Current opinion on large-scale prospective myomectomy databases toward evidence-based preconception and antenatal counselling utilising a standardised myomectomy operation note.

Background: No large-scale databases exist of pregnancy outcomes and rate of uterine rupture for women after myomectomy, resulting in inconsistent antenatal counselling and decision-making regarding mode and timing of delivery. Standardising information collected at myomectomy may facilitate data collection, informing prenatal/ antenatal counselling. Objectives: To determine clinician opinions regarding standardisation of myomectomy operation notes to allow comprehensive data input into a prospective database of pregnancy outcomes, toward an evidence-based approach to decision making regarding timing and mode of delivery in subsequent pregnancies. Materials and Methods: A google forms survey was emailed to all consultant (attending-level) obstetricians and gynaecologists across 25 hospitals in London, Kent, Surrey, and Sussex (UK) between March and May 2022. To enhance response rates, two further email reminders were sent alongside in-person reminders from selected local unit representatives. Main outcome measures: Senior clinician opinion for characteristics necessary to collect at time of surgery to develop a widescale database of post myomectomy pregnancy outcomes. Results: 209/475 (44%) responses received; 95% (198/209) agreed with standardising operation notes. Criteria selected for inclusion included cavity breach (98%, 194/198), location (98%, 194/198), number of fibroids removed (93%, 185/198) and number of uterine incisions (96%, 190/198). Conclusions: Gynaecologists support standardising myomectomy operation notes to inform the development of prospective large-scale databases of pregnancy outcomes after myomectomy. What is new?: Acquisition of clinician opinions on the development and content of a standardised myomectomy operation note to aid the development of a pregnancy-outcome database for women after myomectomy.

Towards a clinical consensus on the management of pregnancy and birth after laparoscopic and open myomectomy: A survey of obstetricians and gynaecologists.

OBJECTIVES: The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. STUDY DESIGN: Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. RESULTS: 209 consultant responses received between 07/03/2022-07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. CONCLUSIONS: We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy.

A novel somatic mutation in GNAQ in a capillary malformation provides insight into molecular pathogenesis.

Sturge-Weber syndrome (SWS) is a sporadic, congenital, neuro-cutaneous disorder characterized by a mosaic, capillary malformation. SWS and non-syndromic capillary malformations are both caused by a somatic activating mutation in GNAQ encoding the G protein subunit alpha-q protein. The missense mutation R183Q is the sole GNAQ mutation identified thus far in 90% of SWS-associated or isolated capillary malformations. In this study, we sequenced skin biopsies of capillary malformations from 9 patients. We identified the R183Q mutation in nearly all samples, but one sample exhibited a Q209R mutation. This new mutation occurs at the same residue as the constitutively-activating Q209L mutation, commonly seen in tumors. However, Q209R is a rare variant in this gene. To compare the effect of the Q209R mutation on downstream signaling, we performed reporter assays with a GNAQ-responsive reporter co-transfected with either GNAQ WT, R183Q, Q209L, Q209R, or C9X (representing a null allele). Q209L showed the highest reporter activation, with R183Q and Q209R showing significantly lower activation. To determine whether these mutations had similar or different downstream consequences we performed RNA-seq analysis in microvascular endothelial cells (HMEC-1) electroporated with the same GNAQ variants. The R183 and Q209 missense variants caused extensive dysregulation of a broad range of transcripts compared to the WT or null allele, confirming that these are all activating mutations. However, the missense variants exhibited very few differentially expressed genes (DEGs) when compared to each other. These data suggest that these activating GNAQ mutations differ in magnitude of activation but have similar downstream effects.

Caesarean section in women following an abdominal myomectomy: a choice or a need?

Delivery options following both open and laparoscopic myomectomy remains a controversial topic and opinions vary between obstetricians and gynaecologists. The historical advice of planned caesarean section before 39-weeks persists despite the movement towards the minimal access approach for myomectomy. The main concern remains the small, but potentially catastrophic risk of uterine rupture. Unfortunately, there remains a paucity of data assessing factors that can affect the uterine integrity following laparoscopic myomectomy, such as number, size and type of fibroids, uterine cavity breach and electro-cautery usage. Despite this, the cited 1% overall risk of rupture following myomectomy is similar to the quoted risk following trial of labour after caesarean section, and a successful and safe vaginal delivery can be achieved in as high as 90%. Patient choice and informed consent are essential in the holistic approach to managing these women and safely supporting their delivery choices.

Healing of the perineal wound after proctectomy in Crohn's disease patients: only preoperative perineal sepsis predicts poor outcome.

BACKGROUND: The aim of our study was to assess perineal wound healing in patients with Crohn's disease (CD) who undergo proctectomy or proctocolectomy with end ileostomy and to evaluate the influence of various factors including types of perineal dissection on eventual wound healing. METHODS: Data for patients with CD who underwent proctectomy or total proctocolectomy with end ileostomy from 1995 to 2012 were reviewed. The relationship between perineal wound healing and demographics, patient characteristics, and other factors was assessed using univariate and multivariate analyses. RESULTS: The perineal wound healed by 12 weeks in 72 (52.9%) out of 136 patients (63.2% female, mean age 41 ± 13 years); delayed healing occurred in 35 patients (25.7%), and in 29 patients (21.3%), there was non-healing. On multivariate analysis, the only factor associated with delayed healing and non-healing was preoperative perineal sepsis (p = 0.001). CONCLUSIONS: After proctectomy or proctocolectomy for CD, perineal wound healing is poor and poses a particular challenge for patients with preoperative perineal sepsis. These findings support a preoperative discussion regarding CD patients that examines potential outcomes and the consideration of measures such as the initial creation of defunctioning ostomy or control/drainage of local sepsis prior to proctectomy.

Cardiovascular effects of exogenous adrenomedullin and CGRP in Ramp and Calcrl deficient mice.

Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) are potent vasodilator peptides and serve as ligands for the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CLR/Calcrl). Three GPCR accessory proteins called receptor activity-modifying proteins (RAMPs) modify the ligand binding affinity of the receptor such that the CLR/RAMP1 heterodimer preferably binds CGRP, while CLR/RAMP2 and CLR/RAMP3 have a stronger affinity for AM. Here we determine the contribution of each of the three RAMPs to blood pressure control in response to exogenous AM and CGRP by measuring the blood pressure of mice with genetic reduction or deletion of the receptor components. Thus, the cardiovascular response of Ramp1-/-, Ramp2+/-, Ramp3-/-, Ramp1-/-/Ramp3-/- double-knockout (dKO), and Calcrl+/- mice to AM and CGRP were compared to wildtype mice. While under anesthesia, Ramp1-/- male mice had significantly higher basal blood pressure than wildtype males; a difference which was not present in female mice. Additionally, anesthetized Ramp1-/-, Ramp3-/-, and Calcrl+/- male mice exhibited significantly higher basal blood pressure than females of the same genotype. The hypotensive response to intravenously injected AM was greatly attenuated in Ramp1-/- mice, and to a lesser extent in Ramp3-/- and Calcrl+/- mice. However, Ramp1-/-/Ramp3-/- dKO mice retained some hypotensive response to AM. These results suggest that the hypotensive effect of AM is primarily mediated through the CLR/RAMP1 heterodimer, but that AM signaling via CLR/RAMP2 and CLR/RAMP3 also contributes to some hypotensive action. On the other hand, CGRP's hypotensive activity seems to be predominantly through the CLR/RAMP1 heterodimer. With this knowledge, therapeutic AM or CGRP peptides could be designed to cause less hypotension while maintaining canonical receptor-RAMP mediated signaling.

Retinitis pigmentosa-associated cystoid macular oedema: pathogenesis and avenues of intervention.

Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16-64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction. There are limited data on efficacy of treatments for RP-CMO. Treatments attempted to date include oral and topical carbonic anhydrase inhibitors, oral, topical, intravitreal and periocular steroids, topical non-steroidal anti-inflammatory medications, photocoagulation, vitrectomy with internal limiting membrane peel, oral lutein and intravitreal antivascular endothelial growth factor injections. This review summarises the evidence supporting these treatment modalities. Successful management of RP-CMO should aim to improve both quality and quantity of vision in the short term and may also slow central vision loss over time.

Assessing the quality of written information provision for surgical procedures: a case study in oesophagectomy.

OBJECTIVE: To examine the content and quality of written information provided by surgical centres for patients undergoing oesophagectomy for cancer. DESIGN: Cross-sectional study of the content of National Health Service (NHS) patient information leaflets (PILs) about oesophageal cancer surgery, using a modified framework approach. DATA SOURCES: Written information leaflets from 41 of 43 cancer centres undertaking surgery for oesophageal cancer in England and Wales (response rate 95.3%). ELIGIBILITY CRITERIA: All English language versions of PILs about oesophagectomy. RESULTS: 32 different PILs were identified, of which 2 were generic tools (Macmillan 'understanding cancer of the gullet' and EIDO 'oesophagectomy'). Although most PILs focused on describing in-hospital adverse events, information varied widely and was often misleading. Just 1 leaflet described survival benefits of surgery and 2 mentioned the possibility of disease recurrence. CONCLUSIONS: Written information provided for patients by NHS cancer centres undertaking oesophagectomy is inconsistent and incomplete. It is recommended that surgeons work together with patients to agree on standards of information provision of relevance to all stakeholders' needs.

Primacy of surgery for colorectal cancer.

BACKGROUND: The optimal technique for curative resection of colonic cancer includes high ligation of the mesenteric vessels, wide excision of the colonic mesentery and prevention of tumour cell spillage. This article reports results from the authors' institution for patients in whom complete mesocolic excision was performed long before the term was coined. METHODS: Patients operated on for cure for primary adenocarcinoma of the colon between January 1994 and December 2004 were identified from a prospectively maintained, institutional review board-approved, colorectal cancer registry. Medical records and operation notes were reviewed. The primary outcomes were recurrence (local and distal) and age-adjusted 5-year survival. RESULTS: Some 1013 patients (560 men and 453 women) were identified, with a median age of 69 (range 21-96) years. The most common location of the cancer was the sigmoid colon (32·9 per cent), followed by the caecum (26·7 per cent) and ascending colon (17·0 per cent). Operations were performed laparoscopically in 134 patients (13·2 per cent). Median duration of hospital stay was 7 (range 1-64, mean 8·2) days. Overall morbidity and mortality rates were 13·5 and 2·2 per cent respectively; there were 20 anastomotic leaks (2·0 per cent). Some 282 patients (27·8 per cent) had stage I, 386 (38·1 per cent) stage II and 345 (34·1 per cent) stage III disease. Median lymph node yield was 28·3 (range 0-241, mean 28·3), and 12 or more nodes were examined in 88·1 per cent of patients. Adjuvant chemotherapy was administered to 277 patients (80·3 per cent) with stage III disease. Overall local and distant recurrence rates at 5 years were 5·1 and 17·1 per cent respectively. The 5-year local recurrence rate was 2·2, 5·3 and 7·7 per cent for American Joint Committee on Cancer stages I, II and III respectively. Corresponding distant recurrence rates were 4·0, 14·7 and 30·5 per cent. The 5-year overall cancer-free age-standardized survival rate was 85·3 per cent. Five-year age standardized survival rates for patients with disease stages I, II and III were 97·7, 90·8 and 69·8 per cent respectively. CONCLUSION: These data define modern results of surgery for colonic cancer with conservative use of chemotherapy.

Reporting outcomes of definitive radiation-based treatment for esophageal cancer: a review of the literature.

Accurate evaluation of radical radiotherapy requires well designed research with valid and appropriate outcomes. This study reviewed standards of outcome reporting and study design in randomized controlled trials (RCTs) of radiation-based therapy for esophageal cancer and made recommendations for future work. Randomized controlled trials reporting outcomes of definitive radiation-based treatment alone or in combination with chemotherapy were systematically identified and summarized. The types, frequency, and definitions of all clinical and patient-reported outcomes (PROs) reported in the methods and results sections of papers were examined. Studies providing a definition for at least one outcome and presenting all outcomes reported in the methods were classified as high quality. From 1425 abstracts, 16 RCTs including 1803 patients were identified. The primary outcome was overall survival in 13 studies, but five different definitions were reported. Outcomes for treatment failure included local, regional, and distant failures, and inconsistent definitions were applied. An observer assessment of dysphagia was reported in seven RCTs but PROs were reported in only one. Only three RCTs were at low risk of bias, with all lacking reports of sequence generation and only a minority reporting allocation concealment. The quality of outcome reporting in RCTs was inconsistent and risked bias. A core outcome set including clinical and PROs is needed to improve reporting of trials of definitive radiation-based treatment for esophageal cancer.

Feasibility RCT of definitive chemoradiotherapy or chemotherapy and surgery for oesophageal squamous cell cancer.

BACKGROUND: The optimal treatment for localised oesophageal squamous cell carcinoma (SCC) is uncertain. We assessed the feasibility of an RCT comparing neoadjuvant treatment and surgery with definitive chemoradiotherapy. METHODS: A feasibility RCT in three centres examined incident patients and reasons for ineligibility using multi-disciplinary team meeting records. Eligible patients were offered participation in the RCT with integrated qualitative research involving audio-recorded recruitment appointments and interviews with patients to inform recruitment training for staff. RESULTS: Of 375 patients with oesophageal SCC, 42 (11.2%) were eligible. Reasons for eligibility varied between centres, with significantly differing proportions of patients excluded because of total tumour length (P=0.002). Analyses of audio-recordings and patient interviews showed that recruiters had challenges articulating the trial design in simple terms, balancing treatment arms and explaining the need for randomisation. Before analyses of the qualitative data and recruiter training no patients were randomised. Following training in one centre 5 of 16 eligible patients were randomised. CONCLUSIONS: An RCT of surgical vs non-surgical treatment for SCC of the oesophagus is not feasible in the UK alone because of the low number of incident eligible patients. A trial comparing diverse treatment approaches may be possible with investment to support the recruitment process.

Evaluating the role of fluorodeoxyglucose positron emission tomography-computed tomography in multi-disciplinary team recommendations for oesophago-gastric cancer.

BACKGROUND: National guidelines recommend that fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is performed in all patients being considered for radical treatment of oesophageal or oesophago-gastric cancer without computerised tomography scan (CTS) evidence of metastasis. Guidance also mandates that all patients with cancer have treatment decisions made within the context of a multi-disciplinary team (MDT) meeting. Little is known, however, about the influence of PET-CT on decision making within MDTs. The aim of this study was to assess the role of PET-CT in oesophago-gastric cancer on MDT decision making. METHODS: A retrospective analysis of a prospectively held database of all patients with biopsy-proven oesophageal or oesophago-gastric cancer discussed by a specialist MDT was interrogated. Patients selected for radical treatment without CTS evidence of M1 disease were identified. The influence of PET-CT on MDT decision making was examined by establishing whether the PET-CT confirmed CTS findings of M0 disease (and did not change the patient staging pathway) or whether the PET-CT changed the pathway by showing unsuspected M1 disease, refuting CTS suspicious metastases, or identifying another lesion (needing further investigation). RESULTS: In 102 MDT meetings, 418 patients were discussed, of whom 240 were initially considered for radical treatment and 238 undergoing PET-CT. The PET-CT confirmed CTS findings for 147 (61.8%) and changed MDT recommendations in 91 patients (38.2%) by (i) identifying M1 disease (n=43), (ii) refuting CTS suspicions of M1 disease (n=25), and (iii) identifying new lesions required for investigations (n=23). CONCLUSION: The addition of PET-CT to standard staging for oesophageal cancer led to changes in MDT recommendations in 93 (38.2%) patients, improving patient selection for radical treatment. The validity of the proposed methods for evaluating PET-CT on MDT decision making requires more work in other centres and teams.

Aorto-conduit fistula developing four years after esophagectomy.

A 71 year old lady was treated for a squamous cell carcinoma of the oesophagus with neo-adjuvant chemotherapy followed by a two phase Ivor-Lewis oesophagectomy with two field lymphadenectomy. She presented four years later with life threatening bleeding from a fistula between the thoracic aorta and the gastric conduit, which was treated successfully with a thoracic aortic stent.

Measuring sexual and urinary outcomes in women after rectal cancer excision.

PURPOSE: This study was designed to investigate sexual and urinary dysfunction in women who underwent rectal cancer excision, and the influence of tumor and treatment variables on long-term outcomes. METHODS: Data were prospectively collected on 295 women who underwent rectal cancer excision at a tertiary referral colorectal center from 1998 to 2006. Sexual and urinary function was assessed preoperatively and at intervals up to five years after surgery. Functional outcomes were assessed by using univariate and multivariate regression analysis, chi-squared test for trend, or Kruskal-Wallis test. RESULTS: The mean age of the patients was 60.9 years. Anterior resection was performed in 222 patients (75.2 percent) and abdominoperineal resection in 73 patients (24.7 percent). Patients who underwent abdominoperineal resection were less sexually active (25 vs. 50 percent; P = 0.02) and had a lower frequency of intercourse than anterior resection patients at one year after surgery (anterior resection, 3 (0-5) (median interquartile range); abdominoperineal resection 0 (0-4); P = 0.029). The frequency of intercourse improved over time for abdominoperineal resection (4 months, 0 (0-0) median interquartile range; 5 years, 3 (0.25-4) median interquartile range; P = 0.028). Abdominoperineal resection was associated with increased dyspareunia (odds ratio, 5.75; 95 percent confidence interval (CI), 1.87-17.6; P = 0.002), urinary urgency (odds ratio, 8.52; 95 percent CI, 2.81-25.8; P < 0.001), incontinence (odds ratio, 2.41; 95 percent CI, 1.11-5.26; P = 0.026), poor stream (odds ratio, 5.64, 95 percent CI, 2.55-12.5; P

Complications and functional results after ileoanal pouch formation in obese patients.

OBJECTIVE: Ileoanal pouch formation (IPAA) can be technically challenging in obese patients, and there is little data evaluating results after the procedure in these patients. We compare outcomes for patients with a body mass index (BMI) > or =30 undergoing IPAA when compared with those for patients with BMI <30. METHODS: Retrospective analysis of prospectively accrued data for patients with BMI > or =30 undergoing IPAA. Patient and disease-related characteristics, complications, long-term function, and quality of life (QOL) using the Cleveland Global Quality of Life scale (CGQL) were determined for this group of patients (group B) and compared with those for patients with BMI <30 (group A). Kruskal-Wallis and Wilcoxon rank sum tests were used to compare quantitative or ordinal data and chi-square or Fisher's exact tests for categorical variables. Long-term mortality and complication rates were estimated using the Kaplan-Meier method with group comparisons performed using log rank tests. RESULTS: There were 345 patients (median BMI 32.7) in group B and 1,671 patients in group A. When the cumulative risk of complications over 15 years was compared, group B patients had a significantly higher chance of getting a complication (94.9% vs 88%, p = 0.006). The rates of pelvic sepsis (6.7% vs 5.3%, p = 0.3), pouchitis (58.1 vs 54.4%, p = 0.9), pouch failure (6% vs 4.5%, p = 0.9), and hemorrhage (5.6% vs 4.8%, p = 0.7) were similar for group B and group A. Group B patients, however, had a significantly higher risk of the development of wound infection (18.8% vs 8.1%, p < 0.001) and anastomotic separation (10.4% vs 5.4%, p < 0.001), whereas group A patients had a higher rate of development of obstruction over time (26.7% vs 22.3%, p = 0.02). Long-term outcome including QOL and function after 15 years was comparable between groups. CONCLUSIONS: Although technically demanding, IPAA can be undertaken in obese patients with acceptable morbidity. Good long-term functional results and QOL that is comparable to nonobese patients may be anticipated.

Risk factors associated with ileal pouch-related fistula following restorative proctocolectomy.

INTRODUCTION: Pouch-related fistula occurs in 5-10 per cent of patients after restorative proctocolectomy. The present study identified risk factors associated with the development of such fistulas. METHODS: Data on preoperative and postoperative risk factors were recorded from 1965 patients who underwent restorative proctocolectomy in a single tertiary centre between 1983 and 2001. Cox regression analysis was used to identify independent predictors of pouch-perineal, pouch-abdominal wall and pouch-vaginal fistula during follow-up. RESULTS: Median patient follow-up was 4.1 (range 0-19) years. By 15 years' follow-up, pouch-vaginal fistulas had occurred in 44 women (5.2 per cent). The prevalence of ileal pouch-perineal and pouch-abdominal wall fistula was 3.6 per cent (70 patients) and 1.5 per cent (30 patients) respectively. Independent predictors of pouch-related fistula identified by multivariate analysis were diagnosis of indeterminate colitis or Crohn's disease (hazard ratio (HR) 1.28 (95 per cent confidence interval (c.i.) 1.00 to 1.65) and 1.73 (95 per cent c.i. 1.07 to 3.48) respectively versus ulcerative colitis or familial adenomatous polyposis), previous anal pathology (HR 3.43 (95 per cent c.i. 2.43 to 4.84) and 4.02 (95 per cent c.i. 1.27 to 12.77) respectively for perineal abscess and fistula in ano versus no previous anal pathology), abnormal anal manometry (HR 4.29 (95 per cent c.i. 2.33 to 7.91)), patient sex (HR 0.74 (95 per cent c.i. 0.58 to 0.95) for men versus women) and pelvic sepsis (HR 3.79 (95 per cent c.i. 2.48 to 5.79)). CONCLUSION: This study suggests that Crohn's disease and the clinical signs that favour the diagnosis of Crohn's disease may contribute to the development of pouch-related fistula.