Risk of continued intravesical therapy and delayed cystectomy in BCG-refractory superficial bladder cancer: an investigational approach.

OBJECTIVES: To assess the risk of continued intravesical therapy and delayed cystectomy in the management of superficial bladder cancer refractory to bacillus Calmette-Guérin (BCG) therapy. METHODS: We retrospectively reviewed the medical records of 24 patients who underwent an experimental intravesical treatment with BCG plus interferon alpha-2b or valrubicin for transitional cell carcinoma of the bladder. All patients had Stage Tis and/or T1 transitional cell carcinoma and had failed multiple prior courses of intravesical therapy, including at least one course of BCG. RESULTS: Patients were followed up for a median of 28.5 months (range 6 to 48). One patient died of unrelated disease. All other patients were alive at last follow-up. Fourteen patients with preserved bladder were continuing cystoscopic surveillance: four had no recurrence, five had recurrence limited to the mucosa (Ta or Tis) and became free of disease after an additional course of intravesical therapy, and five had recurrent Ta or Tis or positive cytologic findings. The remaining 9 patients underwent radical cystectomy. All pathologic specimens showed no evidence of progression to muscle-invasive disease. Tis of the resected ureters in 6 and involvement of the prostate in 4 of the 9 patients (three in the urethral ducts and glands and one in the prostatic stroma) were noted. CONCLUSIONS: A select group of patients with BCG-refractory transitional cell carcinoma and a poor surgical risk for cystectomy may benefit from continued intravesical therapy without a significant risk of progression. However, a cautious approach to this treatment modality is recommended, and very close follow-up is necessary to detect bladder recurrences and involvement of the upper tract and prostatic urethra.

Second opinion of anatomical pathology: a complex issue not easily reduced to matters of right and wrong.

PURPOSE: We discuss the subject of a second opinion for interpretations of anatomical pathology from the perspective of patient care. MATERIALS AND METHODS: We grouped 150 cases involving pathological review at our institution into 3 categories depending on the effect on patient care. RESULTS: Of 29 interpretive discrepancies 14 resulted in treatment changes but 7 of these 14 may have been interpreted differently by other practice groups. CONCLUSIONS: Whether the second opinion represents an interpretive error or a legitimate difference of opinion, the result may affect patient care. Patients referred for treatment among practice groups should have pathological findings reviewed as part of a complete assessment by the new physicians.

A finite element stress analysis of the transmandibular implant system.

PURPOSE: The aim of this work was a simulation of the onset of osseointegration of the transmandibular implant system in the mandible. This was achieved by imposing joint elements at the implant-bone interface. MATERIALS AND METHODS: The geometric model was derived from the anatomic measurement of several mandibles by tomographic scanning. The spring constants of the joint elements interposed at the implant-bone interface were varied between 1 N/mm and 10(9) N/mm to represent the conditions leading to osseointegration. RESULTS: Increasing the value of the spring constant at the joint elements gradually increases the effective stress in an increasing volume of crestal cortical bone. Additionally, a larger volume of crestal cortical bone assumes a higher stress value as the simulation proceeds. CONCLUSION: This work indicates that considerable changes in stress magnitude and distribution occur in the crestal cortical bone margins as osseointegration is simulated, which may be the necessary stimulus for bone remodeling.

Intraepithelial lesions of urinary bladder: morphologic considerations.

Urological pathologists representing the World Health Organization and the International Society of Urological Pathology have reached a new consensus on the definitions of flat, non-invasive lesions of the urothelium. Lesions are classified as: (1) carcinoma in situ (CIS); (2) dysplasia; (3) atypia of unknown significance; and (4) reactive atypia. These terms are intended to describe a histological spectrum of architectural and cytological abnormalities ranging from the unequivocally malignant (CIS) through the probably neoplastic (dysplasia) to the benign (atypia). The biological potential of these lesions in individual patients cannot be accurately predicted, although the degree of risk for an adverse outcome is very likely to be proportional to the degree of architectural and cytological anaplasia. It is likely that each phenotype has two biological potentials: dynamic and effete. It should be emphasized that most of our knowledge concerning these lesions in humans has been obtained from studies of groups of patients who have already developed a papillary or nodular, invasive or non-invasive urothelial carcinoma, as descriptions of primary CIS, dysplasia, and atypia are uncommon. Future knowledge in this area might be enhanced by attention to the following: better definitions of terms and more accurate application of words such as bladder cancer, early lesion, tumor progression, precursor, and premalignant; increased understanding of the biological processes underlying phenotypic changes; development of models (probably computer-based) with the capacity to factor in the complexities of human carcinogenesis in an ongoing fashion, as new information becomes available.

Monitoring patients for bladder neoplasms: what can be expected of urinary cytology consultations in clinical practice.

OBJECTIVES: To determine what practitioners could reasonably expect from urinary cytology (UC) consultations by analyzing their role in our clinical practice. METHODS: Reports of 227 consecutive interpretations on 130 patients collected during a 13-month period were correlated with all available follow-up information. RESULTS: In our practice, UC consultations can predict the presence of bladder carcinoma in nearly 90% of patients, the major mitigating factor being the absence of tumor cells in specimens from patients harboring bladder neoplasms. High-grade neoplasms are most reliably detected with UC. Very low grade neoplasms are difficult to detect, primarily because the cells of these lesions lack features of carcinoma. Significant interobserver variation did not occur. CONCLUSIONS: Pathology consultations based on UC can be associated with high diagnostic yields provided that certain factors are understood. These include that (a) the clinical import of diagnostic terms may vary among observers and should be mutually understood in individual practice settings; (b) UC specimens may not contain tumor cells even when patients have bladder cancer; (c) correlative information may be difficult to obtain and thus seem to inflate calculations for false-positive results; (d) interobserver variation can be reduced if cytopathologists use limited and uniform diagnostic terms; and (e) a high level of diagnostic expertise from cytopathologists should be expected.

The accuracy of urinary cytology in daily practice.

BACKGROUND: Most studies of urinary cytology have been research analyses designed to test the method itself, and many claim that the high diagnostic yields in these studies cannot be achieved in daily practice. The authors examined the clinical and pathologic records in three hospital pathology practice settings--academic, community, and cancer referral settings--to determine the diagnostic yield of urinary cytology under daily clinical conditions. METHODS: Records of consecutive urinary cytology specimens from 1672 patients reported from the years 1990-1994 were reviewed and correlated with histologic and clinical information. Initial analyses were based on the records themselves, without review of pathologic specimens. Subsequently, a subset of specimens was reviewed to determine reasons for noncorrelations. RESULTS: Results confirmed that the diagnostic sensitivity and specificity of urinary cytology for high grade transitional cell neoplasms, as reported in the daily practice of pathology, are very high (79% and >95%, respectively). Disaggregated cells from low grade transitional cell neoplasms usually lack recognizable features of neoplasia, and attempts to classify such lesions cytologically result in low diagnostic yield, with an overall sensitivity of 26%. Of these 1672 patients, 707 had insufficient clinical information for analysis, despite diligent and persistent efforts to acquire it. CONCLUSIONS: The diagnostic yield of consultations based on urinary cytology in the daily practice of pathology is high, regardless of whether the practice setting is referral-based or community-based. The available information indicates that in approximately 79% of patients with high grade transitional cell neoplasms, the neoplasms can be detected using urinary cytology. Conversely, a negative result is predictive of no cancer in more than 90% of cases. Sensitivity for detecting low grade urothelial lesions is low; however, most of these are easily detected cystoscopically. The authors' inability to acquire sufficient information to determine diagnostic yield in a large percentage of their cases was disturbing to them. Not only did this deficiency render their analyses incomplete, but lack of easily accessible follow-up and the apparent low priority for quality assurance activities among pathologists in all types of practice settings is likely to significantly reduce the feedback required for pathologists to acquire and maintain expertise in this very difficult area.

Dental technician education and training--a survey.

As the Dental Auxiliaries Review Group report continues in the consultation stage, the dentist needs to keep up-to-date on all aspects of auxiliary career developments. Dental technician education and training has changed radically during the past 25 years as shown by three surveys--the latest carried out during 1998 and reported in this paper. As leader of the dental team, the dentist needs to be aware of these changes in order to make an informed contribution to the debate.

Prostatectomy tissue for research: balancing patient care and discovery.

The application of modern technology in basic research often requires fresh tissue from human organs. The acquisition of this tissue challenges the anatomic pathologist to balance the needs of the basic scientist with the requirements of quality patient care. Our experience indicates that fresh tissue adequate for research can be obtained from neoplastic prostate glands without compromising patient care. The process requires dedicated, knowledgeable individuals and extensive documentation. Potential problems include low yield for research studies, loss of all residual carcinoma, compromise of the specimen margin, and unforeseen costs. Best collaborations occur in situations in which basic scientists and anatomic pathologists establish a working relationship and develop a mutually supportive means of funding.

The bladder tumor antigen (BTA) test compared to voided urine cytology in the detection of bladder neoplasms.

PURPOSE: Tests to detect recurrent bladder neoplasms are limited and none is consistently accurate. Recent studies suggest that the bladder tumor antigen (BTA) test, an agglutination reaction for basement membrane complexes, is superior to voided urine cytology in clinical practice. We compared BTA and voided urine cytology to bladder washings and cystoscopy, emphasizing diagnostic yield among patients with causes of basement membrane complexes other than bladder cancer. MATERIALS AND METHODS: Random voided urine specimens from 67 patients with a history of bladder neoplasms were collected before cystoscopy and bladder washing. Urine also was obtained from 34 patients with inflammatory bladder conditions including 5 with a history of prostate cancer. Each urine was tested for BTA according to a commercial kit. Positive results were indicated by yellow on a test pad. Blinded to all other results, each urine and each bladder washing were examined microscopically, and a positive test had malignant/suspicious cells. Bladder biopsies were performed when endoscopic lesions were seen. Specimens were grouped into 4 categories: group 1--biopsy proved bladder neoplasm, group 2--history of bladder cancer but not biopsy proved, group 3--history of prostate cancer and group 4--no history of urological cancer. RESULTS: Voided urine cytology was positive in 54% of specimens from patients with biopsy proved bladder neoplasms compared to 29% for BTA. Relative yield for voided urine cytology versus BTA was not changed if all group 2 cases having a positive bladder washing and positive cystoscopy were assumed to have bladder cancer, nor was relative yield altered by subsequent short-term followup. Of voided urine specimens 14% from group 1 patients and 41% from group 2 patients had scant cells. Overall diagnostic yield was superior for bladder washing. False-positive BTA occurred in 7 of 34 patients with no history of urological or prostate cancer. There were no false-positive voided urine cytology interpretations in these groups. CONCLUSIONS: BTA is not superior to voided urine cytology in detecting bladder neoplasms and may be limited by false-positive reactions in patients with other causes of basement membrane complexes in urine. Voided urine samples may be limited by high frequency of hypocellularity. Of 34 patients with a hypocellular urine specimen 4 had biopsy proved bladder cancer. Bladder washing yields best results but requires instrumentation. No test, including cystoscopy, is accurate always.

Conventional bladder wash cytology performed by four experts versus quantitative image analysis.

Bladder wash cytology provides superior results for the detection of bladder malignancies than does voided urine analysis. Image analysis systems have been developed for quantification of cytologic features. In this study, routine bladder wash cytology is compared with an automated image analysis system (QUANTICYT). We studied a random set of 100 bladder wash samples from a population of 1614 patients in follow-up after bladder cancer. Four experienced pathologists interpreted the same 100 Papanicolaou-stained slides. Cytologic and image analysis results were compared for prediction of a cystoscopic lesion, histologic abnormalities, and tumor recurrence. After application of receiver operating characteristic curves, prediction of a cystoscopic lesion by cytology and image analysis was comparable. Both the image analysis system and the cytologic examination detected all of the high-grade lesions. Image analysis was superior to cytologic analysis for the prediction of tumor recurrence after normal findings at cystoscopic examination.

Urogenital involvement by desmoplastic small round-cell tumor.

PURPOSE: We strove to characterize the clinicopathologic features of a rare malignant tumor involving the urogenital system. MATERIALS AND METHODS: Of 109 reported cases of desmoplastic small round-cell tumor, 25 have involved organs ordinarily evaluated and treated by urologists. Experience based on these cases plus 2 from our files forms the basis of this review. RESULTS: The term desmoplastic small round-cell tumor has been applied to a rare, highly malignant neoplasm that occurs most often in the abdominal cavity and is described in the nonurological literature. This cancer has distinctive histological, immunohistochemical and ultrastructural features. Several reports suggest a characteristic genetic abnormality. All reported patients who have tumors involving the genitourinary structures have been treated with chemotherapy, but prognosis has been poor. CONCLUSIONS: The literature on desmoplastic small round-cell tumor indicates that a significant percentage of these rare malignancies involve genitourinary organs. In most cases, tumors have been unresectable surgically and treatment has been multidrug chemotherapy. Response to treatment has been poor, with only 3 of 25 determinate cases free of disease when reported.