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Hematogenous metastases are rarely present at diagnosis of ovarian clear cell carcinoma (OCC). Instead dissemination of these tumors is characteristically via direct extension of the primary tumor into nearby organs and the spread of exfoliated tumor cells throughout the peritoneum, initially via the peritoneal fluid, and later via ascites that accumulates as a result of disruption of the lymphatic system. The molecular mechanisms orchestrating these processes are uncertain. In particular, the signaling pathways used by malignant cells to survive the stresses of anchorage-free growth in peritoneal fluid and ascites, and to colonize remote sites, are poorly defined. We demonstrate that the transmembrane glycoprotein CUB-domain-containing protein 1 (CDCP1) has important and inhibitable roles in these processes. In vitro assays indicate that CDCP1 mediates formation and survival of OCC spheroids, as well as cell migration and chemoresistance. Disruption of CDCP1 via silencing and antibody-mediated inhibition markedly reduce the ability of TOV21G OCC cells to form intraperitoneal tumors and induce accumulation of ascites in mice. Mechanistically our data suggest that CDCP1 effects are mediated via a novel mechanism of protein kinase B (Akt) activation. Immunohistochemical analysis also suggested that CDCP1 is functionally important in OCC, with its expression elevated in 90% of 198 OCC tumors and increased CDCP1 expression correlating with poor patient disease-free and overall survival. This analysis also showed that CDCP1 is largely restricted to the surface of malignant cells where it is accessible to therapeutic antibodies. Importantly, antibody-mediated blockade of CDCP1 in vivo significantly increased the anti-tumor efficacy of carboplatin, the chemotherapy most commonly used to treat OCC. In summary, our data indicate that CDCP1 is important in the progression of OCC and that targeting pathways mediated by this protein may be useful for the management of OCC, potentially in combination with chemotherapies and agents targeting the Akt pathway.

LINE-1 (L1) retrotransposons are a source of insertional mutagenesis in tumor cells. However, the clinical significance of L1 mobilization during tumorigenesis remains unclear. Here, we applied retrotransposon capture sequencing (RC-seq) to multiple single-cell clones isolated from five ovarian cancer cell lines and HeLa cells and detected endogenous L1 retrotransposition in vitro. We then applied RC-seq to ovarian tumor and matched blood samples from 19 patients and identified 88 tumor-specific L1 insertions. In one tumor, an intronic de novo L1 insertion supplied a novel cis-enhancer to the putative chemoresistance gene STC1. Notably, the tumor subclone carrying the STC1 L1 mutation increased in prevalence after chemotherapy, further increasing STC1 expression. We also identified hypomethylated donor L1s responsible for new L1 insertions in tumors and cultivated cancer cells. These congruent in vitro and in vivo results highlight L1 insertional mutagenesis as a common component of ovarian tumorigenesis and cancer genome heterogeneity., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the proportion of patients with advanced ovarian and related cancers (EOC+RC), treated with neoadjuvant chemotherapy and interval debulking surgery (NACT - IDS), and to determine if there was any relationship with optimal cytoreduction rates and overall survival (OS) in a state-wide gynaecologic oncology service over time., Methods: A retrospective review was undertaken using a population-based database of patients with stages 3 and 4 EOC+RC treated from 1982 till 2013 at the Queensland Centre for Gynaecological Cancer (QCGC). The proportion of patients treated with NACT - IDS compared with primary debulking surgery (PDS) was determined and compared with debulking rates and with the moving five-year OS probability., Results: From 1982-2013, 2601 patients with advanced EOC+RC were managed at QCGC. No patients received NACT - IDS till 1995 when the first two patients received this treatment, rising to 55% of patients in 2013. Surgical cytoreduction rates to no macroscopic residual (R0) were achieved 32% of the time by 2006, rising to 48% in 2009, and 62% in 2013. Despite the increase in utilisation of NACT - IDS, our unit has noted a continued rise in the OS probability at five years to 45%., Conclusions: The increasing utilisation of NACT - IDS in the setting of a large centralised clinical service has been associated with increasing rates of optimal cytoreduction and survival rates have continued to rise in excess of those achieved in the trials reported to date., (© 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer., Methods: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis., Results: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts., Conclusions: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.

Background: Malnutrition is common in patients with advanced epithelial ovarian cancer (EOC), and is associated with impaired quality of life (QoL), longer hospital stay and higher risk of treatment-related adverse events. This phase III multi-centre randomised clinical trial tested early enteral feeding versus standard care on postoperative QoL., Methods: From 2009 to 2013, 109 patients requiring surgery for suspected advanced EOC, moderately to severely malnourished were enrolled at five sites across Queensland and randomised to intervention (n=53) or control (n=56) groups. Intervention involved intraoperative nasojejunal tube placement and enteral feeding until adequate oral intake could be maintained. Despite being randomised to intervention, 20 patients did not receive feeds (13 did not receive the feeding tube; 7 had it removed early). Control involved postoperative diet as tolerated. QoL was measured at baseline, 6weeks postoperatively and 30days after the third cycle of chemotherapy. The primary outcome measure was the difference in QoL between the intervention and the control group. Secondary endpoints included treatment-related adverse event occurrence, length of stay, postoperative services use, and nutritional status., Results: Baseline characteristics were comparable between treatment groups. No significant difference in QoL was found between the groups at any time point. There was a trend towards better nutritional status in patients who received the intervention but the differences did not reach statistical significance except for the intention-to-treat analysis at 7days postoperatively (11.8 intervention vs. 13.8 control, p 0.04)., Conclusion: Early enteral feeding did not significantly improve patients' QoL compared to standard of care but may improve nutritional status., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Many cancers are dependent on inappropriate activation of epidermal growth factor receptor (EGFR), and drugs targeting this receptor can improve patient survival, although benefits are generally short-lived. We reveal a novel mechanism linking EGFR and the membrane-spanning, cancer-promoting protein CDCP1 (CUB domain-containing protein 1). Under basal conditions, cell surface CDCP1 constitutively internalizes and undergoes palmitoylation-dependent degradation by a mechanism in which it is palmitoylated in at least one of its four cytoplasmic cysteines. This mechanism is functional in vivo as CDCP1 is elevated and palmitoylated in high-grade serous ovarian tumors. Interestingly, activation of the EGFR system with EGF inhibits proteasome-mediated, palmitoylation-dependent degradation of CDCP1, promoting recycling of CDCP1 to the cell surface where it is available to mediate its procancer effects. We also show that mechanisms inducing relocalization of CDCP1 to the cell surface, including disruption of its palmitoylation and EGF treatment, promote cell migration. Our data provide the first evidence that the EGFR system can function to increase the lifespan of a protein and also promote its recycling to the cell surface. This information may be useful for understanding mechanisms of resistance to EGFR therapies and assist in the design of treatments for EGFR-dependent cancers.

Objective: Folate is essential for DNA synthesis and methylation and is implicated in tumour progression. Few studies have examined its role in ovarian cancer survival. Our objective was to determine relationships between intake of folate, related one-carbon nutrients, single nucleotide polymorphisms (SNPs) in folate-metabolising genes and survival following ovarian cancer diagnosis., Methods: This analysis included 1270 women with invasive epithelial ovarian cancer diagnosed in 2002-2006. Pre-diagnostic and some post-diagnostic lifestyle, dietary, and sociodemographic information was collected via self-administered questionnaires. DNA samples were genotyped for SNPs in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and methionine synthase reductase (MTRR) genes. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression., Results: Multivariate analyses did not identify associations between higher pre-diagnostic intake of folate, folic acid, vitamins B2, B6, and B12, methionine, betaine or choline and survival overall. In stratified analyses, higher folic acid and folate intake was associated with significantly worse survival among women with mucinous tumours (HRs per 100 μg 1.30 and 1.43, respectively) and smokers (HRs per 100 μg 1.23 and 1.16 respectively). There was also a suggestion that higher supplemental folic acid use post-diagnosis was associated with worse survival (HR per 100 μg 1.03, 95%CI 1.00-1.05). MTHFR SNP rs2066470 was significantly associated with survival (per allele HR 0.81, 95%CI 0.67-0.98)., Conclusions: Our data provide little evidence that folate intake affects ovarian cancer survival. However, combined effects with smoking, and findings within the mucinous subtype and for post-diagnosis folic acid, warrant further investigation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The thoroughness of cytoreductive surgery is the largest contributor to survival for patients with advanced ovarian and primary peritoneal carcinoma. For many years the surgery undertaken by Gynaecologic Oncologists has been tailored to match their surgical training. Future surgical training of Gynaecologic Oncologists needs to be tailored to the surgery required to provide complete tumour removal to no residual disease. This means the better teaching of anatomy and an increased scope of surgery to include the general and upper abdominal procedures and management required. This paradigm shift will be a challenge for all and impossible for some. It will require a significant mind-shift not only from our craft group and the profession at large but especially from the speciality Colleges who will need to take these changes on board for future curriculum development. The development of Advanced Cytoreductive Surgical Units needs to be undertaken in a team environment. This requires a commitment from participants at all levels, from the lead oncology surgeon through the hospital administration to the support services involved. While advanced cytoreductive surgery is feasible, it is only in this team environment, limited to major multidisciplinary hospitals, that it can be safely achieved by meticulous attention to detail at all levels.

Background: Since the introduction of the Pap smear screening, the incidence of squamous cell carcinoma (SCC) has decreased significantly, but the incidence of adenocarcinoma (AC) relative to SCC has increased., Aim: To compare the Pap smear history of patients with AC and SCC of the cervix., Methods: Patients for the study were identified from the database of Queensland Centre for Gynaecological Cancer. Patients with AC and SCC were matched for age at diagnosis and International Federation of Gynecology and Obstetrics stage. The final population included 188 matched pairs, being 376 patients in total. Data were collected upon the histological type of cancer, result of the most recent Pap smear, date and result of the Pap smear prior to the most recent Pap smear and symptoms. Chi-squared tests and Fisher's exact test were used to compare the two patient groups for several variables., Results: Patients with AC had significantly more false-negative results on their most recent Pap smear (P<0.0001) than patients with SCC. The incidence of symptoms such as bleeding and/or vaginal discharge was comparable in patients with AC and SCC. The time between the most recent Pap smear and the diagnosis of cervical cancer was significantly shorter for patients with AC (P=0.01)., Conclusions: Patients with AC had Pap smears more regularly than those with SCC, and their most recent Pap smear was significantly more likely to be normal. Thus, Pap smear prior to a diagnosis of AC is more likely than SCC false-negative and therefore not indicative of cervical cancer.

Objective: To evaluate the efficacy of routine follow-up in patients with recurrent uterine cancer., Methods: In a single institution study, a total of 2637 patients were treated curatively for uterine cancer from 1990 to 2006. A total of 438 patients experienced disease recurrence. Data for detailed analysis were available from 280 of the 438 patients. Prior to the diagnosis of recurrence, all patients had regular follow-up and were investigated through internal examination, vaginal vault cytology and imaging. Overall survival (OS) was the main study endpoint and was calculated from recurrence diagnosis to death or date censored., Results: Clinical and histopathological features as well as patterns of recurrence were similar in symptomatic and asymptomatic patients. Eighty-one patients (28.9%) were diagnosed with asymptomatic recurrence while 199 patients (71.1%) presented with symptomatic recurrence. The overall survival probability at 5 years was 41.0% and 28.9% respectively for asymptomatic and symptomatic patients (log-rank p=0.013). Those patients with stage 1 or 2 tumors of endometrioid type were found to have an overall survival probability at 5 years of 38.0% and 25.7% respectively for asymptomatic and symptomatic recurrence (log-rank p=0.05). The absence of symptoms did not impact on the outcome of patients with stage 3 tumors or tumors of non-endometrioid type., Conclusions: While patients at low/intermediate risk of recurrence may benefit from intensive follow-up including internal examinations, routine vaginal vault cytology and imaging, high-risk patients might gain more from an alternate follow-up strategy with emphasis on imaging in conjunction with symptom education.

Objectives: To assess the reliability and validity of the Functional Assessment of Cancer Therapy-Vulvar (FACT-V)., Methods: Seventy-seven patients treated between January 1996 and January 2001 for cancer of the vulva completed the FACT-V, the Eastern Cooperative Oncology Group Performance Status Rating (ECOG-PSR) and the Hospital Anxiety and Depression Scale (HADS) once, 20 consecutive patients treated between February 2001 and October 2001 completed the questionnaires twice, once before surgery and at 2 months follow-up. The FACT-V scores were compared by patients' performance status, FIGO stage, recurrence, and age, and correlated to the HADS scores. Changes in the FACT-V from baseline to 2 months follow-up were evaluated to establish FACT-V's responsiveness to change., Results: The FACT-V's internal consistency was adequate (Chronbach's alpha range, 0.75 to 0.92). Patients with lower performance status, higher FIGO-stage or recurrent disease received lower FACT-V scores, indicating discriminant validity. The correlation between the FACT-V and the HADS were in the expected direction, indicating convergent and divergent validity. From pre- to post-surgery, scores in nine out of fifteen items of the vulvar cancer-specific subscale improved, while those of five items declined, indicating sensitivity of the vulvar cancer specific items to changes in patients' well-being., Conclusions: The newly developed FACT-V provides a reliable and valid assessment of the quality of life of women with vulvar cancer. It can be used as a short measure of quality of life within research studies, and to facilitate communication about quality of life issues in clinical practice.

Objective: To compare patterns of recurrence and disease-free survival (DFS) of node-positive and node-negative patients with advanced vulval squamous cell carcinoma (SCC)., Methods: Fifty-five patients with FIGO stage III/IVA vulval SCC who had surgery at the Queensland Centre for Gynaecological Cancer from 1989 to 1999 were included. Patients were grouped as follows: Group A, pT3 N0; Group B, pT3 N1; Group C, pT4 N2. Treatment included surgery +/- postoperative radiotherapy. Multivariate Cox models were calculated to identify independent prognostic factors., Results: After a median follow-up of 96 months, 25 patients (45.5%) experienced recurrence at the vulva (n = 2), pelvis (n = 8), or distant sites (n = 15). Recurrence in the pelvis and at distant sites was more likely for patients in groups B and C (P 0.003). At 5 years the probability of DFS was 66.6%, 35.3%, and 39.8% for patients in groups A, B, and C, respectively (P 0.085). Patients with negative nodes (n = 15), one microscopic positive node (n = 11), and two or more positive nodes (n = 29) had a probability of DFS of 66.6%, 67.3%, and 26.1% at 5 years, respectively (P 0.005)., Conclusion: Patients with > or =2 positive groin nodes are at risk for distant failure. The DFS of patients with negative groin nodes and those with only one microscopic positive node is very similar. The prognosis of patients with > or =2 positive unilateral or bilateral groin nodes is similar. The current FIGO staging system inaccurately reflects prognosis for patients with advanced vulval cancer. Clinical trials are warranted to investigate the benefit of systemic treatment.

Cervical cancer is one of the commonest cancers in women. It is also the most preventable cancer. Numerous population based studies have shown that the development of a population based screening program can significantly reduce the incidence of and death rate from cervical cancer. However, it is expensive and requires a large and complex infrastructure to run such a program. As the disease goes through a prolonged pre-invasive phase (cervical intraepithelial neoplasia, CIN) there is ample time in which to treat this phase. Furthermore, this treatment only involves the destruction of the surface epithelium of the cervix. There is ample evidence that those women who have undergone cervical diathermy, for whatever reason, have a lower subsequent incidence of cervical cancer.

Borderline ovarian tumours are known to occur in younger women than invasive cancers and to also have a better prognosis. However, there is also much disagreement about the best approaches to management. At the Queensland Centre for Gynaecological Cancer we have had a particular interest in this disease for some years. Regular reviews of our management have indicated many important guides to management. In our most recent review of 606 cases we have concluded that. Early stage disease can and should be treated conservatively if the patient desires to retain her reproductive function, Treatment should be aimed at leaving no visible disease, Adjuvant therapy does not improve survival, Re-staging laparotomy in clinical Stage 1A patients is not justified as the pick-up is too small, The best prognosis is to be expected in the youngest patients. We will continue to track the progress of these patients in the hope that better management can be offered in the future.

To develop a vulvar cancer-specific quality of life (QOL) subscale to accompany the Functional Assessment of Cancer-General (FACT-G) questionnaire, semistructured interviews were performed with 15 patients treated for vulvar cancer (FIGO stage 0-3). All but one patient, who received chemoradiotherapy, were treated by radical vulvectomy and six patients received a groin lymph node dissection. Patients experienced reductions in several aspects of QOL including emotional functioning, physical functioning, social functioning, sexuality, and body image. Six patients suffered from lymphedema of the legs with a mean severity of 3.5 on a 10-point scale. Four patients reported pruritus (severity rating 8.5). Seven patients expressed a need for more information about the illness and treatment. Only four patients returned to employment after treatment, and all of these patients reported work-related problems. Reductions in sexual functioning were a major concern for five patients, all younger than 65 years. Other topics were groin discomfort after removal of the lymph nodes and disturbance by odor from the vulva. Results of this study revealed vulvar cancer-specific reductions in QOL for inclusion in the newly developed vulvar cancer-specific subscale.

Objectives: The aims of this study were to assess outcomes and define prognostic factors for early-stage vaginal carcinoma., Methods: A retrospective analysis was performed of women with FIGO stages I and II vaginal carcinoma identified from the database of the Queensland Centre for Gynaecological Cancer between January 1982 and December 1998., Results: Seventy women were identified. The 5-year survivals for stages I and II carcinomas were 71 and 48%, respectively (P < 0.05). Sixty-one patients (87%) had squamous cell carcinomas with a 5-year survival of 68% versus 22% for adenocarcinomas (P < 0.01). Those women with grade 3 tumors had a 5-year survival of 40% versus 69% for grades 1 and 2 (P < 0.05). Tumor size and site were not significant prognostic factors. Patients treated by surgery alone or with combined surgery and radiotherapy had a significantly improved survival compared to the radiation alone group (P < 0.01). Eighty-five percent of recurrences were locoregional. The median time to relapse was 12 months after initiation of therapy., Conclusion: Tumor morphology, grade, and stage are important prognostic indicators. Measures aimed at improving local control of the disease, including surgery, are necessary.

To determine the impact of anemia before and during chemoradiation in patients with cervical cancer, we collected data on hemoglobin (Hb) levels before and during treatment from 60 unselected patients with cervical carcinoma. All patients had FIGO stage IB to IVA disease and were treated with concurrent chemoradiation for the aim of cure. Patients with an Hb value below or equal to the lower 25th quartile were considered anemic. Progression-free survival (PFS) was evaluated by univariate and multivariate analyses. After a median follow-up of 26.3 months, 20 patients developed disease progression. The lowest Hb during chemoradiation (nadir Hb), the stage of disease, and parametrial involvement were correlated significantly with PFS. On multivariate analysis, the nadir Hb (relative risk [RR] 0.29) and tumor stage (RR 3.4) remained the only prognostically relevant factors predicting PFS. At 60 months the PFS was 39.1% for anemic patients and 48.0% for nonanemic patients (P < 0.0002). In patients undergoing chemoradiation for cervical carcinoma, a low nadir Hb is highly predictive of shortened PFS, whereas the Hb before treatment is prognostically not significant.

Objective: The aim of this study was to determine the prognostic significance of serosal involvement (SER), adnexal involvement (ADN), and positive peritoneal washings (PPW) in patients with Stage IIIA uterine cancer. We also sought to determine patterns of recurrence in patients with this disease., Methods: The records of 136 patients with Stage IIIA uterine cancer treated at the Queensland Centre for Gynecological Cancer between March 1983 and August 2001 were reviewed. One hundred thirty-six patients underwent surgery and 58 (42.6%) had full surgical staging. Seventy-five patients (55.2%) had external beam radiotherapy and/or brachytherapy postoperatively. Overall survival was the primary statistical endpoint. Statistical analysis included univariate and multivariate Cox models., Results: Forty-six patients (33.8%) had adnexal involvement, 23 (16.9%) had serosal involvement, and 40 (29.4%) had positive peritoneal washings. Median follow-up was 55.1 months (95% confidence interval, 36.9 to 73.4 months) after which time 71 patients (52.2%) remained alive. For patients with endometrioid adenocarcinoma, ADN and SER were associated with impaired survival on multivariate analysis (odds ratio 2.8 and 3.2, respectively). In the subgroup of patients with high-risk tumors (including papillary serous carcinomas, clear cell carcinomas, and uterine sarcomas), neither ADN, nor SER, nor PPW influenced survival., Conclusion: Patients with Stage IIIA uterine cancer constitute a heterogeneous group. For patients with endometrioid adenocarcinoma, both ADN and SER, but not PPW, were associated with impaired prognosis. For patients with high-risk histological types, prognosis is poor for all three factors.

MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 isoforms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy., (Copyright 2002 Wiley-Liss, Inc.)

Objectives: The MUC1 antigen can be used to identify epithelial cells from the background of hemopoietic cells. The present investigation describes patterns of overexpression of two novel MUC1 splice variants in human cervical carcinoma cell lines., Methods: RT-PCR was carried out to determine MUC1 splice variants in the cervical cancer cell lines C-4 II, C-33A, DoTc 2 4510, C-4 I, SiHa, HT3, Hs 636 T (C4-I), and HeLa., Results: The novel MUC1 splice variant D was expressed in all cell lines and the novel MUC1 splice variant C was expressed in all cell lines but C-33A. Variants A and B were expressed in all (variant A) and all but one (variant B) cell line. MUC1/REP was expressed in all cell lines and MUC1/SEC was positive in all but two cell lines (C-33 A, DoTc 2 4510). All but one cell line (C-33A) expressed MUC1/X and MUC1/Y, and two cell lines (C-33 A, DoTc 2 4510) did not express MUC1/Z, respectively. MUC1 variants A, D, and REP could be demonstrated consistently among all eight cervical carcinoma cell lines we have examined., Conclusions: The present study describes the feasibility of detecting a large number of MUC1 variants, including MUC1 variants C and D which are described for cervical carcinoma cells for the first time. Further studies will examine the presence of MUC1 splice variants' expression in human cervical carcinoma tissue., (Copyright 2001 Academic Press.)

Objective: To examine the feasibility and safety of a low anterior resection of the rectosigmoid plus adjacent pelvic tumour as part of primary cytoreduction for ovarian cancer., Methods: This study included 65 consecutive patients with primary ovarian cancer who had debulking surgery from 1996 through 2000. All patients underwent an en bloc resection of ovarian cancer and a rectosigmoid resection followed by an end-to-end anastomosis. Parameters for safety and efficacy were considered as primary statistical endpoints for the aim of this analysis., Results: Postoperative residual tumour was nil, <1 cm, and >1 cm in 14, 34, and 14 patients, respectively. The median postoperative hospital stay was 11 days (range, 6 to 50 days). Intraoperative complications included an injury to the urinary bladder in one patient. Postoperative complications included wound complications (n = 14, 21.5%), septicemia (n = 9, 13.8%), cardiac complications (n = 7, 10.8%), thromboembolic complications (n = 5, 7.7%), ileus (n = 2, 3.1%), anastomotic leak (n = 2, 3.1%), and fistula (n = 1, 1.5%). Reasons for a reoperation during the same admission included repair of an anastomotic leak (n = 1), postoperative hemorrhage (n = 1), and wound debridement (n = 1). Wound complications, septicemia, and anastomotic leak formation were more frequent in patients who had a serum albumin level of < or =30 g/L preoperatively. There was one surgically related mortality in a patient who died from a cerebral vascular accident 2 days postoperatively., Conclusions: An en bloc resection as part of primary cytoreductive surgery for ovarian cancer is effective and its morbidity is acceptably low., (Copyright 2001 Academic Press.)

Background: In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma., Methods: The authors collected data on hemoglobin (Hb) levels before and during treatment from 57 patients with cervical carcinoma. The stage of disease ranged between Stage IB and Stage IVA. All patients were treated with concurrent chemoradiation. Response to chemoradiation was evaluated by univariate and multivariate analyses., Results: The mean Hb level at the time of presentation was 12.9 +/- 1.6 g/dL in patients with a complete clinical response (CCR) and 12.1 +/- 1.4 g/dL in those with persistent disease (P = 0.126). In patients with a CCR, the mean nadir Hb level was 11.1 +/- 1.3 g/dL, and in patients with treatment failure, it was 9.8 +/- 1.8 g/dL (P = 0.008). A univariate logistic regression model demonstrated that the nadir Hb level was the most predictive factor for treatment failure (relative risk, 1.92; P = 0.015) followed by disease stage (relative risk, 0.51; P = 0.074). In a multivariate model, the nadir Hb level remained the only prognostically relevant factor predicting the response to chemoradiation. Only patients with nadir Hb values > 11 g/dL throughout chemoradiation had a more than 90% chance of achieving a CCR., Conclusions: In patients undergoing chemoradiation for cervical carcinoma, the nadir Hb level is highly predictive of response to treatment, whereas the Hb level at the time of presentation is prognostically not significant., (Copyright 2001 American Cancer Society.)

Objective: The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma., Methods: Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy)., Results: At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities., Conclusions: Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival., (Copyright 2001 Academic Press.)

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system. While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation. Patients with negative washings had a DFS of 96% at 36 months compared with 67% for patients with positive washings (log-rank P<0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor.

This study reviews our experience with 7 patients with primary Bartholin gland cancer (BGC) treated at the Queensland Gynaecological Cancer Centre (QCGC) and compares this with previously published data. A retrospective clinicopathologic review of all patients with primary BGC treated at QCGC from 1988 to 2000 was performed. Of the 7 patients treated, all underwent primary surgery and 5 of the 7 patients received radiotherapy postoperatively. All patients presented with a local swelling or a lump. Two had associated discharge and 2 had associated pain. Of the 7 patients, 2, 3 and 2 respectively were classified as having Stage IB, II or III disease. Five of the 7 patients had squamous cell carcinoma (SCC), one had adenoid-cystic carcinoma and 1 had a small-cell neuroendocrine cancer of the Bartholin gland. None of the patients with SCC developed recurrent disease. The patient with adenoid-cystic carcinoma experienced local recurrences at 4 years and again at 5 years and 3 months. Nine years after primary treatment she was diagnosed with pulmonary metastases. The patient with small-cell neuroendocrine cancer of the Bartholin gland was considered tumour-free after operation. Thorough imaging, including a CT scan of her chest, abdomen and pelvis showed no evidence of disease. She died 1 year and three months after diagnosis from disseminated pulmonary disease. We present the first report of small cell neuroendocrine cancer of the Bartholin gland. Therapeutic principles in the management of vulval cancer at other sites appear to be appropriate for management of BGC.

The purpose of this study was to review the experience with fallopian tube carcinoma in Queensland and to compare it with previously published data. Thirty-six patients with primary fallopian tube carcinoma treated at the Queensland Gynaecological Cancer Center from 1988 to 1999 were reviewed in a retrospective clinicopathologic study. All patients had primary surgery and 31/36 received chemotherapy postoperatively. Abnormal vaginal bleeding (15/36) and abdominal pain (14/36) were the most common presenting symptoms at the time of diagnosis. Median follow-up was 70.3 months and the median overall survival was 68.1 months. Surgical stage I disease (P = 0.02) and the absence of residual tumor after operation (P = 0.03) were the only factors associated with improved survival. Twenty of the 36 patients (55%) presented with stage I disease and survival was 62.7% at 5 years. No patient with postoperative residual tumor survived. The majority of the patients with fallopian tube carcinoma present with stage I disease at diagnosis, but their survival probability is low compared with that of other early stage gynecological malignancies. If primary surgical debulking cannot achieve macroscopic tumor clearence, the chance of survival is extremely low.

Objectives: The aim of this study is to examine the patterns of failure after extended surgical staging and postoperative vaginal vault brachytherapy as the only adjuvant treatment in high-risk surgical Stage I patients with endometrial carcinoma., Methods: The records of all patients with endometrial carcinoma (adenocarcinoma or adenosquamous) receiving vaginal vault brachytherapy as the only adjuvant treatment from January 1989 to December 1997 were examined. A total of 489 patients were found. Of these, 133 had extended surgical staging. The study group consists of 77 surgical Stage I patients with Substages IBG3 and any grade IC. Recurrences were recorded as in the vagina, pelvis, or distant., Results: The mean follow-up interval was 45 months (range 14 to 96 months). Eleven patients had recurrence (14%). Median time to recurrence was 15 months (range 6 to 56 months). Recurrences occurred in the vagina in 7, pelvis in 1, and distantly in 3 patients. Five of 7 vaginal recurrences occurred within 2 years. All patients with distant recurrence died from disease. One patient with pelvic recurrence is alive with disease. Only 1 patient with vaginal recurrence died from disease. Six patients with isolated recurrences in the vagina were successfully treated with radiotherapy with or without local excision. All 6 have no evidence of disease at follow-up (median survival 29 months, range 20 to 71 months)., Conclusions: The vagina remains the most common site of recurrence for high-risk surgical Stage I patients treated with postoperative vaginal vault brachytherapy. Close follow-up in the first 2 years is essential to detect isolated vaginal recurrences. These are amenable to salvage treatment with good disease-free survival., (Copyright 2000 Academic Press.)

Background: Effective combination chemotherapy has improved the previously dismal prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young patients, conservative surgery with adjuvant chemotherapy has made the preservation of fertility possible, even in patients with advanced disease. The increase in cure rates has shifted the focus of recent studies to the long term menstrual, reproductive, and gynecologic outcomes in these patients., Methods: The current study is a retrospective review of 74 patients with MOGCT treated by conservative surgery, retaining the uterus and contralateral ovary to preserve ovarian function, with or without chemotherapy., Results: The mean age of the patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31 dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%). There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4 Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients (63.5%). The overall mean follow-up period was 52.1 months. There were 7 recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I disease was 98.2% and that for patients with advanced disease stages was 94.4%. During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these women resumed normal menstrual function on completion of chemotherapy. Fourteen healthy live births were recorded in the chemotherapy group and there were no documented birth defects. There was 1 case of infertility (1.4%)., Conclusions: The surgical approach in young patients with MOGCT confined to a single ovary should aim to preserve fertility. Advanced disease is not usually accompanied by contralateral ovarian disease and should not necessarily contraindicate conservative surgery. The majority of these patients who have received combination chemotherapy resume normal ovarian function and can expect a normal fertility rate and healthy offspring., (Copyright 2000 American Cancer Society.)

We evaluated the management of patients with microinvasive adenocarcinoma of the cervix (MIAC), in particular, to determine the place of conservative surgery, and determine if the FIGO classification for MIAC is valid and equivalent to the classification as it applies to microinvasive squamous cancer. A review was undertaken of the database of the Queensland Centre for Gynaecological Cancer (QCGC) from January, 1986 to October, 1998. The records of all patients recorded as having MIAC were retrieved. Microinvasion was defined according to the 1995 FIGO classification as a depth of invasion of no greater than 5 mm and a horizontal dimension of no greater than 7 mm 30 patients were found to have been treated for MIAC. The vast majority (29) were asymptomatic, disease being discovered at the time of routine Papanicolaou smear. There was a 43% incidence of coexisting squamous intraepithelial neoplasia. Multifocal disease was found in 17% of patients and lymph-vascular positivity in 7%. Eighteen patients were treated with radical surgery and 13 with conservative surgery. There were no recurrences over a follow-up interval of 3-116 months. Of the 18 patients treated with radical surgery, none was found to have occult microscopic disease in the parametria or nodal metastases. A total of 27 ovaries were removed, all of which were free of disease. In this small study, MIAC appears to behave in a manner similar to the squamous equivalent. The results provide some justification for the FIGO classification of a microinvasive glandular neoplasm of the cervix. There is some support for a role for conservative surgery in managing this condition, but there is insufficient worldwide experience to make definitive recommendations.

Malignant ovarian germ cell tumours (MOGCT) principally occur in girls and young women and are generally unilateral. Effective combination chemotherapy with conservative surgery has seen a dramatic improvement in survival rates. This increase has shifted the focus to long-term fertility and reproductive outcome. The present study describes 45 patients with MOGCT treated with conservative surgery to preserve fertility, with or without the addition of chemotherapy. The age range was 10 to 32 years with a mean of 20 years. The majority of the subjects had Stage 1 tumours; 44 underwent unilateral salpingo-oophorectomy and 1 patient ovarian cystectomy. Adjuvant chemotherapy was administered in 29 patients. Overall mean follow-up was 58.7 months. There were 4 recurrences and 2 deaths. Survival of those with Stage 1 disease was 97% and for advanced stages 87%. During chemotherapy 50% became amenorrhoeic but 96% resumed normal menstrual function on completion. Seven healthy babies were recorded in the chemotherapy group and no documented birth defects occurred in any of these. There was no case of persistent infertility; 3 patients experienced temporary problems. It is concluded that conservative fertility-sparing surgery is the treatment of choice in these young women and advanced disease is not necessarily a contraindication. The majority can anticipate normal menstrual function and fertility.

The syndrome of adenocarcinoma of unknown primary (ACUP) is a frequent problem in both medical and surgical practice. The prognosis is poor, the median lifespan being 4 months. In general, multiple invasive procedures aimed at determining the primary tumour are not warranted due to the low frequency of detecting a tumour for which adequate treatment exists. In this paper we wish to highlight a subset of female patients presenting with malignant ascites and no evidence of a pelvic mass, who on laparotomy were found to have primary peritoneal papillary serous adenocarcinoma. These tumours must be regarded as a potentially treatable subset of patients with ACUP in view of their frequent response to chemotherapy and relatively good prognosis.

A new treatment for recurrent pelvic lymphocysts is reviewed. Nine women with recurrent symptomatic lymphocyst were treated by marsupialization of the lymphocyst to the peritoneal cavity and functioning omental flap. The omental flap was dissected off the greater curve of the stomach maintaining its blood supply from the appropriate gastroepiploic vessels. The flap functioned by absorbing the lymph that previously accumulated in the lymphocyst. The efficacy of treatment was accessed both clinically and with diagnostic imaging. The pelvic lymphocysts were successfully treated in all 9 cases. There was no significant morbidity and the average hospital stay was 7 days. Marsupialization of pelvic lymphocysts combined with an omental flap is effective, not associated with increased morbidity and has a very low recurrence rate.

Purpose: The role of bipedal lymphangiogram in tailoring radiation portals in radical radiation therapy for Stages II or III cervix cancer is investigated., Methods and Materials: The records and simulation films of 87 patients with Stage II or III carcinoma of the cervix treated with radical radiation therapy alone have been retrospectively reviewed., Results: Sixty-two percent of patients who had a bipedal lymphangiogram, subsequently had their radiation fields altered from a "standard portal." The most frequently altered fields were the lateral margin of the postero anterior field and the anterior margin of the lateral fields. In order to cover the lymphatic channels in the pelvis in 90% of cases as outlined by the bipedal lymphangiogram, the lateral margins of the postero anterior fields would need to be 2.5 cm lateral to the pelvic brim and the anterior border of the lateral field, 0.5 cm anterior to the pubic symphysis., Conclusion: "Standard" fields adequately cover the median distribution of lymphatics, but may result in a geographic miss in some patients. Bipedal lymphangiograms allow a more accurate tailoring of pelvic lymphatic fields.

Two hundred and sixty-nine (5.4%) of the 4,998 patients who delivered in Westmead Hospital, New South Wales in 1985 had immediate postpartum complications. This analysis was compared with figures from a major institution in another state of Australia. Early detection and prompt management without procrastination was the key to a successful outcome in the fourth stage of labour (i.e. within 24 hours of delivery). Nearly three-quarters of the complications were due to postpartum haemorrhage (PPH). The contributory factors are analysed and discussed. Reappraisal of the indications for induction of labour, epidural analgesia and forceps delivery is necessary to reduce the incidence of postpartum haemorrhage. The study reinforces the need for undiminished vigilance in the fourth stage of labour even if the first 3 stages are uncomplicated.

The increasing use of amniocentesis requires that the technique be made as safe as possible. The results of 284 amniocenteses done under ultrasound control are presented and compared with the results of 140 amniocenteses performed without ultrasound control. The use of ultrasound guidance increased the success rate from 80 to 99.6 per cent and decreased the incidence of feto-maternal haemorrhage from 8.5 to 2.8 per cent. The incidence of blood-stained amniotic fluid was reduced from 43.5 to 17.6 per cent. The clinical significance of these findings is discussed and the results interpreted as indicating that amniocentesis done with ultrasound guidance is a safer and less traumatic procedure.

The oestrogen and progestogen receptor status in ovarian cancers from 72 patients was correlated with histological type, primary or secondary origin and peripheral hormone concentrations. Changes occurred in receptor status during malignant transformations of ovarian tissues, with those for oestrogen being found more often, and those for progestogen less often than in non-diseased ovarian fragments. It is suggested that the similarity in sex steroid receptor content between ovarian and breast cancers warrants prospective study of ovarian sex steroid receptor status as a predictive index of survival and response to hormonal therapy in multi-centre clinical trials. Additional data on androgen receptors are also presented.

Using 125I-fibrinogen scanning the incidence of post-operative DVT amongst patients with gynaecological malignancy was shown to be 37.9% which is substantially higher than the 10% to 15% expected in a general gynaecological population. Twenty per cent of the total group studied had isotopic evidence of bilateral venous thrombosis post-operatively. The inaccuracy of clinical diagnosis was demonstrated, and also the need to investigate both limbs if thrombosis was suspected. The incidence of post-operative DVT was found to be significantly lower in smokers (11.5%) compared with non-smokers (68.4%) (p less than 0.00025).

Administration of prophylactic low-dose subcutaneous heparin to prevent postoperative deep vein thrombosis is expensive, entails treating many patients unnecessarily, and causes some side effects. By using a predictive index a population of patients who are at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively. Prophylaxis was given only to these patients, resulting in an incidence of deep vein thrombosis of 3.8% compared with 16.1% in previous studies in which no specific prophylaxis was given. By limiting prophylaxis to the group of patients identified by the predictive index as being at high risk of developing postoperative deep vein thrombosis results may be obtained that are as good as those expected from treating the whole population. Thus many patients are saved from exposure to low-dose subcutaneous heparin.

A longitudinal study of circulating immune complexes (CIC) of the IgG class has been undertaken in patients presenting for operation of active malignant disease of the female reproductive tract. These values were compared with data obtained during subsequent clinical remission and prior to the clinical diagnosis of relapse. The results showed that irrespective of the site of disease (e.g., ovary, fallopian tube, cervix, endometrium, or vagina) values for CIC were elevated in most patients compared to controls. Postoperative remission status was associated with a significant decrease in values for all tumor sites. Similarly, relapse was associated with elevation of CIC levels to values similar to the preoperative concentrations. It is concluded that CIC may provide a useful biochemical marker of the progression of malignant disease.

A prospective study was carried out to confirm the validity of a predictive index for patients at risk of developing deep vein thrombosis. The index, which correctly identified nine out of 10 patients and incorrectly identified seven out of 52 patients as being at risk, is based on five variable--namely, the euglobulin lysis time, serum concentration of fibrin-related antigen, age, percentage overweight for height, and presence of varicose veins. Thus a population of patients at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively by means of this index, so that prophylaxis may be used more rationally.

The use of circulating immune complexes and a commercial monoclonal antibody to ovarian cancer (CA 125 kit) in monitoring progress in patients with ovarian cancer has been assessed. While changes in immune complexes were apparent in some patients with active progression of disease, the marked change in values and linear trend make the use of CA 125 a useful clinical marker.