The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study.

PURPOSE: The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration. METHODS: We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical-pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses. RESULTS: We found only (1) low muscle attenuation (MA)-an established factor for muscle depletion-and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity. CONCLUSION: The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.

Comparison of optimised endovaginal vs external array coil T2-weighted and diffusion-weighted imaging techniques for detecting suspected early stage (IA/IB1) uterine cervical cancer.

OBJECTIVE: To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours. METHODS: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement. RESULTS: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively). CONCLUSION: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging. KEY POINTS: • Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. • Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. • Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.

Introducing robotic surgery into an endometrial cancer service--a prospective evaluation of clinical and economic outcomes in a UK institution.

BACKGROUND: We have assessed how the introduction of robotics in a publicly funded endometrial cancer service affects clinical and economic outcomes. METHODS: The study included 196 women. Costs were divided into those for wards, high dependency, staffing, theatres, pharmacy, blood products, imaging, pathology and rehabilitation. Capital depreciation was included. RESULTS: Prior to the introduction of robotics, 78/130 (60.0%) cases were performed open, compared to 17/66 (25.8%) afterwards (p < 0.0001). The median operative time increased 37 min (95% CI 17-55 min; p = 0.0002); the median blood loss was 55 ml lower (95% CI 0-150 ml; p = 0.0181); the stay was 2 days shorter (95% CI 1-3; p < 0.0001). Complications reduced from 64/130 (49.2%) to 19/66 (28.8%) (p = 0.0045). Costs reduced from £11 476 to £10 274 (p = 0.0065). Conversions for 'straight stick' surgery were 18.2% (14/77) compared to 0.0% (0/24) for robotics (p = 0.0164). CONCLUSIONS: Introducing robotics resulted in fewer laparotomies, shorter stays, fewer complications and lower costs.

Women's experiences after a radical vaginal trachelectomy for early stage cervical cancer. A descriptive phenomenological study.

PURPOSE: This paper reports on a phenomenological study of women's experiences 1-10 years following a radical vaginal trachelectomy and describes the impact on health, sexuality, fertility and perceived supportive care needs. METHOD AND SAMPLE: Qualitative telephone interviews employing a descriptive phenomenological approach were conducted using a purposive sample of 12 women. KEY RESULTS: Several felt their cancer experience was positive; bringing them closer to family and changed their outlook on life. A few experienced delayed psychological reactions and/or fears of recurrence. Many experienced isolation and the desire to contact others with similar experiences. Women recovered well but a few experienced fears/concerns about lymphoedema and intermenstrual bleeding. Sexual function was not a long-term issue for most. Some that could feel the cerclage (stitch) during intercourse, developed techniques to reduce this. Single women felt vulnerable in new relationships. Pregnancy was an anxious time, especially for those that experienced a miscarriage or pre-term birth. Sources of support included the clinical nurse specialist, family/friends, surgical consultant, online patient forums and a support group. Women needed more information on trachelectomy statistics, pregnancy care recommendations as well as access to counselling, peer support, being seen by the same person and increased public awareness. CONCLUSIONS: This study has provided an interesting and detailed insight into women's experiences in the years following a trachelectomy, with results that have important considerations for practice such as provision of statistical information; counselling; peer support; consistent pregnancy recommendations; increased public awareness and increased identification and management or prevention of long-term physical effects.

Preoperative imaging in patients undergoing trachelectomy for cervical cancer: validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T.

AIM: The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy. PATIENTS/INTERVENTIONS: 55 consecutive patients 25-44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded. RESULTS: Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm(3), IQR=0.14-1.06 cm(3)). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer 1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer 2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size correlated between each observer and histology (observer 1 r=0.91, p<0.0001; observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer 2: r=0.21, p=0.16); however, differences between observer measurements and histology were not significant (size p=0.09, volume p=0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p=0.1 both observers). CONCLUSION: In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

OBJECTIVE: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics. SUBJECTS AND METHODS: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion. RESULTS: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion. CONCLUSION: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.

Cervical cancer.

Standard treatment for invasive cervical cancer involves either radical surgery or radiotherapy. Childbearing is therefore impossible after either of these treatments. A fertility-sparing option, however, by radical trachelectomy has been shown to be effective, provided that strict criteria for selection are followed. Fertility rates are high, whereas recurrence is low, indicating that a more conservative approach to dealing with early small cervical tumours is feasible. Careful preoperative assessment by magnetic resonance imaging scans allows accurate measurement of the tumour with precise definition to plan surgery. This will ensure an adequate clear margin by wide excision of the tumour excising the cervix by radical vaginal trachelectomy with surrounding para-cervical and upper vaginal tissues. An isthmic cerclage is inserted to provide competence at the level of the internal orifice. A primary vagino-isthmic anastomosis is conducted to restore continuity of the lower genital tract. Subsequent pregnancies require careful monitoring in view of the high risk of spontaneous premature rupture of the membranes. Delivery by classical caesarean section is necessary at the onset of labour or electively before term. Over 1100 such procedures have been carried out vaginally or abdominally, resulting in 240 live births. Radical vaginal trachelectomy with a laparoscopic pelvic-node dissection offers the least morbid and invasive route for surgery, provided that adequate surgical skills have been obtained.

Screening for ovarian cancer in women with varying levels of risk, using annual tests, results in high recall for repeat screening tests.

BACKGROUND: We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate- or high-risk group for development of ovarian cancer. METHODS: 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000- December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate- and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. RESULTS: The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingo-oophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. CONCLUSION: No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.

Differences in hand movements and task completion times between laparoscopic, robotically assisted, and open surgery: an in vitro study.

Surgical dexterity depends on economy and precision of movements, and this can be objectively measured using electromagnetic motion analysis. We have assessed the differences in hand movements and task completion times between open, laparoscopic and robotically assisted surgery during an exercise performed in vitro. A standard surgical exercise was performed using open, standard laparoscopic (SL) and robotically assisted laparoscopic (RAL) approaches. The total duration of the exercise was studied along with the number and duration of movements required to complete the exercise in each surgical modality. The time taken to complete the exercise was significantly longer in both the SL and RAL approaches when compared to the open route. However, it was found that RAL had significantly decreased number of movements (mean difference = 24 movements, P < 0.006) but a longer duration of each movement when compared to SL (mean difference = 0.13 s, P < 0.001). This study shows objectively that the exercise took longer to complete using the RAL approach than the standard open approach. However, RAL had more purposeful movements and required fewer movements to complete the exercise compared to SL.

Challenging dogma: radical conservation surgery for early stage cervical cancer in order to retain fertility.

INTRODUCTION: Cervical cancer is the second commonest cancer to affect women with over half a million cases world-wide yearly. Screening programmes have reduced the incidence and death rate dramatically in Western societies. At the same time, professional and social pressures may delay child bearing such that a significant number of women will present with early stage disease, but be anxious to retain their fertility potential. Standard treatment by radical hysterectomy or radiotherapy has good results, but inevitably renders the women infertile. The rationale for extensive surgery resecting parametrium or destructive radiotherapy treating the whole pelvis in all cases of cervical cancer has been questioned. PATIENTS AND METHODS: Lessons learnt from the less radical surgical approach to breast cancer can be applied to cervical cancer whilst still observing Halstead's principles of surgical oncology. Wide, local excision of early stage small tumours by radical vaginal trachelectomy combined with a laparoscopic pelvic lymphadenectomy utilises modern technology with traditional surgery. Radical vaginal trachelectomy comprises the distal half of a radical abdominal (Wertheim's) or vaginal (Schauta's) hysterectomy. An isthmic-vaginal anastomosis restores continuity of the lower genital tract after insertion of a cerclage that is necessary to maintain competence during future pregnancies. RESULTS: A total of 142 cases were performed between 1994 and 2006, most (98%) in women with Stage 1B carcinoma of the cervix with a mean follow-up of 57 months. Twelve (9%) had completion treatment, 11 with chemo/radiotherapy and one radical hysterectomy. There were four recurrences (3%) among the women who did not have completion treatment, and two (18%) in those that did. There were 72 pregnancies in 43 women and 33 live births in 24 women. The 5-year accumulative pregnancy rate among women trying to conceive was 53%. Delivery was by classical caesarean section in a high-risk fetomaternal units with 8 babies (25%) born before 32 weeks. CONCLUSIONS: Radical vaginal trachelectomy appears safe when performed in centres with appropriate experience of radical vaginal surgery and laparoscopic techniques. The impact of this new approach questions traditional teaching whilst preserving potential fertility in hitherto impossible circumstances.

Epithelial and stromal metabolite changes in the transition from cervical intraepithelial neoplasia to cervical cancer: an in vivo 1H magnetic resonance spectroscopic imaging study with ex vivo correlation.

To investigate epithelial and stromal metabolite changes in cervical intraepithelial neoplasia (CIN) and cervical cancer in vivo and correlate findings with MR spectroscopy of tissue samples. Forty-seven women (19 with CIN, 28 with cervical cancer) underwent endovaginal MR at 1.5 T with T2-W and localised 2D MR spectroscopic imaging (PRESS, TR = 1,500 ms, TE = 135 ms). tCho, 2 ppm and -CH(2) lipid peaks were measured in epithelial (>50% epithelium, no tumour), stromal (>50% stroma, no tumour) and tumour (>30% tumour) voxels. Unsuppressed water signal from the same voxel provided a concentration reference. (1)H HR-MAS MR spectra were acquired from tissue in 37 patients (11.74 T, pulse-acquire and cpmg sequences, with water pre-saturation). Analysable data from 17 CIN and 25 cancer patients showed significant increases in tCho (p = 0.03) and 2 ppm (p = 0.007) in tumour compared with epithelial voxels from CIN patients, but not with epithelial voxels from cancer patients. No significant differences were seen in stroma from cancer compared with CIN patients. Differences in -CH(2) lipids were not significant between groups. There was no significant correlation between in vivo and ex vivo tCho or -CH(2) lipids. Estimated in vivo concentrations of tCho and 2 ppm resonances increase in tumour and adjacent epithelium in progression from CIN to cervical cancer.

Fertility preserving surgery for carcinoma of the cervix.

PURPOSE OF REVIEW: Cervical cancer remains the second most common female malignancy. Screening programmes have reduced the overall incidence, predominantly in the western world; however, this has led to a disproportionate rise in the incidence of early-stage disease, with a related increase in demand, for fertility-sparing techniques to be developed. RECENT FINDINGS: Standard treatment for cervical cancer compromises fertility. A radical wide local excision of carefully selected early-stage tumours will allow conservation of the body of the uterus with a vaginoisthmic anastomosis enabling continuity of the vagina to be preserved following insertion of an isthmic cerclage suture. Pelvic node dissection may be performed at the same time by laparoscopic techniques. Over 900 cases have been performed and reported in the literature worldwide. Most have been carried out vaginally (radical vaginal trachelectomy and laparoscopic pelvic node dissection). A smaller number have been performed abdominally. There have been over 300 pregnancies reported with 196 live births. There has been a 10% significant prematurity rate with birth prior to 32 weeks. There have been 31 recurrences (4%), and 16 deaths (2%). SUMMARY: Radical vaginal trachelectomy appears safe when performed in centres with appropriate experience of radical vaginal surgery and laparoscopic techniques. The impact of this new approach questions traditional teaching, thus preserving potential fertility in up until now impossible circumstances.

Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer.

PURPOSE: Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. METHODS: Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria. Lymph node sampling was performed in all patients. RESULTS: Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25%). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29%*, 99%, 56%, and 96%, and by USPIO criteria (reader 1/reader 2) were 93%/82%* (*P = .008/.004), 97%/97%, 61%/59%, and 100%/99%, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27%*, 94%, 60%, and 79%, and by USPIO criteria (reader 1/reader 2) were 100%/91%* (*P = .031/.06), 94%/87%, 82%/71%, and 100%/96%, respectively. The kappa statistic was 0.93. CONCLUSION: Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning.

MR imaging appearances of the female pelvis after trachelectomy.

Carcinoma of the cervix has a predilection for affecting young women. In recent years, surgical procedures that combine local radical surgery with maintenance of fertility potential in young women have been investigated. One such procedure is radical trachelectomy with pelvic lymphadenectomy, in which the corpus uteri is preserved, thus maintaining fertility potential. Magnetic resonance (MR) imaging is useful in the selection of suitable patients for trachelectomy and in postsurgical follow-up. The MR imaging findings in 45 patients who underwent trachelectomy at one institution between 1996 and 2004 were retrospectively reviewed. The uterovaginal anastomosis has variable appearances, with an end-to-end anastomotic appearance or a vaginal neofornix seen after surgery; suture artifacts can also occur. Possible changes affecting the vagina include diffuse wall thickening and hematomas, whereas lymphoceles and exaggeration of the pelvic venous plexuses can occur in the pelvis. Adenomyosis and endometriosis may be found incidentally in this patient group. Successful pregnancies after trachelectomy have been reported and should be treated as high-risk pregnancies. Knowledge of these MR imaging appearances will help radiologists distinguish between normal postsurgical variations, benign postsurgical changes, and recurrent disease in patients who have undergone trachelectomy.

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.

Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis.

Cervical carcinogenesis has well-defined stages of disease progression including three grades of pre-invasive lesions--cervical intraepithelial neoplasia grades 1-3 (CIN 1-3)--and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF-C and VEGF-D) involved in new lymphatic vessel formation may play a crucial role in this process. The present study has assessed the expression of VEGF-C and VEGF-D, and their receptor VEGFR-3, in 152 cervical lesions (33 CIN 1, 33 CIN 2, 37 CIN 3, and 49 squamous cell carcinomas) to determine whether expression of lymphangiogenic factors occurs prior to invasion. The presence of lymphatic vessels was determined using LYVE-1 and podoplanin staining, as well as double immunostaining for LYVE-1/CD34 and podoplanin/CD34. In situ hybridization was performed to determine VEGFR-3 mRNA expression. A significant positive correlation was found between VEGF-C, VEGF-D, and VEGFR-3 expression through the different stages of cervical carcinogenesis. Significant differences in protein expression for VEGF-C, VEGF-D, and VEGFR-3 were found between CIN 1-2 and CIN 3 (p<0.001 for all), but not between CIN 3 and cervical cancer. More than 50% of the CIN 3 lesions showed moderate to strong staining for VEGF-C and VEGF-D, whereas most of the early pre-cancerous lesions (CIN 1 and 2) were negative. In cervical cancer, similar observations to those in CIN 3 were found. VEGFR-3 mRNA expression was found in the cytoplasm of epithelial neoplastic cells and VEGFR3 protein expression was found in more than 50% of CIN 3 lesions and cervical cancers, compared with 15% in CIN 1 and 2. These findings suggest an autocrine growth stimulation pattern via VEGFR-3. Adjacent CIN 3 was present in nine cervical cancers and displayed strong expression for VEGF-C, VEGF-D, and VEGFR-3. These results suggest that in cervical carcinogenesis a switch to the lymphangiogenic phenotype may occur at the stage of CIN 3.

Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?

PURPOSE: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. PATIENTS AND METHODS: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. RESULTS: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients' original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). CONCLUSION: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.

Epithelial ovarian cancer metastasizing to the brain: a late manifestation of the disease with an increasing incidence.

PURPOSE: We present the Royal Marsden Hospital experience of cerebral metastases from primary epithelial ovarian carcinoma (EOC) over the last 20 years and examine the evidence for an increasing incidence of EOC metastasizing to this site. PATIENTS AND METHODS: A total of 3,690 women with EOC were seen at the Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed cerebral metastases. RESULTS: Median age at diagnosis of EOC was 52 years (range, 39 to 67). All patients received at least one line of platinum-based chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four lines. The median treatment interval between each line of chemotherapy was 12, 18, and 4 months. The median interval between diagnosis and CNS relapse was 46 months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to 1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the literature also suggests that the incidence of cerebral metastases from EOC has increased over time. CONCLUSION: CNS metastases in EOC are a rare and late manifestation of the disease, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses. An analysis of our data and the data from the literature suggests that the incidence of metastasis at this site in patients with EOC is increasing.

MR imaging of carcinoma of the vulva.

OBJECTIVE: The aim of this study was to describe the MR imaging features of cancer of the vulva and to determine the accuracy of MR imaging in staging the disease. MATERIALS AND METHODS: We reviewed the MR images of 22 patients (range, 21-85 years; median, 74 years) with cancer of the vulva who were treated at our institution between 1995 and 2000. Note was made of the primary tumor size, site, signal characteristics, enhancement, and local extension and of lymph node number, size, and position. The MR imaging features were correlated with surgical and pathologic findings. RESULTS: The tumors were isointense to muscle on T1-weighted images and showed intermediate-to-high signal intensity on T2-weighted scans. After IV gadolinium was administered to four patients, tumor enhancement was seen in two (50%). MR imaging correctly staged the primary site in 14 (70%) of the 20 patients. If superficial inguinal nodes 10 mm or greater in short-axis diameter are considered abnormal, then the sensitivity for detection of malignant nodes was 40% and the specificity, 97%. If deep inguinal nodes 8 mm or greater in short-axis diameter are considered abnormal, then the sensitivity for detection of malignant nodes was 50% and the specificity, 100%. CONCLUSION: MR imaging is highly specific for the detection of nodal involvement in patients with cancer of the vulva but correlates only moderately with clinicopathologic staging of the primary tumor.