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.

Maternal and neonatal complications in pregnancies with and without pre-gestational diabetes mellitus.

OBJECTIVES: To compare pregnancy complications in pregnancies with and without pre-gestational diabetes mellitus (DM) managed in a multidisciplinary high-risk diabetes antenatal clinic. METHODS: This screening cohort study was undertaken at a large maternity unit in the United Kingdom between January 2010 and December 2022. We included singleton pregnancies that booked at our unit at 11-13 weeks' gestation. Univariate and multivariate logistic regression analysis was carried out to determine risks of complications in pregnancies with type 1 and type 2 DM after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (AR) and odds ratio (OR) (95 % confidence intervals [CI]). RESULTS: The study population included 53,649 singleton pregnancies, including 509 (1.0 %) with pre-existing DM and 49,122 (99.0 %) without diabetes. Multivariate logistic regression analysis demonstrated that there was a significant contribution from pre-existing DM in prediction of adverse outcomes, including antenatal complications such as fetal defects, stillbirth, preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age (LGA) neonates; intrapartum complications such as caesarean delivery (CS) and post-partum haemorrhage; and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and hypoxic ischaemic encephalopathy (HIE). In particular, there was a 5-fold increased risk of stillbirth and HIE. CONCLUSIONS: The maternal and neonatal complications in pregnancies with pre-existing DM are significantly increased compared to those without DM despite a decade of intensive multidisciplinary antenatal care. Further research is required to investigate strategies and interventions to prevent morbidity and mortality in pregnancies with pre-gestational DM.

Gestational Diabetes Mellitus: Association with Maternal and Neonatal Complications.

Background and objectives: Gestational diabetes mellitus (GDM) is known to be associated with pregnancy complications but there is limited evidence about the strength of these associations in recent clinical practice, especially after the introduction of strict guidelines for the management of pregnancies with GDM in a multidisciplinary team setting. The objectives of our study were to first compare the rates of complications in pregnancies with GDM with those that had pre-existing diabetes mellitus and those without diabetes; and second, to derive measures of effect size expressed as odds ratios after adjustment for confounding factors to assess the independent association of GDM in prediction of these pregnancy complications. Materials and Methods: This was a prospective cohort study undertaken at a large maternity unit in the United Kingdom between January 2010 and June 2022. We included singleton pregnancies that were booked at our unit at 11-13 weeks' gestation. Multivariate regression analysis was carried out to determine the risks of complications in pregnancies with GDM after adjusting for pregnancy characteristics. Risks were expressed as odds ratio (OR) (95% confidence intervals [CI]) and expressed graphically in forest plots. Results: The study population included 53,649 singleton pregnancies including 509 (1%) with pre-existing DM, 2089 (4%) with GDM and 49,122 (95%) pregnancies without diabetes. Multivariate regression analysis demonstrated that there was a significant independent contribution from GDM in the prediction of adverse outcomes, including maternal complications such as preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age neonates and elective caesarean section (CS); and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and respiratory distress syndrome. Conclusions: GDM is associated with an increased rate of pregnancy complications compared to those without diabetes, even after adjustment for maternal and pregnancy characteristics. GDM does not increase the risk of stillbirth, hypoxic ischaemic encephalopathy or neonatal death.

Maternal and neonatal complications following Kielland's rotational forceps delivery: A systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence regarding the safety of Kielland's rotational forceps delivery (KRFD) in comparison with other modes of delivery for the management of persistent fetal malposition in the second stage of labour. OBJECTIVES: To derive estimates of risks of maternal and neonatal complications following KRFD, compared with rotational ventouse delivery (RVD), non-rotational forceps delivery (NRFD) or a second-stage caesarean section (CS), from a systematic review and meta-analysis of the literature. SEARCH STRATEGY: Standard search methodology, as recommended by the Cochrane Handbook for Systematic Reviews of Interventions. SELECTION CRITERIA: Case series, prospective or retrospective cohort studies and population-based studies. DATA COLLECTION AND ANALYSIS: A meta-analysis using a random-effects model was used to derive weighted pooled estimates of maternal and neonatal complications. MAIN RESULTS: Thirteen studies were included. For postpartum haemorrhage there was no significant difference between Kielland's and ventouse delivery; the rate was lower in Kielland's delivery compared with non-rotational forceps (RR 0.79, 95% CI 0.65-0.95) and second-stage CS (RR 0.45, 95% CI 0.36-0.58). There were no differences in the rates of anal sphincter injuries or admission to neonatal intensive care. Rates of shoulder dystocia were higher with Kielland's delivery compared with ventouse delivery (RR 1.79, 95% CI 1.08-2.98), but rates of neonatal birth trauma were lower (RR 0.49, 95% CI 0.26-0.91). There were no differences seen in the rates of 5-min APGAR score < 7 between Kielland's delivery and other instrumental births, but they were lower when compared with second-stage CS (RR 0.47, 95% CI 0.23-0.97). CONCLUSIONS: Kielland's rotational forceps delivery is a safe option for the management of fetal malposition in the second stage of labour.

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.

Kielland's rotational forceps delivery: comparison of maternal and neonatal outcomes with pregnancies delivering by non-rotational forceps.

We compared complications in pregnancies that had Kielland's rotational forceps delivery (KRFD) with non-rotational forceps delivery (NRFD). Maternal outcomes included post-partum haemorrhage (PPH) and obstetric anal sphincter injury (OASIS); neonatal outcomes included admission to neonatal intensive care unit (NICU), 5-minute Apgar scores <7, hypoxic ischaemic encephalopathy (HIE), jaundice, shoulder dystocia and birth trauma. The study population included 491 (2.1%) requiring KRFD, 1,257 (5.3%) requiring NRFD and 22,111 (93.0%) that had SVD. In pregnancies with NRFD compared to KRFD, there was higher incidence of OASIS (8.5% vs. 4.7%; p = .006) and a non-significant increased trend for PPH (15.0% vs. 12.4%; p = .173). There was no significant difference in rates of admission to NICU (p = .628), 5-minute Apgar score <7 (p = .375), HIE (p = .532), jaundice (p = .809), severe shoulder dystocia (p = .507) or birth trauma (p = .514). Our study demonstrates that KRFD has lower rates of maternal complications compared to NRFD whilst the rates of neonatal complications are similar.IMPACT STATEMENTWhat is already known on this subject? Kielland's rotational forceps is used for achieving vaginal delivery in pregnancies with failure to progress in second stage of labour secondary to fetal malposition. The use of Kielland's forceps has significantly declined in the last few decades due to concerns about an increased risk of maternal and neonatal complications, despite the absence of any major studies demonstrating this increased risk.What do the results of this study add? There are some studies which compare the risks in pregnancies delivering by Kiellands forceps with rotational ventouse deliveries but there is limited evidence comparing the risks of rotational with non-rotational forceps deliveries. Our study compares the major maternal and neonatal complications in a large cohort of pregnancies undergoing rotational vs. non-rotational forceps deliveries.What are the implications of these findings for clinical practice and/or further research? The results of our study demonstrate that maternal and neonatal complications in pregnancies delivering by Kielland's rotational forceps undertaken by appropriately trained obstetricians are either lower or similar to those delivering by non-rotational forceps. Consideration should be given to ensure that there is appropriate training provided to obstetricians to acquire skills in using Kielland's forceps.

Kielland's rotational forceps delivery: A comparison of maternal and neonatal outcomes with rotational ventouse or second stage caesarean section deliveries.

OBJECTIVES: The objective of our study was to derive accurate estimates of risks of maternal and neonatal complications associated with Kielland's rotational forceps delivery (KRFD) compared to rotational ventouse delivery (RVD) or 2nd stage caesarean section (CS). METHODS: This was a retrospective cohort study undertaken at a large tertiary maternity and neonatal unit in the United Kingdom between January 2010 and June 2018. Pregnancies with fetal demise, major fetal defects, those lost to follow-up, those delivering by elective or emergency CS in the first stage of labour and non-rotational instrumental deliveries were excluded. The study population included singleton pregnancies delivering by Kielland's forceps, rotational ventouse, 2nd stage CS or spontaneous unassisted cephalic vaginal delivery; the latter forming the control group. The maternal outcomes examined included post-partum haemorrhage (PPH) and obstetric anal sphincter injury (OASIS). The neonatal outcomes included admission to neonatal intensive care unit (NICU), 5-minute Apgar scores <7, hypoxic ischaemic encephalopathy (HIE), jaundice, shoulder dystocia and birth trauma. Absolute risks with 95 % confidence intervals (CI) were calculated in the study groups. Univariate and multivariate logistic regression analysis was carried out to estimate crude and adjusted odds ratio (OR) with 95 % CI. RESULTS: The study population of 23,786 pregnancies included: 491 (2.1 %) requiring KRFD, 344 (1.4 %) requiring RVD, 840 (3.5 %) that had a 2nd stage CS and 22,111 (93.0 %) spontaneous cephalic vaginal deliveries. With regard to maternal adverse outcomes, in pregnancies that had a KRFD compared to RVD, there was no significant difference in the incidence of OASIS (p = 0.599) or PPH (p = 0.982). In contrast, the risk of PPH was significantly higher in those delivering by a 2nd stage CS compared to KRFD (27.5 % vs. 12.4 %; p < 0.0001). With regard to neonatal adverse outcomes, in those delivering by KRFD compared to RVD and 2nd stage CS, there was no significant difference in the incidence of admission to NICU (p = 0.912; p = 0.746, respectively), 5-minute Apgar score<7 (p = 0.335; p = 0.150, respectively), jaundice (p = 0.810; p = 0.332, respectively), mild shoulder dystocia (p = 0.077), severe shoulder dystocia (p = 0.603) or birth trauma (p = 0.265; p = 0.323, respectively). The risk of maternal composite adverse outcome was highest after 2nd stage CS (OR 7.68; 95 %CI: 6.52-9.04) and lowest after KRFD (OR 3.82; 95 %CI: 2.98-4.91). The risk of composite neonatal adverse outcome was higher in those delivering by RVD (OR 2.87; 95 %CI: 2.10-3.91), compared to KRFD (OR 2.23; 95 %CI: 1.67-2.97) or 2nd stage CS (OR 2.02; 95 %CI: 1.60-2.54). CONCLUSION: Our study demonstrates that KRFD is a safer management option when compared to RVD or 2nd stage CS for the management of persistent fetal malposition in labour.

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.