C3H recipients. Evaluation of NK sensitivity in vitro of individual lines did not predict metastatic ability. However, NK susceptibility in vitro did inversely correlate with the ability of tumor cells to arrest and survive in the lung for the first 48 h after i.v. inoculation. Although the level of H-ras RNA correlated with the ultimate metastatic potential, it did not correlate with the initial rate of tumor cell pulmonary retention or clearing. Over the next 10 to 12 days, however, we detected a preferential survival and outgrowth of high H-ras-expressing variants, which correlated well with the ultimate metastatic ability but not NK susceptibility. These observations argue that the NK cell has its major effect early in the course of the disease, while subsequent tumor growth occurs preferentially in high H-ras-expressing cell lines.

Transient alterations in the expression of protease and extracellular matrix genes during metastatic lung colonization by H-ras-transformed 10T1/2 fibroblasts.

It has been proposed that tumor progression is a selective process and that only a minority of tumor cells survive this selection because they possess the phenotypic traits necessary for metastasis and organ colonization. Both proteases and extracellular matrix proteins have been implicated in invasion and metastasis formation. To examine the nature of the selection process, we transformed 10T1/2 fibroblasts with T24 H-ras and the neoR gene and selected a clonal line expressing the mutant ras gene. After i.v. injection of this line into syngeneic C3H/HeN mice, tumor cells were recovered from lungs by enzymatic treatment and selective outgrowth in G418. Less than one of 10(3) cells survived in the lung 30 min after inoculation, and these exhibited a unique phenotype. This was characterized by a propensity to lodge in the lung on reinjection; markedly enhanced mRNA levels of procollagen alpha 2(I), procollagen alpha 1(III), and fibronectin; and decreased levels of laminin, major excreted protein (procathepsin L), transin, and H-ras. Between 1 and 9 days after tumor injection, the phenotype of the cells surviving in the lung changed dramatically and exhibited a pattern of gene expression with increased protease and low matrix protein mRNA levels. This coincided with a 26-fold increase in the ability to colonize lungs on i.v. injection. Both the phenotype characterized by its propensity to arrest in the lung and that showing enhanced metastatic ability were unstable on prolonged in vitro culture. We hypothesize that two selection events have occurred. The first is for lung arrest and implantation of variants of the injected tumor with high matrix protein and low protease levels. A second selection then occurs for tumor cells that carry a favorable phenotype for invasion and proliferation which is associated with low matrix protein and high protease gene expression. These two phenotypes are represented within a clonal population of recently transformed tumor cells.

[Tumoriform endometriosis of the urinary bladder in advanced pregnancy]. / Tumoriformní endometrióza mocového mechýre v pokrocilém tehotenství.

A case of tumoriform endometriosis of urinary bladder immitating a tumor of the bladder during the first pregnancy of a 25-year-old patient was successfully treated by partial cystectomy allowing continuation of the pregnancy, a normal term delivery and after 5 months a second pregnancy with term delivery.

Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1H NMR spectroscopy.

Apoptosis and necrosis need to be differentiated in order to distinguish drug-induced cell death from spontaneous cell death due to hypoxia. The ability to differentiate between these two modes of cell death, especially at an early stage in the process, could have a significant impact on accessing the outcome of anticancer drug therapy in the clinic. Nuclear magnetic resonance spectroscopy was used to distinguish apoptosis from necrosis in human cervical carcinoma (HeLa) cells. Apoptosis was induced by treatment with the topoisomerase II inhibitor etoposide, whereas necrosis was induced by the use of ethacrynic acid or cytochalasin B. We found that the intensity of the methylene resonance increases significantly as early as 6 h after the onset of apoptosis, but that no such changes occur during necrosis. The spectral intensity ratio of the methylene to methyl resonances also shows a high correlation with the percentage of apoptotic cells in the sample (r2=0.965, P<0.003).

[Endometriosis imitating bladder tumor in 2nd trimester of pregnancy]. / Endometrióa imitující nádor mocového mechýre ve II. trimestru tehotenství.

OBJECTIVE: Case presentation of bladder endometriosis during 2nd trimester imitating urinary bladder tumour. SETTING: Mother and Child Care Institute, Prague. III. Medical School of Charles University, Prague. CASE REPORT: 25-years old patient, 2nd trimester of first pregnancy. TREATMENT: Partial bladder cystectomy. RESULT: Complete recovery succeded by term delivery. CONCLUSION: Tumouriform endometriosis of urinary bladder successfully treated by partial cystectomy allowing normal term delivery.

Growth factor modulation of metastatic lung colonization.

Altered production and response to growth factors is often involved in neoplasia but little is known about their effect on the dissemination of tumors. Therefore, we have examined the effect of growth factors on metastatic lung colonization. Autocrine induction of the metastatic phenotype was demonstrated in NIH-3T3 cells transformed by a signal peptide-bFGF gene but not bFGF in the absence of the signal peptide. In addition, exogenous growth factor regulation of metastasis was demonstrated. Treatment of ras transformed C3H-10T 1/2 cells and ras or src transformed NIH-3T3 cells with bFGF prior to intravenous injection resulted in potent inhibition of metastatic potential. Stimulation of v-fms transformed cells by the natural fms-ligand, CSF-1, resulted in potent stimulation of metastatic behavior in freshly plated or refed cells, whereas following autocrine conditioning of the medium, the metastatic properties of these cells were sensitive to inhibitory effects of CSF-1. These observations indicate that specific growth factors can regulate the metastatic phenotype and, depending on the oncogenes responsible for cell transformation and autocrine conditioning, these effects can be either stimulatory or inhibitory.

[Neurovascular sparing radical prostatectomy]. / Radikální prostatektomie setrící nervove cévní svazky.

Radical prostatectomy means a surgical removal of the whole prostate gland with its capsule and seminal vesicles. The fact that this operation is not performed frequently is usually due to late diagnosis of this condition rather than to involvement indicated for radical prostatectomy. The paper describes a technique which helps to spare the sphincter and posterolateral nervous and vascular bundles, as these are responsible for continence and erectile potency. The experience acquired is based on good results obtained in 13 patients, and the author stresses the importance of early diagnosis of carcinoma of the prostate using preventive per rectum examinations in male patients over 45 years.

[A continent artificial urinary bladder from detubulized ileal or ileocecal segments]. / Kontinentní náhrady mocového mechýre z detubulizovaného ileálního nebo ileocekálního segmentu.

At present, the attention of reconstructive surgery is focused on continent reservoirs constructed from detubulized intestinal segments. Based on two-year experience, the authors present an analysis of the results obtained from 26 patients with continent ileal or ileocecal neovesica. These operations improve the quality of life and guarantee more safety. In most cases, the function of the neovesica approximates the natural physiological condition. The authors also discuss the economical aspect as regards the high cost of materials needed for ureteroileostomy--annual expenditure on flanges and bags (firm Pfizer) per 1 person amounts to 32,000 Czechoslovak crowns fco. The continent neovesica does not narrow the therapeutical spectrum of urinary deviations, on the contrary, it extends them, which is why the authors prefer to use it.

[A continent urinary diversion with a detubularized rectum and sigmoid (sigmo-rectal pouch)]. / Kontinentní mocová derivace s pouzitím detubulizovaného rektosigmatu (sigma-rectum pouch).

BACKGROUND: The continent reservoir is an ideal urinary diversion in patients after cystectomy. The artificial closing mechanism construction in these reservoirs is rather complicated and the results are uncertain. The objective of the present work is to assess own experience with a relatively simple rectosigmoid reservoir created by a method described by M. Fisch. METHODS AND RESULTS: Since 1992 till 1995 the sigma-rectum detubularized reservoir was performed in 30 patients. The intricating bladder cancer was an indication for the operation in 27 patients and the other bladder diseases in 3 patients. The patients age ranged from 18 to 75 years. Diurnal continence was achieved in all 30 patients. 12 of them have to awake during the night to evacuate the reservoir 1 to 3 times. CONCLUSIONS: Sigma-rectum pouch is a good form of cintinent diversion in such patient, which are not suitable for orthoscopic neobladder because of oncologic limitation or bad general conditions. The patients tolerate the procedure very well, heal and adapt quickly to new evacuating mechanisms.

[Problems with indications for extracorporeal lithotripsy in urolithiasis]. / Indikacní problémy extrakorporální litotrypse urolitiázy.

Extracorporeal lithotripsy is a modern noninvasive method for the treatment of urolithiasis. The morphological and functional state of the urinary pathways, the localization of concrement and their size and number call in 35% of the patients for additive and auxiliary operations. Such comprehensive treatment can be provided by departments where all methods for the treatment of lithiasis are readily available. Repeated lithotripsy and combined therapeutic methods of more complicated conditions protract hospitalization and reduce the number of patients. The authors tested in more than 2500 lithotripsies the possibility to apply this treatment in the great majority of lithiases. However, because of the limited capacity they had to reduce the spectrum of indications to a minimum. Retardation of treatment by a protracted waiting period could damage the patient and it is then better to indicate another therapeutic approach; or to provide adequate treatment. We hope that patients who will need treatment after a year's time, will have the opportunity to be treated sooner by lithotriptors which should be installed before long in other departments.

[Magnetic resonance imaging in the diagnosis of prostatic carcinoma]. / Prínos magnetické rezonance (MRI) v diagnostice karcinomu prostaty.

The standard diagnostic and staging evaluation of prostate cancer includes digital rectal examination, transrectal ultrasonography (TRUS), serum prostate-specific antigen (PSA) level measurement, abdominal pelvic CT and radionuclide bone scan. Magnetic resonance imaging (MRI) (especially endorectal magnetic resonance) opens new possibilities for diagnostic imaging of the prostate. It seems to be better for detecting seminal vesicle invasion. Unfortunately, sensitivity in evaluation of minor capsular and seminal penetration is low and differentiation between haemorrhage, chronic inflammatory, fibrotic changes and tumours is impossible.

[Reconstruction of the lower urinary tract in women after cystectomy]. / Rekonstrukce dolních mocových cest u zeny po cystektomii.

BACKGROUND: The first extirpation of the urinary bladder on account of malignant papilomatosis was carried out by Karel Pawlik in 1889 as the first one in the world. At present cystectomy is indicated usually because of an infiltrating carcinoma of the urinary bladder. The objective of the present paper is, based on anatomical investigations, elaboration of a surgical technique of creating a orthotopic neovesica following cystectomy sparing a functional female urethra. METHODS AND RESULTS: In 1993-1998 32 women were operated within the age bracket of 32-72 years with a confirmed infiltration carcinoma of the urinary bladder. The authors describe in detail their own surgical technique. Day continence was achieved in 20 patients. Twelve patients suffer from stress incontinence. Eight patients have a post-micturition residue of 250-300 ml calling for a combination of medicamentous treatment and autocatheterization. The capacity of the neovesicle is the cause of nycturia: 21 patients must micturate once or twice during the night. Urodynamic studies did not reveal significant differences between patients with chronic post-miction residues and without residues. Also the mean functional length of the urethra was in both groups similar (27 mm in patients with a residue and 26.2 mm in patients without a residue). CONCLUSIONS: The elaborated surgical technique of cystectomy and creation of a neovesica makes a good quality of the patients' life possible.

Carcinoma of the prostate in specimens removed for benign hyperplasia.

Unexpected carcinoma was found in 69 cases (7.7%) our of 891 patients subjected to surgery for clinically benign hyperplasia. The incidence was higher in specimens removed by suprapubic or retropubic approach (10.2%) than by transurethral resections (2.7%). Carcinoma was found most frequently in patients aged 70 to 80 years (50.8%), next being the age group 60 to 70 years. A statistically significant prevalence of carcinoma was in th medium sized prostases (30-40 grams = 12.4%) well compared to smaller or larger prostates. The principles for a systematic topographically oriented microscopic examination are described. Morphological categories of latent carcinoma are defined as microcarcinoma, focal, multifocal or diffuse carcinoma. Adenocarcinoma was the uniform pattern of these latent carcinomas. The therapeutic attitude towards the microscopically diagnosed clinically latent prostatic carcinoma is discussed.

[Le Duc's implantation of the ureter into the neovesical]. / Le Ducova implantace ureteru do neoveziky.

Implantation of the ureters into a neovesica should be antireflux and prevent thus their obstruction. These demands are met by Le Duc's implantation which is simple and safe. Le Duc's implantation was used in 16 patients with very favourable results documented by cystography, urography and cystoscopy.