Feasibility of robotic platform to perform R0 resection for locally advanced multi-visceral pelvic malignancy: an institutional experience on outcomes of robotic pelvic exenteration.

BACKGROUND: Exenteration surgery for multi-visceral pelvic malignancy is a complex life-changing operation with high perioperative morbidity and mortality. Traditional open surgery has long been the standard approach for pelvic exenteration for achieving Ro resection which is the main aim of surgery. In the current era of minimally invasive surgery, robotic-assisted pelvic exenteration has provided a promising alternative, offering potential advantages in terms of improved oncological outcomes and enhanced postoperative recovery. This study aims to explore the feasibility of a robotic platform for locally advanced multi-visceral pelvic malignancy. METHODS: A retrospective review from the prospectively maintained robotic colorectal surgery database at University Hospital Coventry and Warwickshire (UHCW) Trust was performed. Demographic details and clinical and surgical details were documented from the case records. Data was analysed using SPSS version 22. RESULTS: Thirteen female patients diagnosed with primary or recurrent pelvic malignancy who underwent robotic pelvic exenteration at UHCW between February 2019 and April 2023 at UHCW were included. The mean age of our patients was 60.4 (± 10.1) years. Complete Ro resection was achieved in all 13 (100%) cases on final histopathology. The median length of hospital stay was 15 days after this extensive surgery. Grade 3 morbidity on Clavien-Dindo classification was observed in four (30.7%) patients, while zero percent 30-day mortality was experienced in this study. At a median follow-up of 21 (3-53) months, we observed tumor recurrence in three (23.7%) patients, while death in four (30.7%) patients. Only few studies have highlighted outcomes of robotic pelvic exenteration, and our results were quite comparable to them. CONCLUSION: Robotic-assisted pelvic exenteration for primary or recurrent pelvic malignancy is feasible with improved oncological and acceptable postoperative outcomes.

Type II or type III radical hysterectomy compared to chemoradiotherapy as a primary intervention for stage IB2 cervical cancer.

BACKGROUND: Cervical cancer is the fourth most common cancer in women, with 528,000 estimated new cases globally in 2012. A large majority (around 85%) of the disease burden occurs in low- and middle-income countries (LMICs), where it accounts for almost 12% of all female cancers. Treatment of stage IB2 cervical cancers, which sit between early and advanced disease, is controversial. Some centres prefer to treat these cancers by radical hysterectomy, with chemoradiotherapy reserved for those at high risk of recurrence. In the UK, we treat stage IB2 cervical cancers mainly with chemoradiotherapy, based on the rationale that a high percentage will have risk factors necessitating chemoradiotherapy postsurgery. There has been no systematic review to determine the best possible evidence in managing these cancers. OBJECTIVES: To determine if primary surgery for stage IB2 cervical cancer (type II or type III radical hysterectomy with lymphadenectomy) improves survival compared to primary chemoradiotherapy.To determine if primary surgery combined with postoperative adjuvant chemoradiotherapy, for stage IB2 cervical cancer increases patient morbidity in the management of stage IB2 cervical cancer compared to primary chemoradiotherapy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 3), MEDLINE via Ovid (1946 to April week 2, 2018) and Embase via Ovid (1980 to 2018 week 16). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies up to April 2018. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs), quasi-RCTs or non-randomised studies (NRSs) comparing surgery to chemoradiotherapy in stage IB2 cervical cancers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data, assessed risk of bias and analysed data using standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 4968 records from the literature searches, but we did not identify any RCTs that compared primary surgery with chemoradiotherapy in stage IB2 cervical cancer.We found one NRS comparing surgery to chemoradiotherapy in IB2 and IIA2 cervical cancers which met the inclusion criteria. However, we were unable to obtain data for stage IB2 cancers only and considered the findings very uncertain due to a high risk of selection bias. AUTHORS' CONCLUSIONS: There is an absence of high-certainty evidence on the relative benefits and harms of primary radical hysterectomy versus primary chemoradiotherapy for stage IB2 cervical cancer. More research is needed on the different treatment options in stage IB2 cervical cancer, particularly with respect to survival, adverse effects, and quality of life to facilitate informed decision-making and individualised care.

Management of Early Cervical Stromal Invasion FIGO Stage 1A1 When Margins Are Involved With Cervical Intraepithelial Neoplasia.

OBJECTIVE: Women with International Federation of Gynecology and Obstetrics stage 1A1 cervical carcinoma were evaluated to determine whether repeat excision for large loop excision transformation zone margins positive with cervical intraepithelial neoplasia (CIN) had been undertaken according to the National Health Service Cervical Screening Programme guidelines and if deviations from guidelines adversely affected patient outcome. MATERIALS AND METHODS: We retrospectively studied patients with 1A1 cervical carcinoma treated in our service between May 2010 and July 2015 to determine whether NHSCSP guidelines (May 2010) were followed. This states that if the invasive disease is excised but CIN extends to the excision margin, then a repeat large loop excision transformation zone should be undertaken to exclude further invasive disease and to confirm excision of CIN. RESULTS: Seventeen patients were identified. In one, neither the invasive lesion nor CIN was fully excised. In 5, the lesion and CIN were fully excised. In eleven, the invasive lesion was excised, but CIN was present at a margin. Of these 11 patients, none opted for a repeat excision. All 11 patients had negative cytology at first follow-up (negative up to 4 years [median = 2 years]). CONCLUSIONS: Our outcomes suggest that it may not be necessary to perform a repeat excision for CIN present at the excision margin in women with 1A1 cervical carcinoma when CIN is present either at the endocervical, deep stromal, or ectocervical margin, as long as the invasive focus is fully excised, and patients have been fully counseled and have regular cytology follow-up. This may be an alternative for patients wanting to minimize the risks to fertility posed by repeat excision.

Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.

BACKGROUND: The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen. METHODS: In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2), or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1.18. This trial is registered, number ISRCTN74802813, and is closed to new participants. FINDINGS: Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22.6 months in the primary-surgery group versus 24.1 months in primary chemotherapy. The HR for death was 0.87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0.98 (95% CI 0.72-1.05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0.0007, and 14 women [6%] vs 1 woman [<1%], p=0.001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0.0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group. INTERPRETATION: In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer. FUNDING: Cancer Research UK and the Royal College of Obstetricians and Gynaecologists.

Robotic and laparoscopic gynaecological surgery: a prospective multicentre observational cohort study and economic evaluation in England.

OBJECTIVE: To compare the health-related quality of life and cost-effectiveness of robot-assisted laparoscopic surgery (RALS) versus conventional 'straight stick' laparoscopic surgery (CLS) in women undergoing hysterectomy as part of their treatment for either suspected or proven gynaecological malignancy. DESIGN: Multicentre prospective observational cohort study. SETTING: Patients aged 16+ undergoing hysterectomy as part of their treatment for gynaecological malignancy at 12 National Health Service (NHS) cancer units and centres in England between August 2017 and February 2020. PARTICIPANTS: 275 patients recruited with 159 RALS, 73 CLS eligible for analysis. OUTCOME MEASURES: Primary outcome was the European Organisation for Research and Treatment of Cancer Quality of Life measure (EORTC). Secondary outcomes included EuroQol-5 Dimension (EQ-5D-5L) utility, 6-minute walk test (6MWT), NHS costs using pounds sterling (£) 2018-2019 prices and cost-effectiveness. The cost-effectiveness evaluation compared EQ-5D-5L quality adjusted life years and costs between RALS and CLS. RESULTS: No difference identified between RALS and CLS for EORTC, EQ-5D-5L utility and 6MWT. RALS had unadjusted mean cost difference of £556 (95% CI -£314 to £1315) versus CLS and mean quality adjusted life year (QALY) difference of 0.0024 (95% CI -0.00051 to 0.0057), non-parametric incremental cost-effectiveness ratio of £231 667per QALY. For the adjusted cost-effectiveness analysis, RALS dominated CLS with a mean cost difference of -£188 (95% CI -£1321 to £827) and QALY difference of 0.0024 (95% CI -0.0008 to 0.0057). CONCLUSIONS: Findings suggest that RALS versus CLS in women undergoing hysterectomy (after adjusting for differences in morbidity) is cost-effective with lower costs and QALYs. Results are highly sensitive to the usage of robotic hardware with higher usage increasing the probability of cost-effectiveness. Non-inferiority randomised controlled trial would be of benefit to decision-makers to provide further evidence on the cost-effectiveness of RALS versus CLS but may not be practical due to surgical preferences of surgeons and the extensive roll out of RALS.

The evolving role of one-step nucleic acid amplification (OSNA) for the intra-operative detection of lymph node metastases: A diagnostic accuracy meta-analysis.

BACKGROUND: One Step Nucleic Acid Amplification (OSNA) assay has recently emerged as a rapid molecular diagnostic tool for the detection of lymph node (LN) metastases. It is a molecular technique that analyses the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumour specific cytoceratin 19 mRNA. AIM: To ascertain the diagnostic accuracy of OSNA assay in detecting LN metastases amongst different types of malignancy. DESIGN: We systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2020. Quality assessment was performed using the Modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We calculated pooled diagnostic indices using the random-effects model. Meta-regression and sub-group analyses were performed to address heterogeneity. RESULTS: 31 studies were included in this meta-analysis, including four different types of cancer. The risk of bias and the overall quality of included studies was moderate to high. There was no evidence of publication bias. The pooled diagnostic odds ratio (DOR) for detecting LN metastases in gynaecological, head & neck/thyroid, gastrointestinal and lung cancer were 100.38, 76.17, 275.14, and 305.84, respectively. CONCLUSIONS: Our findings suggest that OSNA assay had a high diagnostic accuracy in detecting metastatic LNs in different types of malignancy. This evidence is constrained by the limited studies available for few tumour types and the rather high heterogeneity for few outcomes.

Assessing the accuracy of colposcopy at predicting the outcome of abnormal cytology in pregnancy.

OBJECTIVE: To determine the accuracy of colposcopic and cytological assessment at predicting final histological diagnosis in women referred with abnormal cervical smears during pregnancy; to use this data as a basis for a follow up protocol for pregnant patients referred with abnormal cervical cytology. STUDY DESIGN: Retrospective analysis of women referred to Queens Medical Centre, Nottingham, UK with abnormal cytology whilst pregnant between 1994 and 2003. RESULTS: Forty-nine patients in total were included in the study. Colposcopic assessment in the antenatal period had a concordance with final histological diagnosis in 60% of patients and a concordance of 68% when undertaken in the post-natal period. Cytological concordance was lower at 58%. In only six percent of patients was a cervical biopsy undertaken and there were no complications as a result. There was a fall in colposcopically assessed high-grade cervical intraepithelial neoplasia between the antenatal and post-natal period. No cases of invasive cancers were diagnosed antenatally. CONCLUSION: A policy of conservative management of pregnant patients during the antenatal period is supported by this data. A suggested protocol of one colposcopic assessment at the time of the index abnormal smear followed by a post-partum colposcopy, and appropriate treatment is suggested.

The role of Lamin A in cytoskeleton organization in colorectal cancer cells: a proteomic investigation.

Up-regulated expression of lamin A has been implicated in increased cell invasiveness and mortality in colorectal cancer. Here we use quantitative proteomics to investigate lamin A regulated changes in the cytoskeleton that might underpin increased cell motility. Using siRNA knockdown of lamin A in a model cell line (SW480/lamA) we confirm that the presence of lamin A promotes cell motility. Using an enhanced technique to prepare cytoskeleton fractions in combination with 2D DiGE we were able to accurately and reproducibly detect changes in the representation of protein species within the cytoskeleton as low as 20%. In total 64 protein spots displayed either increased or decreased representation within the cytoskeleton of SW480/lamA cells compared to controls. Of these the identities of 29 spots were determined by mass spectrometry. A majority were multiple forms of three classes of proteins, including components of the actin and IF cytoskeletons, protein chaperones and translation initiation and elongation factors. In particular our data reveal that the representation of tissue transglutaminase 2, which is known to modify elements of the cytoskeleton and is associated with cancer progression, was highly over-represented in the cytoskeleton fraction of SW480/lamA cells. Overall, our data are consistent with changed protein cross-linking and folding that favours the formation of dynamic actin filaments over stress fibres accounting for the altered cell motility properties in SW480/lamA cells.