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1.
Arch Gynecol Obstet ; 308(3): 981-988, 2023 09.
Article in English | MEDLINE | ID: mdl-37193821

ABSTRACT

PURPOSE: The aim of this study was to analyze the prognostic factors related to the recurrence rate and overall survival of patients with undifferentiated uterine sarcoma. METHODS: An international multicenter study involving 43 international centers, the SARCUT study, collected 966 uterine sarcoma cases; among them 39 cases corresponded to undifferentiated uterine sarcoma and where included in the present subanalysis. The risk factors related to the oncological outcomes where analyzed. RESULTS: The median age of the patients was 63 (range 14-85) years. Seventeen (43.5%) patients presented FIGO stage I. The 5-year overall survival (OS) was 15.3% and 12-months disease-free survival (DFS) 41%. FIGO stage I was significantly associated with a better prognosis. In addition, patients who received adjuvant radiotherapy showed significant longer disease-free survival compared to those without adjuvant radiotherapy (20.5 vs. 4.0 months, respectively; p = 0.04) and longer overall survival (34.7 vs. 18.2 months, respectively; p = 0.05). Chemotherapy administration was associated with shorter DFS (HR 4.41, 95% CI 1.35-14.43, p = 0.014). Persistent disease after primary treatment (HR = 6.86, 95% CI 1.51-31.09, p = 0.012) and FIGO stage IV (HR 4.12, 95%CI 1.37-12.44, p = 0.011) showed significant worse prognosis for OS. CONCLUSION: FIGO stage seems to be the most important prognostic factor in patients with undifferentiated uterine sarcoma. Adjuvant radiotherapy seems to be significantly associated also to a better disease-free and overall survival. On the contrary, the role of chemotherapy administration remains unclear since was associated to a shorted DFS.


Subject(s)
Endometrial Neoplasms , Sarcoma, Endometrial Stromal , Sarcoma , Uterine Neoplasms , Female , Humans , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Prognosis , Sarcoma/therapy , Sarcoma/pathology , Uterine Neoplasms/therapy , Uterine Neoplasms/pathology , Disease-Free Survival , Sarcoma, Endometrial Stromal/pathology , Radiotherapy, Adjuvant , Endometrial Neoplasms/pathology , Retrospective Studies , Neoplasm Staging , Chemotherapy, Adjuvant
2.
Cancers (Basel) ; 14(22)2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36428724

ABSTRACT

There is an unmet biomedical need for ex vivo tumour models that would predict drug responses and in turn help determine treatment regimens and potentially predict resistance before clinical studies. Research has shown that three dimensional models of ovarian cancer (OvCa) are more realistic than two dimensional in vitro systems as they are able to capture patient in vivo conditions in more accurate manner. The vast majority of studies aiming to recapitulate the ovarian tumour morphology, behaviors, and study chemotherapy responses have been using ovarian cancer cell lines. However, despite the advantages of utilising cancer cell lines to set up a platform, they are not as informative as systems applying patient derived cells, as cell lines are not able to recapitulate differences between each individual patient characteristics. In this review we discussed the most recent advances in the creation of 3D ovarian cancer models that have used patient derived material, the challenges to overcome and future applications.

3.
Eur J Obstet Gynecol Reprod Biol ; 274: 56-61, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35584578

ABSTRACT

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 minimally invasive pelvic exenterationcan feasibly be performed in place of open pelvic exenteration. Furthermore, our findings suggest this may be a safe alternative as we report similar findings to the existing literature, however no firm conclusions can be drawn at such an early stage. Long term follow-up data and a larger cohort study will be needed to establish non-inferiority to open PE.


Subject(s)
Genital Neoplasms, Female , Pelvic Exenteration , Cohort Studies , Female , Genital Neoplasms, Female/surgery , Humans , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Pelvic Exenteration/methods , Retrospective Studies
4.
Int J Gynecol Cancer ; 32(7): 924-930, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35534018

ABSTRACT

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.


Subject(s)
Frailty , Genital Neoplasms, Female , Triallate , Female , Frailty/epidemiology , Frailty/therapy , Genital Neoplasms, Female/therapy , Humans , Ireland/epidemiology , Surveys and Questionnaires , United Kingdom/epidemiology
5.
Cancers (Basel) ; 14(5)2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35267582

ABSTRACT

Epithelial Ovarian Cancer (EOC) is a silent, deadly and aggressive gynaecological disease with a relatively low survival rate. This has been attributed, to some extent, to EOC's high recurrence rate and resistance to currently available platinum-based chemotherapeutic treatment methods. Multiple groups have studied and reported the effect of chemotherapeutic agents on various EOC 3D in vitro models. However, there are very few studies wherein a direct comparative study has been carried out between the different in vitro 3D models of EOC and the effect of chemotherapy within them. Herein, we report, for the first time, a direct comprehensive systematic comparative study of three different 3D in vitro platforms, namely (i) spheroids, (ii) synthetic PeptiGels/hydrogels of various chemical configurations and (iii) polymeric scaffolds with coatings of various extracellular matrices (ECMs) on the cell growth and response to the chemotherapeutic (Cisplatin) for ovary-derived (A2780) and metastatic (SK-OV-3) EOC cell lines. We report that all three 3D models are able to support the growth of EOC, but for different time periods (varying from 7 days to 4 weeks). We have also reported that chemoresistance to Cisplatin, in vitro, observed especially for metastatic EOC cells, is platform-dependent, in terms of both the structural and biochemical composition of the model/platform. Our study highlights the importance of selecting an appropriate 3D platform for in vitro tumour model development. We have demonstrated that the selection of the best platform for producing in vitro tumour models depends on the cancer/cell type, the experimental time period and the application for which the model is intended.

6.
Int Cancer Conf J ; 10(1): 24-30, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33489697

ABSTRACT

Lung cancer is the 3rd most common cancer in the UK and the numbers of new cases increase every year. In contrast to gastrointestinal tumours and breast cancer, lung cancer, metastases to the female genital tract are incredibly rare with only five cases reported with uterine metastases on review of the published English literature. We report an interesting case of successful ongoing management of metastatic lung cancer to the pelvis along with an extensive literature review. A 47-year-old lady with recurrent respiratory tract symptoms and chest pain was diagnosed with advanced stage non-small-cell lung cancer (Stage T4N2M1A). Five years following diagnosis and several cycles of chemotherapy and radiotherapy, aged 52, she complained of post-menopausal bleeding and pelvic discomfort. An endometrial biopsy confirmed a malignancy morphologically and immunohistochemically similar to her lung adenocarcinoma, in keeping with metastatic disease. She underwent robotic surgery to excise the pelvic organs and successfully gain local disease control. The patient remains clinically stable 3 years following hysterectomy. Although metastases of lung cancer to uterus are very rare, any patient with abnormal uterine bleeding with known cancer should be investigated thoroughly to rule out metastatic disease. Combined multimodal treatment as in this case may increase overall survival.

7.
J Obstet Gynaecol Can ; 43(3): 361-364, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33288481

ABSTRACT

BACKGROUND: Ovarian sex cord tumours with annular tubules (SCTAT) are a very rare type of neoplasm and account for 14% of all sex cord tumours. This tumour was first described in 1970 with histopathology characterized by the presence of both complex and simple annular tubules. The tumour may show features of either granulosa cell tumours or Sertoli cell tumours and differentiation into either type can occur. CASE: We report an interesting case of SCTAT in a 60-year-old woman who had a primary diagnosis of granulosa cell tumour. Seven years later she experienced a recurrence. Following excision and review of all pathology, the patient was found to have a SCTAT in both the recurrence and the primary tumour. CONCLUSION: SCTAT is a slow-growing tumour that occasionally exhibits malignant behaviour with metastatic potential, albeit many years following initial diagnosis. SCTAT should be included in the differential diagnosis of sex cord tumours.


Subject(s)
Abdominal Pain/etiology , Ovarian Neoplasms/diagnosis , Sex Cord-Gonadal Stromal Tumors/diagnosis , Fatal Outcome , Female , Humans , Middle Aged , Neoplasm Recurrence, Local , Ovarian Neoplasms/surgery , Sex Cord-Gonadal Stromal Tumors/surgery
8.
Perioper Med (Lond) ; 9: 26, 2020.
Article in English | MEDLINE | ID: mdl-32939254

ABSTRACT

BACKGROUND: Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined. METHODS: We present a case series of consecutive patients who received major gynae-oncology surgery delivered within an Enhanced Recovery After Surgery (ERAS) pathway at a single institution. Patients were electively admitted from theatre directly to the intensive care unit (ICU). Data was collected prospectively into electronic databases (Philips ICCA, Wardwatcher) and then retrospectively collated and appropriate statistical analyses were performed. In the absence of a consensus definition of vasoplegia, we, necessarily arbitrarily, chose a noradrenaline dose of > 0.1 mcg/kg/min at 08:00 on the first post-operative day. The rationale is that this would be more than would typically be expected to counteract the vasodilatory effects of epidural analgesia, which is commonly used at our institution. RESULTS: Data was collected from 324 patients, all treated between February 2014 and July 2016. The average age was 67 years and 39% received neoadjuvant chemotherapy. The commonest tumour type was ovarian (58%). The median estimated blood loss was 800 ml and epidural analgesia was used in 71%. Fifty per cent received post-operative vasopressor infusions: factors associated with this included epidural use and estimated blood loss. Nineteen per cent met our criteria for vasoplegia: factors associated with this included CRP on post-operative day 1 and P-POSSUM morbidity score. Hospital and ICU length of stay was prolonged in those who had vasoplegia. CONCLUSIONS: Patients commonly receive vasopressors following major gynae-oncologic surgery, and this can be at relatively high doses. Clinical factors only accounted for a minority of the variability in vasopressor usage-suggesting considerable biological variability. Optimal care of patients having major abdomino-pelvic surgery may include advanced haemodynamic monitoring and ready availability of infused vasopressors, in a suitable environment.

9.
Int J Womens Health ; 11: 223-228, 2019.
Article in English | MEDLINE | ID: mdl-31015769

ABSTRACT

The presentation of a new vaginal lesion could represent a variety of diagnoses from benign warts to more sinister primary malignancies. Rarely, a new lesion could represent a metastatic deposit from a malignancy elsewhere in the body. Colonic carcinomas are the third most common malignancy, frequently metastasising to the liver and lung. There have been a small number of cases in the literature reporting vaginal metastases from colonic carcinoma and this is usually indicative of advanced disseminated disease. We present an interesting case of a 65-year-old female with a strong family history of bowel cancer who originally presented with a vaginal skin tag that was biopsied and found to be a moderately differentiated adenocarcinoma. The immunohistochemistry profile was cytokeratin (CK) 20 positive/CK 7 negative, highly suggestive of a bowel cancer primary. However, subsequent extensive radiological and endoscopic investigations failed to identify a colonic primary tumor. The vaginal lesion was successfully excised, and no systemic treatments were warranted. To date, no primary cancer has been identified; the patient remains asymptomatic with no clinical signs of disease recurrence 5 years following her initial diagnosis. This case represents a diagnostic dilemma between two very rare diagnoses of either a vaginal metastasis from an occult colonic primary tumor or a primary vaginal adenocarcinoma of endometrioid morphology demonstrating intestinal immunophenotype. Organizing colonic screening is recommended in view of the high risk of colonic adenocarcinoma.

10.
BMJ Open ; 9(1): e024853, 2019 01 24.
Article in English | MEDLINE | ID: mdl-30679297

ABSTRACT

OBJECTIVES: Surgical site infection (SSI) complicates 5% of all surgical procedures in the UK and is a major cause of postoperative morbidity and a substantial drain on healthcare resources. Little is known about the incidence of SSI and its consequences in women undergoing surgery for gynaecological cancer. Our aim was to perform the first national audit of SSI following gynaecological cancer surgery through the establishment of a UK-wide trainee-led research network. DESIGN AND SETTING: In a prospective audit, we collected data from all women undergoing laparotomy for suspected gynaecological cancer at 12 specialist oncology centres in the UK during an 8-week period in 2015. Clinicopathological data were collected, and wound complications and their sequelae were recorded during the 30 days following surgery. RESULTS: In total, 339 women underwent laparotomy for suspected gynaecological cancer during the study period. A clinical diagnosis of SSI was made in 54 (16%) women. 33% (18/54) of women with SSI had prolonged hospital stays, and 11/37 (29%) had their adjuvant treatment delayed or cancelled. Multivariate analysis found body mass index (BMI) was the strongest risk factor for SSI (OR 1.08[95% CI 1.03 to 1.14] per 1 kg/m2 increase in BMI [p=0.001]). Wound drains (OR 2.92[95% CI 1.41 to 6.04], p=0.004) and staple closure (OR 3.13[95% CI 1.50 to 6.56], p=0.002) were also associated with increased risk of SSI. CONCLUSIONS: SSI is common in women undergoing surgery for gynaecological cancer leading to delays in discharge and adjuvant treatment. Resultant delays in adjuvant treatment may impact cancer-specific survival rates. Modifiable factors, such as choice of wound closure material, offer opportunities for reducing SSI and reducing morbidity in these women. There is a clear need for new trials in SSI prevention in this patient group; our trainee-led initiative provides a platform for their successful completion.


Subject(s)
Clinical Audit , Genital Neoplasms, Female/surgery , Laparotomy/adverse effects , Postoperative Complications/epidemiology , Surgical Wound Infection/epidemiology , Aged , Body Mass Index , Female , Genital Neoplasms, Female/pathology , Humans , Incidence , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Prospective Studies , Risk Factors , Suction , Sutures/adverse effects , United Kingdom/epidemiology
11.
BMC Cancer ; 18(1): 943, 2018 Oct 03.
Article in English | MEDLINE | ID: mdl-30285763

ABSTRACT

BACKGROUND: Epithelial ovarian cancer is a common malignancy, with no clinically approved diagnostic biomarker. Engrailed-2 (EN2) is a homeodomain-containing transcription factor, essential during embryological neural development, which is dysregulated in several cancer types. We evaluated the expression of EN2 in Epithelial ovarian cancer, and reviewed its role as a biomarker. METHODS: We evaluated 8 Epithelial ovarian cancer cell lines, along with > 100 surgical specimens from the Royal Surrey County Hospital (2009-2014). In total, 108 tumours and 5 normal tissue specimens were collected. En2 mRNA was evaluated by semi-quantitative RT-PCR. Histological sub-type, and platinum-sensitive/-resistant status were compared. Protein expression was assessed in cell lines (immunofluorescence), and in > 150 tumours (immunohistochemistry). RESULTS: En2 mRNA expression was elevated in serous ovarian tumours compared with normal ovary (p < 0.001), particularly in high-grade serous ovarian cancer (p < 0.0001) and in platinum-resistant tumours (p = 0.0232). Median Overall Survival and Progression-free Survival were reduced with high En2 expression (OS = 28 vs 42 months, p = 0.0329; PFS = 8 vs 27 months; p = 0.0004). Positive cytoplasmic EN2 staining was demonstrated in 78% of Epithelial ovarian cancers, with absence in normal ovary. EN2 positive high-grade serous ovarian cancer patients had a shorter PFS (10 vs 17.5 months; p = 0.0103). CONCLUSION: The EN2 transcription factor is a novel ovarian cancer biomarker. It demonstrates prognostic value, correlating with worse Overall Survival and Progression-free Survival. It is hoped that further work will validate its use as a biomarker, and provide insight into the role of EN2 in the development, progression and spread of ovarian cancer.


Subject(s)
Biomarkers, Tumor , Carcinoma, Ovarian Epithelial/metabolism , Homeodomain Proteins/metabolism , Nerve Tissue Proteins/metabolism , Ovarian Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial/diagnosis , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/therapy , Cell Line, Tumor , Female , Fluorescent Antibody Technique , Gene Expression , Homeodomain Proteins/genetics , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neoplasm Staging , Nerve Tissue Proteins/genetics , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/genetics , Ovarian Neoplasms/therapy , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism
12.
J Obstet Gynaecol Can ; 40(12): 1632-1634, 2018 12.
Article in English | MEDLINE | ID: mdl-30262385

ABSTRACT

BACKGROUND: Epithelial ovarian cancer (EOC) is the deadliest of gynaecological cancers, often manifesting itself at a later stage (stage 3 and 4). Metastases and recurrences tend to be limited to the abdominopelvic cavity, and cutaneous metastases are rare. CASE SUMMARY: We report an interesting case of a 51-year-old who presented 2 years after her initial treatment with surgery and adjuvant chemotherapy for a stage IIB with an isolated recurrence in the external urethral meatus. CONCLUSION: This case highlights the need for clinicians and patients to remain vigilant during follow-up visits to rule out recurrences despite nonspecific symptoms reported by patients.


Subject(s)
Carcinoma, Ovarian Epithelial/diagnosis , Neoplasm Recurrence, Local/diagnosis , Ovarian Neoplasms/diagnosis , Urethral Neoplasms/diagnosis , Carcinoma, Ovarian Epithelial/diagnostic imaging , Carcinoma, Ovarian Epithelial/secondary , Carcinoma, Ovarian Epithelial/therapy , Chemotherapy, Adjuvant , Diagnosis, Differential , Female , Humans , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/secondary , Neoplasm Recurrence, Local/therapy , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Urethral Neoplasms/diagnostic imaging , Urethral Neoplasms/secondary , Urethral Neoplasms/therapy
13.
BMC Womens Health ; 17(1): 119, 2017 Nov 28.
Article in English | MEDLINE | ID: mdl-29179757

ABSTRACT

BACKGROUND: Leiomyosarcoma (LMS) is a malignant tumour formed of cells with distinct smooth muscle features. Leiomyosarcomas rarely metastasise to the oral cavity and this literature review details all reported cases of metastasis to the mandible found in the literature. This offers a unique perspective by specifying mandible as the site of metastasis of leiomyosarcoma. CASE PRESENTATION: A 53-year-old female presented to her General Practitioner (GP) with heavy menstrual bleeding and was diagnosed with multiple fibroids. Folowing a hysterectomy and removal of both tubes and ovaries for these symptomatic uterine fibroids, an incidental diagnosis of low grade leiomyosarcoma was made. A CT scan found no evidence of residual or metastatic disease and no further treatment was deemed necessary. 6 months later she presented to A & E with a numb lower lip but it took another 6 months for the diagnosis of metastatic LMS to the mandible to be made. DISCUSSION: Leiomyosarcomas are aggressive tumours which are liable to metastasise and therefore have a poor prognosis. An extensive literature review was undertaken to explore the frequency of metastasis in the maxillo-facial region. CONCLUSIONS: Although metastasis to the oral region is very rare as suggested from the literature review, when patients present with unusual symptoms after a diagnosis of LMS, physicians should be aware of the possibility of LMS metastases.


Subject(s)
Leiomyosarcoma/complications , Leiomyosarcoma/physiopathology , Neoplasm Metastasis/physiopathology , Trismus/etiology , Trismus/therapy , Uterine Neoplasms/complications , Uterine Neoplasms/physiopathology , Female , Humans , Hysterectomy , Leiomyosarcoma/therapy , Middle Aged , Treatment Outcome , United Kingdom , Uterine Neoplasms/therapy
15.
Cancer Genomics Proteomics ; 14(1): 35-51, 2017 01 02.
Article in English | MEDLINE | ID: mdl-28031236

ABSTRACT

BACKGROUND: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. MATERIALS AND METHODS: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. RESULTS: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. CONCLUSION: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer.


Subject(s)
Drug Resistance, Neoplasm , Ovarian Neoplasms/metabolism , Proteome , Proteomics , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Cell Line, Tumor , Cell Survival/drug effects , Combined Modality Therapy , Computational Biology/methods , Female , Humans , Neoplasm Staging , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Protein Interaction Mapping , Proteomics/methods , Signal Transduction , Ubiquitination
16.
Int J Cancer ; 139(7): 1608-17, 2016 10 01.
Article in English | MEDLINE | ID: mdl-27225067

ABSTRACT

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.


Subject(s)
Adenocarcinoma/genetics , Genes, Homeobox , Ovarian Neoplasms/genetics , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Animals , Apoptosis/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Organoplatinum Compounds/pharmacology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Prognosis
17.
Arch Gynecol Obstet ; 291(5): 961-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25451061

ABSTRACT

INTRODUCTION: Increased progesterone levels during pregnancy may cause decidualisation of endometriomas mimicking malignancies on radiology and causing management dilemmas. CASE: An ovarian cyst was detected in a 33-year-old woman at her routine 12-week gestation ultrasound scan. By 18 weeks, the unilocular mass was increasing in size with features suggestive of early ovarian malignancy. The cyst was monitored throughout pregnancy and caesarean section at 38 weeks delivered a healthy male. Histology confirmed a decidualised endometrioma and benign dermoid cyst with no evidence of malignancy. LITERATURE REVIEW: The evidence for decidualised ovarian endometriomas in pregnancy was explored; 14 papers were identified, which reported 26 cases, excluding our index case. Of the 27 cases, 19 (70%) were managed surgically, 4 of which were delayed till caesarean section with concomitant cyst excision; 8 cases were managed conservatively through serial monitoring of the cyst, which spontaneously regressed following delivery. CONCLUSION: Surgical management of the cyst provides histological diagnosis but may introduce risks to mother and fetus; a conservative approach may cause anxiety but limits interventions. Elective caesarean section following monitoring throughout pregnancy may bridge the gap between surgical and purely conservative approaches if appropriate. Limited available evidence makes a definitive decision regarding management difficult. Decidualisation should be considered as a differential for suspicious ovarian lesions in pregnancy.


Subject(s)
Endometriosis/diagnostic imaging , Ovarian Cysts/diagnostic imaging , Ovarian Neoplasms/diagnosis , Pregnancy Complications/diagnostic imaging , Cesarean Section , Embryo Implantation , Endometriosis/surgery , Female , Gestational Age , Humans , Ovarian Cysts/complications , Ovarian Cysts/surgery , Ovarian Neoplasms/diagnostic imaging , Pelvic Pain/diagnosis , Pelvic Pain/diagnostic imaging , Pregnancy , Pregnancy Outcome , Ultrasonography, Doppler
18.
Gynecol Oncol ; 135(3): 622-3, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25450152

ABSTRACT

OBJECTIVE: We present a novel surgical approach to ovarian cancer debulking using neutral argon plasma (PlasmaJet™). CASE HISTORY: A 48 year-old woman diagnosed with FIGO stage IVB grade 3 serous epithelial ovarian carcinoma received three cycles of neoadjuvant chemotherapy with carboplatin and paclitaxel. OPERATIVE TECHNIQUE: Dissection and radical debulking surgery were performed using PlasmaJet™ as previously described [1,2]. This included diaphragmatic and abdominal peritoneal stripping, supra-colic omentectomy, tumour ablation on the small and large intestines and mesentery, pelvic and para-aortic lymphadenectomy. RESULTS: The only post-operative complication was a superficial wound breakdown, which healed by secondary intention. She remains well two years after surgery, with no sign of recurrence. CONCLUSION: In this case, PlasmaJet™ facilitated diaphragmatic peritoneal stripping as well as dissection of tissue close to bowel and major vessels. Further study is required to assess whether this device can reduce the need for bowel resection while achieving complete cytoreduction.


Subject(s)
Argon/therapeutic use , Neoplasms, Glandular and Epithelial/drug therapy , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Carcinoma, Ovarian Epithelial , Female , Humans , Lymph Node Excision , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging
19.
Arch Gynecol Obstet ; 290(5): 1041-4, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25096953

ABSTRACT

INTRODUCTION: We present an unusual complication following robotic assisted radical hysterectomy. CASE REPORT: A 51-year-old female with stage 1B1 cervical cancer underwent a robotic assisted radical hysterectomy. The procedure was prolonged with difficulties dissecting the left parametrium and vaginal fornix with persistent bleeding from the left vaginal vault. Post-operatively the patient was electively sedated and ventilated. Extubation was difficult due to patient agitation but achieved on day 2. Agitation persisted and a head CT scan was performed and a diagnosis of cerebral oedema was made. DISCUSSION: Factors contributing to this case include prolonged operating time, prolonged Trendelenburg position with high pressures of CO2 pneumoperitoneum and excessive blood loss. These factors may contribute to poor cerebral venous outflow, increasing intracranial pressure leading to increased risk of cerebral oedema. CONCLUSION: The mechanics of robotic assistance may be used to reduce these risks by significantly reducing intra-abdominal pressure improving venous return. The use of robotics in surgery has been increasing over the last 10 years, and the benefits have been well documented. We present an unusual complication following robotic assisted radical hysterectomy performed for cervical cancer.


Subject(s)
Adenocarcinoma/surgery , Brain Edema/diagnosis , Hysterectomy/methods , Robotics/methods , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/pathology , Brain Edema/etiology , Female , Head-Down Tilt/adverse effects , Humans , Middle Aged , Neoplasm Staging , Pneumoperitoneum, Artificial/adverse effects , Severity of Illness Index , Treatment Outcome , Ultrasonography, Doppler, Transcranial/methods , Uterine Cervical Neoplasms/pathology
20.
J Ovarian Res ; 5(1): 46, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23259619

ABSTRACT

BACKGROUND: Epithelial Ovarian Cancer (EOC) is the second most common gynaecological cancer and accounts for more deaths than all gynaecological cancers combined. Despite extensive research, progress has been slow in understanding the pathobiology. EOC is identified as a heterogeneous malignancy with various histological subtypes. It is now well known that these different histological subtypes show differences in terms of presentation, response to treatment, immunohistochemical (IHC) reactivity and molecular profiling. Cell cycle deregulation is key in cancer development and there is some evidence in the literature that this is relevant to the problem of EOC and the development of drug resistant disease. The need to identify prognostic markers has led to several gene profiling studies using tumour tissue with equivocal results. p57kip2 is one such cell cycle regulator and its functions are being explored as recent research has shown that it is more than just a negative regulator of the cell cycle. AIMS: The aim of this review is to evaluate the literature around the IHC expression of p57kip2 in EOC. METHODS: Systematic review of the literature focussing on clinical outcome and immunohistochemical expression in epithelial ovarian cancer. RESULTS: Four papers are discussed in this review and have shown great variation in IHC expression of p57kip2 in EOC. These studies incorporated different histological subtypes of EOC. However they all suggest that p57kip2 has a significant role in prognosis and its therapeutic indication needs to be studied. Multicentre collaborative studies on individual histological subtypes might provide more data and help to increase the number of cases especially for rarer tumours.

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