Khalil Razvi

Ovarian cancer diagnosis with complementary learning fuzzy neural network

DNA microarray is an emerging technique in ovarian cancer diagnosis. However, very often, microarray data is ultra-huge and difficult to analyze. Thus, it is desirable to utilize fuzzy neural network (FNN) approach for assisting the diagnosis and analysis process. Amongst FNN, complementary learning FNN is able to rapidly derive fuzzy sets and formulate fuzzy rules. Complementary learning FNN uses positive and negative learning, and hence it subsides the effect of curse of dimension and is capable of modeling the dynamics of problem space with relative good classification performance. Furthermore, FALCON-AART has human-like reasoning that allows physician to examine its computation in a familiar way. FALCON-AART can generate intuitive fuzzy rule to justify its reasoning, which is important to generate trust among the users of the system. Hence, FALCON-AART is applied in ovarian cancer diagnosis as a clinical decision support system in this work. Its experimental results are encouraging.

E2F5 status significantly improves malignancy diagnosis of epithelial ovarian cancer

BackgroundOvarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.MethodsUsing a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.ResultsAnalysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity, specificity, F-measure and accuracy of 97.92%, 97.37%, 97.92% and 97.67%, respectively.ConclusionsOverall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis.

Family history and women with ovarian cancer: is it asked and does it matter?: An observational study.

Objective The objective of the study was to determine how many women in an ovarian cancer (OC) study cohort had a family history (FH) recorded in their case notes and whether appropriate action was taken on the basis of that FH. Methods This was a review of patient case-note data of women in a randomized controlled trial of follow-up after primary treatment for OC. Available case notes of 114 women recruited at 3 UK gynecologic cancer centers in a 2-year period between January 2006 and 2008 were examined. Case-note entries for the period from first hospital consultation to 2 years after completion of primary treatment were included. Outcome measures were (1) recording of an FH of cancer in the case notes, (2) whether appropriate action had been taken on the basis of the FH in those women with affected relatives, and (3) characterizing insufficient FH records. Results Family history was not consistently recorded. Although FH was recorded in the majority of women, 14 women had no FH recorded. In 63 women, the FH was recorded as not significant, and in 15 cases, FH information was insufficient to complete a risk assessment. Twenty-two women had significant FH meeting criteria for specialist genetics referral. In 15 of these 22 cases, the relevant history suggestive of hereditary breast cancer and OC (due to BRCA1 or BRCA2 mutations) or Lynch syndrome had been documented, but no action was recorded, and its significance was not appreciated. Conclusions These data indicate that training in recognizing relevant FH is needed for clinicians looking after women with OC. Research is necessary to determine the barriers in taking and interpreting an FH and to determine the optimal time for broaching FH issues during a woman’s care pathway. This will improve the accuracy of FH recording and ensure families with OC have access to appropriate surveillance and genetic testing.

Symptoms and risk factors of ovarian cancer: a survey in primary care.

In spite of the increased awareness of ovarian cancer symptoms, the predictive value of symptoms remains very low. The aim of this paper is to obtain the views of general practitioners (GPs) in relation to symptom-based detection of ovarian cancer and to assess their knowledge for family history of breast and/or ovarian cancer as a predisposing factor for ovarian cancer. In this questionnaire survey, postal questionnaires were sent to 402 GPs in 132 primary care clinics, out of which we obtained 110 replies (27.4%). Approximately 26% of respondent GPs thought that the symptoms were more likely to be frequent, sudden, and persistent, and one-fifth were unsure of the importance of family history of breast cancer in relation to ovarian cancer. The participant GPs scored a set of symptoms for their relevance to ovarian cancer from 0 (not relevant) to 10 (most relevant). The highest scored symptoms were abdominal swelling (mean ± SD, 8.19 ± 2.33), abdominal bloating (7.01 ± 3.01), and pelvic pain (7.46 ± 2.26). There was a relative lack of awareness for repetitive symptoms as well as gastrointestinal symptoms as an important feature in a symptom-based detection of ovarian cancer.

Surgical approach to a vulval-pubic cartilaginous cyst: A case report and review of published work.

Cartilaginous cyst of symphysis pubis is rare and to our knowledge 12 cases have been reported in the published work. Although cartilaginous cysts of the vulva and pubis are likely to present to a gynecologist as a vulval–pubic mass, their diagnosis and management warrants a multidisciplinary team approach because of their rarity and anatomical location. Non‐invasive diagnosis includes magnetic resonance imaging and ultrasound scan, while the invasive preoperative biopsy is reserved for cases with a high index of suspicion of malignancy. The surgical approach for the management of vulval–pubic cartilaginous cyst is not well established. The current case demonstrates a joint surgical approach involving a gynecologist and orthopedic surgeon in management of a degenerative cartilaginous cyst. As this condition is benign, every effort should be made to preserve the stability of the pubic symphysis. Symphyseal dysfunction from surgery remains a potential complication for which treatment is not straightforward.

Paraneoplastic vasculitis with digital necrosis: a rare presentation of advanced ovarian cancer.

We report an interesting case of a rare presentation of ovarian cancer. A 64-year-old woman attended the Accident and Emergency department with a complaint of sudden onset of ‘‘painful, cold and blue fingers’’ (see Fig. 1). On further questioning, she revealed symptoms of myalgia and malaise. Several nail fold infarcts were also noticed. She was found to have a tense distended abdomen; however, no obvious masses were felt. She was referred to a Rheumatologist who carried out a battery of tests for autoimmune vasculitis, which were negative. A pelvic ultrasound revealed moderate ascites and a right sided complex adnexal cyst measuring 4.7 9 5.2 cm. Tumour marker serum CA-125 was raised at over 800 U/ mL and ascitic fluid sent for cytology showed cells suspicious of adenocarcinoma of the ovary. Subsequently, CT scan was carried out which revealed the adnexal mass with ascites and extensive omental as well as peritoneal seedlings. During the course of her admission, her vasculitis became more prominent. She was commenced on a short course of oral prednisolone therapy which resulted in symptomatic relief but did not resolve the vasculitis. The clinical presentation with sudden onset of ‘‘painful, cold and blue fingers’’, negative immunological tests and advanced ovarian malignancy led us to the diagnosis of digital vasculitis affecting the fingers secondary to a paraneoplastic phenomenon. She received six cycles of chemotherapy with carboplatin which resulted in good biochemical and radiological response, with a drop in CA125 to 55 U/mL. The symptoms of digital vasculitis also showed improvement and appeared to resolve completely by the time of third cycle of chemotherapy, further raising the suspicion that the paraneoplastic syndrome is caused by an ovarian tumour. The patient underwent debulking surgery and the vasculitis remained stable during the subsequent course of her treatment without relapse. The first report on the association of digital ischaemia and carcinoma was by O’Connor in 1884. He observed a correlation between breast cancer and gangrenous fingertips [1]. The prevalence of paraneoplastic syndromes associated with ovarian cancer is estimated in the order of only one in 1,000 [2]. With regard to the pathogenesis, induction of vasculitis by antibodies to tumour antigens is proposed as a likely method of paraneoplastic phenomenon [3]. The other pathogenesis could be digital vasospasm caused by sympathetic hyperactivity and digital artery obstruction due to increased blood coagulation associated with malignancy, hyperviscosity and arteritis [4]. Some paraneoplastic syndromes are also idiopathic. While investigating a patient with paraneoplastic vasculitis, apart from the haematological tests, immunological and serological investigations are of the utmost importance. Although the imaging studies required will depend on the individual presentation, the following tests may be of value: chest and sinus radiographs, echocardiograph, upper limb arteriography, ultrasound of abdomen and pelvis, erect abdominal X-ray, abdominal and pelvis CT. Biopsy of the digit or biopsy of the underlying malignancy should be considered [1, 5]. The aim of the treatment is to alleviate symptoms of ischaemia, prevent progression and to treat underlying cause. Although the symptoms of digital ischaemia may improve with medical therapies, definite benefits have been S. Robati K. Razvi K. Madhavan K. Gajjar (&) Department of Obstetrics and Gynaecology, Southend University Hospital NHS Foundation Trust, Westcliff on Sea, Essex, UK e-mail: gajjarkb@yahoo.co.uk

Diagnostic accuracy of haptoglobin within ovarian cyst fluid as a potential point-of-care test for epithelial ovarian cancer: an observational study

To investigate haptoglobin within ovarian cyst fluid (OCF) as a diagnostic biomarker for epithelial ovarian cancer (EOC) and develop an in vitro diagnostic point‐of‐care device test (IVDPCT) for use in the operating theatre.

Abstract POSTER-CTRL-1211: Haptoglobin identified within ovarian cyst fluid as an accurate intraoperative diagnostic biomarker for epithelial ovarian cancer

Introduction: Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy, with a poor prognosis and low survival rate; most cases are diagnosed at a late stage due to the fact that symptoms at early stages are usually non-specific in nature. There is currently no screening method proven to be effective in improving the outcome of EOC patients; existing biomarkers for EOC, such as CA-125, generally suffer from a lack of specificity in early stage disease, which is the ideal time for therapeutic intervention. Aim: We hypothesized that a single protein biomarker within the ovarian cyst fluid (OCF) could be identified, isolated, characterized and validated for application in a point-of-care device (POC), which could subsequently be used in operating theaters for triage for frozen section (FS). Methods: We screened the OCF proteome by mass-spectrometry (MALTI-TOF/MS), confirmed the identity of the protein by western blot and SELDI immunocapture analysis. Next, demonstrated using tissue microarray (TMA) that cellular expression of haptoglobin varied in normal, benign and malignant ovarian tissue. We developed a simple ELISA and a rapid colorimetric assay that allowed semi-quantification of OCF haptoglobin intraoperatively. Finally, we validated a point-of-care test kit to accurately identify EOC using OCF with a higher predictive value than can be achieved using RMIs, and an equivalent accuracy to intraoperative FS. Results: The OCF haptoglobin concentration in benign tumors was 0.70±0.09 mg/ml compared to 6.22±0.53 mg/ml and 6.57±0.65 mg/ml in early- and late-stage EOCs, respectively (P Conclusion: This is the first study whereby an intraoperative tumor marker has been utilised in the differentiation between benign and malignant ovarian lesions. Its accuracy suggests that it could be utilised as a replacement or an adjunct to frozen section, particularly in situations where histopathological expertise is scarce. Citation Format: Mahesh Choolani, Loganath Annamalai, Lin Liu, Khalil Razvi, Changqing Zhao, Gregory Rice, Aniza P Mahyuddin, Arijit Biswas, Jerry Chan, Narasimhan Kothandaraman. Haptoglobin identified within ovarian cyst fluid as an accurate intraoperative diagnostic biomarker for epithelial ovarian cancer [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-CTRL-1211.