″I will not cut, even for the stone″: origins of urology in the Hippocratic Collection.

The Hippocratic Collection, including the most of ancient Greek medicine, remains still interesting, despite the recent advances that transformed definitely the urological healing methods. Considering the patient as a unique psycho-somatic entity and avoiding high risk surgical manipulations were the leading principles dictating the everyday practice. Contemporary physicians can still learn from the clinical observations in times of complete absence of laboratory or imaging aid, from the prognostic thoughts, the ethics, and the philosophical concepts, represented by the Hippocratic writings, tracing into them the roots of Rational Medicine in general and Urology in particular.

“I will not cut, even for the stone”: origins of urology in the hippocratic collection

The Hippocratic Collection, including the most of ancient Greek medicine, remains still interesting, despite the recent advances that transformed definitely the urological healing methods. Considering the patient as a unique psycho-somatic entity and avoiding high risk surgical manipulations were the leading principles dictating the everyday practice. Contemporary physicians can still learn from the clinical observations in times of complete absence of laboratory or imaging aid, from the prognostic thoughts, the ethics, and the philosophical concepts, represented by the Hippocratic writings, tracing into them the roots of Rational Medicine in general and Urology in particular.

Tumefactive multiple sclerosis in a young patient with hemiplegia and seizures associated with radiological appearance mimicking cerebral tumour.

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease, affecting approximately one million adults worldwide. This paper describes a young female patient who presented to the acute medical team with generalised tonic-clonic seizures and right hemiplegia on a background of MS. Radiological imaging revealed a large ring enhancing lesion exerting mass effect. We describe an unusual form of MS and discuss diagnostic pitfalls of tumefactive demyelinating lesions which can be mistaken for brain tumours and abscesses.

Imperforate anus associated with atresia of the transverse colon: a case report.

We describe here a rare case of association of imperforate anus with transverse colon atresia in a male neonate. Preoperative X-ray studies demonstrated: a) a distended loop in the epigastrium with fluid levels on plain A/P upright radiography, b) absence of pelvic intestinal gas on the invertogram 16 hours later. A three-stage operative approach was undertaken comprising resection of the atretic loop and colostomy, posterior sagittal anorectoplasty a few months later, and finally closure of the colostomy. The postoperative outcome was good. The association of these anomalies should be kept in mind in neonates with anal atresia and abdominal distention.

Adjuvant intravesical mitoxantrone versus recombinant interferon-alpha after transurethral resection of superficial bladder cancer: a randomized prospective study.

OBJECTIVE: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-alpha (IFNalpha-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. MATERIAL AND METHODS: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNalpha-2b (8 weekly, 8 fortnightly and 6 monthly instillations). RESULTS: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A-D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1-3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). CONCLUSION: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNalpha-2b showed a better combination of efficacy and safety.

Spontaneous rupture of the ureter after cystectomy and creation of orthotopic ileal neobladder: treatment with percutaneous nephrostomy and drainage.

A case of rupture of the upper ureter following creation of a continent orthotopic neobladder, treated conservatively with percutaneous nephrostomy and drainage of a paranephric collection, is reported.

Shockwave lithotripsy in unrecognized pregnancy: interruption or continuation?

A 32-year-old woman underwent SWL of a 4 x 6-mm calculus in the distal third of the right ureter, receiving 2100 shocks at a maximum intensity of 18 kV. Approximately 1 month later, it was discovered that she had been 10 weeks pregnant at the time of SWL. She chose to continue the pregnancy and delivered a normal infant at term. We do not advocate SWL in pregnancy, but further research is mandatory to determine if this procedure can ever be performed safely during pregnancy.

Modified ileal neobladder for continent urinary diversion: experience and results.

OBJECTIVES: To describe the surgical technique we currently use for the construction of an orthotopic ileal neobladder. We report our experience and functional results of the first 35 cases. METHODS: Since 1993, 35 men have been treated with an ileal neobladder substitute after cystoprostatectomy for bladder cancer. According to the technique we call "a modified S-ileal neobladder," we place emphasis, first, on the complete detubularization of a smaller segment of bowel and its folding in an S configuration without creating a nipple mechanism, and second, on an oblique intramural ureteral reimplantation. RESULTS: The mean postoperative observation time was 38.2 months (range 6 to 72). No perioperative or early postoperative mortality was observed, and few serious early complications have occurred. Late complications included local tumor recurrence and distant metastases in 1 patient (2.8%) and a vesicoileal fistula requiring surgical correction in 1 patient (2.8%). As of February 2000, a total of 29 patients (82.8%) were emptying their neobladder by relaxation of the urethral sphincter mechanism and/or passive expression of the neobladder by abdominal straining. Six patients (17.1%) required clean intermittent catheterization. Daytime continence was attained in 31 patients (88.5%) and nocturnal incontinence was noted in 9 (26%). CONCLUSIONS: Several techniques may be used to create an ileal neobladder. A neobladder constructed using a smaller part of ileum that has been completely detubularized and folded in an S configuration without a nipple is easy to perform, has acceptable complication rates, achieves adequate capacity at low pressure, and provides satisfactory continence rates.

Implantation of microballoons in the management of fecal incontinence.

PURPOSE: The implantation of expandable microballoons has proved successful for the treatment of stress urinary incontinence. This led us to test its effectiveness in the treatment of severe fecal incontinence. METHODS: Six patients (four male), of average age of 43 (range, 29-60) years, with severe fecal incontinence, underwent implantation of expandable microballoons in the submucosa of the anal canal. The implantation was performed under intravenous sedation as an outpatient procedure. Anal manometry, endosonography, and incontinence assessment with a scoring system were performed before and after the implantation. RESULTS: With a mean follow-up of 8.6 (range, 7-12) months, the incontinence scores improved in all patients from an average of 16.16 (standard deviation: +/- 1.6) before the implantation to an average of 5 (standard deviation: +/- 1.26) after the procedure. The anal pressure at rest was not improved in any patient (mean: 50.16 before treatment to a mean of 53 after treatment). No significant adverse events were associated with the procedure, and no serious postimplantation complications were noted. DISCUSSION: Anal implantation of expandable microballoons seems to be a simple, safe, and effective method that restores the fecal continence without hindering normal defecation.

Comparative evaluation of the diagnostic performance of the BTA stat test, NMP22 and urinary bladder cancer antigen for primary and recurrent bladder tumors.

PURPOSE: We compared overall sensitivity and specificity of the urinary bladder cancer antigen enzyme-linked immunosorbent assay (UBC, IDL Biotech, Sollentuna, Sweden), BTA stat test (Bion Diagnostic Sciences, Inc., Redmond, Washington) and NMP22 test kit (Matritech, Newton, Massachusetts), and the differential sensitivity regarding the histological pattern of tumors. MATERIALS AND METHODS: A total of 213 patients with clinical and/or imaging signs of bladder cancer provided a single voided urine sample for the bladder cancer antigen, BTA stat test and NMP22 before cystoscopy. Of these patients 95 were monitored for superficial bladder cancer, while the remaining 118 had no history of bladder cancer. All detected bladder tumors or suspicious lesions were resected transurethrally. A group of 21 age and sex matched healthy volunteers were also evaluated with the same tests. RESULTS: Bladder cancer was confirmed histologically in 118 patients, of whom primary and recurrent tumors were in 68 and 50, respectively. The optimal cutoffs calculated with receiver operating characteristics curves were 8 units per ml. for NMP22 and 12 microg./l. for bladder cancer antigen. Overall sensitivity and specificity were 72.9% and 64.6% for the BTA stat test, 63.5% and 75.0% for NMP22, and 80.5% and 80.2%, respectively, for bladder cancer antigen. Bladder cancer antigen proved significantly more sensitive than NMP22 for detecting bladder cancer (p = 0.001) but not more than the BTA stat test, while the specificity of it was significantly higher than that of the BTA stat test (p = 0.009). Bladder cancer antigen had a sensitivity of 80.7% for stage Ta tumors, which was significantly higher than NMP22 (52.6%, p = 0.001) and the BTA stat test (57.9%, p = 0.01). In grade I tumors the sensitivity of bladder cancer antigen (70%) did not differ significantly than that of the BTA stat test (50%) and NMP22 (50%, p = 0.14). Bladder cancer antigen had the least false-positive results in patients with a history of bladder cancer and negative cystoscopy, and those with urological disease other than bladder cancer. CONCLUSIONS: Our data indicate that bladder cancer antigen may be a more potent diagnostic marker for bladder cancer than NMP22 and the BTA stat test based on the higher sensitivity for detecting low stage and low grade tumors, and the higher specificity. The contribution of these tests for detection of bladder cancer should still be considered adjunctive to cystoscopy.

MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: a comparison with clinicopathologic features and survival.

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at several points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their expression in bladder cancer has not been addressed. Immunohistochemistry (Strept-ABC-HRP method) and in situ hybridization were performed to detect MMP-1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cancer, their expression was evaluated in relation to known clinicopathologic parameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant association with deeply invasive and grade III tumors versus superficial and lower grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocalization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with poor patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in bladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.

Predictive value of topoisomerase II alpha immunostaining in urothelial bladder carcinoma.

AIMS: The nuclear enzyme DNA topoisomerase II has been shown to be required for chromatin condensation and chromosomal segregation during mitosis; its isoform topo II alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relation of the expression of topo II alpha to the biological behaviour of conventional urinary bladder cancer. METHODS: Formalin fixed, paraffin wax embedded tissue from 94 specimens of bladder urothelial cancer were immuno-histochemically stained for topo II alpha. For each case, a topo II alpha index was determined. A similar index had been determined for Ki-67, a known cell proliferation marker. Each case had also been graded, staged, and evaluated for DNA ploidy as well as for p53 and bcl-2 immunoreactivity. RESULTS: Raised topo II alpha expression (in > or = 10% of malignant nuclei) correlated with two adverse prognosticators--high grade (p = 0.027) and invasion of the muscularis propria (p = 0.013), but with no other evaluated parameter. By multivariate survival analysis using Cox's proportional hazard model, high expression of topo II alpha was found to be predictive for worse survival (p = 0.0047). Patients' age, tumour stage, and grade were also retained as independent prognostic factors (p = 0.0349, p = 0.00005, and p = 0.0130, respectively). The negative influence of increased topo II alpha immunopositivity on patients' survival was also seen in the subgroup of patients with non-muscle invasive carcinomas (p = 0.0004), in patients with a bcl-2 negative phenotype (p = 0.0330), and in those with low Ki-67 indices (p = 0.0341). CONCLUSIONS: Because topo II alpha and Ki-67 failed to demonstrate a significant interrelation, they appear to be different molecules that both function at separate phases in the complex process of cellular proliferation. The assessment of increased topo II alpha immunoreactivity in specimens from urothelial carcinomas might help to select patients (particularly among those with superficial tumours) in the worse prognostic categories for new therapeutic strategies.

Endoscopic implantation of Plexiglas (PMMA) microspheres for the treatment of GERD.

BACKGROUND: A gelatinous implant containing polymethylmethacrylate (PMMA) beads is successfully used to augment the diminished thickness of the chorium in patients with skin defects and wrinkles. The aim of the present study was to determine whether submucosal injection of PMMA microspheres into the lower esophageal folds decreases the severity of symptoms and acid reflux in patients with GERD. METHODS: Endoscopic submucosal implantation of PMMA was carried out in 10 patients with GERD who were either refractory to or dependent on proton pump inhibitors. Symptom severity score, 24-hour pH monitoring, upper GI endoscopy, and EUS were performed to evaluate the efficacy of implantation. RESULTS: A significant decrease in the symptom severity score and mean total time with esophageal pH less than 4 was noted after the implantation of PMMA (p < 0.05). Seven of 10 patients were taking no medication after PMMA implantation. There were no serious procedure-related complications. CONCLUSIONS: Endoscopic implantation of PMMA into the submucosa of the lower esophageal folds may be a new method for treating GERD. Further studies are required to determine the long-term efficacy of the procedure.

The anatomy of the tendon of infundibulum.

The heart, as we know, is a muscular tissue supported by collagenous structures forming the fibrous skeleton of the heart. A structure by the name of the tendon of infundibulum appeared in the literature with no definite information about its structure or even its existence. The tendon of infundibulum was described as a strip of fibrous tissue structure situated between the aortic root and pulmonary trunk. Our study involved 30, formalin fixed, adult human hearts ranging from 18 to 81 years. Classical macroscopic anatomical methods were applied to observe macroscopically all the connections between the aorto-pulmonary trunk, together with serial transverse histological sections, through roots of the aorta and pulmonary trunk, using eosin-hematoxylin and van Gieson staining. All the hearts seemed to encompass many fascial bands attended by connective tissue. However these fascial bands are not concrete structures and cannot be termed tendons. In our investigation we have been unable to demonstrate macroscopically or histologically any structure which could be significantly approximating to the initial description of the literature. However, as far as we are able to judge, the term tendon of infundibulum has erroneously been introduced into many medical textbooks since the literature cannot still prove its existence.

Extracorporeal shockwave lithotripsy in patients with distal ureteral calculi does not influence the prostate specific antigen value.

BACKGROUND AND PURPOSE: Distal ureteral calculi can be treated with extracorporeal shockwave lithotripsy (SWL) in situ, which has a high rate of success. As the prostate is in vicinity of this part of the ureter, it is possible that the shockwaves may pass through the prostate also. We evaluated the effect of SWL on the serum concentration of prostate specific antigen (PSA). PATIENTS AND METHODS: A total of 44 men with distal ureteral calculi located a maximum of 20 mm from the ureteral orifice and without any history of recent urinary tract infection, benign prostatic hyperplasia, or prostate cancer underwent SWL with the Dornier HM-4 lithotripter. Their serum PSA values were measured 5 minutes before SWL as well as 3 hours and 1, 7, and 30 days afterward. The differences of these PSA values were estimated. From a control group of 10 healthy donors, two consecutive PSA values were obtained 30 days apart. RESULTS: Of these patients, 93% (41/44) were stone free within 1 month according to plain radiographs and ultrasonography. No statistically significant difference was observed between the PSA concentration before and after treatment or between the patients who underwent SWL and the control group. CONCLUSION: Treatment of distal ureteral calculi with SWL does not affect the serum PSA concentration.

Oxidative stress of red blood cells during Bacillus Calmette-Guerin intravesical instillations.

Although Bacillus Calmette-Guerin (BCG) intravesical instillation is widely accepted as a very effective modality in treating bladder carcinoma in situ, and in preventing superficial bladder cancer recurrence, its mechanism of action is not yet fully understood. The antitumor effects of BCG are mostly related to local immunological events but a systemic activation of the immune system cannot be excluded. The objective of the present study was to estimate the systemic production of oxidants during intravesical BCG treatment. Systemic production of oxidants was estimated by assessing the red blood cells (RBC) oxidative stress in twelve patients undergoing BCG immunotherapy for bladder carcinoma in situ. RBC oxidative stress induced by peroxynitrite was determined by luminol-enhanced chemiluminescence. During the treatment period, the RBC oxidative stress revealed a biphasic curve of changes: after an initial 5-fold increase, it dropped to pretreatment levels following the 4th instillation. Intravesical BCG administration induced systemic production of oxygen free radicals that may reflect a systemic activation of the immune system.

Immunohistochemical expression of transforming growth factor beta 1 and nm-23 H1 antioncogene in prostate cancer: divergent correlation with clinicopathological parameters.

BACKGROUND: Prostate cancer is one of the main causes of morbidity and mortality among men. Several oncogenes and growth factors have been studied in an attempt to explain the molecular basis of carcinogenesis and progress of this carcinoma. In this study we correlated the immunohistochemical expression of antioncogene nm-23 H1 and transforming growth factor beta 1 (TGF-beta 1) with the clinical stage, PSA values, Gleason score and survival in prostate cancer. MATERIALS AND METHODS: Fifty nine patients with prostate cancer were evaluated. PSA measurement, Gleason score determination and clinical staging were recorded for all the patients by the time of initial diagnosis and prior to any treatment. Follow-up ranged from 12 to 40 months. Tissue sections from representative areas of the tumors were immunohistochemically stained for nm-23 H1 and TGF-beta 1. The expression of these markers was correlated with stage, PSA values, Gleason score and survival. RESULTS: There was a negative correlation between nm-23 H1 staining and tumor stage and grade. High grade (Gleason score 8-10) and stage D tumors showed weaker staining than low stage and grade tumors. There was a positive correlation between TGF-beta 1 staining, tumor stage and serum PSA levels. Additionally, TGF-beta 1 proved to be a negative predicting factor for patient survival. In tumors expressing both markers, TGF-beta 1 was the one to determine the aggressiveness of the carcinoma. CONCLUSIONS: nm-23 H1 appears to be a tumor suppressor gene in prostate cancer, while TGF-beta 1 may act as a stimulating agent provoking aggressive behavior and metastasis. Their immunohistochemical staining may constitute complementary information in the evaluation of prostate cancer patients.

Double partial nephrectomy in a patient with two adenocarcinomas in a solitary kidney.

We present a 67 year-old female patient with two synchronous adenocarcinomas in a solitary kidney. She underwent thorough clinical and radiographic evaluation. Selective angiography proved to be the most reliable examination in preoperative diagnosis. Double partial nephrectomy was performed and the patient has normal renal function and no evidence of recurrence 27 months postoperatively. Partial nephrectomy in patients with one tumor in a solitary kidney is well documented, though we believe that partial nephrectomy can also be performed in selected cases with multifocal tumors.

The distribution of S-100 protein in hyperplastic and neoplastic prostatic epithelium.

Specimens from 30 cases of benign prostatic hyperplasia and 75 cases of prostatic carcinoma obtained during suprapubic prostatectomy, transurethal resection of the prostate and radical prostatectomy, were stained immunohistochemically for S-100 protein, prostatic acid phosphatase (PAP), prostatic specific antigen (PSA), neuron specific enolase (NSE) and polyclonal keratin. S-100 protein was positive in 9.3% of prostatic carcinomas and negative in all cases of prostatic hyperplasia. PAP and PSA were positive in all cases, while NSE was positive in 16% of the carcinoma cases. Polyclonal keratin was positive in both cell layers of the double layered hyperplastic prostatic epithelium with a more intense staining pattern in the outer cell layer. The authors believe that the S-100 protein immunoreactivity observed in some prostatic carcinomas, reflecting the change in the functional status of the neoplastic cells, might be of prognostic significance. They also emphasize the non-myoepithelial nature of the outer cell layer of the double layered prostatic epithelium.

Prognostic value of E-cadherin, beta-catenin, P120ctn in patients with transitional cell bladder cancer.

BACKGROUND: Loss of E-cadherin-catenin mediated adhesion is known to play a major role in tumour progression in many human carcinomas. MATERIALS AND METHODS: By means of immunohistochemistry, we have investigated the expression of E-cadherin, beta-catenin and p120ctn in 102 transitional cell bladder carcinomas (TCCs) and statistically analysed these expressions with known clinicopathological parameters and patient survival. RESULTS: Abnormal expression of E-cadherin, beta-catenin and p120ctn was associated with high grade and high stage of TCCs (p < 0.001). Abnormal beta-catenin expression demonstrated a statistically significant correlation with poor patient survival (p = 0.03) while abnormal E-cadherin expression was associated with poor survival in patients with muscle invasive TCCs (p = 0.025). However, in multivariate statistical analysis a suggestive association with poor survival was observed only for E-cadherin (p = 0.06). Simultaneous abnormal expression of all the molecules demonstrated an association of suggestive significance with poor patient survival (p = 0.07). CONCLUSION: E-cadherin expression may be a useful prognostic marker in patients with invasive TCCs.