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250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

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BACKGROUND: The term microinvasive germ cell neoplasia denotes the presence of neoplastic germ cells in the tubuli and interstitium of the testis, unaccompanied by clinically detectable tumor. METHODS: Testicular biopsy specimens from three patients (age range, 26-38 years) without clinical evidence of tumor showed microinvasive germ cell neoplasia. The indications for biopsy were gynecomastia and testicular atrophy in Patient 1, infertility in Patient 2, and nonseminomatous cancer in the contralateral testicle in Patient 3. RESULTS: In all three cases, orchiectomy specimens disclosed multifocal intratubular and extratubular growth of neoplastic germ cells, occasionally confluent in seminoma-like infiltrates. In Cases 1 and 2, no malignant cells were found at biopsy of the contralateral testis. CONCLUSIONS: In contrast to intratubular (in situ) germ cell neoplasia, microinvasion constitutes a definitive malignancy and the starting point of differentiation into seminoma or nonseminomatous tumor. Inguinal orchiectomy is recommended as primary therapy. The necessity of complementary therapy is an issue that must be investigated.

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CT in 28 histologically proven carcinomas of the renal pelvis (pTa-2, n = 12; pT3-4, n = 16) in 26 patients was evaluated retrospectively. Twenty-four of 28 tumors could be identified at CT, 17/28 at urography, and 12/14 at retrograde pyelography. Nineteen tumors appeared as a discrete intrapelvic mass with an attenuation close to that of the kidney on noncontrast scans. There was slight to moderate enhancement of the tumors following i.v. contrast medium injection but they appeared hypodense relative to the renal parenchyma. Five tumors caused only a diffuse obliteration of the renal sinus. Criteria to define peripelvic tumor growth are proposed, i.e. tumors obliterating fat planes or abutting of renal parenchyma should not be regarded as signs of extrapelvic extension, while inhomogeneous attenuation of peripelvic fat and renal parenchyma (in the absence of other explanation) should, or if the tumor mass is seen interdigitizing with surrounding structures. Thickening of Gerota's fascia or septa in the perirenal space are unspecific findings. With CT we were able to differentiate tumors confined to the renal pelvic wall from those with more advanced disease including metastases in 22 of 26 patients.

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Mitomycin C was given intravesically over periods of 2-32 months to 34 patients with carcinoma in situ of the urinary bladder. Initial complete response was obtained in 17 patients, 14 of whom remained without evidence of disease during follow-up averaging 28 months from cessation of mitomycin therapy. In three responding patients malignant cells reappeared in the urine during follow-up, although no recurrence of carcinoma could be proven in bladder biopsy specimens. In eight of the 17 non-responders, muscle invasion and/or metastatic disease developed during or after mitomycin treatment. The prostatic urethra was involved in five cases. Chemotherapy had to be discontinued because of chemical cystitis in three cases. Mitomycin C appears to be effective for intravesical treatment of carcinoma in situ of the urinary bladder. Close surveillance of these patients is mandatory, however, and must include monitoring not only of the bladder, but also of the prostatic urethra and the upper urinary tract.

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A prospective study comprised operative specimens from 11 patients with transitional cell carcinoma of the renal pelvis or ureter. DNA analysis of the primary tumor and of multiple biopsy specimens from preselected sites of the surrounding urothelium was performed with flow cytometry. All Grade 3 tumors and 50% of the Grade 2 tumors were aneuploid, and the remainder were Grade 2 and diploid. All invasive tumors were aneuploid. Carcinoma in situ was found in some of the preselected biopsy specimens, all of which were aneuploid, from two patients. Close correlation thus was observed between aneuploidy and tumor invasiveness, whereas diploidy was seen only in noninvasive tumors with lower malignancy grade. Aneuploidy was also associated with increased risk of carcinoma in situ. The study indicated that DNA analysis may be useful for defining the malignant potential of urothelial tumors of the upper urinary tract more fully than conventional grading and staging permit.

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We followed 657 primary bladder carcinoma patients for at least 10 years or until death. Subsequent carcinomas of the renal pelvis or ureter were found in 11 patients (1.7 per cent) 10 months to 13 years after the primary bladder tumor. In 3 patients the tumors were diagnosed or suspected by excretory urography, while in 5 the tumors were not found until autopsy. Four patients had undergone cystectomy and 9 had multiple bladder tumors at the initial assessment or during followup. The initial or recurrent bladder tumor involved the ipsilateral ureteral orifice in 6 patients. We conclude that in bladder cancer patients routine excretory urography is not indicated in the absence of upper urinary tract symptoms but it should be performed in selected patients, that is those with multiple and recurrent bladder tumors or tumors involving the ureteral orifices, or those with a previous cystectomy.

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The comparison of measurements of fibronectin and lactoferrin in ejaculates from vasectomized men, subjects with functional deficiency or aplasia of the seminal vesicles, and reference subjects provided evidence that both the fibronectin and the lactoferrin in human seminal fluid originate from the seminal vesicles and the ampullae. The fibronectin is incorporated in the framework of the seminal gel formed during the immediate postejaculatory phase, whereas the lactoferrin remains in solution. In the seminal gel fibronectin is linked to its predominant structural protein, a high molecular weight seminal vesicle protein (semenogelin). Both the gel-bound fibronectin and semenogelin are progressively fragmented and solubilized by the abundant prostatic kallikrein-like protease (prostate-specific antigen) during and after seminal gel liquefaction. Lactoferrin remains essentially unaffected by the seminal proteases.

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Nine cases of primary malignant melanoma of the penis and male urethra are presented. The age range of the patients was 57-77 years. Five patients had intermittent bleeding, one had pain, and three were asymptomatic. Six patients had the melanoma on the glans or prepuce and three in the urethra; two presented with inguinal lymph node metastases. Penile amputation was performed in six patients, local excision in three, groin dissection in four, and one was given radiotherapy. Postoperative metastases were seen in eight patients, four of whom were treated with surgery, alone or in combination with radiotherapy, and one with chemotherapy. Two patients are still living, at 2 and 14 years after diagnosis, respectively. Seven patients have died of their tumors, five of them within 2 years. This confirms the consensus of available reports that, irrespective of what type of therapy is used, prognosis is poor in patients with malignant melanoma of the penis and urethra.

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The levels of aryl hydrocarbon hydroxylase (AHH) inducibility were assessed in 173 patients with cancers statistically associated with smoking, i.e., squamous cell and transitional cell carcinomas, at various sites. In 34 patients with carcinomas of the oral cavity, 41 patients with laryngeal carcinomas, and 22 patients with pulmonary carcinomas there was a highly significant overrepresentation of high inducers, whereas 30 patients with carcinomas of the renal pelvis and ureter and 46 patients with urinary bladder carcinomas did not differ significantly in this respect from a control population comprising 92 subjects with no history of neoplastic disease. The results add further support to the concept of AHH as a major activator of carcinogens belonging to the group of polycyclic aromatic hydrocarbons (PAH) when these affect the oral cavity and/or the respiratory tract. The role of AHH in urothelial carcinogenesis seems to be less explicit.

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The first experience with iohexol in urography in humans is reported. Injection of iohexol in a dose of 200 mg I/kg body weight into 34 patients with normal renal function was followed by only few and slight subjective adverse effects. A large number of laboratory tests revealed no toxic effects. High radiographic contrast was obtained.

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