Utility of sentinel node biopsy in vulvar and vaginal melanoma: report of two cases and review of the literature.

Sentinel node (SN) biopsy is widely applied for treatment planning of cutaneous melanoma. However, using this strategy in female lower genital tract tumors has not yet been established. We report two cases, one each of vulvar and vaginal melanoma who underwent SN biopsy and review the available literature. Our experience and available limited evidence suggests that this low morbidity technique can be used for obtaining prognostic information and hence treatment planning for this disease. However, a false negative rate perhaps in the order of 15% suggests that careful consideration is necessary before using sentinel lymph node biopsy in the management of vulvar and vaginal melanoma.

Association between glutathione-S-transferase GSTP1 genotypes, GSTP1 over-expression, and outcome in epithelial ovarian cancer.

Ovarian cancer accounts for the majority of deaths from gynaecological malignancy, and polymorphisms in genes encoding the glutathione-S-transferase (GST) GSTP1 detoxifying enzymes may lead to variation in detoxification of carcinogens. We describe a study involving 81 women with invasive epithelial ovarian cancer. A number of important clinical variables and outcome data were obtained. GSTP1 genotyping was undertaken using PCR-based techniques, and GSTP1 expression was quantified using immunohistochemistry (IHC). A Cox's proportional hazard regression model was used to analyze the effects on outcome. We also independently examined 11 women with borderline or low malignant potential (LMP) tumors using IHC only. The mean age of the women was 61.5 years +/- 12 (1 SD) (range 36-88 years), the median overall survival was 26 months, and median progression free interval (PFI) 21 months. There was a significant association between GSTP1 (Val(104)/Val(104)) genotypes, and reduced survival (P = 0.05) and the GTP1 (Ile(104)/Val(104)) genotype appeared to have the best outcome (HR = 0.34, P = 0.045, 95% CI = 0.12-0.98). There was no significant association between the GSTP1 genotypes and any clinico-pathological parameters; there were also no associations between GSTP1 genotypes and response to postoperative chemotherapy. Specific nuclear GSTP1 over-expression was associated with less residual disease (P = 0.05); specific cytoplasmic GSTP1 over-expression with more favourable performance status (P = 0.014)). We found that 10/11 (91%) of the LMP (borderline) tumors over-expressed nuclear GSTP1 compared to only 52% of the invasive tumors (chi(2) ((1)) = 5.95, P = 0.015). There was no significant association between the level of GSTP1 expression and response to postoperative chemotherapy. The overall level of GSTP1 expression and the subcellular localization of GSTP1 expression were not associated with either survival or PFI. There was a significant association between the GSTP1 (Ile(104)/Ile(104)) genotypes and increased overall GSTP1 expression (P = 0.049), and the GSTP1 (Ile(104)/Val(104)) genotypes and reduced overall GSTP1 expression (P = 0.046). We speculate that GSTP1 Ile(104)/Val(104) genotypes are associated with improved outcome because the protein/enzyme, which is expressed, may provide a better balance between the effects of detoxification of carcinogens and the effects of metabolism of chemotherapy agents. In addition, over-expression of nuclear GSTP1 appears to be associated with more favorable ovarian tumor characteristics. In our preliminary study, we also reported a relationship between overall GSTP1 expression and certain GSTP1 genotypes. As far as we are aware, this is the first time that a relationship between the GSTP1 genotypes, GSTP1 expression and outcome has been described in ovarian cancer. Whether the genotype directly determines GSTP1 expression is at present unclear and the precise mechanism of this interaction is unknown.

Glutathione S-transferase GSTM1 and GSTT1 genotypes in ovarian cancer: association with p53 expression and survival.

The objective of this study was to determine whether the association between GSTM1 null/GSTTI null and survival in ovarian cancer is mediated by the influence of these genes on p53 expression. In 81 women with pure invasive ovarian cancer, GSTM1 null and GSTT1 null genotypes were identified using polymerase chain reaction and p53 expression was assessed using immunohistochemistry. The association of these factors with survival was examined using Cox's proportional hazards regression models. Performance status (P < 0.001), operative stage (P = 0.004), residual disease (P = 0.001), histologic subtype (P = 0.05), tumor grade (P = 0.007), and the combined GSTMI null/GSTTl null genotype (P = 0.023) were all individually associated with survival. p53 expression was not associated with survival (P = 0.45). In a multivariate analysis, the effects of GSTM1 null/GSTT1 null on survival were lost when residual disease and tumor grade were included. The effects of p53 expression on survival were unchanged when residual disease, tumor grade, operative stage, and performance score were included. GSTM1 null/GSTT1null did not influence the effects of p53 expression on survival and vice versa. The GSTM1 null/GSTT1 null genotype was associated with response to primary chemotherapy (P = 0.007) but p53 expression was not. We conclude that the association of GSTM1 null/GSTTl null with survival appears to be mediated through different mechanisms to p53 expression in ovarian cancer and in addition, may be a better predictor of outcome.

Fine needle aspiration biopsy of ovarian neoplasm.

Twenty cases of ovarian neoplasm (12 non-coelomic and 8 coelomic and 8 epithelial tumors) have been subjected to fine needle aspiration biopsy (FNAB). FNAB yielded adequate material in all those cases and it was possible to accurately classify the tumors in 16 cases (80%). In eight cases of non coelomic epithelial neoplasms preoperative cytological diagnosis helped in conservative surgery. Cytological features of different groups of ovarian tumors are to some extent characteristic. FNAB is a relatively safe and reliable diagnostic procedure.

A comparison of the side effects of prilocaine with felypressin and lignocaine with adrenaline in large loop excision of the transformation zone of the cervix: results of a randomised trial.

OBJECTIVE: To test the hypothesis that prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline when performing large loop excision of the transformation zone of the cervix. DESIGN: Randomised trial. SETTING: Colposcopy clinic in a large district general hospital. PARTICIPANTS: Two hundred consecutive women undergoing large loop excision of the transformation zone of the cervix. METHODS: Two different local anaesthetic combinations (prilocaine with felypressin and lignocaine with adrenaline) were compared in women undergoing large loop excision of the transformation zone. Prospective collection of clinical and treatment data was undertaken with scoring using an ordinal scale of pain experienced by the women during the procedure. Peri-operative blood loss and any side effects were also recorded. MAIN OUTCOME MEASURES: Side effects associated with the local anaesthetic agents. RESULTS: Lignocaine with adrenaline resulted in less blood loss (P = 0.006) but was more likely to cause side effects, such as feeling faint (P = 0.017) and shaking (P < 0.001). CONCLUSION: Prilocaine with felypressin causes fewer side effects than lignocaine with adrenaline and is therefore the preferred local anaesthetic combination for large loop excision of the transformation zone.

Expression and subcellular localization of cyclin D1 protein in epithelial ovarian tumour cells.

The expression of cyclin D1 protein in tumour sections from 81 patients with epithelial ovarian cancer was analysed using immunohistochemistry. The tumours that overexpressed cyclin D1 in more than 10% of neoplastic cells were considered positive. Thus overexpression of cyclin D1 was observed in 72/81 (89%) of the cases examined. Protein was detected in both the nucleus and the cytoplasm in 24/81 (30%) and localized exclusively in the cytoplasm in 48/81 (59%) of the tumours. Cyclin D1 was overexpressed in both borderline and invasive tumours. There was no association between protein overexpression and tumour stage and differentiation. Furthermore, no correlation between cyclin D1 expression and clinical outcome was observed. However, in tumours overexpressing cyclin D1 (n = 72), the proportion displaying exclusively cytoplasmic localization of protein was higher in those with serous compared with non-serous histology (P = 0.004, odds ratio 4.8, 95% confidence interval 1.4-19.1). Western analysis using a monoclonal antibody to cyclin D1 identified a 36 kDa protein in homogenates from seven tumours displaying cytoplasmic only and one tumour demonstrating both nuclear and cytoplasmic immunostaining. Using restriction fragment length polymorphism polymerase chain reaction and PCR-multiplex analysis, amplification of the cyclin D1 gene (CCND1 was detected in 1/29 of the tumours demonstrating overexpression of cyclin D1 protein. We conclude that deregulation of CCND1 expression leading to both cytoplasmic and nuclear protein localization is a frequent event in ovarian cancer and occurs mainly in the absence of gene amplification.

Prognostic significance of cyclin D1 gene (CCND1) polymorphism in epithelial ovarian cancer.

We have investigated the influence of CCND1 genotype on clinical outcome in 138 women with epithelial ovarian cancer. CCND1 genotypes were identified from peripheral blood DNA by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Patient CCND1 genotypes were compared with clinical details including FIGO tumor stage, residual tumor volume, tumor histology and differentiation, response to chemotherapy, progression free interval, and survival. We observed no association between patient CCND1 genotypes and tumor characteristics or response to chemotherapy. There was no significant difference in overall survival and progression free interval (PFI) among women with different CCND1 genotypes. However, analysis of data from patients who responded to postoperative chemotherapy revealed that women with CCND1 AA genotype were associated with early disease progression (P = 0.020, HR 4.58, 95% CI 1.27-16.48) and reduced survival (P = 0.026, HR 4.48, 95% CI 1.19-16.79) compared with those with CCND1 AG and GG genotypes. These data show that CCND1 genotype does not influence overall prognosis in a cohort of epithelial ovarian cancer patients, however, it is associated with disease progression in a subgroup of patients following initial response to chemotherapy.

Association of glutathione S-transferase GSTM1 and GSTT1 null genotypes with clinical outcome in epithelial ovarian cancer.

Epithelial ovarian cancer is generally associated with a poor outcome, although the mechanisms that determine survival and progression-free interval (PFI) are unclear. Data from ovarian tumors showing associations between (a) null genotypes at the glutathione S-transferase GSTM1 and GSTT1 loci and expression of p53 protein and (b) outcome and expression of p53 suggest that polymorphism at these loci is a factor determining outcome. Accordingly, we have studied the association between the GSTM1 null and GSTT1 null genotypes and survival and PFI in 148 women with epithelial ovarian cancer. Although we did not find an association between individual genotypes and outcome, women with both GSTM1 null and GSTT1 null genotypes demonstrated poorer survival (P = 0.001) and reduced PFI (P = 0.003). Thus, no cases with both these genotypes survived past 42 months postdiagnosis. In contrast, 43% of the women without this combination survived beyond this time. Because response to chemotherapy is a major factor determining outcome in ovarian cancer, we also examined the data for associations between the glutathione S-transferase genotypes and response to such treatment. Thus, in 78 patients treated with chemotherapy, the combination of GSTM1 null and GSTT1 null was associated with unresponsiveness to primary chemotherapy (P = 0.004); none of the eight patients with both these genotypes responded, compared with 38 of 70 (54%) of patients with other genotype combinations. The effect of the combination of genotypes on survival and PFI was lost in a multivariate model that included response to chemotherapy as a confounding factor. This suggests that the combination of GSTM1 null/GSTT1 null is associated with outcome because of its influence on response to chemotherapy. These preliminary findings may provide a basis for the selection of patients for treatment with chemotherapeutic agents.

Significance of nuchal cord.

Perinatal events of 180 babies with nuchal cord (umbilical cord entanglement around foetal neck) over one year have been studied. The incidence of nuchal cord was 5.74% of all hospital deliveries. More than one third (39%) of them had tight nuchal cord (TNC) and 61% had loose nuchal cord (LNC). Babies with TNC were more frequently met with foetal distress (51%), prolonged second stage (11%), non-toxaemic accidental haemorrhage (7%) and operative delivery (56%) when compared to babies with LNC and controls (without nuchal cord). Nearly one fourth (24%) of the babies with TNC were born as small for date, had birth asphyxia (61%) and 8.5% died during perinatal period. Perinatal outcome was adversely affected by TNC in comparison to LNC and controls.

Fine needle aspiration biopsy in gynecologic malignancies. Recurrent and metastatic lesions.

This study evaluated the efficacy of fine needle aspiration biopsy (FNAB) in 80 suspected cases of recurrent and metastatic gynecologic malignancies. RNAB was performed at 90 sites in 80 patients; 42 of the sites were deep seated. The cytologic diagnosis correlated well with either histology (7 cases) or clinical follow-up. FNAB diagnosis of deep-seated lesions precluded exploratory laparotomy, and further therapy was administered accordingly. Thus, FNAB in gynecologic malignancies was safe, reliable and cost effective.

Cytologic evaluation of nipple discharge in relation to mammary neoplasia.

Spontaneous nipple discharge as a presenting symptom was seen in 80 patients out of 3500 patients referred for cytologic examination of breast during last 5 years. Gross appearance of nipple discharge was bloody (33), serous (29), milky (16) and yellowish (2). Cytology smears showed 5 cases of carcinoma and 14 cases of intraductal papilloma. One out of two cases of male nipple discharge revealed malignant cells. Bloody nipple discharge was more often associated with carcinoma and intraductal papilloma. Hence it underscored the importance of cytologic evaluation of bloody nipple discharge.

Nonobstetric lower genital tract trauma.

In a 4-year-period there were 31 admissions to Nehru Hospital, because of nonobstetric injuries of the female genital tract. This constituted 0.8% of all gynaecological admissions over this period. The injuries were caused by voluntary coitus, automobile accidents and various types of astride injuries. Seven of the 18 patients with noncoital injuries presented with vulval haematomas and all were managed by evacuation under general anaesthesia. Two of the 13 patients with coital injury were admitted with haemorrhagic shock and required initial resuscitation with blood transfusion. The vaginal vault, especially the right and posterior fornices were the frequent sites of coital injury for parous women; on the other hand lower vaginal and introital injuries were caused by first acts of coitus. Except for trivial superficial lacerations with minimal bleeding, primary definitive surgical repair other than vaginal packing was favoured for better healing and to reduce morbidity.

Single dose tinidazole prophylaxis in vaginal hysterectomy.

OBJECTIVE: To determine the efficacy and side effects of a single dose of tinidazole for infection following vaginal hysterectomy. METHOD: A randomized double-blind placebo-controlled trial using 2 g tinidazole 12 h before vaginal hysterectomy in 50 patients was conducted. No other antibiotic was used until the development of infection. RESULT: There was a significant reduction (P < 0.01) of post-operative vaginal cuff cellulitis (54-16%). A similar reduction (P < 0.05) in febrile morbidity was also observed. The duration of postoperative hospital stay (P < 0.001) and use of additional antibiotics (P < 0.01) were also reduced. No adverse effect of tinidazole was noted. CONCLUSION: A single dose of tinidazole appears to be a safe and effective alternative prevention against infection in vaginal hysterectomy.

Tinidazole prophylaxis in elective abdominal hysterectomy.

OBJECTIVE: To determine whether a single dose (2 g) of tinidazole before abdominal hysterectomy could reduce the incidence of postoperative infection. METHOD: A randomized double-blind placebo-controlled study was undertaken with a single oral dose (2 g) of tinidazole, 12 h before surgery, in 100 patients undergoing abdominal hysterectomy for various benign diseases. Other antibiotic use was withheld until there was no postoperative infection. RESULT: A significant reduction (P < 0.05) of infectious morbidity (28% vs. 8%) as well as a decrease in additional antibiotic use (P < 0.01) and duration of hospital stay (P < 0.001) was observed. Febrile morbidity was also reduced from 36% to 14% (P < 0.05). Tinidazole was tolerated well by all the patients. CONCLUSION: Tinidazole prophylaxis (2 g oral dose) is considered to be a simple, safe and effective way to reduce postoperative infection in abdominal hysterectomy.