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). (1)H 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). (31)P 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 (1)H-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.

Cost-effectiveness of active versus conservative colposcopic management of mild dyskaryosis.

Management of mild dyskaryosis remains controversial. In this study, we compared the cost-effectiveness of active versus conservative colposcopic management of women presenting with mild dyskaryosis in two different hospital settings. All women presenting in 2001 with a mild dyskaryotic smear and requiring colposcopy were studied in two different clinical settings (70 women at Darent Valley Hospital (DVH) and 327 at St George's Hospital (SGH)). At DVH, treatment is offered should there be any evidence of cervical intraepithelial neoplasia (CIN). On the other hand, a more conservative approach of cytological and colposcopical follow-up is offered to patients with evidence of low-grade disease at SGH. The outcome of both groups of patients was determined in terms of the number of colposcopy visits per patient, the risk of missing disease as a consequence of patients lost to follow-up and hospital costs as well as costs to patient over a four-year period. The majority (70%) of DVH patients had 1-2 colposcopy visits whereas the majority (60%) of SGH patients had 3-7 visits. At SGH 44% of untreated patients were lost to follow-up and an unknown number of those might have had high-grade disease. Active management is more cost-effective compared with conservative management ( pound323 and pound589 as cost per patient effectively treated in the two hospitals respectively). In conclusion, active management of low-grade disease is associated with lower hospital and patient costs compared with the conservative strategy.

A comparative study of two methods of large loop excision of the transformation zone.

OBJECTIVE: To determine whether the conventional large loop excision of the transformation zone (CLLETZ) and the "top-hat" technique (THLLETZ) differ in (a) completeness of excision of the cervical lesion, (b) depth of cervical tissue excised and (c) adequacy of follow up by cytology and colposcopy. DESIGN: Retrospective case review. SETTING: University Teaching Hospital, London. SAMPLE: Five hundred and thirteen consecutive patients matched for age, parity, smoking history and referral cytology who had either CLLETZ (286-5%) or THLLETZ (227-44%) for cervical intraepithelial neoplasia (CIN). METHODS: All procedures were performed or supervised by BSCCP-accredited colposcopists. All cytology and histology were reviewed by two specialist cytohistopathologists. Cervical stenosis was defined as difficulty in or inability in obtaining an endocervical brush smear. MAIN OUTCOME MEASURES: Depth of cervical tissue excised, histology of endocervical margins, post-LLETZ cytologic and colposcopic findings. RESULTS: The mean depth of excision in the CLLETZ group was 12.1 mm (SD = 4.4 mm) and 20.8 mm (SD = 6.4 mm) in the THLLETZ group. The incidence of involved endocervical margins was 2.8% in the CLLETZ group and 5.2% in the THLLETZ group (P= 0.1). There was CIN in the "top-hat specimen" of 10 THLLETZ cases (4.4%, CI = 95%). The first post-treatment cervical smear was inadequate in 5 (4.1%) cases in the CLLETZ group and 20 (11.7%) in the THLLETZ group (P= 0.022). Cervical stenosis was found in 21 (7.7%) cases in the CLLETZ group and in 64 (30.9%) cases in the THLLETZ group (P < 0.0001). Eleven (4%) patients in the CLLETZ group had cytological and/or colposcopic evidence of residual CIN compared with 12(5.8%) patients in THLLETZ group (P= 0.4). In the first follow-up assessment, 21.7% of the CLLETZ group had incomplete colposcopy compared with 48.7% in the THLLETZ group (P < 0.0001). CONCLUSIONS: Compared with the CLLETZ, the THLLETZ (1) removed more cervical tissue but did not have a lower incidence of involved endocervical margins, and (2) resulted in significantly higher incidence of inadequate post-treatment colposcopic and cytological follow up. These data indicate that there is no justification to performing a "top-hat" LLETZ routinely.