Regular follow-up with cervical cytology is of questionable value following surgical treatment of microinvasive cervical cancer.

OBJECTIVES: To assess the follow-up smears and their outcomes of patients with conservatively managed early-stage cervical cancer as per UK guidelines within our service. To evaluate whether intensive follow-up can detect pre-cancer early compared to the standard 3 yearly follow-up. STUDY DESIGN: Retrospective review. METHODS: All patients treated for early stage (stage 1A1 and 1A2) with cervical cancer from 01/2002 to 01/2020 at University Hospitals of Derby and Burton were included. Patients who had initial hysterectomy were excluded from our analysis. Review conducted using electronic patient records for treatment, histology, and follow-up smears. Number of abnormal follow-up smears and number of recurrent cervical cancers were considered the main outcome measures. RESULTS: 98 cases were identified. 81 (82.65 %) were stage 1A1 and 17 (17.35 %) were stage 1A2. 74 (75.51 %) patients had squamous histology and 24 (24.49 %) had adenocarcinomas. Median follow-up was 11.08 years (4043 days). 510 follow-up smears were performed, of which 33 (6.47 %) were abnormal. 5 of these abnormal smears showed low grade dyskaryosis (0.98 %) and 2 smears showed high grade dyskaryosis (0.39 %). The positive predictive value of follow-up smears to detect pre-cancerous changes was 5.71 %. There were no recurrent cancers detected. CONCLUSIONS: Microinvasive cervical cancer is effectively managed with conservative surgery. There were no recurrent cancers detected in our cohort during follow-up and there were only 2 high grade dyskaryoses detected (n = 2/510, 0.39 %). We therefore believe that reducing the intensity of follow up of these patients should be considered.

Neo-adjuvant chemotherapy does not reduce surgical complexity nor the accuracy of intra-operative visual assessment of disease in advanced ovarian cancer.

AIM: Compare the surgical complexity and histological accuracy of visual inspection of disease in patients undergoing primary debulking (PDS) versus delayed debulking surgery (DDS) following neo-adjuvant chemotherapy (NACT) for advanced ovarian cancer (AOC). MATERIALS AND METHODS: All patients undergoing PDS or DDS for stage III / IV AOC at a UK cancer centre between January 2014-October 2021 were included. Retrospective data was collected accessing an electronic gynaecological oncology database, operation and histology records. Comparative frequencies of surgical procedures performed were calculated for primary versus delayed cohorts; and correlation between intra-operative suspicion of disease and specimen histology at PDS and DDS compared. RESULTS: N=232. PDS was performed in 45.3% and DDS in 54.7% of patients; achieving complete cytoreduction in 77.2%. Appendicectomy, pelvic and para-aortic nodal dissection were undertaken significantly more often at primary surgery; whilst right diaphragm stripping, pelvic peritonectomy, splenectomy and cholecystectomy were more likely following NACT. We found no variation in bowel resection rates between cohorts. For the majority of specimens, there was no difference in correlation between intra-operative suspicion of disease and final histopathology - with a significantly lower positive predictive value for visual assessment demonstrated only for liver capsule and pelvic peritoneum at DDS. CONCLUSION: NACT does not appear to reduce the complexity of surgery, including rates of bowel resection; nor accuracy of intra-operative visual assessment of disease. We therefore caution against both deferring to NACT to facilitate less radical delayed debulking; and any presumption that macroscopically abnormal tissue at DDS may represent inert post-NACT 'burn-out', mitigating indication for excision. We instead suggest reservation of the neo-adjuvant pathway for patients with poor PS and radiologically-confirmed surgical stopping points; and advocate equivalent and maximal cytoreductive effort to remove all visibly abnormal tissue in both the upfront and delayed surgical settings.

Evaluation of changes to work patterns in multidisciplinary cancer team meetings due to the COVID-19 pandemic: A national mixed-method survey study.

BACKGROUND: It is not well understood the overall changes that multidisciplinary teams (MDTs) have had to make in response to the COVID-19 pandemic, nor the impact that such changes, in addition to the other challenges faced by MDTs, have had on decision-making, communication, or participation in the context of MDT meetings specifically. METHODS: This was a mixed method, prospective cross-sectional survey study taking place in the United Kingdom between September 2020 and August 2021. RESULTS: The participants were 423 MDT members. Qualitative findings revealed hybrid working and possibility of virtual attendance as the change introduced because of COVID-19 that MDTs would like to maintain. However, IT-related issues, slower meetings, longer lists and delays were identified as common with improving of the IT infrastructure necessary going forward. In contrast, virtual meetings and increased attendance/availability of clinicians were highlighted as the positive outcomes resulting from the change. Quantitative findings showed significant improvement from before COVID-19 for MDT meeting organisation and logistics (M = 45, SD = 20) compared to the access (M = 50, SD = 12, t(390) = 5.028, p = 0.001), case discussions (M = 50, SD = 14, t(373) = -5.104, p = 0.001), and patient representation (M = 50, SD = 12, t(382) = -4.537, p = 0.001) at MDT meetings. DISCUSSION: Our study explored the perception of change since COVID-19 among cancer MDTs using mixed methods. While hybrid working was preferred, challenges exist. Significant improvements in the meeting organisation and logistics were reported. Although we found no significant perceived worsening across the four domains investigated, there was an indication in this direction for the case discussions warranting further 'live' assessments of MDT meetings.

Does the character of the hospital of primary management influence outcomes in patients treated for presumed early stage endometrial cancer and atypical endometrial hyperplasia: a comparison of outcomes from a cancer unit and cancer centre.

A retrospective study from 2015 to 2020 comparing overall survival (OS) outcomes of a cancer unit and centre for presumed early stage endometrial cancers is presented. Cancer centres manage these presumed early endometrial cancer (EC) in situations of complex co-morbidities, surgical challenges as well as their own local unit patients. Our analysis compares 138 patients at KMH (unit) and 282 patients at RDH (centre) on OS, patient demographics, grading histology and final histology. Patients with presumed early stage EC can be reassured regarding no difference in OS between the cancer unit and centre management (p = .05). However, rates of minimal access surgery were higher at the cancer centre compared to the unit (93.2% versus 68.1%). The rates of upstaged disease were 4% and 8.8% at the cancer unit and centre respectively (p = .096). Sentinel node biopsy and genomic assessment may change future thresholds for centre-level management due to rates of upstaged disease.Impact StatementWhat is already known on this subject? Presumed lower risk endometrial cancers (endometrioid grades 1 and 2) have a rate of occult nodal involvement of only 1.4%. The BGCS does not recommend lymphadenectomy for low-risk endometrial cancers. These low-risk endometrial cancers should be managed with a hysterectomy and bilateral salpingo-ophrectomy via minimal access surgery. In view of the low rates of occult nodal involvement in low-risk endometrial cancer, surgery can be offered at a cancer unit.What do the results of this study add? Our study demonstrates there is no disadvantage in overall survival in the surgical management of presumed low-risk endometrial cancers at cancer units and centres. However, cancer centres have higher rates of minimal access to surgery despite managing a more elderly population. Our rates of upstaged disease of 4% and 8.8% at the cancer unit and centre indicate a potential benefit of pelvic lymph node assessment.What are the implications of these findings for clinical practice and/or further research? Sentinel lymph node biopsy does not have the surgical morbidity associated with systematic lymph node dissection. Therefore, when applied to presumed early stage endometrial cancer, there are potential changes in the threshold for centre-level management to improve overall survival.

Cancer multidisciplinary team meetings: impact of logistical challenges on communication and decision-making.

BACKGROUND: Multidisciplinary teams (MDTs) are widely used in cancer care. Recent research points to logistical challenges impeding MDT decision-making and dissatisfaction among members. This study sought to identify different types of logistical issues and how they impacted team processes. METHODS: This was a secondary analysis of a cross-sectional observational study. Three cancer MDTs (breast, colorectal, and gynaecological) were recruited from UK hospitals. Validated observational instruments were used to measure decision-making (Metrics of Observational Decision-making, MDT-MODe), communication (Bales' Interaction Process Analysis, Bales' IPA), and case complexity (Measure of Case Discussion Complexity, MeDiC), including logistical challenges (Measure of Case Discussion Complexity, MeDiC), across 822 case discussions from 30 videoed meetings. Descriptive analysis and paired samples t tests were used to identify and compare frequency of different types of logistical challenges, along with partial correlations, controlling for clinical complexity of cases, to understand how such issues related to the MDT decision-making and communication. RESULTS: A significantly higher frequency of administrative and process issues (affecting 30 per cent of cases) was seen compared with the frequency of equipment issues (affecting 5 per cent of cases; P < 0.001) and the frequency of the attendance issues (affecting 16 per cent of cases; P < 0.001). The frequency of the attendance issues was significantly higher than the frequency of equipment issues (P < 0.001). Partial correlation analysis revealed that administrative and process issues, including attendance, were negatively correlated with quality of information (r = -0.15, P < 0.001; r = -0.11, P < 0.001), and equipment issues with the quality of contribution to meeting discussion (r = -0.14, P < 0.001). More questioning and answering by MDT members was evident with the administrative and process issues (r = 0.21, P < 0.001; r = 0.19, P < 0.001). Some differences were observed in teams' socioemotional reactions to the administrative and process issues with the gynaecological MDT showing positive correlation with positive socioemotional reactions (r = 0.20, P < 0.001), and the breast cancer MDT with negative socioemotional reactions (r = 0.17, P < 0.001). CONCLUSION: Administrative and process issues were the most frequent logistical challenges for the studied teams. Where diagnostic results were unavailable, and inadequate patient details provided, the quality of decision-making was reduced.

What are the implications of radiologically abnormal cardiophrenic lymph nodes in advanced ovarian cancer? An analysis of tumour burden, surgical complexity, same-site recurrence and overall survival.

INTRODUCTION: Our paper evaluates the relationship between radiologically abnormal cardiophrenic lymph nodes (CPLN) in advanced ovarian cancer and pattern of disease distribution, tumour burden, surgical complexity, rates of cytoreduction and same-site recurrence. Impact of suspicious CPLN and CPLN dissection on overall survival also determined. MATERIALS AND METHODS: Retrospective review of index CT imaging for 151 consecutive patients treated for stage III/IV ovarian malignancy in a large UK cancer centre to identify radiologically abnormal CPLN. Corresponding surgical, histo-pathological and survival data analysed. RESULTS: 42.6% of patients had radiologically 'positive' CPLN on index CT. Radiological identification of CPLN involvement demonstrated a sensitivity of 82% within our centre. Patients with cardiophrenic lymphadenopathy on pre-operative CT had significantly more co-existing ascites (p = 0.003), omental (p = 0.01) and diaphragmatic disease (p < 0.0001). At primary debulking (PDS), suspicious CPLN were associated with significantly higher surgical complexity scores, without feasibility of complete cytoreduction being impacted. Cardiophrenic involvement at initial diagnosis was associated with same-site relapse at recurrence (p = 0.001). No significant difference in overall survival was demonstrated according to CPLN status following either PDS or delayed debulking (DDS). CPLN dissection did not improve patient outcomes. CONCLUSION: Radiological identification of abnormal CPLN is reliable. Suspicious CPLN appear to represent a surrogate marker of tumour volume - in particular, heralding upper abdominal disease - and should prompt anticipation of high complexity surgery and referral to an appropriate centre. Patients with prior CPLN involvement are more likely to develop same-site recurrence at relapse. Our survival data suggests cardiophrenic LN disease does not worsen patient prognosis and that the therapeutic benefit of CPLN dissection remains unclear.

Lactate Is a Reliable Predictor of ICU Length of Stay Following Ultra-radical Ovarian Cancer Surgery.

BACKGROUND/AIM: With a greater proportion of women with advanced ovarian cancer (AOC) successfully undergoing radical cytoreductive surgery, the demand on peri-operative resources - including intensive care (ICU) beds - is also on the rise. Extended post-operative ICU length of stay (LOS) confers increased patient morbidity and mortality. Several variables associated with prolonged ICU LOS following AOC surgery have been identified. We aimed to evaluate the predictive value of serum lactate levels. PATIENTS AND METHODS: All patients undergoing ultra-radical surgery for AOC in a large cancer centre over a 34-month period between 2018-2021 were identified via the institution tumour registry. Data were collected retrospectively via electronic care and operating records; biochemistry, radiology, and histopathology databases. RESULTS: In total, 63 patients were identified. Elevated intra-operative serum lactate levels were associated with significantly longer length of ICU post-operative stay. Longer time for hyperlactaemia to normalise following surgery also conferred significantly longer ICU, high dependency and total hospital LOS. Greater blood loss, higher surgical complexity and peritoneal carcinomatosis score, and longer operating time were associated with higher - and persistently elevated - peri-operative lactate levels. CONCLUSION: Serum lactate in the context of ultra-radical surgery for AOC represents an accessible and inexpensive marker with potential to not only reliably predict LOS, but also to serve as a dynamic prompt for early targeted intervention. Early recognition and correction of hyperlactaemia following AOC may reduce ICU LOS limiting both the resource pressure and patient morbidity/mortality sequelae.

Poor anaerobic threshold and VO2 max recorded during cardiopulmonary exercise testing (CPET) prior to cytoreductive surgery in advanced (stage 3/4) ovarian cancer (AOC) is associated with suboptimal cytoreduction but does not preclude maximum effort cytoreduction.

This study assessed Cardiopulmonary Exercise Testing (CPET) in predicting oncological outcomes, post-operative recovery and complications in advanced ovarian cancer (AOC) cytoreductive surgery. We reviewed all patients who had CPET prior to AOC cytoreductive surgery with evidence of upper abdominal disease on preoperative imaging at the University Hospitals of Derby and Burton (UHDB) between August 2016 and July 2019. Patients were stratified by AT and maximum VO2 levels. 43 patients were identified. AT showed no relationship with major complications. 100% of patients in the AT ≥11 group received R0 (n = 21, 91.30%), or R1 (n = 2, 8.70%) cytoreduction, whereas in the AT <11 group, only 75.00% achieved and R0 or R1 resection (p = .02). Surgical complexity was higher in the AT ≥11 group (p = .001) and the VO2 ≥15 group (p = .0006). No other correlations were seen between AT or VO2 max and complications or readmissions. No difference in overall survival was seen if R0 resection was achieved.IMPACT STATEMENTWhat is already known on this subject? CPET testing allows pre-operative assessment of functional capacity to generate variables that can be used as a risk-stratification tool for major surgery. Whilst CPET testing has been shown to predict morbidity in non-gynaecological surgery, it remains unproven in cytoreductive surgery for ovarian cancer surgery despite being increasingly utilised.What do the results of study add? Our data suggest that CPET testing does not predict complication rates or survival in AOC. Patients with poor CPET performance are more likely to receive suboptimal cytoreductive outcomes from surgery.What are the implications of these findings for clinical practice and/or further research? CPET results should not be used to discount patients from cytoreductive surgery further research should address the interplay with nutrition, haematological markers, neoadjuvant chemotherapy and CPET performance.

Does the Performance of Splenectomy as Part of Cytoreductive Surgery Carry a Worse Prognosis Than in Patients Not Receiving Splenectomy? A Propensity Score Analysis and Review of the Literature.

BACKGROUND & OBJECTIVES: Ultra-radical (UR) procedures, including splenectomy, are utilized to increase complete cytoreduction rates during Cytoreductive Surgery (CRS) performed with the aim of complete macroscopic clearance of disease. The purpose of this study was to investigate if splenectomy negatively impacts survival when undertaken during CRS for advanced ovarian cancer (AOC) and compare published splenectomy and cytoreduction rates. METHODS: A retrospective review of all consecutive patients who underwent cytoreductive surgery for AOC between 16/05/2013-28/01/2019. Survival, baseline patient characteristics, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed to reduce bias. RESULTS: 154 patients identified over 71 months. 97 underwent standard, 57 underwent UR surgery, 27 patients received splenectomy (17.5%) No difference was seen in overall survival (OS) between all patients (median OS 34 months (95%CI 25.9-41.1) and patients who underwent splenectomy (median OS not yet reached) (p = >0.05). After PSM for various baseline covariates, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56%) (P > 0.05). Three splenectomy specific complications occurred; one each of pancreatic tail injury, left pleural effusion and streptococcal pharyngitis during chemotherapy. We found wide variation in utilization of splenectomy in published case series; from 9% to 35%. CONCLUSIONS: Splenectomy performed as part of CRS is not detrimental to survival in AOC. There is a wide variation in utilization of splenectomy in published case series with little correlation with cytoreduction rates.

A multicentre cross-sectional observational study of cancer multidisciplinary teams: Analysis of team decision making.

BACKGROUND: Multidisciplinary teams (MDT) formulate expert informed treatment recommendations for people with cancer. We set out to examine how the factors proposed by the functional perspective of group decision making (DM), that is, interaction process, internal factors (factors emanating from within the group such as group size), external circumstances (factors coming from the outside of the team), and case-complexity affect the quality of MDT decision making. METHODS: This was a cross-sectional observational study. Three cancer MDTs were recruited with 44 members overall and 30 of their weekly meetings filmed. Validated observational instruments were used to measure quality of DM, interactions, and complexity of 822 case discussions. RESULTS: The full regression model with the variables proposed by the functional perspective was significant, R2  = 0.52, F(20, 801) = 43.47, P < .001, adjusted R2  = 0.51. Positive predictors of DM quality were asking questions (P = .001), providing answers (P = .001), team size (P = .007), gender balance (P = .003), and clinical complexity (P = .001), while negative socioemotional reactions (P = .007), gender imbalance (P = .003), logistical issues (P = .001), time-workload pressures (P = .002), and time spent in the meeting (P = .001) were negative predictors. Second half of the meetings also saw significant decrease in the DM quality (P = .001), interactions (P = .001), group size (P = .003), and clinical complexity (P = .001), and an increase in negative socioemotional reactions (P = .001) and time-workload pressures (P = .001). DISCUSSION: To the best of our knowledge, this is the first study to attempt to assess the factors proposed by the functional perspective in cancer MDTs. One novel finding is the effect of sociocognitive factors on team DM quality, while another is the cognitive-catch 22 effect: while the case discussions are significantly simpler in the second half of the meeting, there is significantly less time left to discuss the remaining cases, further adding to the cognitive taxation in teams who are now rapidly attempting to close their time-workload gap. Implications are discussed in relation to quality and safety.

Primary and Interval Debulking Surgery Provide Similar Survival and Platinum Sensitivity Outcomes in Advanced Ovarian Cancer: A Retrospective Study.

BACKGROUND/AIM: CHORUS and EORTC55971 trials demonstrated that neoadjuvant chemotherapy followed by interval debulking surgery (IDS) or primary debulking surgery (PDS) offered the same survival rates. These trials have since been criticised due to poor surgical complexity. We compared overall (OS), progression free (PFS), and platinum sensitivity in advanced ovarian cancer (AOC) patients undergoing IDS or PDS, who had received either intermediate or high complexity surgery to achieve complete cytoreduction. PATIENTS AND METHODS: All patients with AOC treated between February 2014 and May 2019 obtaining complete cytoreduction with intermediate/high surgical complexity were included. Recurrence was defined according to GCIG criteria on radiological findings and/or CA125 levels. RESULTS: Seventy-one patients (38 PDS and 33 IDS) with full recurrence data were identified. No statistical difference was seen between groups in OS, PFS or platinum sensitive interval. CONCLUSION: PDS or IDS were both acceptable treatment options for AOC, showing similar survival and platinum sensitivity outcomes in patients undergoing intermediate or high complexity surgery.

Experiences of enhanced recovery after surgery in general gynaecology patients: An interpretative phenomenological analysis.

There is little qualitative research exploring non-cancer gynaecology patients' experiences of enhanced recovery after surgery (ERAS) protocols. Seven women participated in audio-recorded interviews, discussing their experiences of enhanced recovery after surgery for gynaecological surgery. Data were transcribed and analysed using interpretative phenomenological analysis. Three themes were identified: meeting informational needs, taking control of pain, and mobilising when feeling fragile. Control emerged as a key element throughout the themes and was supported by provision of factual information. While participants were generally satisfied with their experience, topics such as concerns about analgesic use, the informal role of staff in mobilisation, and the expressed desire for more experiential information for participants require further research.

Comparing the experience of enhanced recovery programme for gynaecological patients undergoing laparoscopic versus open gynaecological surgery: a prospective study.

BACKGROUND: Enhanced recovery has been shown to improve patients' experience after surgery. There are no previous studies comparing patients' experience between those undergoing laparoscopic and open gynaecological surgery. Therefore, the aim of this prospective study is to compare patients' functional recovery based on milestones set by the enhanced recovery programme and patients' satisfaction between the two groups. METHODS: All eligible patients undergoing gynaecological surgery within an enhanced recovery after surgery (ERAS) programme from March to August 2014 were involved in this study. All patients received the questionnaires on admission which were then collected prior to discharge. They were followed up by telephone within 7 days. RESULTS: Two hundred sixty-three patients were involved. One hundred forty-four questionnaires were returned (54% response rate). Fifty-one percent (n = 74) were from the laparoscopic group and 49% (n = 70) were from the laparotomy group. In terms of achieving milestones, more patients in the laparotomy group performed the deep breathing exercises (laparoscopic versus open; 66.2% versus 87.1% (p = 0.003). The laparoscopic group were more able to eat on day 0, but by day 1, there was no difference between the groups. Both groups were similar in their ability to drink (p = 0.98), mobilise (p = 0.123) and sit out in a chair (p = 0.511). In the laparoscopic group, the patients' experience was better for pain control (p < 0.0001) and nausea control (p = 0.003) from recovery to day 1, and they were more able to put on their own clothes (p = 0.001) and were more confident in mobilising (p < 0.0001) and in going home (p < 0.0001). The laparoscopic group had greater patient satisfaction with their pain always being well controlled (p < 0.0001) whilst more patients in the laparotomy group reported being satisfied to very satisfied with their overall care on the gynaecology ward (p = 0.04). Both groups were equally satisfied with their care from nursing staff (p = 0.709) and doctors (p = 0.431). CONCLUSION: The two groups were in general equally able to achieve the majority of the milestones despite differences in symptoms such as pain, nausea and confidence in mobilising and going home. Pre-operative education can empower patients to engage in their recovery. There is a high level of patient satisfaction in both groups.

Exploring the experience of an enhanced recovery programme for gynaecological cancer patients: a qualitative study.

BACKGROUND: Perioperative enhanced recovery programmes (ERPs), identified as initiatives that improve care and save money, have been adopted by NHS Improvement and are currently being rolled out across many surgical departments within the NHS. To date, five papers have specifically explored patients' experiences of ERPs; none, however, has explored the gynaecological cancer patient experience. METHODS: In total, 14 women (mean age, 66 years) participated in an audio-recorded face-to-face or telephone interview in which they discussed their experience of taking part in an ERP. The resulting data were transcribed verbatim and analysed using interpretative phenomenological analysis. RESULTS: Two main themes emerged from the analysis. The first, 'Taking part in the programme', highlights two important aspects of the ERP: being given an opportunity to receive information and, following this, to build knowledge about the programme. The theme also explores the challenges associated with the programme, particularly around getting mobile and complying with its demands - the women report experiencing a constant battle between intuition and instruction. The second theme, 'Home', focuses on the role home plays in motivating the patients to aim for an early discharge from hospital. Patients describe their need to return to a suitable home and the need for support from others. They also discuss the importance of the follow-up phone call. CONCLUSION: Overall, the patients in this study positively assessed the individual aspects of the ERP, in particular, information resources, the availability of the physiotherapist and the delivery of follow-up phone calls. These findings highlight the importance of developing and maintaining individual aspects of ERPs over time, to ensure their sensitivity and responsiveness to patient needs.

Expression and prognostic significance of the oncogenic K2P potassium channel KCNK9 (TASK-3) in ovarian carcinoma.

BACKGROUND/AIMS: The TWIK-related acid sensitive K(+) channel-3 (TASK-3) is an oncogenic potassium channel. We investigated the expression of TASK-3 in human ovaries, examined its prognostic significance, and determined effects of TASK-3 blockers on cell proliferation and apoptosis. MATERIALS AND METHODS: Immunofluorescence and western blotting were used to investigate TASK-3 expression in two ovarian cancer cell lines, normal ovarian surface epithelium and cancer. Immunohistochemistry quantified expression in an ovarian cancer tissue microarray. The effect of TASK-3 blocking agents on cell proliferation was investigated with the CellTiter 96® Aqueous Non-Radioactive Cell Proliferation assay and on apoptosis with flow cytometry. RESULTS: TASK-3 expression was confirmed by immunofluorescence in the SKOV-3 and OVCAR-3 cell lines, normal ovaries (n=4) and ovarian tumours (n=4) and by western blotting in normal ovaries (n=6) and ovarian tumours (n=22). Immunohistochemistry demonstrated immunostaining in 99% of tumours (n=230). Increased immunostaining conferred a survival advantage (p=0.002; median survival of >24 months). TASK-3 blockers caused a significant reduction in cell proliferation and an increase in apoptosis in the SKOV-3 and OVCAR-3 cell lines. CONCLUSION: TASK-3 is expressed in epithelial ovarian cancer, conferring a significant survival advantage on patients with increased expression. TASK-3-modulating agents have a significant effect on cell proliferation and apoptosis. Based on these results, we propose that TASK-3 could prove to be both a novel tumour marker and a new therapeutic target in ovarian cancer, but further investigation is required.

Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer.

INTRODUCTION: Ovarian cancer is associated with high mortality due to presentation at advanced stage and high recurrence following treatment with chemotherapy. Most of the prognostic variables in ovarian cancer, including stage and residual disease, are amenable for assessment only after surgery. Currently there are no established preoperative markers including, CA-125, that can predict overall survival in patients with ovarian cancer. The aim of our study was to evaluate the prognostic significance of the preoperative haematological markers platelet lymphocyte ratio (PLR) and neutrophil lymphocyte ratio (NLR) in patients with ovarian cancer. METHOD: Preoperative PLR and NLR were evaluated in 235 patients undergoing surgery for ovarian cancer. The prognostic significance of both markers was then determined by both uni- and multivariate analytical methods. RESULTS: High preoperative PLR (p < 0.001) and NLR (p = 0.001) were significantly associated with poor survival using univariate Cox survival analysis. The median overall survival in patients with a PLR of < 300 was 37.4 months (95% CI 26.1-48.7) and 14.5 months (95% CI 11.7-17.2) in those with a PLR of > 300. PLR (p = 0.03) but not NLR (p = 0.575) retained its significance as a prognostic marker on multivariate Cox's regression analysis, along with stage (p < 0.001) and residual disease (p = 0.015). CONCLUSION: We have shown for the first time that PLR is a novel independent prognostic marker in patients with ovarian cancer.

The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line.

BACKGROUND: The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells. METHODS: The presence of Eag and HERG was determined in SK-OV-3 cells using immunofluorescence and western blotting. The effect of the Eag blockers (imipramine and clofilium) and HERG blockers (E-4031 and ergtoxin) on cell proliferation was assessed using the MTS assay with further investigation of their role in the cell cycle and apoptosis determined by flow cytometry. RESULTS: Eag and HERG channels were present in the cytoplasm and nuclei of SK-OV-3 cells. There was significant inhibition of proliferation of SK-OV-3 cells by imipramine (P < 0.001) and ergtoxin (P < 0.05) at 72 hours of culture. Incubation of cells with ergtoxin led to the accumulation of cells in the S and G2/M phase, while cells accumulated in S phase after incubation with E-4031, with no effect on apoptosis. Imipramine did not affect the cell cycle but increased the proportion of SK-OV-3 cells undergoing early apoptosis. CONCLUSION: Both Eag and HERG channels are expressed in SK-OV-3 ovarian cancer cells and have a role in cell proliferation. HERG channels affect the cell cycle while Eag channels are implicated in the inhibition of apoptosis of ovarian cancer cells. The family of Eag channels may represent a new therapeutic target for the treatment of ovarian cancer.

Synovial sarcoma of the vulva: a case report.

INTRODUCTION: Contrary to its name, synovial sarcoma does not arise from the synovial membrane but from multipotent stem cells and can present in any part of the body. Very few cases of vulval synovial sarcoma have been reported in the literature; we report on such a presentation. These tumors can present as painless lumps, which must be completely excised to give the best prognosis. Therefore the diagnosis of synovial sarcoma should always be kept in mind in the management of vulval masses, especially in young patients. CASE PRESENTATION: We report the case of a 28-year-old Caucasian woman with synovial sarcoma of the vulva. Complete excision was possible in this case. CONCLUSION: We have presented a rare case of synovial sarcoma of the vulva, which can be easily confused with lipoma of the vulva. The management of this tumor requires referral to a cancer centre, with a multidisciplinary approach.

The Eag potassium channel as a new prognostic marker in ovarian cancer.

BACKGROUND: Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression. OBJECTIVES: To determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation. METHODS: The expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3). RESULTS: We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K+ channel blockers. CONCLUSION: This novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.

Eag and HERG potassium channels as novel therapeutic targets in cancer.

Voltage gated potassium channels have been extensively studied in relation to cancer. In this review, we will focus on the role of two potassium channels, Ether à-go-go (Eag), Human ether à-go-go related gene (HERG), in cancer and their potential therapeutic utility in the treatment of cancer. Eag and HERG are expressed in cancers of various organs and have been implicated in cell cycle progression and proliferation of cancer cells. Inhibition of these channels has been shown to reduce proliferation both in vitro and vivo studies identifying potassium channel modulators as putative inhibitors of tumour progression. Eag channels in view of their restricted expression in normal tissue may emerge as novel tumour biomarkers.