Claes Anderström

RECURRENCE AND PROGRESSION IN LOW GRADE PAPILLARY UROTHELIAL TUMORS

PURPOSE We report long-term followup data on patients with World Health Organization (WHO) grade I bladder tumors, and determine whether histopathological subgrouping as papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical value. MATERIALS AND METHODS All 680 patients in western Sweden with first diagnosis of bladder carcinoma in 1987 to 1988 were registered and followed for at least 5 years. Of the tumors 255 (37.5%) were stage Ta, WHO grade I. Tumors were further classified as papillary neoplasm of low malignant potential in 95 patients and low grade papillary carcinoma in 160 according to WHO and the International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the bladder. RESULTS Mean age of patients at first diagnosis of low grade papillary carcinoma was 69.2 years, which was 4.6 years higher than those with papillary neoplasm of low malignant potential (p<0.005). During a mean observation time of 60 months our 255 patients underwent 577 operations for recurrences and had 1,858 negative cystoscopies. The risk of recurrence was significantly lower in patients with papillary neoplasm of low malignant potential compared to those with low grade papillary carcinoma (35 versus 71%, p<0.001). The risk of recurrence was higher in patients with multiple tumors at first diagnosis as well as those with recurrence at the first followup after 3 to 4 months. Stage progressed in 6 patients (2.4%), all with low grade papillary carcinoma at diagnosis. CONCLUSIONS More than 90% of patients with stage Ta, WHO grade I have a benign form of bladder neoplasm, and few have truly malignant tumors. Future research should focus on reducing the number of recurrences and followup cystoscopies, and finding methods to identify malignant tumors so that pertinent treatment can be instituted. Subgrouping of WHO grade I bladder tumors as papillary neoplasm of low malignant potential and low grade papillary carcinoma seems to add valuable prognostic information.

The significance of lamina propria invasion on the prognosis of patients with bladder tumors

We reviewed 177 patients with superficial bladder tumors. The prognosis for 78 patients with non-invasive grades 1 to 3 tumors was excellent regardless of treatment. In 99 patients with tumors infiltrating the lamina propria the 5 and 10-year survival rates were 71 and 64 per cent, respectively. The prognosis of patients with grades 2 and 3 tumors infiltrating the lamina propria submitted to transurethral resection or cystectomy was excellent. In contrast, the prognosis was poor among patients with signs of tumor invasion of the lymphatic vessels of the lamina propria and patients undergoing transurethral resection and supervoltage irradiation. Our study indicates that patients with grade 1 to 3 bladder tumors, which are confined to the mucosa or do not infiltrate deeper than into the lamina propria should, if possible, be managed by transurethral resection. However, if lymphatic invasion is present the patient does not seem to benefit from an operation alone. Thus, the combined treatment of supervoltage irradiation and an extensive operation may be considered in these patients.

Primary adenocarcinoma of the urinary bladder. A clinicopathologic and prognostic study

The study is a clinicopathologic report on 64 patients with primary adenocarcinoma of the urinary bladder and urachus, with particular reference to important prognostic and therapeutic factors. All tumors exhibited adenocarcinomatous features in at least two thirds of the examined tumor area. Pure forms of the different histological patterns were seen in 50% of the cases and in the remaining tumors a mixture was recorded. Poorly differentiated tumors were found in 41 cases. All tumors were invasive and in 40 cases the tumors penetrated through the bladder wall. The pattern and frequency of metastasis was similar to that of conventional bladder tumors of high stage. The prognosis for patients with primary adenocarcinoma of the bladder was poor and the 5‐year survival rate in this study was 18%. Important prognostic factors were tumor stage, size and grade and treatment. The location of the tumor seemed less important and tumors located in the dome or anterior wall did not indicate a poorer prognosis. The adenocarcinomas of the urinary bladder were predominantly solitary tumors. They were poorly differentiated, deeply invasive large tumors associated with an exceedingly poor prognosis. Partial bladder resection appears to be adequate therapy only in patients with moderately well differentiated small tumors. In other cases more radical therapy must be considered.

Carcinoma of the Ureter: A Clinicopathologic Study of 49 Cases

We reviewed 49 patients with urothelial tumors of the ureter: 33 male and 16 female patients with a mean age of 64.8 and 66.3 years, respectively. Median followup was 83 months. Gross hematuria was present in 29 patients and a silent kidney was found in 21. The majority of the tumors were in the distal ureter and approximately 50 per cent of the patients had synchronous or asynchronous urothelial tumors. The majority of the patients had low grade, low stage tumors (75 per cent). A total of 21 patients underwent local resection and none died of tumor. Only 1 of these 21 patients had an ipsilateral recurrence. Nephroureterectomy was performed in 24 patients and 5 of them died of ureteral tumor, including 4 in whom periureteral tumor growth initially was recorded. The prognosis of patients with papillomas or grades 1 to 3, stages Pa to P1 ureteral tumors was excellent and a conservative approach is recommended for these patients. Abuse of combination analgesics containing phenacetin, phenazone and caffeine may be a risk factor for development of ureteral tumors.

Inverted papilloma of the urinary tract

We report 9 clinicopathological cases of inverted papilloma. The occurrence of associated true malignant epithelial tumors in the urinary tract in 4 patients is not concurrent with previous reports. Even though inverted papilloma per se is a benign lesion it may be associated with malignant epithelial tumors of the urinary tract. The similarity between proliferative lesions of the bladder and inverted papilloma is discussed. The possibility of common etiologic factors of proliferative cystitis, cystitis cystica, cystitis glandularis, inverted papilloma and ordinary bladder tumors may be considered.

The reversibility of catheter-associated polypoid cystitis.

Cystoscopic and histologic evidence of polypoid cystitis was recorded in 20 hospitalized patients with indwelling urethral catheters followed by cystoscopy, biopsies and repeated urine samples before and after catheter removal. The majority of the lesions were located in the posterior wall or dome. The lesions disappeared after removal of the catheter in 13 of the 15 patients followed for up to 28 weeks despite persistent bacteriuria. Polypoid cystitis still remained 28 weeks after catheter removal in 1 patient. The lesion is important as a differential diagnosis to bladder tumor. The importance of adequate biopsies is emphasized.

Scanning electron microscopy of polypoid cystitis. A reversible lesion of the human bladder

Scanning electron microscopy was performed on forceps biopsies from 13 patients with catheter-associated polypoid cystitis. Pleomorphic microvilli, which varied considerably in appearance, were found on surface cells of all cases with polypoid cystitis. Practically all of the characteristics of pleomorphic microvilli assigned earlier to bladder tumor cells in humans were identified on specimens from patients with polypoid cystitis. Pleomorphic microvilli were not observed in the bladder biopsies from control patients. The appearance of pleomorphic microvilli was consistent with reversible lesions of the human bladder and they are not specific markers of pre-neoplastic hyperplasia or malignancy.

The influence of urinary tract infection on the incidence of urinary tract tumors in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide induced carcinogenesis in male Sprague-Dawley rats

Epidemiological studies have demonstrated an association between urinary tract infection and the development of bladder cancer. The present study aimed at evaluating the influence of urinary tract infection in male Sprague-Dawley rats exposed to a sub-carcinogenic dose of N-[4-(nitro-2-furyl)-thiazolyl]formamide (FANFT). A single injection of Escherichia coli into the bladder resulted in a persistent upper urinary tract infection in a high percentage of the rats. Thirty-two percent of the rats exposed to FANFT and E. coli infection developed urinary tract tumors, all but one occurring in the renal pelvis. Urinary tract tumors were not found in rats treated with FANFT or E. coli alone. The present results support that inflammation resulting from infection is actively involved in urinary tract tumorigenesis and may support the epidemiological studies showing an association between infection and human urinary tract cancer. The formation of dimethylnitrosamine or other nitroso compounds from nitrates in the urine or increased cell proliferation due to chronic inflammation or both may be important pathogenetic factors in tumor development.

Funneled Ureteroileal Anastomosis

We analyzed the functional results of urinary diversion in 21 patients who had a funneled ureteroileal anastomosis to avoid stricture and stenosis. No attempt was made to avoid reflux from the conduit to the ureter but special care was taken to construct a cutaneous stoma to prevent reflux from the appliance. The results of the procedure were satisfactory. No urinary leakage, or stricture of the ureters or ureteroileal anastomosis was observed in any patient and kidney function was preserved. One of the main advantages of this technique is simplicity in construction, which means increased safety when used by surgeons not extensively trained in urinary diversion operations.

Scanning electron microscopy of upper urinary tract tumors

Scanning electron microscopy (SEM) was performed on specimens from 16 patients with low‐grade tumors, and 4 patients with benign lesions of the upper urinary tract. Pleomorphic microvilli could be seen at a low frequency on the majority of the tumor specimens as well as on surface cells of specimens from patients with inverted papilloma, fibroepithelial polyp, and hydronephrosis. The SEM appearance of the lining cells was similar whether the specimen was obtained from a patient with a tumor, or an inflammatory or proliferative lesion. Furthermore, pleomorphic microvilli were observed in five histologically normal bladders in which the covering cells had been rubbed off with a cold loop of a resectoscope. Pleomorphic microvilli are thus not morphologic markers of preneoplastic hyperplasia or tumor. It is likely that their presence merely reflects an increased rate of detachment of superficial epithelial cells which are replaced by cells from the deeper part of the epithelium. The demonstration of pleomorphic microvilli is therefore of questionable value in the preoperative diagnosis of tumors of the upper urinary tract and, consequently, their significance must be re‐evaluated.