Thomas Ind

Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment

PURPOSE Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Radical vaginal trachelectomy as a fertility‐sparing procedure in women with early‐stage cervical cancer—cumulative pregnancy rate in a series of 123 women

Objective  To analyse the fertility rates, complications and recurrences in a group of women who have undergone radical vaginal trachelectomy and pelvic lymphadenectomy for early‐stage cervical cancer.

Evaluation of magnetic resonance diffusion and spectroscopy measurements as predictive biomarkers in stage 1 cervical cancer

OBJECTIVE To establish whether ADC and total choline were significantly different between cervical tumors with different histological characteristics (type, degree of differentiation, presence or absence of lymphovascular invasion, lymph-node involvement) in order to establish their role as predictive biomarkers. METHODS 62 patients with stage 1 cervical cancer were scanned at 1.5 T. T2-weighted imaging (TR/TE=4500/80 ms), to identify tumor and normal cervix, was followed by diffusion-weighted imaging (TR/TE=2500/69 ms; 5 b-values 0, 100, 300, 500 and 800 s/mm(2)) and MR spectroscopic imaging (15 mm slice, 7.5 mm in-plane resolution, TR=888 ms). Regions of interest in normal cervix and tumor were drawn on apparent diffusion coefficient (ADC) maps by an expert observer with reference to the T2-weighted images. ADCs were calculated using a monoexponential fit of data from all b-values. MR spectra in voxels designated as tumor (>30% tumor) or non-tumor were quantified using LCModel and referenced to tissue water. RESULTS There was a statistically significant difference between the ADC of tumor regions (1117+/-183x10(-6) mm(2)/s) and of selected normal regions (1724+/-198x10(-6) mm(2)/s; p<0.001), and between tumors that were well/moderately differentiated (1196+/-181x10(-6) mm(2)/s) compared with those that were poorly differentiated (1038+/-153x10(-6) mm(2)/s; p=0.016). There was no significant difference between the ADCs of the tumors when separated by other characteristics (tumor type, lymphovascular invasion, lymph-node metastases), or between measured total choline in any of the groups. CONCLUSION ADCs are lower in cancer compared to normal cervical tissue, with degree of tumor differentiation contributing to this difference.

MR Imaging Features of Vaginal Malignancies

Primary vaginal malignancies are rare, accounting for only 1%-2% of all gynecologic malignancies. Squamous cell carcinoma makes up about 85% of primary vaginal malignancies. This tumor characteristically arises from the posterior wall of the upper third of the vagina. The main patterns of disease are an ulcerating or fungating mass or an annular constricting lesion. At magnetic resonance (MR) imaging, squamous cell carcinoma has intermediate signal intensity on T2-weighted images and low signal intensity on T1-weighted images. The tumors that account for the remaining 15% of primary vaginal malignancies are adenocarcinoma, melanoma, and sarcomas. The signal intensity characteristics on MR images correlate with the histologic subtypes and reflect the MR imaging appearances of these histologic subtypes elsewhere in the body. Secondary malignancy of the vagina is far more frequent than primary vaginal malignancy. Most vaginal metastases occur by means of direct local spread from the cervix, uterus, or rectum. The MR imaging appearances of these metastases reflect the MR imaging appearances of the primary tumor.

Measurement of urinary beta core fragment of human chorionic gonadotrophin in women with vulvovaginal malignancy and its prognostic significance.

Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary measurement of the core fragment of the beta-subunit of hCG has been proposed as a useful tumour marker in non-trophoblastic gynaecological malignancies. This study describe the measurement of urinary beta-core in 50 patients with vulvovaginal malignancy. In contrast to other studies corrections were made for both the effect of urine concentration and the age of the patient. Each patient was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary beta-core. The sensitivity of beta-core was only 38%, but of those patients with elevated levels 90% had died within 24 months, while only 32% of those with normal levels had died. For both patients at initial presentation and those with recurrent disease, there was a highly significant difference in the survival curve between those with elevated beta-core levels and those with normal levels. This is similar to findings in cervical carcinoma, and suggests that for lower genital tract cancer the measurement of urinary beta-core may be valuable as a prognostic indicator, allowing a more informed approach to treatment and follow-up.

Serum concentrations of cancer antigen 125, placental alkaline phosphatase, cancer-associated serum antigen and free beta human chorionic gonadotrophin as prognostic markers for epithelial ovarian cancer

Objective To investigate the prognostic significance of elevated levels of cancer antigen 125 (CA125), placental alkaline phosphatase (PLAP), free β human chorionic gonadotrophin (hCG) and cancer‐associated serum antigen (CASA) in women with primary epithelial ovarian carcinoma.

Characterisation of the differential expression of marker antigens by normal and malignant endometrial epithelium.

In order to examine the production of marker proteins, a reproducible method has been established for culturing purified epithelial cells from normal and malignant endometrium. We have examined the differential expression of secretory proteins using immunohistochemistry in frozen tissue sections, immunocytochemistry in cell cultures derived from the same specimens and protein assays on the culture supernatants. Placental protein 14 (PP14) was produced by normal premenopausal epithelium but not by the post-menopausal or malignant endometrial epithelium. In contrast, placental alkaline phosphatase (PLAP) was produced by endometrial cancers and the endometrial adenocarcinoma-derived cell line Ishikawa, but not by the normal endometrial epithelium. Other markers such as CA-125, which was produced by both normal and malignant endometrium but not by the cell line, and human chorionic gonadotrophin (beta-hCG), which was produced by Ishikawa cells but not by any of the fresh tissues, were less cancer specific. Placental alkaline phosphatase is a direct product of endometrial cancers that can be readily assayed in serum using this two-site assay to test its clinical usefulness in monitoring patients at risk for endometrial cancer.

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC)

OBJECTIVE To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. METHODS 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008. RESULTS Median age at time of surgery for bowel obstruction was 57 years (range, 26 to 85 years). All patients had received at least one line of platinum-based chemotherapy. Median time from diagnosis of primary disease to documented bowel obstruction requiring surgery was 19.5 months (range, 29 days-14 years). Median interval from date of completed course of chemotherapy preceding surgery for bowel obstruction was 3.8 months (range, 5 days-14 years). Ascites was present in 38/90(42%). 49/90(54%) underwent emergency surgery for bowel obstruction. The operative mortality and morbidity rates were 18% and 27%, respectively. Successful palliation, defined as adequate oral intake at least 60 days postoperative, was achieved in 59/90(66%). Only the absence of ascites was identified as a predictor for successful palliation (p=0.049). The median overall survival (OS) was 90.5 days (range, <1 day-6 years). Optimal debulking, treatment-free interval (TFI) and elective versus emergency surgery did not predict survival or successful palliation from surgery for bowel obstruction (p>0.05). CONCLUSION Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

Investigation of metabolite changes in the transition from pre-invasive to invasive cervical cancer measured using (1)H and (31)P magic angle spinning MRS of intact tissue.

The aim of this study was to determine the metabolic changes in the transition from pre‐invasive to invasive cervical cancer using high‐resolution magic angle spinning (HR‐MAS) MRS. Biopsy specimens were obtained from women with histologically normal cervix (n = 5), cervical intraepithelial neoplasia (CIN; mild, n = 5; moderate/severe, n = 40), and invasive cancer (n = 23). 1H HR‐MAS MRS data were acquired using a Bruker Avance 11.74 T spectrometer (Carr–Purcell–Meiboom–Gill sequence; TR = 4.8 s; TE = 135 ms; 512 scans; 41 min acquisition). 31P HR‐MAS spectra were obtained from the normal subjects and cancer patients only (as acetic acid applied before tissue sampling in patients with CIN impaired spectral quality) using a 1H‐decoupled pulse‐acquire sequence (TR = 2.82 s; 2048 scans; 96 min acquisition). Peak assignments were based on values reported in the literature. Peak areas were measured using the AMARES algorithm. Estimated metabolite concentrations were compared between patient diagnostic categories and tissue histology using independent samples t tests. Comparisons based on patient category at diagnosis showed significantly higher estimated concentrations of choline (P = 0.0001) and phosphocholine (P = 0.002) in tissue from patients with cancer than from patients with high‐grade dyskaryosis, but no differences between non‐cancer groups. Division by histology of the sample also showed increases in choline (P = 0.002) and phosphocholine (P = 0.002) in cancer compared with high‐grade CIN tissue. Phosphoethanolamine was increased in cancer compared with normal tissue (P = 0.0001). Estimated concentrations of alanine (P = 0.01) and creatine (P = 0.008) were significantly reduced in normal tissue from cancer patients compared with normal tissue from non‐cancer patients. The estimated concentration of choline was significantly increased in CIN tissue from cancer patients compared with CIN tissue from non‐cancer patients (P = 0.0001). Estimated concentrations of choline‐containing metabolites increased from pre‐invasive to invasive cervical cancer. Concurrent metabolite depletion occurs in normal tissue adjacent to cancer tissue. Copyright

Diffusion Weighted Imaging of the Uterus: Regional ADC Variation with Oral Contraceptive Usage and Comparison with Cervical Cancer

Background: There is growing interest in diffusion weighted magnetic resonance imaging (MRI) of cervical carcinoma but normal uterine appearances and effects of the oral contraceptive pill (OCP) have not been described. Purpose: To establish apparent diffusion coefficient (ADC) values for normal regions of uterus, determine the effect of the OCP on these values, and compare them with ADCs from cervical cancer. Material and Methods: Twenty-seven premenopausal women (19 taking the OCP) with cervical intraepithelial neoplasia (CIN) were studied with T2W and diffusion weighted MRI (DW-MRI). Regions of interest were drawn on ADC maps by visual matching with T2W images on different zones of the uterus and values compared between women not taking and taking the OCP. A further group of 25 women with clinically obvious tumors of the cervix were also studied with T2W and DW-MRI and ADC values of tumor were compared with ADC values of cervical epithelium and stroma. Results: The ADC values of adjacent zones of the uterus and cervix were significantly different from one another (P<0.001). The junctional zone was seen as a band of restricted diffusion between endometrium and outer myometrium. The ADC value of the junctional zone of the uterus was significantly greater (P<0.001) in patients taking the OCP than those patients not taking the OCP. There was no significant affect of the OCP on the ADC values of other uterine zones. Conclusion: The zonal anatomy of the uterus is well demonstrated by DW-MRI with hormonal effects secondary to the OCP affecting junctional zone alone. ADC of cervical tumor is significantly different to cervical epithelium and stroma indicating a role in cervical cancer detection and local staging.