Prognostic value of the involvement of the urinary collecting system in renal cell carcinoma.

OBJECTIVES: The prognostic role of the invasion of the urinary collecting system (UCS) by renal cell carcinoma (RCC) has not attracted a notable amount of attention. The aim of this study was to investigate incidence and prognostic value of UCS involvement in RCC. MATERIAL AND METHODS: All pathological reports of radical nephrectomies performed in two centres of urology from November 1983 to December 1999 were reviewed in order to evaluate the invasion of the UCS (calices, renal pelvis, ureter). Patients were divided into two groups according to presence (Group 1) or absence (Group 2) of UCS invasion. The stage was determined according to the TNM 6th edition. Overall and cause-specific survival rates were evaluated. Univariate and multivariate analyses were performed. RESULTS: The evaluable specimens were 671 from the 735 examined; in 64 cases it was not possible to ascertain or to exclude UCS involvement. Invasion of the UCS was found in 59 cases (8.8%). Median follow-up was 59.0 months (range 0-216). Tumours invading the UCS were usually symptomatic, with high nuclear grade and predominantly high stage. At univariate analysis the 5 year overall and cause-specific survival rates of tumours invading the UCS were significantly lower when compared to those without UCS invasion (42.8% versus 60.8% and 45.5% versus 64.7%, respectively). When groups were stratified, according to the pT category, the 5-year cause-specific survival rate was only significantly different for the pT2 category (33.3% versus 76.9%). At the multivariate analysis TNM staging, symptoms at diagnosis and tumour grade were the only independent prognostic factors. CONCLUSION: The invasion of the UCS by RCC is unusual, particularly in small tumours. UCS involvement does not represent an independent prognostic factor. However, in organ-confined tumours (i.e. pT2) UCS involvement has an influence on the prognosis and should be taken into account when planning adjuvant treatments and follow-up.

The number of lymph nodes examined and staging accuracy in renal cell carcinoma.

OBJECTIVE: To determine the number of lymph nodes that need to be examined to accurately stage the pN variable in patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). PATIENTS AND METHODS: We reviewed the operative and pathology reports of 725 patients with RCC submitted for RN. All tumours were classified using the fifth edition of the Tumour-Nodes-Metastasis classification. For each patient the number of lymph nodes removed was recorded. The patients were divided into five different groups according to the number of nodes removed, i.e. group 1, 1-4; group 2, 5-8; group 3, 9-12; group 4, 13-16; and group 5, >or= 17. We evaluated the factors that affected the number of lymph nodes removed with nodal dissection and the variables that influenced the incidence of nodal involvement. RESULTS: Lymphadenectomy was performed in 608 patients (83.8%); in these patients the rate of lymph node metastases was 13.6%. The median (range) number of nodes removed was 9 (1-43); there was a statistically significant correlation between the number of nodes removed and the percentage of nodal involvement (r = 0.6; P < 0.01). The rate of pN+ was significantly higher in the patients with >or= 13 than in those with < 13 nodes examined (20.8% vs 10.2%; P < 0.001). For organ-confined and locally advanced tumours there was a statistically significant difference in the pN+ rate between patients with < 13 or >or= 13 nodes examined (3.4% vs 10.5%, and 19.7% vs. 32.2%, respectively). CONCLUSIONS: The proportion of tumours classified as pN+ increased with the number of lymph nodes examined. In RCC,> 12 lymph nodes need to be assessed for optimal staging.

Symptoms, bothersomeness and quality of life in patients with LUTS suggestive of BPH.

The QUIBUS study is the largest investigation ever performed in Italy with an extensive use of the ICS-BPH questionnaire. The internal consistency of each of its three domains was high for ICS-Male (Cronbach's alpha = 0.83 and 0.89 for symptoms and bother, respectively) and lower for ICS-Sex (Cronbach's alpha = 0.63 and 0.75, see a following paper of this issue) and ICS-QoL (Cronbach's alpha = 0.53), as previously reported in the validation study of this tool. Voiding symptoms were more frequently reported, with reduced urinary stream, terminal dribble and incomplete bladder emptying as the most frequently represented. The first storage symptom in the ranking by frequency was 'rush to toilet' (70% of the population), in 7th position; however, the relevant bother was among the highest reported. Items related to urinary incontinence appeared, when present, highly bothersome (87-92% of patients), even though exhibited by a minority of the population (5-34%). The mean (+/-SD) IPSS, calculated on 970 patients, was 15 (+/-7). Two major discrepancies were found in the comparison between IPSS and ICS-Male. First, terminal dribble, which is not considered in the IPSS, is often reported in the ICS-Male. Second, some storage symptoms (nocturia and day-time frequency) are less frequently reported in the ICS-Male than in the IPSS, while being, in general, highly bothersome. As regards QoL, 95% of subjects declared that they would not be completely happy to spend the rest of their life with their actual symptoms (ICS-QoL item 33) and 79% that BPH influences their life from 'a little' to 'a lot' (ICS-QoL item 30). The mean (+/-SD) IPSS-QoL single question score was 3.0 +/- 1.4 (n = 970), and the frequency distribution of scores was equivalent to the one detected by the corresponding question of ICS-QoL (item 33). SF-36, a disease-independent questionnaire about QoL, after a 1-year follow-up is expected to clarify which among the IPSS and ICS-BPH items better describe the impact of BPH on QoL.

Iatrogenic ejaculation disorders and their prevention.

Ejaculation is mediated by sympathetic fibers originating from the D10-L2 medullar center. These nerves rise from the lumbar ganglia of the paravertebral sympathetic trunk and travel posteriorly to the vena cava and then to the interaortocaval space, on the right side, and laterally to the aorta, on the left side. They are the principal constituents of the superior hypogastric plexus. Many surgical operations can cause an ejaculation disorder, but the most important is retroperitoneal lymphadenectomy (RL) for testis cancer, because it involves young patients and it has been the subject of important researches in order to perform lymph node dissection without ejaculation loss (unilateral lymphadenectomy and nerve sparing lymphadenectomy). Our experience concerns 41 patients who underwent RL for testis cancer from 1983 to 1998. Survival rate was 95.2% (mean follow up 64 months). RL was performed bilaterally in 14 patients. Two of them died of metastases within 2 years after the operation. Ejaculation was maintained in only 4 of the 12 surviving patients (33%). All the 17 patients (100%) underwent right monolateral RL and 7 of the 10 (70%) underwent left monolateral RL preserved ejaculation. The anatomosurgical concepts of the RL sparing the ejaculation can be adopted in other retroperitoneal surgical operations that can produce ejaculation disorders, such as wide lymphadenectomy for renal cell carcinoma or tumors of the upper urinary tract, exeresis of pre- aortic tumors, exeresis or disjunction of horseshoe kidney and aorto-iliac revascularization. Surgical therapy of benign prostatic hyperplasia (BPH) (open surgery or transurethral prostatic resection) is associated with retrograde ejaculation in nearly 100% of cases. The mechanism of the dysfunction is clear, if following the procedure the bladder neck remains opened. Loss of ejaculation is reported in variable percentage after the newer endoscopic techniques for the treatment of BPH. Transurethral needle ablation (TUNA) seems to have the lower risk of retrograde ejaculation. Retrograde ejaculation can also be related to a traumatic injury of the posterior urethra, because of the trauma itself or the therapy. Finally, the ejaculation disorder can be produced by several drugs that block, as a main or secondary effect, the alpha-adrenoreceptors or act at the central level. This side effect has to be kept in mind when these drugs are used in young or sexually active patients.

Surgical repair of abdominal aortic or iliac aneurysms associated with treatment of urological neoplasias.

Safe surgical repair of an abdominal aortic aneurysm in conjunction both with nephrectomy (for monolateral or bilateral kidney carcinoma) or with radical cystectomy and orthotopic urinary diversion (for bladder carcinoma) can be performed. These combined surgical procedures can be performed without morbidity due to excessive blood loss, increased operative time or vascular graft infection. A nephrectomy associated with abdominal aortic aneurysm repair can be performed both by a median single surgical approach or by a double one during the same intervention. The authors describe and discuss 4 case reports and the techniques required for these combined procedures.

[Preservation of potency by supra-ampullar cystectomy in patients with bladder neoplasms]. / Preservazione della potenza sessuale mediante cistectomia sovrampollare nei pazienti con neoplasia vescicale.

Between May 1984 and November 1998 a total of 27 consecutive patients with bladder tumor (26 transitional cell carcinomas and 1 leiomyosarcoma) underwent supra-ampullar cystectomy and ileal orthotopic neobladder (2 Camey I and 25 Camey II). Mean patients age was 51.1 years (range 23-65). Pre-operatively 22 patients had superficial bladder carcinoma. An involvement of prostatic urethra was excluded by biopsy. The bladder, part of the prostate with prostatic urethra and regional lymph nodes were removed while was deferens, deferential ampullae, seminal vesicles, ejaculatory ducts and peripheral portion of the prostate were saved. Mean follow-up was 56.5 months (range 4-178). One patient was lost to follow-up at 60 months. Of the 27 patients 6 died of bladder cancer (1 with local relapse, 1 with local and distant recurrence and 5 with metastases) and the remaining 21 had neither local nor distant relapse. Four patients died of other causes. Potency was preserved in 25 patients (92.5%) who reported satisfactory sexual intercourse. Sixteen patients (59.2%) also maintained ejaculation allowing procreation in two of them. Supra-ampullar cystectomy provides good results in term of quality of life allowing to preserve sexual function in nearly all the cases without compromise the control of the neoplastic disease. The indication must be restricted to bladder cancer without risk of local recurrence and concomitant prostatic carcinoma.

Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase in a HPRCC family.

Germline mutations in the tyrosine-kinase domain of the MET proto-oncogene were found in patients suffering from the hereditary predisposition to develop multiple papillary renal-cell carcinomas (hereditary PRCC, HPRCC). PRCCs are often multiple and bilateral even in patients without a family history. We analyzed the germline of patients carrying multiple or single papillary tumors with and without family history. One patient had a familial cancer and carried a novel (V1110I) germline MET mutation, located in MET gene exon 16. This mis-sense mutation was found in affected members of this patient's family. Interestingly, the V1110I mutation is located in the ATP-binding site of the MET kinase and is homologous to the V157I mutation that triggers the sarcomagenic potential of the v-erbB oncogene. The V1110I mutated MET receptor is an active kinase and transforms NIH-3T3 fibroblasts in the in vitro assays. Patients without familiality did not show germline mutations in the MET kinase domain, showing that multiple and bilateral papillary kidney tumors develop in the absence of these mutations. In conclusion, we describe a new mutation in the MET oncogene kinase domain, associated to HPRCC, affecting an amino-acid residue critical for kinase activation in different oncogenes.

[The therapy of metastatic renal carcinoma]. / Terapia del carcinoma renale metastatico.

Nowadays, renal cell carcinomas (RCC) are mostly detected incidentally, following abdominal ultrasound performed for non-urological complaints. These asymptomatic tumors are often small and with low stage. However, about 25% of the RCC are still detected in advanced stage, with synchronous metastasis. Since few years ago, there was no effective treatment for the advanced RCC that shows resistance to the traditional systemic chemotherapy and radiotherapy. Today, two different treatments, either alone or in association, have provided interesting results in these setting, mostly in term of stabilization of the disease. Continuous systemic chronobiological chemotherapy with Floxuridine and immunotherapy with recombinant Interleukin-2 administered intravenously or subcutaneously, represent the treatment of choice of advanced RCC. Both treatment are well tolerated by the patients (except the intravenous Interleukin-2) and do not preclude radical nephrectomy. This paper reports a review of recent literature and the results of the authors' experience.

Aetiopathogenesis and treatment of idiopathic retroperitoneal fibrosis.

Idiopathic retroperitoneal fibrosis (IRF) is a rare urological disease, for which many pathogenic theories have been proposed. The authors report a series of 13 cases of IRF in order to evaluate the clinical, diagnostic, laboratory, therapeutic and prognostic aspects. They also report a rare case (the ninth case reported in the literature) of multifocal fibrosclerosis. A possible genetic predisposition was studied by testing for the presence of immunophenotype HLA-B27; this test was positive in 44% of cases. A study of the immunological profile and lymphocyte populations revealed the typical features of chronic immune disease. Experience with medical and surgical treatment is reported, comparing various procedures: ureterolysis followed by application of a vascularized omental flap over the ureter (without subsequent corticosteroid therapy) gave the best results, with complete resolution of the symptoms and long-term successful alleviation of ureteric obstruction in 100% of patients, with a mean follow-up of 58 months.

Conservative surgery for renal cell carcinoma.

Conservative surgery was initially limited to patients with localized RCC present bilaterally or in a solitary kidney, in whom radical nephrectomy would necessitate immediate renal replacement therapy. Today, the widespread use of abdominal ultrasound as screening modality in patients with nonspecific or unrelated symptoms allows the detection of renal parenchymal tumors rarely seen before: asymptomatic, small and unilateral neoplasms, often surrounded by a thick and complete pseudocapsule. Global renal function and contralateral kidney are usually normal and the patients show good performance status. For these reasons and because of the generally good results of the first experiences, several authors advocate conservative surgery as an elective indication. Recently, some studies have reported promising results with this approach. On the other hand, some controversial issues persist (multifocality of RCC, low risk of local relapse and renal failure after radical surgery, low incidence of tumor in the contralateral kidney) reducing the opportunity to perform nephron-sparing surgery when the contralateral kidney is normal. In the present study, we report our experience of nephron-sparing surgery for RCC and we review the current and international opinion concerning this treatment.

Chemotherapy with FUDR in the management of metastatic renal cell carcinoma.

SUMMARY: Metastatic renal cell carcinoma has a poor prognosis, requiring systemic therapy, in addition to radical nephrectomy. Since August 1989, 50 patients were treated with continuous, systemic, chronobiological infusion of FUDR (floxuridine) at our Institution. We reported 11.7% of objective responses, a long period of stable disease and low toxicity. We also compared our actuarial survival with the results obtained with recombinant IL-2 treatment.

[Obstructive azoospermia and malformations of seminal tract]. / Azoospermia ostruttiva e malformazioni della via seminale.

About 10% of the cases of male infertility is represented by the obstruction of the seminal tract, which may be congenital or secondary to inflammatory events or surgery. The most frequent obstructive malformation of the seminal tract is the bilateral agenesia of the vas deferens. Such malformation is typical of the cystic fibrosis (CF), an autosomal recessive disorder determining chronic respiratory infections with bronchiectasia, and pancreatic failure. Recently the defective gene responsible for CF has been identified on the long arm of the chromosome 7. Congenital bilateral absence of the vas deferens (CBAVD) may be present in otherwise healthy males without clinical evidence of CF. Genetics studies demonstrated that most CBAVD display at least one detectable CF mutation, therefore this disease can be considered as an incomplete clinical form of CF. With the realization that a man with CBAVD may have CF, albeit a genital form, considerable care is required not only to document his specific mutations, but also to test his partner for CF mutations to evaluate the risk that their child would have CF. The association of chronic suppurating respiratory disease with obstructive azoospermia characterizes also the Young's syndrome. In this disease the obstruction could possibly be the result of defective epididymal sperm transport, related to an abnormality in the mucus. Despite some clinical common aspects, CF and Young's syndrome are two distinct entity. In fact, no CF mutations have been demonstrated in Young's syndrome. Congenital obstructive abnormalities of the vas deferens and epididymis are often associate to cryptorchidism (36-68% of the cases) and to patent processus vaginalis. The degree of testicular retention and processus vaginalis closure correlates well with the incidence of associated epididymal defects. Rare causes of congenital obstructive azoospermia are represent by the cyst of Müllerian or Wolffian origin. An obstruction to the progression of the sperm along the seminal tract can also be present in complex malformations, such as pseudohermaphroditism in which the infertility has a multifactorial etiology.

REICAP: prospective epidemiologic study of prostate cancer in Italy. Preliminary results. Ricerca Epidemiologica Italiana sul Carcinoma Prostatico.

OBJECTIVES: Prostatic carcinoma is a common disease of aging male subjects. Owing to structural population changes, its incidence is increasing, making it a major social problem. Epidemiological studies are useful but often do not fully rely on clinical data. The purpose of the present study was to investigate characteristics of prostatic carcinoma from both a clinical and epidemiological point of view. METHODS: A multiphased clinicoepidemiological study was initiated in Italy, involving 26 urological centers operating in districts where national tumor registries are active. Demographic and clinical data on stage, pathology, prostate-specific antigen (PSA), and first-line treatment of 819 patients recruited during the prospective 1-year clinical phase of the study were examined. RESULTS: The study showed that most patients with prostate carcinoma were symptomatic, that incidental cases were 10% and distant metastases were present at first observation in 15.3% of patients. PSA within the normal range was found in about 60% of incidental cases and in about a third of stage B cases. Most patients were treated with hormonal therapy. Radical surgery showed a limited incidence of capsular involvement and lymph node metastases. CONCLUSIONS: These preliminary data show that in Italy, prostate carcinoma is diagnosed mainly when symptoms are present and that in 53% of cases the disease is locally advanced or disseminated. Treatment appears quite homogeneous for advanced cases but controversies exist for stage A1 (19% treated with hormones, 23% with radical surgery and 52% with watchful waiting), for stage A2 (52% treated with hormones, 23% with watchful waiting), and for stage B (58% of B2 treated with hormones against 27% only treated with radical prostatectomy). A special analysis is planned to investigate the cause of the low incidence of capsular invasions and D1 in operated cases.

Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study.

The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure.

[A case of pheochromocytoma with atypical clinical presentation]. / Un caso di feocromocitoma con presentazione clinica atipica.

A case of pheochromocytoma that had undergone coronary arteriography because it stimulated coronary heart disease is presented. The correct diagnosis was suspected while checking the signs and symptoms during an episode of pulmonary edema and was definitely proved by computed tomography and scintigraphy with I 131 metaiodobenzylguanidine. The authors stress the importance of these new non invasive procedures in the diagnosis of site and nature of this disease.

Single-shot vs conventional therapy with amikacin for treatment of uncomplicated urinary tract infections: a multicenter study.

Results are discussed of a national Italian survey carried out by 1,689 general practitioners supervised by 112 hospital specialists. The goal of the survey was to check the efficacy and tolerance of single-shot (single dose) treatment of uncomplicated urinary tract infections with amikacin. 22,216 patients were evaluated, over 23,521 treated, and positive results were obtained in 73.7% with single-shot amikacin, 25.6% with conventional therapy with amikacin 15 mg/kg/day X 7 days, resulting in a total effectiveness of 99.3%. Adverse effects (tinnitus, equilibrium disorders, azotemia and creatinine levels higher than standards) were reported in 0.96% of the patients (0.37% in single-shot, 2.63% in conventional treatment). These data indicate that a single dose (single-shot) administration of amikacin can be a rational and advantageous treatment of uncomplicated urinary tract infections.

[Blood and urinary values of CEA and CA 19-9 in patients with bladder carcinoma]. / Valori ematici ed urinari di CEA e Ca 19-9 in pazienti affetti da carcinoma vescicale.

Carcinoembryonic antigen (CEA) and Ca 19-9 levels in urine and serum from 46 patients with bladder cancer in varying stages have been evaluated. All samples of urine were obtained germ-free and without bacterial infection in the bladder. The sensitivity of CEA monoclonal antibody is 60.8% and specificity is 80%. Ca 19-9 test has higher sensitivity (74%) and the same specificity. Correlation between staging, grading and CEA or Ca 19-9 values were also evaluated.