Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome.

The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients (methotrexate 300 mg x m(-2) (with folinic acid rescue), bleomycin 30 mg x m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age (mean, s.d. 43.3+/-10, 44.7+/-8.5 years, respectively, P=0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P=0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant (P=0.002). The reduction in -CH(2) triglyceride approached significance (P=0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P=0.94). There is a significant reduction in tumour volume and -CH(2) triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage.

Adenomyoma mimicking an aggressive uterine neoplasm on MRI.

This case report concerns a nulliparous female with prolonged vaginal bleeding, where MRI demonstrated a mass with an aggressive, tumour like appearance involving the posterior aspect of the uterus. Histological examination confirmed that this was an adenomyoma. The unusual imaging appearance of this lesion and its differential diagnosis are discussed. Adenomyoma should be considered in the differential diagnosis of aggressive-appearing uterine masses.

Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography.

OBJECTIVE: Accurate assessment of lymph node status before treatment is critical in the treatment of gynecologic cancers because the 5-year survival and treatment of women is influenced by lymph node involvement. The aims of this study were to investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission tomography (PET) to detect pelvic lymph node metastases by comparing imaging with histopathologic findings after lymph node dissection. MATERIALS AND METHODS: Eighteen patients with gynecologic cancers were studied by all three imaging methods before surgery. The images were initially reviewed with routine diagnostic conditions and then, subsequently, by two observers who were unaware of the clinical and histopathologic findings of the patients. The nodal sites were split into upper (aortic to common iliac bifurcations) and lower (common iliac bifurcations to inguinal ligament) iliac chains. All observers' results were statistically analyzed with specificity, sensitivity, positive and negative predictive values, Fisher's exact test (individual observers) or chi-square test (combined observers), and Cohen's kappa test. RESULTS: Eight of 18 patients had lymph node metastases at histology. Findings of all three modalities agreed in full in only one patient. CT correctly revealed 10 node-negative patients, whereas MR imaging was correct in eight of these patients. (18)F-FDG PET correctly depicted one patient with lymph nodes negative for tumor. CT was the most specific imaging modality (97.0%), with MR imaging and PET rendering values of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT, 48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and 0.72 for PET. CONCLUSION: CT is the most specific modality for detecting lymph nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F-FDG in the ureters or bladder, which may mask or imitate lymph node metastases.

Is conservative treatment for adenocarcinoma in situ of the cervix safe?

OBJECTIVE: To determine the long term results of treatment of adenocarcinoma in situ by conisation of the cervix using survival analysis. DESIGN: A retrospective study in six teaching hospitals in North West Thames. POPULATION: Eighty-five women with a histological diagnosis of adenocarcinoma in situ of the cervix in punch or cone biopsy were identified from pathology and clinical databases. RESULTS: In one patient a small focus of adenocarcinoma in situ was found in a cervical polyp. Subsequent cytology was normal and no further treatment was undertaken. The 84 remaining women underwent diathermy loop, cold knife cone biopsy, laser cone biopsy, or needle excision of the transformation zone. A hysterectomy or second conisation was performed in 31/84 women (36.9%) as part of the initial treatment. In all, nine (10.6%) had early invasive lesions of which four were squamous. Fifty-nine patients were treated conservatively following one or two conisations (median follow up 78 weeks, range 0-543 weeks). One had a subsequent hysterectomy for menorrhagia. Five women have undergone treatment for suspected recurrence, a 21.5% cumulative rate of further treatment by four years. The cumulative rate of histologically proven recurrence after conservative management was 4.3% at one year and 15% at four years. CONCLUSIONS: In those cases with clear margins in the cone biopsy, there is a place for conservative management of a selected group of patients who wish to preserve fertility. However, 16.7% of these will require further treatment after four years because of recurrent cytological abnormalities. Women who opt for conservative management should undergo regular, long term surveillance in a colposcopy clinic. Among those women with involved margins in the initial cone biopsy, there is a high incidence of residual disease. A second cone biopsy may be appropriate 'definitive treatment' for young women who wish to preserve their fertility if the margins of the second biopsy are clear and there is no evidence of invasion. Even among those for whom a hysterectomy is the proposed 'definitive treatment', a second cone biopsy may be required before hysterectomy to avoid inappropriate treatment of an occult invasive lesion.

Magnetic resonance imaging of the primary site in stage I cervical carcinoma: A comparison of endovaginal coil with external phased array coil techniques at 0.5T.

OBJECTIVE: To compare endovaginal with pelvic phased array coil magnetic resonance imaging (MRI) in detection of Stage I cervical carcinoma by correlating the findings with histopathology. PATIENTS AND METHODS: Forty consecutive patients with Stage I cervical carcinoma confirmed histologically were studied using an endovaginal coil alone immediately followed by a pelvic phased array coil. T1-W transverse and T2-W FSE sagittal images made with each coil were analyzed independently by two radiologists noting the presence and size of a mass within the cervix and any parametrial extension or involvement of adjacent organs. Tumor volumes were measured using the electronic calliper to compute tumor area on each slice and multiplying by the slice thickness. Thirty patients underwent radical hysterectomy, one a trachylectomy, one simple hysterectomy and four extended cone biopsies. Four patients had radiotherapy to the primary tumor. Following surgery, histopathologic findings were recorded and tumor volumes measured. RESULTS: Tumor volumes ranged from 0-106 cm(3)(median 1.4 cm(3), mean 9 +/- 19.4 cm(3)). Thirty-six patients had correlation of the primary site with the surgical specimen. Agreement between observers was excellent for both endovaginal (k = 0.90) and pelvic phased array (k = 0.96) techniques. Combined sensitivity and specificity for both observers of endovaginal MR imaging for detection of tumor was 96% and 70%, respectively; for pelvic phased array imaging sensitivity was substantially less at 54%. Specificity was higher at 83.7%, probably because small abnormalities were seldom visible. In patients treated surgically, early parametrial involvement in four women on endovaginal MRI was confirmed histologically in two. Pelvic phased array imaging showed early parametrial involvement in four women and was confirmed in one. CONCLUSION: Endovaginal MRI adds substantially to information from pelvic phased array images in the preoperative assessment of patients with early cervical cancer. J. Magn. Reson. Imaging 2000;12:1020-1026.

Value of magnetic resonance imaging with an endovaginal receiver coil in the pre-operative assessment of Stage I and IIa cervical neoplasia.

OBJECTIVE: To assess the value of high resolution endovaginal magnetic resonance images (MRI) of the uterine cervix in planning management of early cervical cancer. DESIGN: Prospective cross-sectional study. SETTING: Specialist gynaecological oncology unit of a postgraduate teaching hospital. PARTICIPANTS: Thirty nine women aged 25-76 years old (mean 42.5 years) with invasive carcinoma Stage I or IIa of the cervix. METHODS: A ring coil was positioned endovaginally around the cervix. Imaging was performed on a 1.0 T HPQ Vista or 0.5 T Asset (Picker, Highland Heights, Ohio, USA) using T1 weighted and T2 weighted sequences in transverse and sagittal planes with thin slices (2.5 mm) and small fields of view (12 cm). Tumour volumes were measured and any extension into adjacent organs and parametrium was noted. The patients were followed up after treatment and the outcome related to the MRI findings. RESULTS: There was one false positive and one false negative result among five Stage Ia patients being assessed for residual disease after cone biopsy or LLETZ. The MRI assessment of the size and distribution of the tumour was confirmed histologically in all 31 patients with Stage Ib or IIa disease who were treated surgically. One of these patients in whom no endocervical tumour was visible on MRI underwent radical trachelectomy. Three patients had radiotherapy as primary treatment. Patients with Stage Ib or IIa disease who had tumour volumes > 10 cm3 with early parametrial extension on MRI had a substantially worse prognosis at 24 months (disease-free survival 58.3% vs 95.5%, P = 0.003). CONCLUSION: High resolution MRI with an endovaginal coil allows precise measurement of tumour volume and identifies patients with small volume disease who might be considered for more conservative therapy. This technique also reveals early parametrial invasion that cannot be identified reliably by any other method. Early parametrial invasion in women with large tumours appears to have a very much worse prognosis.

Analysis and outcome of 502 cases of laser excision cone (LEC) at the Samaritan Hospital for Women, London.

When performed based on cytology, histological accuracy of the laser cone specimen improved with the more severe cytology. The incidence of adenocarcinoma in situ is 1.0%. With and without residual disease, the rate of abnormal cytology after laser excision cone are 0.6% and 1.6% respectively. There is good correlation between colposcopic biopsy and cone specimen in the more severe lesions. Out of 139 cases of incomplete excision, only 3 cases had abnormal cytology at follow-up. The complication rates are very low.

The constitutively expressed octamer binding protein OTF-1 and a novel octamer binding protein expressed specifically in cervical cells bind to an octamer-related sequence in the human papillomavirus 16 enhancer.

A novel octamer binding protein expressed specifically in cervical cells but not in other cell types has been identified. This protein differs in size and sequence specificity from the constitutively expressed octamer binding protein OTF-1. In particular it binds with higher affinity to a sequence in the human papillomavirus 16 (HPV) upstream regulatory region which has a seven out of eight base pair match compared to the consensus octamer motif. This is the first example of a tissue specific protein which has been observed to bind to the papillomavirus enhancer. The possible role of this protein in producing the observed tissue specific activity of the enhancer and in cervical carcinogenesis induced by HPV is discussed.

Human T cell responses to human papillomavirus type 16 L1 and E6 synthetic peptides: identification of T cell determinants, HLA-DR restriction and virus type specificity.

Four T cell determinants in the major capsid protein of human papillomavirus (HPV) type 16 L1 and one in the E6 protein associated with cellular transformation were defined using synthetic peptides to stimulate peripheral blood mononuclear cells from asymptomatic individuals. HLA-DR restriction was defined using murine L cells transfected with HLA-DR genes to present antigen. Responses to two of the five determinants by T cell lines and clones were shown to be specific for HPV-16 based on the lack of cross-recognition of the corresponding sequences of other known papillomavirus sequences (types 1a, 5, 6b, 8, 11, 18 and 33). The T cells raised against two of the other peptides cross-reacted with corresponding peptides from other strains to varying extents, depending on their structural homology. The implications of these results regarding the prevalence of HPV-16 infection in the population and the possible diagnostic role of these responses in papillomavirus infection is discussed.

Laser excision rather than vaporization: the treatment of choice for cervical intraepithelial neoplasia.

We are concerned that the use of ablative therapy in the treatment of cervical intraepithelial neoplasia may lead to a failure to diagnose early invasive carcinoma. In view of this, since June 1986, 196 patients considered suitable for laser vaporization were treated by a shallow laser excision cone biopsy instead. The mean age of the women treated was 31 years, and the mean length of the excised specimen, measured after fixation, was 14 mm. All procedures were completed in the colposcopy clinic and took no longer to perform than vaporization. The complication rate was low, and an excellent specimen was available for pathologic examination. In this series, histology on the excised cone revealed that two patients had microinvasive carcinoma and one had adenocarcinoma in situ. In addition, 16 patients had a lesion two or three grades worse on the laser excision biopsy than was predicted by the colposcopically directed biopsy. Because of the inaccuracy of colposcopic biopsy, we now recommend a small laser excision cone biopsy as the treatment of choice for all patients with cervical intraepithelial neoplasia.

Staging of carcinoma of the uterine cervix: MRI-surgical correlation.

Forty-six patients with carcinoma of the uterine cervix were examined with spin-echo magnetic resonance imaging (MRI) using a superconducting magnet operating at a field strength of 0.5 T. All subjects later underwent lymphadenectomy and, when appropriate, radical hysterectomy. Surgical-pathologic correlation was carried out in order to assess the accuracy of the imaging modality in the staging of the disease. In the detection of nodal involvement, the accuracy of MR was 76%. The accuracy in determination of tumour size approached 100%. In the assessment of parametrial and vaginal involvement, the accuracy was 85% and 100% respectively.

The Aldridge sling procedure in the treatment of urinary stress incontinence.

The long-term results of the Aldridge sling procedure for the treatment of recurrent urinary stress incontinence was assessed in 50 women most of whom had had previous failed vaginal surgery; 78% of patients were cured of all symptoms and a further 20% were symptomatically improved--a 2% failure rate. Only one patient reverted from a cure to improved during the lengthy follow-up. The procedure is not difficult to perform and is a good surgical option in patients with failed vaginal surgery.

'Spontaneous' rupture of the diaphragm.

A case of 'spontaneous' rupture of the diaphragm with herniation and strangulation of the stomach is reported. The diagnosis was made by endoscopy and repair achieved via laparotomy. The patient has made a full recovery.