Pelvic exenteration: a retrospective study in a tertiary referral cancer center in the UK.

BACKGROUND: Pelvic exenteration (PE) is an extensive surgery that is indicated in cases of recurrent advanced gynecological cancer with curative and sometimes palliative intent. The procedure is associated with both high morbidity and mortality and as such is considered a highly specialist procedure. The aim of the study was to analyze surgical outcomes in women who underwent PE for advanced gynecological malignancy in a tertiary cancer referral center over 11 years. METHODS: This is an observational retrospective single-center study. There were 17 patients included who underwent PE in Hull Royal Infirmary Hospital (Hull, UK) between 2010 and 2021. The main outcome measures were the perioperative complications, overall survival (OS), and recurrence free survival (RFS). Cumulative survival rates were reported at 1, 3 and 5 years. Univariate Cox regression analysis was undertaken to analyze factors that are prognostic for OS and RFS. Hazard Ratios (HR) with 95% confidence intervals (95% CI) were computed from the results of the Cox regression analyses. Kaplan-Meier survival curves were generated to visually display estimates of OS and RFS over the follow-up period. RESULTS: The median age at the time of surgery was 63.0 (IQR: 48.0-71.0). All patients received surgery with curative intent and complete tumor resection (R0) was achieved in 94.1% of cases. An overall 5-year survival was achieved in 63.7% of patients. Mean overall survival (OS) was 8.4 years (95% CI: 7.78-9.02). The RFS was 5.0 years (95% CI: 4.13-5.87). Both OS and RFS were significantly negatively affected by the hospital stay (P=0.020 and P=0.035, respectively), but not by the type of surgery (P=0.263 and P=0.826, respectively). CONCLUSIONS: The results of the study demonstrated stable and comparable outcomes in patients undergoing pelvic exenteration.

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma.

BACKGROUND: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). METHODS: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. RESULTS: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. CONCLUSIONS: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.

Diagnostic Accuracy of Liquid Biomarkers for the Non-Invasive Diagnosis of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Endometrial cancer rates are increasing annually due to an aging population and rising rates of obesity. Currently there is no widely available, accurate, non-invasive test that can be used to triage women for diagnostic biopsy whilst safely reassuring healthy women without the need for invasive assessment. The aim of this systematic review and meta-analysis is to evaluate studies assessing blood and urine-based biomarkers as a replacement test for endometrial biopsy or as a triage test in symptomatic women. For each primary study, the diagnostic accuracy of different biomarkers was assessed by sensitivity, specificity, likelihood ratio and area under ROC curve. Forest plots of summary statistics were constructed for biomarkers which were assessed by multiple studies using data from a random-effect models. All but one study was of blood-based biomarkers. In total, 15 studies reported 29 different exosomal biomarkers; 34 studies reported 47 different proteomic biomarkers. Summary statistic meta-analysis was reported for micro-RNAs, cancer antigens, hormones, and other proteomic markers. Metabolites and circulating tumor materials were also summarized. For the majority of biomarkers, no meta-analysis was possible. There was a low number of small, heterogeneous studies for the majority of evaluated index tests. This may undermine the reliability of summary estimates from the meta-analyses. At present there is no liquid biopsy that is ready to be used as a replacement test for endometrial biopsy. However, to the best of our knowledge this is the first study to report and meta-analyze the diagnostic accuracy of different classes of blood and urine biomarkers for detection of endometrial cancer. This review may thus provide a reference guide for those wishing to explore candidate biomarkers for further research.

Minimally invasive pelvic exenteration for gynaecological malignancy: A single-centre case series and review of the literature.

For those with certain recurrent gynaecological cancers where primary management such as chemo-radiotherapy has failed, or in cases of recurrence following primary surgery, pelvic exenteration (PE) is considered the only curative option. Whilst initially considered a morbid procedure, improved surgical techniques, advancing technology, and nuanced reconstructive options have facilitated more radical resections and improved morbidity and mortality. Open PE remains the gold standard approach, however, minimally invasive techniques for PE may lessen morbidity whilst achieving the same oncological outcomes. The objective of this study was to assess the feasibility and safety of minimally invasive PE with a laparoscopic or robot-assisted approach. We also performed a review of the literature on robot-assisted PE which has not been widely reported for cases of recurrent gynaecological malignancy. Between 2015 and 2021six minimally invasive PE were performed. All patients underwent extensive multi-disciplinary assessment and counselling pre-operatively. Patient characteristics, treatment indication, perioperative data, short-term complications, and histological outcomes were recorded. There were two anterior exenterations, three posterior exenterations and one total exenteration performed. The primary cancer stage varied from stage 1a-3b. Five out of six patients had pre-operative chemo-radiotherapy. The average operative time (including surgical docking) was 600 min. Mean blood loss was 400 mL and the average length of stay was eight days. Enhanced recovery practices were used where possible. There were no intraoperative complications and one major post-operative complicationwhich was breakdown of an inferior gluteal artery perforator flap perineal reconstruction. All patients had negative margins at post-operative histopathology. All patients are alive and recurrence free at follow-up, but long-term outcome data is needed. This initial case series suggest that minimally invasive pelvic exenterationcan feasibly be performed in place of open pelvic exenteration. Furthermore, our findings suggest this may be a safe alternative as we report similar findings to the existing literature, however no firm conclusions can be drawn at such an early stage. Long term follow-up data and a larger cohort study will be needed to establish non-inferiority to open PE.

Hysterectomy and Adenextomy via transvaginal natural orifice transluminal endoscopic surgery (vNOTES): A UK perspective with a case series of 33 patients.

OBJECTIVE: To evaluate operative outcomes of hysterectomy +/- adnexectomy by Trans-vaginal Natural Orifice Endoscopic Surgery (vNOTES) in a case series of 33 patients. STUDY DESIGN: It was a prospective case series study carried out in Darent Valley and Benenden Hospital, to our knowledge, the first units in the United Kingdom to have undertaken VNOTE Hysterectomy. We collected data on a private shared drive noting patient demographics, indications for surgery, operation outcomes and patient follow-up details. RESULTS AND CONCLUSIONS: Between January and December 2018, 33 patients underwent surgery between two units. Indications for surgery included dysfunctional uterine bleeding, endometrial hyperplasia, pelvic pain, post-menopausal bleeding, prophylactic surgery in BRCA positive patients and one grade 1 stage 1 endometrial cancer in whom laparoscopic hysterectomy was technically difficult and complicated by previous midline laparotomy. Ages ranged from 35 to 75 and BMI from 20-53. Mean operation time was 68.5 min and mean blood loss intraoperatively was 269mls. 15.2% (n = 5) had a blood loss equal or more than 500 mls. There were no intraoperative complications and no conversions to open surgery. The median visual analogue pain score at 6 h post operatively and at discharge was 0. All patients received regular Paracetamol and Ibuprofen and opiate based analgesics were only used on an as required basis. Postoperative complication which included failed trial without catheter, urinary tract infection and urinary dysfunction were reported by four women (12.4%). Only 2 patients re-presented to hospital over a 30-day period and neither required inpatient management. Hysterectomy by vNOTES has advantages over traditional laparoscopic and vaginal hysterectomy that include reduced requirement for intra-abdominal insufflation and head down, absence of trocar related injuries and easier operative access in patients with morbid obesity, or previous abdominal surgery such as midline laparotomy or mesh hernia repair. In addition, both tubes and ovaries can be removed easily due to easier access and visibility and there is no requirement for vaginal descent in order to do so. Plans for a comparative study between laparoscopic hysterectomy and vNOTES hysterectomy are underway.