Sverker Hellsten

LYMPHATOGENOUS SPREAD OF RENAL CELL CARCINOMA: AN AUTOPSY STUDY

PURPOSE We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.

Guidelines on Renal Cell Cancer

Objectives: On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and Follow–Up of Renal Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost–effectiveness and clinical feasibility. Method: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts on renal cell carcinoma (RCC). Results: RCC is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There is no risk factor established and the current TNM system (UICC, 1997) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent, incidental discovery constitutes already a majority of cases. Diagnosis is established by ultrasound and abdominal CT, extension assessment in routine cases is done by chest X–ray. Additional examinations may be required in select cases. The therapy of choice in organ–confined RCC is surgery. Radical tumour nephrectomy is considered as a standard. Efficacy and side–effects of organ–sparing surgery, lymphadenectomy and inclusion/omission of ipsilateral adrenalectomy in selected cases is a matter of ongoing clinical research. In metastatic cases, tumour nephrectomy should only be considered in the context of modern systemic immunotherapy. A follow–up at regular intervals is recommended because certain cases of recurrences may be candidates for surgery and/or immunomodulating therapy. Conclusion: A rise in incidence, improved diagnostic procedures, and evolving multimodality therapeutic concepts justify the need for rational guidelines on this most challenging urologic malignancy.

Carcinoma of the Renal Pelvis and Ureter Following Bladder Carcinoma: Frequency, Risk Factors and Clinicopathological Findings

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.

Results of second-look resection after primary resection of T1 tumour of the urinary bladder.

Objectives. To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. Material and methods. Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35 223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. Results. Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged <70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA >100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8–10) had a markedly reduced relative 5-year survival rate. Conclusions. It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Alternating Mitomycin C and BCG Instillations versus BCG Alone in Treatment of Carcinoma in Situ of the Urinary Bladder: A Nordic Study

OBJECTIVES To evaluate whether, in patients with carcinoma in situ (CIS) of the urinary bladder, alternating instillation therapy with mitomycin C (MMC) and bacillus Calmette-Guerin (BCG) was more effective and less toxic than conventional BCG monotherapy. METHODS Patients were stratified prospectively for primary, secondary, and concomitant CIS and randomized to one of two regimens. Patients in the alternating group received six weekly intravesical instillations of MMC 40 mg, followed by alternating monthly instillations of BCG 120 mg and MMC for one year. In the monotherapy group, only BCG was instilled on the same schedule. RESULTS Of 323 enrolled patients, 304 were eligible for analysis. After an overall median follow-up of 56 months, the Kaplan-Meier disease-free estimate for BCG monotherapy was significantly better than that for alternating therapy (p=0.03; log rank test). Risk for progression appeared lower in the BCG monotherapy group (p=0.07), but no differences existed in survival. Besides the regimen, CIS category also predicted outcome to some extent. BCG monotherapy caused significantly more local side-effects and premature cessation of instillation treatment than did the alternating therapy. However, no differences were observed in the number of serious side-effects. CONCLUSION One-year BCG monotherapy was more effective than the alternating therapy for reducing recurrence and compared well with the best regimens reported from substantially smaller series. The alternating therapy was better tolerated.

Bacillus Calmette-Guérin Is Superior to a Combination of Epirubicin and Interferon-α2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study ☆

BACKGROUND Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. OBJECTIVE To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours. DESIGN, SETTING, AND PARTICIPANTS This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. MEASUREMENTS The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. RESULTS AND LIMITATIONS A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. CONCLUSIONS For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

Controlled trial of a short and a prolonged course with ciprofloxacin in patients undergoing transurethral prostatic surgery

The efficacy of a short (Group I) and a prolonged (Group II) course with ciprofloxacin was assessed in patients undergoing transurethral prostatic resection for benign hyperplasia or cancer of the prostate and compared with that of controls without antibiotic (Group III). Both regiments significantly reduced the frequency of postoperative bacteriuria (p < 0.01) and of severe infectious complications (p=0.004) as compared to the controls. Both regimens were equally effective in preventing perioperative and postoperative acquisition of bacteriuria in patients without bacteriuria at surgery. In patients with bacteriuria before surgery, bacteriuria was found postoperatively in 35% in Group I and 10% in Group II (p=0.012), but in 82 % of the patients in Group III. Ciprofloxacin inhibited all but 7 of 176 bacterial strains at an MIC of ⩽ 1μg/ml. Given orally ciprofloxacin is a valuable alternative antimicrobial for use in conjunction with transurethral prostatic resection. A short course is sufficient for prophylaxis, and adequate therapy is achieved with a prolonged regimen.

Laser Treatment of Localized Squamous Cell Carcinoma of the Penis

PURPOSE We evaluate the efficacy and morbidity of laser and conventional treatment in 32 men with penile cancer. MATERIALS AND METHODS Of 32 men treated for squamous cell carcinoma of the penis observed for an average of 44 months 19 were treated with the combined carbon dioxide and neodymium: YAG lasers. The 13 patients treated conventionally had more advanced disease and they were a mean 17 years older than those in the laser treated group. RESULTS All laser treated patients were disease-free after a mean of 31 months. Among the 13 conventionally treated patients there were only 5 long-term survivors. CONCLUSIONS The cosmetic and functional outcome of laser treatment for stages Tis to T2N0M0, grades 1 and 2 squamous cell carcinoma of the penis is excellent, and the associated morbidity rate is low.

Precancerous lesions in the kidney.

Renal cell carcinoma (RCC), although occurring less frequently than prostate and bladder cancer, is actually the most malignant urologic disease, killing >35% of affected patients. Therefore, investigation of the nature of premalignant lesions of the kidney is a relevant issue. Following the most recent histological classification RCC can be subdivided into four categories: conventional RCC; papillary RCC; chromophobe RCC; and collecting duct carcinoma. In contrast to many genitourinary malignancies, premalignant alterations in the kidney are scarcely described. Intratubular epithelial dysplasia has been recognized as the most common precursor of RCC. In analogy to prostatic intraepithelial neoplasia (PIN), the premalignant lesions of the kidney are described as high or low-grade renal intratubular neoplasia. In contrast, precancerous lesions have been described as part of the von Hippel-Lindau syndrome (VHL) where the evolution from a simple cyst to an atypical cyst with epithelial hyperplasia to cystic or solid conventional-type RCC is well documented. Finally, in the genesis of papillary RCC an adenoma-carcinoma sequence has been recognized with specific genetic changes. There are no data on the epidemiology of premalignant lesions of the kidney, but research into the etiology of RCC has been extended substantially. Familial and genetic factors are well documented in VHL disease, in hereditary papillary RCC, in the tuberous sclerosis complex and in familial RCC. Cigarette smoking and obesity are established risk factors for RCC. Hypertension or its medication has also been associated with an increased risk. Among dietary factors an inverse relation between risk and consumption of vegetables and fruit has been found. Occupational exposure to substances such as asbestos and solvents has been linked to an increased risk of RCC. Specific RCC variants have distinctive chromosome alterations and several genes have been implicated in the development of RCC. Loss of material from the 3p chromosome characterizes conventional RCC and the deletion of the VHL suppressor gene plays an important role in the genesis of this RCC variant. In contrast, numerical changes with trisomy of chromosomes 7 and 17 and loss of the sex chromosome are typical changes in papillary tumors, whereas papillary RCC have additional trisomies. Chromophobe RCC is characterized by loss of chromosomes with a combination of monosomies. Less consistent genetic alterations are associated with collecting duct carcinoma. The traditional treatment of RCC is surgery by radical or partial nephrectomy. The latter approach carries a risk of tumor recurrence as a result of unrecognized satellite lesions or premalignant lesions that might have been present at the time of surgery. However, the reported recurrence rates after partial nephrectomy are <1% and therefore the possible presence of premalignant disease does not alter the actual treatment strategy advocated. Although multifocality and bilateral occurrence of RCC are much more likely in cases of papillary RCC, biopsy of the renal remnant or contralateral kidney is not justified even in patients with this tumor type. Conversely, patients with RIN in a partial or radical nephrectomy specimen or in a renal biopsy taken for whatever reason should be subjected to closer follow-up with regularly repeated ultrasound. When an effective chemopreventive regimen becomes available it might be useful for patients with an inherited risk of RCC as well as in those who are at risk of tumor recurrence after intervention. Mass screening with the purpose of detecting RCC at its earliest stage is not recommended at the present time, but screening focused on certain risk groups can be advocated. Further research is needed to identify avoidable risks, develop effective chemoprevention and recognize patients at risk.

The Effect of a Short Antibiotic Course in Transurethral Prostatic Resection

In a prospective randomized study of 192 patients, the effect of a short course of cefotaxime in connection with transurethral prostatic resection was analyzed. The antibiotic was given to 98 patients, while 94 were assigned to a control group without antibiotic. The frequency of bacteriuria in the cefotaxime group was 43% preoperatively and 18% six weeks postoperatively. In the control group the corresponding figures were 40 and 42% (p less than 0.01). Complicated postoperative infection did not occur in the cefotaxime group, but in the control group there was one case of septicemia and seven patients had upper urinary tract infections (p less than 0.01). In the cefotaxime group, patients with preoperatively negative urine culture were prevented from acquiring bacteriuria, and 67% of preoperatively present infections were eliminated at six weeks after the operation, as compared with 30% in the control group. There were essentially no side effects of cefotaxime. Renal function was not influenced by the combination of cefotaxime and furosemide.