Elevated CDCP1 predicts poor patient outcome and mediates ovarian clear cell carcinoma by promoting tumor spheroid formation, cell migration and chemoresistance.

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.

Consideration for safe and effective gynaecological laparoscopy in the obese patient.

BACKGROUND: The number of obese and morbidly obese patients within the developed world is dramatically increasing within the last 20 years. Apart from demographical changes, obese patients are especially prone to have oestrogen-dependent morbidities and neoplasias, of which laparoscopic treatment should be the standard of care. The increasing number of patients with BMI >40 is concerning, making it necessary to summarise considerations for safe and effective Gynaecological Laparoscopic Surgery. CONSIDERATIONS: The sequel to successful laparoscopic surgery in obese patients comprises an interdisciplinary appreciation of laparoscopy. Preoperatively, anaesthetics and medical review are suggested to optimise treatment of comorbidities (i.e. infections and blood sugar levels). Positioning of the patient should consider anti-slip options and pannus fixation to ease laparoscopic access and decrease pressure to the chest. There is no standard port placement in obese patients and landmarks have to be the bony structures of the pelvis and ribs. Retraction of the bowel is essential and mobilisation of the sigmoid with fan retractors or endoloops can accomplish adequate vision. 30° scopes can be considered for vision "around the obstacle". An experienced assistant with anticipation of surgical steps is favourable for successful surgery completion. Intra-operatively, good surgical techniques are essential. Vessel sealing systems reduce the need for instrument changes and may be helpful in following visualised tissue planes. A transvaginal vault closure may be advantageous compared to laparoscopic closure and Endostiches may be preferred to close the fascia of large trocar sites under vision.

EGF inhibits constitutive internalization and palmitoylation-dependent degradation of membrane-spanning procancer CDCP1 promoting its availability on the cell surface.

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.

Dietary folate and related micronutrients, folate-metabolising genes, and ovarian cancer survival.

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.

Vulvar cancer patients' quality of life: a qualitative assessment.

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.

Early-stage vaginal carcinoma--an analysis of 70 patients.

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.

Anemia before and during concurrent chemoradiotherapy in patients with cervical carcinoma: Effect on progression-free survival.

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.

Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer.

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.

Novel MUC1 splice variants are expressed in cervical carcinoma.

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.

Impact of hemoglobin levels before and during concurrent chemoradiotherapy on the response of treatment in patients with cervical carcinoma: preliminary results.

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.

Postoperative vaginal vault brachytherapy for node-negative Stage II (occult) endometrial carcinoma.

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.

Primary Bartholin gland carcinoma: a report of seven cases.

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.

Primary fallopian tube carcinoma: the Queensland experience.

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.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus.

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.

Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy.

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.

Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases.

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.

Fertility and ovarian function after conservative surgery for germ cell tumours of the ovary.

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.

Microinvasive adenocarcinoma of the cervix.

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.

Low malignant potential ovarian tumours: a review of 175 consecutive cases.

Epithelial ovarian tumours of low malignant potential (LMP) are known to have a generally good prognosis, although there is not universal agreement on all aspects of treatment. We report a series of 175 patients with LMP ovarian tumours referred to the Queensland Centre for Gynaecological Cancer between January, 1982 and December, 1993. Stage I disease accounted for 142 cases, with only 1 patient dead from disease at 293 months. Twenty nine patients in this group had conservative surgery with 1 recurrence only (in the contralateral ovary) giving a recurrence rate of 3.5%. Survival and treatment data for other stages are presented, and the current literature reviewed. It is suggested that early stage disease may be treated conservatively depending upon the patient's desire to retain reproductive capacity. While adjuvant therapy is not recommended, long-term follow-up is indicated. More advanced disease should be debulked to the smallest practical volume. The role of lymphadenectomy has been questioned, as survival has not been shown to be affected by treatment decisions made as a result of knowing the lymph node status. Whilst some centres give platinum-based adjuvant therapy, the evidence that it is beneficial is not supported by any prospective randomized trials.

Primary peritoneal carcinoma: a treatable subset of patients with adenocarcinoma of unknown primary.

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.