54 results found
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, 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.
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
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
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, Recurrent ovarian cancer, Challenging Concepts in Obstetrics and Gynaecology Cases with Expert Commentary, Publisher: Oxford University Press, USA, ISBN: 9780199654994
Expert comment Within 12 months of completion of chemotherapy, there was recurrent disease evident on Mrs M's CT ... Learning point Recurrent Ovarian Cancer (ROC) ○ 70–90% of patients diagnosed with advanced ovarian cancer will at ...
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 ...
Wali S, Chatterjee J, Zeegen R, et al., 2015, Concealed haematometra causing chronic upper abdominal pain., J Obstet Gynaecol, Vol: 35, Pages: 537-539
Saso S, Petts G, Chatterjee J, et al., 2014, Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: a long-term viability study, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 182, Pages: 185-193, ISSN: 0301-2115
Datta S, Chatterjee J, Butt S, et al., 2014, Individual medical indemnity is essential for twenty-first century Obstetrics and Gynaecology practice, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 121, Pages: 1444-1445, ISSN: 1470-0328
Saso S, Hurst S, Chatterjee J, et al., 2014, Test of long- term uterine survival after allogeneic transplantation in rabbits, JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, Vol: 40, Pages: 754-762, ISSN: 1341-8076
Maine CJ, Aziz NHA, Chatterjee J, et al., 2014, Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer, CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol: 63, Pages: 215-224, ISSN: 0340-7004
Kyrgiou M, Chatterjee J, Lyus R, et al., 2013, The role of cytology and other prognostic factors in endometrial cancer, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 33, Pages: 729-734, ISSN: 0144-3615
Saso S, Chatterjee J, Pai P, et al., 2013, Training the trainees: An evaluation exercise using the TLH and BSO model, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 33, Pages: 548-552, ISSN: 0144-3615
Saso S, Chatterjee J, Thum Y, et al., 2013, Uterine viability following allogenic uterine transplantation in a rabbit model, RCOG World Congress, Liverpool, UK
Chatterjee J, Datta S, Butt S, et al., 2013, Personal professional indemnity and contractual issues for trainees in obstetrics and gynaecology, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 33, Pages: 125-127, ISSN: 0144-3615
Saso S, Chatterjee J, Yazbek J, et al., 2012, A case of pregnancy following a modified Strassman procedure applied to treat a placental site trophoblastic tumour, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 119, Pages: 1665-1667, ISSN: 1470-0328
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