Impact of hospital type and treatment on long-term survival among patients with FIGO Stage IIIC epithelial ovarian cancer: follow-up through two recurrences and three treatment lines in search for predictors for survival.

The purpose of this study was to investigate the impact of hospital type determined at primary treatment and find possible predictors of survival in a cohort of patients with advanced epithelial ovarian cancer (EOC) who recurred twice and received three lines of treatment during eight-year follow-up. Using the Norwegian Cancer Registry, the authors identified 174 women with FIGO Stage IIIC EOC diagnosed in 2002. First-line treatment consisted of up-front debulking surgery and chemotherapy, received in either a teaching hospital (TH, n = 84) or a non-teaching hospital (NTH, n = 90). After recurrence all patients in Norway are equally consulted at TH. Survival determined for three time intervals (TI): TI-1, from end date of first-line treatment to first recurrence or death, TI-2, from beginning of second-line treatment until second recurrence or death, and TI-3, from beginning of third-line treatment to death or end of follow-up. Extensive surgery carried out in TH followed by at least six cycles of platinol-taxan chemotherapy resulted in longer survival in the TH group during TI-1. Altogether, the majority of those who receive treatment for recurrences were primary better debulked with following platinol-taxane chemotherapy. Survival in TI-2 was influenced by platinol-sensitivity. During TI-3 the majority (96%) had good performance status and their mean age at primary diagnosis at either hospital type was 57 years. Extensive primary surgery at TH, platinol sensitivity, age, and performance status were predictors of survival in this cohort.

Fertility and gonadal function after adjuvant therapy in women diagnosed with a malignant ovarian germ cell tumor (MOGCT) during the "cisplatin era".

PURPOSE: By self-report and serum levels of anti-Mullerian hormone (AMH) this study aims to assess post-treatment fertility after modern treatment of women with malignant ovarian germ cell tumors (MOGCT). PATIENTS AND METHODS: In 2013 a questionnaire-based survey was performed in 61 MOGCT patients diagnosed at age <40years from 1980-2009. Forty-nine of them also attended the out-patient clinic. The event of first post-treatment pregnancy ("fertility") was documented as cumulative estimates for all 61 patients and within each of 4 treatment groups: Group 1: Surgery only (n=10); Group 2: ≤3cycles of cisplatin-based chemotherapy (CBCT) (n=20); Group 3: >3cycles of CBCT (n=15) and Group 4: other adjuvant treatment (n=16). AMH was determined in 22 women <40years at survey. Statistics were based on Kaplan Meier procedure, log-rank test and a significance level p<0.05. RESULTS: At least one post-treatment pregnancy was reported by 34 of 39 MOGCT survivors who attempted motherhood after treatment. The 15-year cumulative post-treatment fertility estimate was 28% (95% CI: 26-30) for all 61 survivors and was significantly higher in patients treated with 3 or fewer cycles of CBCT (53% [95% CI: 50-55]) than those treated with more than 3cycles (20% [95% CI: 17-22]) (P=0.03). Of 22 AMH levels, two were <3pmol/l, with one women being pregnant at survey. CONCLUSION: After fertility-sparing surgery and modern cisplatin-based chemotherapy, fertility is preserved in most MOGCT survivors though dependent on the number of cycles. AMH's role as a biomarker of gonadal function seems promising but requires further research.

Prognostic factors in malignant ovarian germ cell tumours (The Surveillance, Epidemiology and End Results experience 1978-2010).

PURPOSE: To evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil status, residency) on cause specific survival (CSS) in patients with malignant ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors. PATIENTS AND METHODS: 2541 patients with MOGCT, reported to the Surveillance, Epidemiology and End Results programme (1978-2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan-Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI). RESULTS: Five-year CSS was 97% (95% CI, 96-98%), and 92% (95% CI, 91-93%), respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis and presence of metastases were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR), 1.59; 95% CI, 1.11-2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83-3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95% CI, 1.17-5.25). Second cancer was diagnosed in 10% of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group (p=.002). CONCLUSIONS: Increased attention should be directed towards the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.

Malignant ovarian germ cell tumors: presentation, survival and second cancer in a population based Norwegian cohort (1953-2009).

PURPOSE: To quantify and compare survival in women with malignant ovarian germ cell tumors (MOGCTs) in Norway before and after the introduction of cisplatin-based chemotherapy (around 1980), and to explore the association between different types of treatment and the development of a second cancer. PATIENTS AND METHODS: We identified 351 patients diagnosed with MOGCTs from 1953 to 2009 in the Cancer Registry of Norway. Ovarian cancer-specific survival was calculated separately for patients diagnosed before and after 1980. Patients were divided into subgroups by histological subtype (pure dysgerminoma, malignant teratoma, other MOGCTs) and extent of disease (localized and metastatic). We estimated the cumulative incidence of a second cancer in 10-year MOGCT survivors. Kaplan-Meier estimates were used, and p<0.05 was considered significant. RESULTS: 20-Year ovarian cancer-specific survival increased from 59% (95% CI 51% to 66%) before 1980 to 88% (95% CI 83%-93%) thereafter. Significant improvement was observed in all subgroups. No second cancer was diagnosed in any of 31 10-year MOGCT survivors treated with surgery only; second cancer was diagnosed in 23 of 139 patients who underwent cytotoxic treatment (98 radiotherapy ± chemotherapy, 41 chemotherapy only; p=0.08). Patients aged >50 years had a significantly poorer ovarian cancer-specific survival than younger patients (HR=5.98, 95% CI 3.39-10.57) after adjustment for histological subtype and stage at presentation. Our results favor the treatment of patients with metastatic MOGCTs at large cancer centers. CONCLUSION: Today women with MOGCTs have an excellent prognosis if treated according to modern therapeutic principles.

Prognostic importance of DNA ploidy and DNA index in stage I and II endometrioid adenocarcinoma of the endometrium.

BACKGROUND: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. PATIENTS AND METHODS: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤ 1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤ 1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤ 1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. CONCLUSIONS: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.

Flow cytometric measurement of cellular FLICE-inhibitory protein (c-FLIP) in ovarian carcinoma effusions.

OBJECTIVE: The objective of this study was to establish a flow cytometry assay for measuring c-FLIP in serous effusions. In addition, we studied the clinical relevance in ovarian carcinoma effusions of this inhibitor protein in the death receptor signalling pathway of apoptosis. METHODS: Two c-FLIP antibodies were tested using Western blotting and the best performing one was used for titration of c-FLIP expression in a panel of five cell lines, consisting of ovarian carcinoma, breast carcinoma and malignant mesothelioma. The concentration that provided the best signal-to-noise ratio was used for comparison of the performance of three fixation and permeabilization protocols. The best performing protocol was chosen for analysis of 69 ovarian carcinoma effusions. c-FLIP expression was analysed for association with clinicopathological parameters and survival. RESULTS: Rabbit polyclonal c-FLIP by Abcam and the IntraStain kit by Dako performed best. c-FLIP expression was detected in tumour cells in all 69 effusions (expression range 21-100%, median = 80%). No association was found between c-FLIP expression and clinicopathological parameters, including chemoresponse and survival. However, an inverse correlation was found between c-FLIP levels and expression of the previously studied apoptosis marker cleaved caspase-3 (P = 0.029). CONCLUSIONS: An assay for measuring c-FLIP in cytology specimens is presented. c-FLIP is frequently expressed in ovarian carcinoma effusions, but its expression appears to be unrelated to disease aggressiveness.

The role of surgery in the second relapse of epithelial ovarian cancer. Selection criteria, morbidity and survival outcome.

BACKGROUND: The aim of this study was to investigate the benefit of cytoreductive surgery (CS) and palliative surgery (PS) because of bowel obstruction in the second relapse (SR) in epithelial ovarian cancer. METHODS: A retrospective population-based study on recorded information from 490 consecutive patients treated at the Norwegian Radium Hospital during 1985-2001 for their SR. In all, 80 had surgery, 28 and 52 of which had their tertiary surgery (TS) and secondary surgery (SS), respectively and 410 were treated with chemotherapy or other therapy. RESULTS: Median survival time (MST) was nine months for the last group. Complete optimal cytoreduction (COC) was achieved in 56% of the patients operated with CS. At SS and TS 33% and 38%, respectively, achieved COC. MST was 46 versus seven months for 0 versus > 2 cm residual disease. MST for the CS and PS was 31 versus five months, respectively. Twenty-eight percent with CS experienced complications versus 42% with PS including two deaths. On univariate analysis initial stage, residual tumor at first relapse, residual tumor at SR, treatment-free interval from primary treatment to first relapse (TFI 0-1), type of chemotherapy at SR, WHO performance status, ascites, elevated CA 125 values, number of lesions, localization of tumor and tumor size were found to be significant prognostic factors for survival in the surgery group. CONCLUSIONS: The combination of COC, TFI 0-1 > or = 24 months, CA 125 < or = 35, < or = 3 tumor lesions and WHO 1 performance criteria identifies a group of patients with the best overall survival in SR.

Predictors of survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery based on the pooled analysis of an international collaborative cohort.

BACKGROUND: This study aims to identify prognostic factors and to develop a risk model predicting survival in patients undergoing secondary cytoreductive surgery (SCR) for recurrent epithelial ovarian cancer. METHODS: Individual data of 1100 patients with recurrent ovarian cancer of a progression-free interval at least 6 months who underwent SCR were pooled analysed. A simplified scoring system for each independent prognostic factor was developed according to its coefficient. Internal validation was performed to assess the discrimination of the model. RESULTS: Complete SCR was strongly associated with the improvement of survival, with a median survival of 57.7 months, when compared with 27.0 months in those with residual disease of 0.1-1 cm and 15.6 months in those with residual disease of >1 cm, respectively (P<0.0001). Progression-free interval (≤23.1 months vs >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR: 1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model. CONCLUSION: This prognostic model may provide evidence to predict survival benefit from secondary cytoreduction in patients with recurrent ovarian cancer.

Improved 5-year disease-free survival for FIGO stage I epithelial ovarian cancer patients without tumor rupture during surgery.

OBJECTIVE: To investigate the impact of perioperative capsule rupture on disease-free survival (DFS) and cancer-specific survival (CSS) in patients with FIGO stage I epithelial ovarian cancer (EOC I). METHODS: This prospective population-based study enrolled all 279 patients with EOC I diagnosed in Norway between 2002 and 2004. All patients underwent primary surgery. The data were collected from notification reports to the Norwegian Cancer Registry and included medical, surgical and histopathological records. Kaplan-Meier plots were used to show differences in DFS and CSS. Cox regression analyses were used to show the effect of prognostic factors on survival, expressed as hazard ratios (HRs). RESULTS: Significantly more patients in the capsule rupture group (Cr group) had clear cell tumors (28%) than in the FIGO stage IA and IB (AB group: 14%) groups, and the FIGO stage IC (C group: 17%; p<0.05) group. Despite adjuvant chemotherapy (AC), these patients had a poor 5-year DFS, 94% in the non-AC group and 81% in the AC group (p<0.01). After five years of follow-up, there was a lower DFS among patients in the Cr group (79%) and the C group (81%), compared with patients in the AB group (91%; p<0.05). Independent prognostic factors at the time of diagnosis were grade, histological type, ascites, adhesions, performance status, CA125 and DNA ploidy. After correcting for the four most important prognostic factors (grade, histological type, ascites, and DNA ploidy), the HR for recurrence was 4.0 (95% CI 1.3-12.7; p<0.05) for the Cr group and 1.8 (95% CI 0.5-6.1; p=0.3) for the C group, compared with the AB group. CONCLUSIONS: Improvement was observed in the 5-year DFS for EOC I patients without tumor rupture during surgery compared with those with tumor rupture. Since AC did not improve the long-term DFS and CSS rates, it is of utmost importance that surgeons avoid tumor rupture during surgery.

Diagnosis and treatment of borderline ovarian neoplasms "the state of the art".

The 5-year survival for women with Stage-I borderline tumours (BOT) is favourable, about 95-97%, but the 10-year survival is only between 70 and 95%, caused by late recurrence. The 5-year survival for Stage II-III patients is 65-87%. Standard primary surgery includes bilateral SOEB, omentectomy, peritoneal washing and multiple biopsies. Second cytoreductive surgery is recommended for patients with recurrent disease. Adjuvant postoperative therapy is not indicated in Stage-I diploid tumors. Occasional responses to chemotherapy have been reported in advanced BOTs but no study has shown improved survival. Recently a new theory has been developed describing a subset of S-ovarian cyst adenomas that evolve through S-BOT to low-grade carcinoma. A more correct staging procedure, classification of true serous implants and agreement on the contribution to stage of the presence of gelatinous ascites in mucinous tumours may in the future change the distribution of stage and survival data by stage for women with BOT. Independent prognostic factors in patients with epithelial ovarian BOT without residual tumour after primary surgery are DNA-ploidy, international FIGO-stage, histologic type and patient age. Studies on other molecular markers have not yet uncovered a reliable prediction of biologic behaviour, however, there is hope that future studies of genetics and molecular biology of these tumours will lead to useful laboratory tests. Future questions to be addressed in this review include the following: Have patients with borderline tumours in general been over-treated and how should these patients be treated? How to define the high-risk patients? In which group of patients is fertility-sparing surgery advisable and, do patients with borderline tumours benefit from adjuvant treatment?

A review of molecular pathological markers in vulvar carcinoma: lack of application in clinical practice.

Vulvar carcinoma is a rare female genital neoplasia. Radical surgery, which has been the standard treatment approach, is often accompanied by considerable morbidity. To reduce the incidence of complications there has been a movement toward individualised therapy and less radical surgery. Associated with this, new tumour markers that could serve as prognostic indicators would be of considerable value to guide treatment decision. In this review, a brief update of molecular pathological markers of vulvar carcinomas is provided, and their impact as prognostic markers is addressed. p16, p21, p14, p27, cyclin A, cyclin D1, p53, vascular endothelial growth factor (VEGF), transforming growth factor alpha, HER-2 and epidermal growth factor receptor (EGFR) have been found to be important in the pathogenesis and/or progression of vulvar carcinomas. Furthermore, human papillomavirus, p16, p21, p14, p53, VEGF, CD44v3, CD44v6, CD44v4, CD44v9, CD44v10, HER-2, EGFR, matrix metalloproteinase-12, caspase 3, Bcl-2 and nm23-H1 have been correlated to clinical outcome of patients with vulvar carcinomas. However, due to the relative small number of studies reported for each molecular pathological marker, and the relative small number of vulvar carcinomas included and the lack of multivariate analysis in the majority of these studies, no conclusion regarding the prognostic value of these markers can be drawn. Therefore, the investigated markers have not yet earned a place in standard clinical diagnostics or treatment, and further studies are needed to clarify the clinical value of these markers.

The role of secondary cytoreduction in the management of the first relapse in epithelial ovarian cancer.

BACKGROUND: The aim of this study was to investigate the benefit of secondary cytoreduction (SCR) in the first relapse in epithelial ovarian cancer and to attempt to define selection criteria for SCR. PATIENTS AND METHODS: A retrospective population-based study on recorded information from 789 patients treated at the Norwegian Radium Hospital during 1985-2000 for their initial recurrence. In all, 217 had SCR and 572 were treated with chemotherapy alone. RESULTS: Median survival time (MST) was 1.1 years for the chemotherapy group. Complete optimal cytoreduction (COC) was achieved in 35% of all 217 patients, in 49% of the patients operated with debulking intent and in 52% if bowel surgery was done with debulking intent. MST was 4.5 versus 0.7 years for 0 versus>2 cm residual disease, respectively. Residual disease after SCR, treatment-free interval (TFI) and age were found to be prognostic factors for overall survival (OS) in multivariate analysis. Localised tumour was found to be the only significant factor to predict COC. CONCLUSIONS: SCR followed by chemotherapy gives a clear survival benefit compared with chemotherapy and should be offered when the tumour is localised. The combination of COC, TFI >24 months and age

Expression of ZNF652, a novel zinc finger protein, in vulvar carcinomas and its relation to prognosis.

AIMS: To determine the levels of expression of ZNF652 and its relevance to prognosis in vulvar squamous cell carcinomas. METHODS: 22 cases of vulvar intraepithelial neoplasia (VIN) and tumours from 217 patients with vulvar squamous cell carcinomas were investigated for expression of ZNF652 using immunostaining methods. The effect of ZNF652 ectopic expression was determined in the vulvar carcinoma cell line SW954 by western and cell-based assays. RESULTS: High levels of ZNF652 nuclear expression were observed in 5 (100%) of VIN I, 6 (75%) of VIN II and 109 (50.2%) of the vulvar carcinomas, whereas low levels were seen in 2 (25%) VIN II, 9 (100%) of VIN III and 108 (49.8%) of the vulvar carcinomas. High levels of ZNF652 expression in the vulvar carcinomas were significantly correlated to high expression of EphA2. However, when correcting for multiple testing this correlation was lost. No association was identified between ZNF652 expression and p16, p21, p27, p53, cyclin A, D1, D3, E, EphrinA-1 and human papillomavirus. Variations in levels of ZNF652 were not related to prognosis. Low levels of ZNF652 protein were identified in the vulvar carcinoma cell line SW954. Furthermore, SW954 cells ectopically expressing ZNF652 showed reduced cell proliferation and the ability to form colonies on plastic. CONCLUSIONS: ZNF652 protein expression is reduced in 25% of VIN II, 100% of VIN III and approximately 50% of the cases of vulvar squamous cell carcinoma, and may be an early event in the pathogenesis of vulvar squamous cell carcinoma. Variations in the levels of ZNF652 were not related to patient's prognosis.

Is the watch and wait approach adequate after comprehensive surgical staging in invasive stage I epithelial ovarian cancer? The Norwegian Radium Hospital experience.

OBJECTIVES: The aim of this study on stage I epithelial ovarian cancer (EOC) was to see if our different treatment policies after 1995, when lymph node staging and paclitaxel were introduced, have affected the survival, try to define risk groups for relapse and who should get adjuvant chemotherapy (AC). METHODS: A retrospective study based on record information from all patients with invasive EOC stage I operated at the Norwegian Radium Hospital (NRH) 1984-2001, in total 252 patients. RESULTS: Total 5-year survival was 83 and 82%, respectively, in both time periods. We found age and histology to be significant prognostic factors for overall survival (OS) (p < 0.01). From 1995 survival was significantly better for those who had been properly staged than for the others (p = 0.02), with a 5-year survival rate of 87 vs 64%. Those who did not get chemotherapy but were staged, had a significantly better overall survival than those who were not (p = 0.02), with a 5-year survival of 93 vs 77%. In the period 1995-2001 the patients who received no adjuvant treatment lived longer than those who underwent chemotherapy and/or radiotherapy (p = 0.03). In the first period 17% had no adjuvant treatment vs 58% in the last. Patients in a high-risk group getting AC had a tendency toward better survival than those who did not (p = 0.08). CONCLUSIONS: Patients with Stage I low and medium risk EOC do not need AC if properly staged. For the high-risk group the optimal AC has not yet been established.

Expression of matrix metalloproteinase-2 in serous borderline ovarian tumors is associated with noninvasive implant formation.

OBJECTIVE: To investigate matrix metalloproteinase (MMP) proteolytic and vascular endothelial growth factor (VEGF) and receptor (VEGFR-1, VEGFR-2) angiogenetic capacity in serous borderline ovarian tumors (S-BOTs) for women with and without noninvasive implants. METHODS: The population was made up of 99 patients with S-BOTs as the primary diagnosis between 1985 and 1995, 44 of whom had noninvasive implants and 55 without implants. MMP-2, MMP-14, the type-2 tissue inhibitor of MMPs (TIMP-2), and VEGF and receptors (VEGFR-1, VEGFR-2) were examined by immunhistochemistry. RESULTS: Strong positive (+++) MMP-2 staining was found more frequently in women with primary S-BOTs and noninvasive implants (76%) than in those without implants (53%; p < 0.05). In contrast, staining for MMP-14 and TIMP-2 was not significantly different in the two groups. Furthermore, expression of MMP-2, MMP-14, and TIMP-2 was similar in primary tumors and in their noninvasive implants. Most tumors in both groups had no VEGF expression (84% in the noninvasive implant group and 82% in the group without implants), while moderate (++) to strong (+++) expression of VEGFR-1 and VEGFR-2 was detected in 79% and 94% of the two tumor groups, with no significant difference between the groups. CONCLUSIONS: Enhanced MMP-2 was seen in primary S-BOT with noninvasive implants. The presence of noninvasive implants was prognostic for disease-free survival.

Improved survival for stage IIIC ovarian cancer patients treated at the Norwegian Radium Hospital between 1984 and 2001.

BACKGROUND: The aim of this study was to evaluate the treatment of FIGO Stage IIIC patients who were primarily treated completely or partially at the Norwegian Radium Hospital (NRH) during a 15-year period in order to discover possibilities for improvement of prognosis of advanced ovarian cancer. MATERIALS AND METHOD: A retrospective study based on record information from all patients with epithelial ovarian cancer Stage IIIC treated at NRH from 1985-2000, in total 776 patients. RESULTS: We found age, amount of residual tumour after surgery for primary treatment and type of chemotherapy to be the most significant prognostic factors for overall survival. During the last 5-year period primary surgery was increasingly centralised, and surgery was improved with lymph node staging and use of paclitaxel. Survival was significantly better during the last 5-year period and after macroscopic radical surgery. Also progression-free survival was better with no macroscopic tumour remaining. INTERPRETATION: Improved survival during the last 5-year period is partly attributed to improved surgery and partly to the addition of paclitaxel. We believe that further centralisation of primary surgery for advanced ovarian cancer can contribute to a better prognosis.

Expression of EphA2 and EphrinA-1 in vulvar carcinomas and its relation to prognosis.

AIMS: To examine the expression of EphA2 and EphrinA-1 in vulvar squamous cell carcinomas and investigate their prognostic relevance. METHODS: Tumours from 224 patients with vulvar squamous cell carcinomas were investigated for expression of EphA2 and EphrinA-1 using single and double immunostaining methods. RESULTS: High expression (strong/moderate staining intensity) of EphA2 and EphrinA-1 was observed in 114 (51%) and 126 (56%) vulvar carcinomas, respectively. In the three cases tested using the double immunostaining method, colocalisation of EphA2 and EphrinA-1 proteins was identified in the same neoplastic cells. High EphA2 expression was significantly correlated to high expression of EphrinA-1 (p<0.01) and cyclin A (p<0.01), large tumour size (p = 0.03), deep invasion (p<0.01) and higher FIGO stage (p = 0.05). A correlation between high EphrinA-1 expression and high levels of cyclin A (p<0.01) and p21 (p<0.01), deep invasion (p<0.01) and higher FIGO stage (p = 0.01) was also seen. In univariate analysis, high expression of EphrinA-1 was associated with poor survival (p = 0.03). However, in the multivariate analysis neither EphrinA-1 nor EphA2 were significantly correlated to survival. CONCLUSIONS: EphA2 and EphrinA-1 were overexpressed in 51% and 56% of the vulvar squamous cell carcinomas, respectively, and high levels of EphA2 and EphrinA-1 proteins were associated with deep tumour invasion and high FIGO stage. However, EphA2 and EphrinA-1 were not independently associated with clinical outcome in vulvar carcinomas.

A new approach to treatment of early-stage cervical carcinoma: entire laparoscopic abdominal radical hysterectomy with bilateral pelvic lymphadenectomy without vaginal cuff closure--case reports.

OBJECTIVE: The objective of this study is to describe a new technique of laparoscopic radical hysterectomy without vaginal cuff closure. METHODS: Three patients underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymph node dissection using an Argon Beam Coagulator. Four trocars were used: umbilical port for the camera, two ports for the operating surgeon and a fourth port for use by the surgical assistant. RESULTS: All patients were clinically staged IB1. Ages were 53, 64 and 58 and BMI was 19.5, 25.2 and 21.4, respectively. Duration of surgery was 375, 325 and 335 minutes, respectively, from first trocar insertion to last closing stitch. Estimated blood loss was 300, 100 and 400 ml and removed pelvic lymph nodes 18, 15 and 26, respectively. The patients tolerated the surgical technique and recovered satisfactorily. CONCLUSION: These are the first three cases of early-stage cervical carcinoma patients who have been treated with entirely laparoscopic abdominal radical hysterectomy (LARH) and bilateral pelvic lymphadenectomy (BPL) without vaginal cuff closure. To our knowledge, this has not been previously described in the literature. It is feasible and was well tolerated in this small series of patients.

Ovarian cancer stage IIIC. Consequences of treatment level on overall and progression-free survival.

BACKGROUND: Maximum cytoreduction at primary surgery has been found to be one of the strongest prognostic factors for survival of ovarian cancer. The aim of the study was to investigate the influence of hospital level (primary vs secondary care centre), number and timing of surgery and chemotherapy on how radical the surgery was at primary treatment of epithelial ovarian cancer Stage IIIC. MATERIAL AND METHODS: A retrospective study based on record information from all patients with epithelial ovarian cancer Stage IIIC treated at the Norwegian Radium Hospital (NRH) 1985-2000, in total 776, subdivided into four groups: 1) Local primary surgery, no direct re-operation at NRH, no interval debulking; 2) local primary surgery, no direct re-operation, but interval debulking after 3-4 courses of chemotherapy at NRH; 3) local primary surgery, direct re-operation at NRH, no interval debulking; 4) primary surgery at NRH. Lymph node biopsies at re-operation in early stages and upgrading of stage where necessary were registered. RESULTS: Whether surgery was radical or not was an independent prognostic factor for overall and progression-free survival. The treatment group was an independent prognostic factor for overall, but not for progression-free survival. Group 3 had significantly the best overall and progression-free survival (p = 0.01 and 0.05). For macroscopically radical surgery both overall and progression-free survival were found significantly better for groups 3, 4 and 1 than for group 2. Most lymph node biopsies were performed during the last period and 28% were upgraded from Stage I and II to IIIC. More patients were referred for primary surgery at NRH during the last 5-year period during which overall survival and time to progression were significantly better. INTERPRETATION: Whether primary surgery is radical or not is a significant prognostic factor for survival and primary surgery is best performed by specialists in gynaecological oncology.