Tumor oncogenic expression in malignant effusions as a possible method to enhance cytologic diagnostic sensitivity. An immunocytochemical study of 87 cases.

The diagnostic ability of cytological preparations can be hampered by specimen inadequacy and the presence of representative cells, which may result in a diagnostic accuracy of only 70%. An immunocytochemical battery (ICC), which included anti-p53, anti-c-erbB-2, and B72.3 MoAbs, was used to enhance sensitivity in 87 specimens of body effusions. Thirty-six cases were positive for malignancy using conventional cytology. Forty cases were negative and 11 cases were inconclusive or had an equivocal diagnosis. Sensitivity was 65%, and there was a negative predictive value (NPV) of 62%. p53 was expressed in 50 cases (56%, sensitivity = 83%, NPV = 73%), and B72.3 MoAb was positive in 36 cases (37%, sensitivity = 66%, NPV = 64%). Forty-eight cases (56%) displayed reactivity with anti-c-erbB-2 (sensitivity = 75%, NPV = 63%). The authors concluded that application of an ICC panel of anti-p53, B72.3 and c-erbB-2 to complement conventional cytology increases sensitivity to 98% (P < .0005) with an NPV of 96% (P = .001).

Comparative study between cytology and dot-ELISA for early detection of bladder cancer.

Schistosomiasis remains one of the major public health problems of the tropics. Conservative estimates place the number of infected individuals at about 200 millions. In Egypt, carcinoma of the urinary bladder associated with schistosomiasis is the foremost oncologic problem, because of its high frequency and the late presentation of cases. A newly developed monoclonal antibody CK1K10 to keratinized grade 1 squamous cell carcinoma was used in a dot enzyme-linked immunosorbent assay (Dot ELISA) to test urine samples of 118 patients with bladder carcinoma, 291 patients with genitourinary pathology other than bladder carcinoma, in addition to 550 healthy controls. The overall sensitivity of the dot ELISA was 90% among 118 patients with bladder carcinoma. Twenty-seven of 33 transitional cell carcinoma cases (82%), 68 of the 71 squamous cell carcinoma cases (96%), 7 of 10 undifferentiated tumors cases (70%), and 4 of 4 adenocarcinoma were positive with this assay. The specificity was 90% in our sample population. A comparative study of diagnosis by cytology and dot ELISA was carried out in 57 patients with bladder carcinoma. Dot ELISA was found to be superior as a screening tool for high risk groups (P < .001 using chi-square test). Cytology detected 21% of transitional cell carcinoma, 68% of squamous cell carcinoma, 50% of adenocarcinoma, and 86% of undifferentiated tumors. The dot ELISA assay should be useful for screening high-risk groups because it does not require sophisticated equipment, is noninvasive, does not require highly trained staff, and can be performed in less than 30 minutes.

PREVENTION OF CISPLATIN-INDUCED NEPHROTOXICITY BY METHIMAZOLE.

Nephrotoxicity is a dose-limiting factor in the use of cisplatin against solid tumours. Methimazole, an antithyroid drug containing a free SH group, has a nephroprotective potential against chemically-induced nephrotoxicity. We tried to explore the nephrotoxic effect of the experimentally therapeutic dose of cisplatin (7 mg kg(-1), i.p.), particularly on the nuclear level of kidney cells in male albino rats, as well as the possible protective effect of methimazole. Furthermore, the drug interaction regarding the oncolytic effect of cisplatin was examined in Ehrlich ascites carcinoma (EAC)-bearing mice. A single dose of cisplatin caused kidney damage, 6 days after injection, manifested by 219% increase in serum creatinine, 384% increase in blood urea nitrogen and 170% increase in kidney content of lipid peroxides. Kidney DNA showed clear fragmentations detected by gel electrophoresis. However, kidney reduced glutathione was unchanged at that time period. Histological examination of kidney confirmed the toxic effect of cisplatin. Methimazole (40 mg kg(-1), i.p., 30 min before cisplatin injection) significantly protected the kidney from the nephrotoxic effect of cisplatin as judged from the biochemical parameters investigated as well as the histopathological examination. On the other hand, the survival data in EAC-bearing mice treated with both drugs indicated the persistence of an effective cytotoxic action. This study points to a promising use of this combination and necessitates further experimental and clinical studies. 2000 Academic Press@p$hr Copyright 2000 Academic Press.

Breast conservative surgery: is it appropriate for locally advanced breast cancer following downstaging by neoadjuvant chemotherapy? A pathological assessment.

The application of breast conserving surgery to down-staged cases with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue with a variable incidence of locoregional failures. In this study, the response of LABC to NACT was assessed pathologically and the eligible candidates for breast conserving surgery were identified retrospectively. The efficacy of preoperative clinical examination and mammography in detecting these pathological changes were also evaluated. The study included 41 LABC cases. They received NACT (FAC) and were then subjected to a mastectomy. The cases were examined clinically and by mammography before starting treatment and immediately before surgery. Residual tumours in the mastectomy specimens were correlated with the pretreatment and preoperative clinical and mammographic findings in order to assess the efficacy of these tools for detection of NACT-induced changes. After 3 cycles of NACT, 78% of women showed an objective response. However, only 25% of them would have been eligible for breast conserving surgery. The remaining responders had an increased incidence of either multifocality and or peritumoural in situ carcinoma. Both clinical examination and mammography were inadequate for detection of these chemotherapy-induced changes and hence for selecting suitable candidates for breast conservation. This study has shown that tumour regression by NACT is probably induced by a process of tumour segmentation and is associated with an increased incidence of ductal in situ lesions in the original tumour bearing area.

A new surgical strategy for breast conservation in locally advanced breast cancer that achieves a good locoregional control rate: preliminary report.

The scope of breast conserving surgery has recently expanded to include locally advanced breast cancer (LABC) patients who are downstaged following neoadjuvant chemotherapy (NACT). However, the efficacy of this approach in achieving adequate locoregional control of disease is in doubt. Some reports have attributed the failure to the association of NACT-induced tumour downstaging which can leave multifocal in situ and invasive lesions around the main tumour mass. In the present study, in order to eradicate all possible tumour satellites, a very wide local excision that included the whole original tumour-bearing area was performed regardless of the expected wide defect. This defect was then immediately reconstructed by an ipsilateral pedicled latissimus dorsi myocutaneous (LDM) flap. The study included 26 patients with LABC without evidence of primary tumour-multicentricity. Tumours were downstaged following NACT. The early cosmetic outcome was good in the majority of cases. Early complications were minimal. Twenty-two patients had a mean follow up period of 30.2 (range 7-50) months. In those evaluable cases, locoregional control of the disease was excellent (100%) but distant metastases occurred in seven cases (31.8%).

DNA ploidy and proliferating cell nuclear antigen image analysis of peritoneal and pleural effusions. A possible diagnostic role.

OBJECTIVE: To determine the role of DNA and proliferating cell nuclear antigen (PCNA) image analysis (IA) in enhancing the diagnostic sensitivity of conventional cytology (CC). STUDY DESIGN: The histopathologic and clinical data on 87 consecutive pleural and peritoneal effusions were used to evaluate the accuracy of CC and DNA IA results. RESULTS: CC showed a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 65%, 100%, 100% and 62%, respectively. Aneuploidy peaks were seen in 49 cases; 47 of them were true positives. Thirty of 38 diploid cases were true negatives. The sensitivity, specificity, PPV and NPV were 85%, 94%, 96% and 80%, respectively. There were positive correlations between DNA ploidy profile and PCNA proliferative index (PI), (R = .697) and significant differences in PCNA PI between malignant and benign effusions (P < .001). CONCLUSION: The DNA IA PI by PCNA can be used as a complementary diagnostic tool with CC in cytologically inconclusive cases.

Pathological assessment of the response of locally advanced breast cancer to neoadjuvant chemotherapy and its implications for surgical management.

The effectiveness of breast-conserving surgery for patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NACT) is still a controversial issue, and variable incidences of locoregional failures have been reported. The present study was conducted to pathologically assess the response of LABC to NACT, and also to evaluate the efficacy of preoperative clinical examination and mammography in detecting these pathological changes. A total of 38 patients with LABC received NACT in the form of three cycles of fluorouracil/adriamycin/cyclophosphamide and were then subjected to a mastectomy. The residual tumors in the mastectomy specimens were measured, mapped, and compared to the pretreatment and preoperative clinical and mammographic findings for evaluation. An objective response to NACT was observed in 70.4% of the patients; however, only 26.7% of them were suitable candidates for conservative surgery. The rest of the responders showed an increased incidence of multifocality and in situ lesions localized within the original tumor-bearing area. Both clinical examinations and mammography were inadequate for the selection of candidates for breast conservation. Tumor regression by NACT is probably induced by a process of tumor segmentation. It is also associated with an increased incidence of multifocality and in situ lesions.

Evaluation of the BTA tests for the detection of bilharzial related bladder cancer: the Cairo experience.

OBJECTIVE: To evaluate the clinical performance of the BTA stat test and the BTA TRAK assay in the diagnosis of bilharzia-related bladder cancer and to calculate a new 'Egyptian' cut-off value for the BTA TRAK (quantitative) assay. METHODS: Urine samples of 149 individuals were tested for the presence of the human complement factor H-related protein, the antigen detected by the BTA stat and BTA TRAK tests. The group consisted of 53 healthy volunteers, 20 patients with active bilharziasis, 11 patients with other urologic disorders including prostate cancer, and 65 patients with histologically proven bladder cancer. All samples were obtained prior to surgery or therapy. RESULTS: The BTA stat test was positive in 64 of 65 samples from patients with bladder cancer, for an overall sensitivity of 99%. With a BTA TRAK assay cut-off of 60 U/ml (set at 97% specificity in the healthy population), the sensitivity of the TRAK assay was 94%. There was no statistically significant difference between the sensitivities of the two BTA tests in patients diagnosed with squamous cell carcinoma and those with transitional cell carcinoma. The overall specificity of the BTA stat test was 67% ranging from 15% in patients with bilharziasis to 94% in healthy volunteers. The overall specificity of the TRAK assay was 66%, again with negative results in 15% of the patients with bilharziasis. CONCLUSIONS: The BTA stat test and TRAK tests are extremely sensitive in the detection of bladder cancer in the Egyptian population. Positive results (85%) are also observed in patients with active bilharziasis, which often leads to bladder cancer. Longitudinal follow-up of these positive cases is needed to determine whether these positive results are false or predictive of bladder cancer.

Prevention of cisplatin-induced nephrotoxicity by methimazole.

Nephrotoxicity is a dose-limiting factor in the use of cisplatin against solid tumours. Methimazole, an antithyroid drug containing a free SH group, has a nephroprotective potential against chemically-induced nephrotoxicity. We tried to explore the nephrotoxic effect of the experimentally therapeutic dose of cisplatin (7 mg kg(-1), i.p.), particularly on the nuclear level of kidney cells in male albino rats, as well as the possible protective effect of methimazole. Furthermore, the drug interaction regarding the oncolytic effect of cisplatin was examined in Ehrlich ascites carcinoma (EAC)-bearing mice. A single dose of cisplatin caused kidney damage, 6 days after injection, manifested by 219% increase in serum creatinine, 384% increase in blood urea nitrogen and 170% increase in kidney content of lipid peroxides. Kidney DNA showed clear fragmentations detected by gel electrophoresis. However, kidney reduced glutathione was unchanged at that time period. Histological examination of kidney confirmed the toxic effect of cisplatin. Methimazole (40 mg kg(-1), i.p., 30 min before cisplatin injection) significantly protected the kidney from the nephrotoxic effect of cisplatin as judged from the biochemical parameters investigated as well as the histopathological examination. On the other hand, the survival data in EAC-bearing mice treated with both drugs indicated the persistence of an effective cytotoxic action. This study points to a promising use of this combination and necessitates further experimental and clinical studies.