Health of urban Ghanaian women as identified by the Women's Health Study of Accra.

OBJECTIVE: The purpose of the Women's Health Study of Accra was to provide an assessment of the prevalence of communicable and non-communicable illnesses. METHOD: This was a prospective, community-based study that included an interview for medical illnesses, a comprehensive physical examination, and laboratory testing. A total of 1328 women were examined at Korle Bu Teaching Hospital, University of Ghana. RESULTS: Prevalent conditions included poor vision (66.8%), malaria (48.7%), pain (42.8%), poor dentition (41.6%), hypertension (40.2%), obesity (34.7%), arthritis (27.1%), chronic back pain (19.4%), abnormal rectal (16.0%) and pelvic examinations (12.7%), HIV in women age 24-29 (8.3%), and hypercholesterolemia (22.7%). Increasing age, lack of formal education, and low-income adversely affected health conditions. CONCLUSION: The high prevalence of preventable illnesses in this expanding urban population indicates that the health care services are obligated to develop and provide screening, preventive strategies and treatment for both general health and gynecologic health conditions.

Testis imaging with 111In-labeled anticarcinoembryonic antigen monoclonal antibody: identification of carcinoembryonic antigen in normal germ cells.

A monoclonal antibody to carcinoembryonic antigen (CEA) labeled with 111In (Indacea) was used to image tumors in patients with colorectal cancer. The anti-CEA antibody has a high affinity (2.6 X 10(10) M-1) for CEA and does not cross-react with normal cross-reacting antigen, biliary glycoprotein-1, or tumor-extracted, CEA-related antigen. During the course of these studies, it was noted that a significant number of male patients (20 of 27, 74%) showed uptake of Indacea in the testes. In order to determine if the Indacea uptake was specific, 20 testicular specimens were analyzed by immunohistological methods using five different anti-CEA CEA monoclonal antibodies recognizing five different epitopes on CEA. In 18 cases (90%) germ cells were uniformly stained by all five antibodies. Fresh frozen testis tissue was homogenized in water and precipitated with 1.0 M perchloric acid. The supernatant contained a CEA-like material as measured by an enzyme immunoassay specific for CEA. The same supernatant was radiolabeled with 125I and immunoprecipitated with anti-CEA monoclonal antibodies. Sodium dodecyl sulfate:polyacrylamide gel electrophoresis of the immunoprecipitates revealed a single species (Mr 180,000) which was indistinguishable from CEA. This study documents the first description of CEA in the germ cells of normal testis. The CEA in the testis was accessible to circulating monoclonal antibodies in the majority of male patients tested.

Preoperative imaging of colorectal carcinoma with 111In-labeled anticarcinoembryonic antigen monoclonal antibody.

Patients with primary, recurrent, or metastatic colorectal adenocarcinoma were given injections of 200 micrograms of anticarcinoembryonic antigen (CEA) monoclonal antibody labeled with 2 mCi of 111In (Indacea). Patients were imaged at 24 and 48 h. Celiotomy was performed on 40 patients between 3 and 17 days post-Indacea injection. Of 16 primary tumors, 11 (69%) were imaged. Of six extrahepatic recurrences, none was imaged. Intrahepatic metastases were visualized as negative images in 10 of 24 (42%) patients. On the basis of the activity in tissue expressed as a percentage of the total radioactive dose per kg injected into the patient (% ID/kg), extrahepatic tumors that were imaged using Indacea had a significant uptake of radiolabel in the tumor [5.99 +/- 0.91% ID/kg (SE)] and in the associated normal mesenteric lymph nodes (12.0 +/- 2.4% ID/kg). The CEA content of these tumors was high (13.3 +/- 4.7 micrograms/g), and, histologically, the CEA was located primarily apically or intraluminally. Intrahepatic tumor imaging correlated only with tumor size. The greatest Indacea uptake was seen in normal liver (22.1 +/- 3.2% ID/kg). Low Indacea uptake was seen in fat (0.21 +/- 0.05% ID/kg) and bowel wall (1.11 +/- 0.17% ID/kg). In conclusion, Indacea imaging of colorectal carcinoma is specific for high concentrations of accessible CEA in CEA-bearing tumors or in lymph nodes draining these tumors. The successful clinical use of monoclonal antibodies for tumor imaging and therapy will require careful selection of patients for a number of antigen-related parameters including antigen content and distribution in tumors. This information will only come from careful correlation between image results and tissue analysis. High uptake by normal liver tissue is the major unresolved problem with labeled antibody imaging.

Tumor uptake as a function of tumor mass: a mathematic model.

Inverse correlations of tumor uptake (u), measured in percent injected dose per gram, with tumor mass (m) are demonstrated for phospholipid vesicle, nonspecific and specific monoclonal antibody tracers. Correlation coefficients implied u = B mA in 11 different animal experiments. Experimental exponent (A) values lay in the range -0.28-0.64 with a mean of -0.43 while intercept (B) values varied from 3 to 18. Spherical and cylindrical tumor models implied exponents of -0.33 and -0.5, respectively. Comparison of three implantation sites of the human LS174T xenograft revealed a narrow range of exponents (-0.38- -0.46) indicating a consistent geometry for this tumor. Blood flow to the lesion site and inside its volume (as dictated by tumor size) are factors in tumor uptake. Our results indicate that biodistribution data should include the variation of tumor uptake with mass. For less than 10 g lesions, we predict that radiation absorbed dose will be highly dependent upon tumor size.

Ovarian carcinoma metastatic to the breast and axillary node.

Breast cancer is a common primary malignancy in women. On rare occasion the breast is also the site of metastatic disease. This report describes the evaluation of breast and axillary masses in a patient with known ovarian cancer, including the radiographic evaluation and special immunohistochemical stains with CA-125. Flow cytometric determinations and hormonal receptor analysis on both the primary and metastatic tumors demonstrate similar biologic characteristics. Both tumor sites demonstrated positive CA-125 staining, aneuploid DNA populations, moderately positive estrogen receptor content, and negative progesterone receptors. The mammogram demonstrated a well-circumscribed lesion with several areas of microcalcifications. Blood-borne metastasis from the ovary to the breast can show a varied clinical picture that can be differentiated from that of a primary breast carcinoma.

Tumor DNA content in primary and metastatic colorectal carcinoma.

We performed this study to determine if tumor DNA content was an independent prognostic indicator in patients with primary tumors or hepatic metastases from colorectal cancer. We analyzed tumor DNA content by flow cytometry from paraffin-embedded specimens in 133 patients. In the 77 patients with primary colorectal cancer who had had "curative" resection, DNA content of the tumor was an independent prognostic indicator in predicting both relapse-free and overall survival. Logistics regression analysis demonstrated that aneuploidy, ie, tumors that exhibited a population of cells with an "abnormal" DNA content, was the single most important variable in predicting both recurrence and death from disease, even more important than stage. However, in 56 patients with hepatic metastases from colorectal cancer, the DNA content of the liver metastases bore no relationship to the patients' survival or their response to therapy. These data suggest that tumor DNA content is an important prognostic indicator in patients with primary colorectal carcinoma but does not reflect the natural history of patients with liver metastases.

Radioimmune localization of occult carcinoma.

Patients with a rising serum carcinoembryonic antigen level and no clinical or roentgenographic evidence of recurrent or metastatic cancer present a treatment dilemma. Eleven such patients, 10 with a previously treated colorectal carcinoma and 1 with a previously treated breast carcinoma, received an injection of the anticarcinoembryonic antigen monoclonal antibody ZCE-025 labeled with the radioisotope indium 111. Nuclear scintigraphy was performed on days 3 and 5 through 7 to detect potential sites of tumor recurrence. The monoclonal antibody scan accurately predicted the presence or absence of occult malignancy in 7 (64%) patients. Second-look laparotomy confirmed the monoclonal antibody scan results in the patients with colorectal cancer, and magnetic resonance imaging confirmed metastatic breast cancer. This study demonstrates that In-ZCE-025 can localize occult carcinoma and may assist the surgeon in facilitating the operative exploration. In-ZCE-025 assisted in the initiation of adjuvant therapy for the patient with breast cancer.

The importance of DNA flow cytometry in node-negative breast cancer.

DNA flow cytometric analysis and conventional clinical factors were compared with disease outcome in 257 patients with node-negative infiltrating ductal carcinoma who had been treated between 1976 and 1983. Median follow-up was 80 months; none of the patients received adjuvant therapy. The relative prognostic importance of clinical variables, ploidy, and S-phase fraction was analyzed by Cox multivariate analysis. Ploidy was analyzable for 198 tumors and did not predict survival. Nuclear grade predicted disease-free survival for all patients. For 71 patients with diploid tumors, only high S-phase had a statistically significant association with relapse. For 127 patients with aneuploid tumors, tumor diameter predicted both disease-free survival and cancer death; histologic grade was also significant for predicting disease-free survival. In conclusion, flow cytometric determination of ploidy and S-phase fraction can provide valuable predictive information in node-negative breast cancer in addition to conventional variables.

Imaging of human colorectal adenocarcinoma with indium-labeled anticarcinoembryonic antigen monoclonal antibody.

Twenty patients with 21 primary colorectal adenocarcinomas were studied with 2 mCl (7.6 X 10(7) becquerels) of indium-labeled monoclonal antibody (200 micrograms) specific for carcinoembryonic antigen (CEA). Fifteen lesions (71%) were visualized by gamma camera scintigraphy at 48 hours postinjection. Tumors that were identified by immunoscintigraphy were large (38.10 +/- 17.76 cm3 vs 6.00 +/- 1.65 cm3), had a grossly fungating component, had a high content of CEA by enzyme immunoassay (12.9 +/- 3.6 micrograms/g vs 3.3 +/- 1.7 micrograms/g), and had an apical and/or intraluminal staining pattern on immunohistologic section. Patients whose tumors were visualized had a low serum CEA level (1.9 +/- 0.4 ng/mL vs 14.6 +/- 8.0 ng/mL). Prospective selection of patients for follow-up imaging or therapy with radiolabeled monoclonal antibodies may be feasible using these measurements.

Survival discriminants for differentiated thyroid cancer.

Since 1975, the American Cancer Society, Illinois Division, has published end results of major cancer sites drawn from patient data contributed voluntarily by hospital cancer registries throughout the state. The current study was undertaken, in part, to apprehend information regarding contested areas in the management of patients having differentiated (papillary/follicular) thyroid cancer. A total of 2,282 patients with either papillary or follicular carcinoma of the thyroid from 76 different Illinois hospitals and providing 10 years of follow-up information (life-table analysis) were retrospectively analyzed for demographic, disease, and treatment-related predictors of survival. Multivariate analysis using the Cox proportional hazards method was made for stage, age, race, sex, morphology, history of radiation exposure, presence of positive lymph nodes, initial surgical treatment, postoperative iodine 131 therapy, and replacement/suppressive thyroid hormone treatment. Statistically significant (p less than or equal to 0.05) predictors of favorable survival after thyroid cancer were low stage (I and II), young age (less than 50 years), white race, female sex, and the administration, postoperatively, of either thyroid hormone or radioactive iodine. Factors that had no influence on survival were lymph node status, choice of initial surgical treatment, and a history of prior irradiation. We suggest that where a prospective clinical trial is impracticable, a retrospective analysis of a large and detailed database, such as that available from cooperating hospital-based tumor registries, may yet provide useful insights to solutions of cancer management problems.

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.

The health of adult women in Accra, Ghana: self-reporting and objective assessments 2008-2009.

OBJECTIVES: The study provides a full description of the state of women's health in Accra, Ghana using self-reported as well as objective health measures. Using data from the Women's Health Survey of Accra, Wave 2 (WHSA-2), the authors a) examine the consistency of the objective measures of health status (anthropometry and blood pressures) with self-report measures, including the Short Form 36 indices for 8 separate domains of health; and b) describe the main socio-economic differentials in morbidity. METHODS: Cross-sectional household survey with field measurements. 2814 women aged 18 and over were interviewed and measured in their homes in late 2008 and early 2009. The physical measurements included height, weight, waist and hip measurement and 3 or more measures of resting blood pressure. RESULTS: Using the 8 domains of self-reported health captured by the Short Form 36 instrument, we find that physical health worsens more sharply with age than mental health. Social class differentials are narrow in the younger cohorts but widen amongst the elderly. The physical measurements reveal unhealthy levels of obesity and hypertension, worsening steadily with rising age. Age and the wealth of the household influence women's health more than their individual characteristics such as education. CONCLUSIONS: Younger women appear to be in good health with steady declines in physical and mental health with age. The major threat to women's health appears to be the rising levels of obesity and hypertension with mean BMIs for all women over age 45 in excess of 30, producing elevated blood pressures and associated high risks of heart attacks and stroke rising sharply amongst the elderly.

Secular trends in menarcheal age among Ghanaian women in Accra.

The Women's Health Study of Accra is a population-based cross-sectional survey that was conducted between March and September 2003 to assess the burden of disease in women in Accra. In addition to data relating to general health and living conditions, data on age at first menstruation was collected during the survey. A retrospective cohort analysis of the reported age at menarche was conducted using data from 2,644 women aged between 18 and 100 years. The median age of first menstruation of the entire cohort was 15.5 years and the median age of first menstruation among those aged <20 was 14.5 years. There was a statistically significant difference in median age at menstruation among the different age and socioeconomic groups. Multiple linear regression showed a significant decline of 0.2 years per decade in the mean age at menarche among Ghanaian women.

Diagnostic utility of DNA content flow cytometry in follicular neoplasms of the thyroid.

Preoperative diagnosis of follicular carcinoma of the thyroid remains a clinical challenge. This study determined the DNA content parameters of ploidy and proliferative activity levels from cells of normal thyroid tissue, follicular adenomas, and follicular carcinomas to evaluate if these parameters could be used as an adjunct to fine needle aspiration in their diagnosis. Statistically significant higher proliferative activity levels were found in the carcinoma groups (mean S-phase fraction [SPF] = 5.0%) compared to 2.9% for follicular adenomas and 1.3% for normal thyroid. DNA aneuploidy was identified in 73% of carcinomas and 36% of adenomas. Because of overlap of SPF values between groups, one could not rule out the presence or absence of malignancy based on DNA content parameters alone. These measurements may, however, be an aid to the decision making in patients who are poor surgical risks.

Growth factor receptor and related oncogene determination in mesenchymal tumors.

BACKGROUND: Sarcoma are rare malignant neoplasms that originate from a mesenchymal cell line. The epidermal growth factor receptor (EGF-R) has been identified in these malignant neoplasms by immunohistochemical techniques. METHODS: This investigation has evaluated the gene amplification and expression of EGF-R and the homologous oncogene c-erbB-2 in soft tissue and osseous sarcomas by Southern and northern blot analysis. RESULTS: Amplification of EGF-R and c-erbB-2 was identified in 2 of 117 (1.7%) and 6 of 105 (5.7%) of the sarcomas, respectively. Increased expression of EGF-R and c-erbB-2 was identified in 21 of 43 (49%) and 35 of 94 (37%) sarcomas, respectively. CONCLUSIONS: The expression of these two genes in sarcomas appears to occur independently and not be associated with tumor histologic characteristics, grade, size, DNA content, or proliferative activity.

Monoclonal antibody 44-3A6 as a marker for breast carcinoma.

The monoclonal antibody (MAb) 44-3A6 detects a 40-kD cell surface protein on adenocarcinomas and may serve as an effective marker for glandular differentiation. Immunohistochemical analysis of 123 paraffin-embedded malignant breast tissue specimens, 27 normal or benign breast disease specimens and 10 atypical hyperplasia specimens from patients without breast cancer was performed with MAb 44-3A6. The antigen was identified in 76% of breast cancer specimens, 0% of normal or benign breast disease specimens and 88% of the atypical hyperplasia specimens. MAb 44-3A6 also detected this antigen on adjacent normal breast ductal cells in 88% of the breast cancer specimens. There was no statistically significant correlation between immunoreactivity and histological mitotic or nuclear grade, recurrence or overall survival. This study suggests that the cell surface antigen detected by the MAb 44-3A6 may serve as an important marker in the differentiation of normal breast epithelium into an atypical or malignant lesion.

Recombinant BCG therapy suppresses melanoma tumor growth.

BACKGROUND: Melanoma is the fastest rising cancer in the United States. Bacillus Calmette-Guerin (BCG) has been genetically engineered to actively express and secrete the cytokine interleukin-2 (IL-2). Both BCG and IL-2 have known potent antitumor and immunomodulatory properties. METHODS: This recombinant BCG (rBCG 3A) has been tested as an intratumoral injection and a vaccine therapy in conjunction with irradiated tumor cells against melanoma in the murine B16 melanoma model. RESULTS: The transfection process did not adversely alter the function of the wild-type (WT) BCG. rBCG 3A and WT BCG are equally effective intratumoral and vaccine therapies against melanoma when compared with normal saline control groups. Tumor burdens were significantly smaller (p < or = 0.01 and 0.05) for the treatment groups for both intratumoral and vaccine administration of therapy. Immunization with rBCG 3A and WT BCG 14 days before a B16 challenge resulted in an approximately 45% smaller tumor burden when compared with controls. CONCLUSIONS: Novel therapies based on the immunogenic properties of melanoma combined with molecular technologies may offer promise for an effective and safe treatment of melanoma.