Effect of increased serum 25(OH)D and calcium on structure and function of post-menopausal women: a pilot study.

The purpose was to determine if increasing serum 25(OH)D and calcium in postmenopausal women increased skeletal muscle size, strength, balance, and functional task performance while decreasing muscle fatigue. PCSA of the vastus lateralis increased and ascent of stairs time decreased after 6 months of increased serum 25(OH)D. PURPOSE: The Institute of Medicine recommends ≥ 20 ng/ml of serum 25-hydroxyvitamin D [25(OH)D] for bone and overall health. Serum 25(OH)D levels have been associated with physical performance, postural sway, and falls. The purpose of this study was to determine if increasing postmenopausal women's serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml improved skeletal muscle size, strength, balance, and functional performance while decreasing skeletal muscle fatigue. METHODS: Twenty-six post-menopausal women (60-85 years old) with baseline serum 25(OH)D levels between 20 and 30 ng/ml were recruited. Oral over-the-counter (OTC) vitamin D3 and calcium citrate were prescribed to increase subjects' serum 25(OH)D to levels between 40 and 50 ng/ml, serum calcium levels above 9.2 mg/dl, and PTH levels below 60 pg/ml, which were confirmed at 6 and 12 weeks. Outcome measures assessed at baseline and 6 months included muscle physiological cross-sectional area (PCSA), muscle strength, postural balance, time to perform functional tasks, and muscle fatigue. Repeated measures comparisons between baseline and follow-up were performed. RESULTS: Nineteen subjects completed the study. One individual could not afford the time commitment for the repeated measures. Three individuals did not take their vitamin D as recommended. Two subjects were lost to follow-up (lack of interest), and one did not achieve targeted serum 25(OH)D. Vastus lateralis PCSA increased (p = 0.007) and ascent of stair time decreased (p = 0.042) after 6 months of increasing serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml. Isometric strength was unchanged. Anterior-posterior center of pressure (COP) excursion and COP path length decreased (p < 0.1) albeit non-significantly, suggesting balance may improve from increased serum 25(OH)D and calcium citrate levels. CONCLUSIONS: Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.

The role of neurosurgery in the treatment of cerebral metastases from choriocarcinoma: a report of two cases.

Cerebral metastases from choriocarcinoma are a poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. However, with the increased experience with chemotherapy and radiotherapy the prognosis of this group of patients has improved substantially. Neurosurgery remains an option for selected patients. We present two patients who underwent craniotomy as part of their management of choriocarcinoma, and review the role of neurosurgery in the treatment of gestational trophoblastic disease.

Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia.

This study investigated the relationship between human papillomavirus type 16 (HPV-16) antibodies detected in oral fluid from women with cervical neoplasia, their HPV-16 antibody seroprevalence, and their cervical HPV-16 DNA presence. Cervical HPV-16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of these women. The prevalence of IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) in oral fluid and was investigated by enzyme-linked immunosorbent assay. Anti-VLP-16 IgA antibodies were detected in oral fluid from 54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in controls (P = 0.000002). Anti-VLP-16 IgG was detected in oral fluid from 43.2.9% (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV-16 DNA positive at their cervical lesion, displayed an oral fluid anti-VLP-16 IgA prevalence of 60.7% (17/28) and HPV-16 DNA negative women an oral fluid anti-VLP-16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti-VLP-16 IgG prevalence in HPV-16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral fluid from HPV-16 DNA negative women (P = 0.3). Amongst HPV-16 DNA positive women, the anti-VLP-16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence 35.7% (10/28) and for the HPV-16 DNA negative women these values were 60% (24/40) and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more sensitive than serum antibody detection for the determination of HPV infection but could be useful as a non-invasive screening method for women with cervical neoplasia and for estimating the mucosal antibody response to HPV vaccines.

Cyclooxygenase-2 expression and prostaglandin E(2) synthesis are up-regulated in carcinomas of the cervix: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors.

The prevalence of cervical cancer in South African women is reported as being the highest in the world, occurring, on the average, in 60 of every 100,000 women. Cervical cancer is thus considered an important clinical problem in sub-Saharan AFRICA: Recent studies have suggested that epithelial tumors may be regulated by cyclooxygenase (COX) enzyme products. The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) expression and PGE(2) synthesis are up-regulated in cervical cancers. Real-time quantitative RT-PCR and Western blot analysis confirmed COX-2 ribonucleic acid and protein expression in all cases of squamous cell carcinoma (n = 8) and adenocarcinoma (n = 2) investigated. In contrast, minimal expression of COX-2 was detected in histologically normal cervix (n = 5). Immunohistochemical analyses localized COX-2 expression and PGE(2) synthesis to neoplastic epithelial cells of all squamous cell (n = 10) and adenocarcinomas (n = 10) studied. Immunoreactive COX-2 and PGE(2) were also colocalized to endothelial cells lining the microvasculature. Minimal COX-2 and PGE(2) immunoreactivity were detected in normal cervix (n = 5). To establish whether PGE(2) has an autocrine/paracrine effect in cervical carcinomas, we investigated the expression of two subtypes of PGE(2) receptors, namely EP2 and EP4, by real-time quantitative RT-PCR. Expression of EP2 and EP4 receptors was significantly higher in carcinoma tissue (n = 8) than in histologically normal cervix (n = 5; P < 0.01). Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation after in vitro culture of cervical cancer biopsies and normal cervix in the presence or absence of 300 nmol/L PGE(2). cAMP production was detected in all carcinoma tissue after treatment with exogenous PGE(2) and was significantly higher in carcinoma tissue (n = 7) than in normal cervix (n = 5; P < 0.05). The fold induction of cAMP in response to PGE(2) was 51.1 +/- 12.3 in cervical carcinoma tissue compared with 5.8 +/- 2.74 in normal cervix. These results confirm that COX-2, EP2, and EP4 expression and PGE(2) synthesis are up-regulated in cervical cancer tissue and suggest that PGE(2) may regulate neoplastic cell function in cervical carcinoma in an autocrine/paracrine manner via the EP2/EP4 receptors.

Seroresponses to human papillomavirus types 16, 18, 31, 33, and 45 virus-like particles in South African women with cervical cancer and cervical intraepithelial neoplasia.

The aim of the study was to determine the prevalence of antibodies to human papillomavirus (HPV) types 16, 18, 31, 33, and 45 in woman in Cape Town with cervical intraepithelial neoplasia (CIN) (n = 95), cervical cancer (n = 40), female blood donors (n = 95) and children (n = 110). The enzyme-linked immunosorbent assay (ELISA) made use of baculovirus synthesised HPV virus like particles (VLPs) as antigen. Antibodies to at least one HPV type were detected in sera from 75% of cancer patients, 71.6% of CIN patients, 44.2% of blood donors and 27.3% of children. Sera from 95 women with CIN were compared with age-matched female blood donors. There was a significant association of seropositivity to VLP-16 (P = 0.006) and VLP-45 (P = 0.008) with CIN compared with the blood donors. There was also a significant difference in the seropositivity of women with CIN to any of the five virus-like particle (VLP) types compared to the blood donors (P = 0.0002: OR = 3.2). Thirty-nine of sixty-nine (56.5%) women with CIN were found to be HPV-16 DNA positive. The average age of women in this group that were VLP-16 seropositive was 34 years and those found to be VLP-16 seronegative was 52 years of age. Antibodies to all five VLP types were detected in these populations, thus an ideal vaccine should induce protection from infection by a wide range of HPV types.

Is there an effect of perioperative blood transfusion on the outcome of radical hysterectomy with lymphadenectomy for cervical cancer in South Africa?

The aim of this study was to investigate whether there is an effect of perioperative blood transfusion on the outcome of radical hysterectomy with lymphadenectomy for cervical cancer. One hundred and thirty-one patients with cervical cancer were treated by Wertheim radical hysterectomy in the period from 1984-1991. Eighty-six patients received blood transfusions during surgery or within two weeks, whereas 45 patients did not receive any blood transfusion. Transfused and non-transfused patients did not differ with respect to mean age, race, weight, FIGO-stage, cell-type, grade, size, depth of invasion and nodal involvement. Transfused patients had more blood loss, longer surgical time and lower haemoglobin levels. Using log rank analysis, the calculated five-year survival was 81% for the transfused group and 84% for the non-transfused group, a non-significant difference. The five-year disease-free survival rate was 87% for the transfused group and 88% for the non-transfused group. This study suggests that perioperative blood transfusion does not adversely influence survival after the Wertheim operation for cervical cancer.

Human papillomavirus in normal cervical smears from Cape Town.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) types in South African women with normal cervical cytology and to determine whether our results are comparable to what has been found elsewhere in the world. DESIGN: Cervical smears were collected from 262 women. SETTING: The Cape Town metropolitan area. PARTICIPANTS: A total of 262 women, aged 19-85 years. Eighty-five women attended the family planning clinic of the Gynaecology Department at Groote Schuur Hospital and 177 women consulted private gynaecological practices. MAIN OUTCOME MEASURES: The prevalence and types of HPV in 192 women with normal cervical cytology. RESULTS: The incidence of HPV DNA in cervical smears from Cape Town women with normal cytology was found to be 13% (25/192) using Southern blot hybridisation. The types of HPV found in normal cervical tissue from Cape Town did not differ significantly from those found elsewhere in the world. Nine per cent (17/192) were positive for "high-risk' HPV types which are associated with premalignant and malignant cervical lesions. In the age group 20-39 years, 15 of 92 (16%) were positive for HPV DNA, while in the age group above 39 years, 3 of 53 (6%) women were positive for HPV DNA. CONCLUSIONS: In this study, 25 of 192 (13%) women with normal cytology were positive for HPV.

Acetic acid visualization of the cervix: an alternative to cytologic screening.

OBJECTIVE: To investigate the value of acetic acid visualization of the cervix as an alternative to cytologic screening. METHODS: A prospective study was conducted in a squatter area in Cape Town, South Africa, on 2426 women who underwent speculum examination, naked-eye inspection of the cervix after application of acetic acid, and cytologic smear. The smears were stained and processed at the screening site. Patients with a positive reading after acetic acid or a smear indicating a high-grade squamous intraepithelial lesion (SIL) were referred for immediate colposcopy, biopsy, and when indicated, treatment by large loop excision of the transformation zone. Therefore, histology was obtained on all patients with a positive acetic acid test or a positive cytology. RESULTS: Seventy-six women with positive reactions to acetic acid. Among the 2350 women with negative reactions, 254 had positive cervical smears; only 11 of these had histologic high-grade SIL. In contrast, 20 of the 61 women with positive cytology and positive acetic acid test had high-grade SIL on histology. Therefore, the acetic acid reaction enabled the observer to detect 20 of the 31 women (64%) who exhibited a high-grade SIL both on cytology and histology. CONCLUSION: In locations where access to cytopathology is limited, naked-eye visualization of the cervix after application of diluted acetic acid warrants consideration as an alternative in the detection of cervical premalignant lesions.

The influence of hormonal status on excision margins after large loop excision of the transformation zone (LLETZ).

To evaluate the influence of the type of contraception used and post-menopausal status on the involvement of excision margins with CIN after Large Loop Excision of the Transformation Zone (LLETZ), the authors reviewed a computerised database and the clinical files of 451 sequential women treated by LLETZ, for CIN diagnosed on cytology and colposcopy. There was a statistically significant association between both the use of Long Acting Injectable Progesterone (LAIP) and post menopausal status with histological report of incomplete excision of CIN on the endocervical excision margin. Therefore, the authors conclude that both progesterone-only containing contraception and menopause induced atrophy of the endocervical epithelium significantly increase the risk of involvement of the endocervical excision margin with CIN in the treatment by LLETZ. This parameter is of particular importance, as it is one of the known factors for recurrence.

Placental site trophoblastic tumor: three case reports and literature review.

The clinical features of three patients with placental site trophoblastic tumour (PSTT) are presented. Two patients had probable nephrotic syndrome, which was unrecognized at the time. The nephrotic syndrome disappeared after hysterectomy in one patient and the other demised after one cycle of chemotherapy. The use of hysteroscopy in one patient and the management of a pulmonary metastasis in another are described.

Does colposcopically directed punch biopsy reduce the incidence of negative LLETZ?

OBJECTIVE: To evaluate the role of punch biopsy in reducing the occurrence of negative histology provided by large loop excision of the transformation zone in the management of cervical intraepithelial neoplasia. DESIGN: Retrospective review of computerised data base and clinic files. SETTING: Colposcopy Clinic, Groote Schuur Hospital, Cape Town, South Africa. SUBJECTS: Two hundred and ninety-eight women considered suitable for the local outpatient management of cervical intraepithelial neoplasia. METHODS: Two groups of patients were identified: group A consisted of women who had cervical intraepithelial neoplasia confirmed colposcopically and who underwent directed punch biopsy; group B consisted of women who had cervical intraepithelial neoplasia confirmed colposcopically and were referred for large loop excision of the transformation zone without confirmatory punch biopsy. RESULTS: In Group A (n = 184) 123 women had cervical intraepithelial neoplasia diagnosed on punch biopsy. Large loop excision of the transformation zone was performed on 116 women and 7 were lost to follow up. The procedure confirmed cervical intraepithelial neoplasia in 95 cases (82%), but there was no cervical intraepithelial neoplasia in 21 cases (18%). Sixty-one women had negative punch biopsies. Of these, 13 underwent large loop excision of the transformation zone, 31 had persistently negative follow up cytology, and 9 had positive cervical smears of which 7 were treated with large loop excision of the transformation zone, and 8 were lost to follow up. Overall, 25% of all negative punch biopsies were falsely negative. In group B 114 were treated with large loop excision of the transformation zone and cervical intraepithelial neoplasia was confirmed in 97 cases (85%); one woman had unsuspected microinvasion (1%) and 16 women (14%) had no cervical intraepithelial neoplasia. Negative histology after large loop excision of the transformation zone was not statistically different in groups A and B. CONCLUSION: Punch biopsy does not reduce the occurrence of negative histology after large loop excision of the transformation zone.

Cervical carcinoma associated with pregnancy.

Because of the uncommon synchronous occurrence of pregnancy and invasive cervical carcinoma, this disease entity remains poorly understood. In addition inconsistent reporting has precluded meaningful meta-analysis. About 1 in 2000 pregnancies are associated with cervical cancer and pregnancy is a complication in approximately 3 percent of patients with cervical cancer. There is little evidence to suggest that the pregnancy has an influence on prognosis. Although not firmly established, vaginal delivery may have an adverse effect on outcome. Timing of delivery must be individualized inasmuch as there is a role for delaying treatment in order to achieve fetal lung maturity. Surgery and radiotherapy should be utilized in the same stage-dependent manner as in nonpregnant patients but management should be individualized and undertaken by a multidisciplinary team. These and other issues are discussed more fully in this review.

Primary chemotherapy with bleomycin, ifosfamide and cisplatinum (BIP) followed by radiotherapy in the treatment of advanced cervical cancer. A pilot study.

Bleomycin, Ifosfamide and Cisplatinum were combined in a 3 cycle regime of neoadjuvant chemotherapy given prior to radiotherapy in the treatment of 26 patients with late Stage (FIGO IIB-IIIB) cervical cancer. Seven patients were withdrawn for reasons of compliance and 1 patient due to toxicity. The response rate to chemotherapy in the remainder (18 patients) was 44.4%. Sixtyfour per cent of 17 patients who completed chemoradiotherapy responded completely. This regime was generally well tolerated and neurotoxicity was less problematic than in other reports, although fatal pneumotoxicity occurred in one patient. It is too early to comment on survival; this is an interim report of responses and toxicities. The results are less impressive than in other reported studies and cast doubt on the role of neoadjuvant chemotherapy in the management of advanced cervical cancer in developing countries.