Treatment of advanced bladder cancer with combined preoperative irradiation and radical cystectomy versus radical cystectomy alone: a phase III intergroup study.

PURPOSE: Our study was designed to compare the effects of preoperative irradiation and cystectomy to surgery alone in patients with transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A total of 140 patients with documented invasive bladder cancer or rapidly recurring superficial high grade tumors was randomized to receive 2,000 rad of pelvic irradiation followed by cystectomy within 1 week or surgery alone. RESULTS: The 5-year survival rate was 53% (95 confidence intervals 41 to 65%) in the surgery only group and 43% (95% confidence intervals 30 to 56%) in the irradiation plus surgery group. The p value for the log rank statistic comparing the survival distributions was 0.23. CONCLUSIONS: Although this trial showed no benefit for preoperative irradiation and cystectomy, the confidence intervals were wide. This finding does not exclude the possibility of a favorable effect of radiation in a subset of patients with high stage tumors. Overall, however, the dominant effect of distant disease as a cause of treatment failure diminishes any potential impact of radiation on results.

Carcinoma metastatic to both cerebellopontine angles masquerading as acoustic neuromas.

Metastases to the cerebellopontine angles (CPAs) are rare. Typically, the clinical course is one of rapid onset and progression of crarial nerve deficits. The clinical presentation and course of carcinoma metastatic to the CPAs are reviewed. We report a case of bilateral CPA metastases with a radiographic appearance similar to neurofibromatosis type 2 presenting with rapidly progressive bilateral hearing loss followed by unilateral facial nerve palsy.

The viability of revascularized calvarial bone graft in a pig model.

This study compared the vascularity and resorption of calvarial bone flaps based on an undisturbed pedicle and on a previously (4 weeks) detached pedicle of the superficial fascia (galea) and periosteum and free calvarial bone grafts. Nine adult pigs were used, in three of which a silicone rubber compound was injected intravascularly immediately after the transfer confirmed the vascularity of both pedicled bone flaps. In six pigs, volume changes were assessed intraoperatively by a water displacement method and also 12 weeks postoperatively. Both pedicled bone flaps preserved their original volume, whereas free skull grafts showed approximately 50% of volume loss (p less than 0.001). Decalcified hematoxylin and eosin sections of the specimens obtained 12 weeks postoperatively showed a normal calvarial appearance in both pedicled bone flaps and extensive fibrous tissue infiltration into free grafts. It is suggested that a previous detachment of galea and periosteum does not interfere with the use of vascularized calvarial bone graft, which may provide a more predictable result than a free bone graft.

The vascular anatomy of the galeal flap in the interparietal and midline regions.

The potential extension of the galeal flap in the interparietal area was studied on 17 fresh human cadaver heads by intravascular dye injection technique. It was demonstrated that an ipsilateral superficial temporal artery that supplies the galeal flap does not cross the midline or anastomose with the contralateral superficial temporal artery but ensures the survival of a flap extended up to 1 cm proximal to the sagittal suture line. The width of the temporoparietal flap can be extended up to 15 cm, depending on the vascular pattern of the superficial temporal artery. When required, the lateral extension may provide the required soft-tissue bulk despite the reduced flap length.

Comparison of IDEIA III and cell culture for the detection of Chlamydia trachomatis in endocervical specimens.

A total of 803 endocervical samples were obtained from females with clinical or epidemiological histories suggesting chlamydia infection. These specimens were tested by IDEIA III and cell culture for the presence of Chlamydia trachomatis. After resolution of discrepant results by direct fluorescent-antibody staining of pelleted cell culture transport materials, IDEIA III demonstrated sensitivity, specificity, and positive and negative predictive values of 93.8, 99, 92.9, and 99.1%, respectively.

Genital warts and cervical cancer. VI. The relationship between aneuploid and polyploid cervical lesions.

Human papillomaviral infection is now widely implicated in the causation of cervical neoplasia. Genotype analysis provides the best guide to biologic outcome; most polyploid lesions regress and most aneuploid ones persist or progress. This prospective survey examined the relationships between cell ploidy and 24 objectively validated criteria of human papillomaviral infection or premalignant change in 52 biopsies from a dysplasia clinic. Histologic evidence of benign warty expression and human papillomaviral capsid antigen production decreased steadily as DNA content ranged from diploidy to polyploidy to aneuploidy. In contrast, premalignant change increased with progressive distortion of nuclear DNA content. No absolute discriminants were found between polyploidy and aneuploidy, as evidenced by the detection of human papillomaviral proteins in three of 21 aneuploid epithelia and the recognition of abnormal mitotic figures in five of 17 polyploid lesions. Polyploid and aneuploid lesions differed only in severity, and it appears that some polyploid epithelia may be transition forms between diploidy and aneuploidy.

Genital warts and cervical cancer. IV. A colposcopic index for differentiating subclinical papillomaviral infection from cervical intraepithelial neoplasia.

Five colposcopic signs (thickness, color, contour, vascular atypia, and iodine staining) were graded into three objective categories representing (1) subclinical papillomaviral infection, (2) lower-grade dysplasia, and (3) grade 3 cervical intraepithelial neoplasia. Seventy-two colposcopically different biopsy specimens (25 of subclinical papillomaviral infection and 18 of grade 1, 18 of grade 2, and 11 of grade 3 cervical intraepithelial neoplasia) were collected from 52 women and interpreted by validated, quantitative histologic analysis. Attempts to grade lesions by the prominence of the acetowhitening reaction or the mere presence of aberrant surface capillaries were unsuccessful. In contrast, each of five new colposcopic criteria were significantly correlated with histologic severity. Differences in color, vascular atypia, and iodine staining were more predictive than those of thickness and contour. Combined into a weighted index, these colposcopic features were 96% correct in forecasting approximate histologic findings. Because this method relies upon critical analysis rather than pattern recall, the use of this colposcopic index greatly simplifies the learning of colposcopy.

Genital warts and cervical cancer. V. The tissue basis of colposcopic change.

Histologic differences between subclinical papillomaviral infection and cervical intraepithelial neoplasia are quantitative rather than qualitative. Both entities are characterized colposcopically by acetowhite epithelium and aberrant surface capillaries. This study correlates five new colposcopic signs (variations in contour, thickness, color, vascular patterns, and iodine staining) with 12 histologic signs of human papillomaviral infection and 12 features of premalignant change. Acetowhitening and capillary abnormalities in minor colposcopic lesions are attributable to human papillomaviral disturbance of cell growth and maturation, seen histologically as parabasal layer proliferation, papillomatosis, koilocytosis , and dyskeratosis. Alteration in cell ploidy is usually minimal. Major colposcopic abnormalities reflect extensive disorganization of cell phenotype and tissue architecture, increased DNA content, and aneuploid stem cell populations. Intermediate colposcopic patterns generally denote polyploid lesions in which tissue changes are a composite of two reciprocal events: the extent of benign warty expression and the severity of premalignant change.

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change.

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Genital warts and cervical cancer. I. Evidence of an association between subclinical papillomavirus infection and cervical malignancy.

A blind comparative survey was undertaken to study the prevalence of subclinical papillomavirus infection (SPI) in a representative sample of women treated surgically for invasive or preinvasive cervical neoplasia. According to a semiobjective rating system, 73 of 80 women (91%) with cervical neoplasia and ten of 80 matched controls (12.5%) showed histologic evidence of human papillomavirus (HPV) infection. Sixty of the controls (75%), but none of the study group, had normal cervicovaginal epithelium. A highly significant statistical relationship exists between subclinical papillomavirus infection of the lower genital tract and the occurrence of cervical neoplasia (F = 378; P less than 0.001; X2 = 109, P less than 0.001). The prevalence of SPI was seven times greater in the study group than in comparable controls of equivalent disease status. Because both are covariables of promiscuity, statistical association exist between cervical neoplasia and all sexually transmitted diseases. However, the strength, specificity and consistency of this relationship suggest that SPI may be a precursor or cervical malignancy. This contention is given biologic plausibility by a broad fabric of supporting epidemiology, virologic and clinicopathologic evidence.

Tetracycline-induced esophageal ulcers. Report of two cases.

Delayed passage of irritant drugs like tetracycline hydrochloride can cause esophageal ulceration, especially when the medication is taken with only a sip of water before sleeping or by a patient with stricture or motor abnormality of the esophagus. Certain precautions should be taken when prescribing irritant drugs. Patients should be advised to take sufficient quantities of water with the medication and to avoid taking the capsules at bedtime. These drugs should not be given to patients with esophageal obstruction or motility disorders.