Multidisciplinary Surgical Approach to Increase Survival for Advanced Ovarian Cancer in a Tertiary Gynaecological Oncology Centre.

PURPOSE: The purpose of this paper is to report on changes in overall survival, progression-free survival, and complete cytoreduction rates in the 5-year period after the implementation of a multidisciplinary surgical team (MDT). METHODS: Two cohorts were used. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients from January 2017 to September 2021. RESULTS: This study included 146 patients in cohort A (2006-2015) and 174 patients in cohort B (2017-2021) with FIGO stage III/IV ovarian cancer. Median follow-up in cohort A was 60 months and 48 months in cohort B. The rate of primary cytoreductive surgery increased from 38% (55/146) in cohort A to 46.5% (81/174) in cohort B. Complete macroscopic resection increased from 58.9% (86/146) in cohort A to 78.7% (137/174) in cohort B (p < 0.001). At 3 years, 75% (109/144) patients had disease progression in cohort A compared with 48.8% (85/174) in cohort B (log-rank, p < 0.001). Also at 3 years, 64.5% (93/144) of patients had died in cohort A compared with 24% (42/174) of cohort B (log-rank, p < 0.001). Cox multivariate analysis demonstrated that MDT input, residual disease, and age were independent predictors of overall (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.203-0.437, p < 0.001) and progression-free survival (HR 0.31, 95% CI 0.21-0.43, p < 0.001). Major morbidity remained stable throughout both study periods (2006-2021). CONCLUSIONS: Our data demonstrate that the implementation of multidisciplinary-team, intraoperative approach allowed for a change in surgical philosophy and has resulted in a significant improvement in overall survival, progression-free survival, and complete resection rates.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Placenta accreta spectrum ultrasound stage and fetal growth.

OBJECTIVE: to evaluate fetal growth in pregnancies complicated by placenta accreta spectrum (PAS) and to compare fetal growth between cases stratified by ultrasound stage of PAS. METHODS: This was a prospective multicenter cohort study of women diagnosed with PAS between January 2018 and December 2021. We grouped participants into cases by ultrasound stage (PAS stage 1-3) and controls (PAS0). Fetal growth centiles at three timepoints with median gestational ages of 21 ± 1 weeks (interquartile range [IQR], 20 ± 1-22 ± 0 weeks), 28 ± 0 weeks (IQR, 27 ± 0-28 ± 5 weeks), and 33 ± 0 weeks (IQR, 32 ± 1-34 ± 0 weeks) and birth weight centiles were compared between cases and controls and between those with PAS stratified by ultrasound stage. RESULTS: A total of 53 women met inclusion criteria, with a mean age of 37 years (standard deviation, ±4.0 years) and body mass index of 27 kg/m2 (standard deviation, ±5.8 kg/m2 ). Median (IQR) fetal weight centiles were around the 50th centile at each timepoint, with no difference between groups. The incidence of small for gestational age (birth weight ≤ 10th percentile) and large for gestational age (birth weight ≥ 90th percentile) was 11.3% (n = 6) and 15.1% (n = 8), respectively, with no differences by ultrasound stage. The median birth weight centile was 64 (IQR, 26-85), with no differences between cases and controls or by ultrasound stage. CONCLUSIONS: In our cohort, a diagnosis of PAS was not associated with fetal growth restriction.

Endometrial Mesonephric-like Adenocarcinoma Presenting as an Ocular Lesion: A Case Report.

Endometrial mesonephric-like carcinoma (ML-CA) is a recently recognized subtype of aggressive endometrial adenocarcinoma that is morphologically and immunophenotypically similar to mesonephric carcinoma but not typically associated with mesonephric remnants. Here, we report a case of 58-yr-old female who had a past medical history of fibroids and of irregular menstrual bleeding for ~20 yr who presented with visual disturbance. On further investigation, she was found to have a large choroidal peri-papillary tumor of the right eye. A presumptive diagnosis of choroidal melanoma was made. Right eye enucleation was performed, and microscopy revealed moderately differentiated metastatic adenocarcinoma. Further work up was advised. A uterine mass was identified on imaging followed by endometrial biopsy that showed a morphologically and immunohistochemically similar tumor to that in the eye. A hysterectomy was carried out and a malignant neoplasm with varying morphologic patterns including gland formation, solid sheets of tumor cells, cribriform, glomeruloid, spindled and papillary areas was seen. The immunohistochemical profile showed diffuse strong positivity for AE1/AE3, TTF1, P16, and vimentin. CD56, GATA3, Napsin A, and CD10 were focally positive. The neoplastic cells were negative for the following markers ER, PR, WT1, calretinin, and synaptophysin. PDL-1 was negative and mismatch repair protein was proficient. An identical KRAS mutation was detected in both the uterine corpus and ocular tumors. The findings are in keeping with a uterine mesonephric-like adenocarcinoma with an ocular metastasis. An Oncomine Focus-Mutation profile, Thermo-Fisher Scientific Inc., a 60 gene oncologic panel, performed on the ocular tumor, revealed no further mutations.

From physical to virtual: How the COVID-19 pandemic changed a tertiary gynaecologic oncology surveillance program in Ireland.

•Virtual follow up is acceptable to gynecological oncology patients.•Some patients may be reluctant to sit in waiting rooms post pandemic.•Lack of physical examination did not affect most patients' appointments.

The addition of sodium thiosulphate to hyperthermic intraperitoneal chemotherapy with cisplatin in ovarian cancer.

Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. METHOD: This is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. RESULTS: Sixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. CONCLUSION: The renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.

Maternal morbidity in placenta accreta spectrum following introduction of a multi-disciplinary service compared to standard care: an Irish perspective.

AIM: The purpose of this study is to compare maternal outcomes in patients with placenta accreta spectrum (PAS) when managed as part of a multi-disciplinary team (MDT) compared to standard care. METHODS: Patients in the standard care group were retrospectively identified from pathology records, with patients in the MDT group prospectively collected on an electronic database. Data on maternal demographics, delivery, estimated blood loss (EBL), transfusion requirements, and morbidity were recorded. RESULTS: Sixty patients were diagnosed with PAS between 2006 and 2019, of whom 32 were part of the standard care group and 28 in the MDT group. Compared to standard care, MDT care was associated with an increase in antenatal diagnosis from 56.3 to 92.9% (p < 0.0001), a significant reduction in EBL (4150 mL (800-19500) vs 1975 (495-8500), p < 0.0001), and transfusion requirements (median 7 (0-30) units of RCC vs 1 (0-13), p < 0.0001). CONCLUSION: PAS is associated with significant maternal morbidity and warrants management in an MDT setting with specialist input, which is associated with improved outcomes.

A meta-analysis of morbidity and mortality in primary cytoreductive surgery compared to neoadjuvant chemotherapy in advanced ovarian malignancy.

Aim The aim of this meta-analysis is to review the morbidity and mortality associated with primary cytoreductive surgery (PCS) compared to neoadjuvant chemotherapy and interval cytoreductive surgery (NACT + ICS) for advanced ovarian cancer. METHODS: A literature search was performed for publications reporting morbidity and mortality in patients undergoing PCS compared to NACT + ICS. Databases searched were Cochrane, Medline, Pubmed, Pubmed Central, clinicaltrials.gov and Embase. Two independent reviewers applied inclusion and exclusion criteria to select included papers, with differences agreed by consensus. A total of 1341 citations were reviewed; 17 studies comprising 3759 patients were selected for the analysis. The literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Patients in the PCS group were significantly more likely to have a Clavien-Dindo grade ≥ 3 morbidity with an overall rate of 21.2% compared to 8.8% (95%CI 1.9-4.0, p < 0.0001) and were more likely to die within 30 days of surgery (OR 6.1, 95% CI 2.1-17.6, p = 0.0008). Patients who underwent NACT + ICS had significantly shorter procedural times (MD -35 min, p = 0.01), lost less blood intraoperatively (MD-382 ml, p < 0.001) and had an average admission 5.0 days shorter (MD -5.0 days, 95% CI -8.1 to -1.9 days, p = 0.002) than those undergoing PCS. While NACT was associated with significantly increased optimal and complete cytoreduction rates (OR 1.9, 95% CI 1.3-2.9, p = 0.001, and OR 2.2, 95% CI 1.5-3.3, p = 0.0001 respectively), this did not confer any additional survival benefit (OR 1.0, p = 0.76). CONCLUSION: NACT is associated with less morbidity and mortality and improved complete cytoreduction compared to PCS, with no survival benefit. Hence NACT is an acceptable alternative in selected patients in particular with medical co-morbidities or a high tumour burden.

Association of Implementing a Multidisciplinary Team Approach in the Management of Morbidly Adherent Placenta With Maternal Morbidity and Mortality.

OBJECTIVE: To compare maternal outcomes in patients with morbidly adherent placenta managed in a multidisciplinary team setting compared with standard care. DATA SOURCES: A literature search was performed for publications reporting multidisciplinary pathways in the management of cesarean delivery for patients with morbidly adherent placenta. EMBASE, MEDLINE, PubMed, PubMed Central, ClinicalTrials.gov, and Cochrane databases were searched. METHODS OF STUDY SELECTION: Databases were searched for studies reporting maternal morbidity of patients with morbidly adherent placenta managed by a multidisciplinary team in a specialist center compared with standard care. Two independent reviewers applied inclusion and exclusion criteria to select included articles, with differences agreed by consensus. A total of 252 citations were reviewed; six studies comprising 461 patients were selected for the analysis. TABULATION, INTEGRATION, AND RESULTS: Literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results were reported as mean differences or pooled odds ratios (ORs) with 95% CIs. Estimated blood loss was significantly reduced in the multidisciplinary team group (mean difference -1.1 L, 95% CI -1.9 to -0.4, P=.004) and these patients had lower transfusion requirements (mean difference -2.7 units, 95% CI -4.1 to -1.2, P=.040). Those treated in a standard care setting were more likely to develop complications (OR 2.5, 95% CI 1.5-4.0, P<.001); however, there was no difference in length of stay between the two groups. CONCLUSION: This meta-analysis highlights the improved maternal outcomes in patients with morbidly adherent placenta when managed by a multidisciplinary team in a specialist center. High-risk complex cases warrant expert management in centralized units.

Baseline Laparoscopic Skill May Predict Baseline Robotic Skill and Early Robotic Surgery Learning Curve.

INTRODUCTION: Robotic surgery is associated with a learning curve unique to each trainee. Knowledge about a trainee's baseline skill and learning curve would facilitate the development of a more individualized training curriculum. The aim of our study was to determine whether baseline laparoscopic skill is predictive of one's baseline robotic skill and short-term learning curve. METHODS: Trainees from four different surgical specialties were included in the study. Each trainee participated in a 4-week, simulation-based robotic surgery basic skills training course. Precourse, baseline laparoscopic and robotic skills were assessed using validated test tasks; a basic peg transfer (PT) and an advanced intracorporeal suturing and knot tying (ISKT) task. Trainee robotic skill was assessed again 1 week postcourse. Each task performance was video recorded and scored by two blinded expert surgeons. RESULTS: A total of 32 trainees were included; 14 urology, 7 gynecology, 8 thoracic Sx, 3 general Sx. Most (91%) were senior residents or clinical fellows and 50% had no prior robotic experience. There were no differences in baseline laparoscopic and robotic skill related to reported prior robotic experience. Between specialties, no differences were seen on baseline laparoscopic skill and only small differences were seen on baseline robotic skill. Both baseline Lap PT (p = 0.01) and Lap ISKT (p = 0.01) performances correlated with baseline robotic ISKT performance, but not robotic PT scores. Only baseline Lap ISKT performance correlated with postcourse robotic PT (p = 0.01) and ISKT (p < 0.01) performance. Baseline robotic ISKT scores, but not PT scores, correlated with postcourse robotic performance (p = 0.02 for PT, p < 0.01 for ISKT). CONCLUSIONS: In this study, a trainee's baseline laparoscopic skill correlated with certain baseline robotic skills. Better baseline performance on an advanced, but not basic, laparoscopic and robotic skill task may correlate with a shorter learning curve for basic robotic skills. Further exploration of this finding may yield better training curricula.

Determining the role of a national objective assessment of surgical skills in gynecological oncology: an e-Delphi methodology.

OBJECTIVE: The aim of this study is to determine a national consensus on the role of an objective assessment of technical surgical skills in gynecological oncology (GO). METHODS: After approval was obtained from Society of Gynecologic Oncology of Canada, A panel of 20 GO leaders was assembled, representing all GO fellowship programs, and was asked to participate in an anonymous group and respond to an online 49-item questionnaire using a modified Delphi methodology. RESULTS: Ninety-five percent (n = 19) of those invited to participate did so. Seventeen of the panelists (89.5%) believed there was no sufficiently standardized technical skills assessment for GO fellows, whereas 18 responders (95%) believed that fellows should be objectively assessed on more than 1 occasion during their training. Consensus was predefined as Cronbach α greater than 0.8. The panel agreed on what procedures should be objectively assessed with a Cronbach α of 0.967. An overall Cronbach α of 0.993 was achieved after a single Delphi round. CONCLUSIONS: We achieved consensus on the possible components and logistics of a skills assessment process among a group of highly experienced GO trainers in Canada. This study provides the basis for further investigation and debate on the potential value, necessity, and feasibility of an assessment of advanced surgical and nonsurgical skills of GO trainees.

The fallopian tube as the origin of high grade serous ovarian cancer: review of a paradigm shift.

Research published over the past 10 years has suggested that most "ovarian cancer," and specifically the high-grade serous carcinoma (HGSC) subtype of ovarian cancer, actually originates in the fallopian tube. In this review, we examine the evidence supporting the tubal origin hypothesis for HGSC, and discuss the clinical implications of our improved understanding of the pathogenesis of ovarian cancer. We searched Medline R and Medline in-process and non-indexed citations from inception to December 15, 2012, to identify all English or French language articles discussing the origins of HGSC. Articles and findings were summarized descriptively. A step-wise transformation from normal epithelium to a lesion with the ability to invade and metastasize has been demonstrated within the fallopian tube. Intraepithelial or early invasive carcinoma of the fallopian tube is frequently identified in BRCA mutation carriers who undergo prophylactic risk-reducing salpingo-oophorectomy. In both BRCA mutation carriers and women from the general population, pre-invasive changes within the fimbriated end of the fallopian tube appear in association with early HGSC. Molecular and genetic studies, as well as in vitro and animal models, have also supported a tubal origin for HGSC. Whether the removal of fallopian tubes (salpingectomy) at the time of pelvic surgery for other reasons will lead to reductions in mortality from ovarian cancer is currently unknown, but it is an important area for future clinical research.

Les recherches publiées au cours des 10 dernières années ont laissé entendre que la plupart des « cancers de l'ovaire ¼ (et plus particulièrement le sous-type « carcinome séreux de haut grade histologique ¼ [CSHG] du cancer de l'ovaire) trouvent en fait leur origine dans la trompe de Fallope. Dans le cadre de cette analyse, nous examinons les données soutenant l'hypothèse de l'origine tubaire du CSHG et nous discutons des implications cliniques de notre compréhension améliorée de la pathogenèse du cancer de l'ovaire. Nous avons mené des recherches dans Medline R et dans les citations en traitement et non répertoriées de Medline en vue d'en tirer tous les articles publiés en anglais ou en français discutant des origines du CSHG, et ce, du début de notre étude jusqu'au 15 décembre 2012. Les articles et les constatations ont été résumés de façon descriptive. Une transformation progressive de l'épithélium normal en lésion ayant la capacité d'envahir les tissus voisins et de produire des métastases a été démontrée au sein de la trompe de Fallope. La présence d'un carcinome intraépithélial ou invasif précoce de la trompe de Fallope est fréquemment identifiée chez les porteuses de la mutation BRCA qui subissent une salpingo-ovariectomie prophylactique d'atténuation du risque. Tant chez les porteuses de la mutation BRCA que chez les femmes de la population générale, des modifications préinvasives affectant la frange ovarienne se manifestent en association avec l'apparition d'un CSHG précoce. Des études moléculaires et génétiques (ainsi que des études in vitro et menées sur des modèles animaux) ont également soutenu l'hypothèse de l'origine tubaire du CSHG. Bien que nous ne disposions toujours pas d'une réponse à la question de savoir si le retrait des trompes de Fallope (salpingectomie) au moment d'une chirurgie pelvienne effectuée pour d'autres raisons mène à une baisse du taux de mortalité attribuable au cancer de l'ovaire, elle demeure néanmoins un domaine d'intérêt important pour les futures recherches cliniques.

Toward a wiki guide for obstetrics and gynecology trainees in Ireland.

BACKGROUND: The present paper describes the implementation of a novel, web-based, comprehensive national information hub for trainees in obstetrics and gynecology in Ireland. This was a unique development in the context of an entire medical specialty and was aligned with the communication strategy of the governing professional body. To date, trainee doctors working in Ireland undergo an incoherent and inconsistent new-staff induction and handover. In the healthcare setting, staff integration can have a major impact on the quality of patient care. METHODS: A free wiki software platform (PBworks) was used for the website, and freely available software (Google Analytics) was used to determine user interaction and level of engagement. RESULTS: In the first year, 442 user visits were recorded. The average duration of site visits was 4 minutes 39 seconds, which compared favorably with the 4-minute duration for visits to Wikipedia. CONCLUSION: The project was successful as a proof concept and in practice. Other medical faculties have expressed an interest in adopting the concept and developing it for their trainees. The concept is widely applicable to other countries, with the negligible cost relevant to resource-poor areas.