65 results found
Karkia R, Tailor A, Ellis P, et al., 2022, Minimally invasive pelvic exenteration for gynaecological malignancy: A single-centre case series and review of the literature., Eur J Obstet Gynecol Reprod Biol, Vol: 274, Pages: 56-61
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
Zahra A, Hall M, Chatterjee J, et al., 2022, In Silico Study to Predict the Structural and Functional Consequences of SNPs on Biomarkers of Ovarian Cancer (OC) and BPA Exposure-Associated OC., Int J Mol Sci, Vol: 23
BACKGROUND: Recently, we have shown that seven genes, namely GBP5, IRS2, KRT4, LINCOO707, MRPL55, RRS1 and SLC4A11, have prognostic power for the overall survival in ovarian cancer (OC). METHODS: We present an analysis on the association of these genes with any phenotypes and mutations indicative of involvement in female cancers and predict the structural and functional consequences of those SNPS using in silico tools. RESULTS: These seven genes present with 976 SNPs/mutations that are associated with human cancers, out of which 284 related to female cancers. We have then analysed the mutation impact on amino acid polarity, charge and water affinity, leading to the identification of 30 mutations in gynaecological cancers where amino acid (aa) changes lead to opposite polarity, charges and water affinity. Out of these 30 mutations identified, only a missense mutation (i.e., R831C/R804C in uterine corpus endometrial carcinomas, UCEC) was suggestive of structural damage on the SLC4A11 protein. CONCLUSIONS: We demonstrate that the R831C/R804C mutation is deleterious and the predicted ΔΔG values suggest that the mutation reduces the stability of the protein. Future in vitro studies should provide further insight into the role of this transporter protein in UCEC.
Uwins C, Patel H, Prakash Bhandoria G, et al., 2021, Laparoscopic and Robotic Surgery for Endometrial and Cervical Cancer., Clin Oncol (R Coll Radiol), Vol: 33, Pages: e372-e382
Minimally invasive surgery (MIS) has many benefits, in the form of reduced postoperative morbidity, improved recovery and reduced inpatient stay. It is imperative, however, when new techniques are adopted, in the context of treating oncology patients, that the oncological efficacy and safety are established rigorously rather than assumed based on first principles. Here we have attempted to provide a comprehensive review of all the contentious and topical themes surrounding the use of MIS in the treatment of endometrial and cervix cancer following a thorough review of the literature. On the topic of endometrial cancer, we cover the role of laparoscopy in both early and advanced disease, together with the role and unique benefits of robotic surgery. The surgical challenge of patients with a raised body mass index and the frail and elderly are discussed and finally the role of sentinel lymph node assessment. For cervical cancer, the role of MIS for staging and primary treatment is covered, together with the interesting and highly specialist topics of fertility-sparing treatment, ovarian transposition and the live birth rate associated with this. We end with a discussion on the evidence surrounding the role of adjuvant hysterectomy following radical chemoradiation and pelvic exenteration for recurrent cervical cancer. MIS is the standard of care for endometrial cancer. The future of MIS for cervix cancer, however, remains uncertain. Current recommendations, based on the available evidence, are that the open approach should be considered the gold standard for the surgical management of early cervical cancer and that MIS should only be adopted in the context of research. Careful counselling of patients on the current evidence, discussing in detail the risks and benefits to enable them to make an informed choice, remains paramount.
Hutt S, Mihaies D, Karteris E, et al., 2021, Statistical meta-analysis of risk factors for endometrial cancer and development of a risk prediction model using an artificial neural network algorithm, Cancers, Vol: 13
Objectives: In this study we wished to determine the rank order of risk factors for en-dometrial cancer and calculate a pooled risk and percentage risk for each factor using a statistical meta-analysis approach. The next step was to design a neural network computer model to predict the overall increase or decreased risk of cancer for individual patients. This would help to determine whether this prediction could be used as a tool to decide if a patient should be considered for testing and to predict diagnosis, as well as to suggest prevention measures to patients. Design: A meta-analysis of existing data was carried out to calculate relative risk, followed by design and implementation of a risk prediction computational model based on a neural network algorithm. Setting: Meta-analysis data were collated from various settings from around the world. Primary data to test the model were collected from a hospital clinic setting. Participants: Data from 40 patients notes currently suspected of having endometrial cancer and undergoing investigations and treatment were collected to test the software with their cancer diagnosis not revealed to the software developers. Main outcome measures: The forest plots allowed an overall relative risk and percentage risk to be calculated from all the risk data gathered from the studies. A neural network computational model to determine percentage risk for individual patients was developed, implemented, and evaluated. Results: The results show that the greatest percentage increased risk was due to BMI being above 25, with the risk increasing as BMI increases. A BMI of 25 or over gave an increased risk of 2.01%, a BMI of 30 or over gave an increase of 5.24%, and a BMI of 40 or over led to an increase of 6.9%. PCOS was the second highest increased risk at 4.2%. Diabetes, which is incidentally also linked to an increased BMI, gave a significant increased risk along with null parity and noncontinuous HRT of 1.54%, 1.2%, and 0.56% respectively
Uwins C, Bhandoria GP, Shylasree TS, et al., 2020, COVID-19 and gynecological cancer: a review of the published guidelines., Int J Gynecol Cancer, Vol: 30, Pages: 1424-1433
On March 11, 2020 the COVID-19 outbreak was declared a 'pandemic' by the World Health Organization. COVID-19 is associated with higher surgical morbidity and mortality. An array of guidelines on the management of cancer during this pandemic have been published since the first reports of the outbreak. This narrative review brings all the relevant information from the guidelines together into one document, to support patient care. We present a detailed review of published guidelines, statements, comments from peer-reviewed journals, and nationally/internationally recognized professional bodies and societies' web pages (in English or with English translation available) between December 1, 2019 and May 27, 2020. Search terms included combinations of COVID, SARS-COV-2, guideline, gynecology, oncology, gynecological, cancer. Recommendations for surgical and oncological prioritization of gynecological cancers are discussed and summarized. The role of minimally invasive surgery, patient perspectives, medico-legal aspects, and clinical trials during the pandemic are also discussed. The consensus is that elective benign surgery should cease and cancer surgery, chemotherapy, and radiotherapy should continue based on prioritization. Patient and staff face-to-face interactions should be limited, and health resources used efficiently using prioritization strategies. This review and the guidelines on which it is based support the difficult decisions currently facing us in gynecological cancer. It is a balancing act: limited resources and a hostile environment pitted against the time-sensitive nature of cancer treatment. We can only hope to do our best for our patients with the resources available to us.
Patel H, Madhuri K, Rockell T, et al., 2020, Robotic radical hysterectomy for stage 1B1 cervical cancer: A case series of survival outcomes from a leading UK cancer centre., Int J Med Robot, Vol: 16
BACKGROUND: We present the largest UK single institute robotic radical hysterectomy (RRH) case series for the management of cervical cancer (CC). METHODS: Data were collected on women who had a RRH as primary treatment for stage 1b1 CC between December 2009 and December 2018. RESULTS: Ninty women had a robotic hysterectomy. Five-year follow-up data were available for 30%. The disease-free survival at 5 years was 89.6%. Overall survival at 3 and 5 years for death from any cause was 96.1% and 91.4%, respectively. The overall 5-year survival for death from disease only was 92.8%. Overall survival by tumour size alone showed that women with tumours less than 2 cm had a 98.3% 5-year survival compared to 83.4% for tumour size greater than 2 cm. Irrespective of tumour size, those that had no evidence of lymphovascular space invasion had a 100% 5-year survival. CONCLUSION: Our preliminary data supports the oncological safety of RRH in a selective cohort of patients with stage 1b1 CC.
Nepogodiev D, 2020, Elective surgery cancellations due to theCOVID-19 pandemic: global predictive modelling to inform surgical recovery plans, British Journal of Surgery, Vol: 107, Pages: 1440-1449, ISSN: 0007-1323
BackgroundThe COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19.MethodsA global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations.ResultsThe best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption.ConclusionA very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely.
Otter SJ, Chatterjee J, Stewart AJ, et al., 2019, The Role of Biomarkers for the Prediction of Response to Checkpoint Immunotherapy and the Rationale for the Use of Checkpoint Immunotherapy in Cervical Cancer., Clin Oncol (R Coll Radiol), Vol: 31, Pages: 834-843
Checkpoint immunotherapy has revolutionised the way that melanoma is treated and has also shown significant effectiveness in lung, bladder, renal, and head and neck cancers. At the present time, trials of checkpoint immunotherapy in cervical cancer are at early phases, but there is very good rationale for pursuing this as a treatment option, especially as cervical cancer is a virally driven cancer and therefore should be recognised by the immune system as being foreign. This review explores the biomarkers for the selection of patients for immunotherapy in other cancers, such as programmed death ligand 1 (PD-L1) expression, tumour infiltrating lymphocytes and total mutational burden, and relates these biomarkers to cervical cancer. A PubMed search was carried out for publications published in English with the terms 'immunotherapy' OR 'cervical cancer' OR 'checkpoint blockade' OR 'tumour infiltrating lymphocytes' OR 'total mutational burden'. Articles that met these criteria and were available on PubMed before 8 October 2018 were included. The results showed that PD-L1 is positive in up to 90% of cervical cancers and that the total mutational burden is moderately high, with 5-6 mutations per megabase. In addition, the tumour microenvironment in cervical cancer has an impact on prognosis, with higher ratios of CD8+ tumour infiltrating lymphocytes to CD4+ T regulatory cells being associated with improved survival. Clinical studies to date have shown the response rate of cervical cancer to checkpoint immunotherapy to be in the region to 10-25%. Cervical cancer exhibits many of the features that have been shown to be correlated with response to checkpoint immunotherapy in other tumour sites. However, response rates to date are in the region of 10-25%. Therefore, combinations of immunotherapeutic agents or checkpoint inhibitors with radiotherapy may be required to maximise the therapeutic benefit of harnessing the host immune system to fight cancer.
Kumar J, Murugaiah V, Sotiriadis G, et al., 2019, Surfactant Protein D as a Potential Biomarker and Therapeutic Target in Ovarian Cancer, Frontiers in Oncology, Vol: 9
Surfactant protein D (SP-D) is an important innate immune molecule that is involved in clearing pathogens and regulating inflammation at pulmonary as well as extra-pulmonary sites. Recent studies have established the role of SP-D as an innate immune surveillance molecule against lung and pancreatic cancer, but little is known about its involvement in signaling pathways it can potentially activate in ovarian cancer. We focused our study on ovarian cancer by performing bioinformatics analysis (Oncomine) of datasets and survival analysis (Kaplan-Meier plotter), followed by immunohistochemistry using ovarian cancer tissue microarrays. SP-D mRNA was found to be expressed widely in different types of ovarian cancer irrespective of stage or grade. These in silico data were further validated by immunohistochemistry of clinical tissues. High transcriptional levels of SP-D were associated with unfavorable prognosis (overall and progression-free survival). We also detected SP-D protein in Circulating Tumor Cells of three ovarian cancer patients, suggesting that SP-D can also be used as a potential biomarker. Previous studies have shown that a recombinant fragment of human SP-D (rfhSP-D) induced apoptosis in pancreatic cancer cells via Fas-mediated pathway. In this study, we report that treatment of SKOV3 cells (an ovarian cancer cell line) with rfhSP-D led to a decrease in cell motility and cell proliferation. This was followed by an inhibition of the mTOR pathway activity, increase in caspase 3 cleavage, and induction of pro-apoptotic genes Fas and TNF-α. These data, suggesting a likely protective role of rfhSP-D against ovarian cancer, together with the observation that the ovarian cancer microenvironment overexperesses SP-D leading to poor prognosis, seems to suggest that the tumor microenvironment components manipulate the protective effect of SP-D in vivo.
Kumar J, Chudasama D, Roberts C, et al., 2019, Detection of Abundant Non-Haematopoietic Circulating Cancer-Related Cells in Patients with Advanced Epithelial Ovarian Cancer, CELLS, Vol: 8
Hutt S, Tailor A, Ellis P, et al., 2019, The role of biomarkers in endometrial cancer and hyperplasia: a literature review., Acta Oncol, Vol: 58, Pages: 342-352
INTRODUCTION: Endometrial cancer is the most common gynaecological cancer and its incidence is rising due to increasing obesity rates. We are also seeing an increasing trend of young women diagnosed with either endometrial cancer or its precancerous state, endometrial hyperplasia. Diagnosis is dependent on invasive testing and there is no screening tool available for either general or high-risk population groups. Whilst vast amounts of research have been undertaken in higher-profile cancers such as ovarian and cervical, endometrial cancer is comparatively less investigated. AIM: In this literature review, we summarise the existing literature in understanding the role of tumour biomarkers for endometrial cancer and its preceding condition of endometrial hyperplasia. METHOD: NICE Healthcare Databases Search tool was used to search Embase, Medline and PubMed databases for relevant articles. CONCLUSION: There is currently no routinely used biomarker in endometrial cancer for diagnostic or prognostic purposes. Given the establishment of new genomic classifications of endometrial cancers, the use of biomarkers to drive therapeutic approaches will be the cornerstone for individualised cancer care in the coming decades.
Otter S, Whitaker S, Chatterjee J, et al., 2019, The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers., Clin Oncol (R Coll Radiol), Vol: 31, Pages: 81-90
The burden of human papillomavirus (HPV)-related cancers worldwide is significant. Although the incidence of cervical cancer is decreasing due to cervical screening programmes, the incidences of oropharyngeal, anal and vulval cancers are increasing. The introduction of HPV vaccination programmes in many countries has had an impact on HPV infection rates but due to the time-lag from initial HPV infection to the development of invasive carcinoma, the impact on the incidence of HPV-related cancer will take more time to become evident. This review explores the common aspects of HPV-related cancers and how they differ from their HPV-negative counterparts, both clinically and molecularly. It also covers the implications this has on future treatment strategies, including the possible role of immunotherapy.
International Surgical Outcomes Study ISOS group, 2019, Prospective observational cohort study on grading the severity of postoperative complications in global surgery research., Br J Surg, Vol: 106, Pages: e73-e80
BACKGROUND: The Clavien-Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien-Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). METHODS: This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien-Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. RESULTS: A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien-Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). CONCLUSION: Caution is recommended when using a treatment approach to grade complications in global sur
Rogers-Broadway K-R, Kumar J, Sisu C, et al., 2019, Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry., Int J Mol Med, Vol: 43, Pages: 47-56
Endometriosis is a well‑known risk factor for ovarian cancer. The genetic changes that characterise endometriosis are poorly understood; however, the mechanistic target of rapamycin (mTOR) pathway is involved. In this study, we investigated the expression of key mTOR components in endometriosis and the effects of rapalogues using an endometrioid ovarian carcinoma cell line (MDAH 2774) as an in vitro model. Gene expression of mTOR, DEPTOR, Rictor and Raptor was assessed by qPCR in 24 endometriosis patients and in silico in ovarian cancer patients. Furthermore, the effects of Rapamycin, Everolimus, Deforolimus, Temsirolimus, Resveratrol, and BEZ235 (Dactolisib, a dual kinase inhibitor) on mTOR signalling components was assessed. mTOR showed a significant increase in the expression in endometriosis and ovarian endometrioid adenocarcinoma patients compared to non‑affected controls. DEPTOR, an inhibitor of mTOR, was downregulated in the advanced stages of ovarian cancer (III and IV) compared to earlier stages (I and II). Treatment of MDAH‑2774 cells with the mTOR inhibitors resulted in the significant upregulation of DEPTOR mRNA, whereas treatment with rapamycin and BEZ‑235 (100 nM) resulted in downregulation of the mTOR protein expression after 48 h of treatment. None of the treatments resulted in translocation of mTOR from cytoplasm to nucleus. Upregulation of DEPTOR is a positive prognostic marker in ovarian cancer and is increased in response to mTOR pathway inhibition suggesting that it functions as a tumour suppressor gene in endometrioid ovarian carcinoma. Collectively, our data suggest the mTOR pathway as a potential connection between endometriosis and ovarian cancer and may be a potential target in the treatment of both conditions.
Ayakannu T, Murugesu S, Taylor AH, et al., 2019, The Impact of Focality and Centricity on Vulvar Intraepithelial Neoplasia on Disease Progression in HIV+ Patients: A 10-Year Retrospective Study., Dermatology, Vol: 235, Pages: 327-333
BACKGROUND: The impact of lesion focality and centricity in relation to patient outcome and disease recurrence of vulvar intraepithelial neoplasia (VIN) is an understudied area of research, especially in immunocompromised women. The prevalence and incidence of VIN have increased steadily since the 1980s because of the co-existence of human papillomavirus (HPV) and human immunodeficiency virus (HIV). In this study, we retrospectively examined the records of VIN patients to determine the effect of lesion focality and centricity with respect to the interval to disease recurrence. MATERIALS AND METHODS: All women diagnosed with VIN and managed between January 2002 and December 2011 were included (n = 90) and followed up until December 2017. Symptoms at the time of presentation, including HIV positivity (n = 75), were collated, including the influences of multifocality and multicentricity on time to disease recurrence. RESULTS: Multicentricity caused a more rapid recurrence of disease than unicentricity (p = 0.006), whereas multifocality increased the risk of recurrence more than unifocality (p < 0.0001). Viral load in the HIV+ patients was not associated with time to disease recurrence, but the reduced number of CD4+ lymphocytes present in HIV+ patients was. Treatment modalities had no effect on disease recurrence. CONCLUSION: Both focality and centricity have effects on interval to recurrence and final patient outcome, with multifocal disease having a poorer prognosis. Centricity and focality should be recorded at the time of diagnosis and act as a warning for disease recurrence. HIV+ VIN patients with multifocal disease and/or known immunosuppression (low CD4+ lymphocyte counts) should be regarded as "high-risk" patients and treated accordingly.
Bharathan R, Madhuri K, Fish A, et al., 2018, Effect of blue dye guided lymph channel ligation on the surgical morbidity of groin lymphadenectomy for vulval cancer: a feasibility study., J Obstet Gynaecol, Vol: 38, Pages: 674-677
Inguinal lymphadenectomy has significant morbidity. Blue dye-guided lymph channel ligation is an effective technique for resolving lymphocele. This was a feasibility study in a preventative setting. Patients with vulval cancer requiring bilateral inguinal lymphadenectomy were recruited. After lymphadenectomy, patent blue V dye was injected and the severed lymph channels leaking blue dye, on the randomly-designated side were ligated. The median age was 72.5 years and the median body mass index was 25. The median lymph node harvest was 18.5. There were no significant surgical procedural differences between the right and the left sides. There was no significant difference between the two arms in terms of the duration or the volume of drainage and post-operative complications. All patients were alive at the follow-up period of 40.5 months. In this feasibility study, blue dye-guided lymph channel ligation did not significantly impact on post-operative outcomes. Impact statement What is already known on this subject? Lymph channel ligation with blue dye-guidance is an effective strategy for managing recalcitrant inguinal lymphocyst. This strategy was prospectively-studied in a small series of patients with non-gynaecological cancers. This particular study by Nakamura et al. ( 2011 ) revealed that such a strategy might be efficacious in reducing wound drain output. What do the results of this study add? Our study is the first study to assess this technique exclusively in vulval cancer. Blue dye-guided lymph channel ligation at the time of inguinal lymphadenectomy does not appear to reduce wound drainage. However, this study suggests that primary lymphocyst predominantly results from inflammatory exudates, whereas persistent secondary lymphocysts are likely to result from lymphorrhoea. What are the implications of these findings for clinical practice and/or further research? Future studies, which aim to reduce the morbidity of open inguinal lymphadenectomy, should empl
Abbott TEF, Ahmad T, Phull MK, et al., 2018, The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis, BRITISH JOURNAL OF ANAESTHESIA, Vol: 120, Pages: 146-155, ISSN: 0007-0912
Ahmad T, Bouwman RA, Grigoras I, et al., 2017, In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study, EJSO, Vol: 43, Pages: 2324-2332, ISSN: 0748-7983
Ahmad T, Bouwman RA, Grigoras I, et al., 2017, Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery, BRITISH JOURNAL OF ANAESTHESIA, Vol: 119, Pages: 258-266, ISSN: 0007-0912
Kahan BC, Koulenti D, Arvaniti K, et al., 2017, Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries, INTENSIVE CARE MEDICINE, Vol: 43, Pages: 971-979, ISSN: 0342-4642
Phelps DL, Borley J, Flower K, et al., 2017, Methylation of MYLK3 gene promoter region: a biomarker to stratify surgical care in ovarian cancer in a multi-centre study, British Journal of Cancer, Vol: 116, Pages: 1287-1293, ISSN: 1532-1827
BackgroundSurvival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.MethodsClinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.ResultsAltogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)). ConclusionMYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.
Chatterjee J, Dai W, Abd Aziz NH, et al., 2016, Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer, Clinical Cancer Research, Vol: 23, Pages: 3453-3460, ISSN: 1557-3265
Purpose We aimed to establish whether PD-1 and PD-L1 expression, in ovarian cancer (OC) tumour tissue and blood, could be used as biomarkers for discrimination of tumour histology and prognosis of OC. Experimental Design Immune cells were separated from blood, ascites and tumour tissue obtained from women with suspected OC and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumour associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumours and epithelial ovarian cancers (EOC) - confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumour marker CA-125 alone. Plasma soluble PD-L1 was elevated in EOC patients compared to healthy women and patients with benign ovarian tumours. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti PD-1/PD-L1 therapy in ovarian cancer.
Ahmad T, Bouwman RA, Grigoras I, et al., 2016, Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries., British Journal of Anaesthesia, Vol: 117, Pages: 601-+, ISSN: 0007-0912
BackgroundAs global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care.MethodsWe designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries.ResultsA total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2–7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries.ConclusionsPoor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care.
Jones B, Jeevananthan P, Sayasneh A, et al., 2016, The novel application of plasma energy as a tissue preserving treatment modality for vulval and perianal intraepithelial neoplasia, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 123, Pages: 81-81, ISSN: 1470-0328
Chatterjee J, Howden S, Saso S, et al., 2016, Metastatic low-grade fibromyxoid sarcoma of the broad ligament: A case report and literature review., Journal of Obstetrics and Gynaecology, Pages: 1-3, ISSN: 1364-6893
Saso S, Louis LS, Doctor F, et al., 2015, Does fertility treatment increase the risk of uterine cancer? A meta-analysis, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 195, Pages: 52-60, ISSN: 0301-2115
Rizzuto I, Stavraka C, Chatterjee J, et al., 2015, Risk of Ovarian Cancer Relapse Score A Prognostic Algorithm to Predict Relapse Following Treatment for Advanced Ovarian Cancer, International Journal of Gynecological Cancer, Vol: 25, Pages: 416-422, ISSN: 1525-1438
Objective: The aim of this study was to construct a prognostic index that predicts risk ofrelapse in women who have completed first-line treatment for ovarian cancer (OC).Methods: A database of OC cases from 2000 to 2010 was interrogated for InternationalFederation of Gynecology and Obstetrics stage, grade and histological subtype of cancer,preoperative and posttreatment CA-125 level, presence or absence of residual disease aftercytoreductive surgery and on postchemotherapy computed tomography scan, and time toprogression and death. The strongest predictors of relapse were included into an algorithm,the Risk of Ovarian Cancer Relapse (ROVAR) score.Results: Three hundred fifty-four cases of OC were analyzed to generate the ROVARscore. Factors selected were preoperative serum CA-125, International Federation ofGynecology and Obstetrics stage and grade of cancer, and presence of residual disease atposttreatment computed tomography scan. In the validation data set, the ROVAR score had asensitivity and specificity of 94% and 61%, respectively. The concordance index for thevalidation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patientstratification into low (G0.33), intermediate (0.34Y0.67), and high (90.67) probability ofrelapse.Conclusions: The ROVAR score stratifies patients according to their risk of relapsefollowing first-line treatment for OC. This can broadly facilitate the appropriate tailoring ofposttreatment care and support.
Saso S, Petts G, David AL, et al., 2015, Achieving an early pregnancy following allogeneic uterine transplantation in a rabbit model, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 185, Pages: 164-169, ISSN: 0301-2115
Chatterjee J, 2015, Cervical Cancer, Challenging Concepts in Obstetrics and Gynaecology Cases with Expert Commentary, Publisher: Oxford University Press, USA, ISBN: 9780199654994
Evidence base Clinical trials in cervical cancer There are several ongoing clinical trials in cervical cancer: ○ The surgical trials include study on sentinel nodes and various techniques for surgical staging. ○ CIRCCa (Cediranib in Recurrent ...
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