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To investigate prognostic factors in patients with recurrent cervical cancer after treatment of early-stage disease in order to identify high-risk patients who might benefit from alternative treatment strategies.The authors retrospectively analyzed clinical and pathology data from 130 recurrent cervical cancer patients after surgical treatment for early-stage disease. Patients were compared with a recurrence-free control group matched for age, FIGO Stage, and adjuvant treatment. Univariate and multivariate Cox regression analyses were performed to determine prognostic factors for recurrence and survival.Of 889 patients, 130 (14.6%) developed recurrent disease after primary treatment for early-stage cervical cancer. Local or loco-regional metastasis was observed in 45%, distant metastasis in 31%, and combined pelvic and distant metastasis in 24%. Median survival after recurrence was 12 months (range 1-107 months). Median five-year survival was 96% in the control group and 29% in the recurrence group. Tumor size ≥ 40 mm and lymph node metastasis were independent unfavorable prognostic factors for overall survival (OS) and disease-free survival (DFS). The number of positive lymph nodes (≥ one) and bilateral occurrence of pelvic lymph node metastasis were associated with adverse clinical outcome.Tumor size ≥ 40 mm and lymph node metastasis were independent unfavorable prognostic factors in surgically treated, early-stage cervical cancer patients. The combination of these factors was particularly associated with recurrence. Future trials should focus on the role of alternative adjuvant treatment strategies in patients at high risk of recurrent disease (e.g., by chemotherapy, immunotherapy or combinations thereof).

Background and aims Survival after radical hysterectomy (RH) for early-stage cervical cancer is good. Hence quality of life (QOL) after treatment is an important issue. Nerve-sparing radical hysterectomy (NSRH) improves QOL by selectively sparing innervation of bladder, bowel and vagina, reducing therapy-induced morbidity. However, the oncological outcome and the functional outcome after NSRH are subjects of debate. We aim to present the best possible evidence available regarding both QOL and survival after NSRH in early-stage cervical cancer. Methods Systematic review and meta-analysis on studies comparing NSRH and RH. Results Forty-one studies were included, and 27 were used for the meta-analysis. There was no difference in 2-, 3- and 5-year overall survival: the risk ratios (RRs) were respectively 1.02 (95% CI 0.99–1.05, n = 879), 1.01 (95% CI 0.95–1.08, n = 1324) and 1.03 (95% CI 0.99–1.08, n = 638). No difference was found in 2-, 3- and 5-year disease-free survival: RR 1.01 (95% CI 0.95–1.05, n = 1175), 0.99 (95% CI 0.94–1.03, n = 1130) and 1.00 (95% CI 0.95–1.06, n = 933) respectively. Post-operative time to micturition was significantly shorter in the NSRH group: standardized mean difference (SMD) −0.84 (CI 95% −1.07 to −0.60). Conclusions NSRH can be considered safe and effective for early-stage cervical cancer since short- and long-term survival do not differ from those of conventional RH, while bladder function after NSRH is significantly less impaired.

Background: The CXC chemokine receptor (CXCR)7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients. Methods: CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed. Results: CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P=0.013), lymph node metastasis (P=0.001) and EGFR expression (P=0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR)=4.3, 95% confidence intervals (CI) 1.7–11.0, P=0.002), and strongly associated with disease-specific survival (HR=3.9, 95% CI 1.5–10.2, P=0.005). Conclusion: CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction.

Background: Early ovarian cancer patients are often incompletely staged during initial surgery.(1-3) This omission can have serious adverse consequences for the prognosis of patients as the completeness of surgical staging has been identified as an independent prognostic parameter for survival.(4,5) The reasons for the problem of inadequate staging of early ovarian cancer are largely unknown. We have analysed the data of a large randomised trial in early ovarian cancer in which detailed information of the surgical staging procedure was monitored.(5) Methods: Data of the EORTC Adjuvant ChemoTherapy In Ovarian Neoplasm (ACTION) Trial were used in which 448 early ovarian cancer patients were randomised between postoperative chemotherapy in one arm and observation following surgery in the other. In this trial strict criteria for surgical staging were advised but optimal, complete staging was performed in only 1/3 of patients. Staging characteristics of the incompletely staged patients were analysed and factors that could explain the failure to perform a complete staging were studied. Results: Sampling of para-aortic nodes was omitted in 78% of the incompletely staged patients, while 52% of these patients had no pelvic lymph node dissection. Taking blind biopsies from different peritoneal sites was not performed in more than 1/3 of the incompletely staged group. Omission of the staging steps ranged from 3% (infracolic omentectomy) to 55% (biopsy of the right hemi-diaphragm). A significant difference (p = 0.04) between the fraction of completely staged patients was found when comparing institutes who entered less than 5 patients (21%) versus those who included more than 20 patients (37%) in the trial. Conclusions: Even in a randomised trial in which comprehensive surgical staging was strongly advised in the study protocol the majority of patients (66%) were incompletely staged. Factors relating to a lack of surgical skills attributed most to the number of incompletely staged patients, but insufficient knowledge of the tumour behaviour and routes of spread of ovarian cancer also contributed substantially to this problem. Multicentre trials recruiting patients from many institutes with small volume contribution to the study, run the risk of inadequate adherence to the study protocol. (C) 2009 Elsevier Ltd. All rights reserved.

Background:An analysis was performed comparing survival of patients with clear cell carcinoma (CCC) to patients with serous adenocarcinoma (SAC) in early ovarian cancer. Furthermore, a literature search was done to clarify the clinical and histopathological features of clear cell tumors of the ovary.Methods:Between November 1990 and March 2000, 448 patients with ovarian cancer International Federation of Gynecology and Obstetrics stages I to IIa were enrolled in the European Organisation for Research and Treatment of Cancer-Adjuvant Chemotherapy in Ovarian Neoplasm Trial, a randomized study comparing adjuvant platinum-based chemotherapy to observation after surgical treatment in patients with early ovarian cancer.Results:Sixty-three patients (14.1%) with CCC were compared with 156 patients (34.8%) with serous tumors. A significant difference was found in the International Federation of Gynecology and Obstetrics stage Ic with capsule rupture, 28 (44.4%) of 63 patients with CCC and 29 (18.6%) of 156 patients with SAC (P < 0.001). Recurrences occurred in 25% of the patients, and this was similar in the CCC and SAC groups. No significant difference was found in overall survival between patients with CCC and patients with SAC in both treatment arms together. In the observation arm, the 5-year disease-free survival was 71% in the CCC group versus 61% in the SAC group, whereas in the chemotherapy arm, the 5-year disease-free survival was higher in the SAC group compared with the CCC group (78% vs 60%). Both differences were not statistically significant.Conclusions:The present study showed no worse prognosis in patients with CCC as compared with patients with serous carcinoma in early ovarian cancer.

Background This study was conducted to assess the accuracy and feasibility of diagnostic hysteroscopy in the evaluation of intrauterine abnormalities in women with abnormal uterine bleeding. Search strategy Electronic databases were searched from 1 January 1965 to 1 January 2006 without language selection. The medical subject heading (MeSH) and textwords for the following terms were used: hysteroscopy, diagnosis, histology, histopathology, hysterectomy, biopsy, sensitivity and specificity. Setting University Hospital. Selection criteria The inclusion criteria were report on accuracy of diagnostic hysteroscopy in women with abnormal uterine bleeding compared to histology collected with guided biopsy during hysteroscopy, operative hysteroscopy or hysterectomy. Data collection and analysis Electronic databases were searched for relevant studies and references were cross-checked. Validity was assessed and data were extracted independently by two authors. Heterogeneity was calculated and data were pooled. Subgroup analysis was performed according to validity criteria, study quality, menopausal state, time, setting and performance of the procedure. The pooled sensitivity, specificity, likelihood ratios, post-test probabilities and feasibility of diagnostic hysteroscopy on the prediction of uterine cavity abnormalities. Post-test probabilities were derived from the likelihood ratios and prevalence of intrauterine abnormalities among included studies. Feasibility included technical success rate and complication rate. Main results One population of homogeneous data could be identified, consisting of patients with postmenopausal bleeding. In this subgroup the positive and negative likelihood ratios were 7.9 (95% CI 4.79–13.10) and 0.04 (95% CI 0.02–0.09), raising the pre-test probability from 0.61 to a post-test probability of 0.93 (95% CI 0.88–0.95) for positive results and reducing it to 0.06 (95% CI 0.03–0.13) for negative results. The pooled likelihood ratios of all studies included, calculated with the random effects model, were 6.5 (95% CI 4.1–10.4) and 0.08 (95% CI 0.07–0.10), changing the pre-test probability of 0.46 to post-test probabilities of 0.85 (95% CI 0.78–0.90) and 0.07 (0.06–0.08) for positive and negative results respectively. Subgroup analyses gave similar results. The overall success rate of diagnostic hysteroscopy was estimated at 96.9% (SD 5.2%, range 83–100%). Conclusions This systematic review and meta-analysis shows that diagnostic hysteroscopy is both accurate and feasible in the diagnosis of intrauterine abnormalities.

Drainage, following radical hysterectomy and pelvic lymph node dissection to prevent postoperative lymphocyst formation and surgical morbidity, is controversial. To study the clinical significance of drainage, 253 patients were registered and 234 patients were randomised into two arms. In one arm (n=117) postoperative drainage was performed, in the other arm (n=117) no drains were inserted. In both arms closure of the peritoneum of the operating field was omitted. The main exclusion criteria were blood loss of more than 3000 ml during surgery or persistent oozing at the end of the operation. Clinical and ultrasound or CT-scan evaluation was done at one and 12 months postoperatively. The median follow-up amounted to 13.3 months. No difference in the incidence of postoperative lymphocyst formation or postoperative complications was found between the two study arms. The late (12 months) incidence of symptomatic lymphocysts was 3.4% (drains: 5.9%; no drains: 0.9%). The difference showed a p-value of 0.06 in Fisher's Exact test. The operating time was related to the occurrence of postoperative lymphocyst formation. It was concluded that drains can be safely omitted following radical hysterectomy and pelvic node dissection without pelvic reperitonisation in patients without excessive bleeding during or oozing at the end of surgery.

In view of the current emphasis on increasing patient safety and quality control in laparoscopic surgery, there is a growing need to improve laparoscopic training. This study was conducted to investigate if and when residents reached performance standards for basic laparoscopic skills on a boxtrainer and to analyze the current state of implementation of laparoscopic simulators in a gynecological residency curriculum. Residents across all 6 years of residency (postgraduate year [PGY] 1–6) were tested once on our boxtrainer by performing five inanimate tasks (pipe cleaner, rubber band, beads, cutting circle, intracorporeal knot tying). A sumscore for the five tasks was calculated for each participant (sum of all scores). Scores were calculated by adding completion time and penalty points, thus rewarding both speed and precision. These data were compared with scores of laparoscopic experts, which were set as performance standards. Of the participants, 111 were residents (7 PGY1, 27 PGY2, 29 PGY3, 28 PGY4, 14 PGY5, 6 PGY6) and 8 were experts. At the end of residency, PGY6 residents reached the performance standard for all tasks except intracorporeal knot tying. It was not until PGY5 that residents reached the performance standard for the pipe cleaner task; PGY1, for rubber band; PGY5, for beads; PGY4, for circle cutting; and PGY6, for sumscore. Throughout residency PGY6 had a mean total of only 3.6 h of simulator training experience. No correlation was found between this previous voluntary simulator training experience and performance on our boxtrainer during this study (sumscore), and between previous voluntary simulator training and total laparoscopic procedures performed. In a combined multivariate analysis, sumscore performance remained significantly associated with the number of laparoscopic procedures performed by residents when they were working as as a primary surgeon (p = 0.002), and not with the cumulative hours of simulator training during residency prior to participating in this study (p = 0.15). In a current Dutch gynecological residency curriculum, residents do not reach all performance standards for basic laparoscopic skills on the boxtrainer. We conclude that the voluntary simulator training program has a substantial risk to fail and that the implementation of the laparoscopic skills simulator in the current residency curriculum is in its infancy.

Background. In this study the MIB-1 immunostaining pattern as an index of cellular proliferation was analyzed in smears diagnosed as borderline dyskaryosis in order to establish whether the combination of human papillomavirus testing and MIB-1 staining could resolve equivocal cytology. Methods. Conventional Pap smears of 108 women diagnosed as borderline dyskaryosis were stained with MIB-1 and the proliferation index was assessed. These women were evaluated by colposcopy, histological sampling, and human papillomavirus, semi-quantitative evaluated by hybrid Capture II test. Results. All 64 human papillomavirus- and MIB-1-negative women had no underlying high-grade cervical intraepithelial neoplasia or cervical cancer. Forty of the 104 women with normal histology or cervical intraepithelial neoplasia I were positive for human papillomavirus, compared to only one positive MIB-1 test (i.e. proliferation index of more than 35%). Conclusions. Adding a MIB-1-test in human papillomavirus-positive women with equivocal cytology might reduce the number of colposcopies needed to predict ≥ cervical intraepithelial neoplasia II. With this approach only four instead of 43 human papillomavirus-positive women would have been referred for colposcopy.

The objective of this study was to evaluate the problems with miction, defecation, and sexuality after a radical hysterectomy with or without adjuvant radiotherapy for the treatment of cervical cancer stage I–IIA. This study included an observational longitudinal study of self-reported bladder, defecation, and sexual problems with a baseline score. Ninety-four women were included in the study. An age-matched control group consisted of 224 women. The patients showed significantly more negative effects on sexual function compared with both the controls and their situation before the treatment throughout 24 months of follow-up. The problems included less lubrication, a narrow and short vagina, senseless areas around the labia, dyspareunia, and sexual dissatisfaction. Up to 12 months after the treatment, the patients complained significantly more of little or no urge to urinate and diarrhea as compared with the controls. Adjuvant radiotherapy did not increase the risk of bladder dysfunction, colorectal motility disorders, and sexual functions. We conclude that a radical hysterectomy for the treatment of early-stage cervical carcinoma is associated with adverse effects mainly on sexual functioning.

The objective of this study was to assess the role of postoperative radiotherapy (RT) in early-stage cervical carcinoma with risk factors other than positive nodes, parametrial invasion, or positive margins and to compare outcomes using the Leiden University Medical Center (LUMC) modification of the Gynecologic Oncology Group (GOG) system with the GOG prognostic scoring system itself. Between January 1984 and April 2005, 402 patients with early-stage cervical cancer underwent radical hysterectomy. A total of 51 patients (13%) had two of the three risk factors and had pathologic tumor size (≥40 mm), invasion (≥15 mm), and capillary lymphatic space involvement, and were identified as the so-called high-risk (HR). We compared 34 patients who received RT based on the LUMC risk profile (67%) with 17 who did not (33%). The GOG score was calculated as well. We compared the GOG scores within the LUMC risk groups: HR+ (two out of three risk factors) and HR− (less than two out of three risk factors). Differences in 5-year cancer-specific survival (CSS) and 5-year disease-free survival (DFS) between the HR group treated with RT (86%, 85%) and without RT (57%; 43%) were statistically significant. The LUMC criteria did not significantly differ from the GOG risk profile, concerning recurrence, CSS, and DFS. HR patients benefit from adjuvant RT. The LUMC modification of the GOG system seems to be simpler and has a slightly higher threshold for the indication for RT but without a difference in outcome.

OBJECTIVE: The aim of the study was to evaluate the prognostic significance of tumor geography, defined as exophytic or barrel-shaped growth, in bulky (>4 cm) cervical cancer. METHODS: Four hundred women with cervical cancer, treated by primary radical hysterectomy between January 1984 and November 2000, were followed in a prospective cohort study. Clinical and pathology data were stored in a databank and the clinical protocol was unchanged during the study except for the amendment of additional indications of postoperative radiation in 1997. The assessment of tumor geography was based on pelvic examination at the time of tumor staging or radical hysterectomy or from the pathology report. Survival probabilities were calculated by the Kaplan-Meier method and compared with the log-rank test. RESULTS: The mean age of the patients was 45 years and the mean follow-up duration 48 months. Tumors were of squamous cell type in 291 patients (73%). Lymph node metastases were present in 91 patients (24%) and postoperative radiation was given in 179 patients (45%). In 291 patients, tumor diameter was

Objective The potential contribution of psychological and anatomical changes to sexual dysfunction following hysterectomy is not clear. Radical hysterectomy for cervical cancer causes surgical damage to the autonomic nerves which are responsible for the increased vaginal blood flow during sexual arousal. Simple hysterectomy causes more limited nerve disruption. Photoplethysmographic assessment of vaginal pulse amplitude objectively measures vaginal blood flow during sexual arousal. We hypothesised that damage of the autonomic nerves results in a disrupted vaginal blood flow response during sexual stimulation. Design Between-groups comparison of vaginal pulse amplitude. Setting University hospital. Sample Twelve women with a history of radical hysterectomy, 12 women with a history of simple abdomonal hysterectomy and 17 aged-matched controls. Methods Photoplethysmographic assessment of vaginal pulse amplitude during sexual stimulation by erotic films. Self-reported ratings of subjective sexual arousal were collected after each erotic stimulus condition. Main outcome measure Maximum vaginal pulse amplitude. Results Maximum vaginal pulse amplitude differed between the three groups (P= 0.043). Women with a history of radical hysterectomy had a lower response than controls (P= 0.015). Women in the radical hysterectomy group and controls reported an equally strong subjective arousal. Women with a history of simple hysterectomy showed an intermediate maximum vaginal pulse amplitude. Conclusions Radical hysterectomy seems associated with a disturbed vaginal blood flow response during sexual arousal. This cannot be explained solely by uteric extirpation, since it was not observed to the same extent after simple hysterectomy, but might be related to a denervation of the vagina which increases with increasing radicality of surgery.

In 1962, the European Organisation for Research and Treatment of Cancer (EORTC) was founded, and in the course of the years it developed into the leading European organisation in cancer research. Currently, the EORTC is organised into (Pre-)Clinical Groups and Task Forces consisting of scientists and/or clinicians. One of these groups with a specific area of interest in cancer research is the Gynaecological Cancer Group (GCG). The EORTC offers fellowship programmes to physicians and scientists from all over the world to create a possibility to be temporarily linked to an EORTC group or a specific research project. Over the past decade, 76 research fellowships have been appointed at the EORTC Data Center. This paper shows an overview of the activities of one EORTC/GCG medical fellow.

Objective. The aim of this study was to evaluate the predictive value of pretherapeutic magnetic resonance imaging (MRI)-based measurements of tumor diameter and volume with regard to recurrent disease. Methods. NM on 0.5- or 1.5-T scanners was performed in 126 consecutive women with invasive carcinoma of the uterine cervix. Initial tumor diameter and volume were determined on T-2-weighted images; volume was calculated by the standard technique of multiplying the sum of the areas by the slice thickness. Patients were treated by radical surgery, radiotherapy, or a combined approach based on clinical International Federation of Gynecology and Obstetrics (FIGO) stage and individual patient criteria. Clinical data (patient age and FIGO stage), MRI-derived tumor dimensions (diameter and volume), and histological findings (tumor invasion depth and lymph-node involvement) were associated and linked to patient outcome. Results. MRI-based tumor diameter correlated strongly with histological tumor invasion depth and lymph-node status (P < 0.01 and P = 0.01) while tumor volume on MRI was significantly associated only with tumor invasion depth into adjacent tissues (P < 0.01). Univariate analysis demonstrated graphically that MRI-derived tumor diameter and volume and clinical FIGO stage are associated with progression-free survival. Correlation analysis showed a strong association between MRI-derived tumor diameter and volume on MRI (r = 68%, P < 0.01) and also demonstrated a correlation between tumor diameter on MRI and FIGO stage Ib (Ib1 versus Ib2) cervical tumors (r = 46.7%, P < 0.01). Conclusion. Tumor diameter and volume, determined by pretreatment MRI examinations, predict progression-free survival for patients with invasive cervical carcinoma. This study demonstrates the value of MRI as an adjunct to clinical evaluation of invasive cervical cancer, providing more complete assessment of morphological risk factors important in patient prognosis and treatment planning. (C) 2001 Academic Press.

Objective To study the development of surgical performance of an unchanging surgical team over 13 years. Design Prospective, observational study. Setting A university hospital, The Netherlands. Participants Three hundred and eight women who underwent surgical treatment for early cervical cancer. Interventions Radical hysterectomy and pelvic lymphadenectomy between 1 January 1984 and 31 December 1996. Results The surgical procedure and indication for treatment remained unchanged during the study period. This applied also to the surgical team. The women's age increased significantly during the study years, as was the case with the number of nodes removed. The depth of infiltration by the tumour increased steadily throughout the study, but this failed to reach statistical significance. The distribution of FIGO stages, percentage of positive lymph nodes, radicality of the surgical margins and post-operative morbidity remained the same. Overall, the five year survival rate was 83%; for women with negative nodes 91%, and for women with positive nodes 53%. Survival tended to improve during the course of the study, but this was not statistically significant. Blood loss during surgery decreased consistently during the whole study period, from a mean of 1515 mL at the beginning of the study to a mean of 1071 mL at the end (P < 0.0001). The operating time also diminished significantly by 8 minutes per year (P < 0.0001). In 1985 the average operating time was 270 minutes, compared with 187 minutes in 1996. Conclusions These findings indicate that it takes a long time to acquire skill in the surgical treatment of early cervical cancer. Centralisation of relatively infrequent operations for cancer should be encouraged.

Objective. The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer. Methods. Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis. Results. Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size ( P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status ( P = 0.0014), tumor size ( P = 0.004), and parametrial involvement ( P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size ( P = 0.0001) and TPA level ( P = 0.026) were independent risk factors for disease-free interval, whereas tumor size ( P = 0.0001) and parametrial involvement ( P = 0.0002) were risk factors for survival. Conclusions. Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer.

The Piver classification of radical hysterectomy for the treatment of cervical cancer is outdated and misused. The Surgery Committee of the Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer (EORTC) produced, approved, and adopted a revised classification. It is hoped that at least within the EORTC participating centers, a standardization of procedures is achieved. The clinical indications of the new classification are discussed

Objectives. Pelvic lymph node dissection as part of the staging surgery for cervical carcinoma interrupts the afferent lymphatics, so the lymph drains retroperitoneally. New surgical techniques designed to leave the peritoneum open after the retroperitoneal dissection, in particular the application of a pedicled omentoplasty along the dissection route, have been advocated to prevent the formation of lymphocysts and lymphedema. We investigated the possible benefit of pedicled omentoplasty in preventing lymphocysts and lymphedema following pelvic lymph node dissection. Methods. In this pilot study with historical controls we compared the formation of lymphocysts and lymphedema following two different surgical techniques for pelvic node dissection: group I (historical controls), in which the dorsal peritoneum was left open, and group II, in which the dorsal peritoneum was left open with application of a pedicled omentoplasty. In these two groups of gynecologic patients, we compared the lymph flow patterns and the occurrence of lymphedema following systemic pelvic lymphadenectomy. The two groups were of comparable clinical status and consisted of 12 (group I) and 10 (group II) patients. Lymphocysts, if any, were detected by CT scan, the lymph flow patterns were visualized by dynamic lymphscintography, and lymphedema was visualized by physical examination and magnetic resonance imaging of the groin and the upper leg. Results. In both groups a distinct intraperitoneal absorption of the lymph fluid was observed. Pedicled omentoplasty seemed to facilitate the absorption or transport of lymph fluid, resulting in less lymphedema in the upper leg. Conclusion. It appeared that leaving the dorsal peritoneum open to give the lymph stream the opportunity to pour into the abdominal cavity is important in preventing lymphocysts and lymphedema. The dynamic lymphscintigraphy described in this paper showed that the intraabdominal lymph flow is absorbed by the peritoneum and even more quickly by the pedicled omentum.

Background and purpose : The aim of this study was to assess the results of treatment (surgery alone or surgery and postoperative radiotherapy) for early-stage cervical carcinoma and to determine the morbidity associated with adjuvant radiotherapy. A subset of these patients ( n =10) was irradiated postoperatively for tumor related negative prognostic factors only and this retrospective analysis was also performed to determine if this decision was right and if the selection for this treatment was based on the right criteria. Material and methods: From 1984 to 1996, 233 women underwent radical hysterectomy as primary treatment of stage I or IIA cervical carcinoma. One hundred and fifty-six patients were treated with surgery alone (67%) and 77 patients (33%) received adjuvant radiotherapy for a, tumor related negative prognostic factors: the combinaton CLS⊕, tumor size ≥40 mm and poor differentiation grade or the combination tumor size ≥40 mm and depth of invasion ≥15 mm ( n =10), or b, positive surgical margins ( n =17), and/or c. lymphnode metastases ( n =42) and/ or d. parametrial involvement ( n =6). Results : For the entire group the most important prognostic factor for survival and disease free survival was node positivity. Additional factors were depth of invasion and positive surgical margins. Thirty-five patients recurred of which 12 after surgery alone. In all these cases the relapse was in the pelvis (100%). Of the 23 recurrences after surgery and adjuvant radiotherapy 13 were seen in the pelvis (56%) ( P =0.003). All patients with negative prognostic factors and N 0, received adjuvant radiotherapy ( n =10) and none of these patients recurred. The incidence of severe gastrointestinal radiation related side effects was low (2%). The incidence of lymphedema of the leg was 11% which was similar in the surgery alone group. Conclusions : The relatively low percentage of radiation related side effects together with 0% recurrence in a subgroup of node negative patients with high risk of recurrence, and a relatively low percentage of recurrence in the surgery alone group lead us to the conclusion that postoperative radiotherapy in special subsets of node negative patients is justified.

to investigate whether morphologic characteristics determined by magnetic resonance imaging (MRI) can discriminate between bulky cervical tumours with a favourable or worse prognosis.MRI examinations were performed in 24 patients with cervical cancer Stageor= 1B2. The ratio between tumour width and length (barrel index: BI) and the presence of intrauterine fluid retention were related to survival in a multivariate regression analysis.BI and intracavital fluid were predictors of survival, independent from tumour diameter and other known important factors for survival. A cut-off value of 1.40 for the BI proved to be the best prognostic factor with respect to recurrence and death: the hazard ratios of BI1.40 as compared to BIor= 1.40 were 18.9 (95% CI 2.8 to 125.6) for recurrent disease and 16.4 (95% CI 2.9 to 93.9) for death by cervical cancer. The hazard ratios of intracavital fluid retention were 73.6 (95% CI 5.3 to 1,016.4) and 48.1 (95% CI 4.7 to 491.6) for recurrence and death, respectively.The morphologic characteristic BI and the presence or absence of intracavital fluid as determined by MRI might have predictive value for survival in patients with bulky cervical tumours.

Background: We performed a cross-sectional study in Indonesia to evaluate the performance of a single-visit approach of cervical cancer screening, using visual inspection with acetic acid (VIA), histology and cryotherapy in low-resource settings. Methods: Women having limited access to health-care facilities were screened by trained doctors using VIA. If the test was positive, biopsies were taken and when eligible, women were directly treated with cryotherapy. Follow-up was performed with VIA and cytology after 6 months. When cervical cancer was suspected or diagnosed, women were referred. The positivity rate, positive predictive value (PPV) and approximate specificity of the VIA test were calculated. The detection rate for cervical lesions was given. Results: Screening results were completed in 22 040 women, of whom 92.7% had never been screened. Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The approximate specificity was 98.1%, and the detection rate for CIN I or greater was 2.6%. Conclusion: The single-visit approach cervical cancer screening performed well, showing See and Treat is a promising way to reduce cervical cancer in Indonesia.

To evaluate the possibility to give a prediction of the future (disease-free) survival, given the fact that a patient with a history of early-stage cervical cancer has been disease free for a specific period after treatment. Between January 1984 and April 2005, 615 patients with cervical cancer stages I–IIA underwent radical hysterectomy with or without adjuvant radiotherapy. The Kaplan–Meier method was used to detect statistical significance and multistate risk models to estimate the influence of covariates and to generate predicted survival curves by simulation. Simulations were done for patients with positive lymph nodes (n= 123), patients with negative lymph nodes (n= 492), and 4 hypothetical patients. The 5-year cancer-specific survival and disease-free survival of the entire group was 84% and 76%, respectively. The probability of death of the two lymph node groups and the four hypothetical patients was demonstrated in predicted cumulative probability plots. It is possible with multistate risk models to give a detailed prediction of the future (disease-free) survival, given the fact that a patient has been disease free for a specific period after treatment. This possibility is an important step forward to improve the quality of cancer care.

Aims To determine if the number of removed lymph nodes in radical hysterectomy with lymphadenectomy (RHL) influences survival of patients with early stage cervical cancer and to analyze the relation of different factors like patient age, tumour size and infiltration depth with the number of nodes examined in node-negative early stage cervical cancer patients. Methods Of consecutive patients, who underwent RHL between January 1984 and April 2005, 331 had negative nodes (group A) without adjuvant therapy and 136 had positive nodes (group B). The Kaplan–Meier method and Cox regression model were used to detect statistical significance. Factors associated with excision of nodes were confirmed with linear regression models. Results The median number of removed nodes was 19 and 18 for group A and group B, respectively. There was no significant relationship between the number of removed nodes and the cancer specific survival (CSS) or disease free survival (DSF) for patients of group A ( p =0.625 and p =0.877, respectively). The number of removed nodes in group B was not significantly associated with the CSS ( p =0.084) but it was for the DSF ( p =0.014). Factors like patient age, tumour size and infiltration depth were not associated with the number of nodes. Conclusions No relation was found between the number of negative nodes examined after RHL for the treatment of early stage cervical cancer and CSS or DFS. However, a higher amount of removed lymph nodes leaded to a better DFS for patients with positive nodes. It is suggested that patients with positive nodes benefit from a complete pelvic lymphadenectomy and a sufficient yield of removed nodes.

1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome.In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women.Absence or clearance of HPV showed significantly more regression to normal cytology than persistent or newly acquired infected women, odds ratio 27 (95% confidence interval; 7-103). The viral load of the HPV test at enrollment was not correlated with the follow-up cytological outcome (Spearman correlation coefficient 0.2, p = 0.2). A marked association between viral load and histological outcome at enrollment was shown (Spearman correlation coefficient 0.43, p0.0001).Absence or clearance of HPV can predict regression to normal cytology. Viral load at enrollment cannot predict cytological regression. There was a marked association between viral load and the underlying CIN at enrollment. However, there was large overlapping of viral loads among the grades of CIN. Therefore, viral load is not a useful parameter to predict high-grade lesions in women with ASCUS/AGUS cytology.

The focus of this study was to document postoperative complications after vulvectomy and inguinofemoral lymphadenectomy using separate incisions. Data from 172 consecutive patients with newly diagnosed carcinoma of the vulva were studied. One hundred and one patients primarily treated with modified radical vulvectomy and complete inguinofemoral lymphadenectomy using separate groin incisions (n = 187) were included in this study. One or more complications were documented in 77 of the 101 (76%) patients. Complications after groin dissection were observed in 66% of the patients. The main complications were wound breakdown (17%) and/or infection (39%) of the groin, lymphocyst formation (40%), and lymphedema (28%). In 98 of 187 (52%) groin dissections, one or more complications were documented. The presence of lymph node metastases, postoperative radiation, age older than 65 years, and removal of the vena saphena magna were not significant risk factors for the occurrence of complications. The occurrence of early complications after groin dissection was significantly related to the late-complication lymphedema (P = 0.002). Our results confirm relatively high rates of wound breakdown, infection, lymphocyst formation, and lymphedema even with separate groin incisions. The occurrence of early complications was related to lymphedema. No other risk factors could be identified.

The completeness and associated morbidity of surgical staging in 86 patients with early ovarian carcinoma were analyzed. According to strict criteria for completeness of the procedure established before the onset of the study, surgical staging after one or two laparotomies was complete in only 53% of cases. Initial staging in a peripheral hospital was complete in only 15% of patients. Intraoperative complications occurred in between 8 and 15% of patients and included injury of the vena cava (5), small bowel injury (2), myocardial infarction (1), transection of the ureter (1), and splenic rupture (1). The most frequently omitted staging steps were biopsy of the paracolic gutter, biopsy of the pelvic peritoneum, and sampling of retroperitoneal lymph nodes. Reasons for incomplete surgical staging were divided into factors associated with increased risk or difficulty of the procedure and lack of knowledge of the sites at risk for ovarian cancer metastases. It was found that both phenomena should be held responsible to the same extent for the large number of incomplete surgical staging procedures. The conclusion was made that either gynecologists should be better educated in the staging of ovarian cancer or a more efficient patient referral policy should be considered.

Objective. To investigate the prevalence of human papillomavirus (HPV) infection in various vulvar lesions. Methods. HPV infection using consensus primer-PCR was studied in 66 patients with vulvar carcinoma and in the synchronous epithelial lesions. Results. HPV infection was present in 13/66 carcinoma, in 1/33 VIN I, in 3/11 VIN II, in 8/16 VIN III, in 2/30 lichen sclerosus, in 1/37 squamous cell hyperplasia, and in 2/55 normal skin specimens. Normal skin from healthy controls showed HPV-negative specimens only. Patients with HPV-positive carcinomas were younger, presented in lower stages, and had high-grade VIN more often than those with HPV-negative carcinomas. Conclusions. In sum we found that all types of epithelial changes synchronous with carcinoma of the vulva showed HPV infection, indicating that they all might have malignant potential.

One hundred ninety-one patients with advanced epithelial ovarian carcinoma were treated with either a combination of doxorubicin and a five-day course of cisplatin alternating with cyclophosphamide and hexamethylmelamine orally for 14 days (CHAP-5) or cyclophosphamide and cisplatin both administered intravenously (IV) on a single day at 3-week intervals (CP). At a median follow-up time of 45 months, treatment with each of these combinations resulted in the same remission rates (80% and 74%, respectively) and exactly the same progression-free survival and overall survival (median, 26 months). Despite adequate hydration, more renal toxicity was encountered in the CP-treated patients than in those who received CHAP-5. Disabling neurotoxicity and severe myelosuppression were encountered more frequently in the patients treated with CHAP-5. Because the toxicity was lower and CP treatment required shorter hospitalization, the single-day regimen was considered preferable for future use. The Karnofsky index was the only independent predictor for response, whereas both this index and the size of residual tumor before chemotherapy were predictive of survival. After correcting for other prognostic factors, it was determined that tumor size associated with improved survival was less than 1 cm. The site of metastases in International Federation of Gynecology and Obstetrics (FIGO) stage IV patients did not influence survival within this category. The results of this study confirm our previous findings that patients with microscopic remnants at second-look have a survival similar to that of patients who are histopathologically free of disease. This makes the significance of so-called pathologically confirmed complete remission questionable. The survival benefit of debulking surgery performed during chemotherapy seems only minimal for patients in whom debulking has already been attempted before treatment. Like others, we have found the CP regimen to have a good therapeutic index.