Can natural language processing be effectively applied for audit data analysis in gynaecological oncology at a UK cancer centre?

BACKGROUND: The British Gynaecological Cancer Society (BGCS) has highlighted the disparity of ovarian cancer outcomes in the UK compared to other European countries. Therefore, cancer quality assurance audits and subspecialty training are important in improving the UK standard of care for these patients. The current workforce crisis afflicting the NHS creates difficulty in dedicating teams of clinicians to these audits. We present a single institution study to evaluate if NLP-generated code can improve the efficiency of ovarian cancer and subspeciality reaccreditations audits. We used the chat bot Google Bard to write Visual Basic Applications algorithms that utilise Excel files from electronic health records. METHODS: Primary ovarian cancer data from 2019 to 2022 was retrospectively collected from the Cambridge University Hospital electronic health records. The surgical subspecialty reaccreditation audit analysed the 2022 surgical database. A modular coding approach with Google Bard was applied to generate audit algorithms. The time to complete these current audits was compared against the 2016 ovarian cancer and 2020 subspeciality reaccreditation audits. RESULTS: The previous ovarian cancer audit conducted in 2016 required 3 clinicians for the 135 cases and data collection required 1800 min. Data analysis was completed in 300 min. The current ovarian cancer audit allocated 2 clinicians to the 600 surgical cases. Data collection was completed in 3120 min, 3360 min for code development and 720 min for testing. The 2020 subspecialty reaccreditation audit was completed in 360 min. The 2022 subspecialty reaccreditation audit was completed in 1680 min, with 960 min for code development, 240 for debugging and 480 min for testing. CONCLUSION: We have demonstrated that NLP-generated code can significantly increase the efficiency of surgical quality assurance audits by eliminating the need for manual data analysis. With the current trajectory of NLP development, increasingly complex algorithms can be developed with minimal programming knowledge.

Incidental Finding of Thickened Endometrium in Postmenopausal Women: A Survey of Endometrial Cancer.

Objectives The primary objective was to determine the prevalence of endometrial cancer in asymptomatic and symptomatic postmenopausal women referred to the hysteroscopy service for incidental finding of thickened endometrium. The secondary objectives were to identify, for the asymptomatic cohort, an acceptable threshold of endometrial thickness (ET) which should trigger endometrial sampling and its related sensitivity and specificity. Methods This was a retrospective cohort study of 136 asymptomatic and 602 symptomatic postmenopausal women with an ET of >4 mm referred to the endometrial cancer diagnostic service in a gynecology oncology center over a period of one year. Clincal and demographic data were analyzed. Histopathological diagnosis was completed and receiver operating characteristic (ROC) curves for acceptable ET cutoff in asymptomatic women were evaluated. Results The prevalence of malignancy and atypical hyperplasia in asymptomatic women was 3.7% and 4.4%, respectively. Within the asymptomatic subgroup with ET <11 mm, the yield rate for atypical hyperplasia (AH)+cancer was 2.2%. An ET <10 mm gave a similar yield; however, specificity decreased. ET (t-test p-value=0.037) correlates with endometrial pathology. Receiver operating characteristic (ROC) curves identified a cutoff of 11 mm as an acceptable threshold for triggering further investigations. Conclusion Based on our findings, 11 mm may represent an acceptable threshold for further investigation in asymptomatic postmenopausal women. We strongly advocate qualitative assessment of the endometrium and evaluation of individual risk factors in women with ET between 4 mm and 11 mm. This study will contribute to the existing body of evidence for the management of asymptomatic postmenopausal women with incidental increased ET. Further studies are required.

Lesion-specific 3D-printed moulds for image-guided tissue multi-sampling of ovarian tumours: A prospective pilot study.

Background: High-Grade Serous Ovarian Carcinoma (HGSOC) is the most prevalent and lethal subtype of ovarian cancer, but has a paucity of clinically-actionable biomarkers due to high degrees of multi-level heterogeneity. Radiogenomics markers have the potential to improve prediction of patient outcome and treatment response, but require accurate multimodal spatial registration between radiological imaging and histopathological tissue samples. Previously published co-registration work has not taken into account the anatomical, biological and clinical diversity of ovarian tumours. Methods: In this work, we developed a research pathway and an automated computational pipeline to produce lesion-specific three-dimensional (3D) printed moulds based on preoperative cross-sectional CT or MRI of pelvic lesions. Moulds were designed to allow tumour slicing in the anatomical axial plane to facilitate detailed spatial correlation of imaging and tissue-derived data. Code and design adaptations were made following each pilot case through an iterative refinement process. Results: Five patients with confirmed or suspected HGSOC who underwent debulking surgery between April and December 2021 were included in this prospective study. Tumour moulds were designed and 3D-printed for seven pelvic lesions, covering a range of tumour volumes (7 to 133 cm3) and compositions (cystic and solid proportions). The pilot cases informed innovations to improve specimen and subsequent slice orientation, through the use of 3D-printed tumour replicas and incorporation of a slice orientation slit in the mould design, respectively. The overall research pathway was compatible with implementation within the clinically determined timeframe and treatment pathway for each case, involving multidisciplinary clinical professionals from Radiology, Surgery, Oncology and Histopathology Departments. Conclusions: We developed and refined a computational pipeline that can model lesion-specific 3D-printed moulds from preoperative imaging for a variety of pelvic tumours. This framework can be used to guide comprehensive multi-sampling of tumour resection specimens.

Organ-sparing central pelvic compartment resection for the treatment of vulvo-vaginal melanomas.

Vulvo-vaginal melanomas are one of the rarest gynecological oncology diseases with a poor survival compared with other malignancies. The 5-year survival varies from 13% to 32.3%. Vulvo-vaginal melanomas involving the upper 2/3rds of the vagina are usually treated with total pelvic exenteration (TPE). TPE surgery carries a 50% risk of major complications and also morbidity associated with double stomas. Central pelvic compartment resection is a novel organ-sparing surgical approach entailing radical total laparoscopic hysterectomy, bilateral salpingo-oophrectomy, laparoscopic vaginectomy and vulvectomy to reduce morbidity compared with TPE. Permanent suprapubic catheters are used if there is urethral involvement but require quality of life studies to assess their long-term outcomes.

Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells.

Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.

Ano-uro-genital mucosal melanoma UK national guidelines.

Ano-uro-genital (AUG) mucosal melanomas are rare cancers associated with poor outcomes and limited evidence-based management. The United Kingdom AUG mucosal melanoma guideline development group used an evidence-based systematic approach to make recommendations regarding the diagnosis, treatment and surveillance of patients diagnosed with AUG mucosal melanomas. The guidelines were sent for international peer review, and are accredited by The National Institute for Health and Clinical Excellence (NICE). A summary of the key recommendations is presented. The full documents are available on the Melanoma Focus website.

Results from Survey to Assess Current Trends in Surgical Practice in the Management of Women with Early Stage Cervical Cancer within the BGCS Community with an Emphasis on Routine Frozen Section Examination.

In the UK, more than 3,200 new cases of cervical cancer are diagnosed each year. Early stage cervical cancer (IA2-IB1) treatment comprises central surgery mainly in the form of radical hysterectomy or fertility sparing surgery including trachelectomy as well as systematic pelvic lymphadenectomy to detect metastases and adjust treatment accordingly. Given the variation in determining the lymph node (LN) status, a major prognosticator, we reviewed the current UK practice of LN assessment in women undergoing surgery for early cervical cancer. A 7-question, web-based survey, screened by the BGCS committee, was circulated amongst BGCS members. The overall response rate was 51%. Only 12.5% of the respondents routinely performed frozen section examination (FSE); the main reasons for not doing FSE were the pressure on theatre time (54.5%) and the lack of available facilities (48.5%). When positive pelvic nodal disease was detected, in 21 out of 50 (42%) the planned radical hysterectomy (RH) was aborted. More than 70% of the respondents routinely performed RH without any prior resort to pelvic lymphadenectomy. Pretreatment surgical para-aortic LN assessment was performed by 20% of the respondents. The survey confirms the diversity of the UK practice patterns in the surgical treatment of early cervical cancer.

Routine Intraoperative Frozen Section Examination to Minimize Bimodal Treatment in Early-Stage Cervical Cancer.

OBJECTIVE: In early-stage cervical cancer, single modality therapy is the main objective, to minimize patient morbidity while offering equivalent cure rates. Intraoperative frozen section examination (FSE) of lymph nodes (LNs) can facilitate this aim, ensuring that radical surgery is avoided in patients requiring adjuvant therapy for metastatic LN involvement. We aimed to evaluate the accuracy of routine intraoperative FSE of pelvic LNs during the surgical staging of early-stage cervical cancers and identify a group at low risk for nodal metastases. METHODS: A retrospective cohort study of 94 women aged 23 to 80 years who underwent primary surgery and planned intraoperative FSE of the pelvic LNs at the gynecological cancer center in Oxford was performed. The diagnostic value of FSE and the prediction of metastatic nodal disease were assessed by use of preoperative and intraoperative variables. RESULTS: A total of 1825 LNs were submitted for FSE. Of 94 women (13.8%), 13 had positive LNs at FSE. Two false-negative cases were reported with micrometastases but no false-positive cases. Frozen section examination as a diagnostic test reached a sensitivity of 86.7% and a specificity of 100%. A regression model including grade I to II and tumor size of less than 20 mm identified a low-risk group for LN involvement. CONCLUSIONS: In light of diverse practice patterns, FSE should be routinely offered to women with early-stage cervical cancer in a 1-step protocol. We equally devised a model to predict those patients at least risk of nodal disease, who may be spared of FSE.

A prospective pilot study of detection of sentinel lymph nodes in gynaecological cancers using a novel near infrared fluorescence imaging system.

BACKGROUND: Sentinel Lymph Node (SLN) sampling may significantly reduce surgical morbidity by avoiding needless radical lymphadenectomy. In gynaecological cancers, the current practice in the UK is testing the accuracy of SLN detection using radioactive isotopes within the context of clinical trials. However, radioactive tracers pose significant logistic problems. We, therefore, conducted a pilot, observational study to assess the feasibility of a novel optical imaging device for SLN detection in gynaecological cancers using near infrared (NIR) fluorescence. METHODS: A novel, custom-made, optical imaging system was developed to enable detection of multiple fluorescence dyes and allow simultaneous bright-field imaging during open surgery and laparoscopic procedures. We then evaluated the performance of the system in a prospective study of 49 women with early stage vulval, cervical and endometrial cancer who were scheduled to undergo complete lymphadenectomy. Clinically approved fluorescent contrast agents indocyanine green (ICG) and methylene blue (MB) were used. The main outcomes of the study included SLN mapping detection rates, false negative rates using the NIR fluorescence technique and safety of the procedures. We also examined the association between injection sites and differential lymphatic drainage in women with endometrial cancer by fluorescence imaging of ICG and MB. RESULTS: A total of 64 SLNs were detected during both open surgery and laparoscopy. Following dose optimisation and the learning phase, SLN detection rate approached 100 % for all cancer types with no false negatives detected. Fluorescence from ICG and MB detected para-aortic SLNs in women with endometrial cancer following uterine injection. Percutaneous SLN detection was also achieved in most women with vulval cancer. No adverse reactions associated with the use of either dyes were observed. CONCLUSIONS: This study demonstrated the successful clinical application of a novel NIR fluorescence imaging system for SLN detection across different gynaecological cancers. We showcased the first in human imaging, during the same procedure, of two fluorescence dyes in women with endometrial cancer.

Outcomes of ovarian transposition in gynaecological cancers; a systematic review and meta-analysis.

BACKGROUND: Pelvic irradiation is essential for improving survival in women with pelvic malignancies despite inducing permanent ovarian damage. Ovarian transposition can be performed in premenopausal women in an attempt to preserve ovarian function. As uncertainty occurs over the proportion of women who are likely to benefit from the procedure, we performed a systematic review and meta-analysis of the proportion of women with ovarian function preservation, symptomatic or asymptomatic ovarian cysts and metastatic ovarian malignancy following ovarian transposition. METHODS: Medline, Embase and The Cochrane Library databases were systematically searched for articles published from January 1980 to December 2013. We computed the summary proportions for ovarian function preservation, ovarian cyst formation and metastatic ovarian disease following ovarian transposition by random effects meta-analysis with meta-regression to explore for heterogeneity by type of radiotherapy. RESULTS: Twenty four articles reporting on 892 women undergoing ovarian transposition were included. In the surgery alone group, the proportion of women with preserved ovarian function was 90% (95% CI 92-99), 87% (95% CI 79-97) of women did not develop ovarian cysts and 100% (95% CI 90-111) did not suffer metastases to the transposed ovaries. In the brachytherapy (BR)± surgery group, the proportion of women with preserved ovarian function was 94% (95% CI 79-111), 84% (95% CI 70-101) of women did not develop ovarian cysts and 100% (95% CI 85-118) did not suffer metastases to the transposed ovaries. In the external beam radiotherapy (EBRT) +surgery ± BR group, the proportion of women with preserved ovarian function was 65% (95% CI 56-74), 95% (95% CI 85-106) of women did not develop ovarian cysts and 100% (95% CI 90-112) did not suffer metastases to the transposed ovaries. Subgroup meta-analysis revealed transposition to the subcutaneous tissue being associated with higher ovarian cyst formation rate compared to the "traditional" transposition. CONCLUSION: Ovarian transposition is associated with significant preservation of ovarian function and negligible risk for metastases to the transposed ovaries despite common incidence of ovarian cysts.

Differentiating pelvic actinomycosis from advanced ovarian cancer: a report of two cases, management reflections and literature review.

Pelvic actinomycosis comprises a rare, subacute to chronic bacterial infection characterised by suppurative and granulomatous inflammation. Diagnosis is difficult as it may simulate pelvic malignancies. Laboratory and radiological findings are non-specific. We reported on 2 cases of pelvic actinomycosis mimicking ovarian malignancy with different management approaches that lead to opposite outcomes. We reviewed the literature on pelvic actinomycosis imitating ovarian cancer with a focus on its surgical management. Despite agreement on the duration of antibiotic therapy following surgical management, consensus regarding surgical approach was rather equivocal. We concluded that pelvic actinomycosis should be strongly suspected in women with presumed ovarian cancer of atypical presentation and a history of intrauterine devices (IUD).

Advances in gynaecological oncology surgery.

Latest surgical advances in the field of gynaecological oncology, a sub-specialty of gynaecology, are reviewed in this chapter. The surgery is mainly practised in cancer centres by board-certified gynaecologists, and requires a 2-3 year period of additional training in gynaecological oncology. Surgical treatment of gynaecological malignancies has progressed in two directions: reduction of the invasiveness of the surgery and expansion of the number and type of procedures performed. Gynaecological oncology focuses on the pelvis to the upper abdomen and the thorax to target (all visible disease) the last cancer cell in women with advanced ovarian cancer. Minimal-access surgery has evolved to include any operation by laparoscopy. It uses fewer ports (single-port surgery), and robotic assistance improves the comfort of the surgeon. The concept of fertility-sparing surgery for women with cervical cancer is now supported by mature data. The indication and the aggressiveness of the exenterative surgery are also broader than originally recommended. The ideal timing of surgery is under investigation in several areas, mainly in women with ovarian and cervical cancer. The aim is to reduce morbidity and mortality of surgical procedures while maintaining the survival outcome.