Biomedical subjects
Publications and source records attributed to W C Bauer.
The authors described a case in which the capsule surrounding a breast implant was lined by benign squamous epithelium. A second case, in which a woman was found to have a squamous cell carcinoma in the capsule surrounding a breast implant, was also reported.
Since 1987, 10 patients have been treated with irradiation to a limited pelvic volume for elevation of serum prostate-specific antigen (PSA) level above expected post-radical prostatectomy levels without clinical or radiological evidence of either metastatic or locoregional disease. The patients were treated 3 to 43 months after radical prostatectomy, using bilateral 120 degrees arcs to deliver 6000 cGy to the prostatic bed. The pathologic findings of the initial surgical specimens for all patients were reviewed. Eight patients had pathologic Stage C disease, and five patients had one or more positive margins. All patients had negative staging lymphadenectomies. After irradiation, eight patients had decreases in PSA levels indicative of response of isolated local disease. Through preliminary, these results suggest that post-prostatectomy PSA levels are useful for detecting subclinical local recurrence or persistence in the prostatic bed, as well as monitoring these patients' response to therapy. The value of this elective treatment remains to be documented.
Explore the source record for details and available documents.
Flow cytometric DNA analysis was performed on 168 consecutive primary operable breast cancers and the results correlated with thymidine labeling, estrogen receptor (ER) and progesterone receptor values, and various histologic parameters. Seventy-five cancers (45.0%) were diploid and 93 (55.0%) aneuploid. In 83.9% of aneuploid cancers, the DNA index fell between 1.1 and 2.0. Thirteen cancers were hypertetraploid and three hypodiploid. The percent of S-phase cancers (SpF) varied from 1.1% to 24.4%, with a mean of 8.0% and a median of 7.1%. The mean SpF of diploid cancers was 5.2%; of aneuploid cancers, 10.3%. There was no significant correlation between SpF or ploidy and tumor size or axillary lymph node status. The thymidine labeling index (TLI) varied from 0.2 to 23.1, with a mean of 7.5 and a median of 6.1. There was good correlation between TLI and SpF (r = 0.892, P = 0.0001). ER-negative tumors had a significantly higher mean SpF (10.3%) than did ER-positive tumors (6.7%), but there was no significant correlation between ploidy and receptor positivity or negativity. There was a good correlation between invasive tumor necrosis, poor cytologic differentiation, aneuploidy, and above-median SpF. Only a fair correlation was observed between mitotic rate and SpF. A classification of invasive breast cancers based on ploidy and SpF is proposed.
We evaluated the prognostic value of purified protein derivative skin test reactivity and a granulomatous response in intravesical bacillus Calmette-Guerin therapy. We treated 62 patients with intravesical bacillus Calmette-Guerin once a week for 6 weeks. Purified protein derivative skin tests were performed before and after therapy. Cold cup bladder biopsies were examined in a blind retrospective manner for the presence of granulomas 6 weeks after completion of therapy. A significant correlation between status free of tumor and the presence of either granulomas or positive purified protein derivative skin tests was observed for the total patient population. Of 25 patients whose purified protein derivative test was converted from negative to positive 19 (77 per cent) remained free of tumor, while only 11 of 32 (34 per cent) whose test did not convert to purified protein derivative positive remained free of tumor (p equals 0.0006, chi-square). Similarly, 28 of 37 patients (77 per cent) who had a granulomatous response remained free of tumor, while only 8 of 25 (32 per cent) without a granulomatous response remained free of tumor (p less than 0.003, chi-square). The correlation was similar for each parameter when the total patient population was subdivided into patients treated for carcinoma in situ, residual tumor or prophylaxis. Calculation of predictive values showed that neither purified protein derivative responsiveness, granuloma formation nor a combination of both provided a highly accurate predictive index of therapeutic response in individual patients. False positive or negative rates, ranging from 23 to 24 per cent and 32 to 39 per cent, respectively, were observed. These results suggest that a link between immunological responsiveness and response to therapy exists but that neither the purified protein derivative skin test nor the granulomatous response exhibits sufficient immunological specificity to serve as accurate prognostic indicators in individual patients.
We report the morphological effects of intravesical bacillus Calmette-Guerin therapy on early post-treatment biopsies of the bladder in 39 patients with superficial transitional cell carcinoma (stage Ta, T1 or Tis) of the bladder. Although submucosal granulomatous inflammation in bladder biopsies of patients receiving intravesical bacillus Calmette-Guerin treatment has been described previously, a complete morphological description of the early effects of bacillus Calmette-Guerin on all bladder layers and the prostatic urethra has not been reported. In the majority of cases the superficial epithelium was eroded and the edematous submucosa contained noncaseating granulomas with a surrounding lymphoplasmocytic and eosinophilic infiltrate. Langhans' giant cells occasionally were found, and acid-fast bacilli were demonstrated only rarely by special stains in the 6-week post-treatment biopsy. In some cases the prostatic urethra and muscle bundles contained noncaseating granulomas. Features distinguishing epithelial atypia resulting from bacillus Calmette-Guerin treatment and superficial cancer include the presence of epithelial maturation, preserved nuclear/cytoplasmic ratio, smooth nuclear contours and lack of nuclear pleomorphism, nucleoli or cytomegaly.
We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. A single course of intravesical bacillus Calmette-Guerin therapy was successful in 6 of 11 patients (55 per cent) treated for residual carcinoma and 6 of 12 (50 per cent) treated for carcinoma in situ. Of 17 patients receiving a single course of bacillus Calmette-Guerin for prophylaxis 11 remained free of tumor during short-term followup. A second course of therapy was administered to failures in each treatment category, which resulted in favorable responses in 5 of 6 patients treated for prophylaxis, 2 of 5 treated for residual tumor and 3 of 6 treated for carcinoma in situ. Over-all complete responses were achieved in 16 of 17 patients (94 per cent) treated for prophylaxis, 8 of 11 (73 per cent) for residual carcinoma and 8 of 12 (66 per cent) for carcinoma in situ, with a mean followup from the final treatment of 9.3, 12.3 and 7.9 months, respectively. Favorable results occurred more frequently among patients who exhibited a granulomatous inflammatory response in the bladder and delayed hypersensitivity skin test response to purified protein derivative. Marked variability in viability of bacillus Calmette-Guerin organisms was observed among different lots of bacillus Calmette-Guerin, and a direct relationship was observed between bacillus Calmette-Guerin vaccine viability and therapeutic efficacy. Most patients who failed initial therapy with a low viability lot of bacillus Calmette-Guerin responded favorably to re-treatment with a higher viability lot. The results suggest that the level of viability of each lot of bacillus Calmette-Guerin vaccine should be verified before clinical use.
A primary human renal clear cell carcinoma has been developed as a xenograft (JDF-1). Passage 7 of the JDF-1 tumor retained the microscopic morphology of the primary tumor, electron micrographs have confirmed its epithelial characteristics and karyotyping of a subsequent passage has proved it is not a murine hybrid. Immunoperoxidase studies using a panel of murine monoclonal antibodies demonstrate an antigenic phenotype specific for human renal cancer. In vitro chemosensitivities of the JDF-1 tumor were determined by the double-layer soft-agar clonogenic assay method. JDF-1 showed no significant sensitivities to several standard chemotherapeutic agents, but alpha-2-interferon and difluoromethylornithine in combination synergistically inhibited its growth by 74 per cent.
The S-phase fraction (SP) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100) the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50-80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.
The role of granulocytes and monocytes during the induction and course of Escherichia coli endocarditis was investigated in rabbits by selectively depleting monocytes from the circulation with the drug VP16-213 and granulocytes and monocytes with nitrogen mustard. For induction, the number of E. coli needed to infect the vegetations in 50% of the rabbits was significantly lower in rabbits with combined granulocytopenia and monocytopenia than in those with selective monocytopenia or in control rabbits, whereas the number of E. coli needed to infect 50% of the rabbits did not differ between the latter two. During the course of the endocarditis in endocardial vegetations, the numbers of CFU per gram of vegetation were significantly higher in the rabbits with combined granulocytopenia and monocytopenia than in the monocytopenic and control rabbits but did not differ between the latter two. The numbers of granulocytes in the circulation and the numbers of CFU per gram of vegetation showed a significant negative correlation that was not measurably influenced by the duration of the disease but was dependent on the number of E. coli injected for the induction of endocarditis. Granulocytes were found to be most effective at the lowest numbers of bacteria injected. In the circulation, too, the numbers of CFU per milliliter were significantly higher in rabbits with combined granulocytopenia and monocytopenia than in those with selective monocytopenia and control rabbits, and there was a significant negative correlation between the numbers of granulocytes and CFU per milliliter of blood. From these findings we conclude that granulocytes play a protective role during the induction and course of E. coli endocarditis in rabbits, whereas no role is demonstrable for monocytes.
The thymidine labeling index (TLI) was measured in vitro in 278 primary breast carcinomas. In 227 operable women treated by radical mastectomy, TLI's below the median of 4.55% carried a probability of relapse of 20% at four years, in contrast to 52% for TLI's above the median (P = 0.0001). The probability of relapse was significantly related to the TLI independent of TNM pathologic stage, axillary lymph nodal status alone, estrogen receptor (ER) content, or menopausal status. The abilities of the TLI and nodal status to predict early relapse were equally strong and independent, whereas other variables tested had less or no independent predictive capacity. The predictive value of the ER content depended largely on its relationship to the TLI, and ER was related to the probability of relapse in the below median TLI group only. The TLI can select a subgroup of node-negative patients with a relapse-expectancy of approximately 50% at four years.
Explore the source record for details and available documents.
The role of granulocytes and monocytes during the induction and course of Staphylococcus epidermidis endocarditis was investigated by the selective depletion of monocytes with the drug VP16-213 and of both granulocytes and monocytes with nitrogen mustard. The induction of endocarditis was influenced only by the depletion of monocytes: the 50% infective dose differed significantly, being 3.4 X 10(5) CFU in control rabbits and 3.4 X 10(4) CFU in the monocyte-depleted rabbits, whereas no significant differences were found between the latter and those depleted of both granulocytes and monocytes. Also, control rabbits injected with 10(6) or 10(7) CFU had a significantly higher incidence of sterile vegetations than did rabbits selectively depleted of granulocytes or monocytes. Compared with baseline values, mean monocyte numbers at the time of bacterial inoculation were significantly increased in control rabbits whose vegetations remained sterile, whereas this effect was not seen in rabbits whose vegetations became infected. The course of the endocarditis appeared to be significantly influenced by both granulocytes and monocytes. Comparison showed that a decrease of the same numbers of these cells per microliter of blood was accompanied for the monocytes by an approximately fourfold higher increase of the number of staphylococci in the vegetations. The correlation between the number of granulocytes and of monocytes on the one hand and the number of staphylococci in the vegetations on the other was not substantially influenced by the duration of the disease or the number of staphylococci injected to induce the endocarditis. The number injected proved to be significantly correlated with the number of staphylococci in the vegetations. In rabbits with numbers of CFU per gram of vegetation exceeding 10(7), blood cultures were usually positive. This finding applied rarely to control rabbits, but generally to drug-treated rabbits. In the latter animals a significant correlation between the number of staphylococci in the vegetations and in the circulation was found. We conclude that only monocytes have a measurable effect on the induction of Staphylococcus epidermidis endocarditis but during its course both granulocytes and monocytes keep the endocardial infection in check.
We investigated the role of granulocytes during the induction and course of experimental Streptococcus sanguis endocarditis in rabbits by depleting blood granulocytes with nitrogen mustard. The induction of the endocarditis was not influenced by granulocytopenia: the 50% infectious dose was 5.4 X 10(4) colony-forming units in normal and granulocytopenic rabbits. However, granulocytopenia influenced the curse of the endocarditis, as shown by a significant increase in the number of colony-forming units per gram of vegetation (P less than 0.02) from 24 to 72 h after the injection of 10(5) colony-forming units of S. sanguis. This rise did not occur in the control rabbits. Furthermore, bacteremia was significantly higher in the granulocytopenic rabbits (P less than 0.05) during the first 48 h compared with the control rabbits. This was not because of altered clearance of the streptococcus inoculum or seeding of streptococci from extracardiac bacterial foci. We concluded that granulocytes have no measurable effect on the induction of S. sanguis endocarditis, but during the course of the endocarditis, granulocytes keep the endocardial infection in check.
Ninety-one patients were treated for squamous cell carcinoma of the base of the tongue between 1960 and 1974. Eighty-one of those patients were treated in a consistent manner, either by radiotherapy alone or preoperative radiotherapy plus total en bloc excision with a radical neck dissection. Eighteen patients were treated by radiotherapy alone (1800-7900 rads) to the primary site and bilaterally to the neck. Fifteen of these patients died within five years. Sixty-three patients were treated with preoperative irradiation (1800-7900 rads) followed by total primary excision with ipsilateral neck dissection. This latter group had a 50% five-year survival. Death due to uncontrolled tumor occurred within five years, whereas death after five years postinitial therapy was due to unrelated reasons. Unfavorable prognostic features were poor differentiation of the tumor, lack of histologic evidence of radiation-induced regression of the tumor, and more than three neck lymph node metastases in the initial neck dissection. Cox regression analysis showed that absence of histologic response to therapy was associated with a failure rate 4.05 times higher than that seen in patients whose tumors did respond. Primary tumor size did not affect prognosis as long as the tumor was technically resectable. Primary recurrences occurred in at least 20% of cases regardless of the presence or absence of surgical margin involvement.
Juvenile laryngeal papillomas, solitary laryngeal papillomas of the adult, and cylindric cell papillomas of the nose and sinuses were examined for the presence of papillomavirus antigens by means of immunocytochemistry. By using an antiserum capable of recognizing a common group antigen that reacts with papillomavirus antigens of different species, it was found that half of the juvenile laryngeal papillomas studied contained cells staining for papillomavirus antigens. No positive cells were found in adult solitary papillomas or cylindric cell papillomas. These results strongly implicate a human papillomavirus as the causative agent of juvenile multiple laryngeal papillomas.
To determine predictors of TNM relapse and survival for 108 patients with epidermoid carcinoma of the pyriform sinus, the histopathologic features of tumor-related and host-related characteristics were correlated with primary and/or cervical nodal failure, distant metastases, and actuarial three-year survival. Patients in this study received preoperative irradiation and partial laryngopharyngectomy (PLP) or total laryngopharyngectomy (TLP) with en bloc radical neck dissection. Higher rates of local failure were observed in patients with keratinizing tumors (34 vs. 15%), with tumors having an "infiltrating" tumor-stromal interface (30 vs. 14%), with positive surgical margins in PLP or TLP specimens (30 vs. 16%), and with extranodal extension of tumor (39 vs. 22%). The development of distant metastases was significantly correlated with nonkeratinizing carcinomas (30 vs 11%, P = 0.02), and was observed more often in patients with positive lymph nodes (17 vs. 7%). Patients with negative surgical margins in PLP or TLP excision (50 vs. 21%, P = 0.01) survived significantly longer.
Juvenile nasopharyngeal angiofibromas (JNA) are rare. They have been frequently treated with estrogens, either solely or as an adjuvant therapy prior to surgery or irradiation. Clinical trials have proveded no evidence to explain the objective respose to estrogens observed in some tumors. Since the mechanism of steroid hormone action is mediated via specific receptors, we analyzed 8 JNA for tumor cytosol estrogen receptors. None were positive for estrogen receptors. Additionally, all were also negative for progesterone receptors. Nasopharyngeal angiofibromas occur predominantly in adolescent boys at a time when there is a gradual change in androgen availability. Therefore, three latter angiofibromas were also analyzed for the presence of cytosol androgen receptor. Specific testosterone and dihydrotestosterone binding components in the tumor cytosol were detected. This observation raises for the first time the possibility that JNA may be an androgen-dependent tumor. Estrogen may act as an antiandrogen on these tumors, an action similar to that on prostate cancer.