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.

Combined direct hysteroscopic and real-time ultrasound guidance facilitating safe insertion of intra-uterine brachytherapy applicator for locally advanced cervical cancer with significant endocervical stenosis: A novel collaborative approach.

Locally advanced cervical cancer is treated with combined chemoradiation (CCRT) - with the radiotherapy component comprising delivery of both external beam (EBRT) and intra-uterine brachytherapy (IUBT). Following initial pelvic and tumour irradiation via EBRT, secondary tissue fibrosis can obliterate the vagina and / or endocervical canal. 30-88% of women will develop some degree of stenosis, with complete stenosis reported in up to 11% of patients - making accessing the uterine cavity to insert brachytherapy applicators challenging and high risk (Bran et al., 2006). This can result in inadvertent uterine perforation, occurring in 2-10% of cases (Irvin et al., 2002); with subsequent abandonment of both the procedure and proceeding to IUBT to complete treatment. Omission of IUBT confers an at least 10% reduction in overall survival (Karlsson et al., 2017). Whilst ultrasound-guided insertion has been previously described (Van Dyk et al., 2021), we present a surgical video demonstrating a novel technique. We instead utilise a combination of both real-time ultrasound and direct hysteroscopic guidance to achieve successful IUBT applicator insertion following CCRT in a patient with stage IIa1 SCC cervix and previous failed insertion attempt due to complete stenosis of the endocervical canal. We demonstrate how post-radiation changes can be safely navigated - avoiding morbidity from procedural complications and ensuring successful outcome. Our case supports a collaborative approach to complex gynaecological cancer cases; with the combined skills of the oncology, radiology and surgical teams maximising patient safety - and optimising oncological treatment. Use of portable hand-held hysteroscopic devices would increase the feasibility of replicating our described technique in brachytherapy suites, mitigating need for theatre capacity; with MDT discussion central to the planning and staffing of cases.

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.

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.

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.

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.

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.

Selection of suitable reference genes for gene expression studies in normal human ovarian tissues, borderline ovarian tumours and ovarian cancer.

The use of reference genes is the most common method of controlling the variation in mRNA expression during quantitative polymerase chain reaction, although the use of traditional reference genes, such as ß­actin, glyceraldehyde­3­phosphate dehydrogenase or 18S ribosomal RNA, without validation occasionally leads to unreliable results. Therefore, the present study aimed to evaluate a set of five commonly used reference genes to determine the most suitable for gene expression studies in normal ovarian tissues, borderline ovarian and ovarian cancer tissues. The expression stabilities of these genes were ranked using two gene stability algorithms, geNorm and NormFinder. Using geNorm, the two best reference genes in ovarian cancer were ß­glucuronidase and ß­actin. Hypoxanthine phosphoribosyltransferase­1 and ß­glucuronidase were the most stable in ovarian borderline tumours, and hypoxanthine phosphoribosyltransferase­1 and glyceraldehyde­3­phosphate dehydrogenase were the most stable in normal ovarian tissues. NormFinder ranked ß­actin the most stable in ovarian cancer, and the best combination of two genes was ß­glucuronidase and ß­actin. In borderline tumours, hypoxanthine phosphoribosyltransferase­1 was identified as the most stable, and the best combination was hypoxanthine phosphoribosyltransferase­1 and ß­glucuronidase. In normal ovarian tissues, ß­glucuronidase was recommended as the optimum reference gene, and the most optimum pair of reference genes was hypoxanthine phosphoribosyltransferase­1 and ß­actin. To the best of our knowledge, this is the first study to investigate the selection of a set of reference genes for normalisation in quantitative polymerase chain reactions in different ovarian tissues, and therefore it is recommended that ß­glucuronidase, ß­actin and hypoxanthine phosphoribosyltransferase­1 are the most suitable reference genes for such analyses.

Detection of cervical intraepithelial neoplasia using impedance spectroscopy: a prospective study.

OBJECTIVE: To compare cervical impedance spectrometry in the cervical epithelium of women with cervical intraepithelial neoplasia (CIN) and normal epithelium. DESIGN: Prospective observational study. SETTING: Colposcopy clinic, Jessop Wing, Royal Hallamshire Hospital, Sheffield, UK. POPULATION: Eighty-seven women referred to colposcopy with a moderate or severely dyskaryotic smear. METHODS: A pencil probe incorporating four gold electrodes was used to measure an electrical impedance spectrum from cervical epithelium. Colposcopy examinations, including probe positioning, were recorded by video to allow for correlation between results obtained from colposcopic impression, histopathological examination of colposcopically directed punch biopsies and the impedance measurements. MAIN OUTCOME MEASURES: Cervical impedance derived parameters R, S and C were assessed to see if there was a significant difference in values obtained in CIN and normal squamous epithelium. Analysis was based upon matching the electrical components measured to those identified by cellular modelling as being most sensitive for premalignancy. RESULTS: From normal epithelium through CIN 1 to CIN 2/3, R decreased by a factor of 4.5, S increased by a factor of 2.5 but C remained unchanged. CONCLUSIONS: Cervical impedance spectrometry provides a potentially promising screening tool with similar sensitivity and specificity to currently used screening tests, but with the potential advantage of providing instant results. Further work is currently being undertaken to improve the probe in its clinical use.