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Biomedical subjects

Michael Quinn

Publications and source records attributed to Michael Quinn.

At least 19 recordsLinked to original sources

A new prognostic model for FIGO stage 1 epithelial ovarian cancer.

BACKGROUND: No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories. METHODS: Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated. RESULTS: Two hundred and one patients (33.5%) had preoperative CA-125 < or =30 U/ml and CA-125 levels < or =30 U/ml were associated with lower grade, sub-stage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125 < or =30 U/ml and >30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-125 >30 U/ml (OR 2.7) and age at diagnosis >70 years (OR 2.6) as the only independent predictors for overall survival. CONCLUSION: Pretreatment of CA-125 < or =30 U/ml dominates over histologic cell type, sub-stage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy.

Adult↗

Chapter 8: Screening for cervical cancer in developing countries.

Organised and quality assured cytology-based screening programmes have substantially reduced cervical cancer incidence in many developed countries. However, there are considerable barriers to setting up cytology-based screening programs, particularly in developing countries. This has stimulated the search for novel and alternative approaches to cytology for cervical cancer prevention. These approaches generally perform as well as cytology, and sometimes better, although many of them have a lower specificity, resulting in higher false-positive rates. The possibility of linking screening to treatment in a one- or two-visit strategy appears to be safe, feasible and effective. Barriers to establishing screening programs and the pitfalls encountered differ from one country to the next. Country-specific solutions need to be found, while being cognizant of the criteria that have enabled successful screening programmes.

Developing Countries↗

The impact of PET/CT in the management of recurrent ovarian cancer.

OBJECTIVES: To evaluate the impact of PET/CT on the restaging and management of recurrent ovarian cancer. METHODS: From January 2002 to July 2003, all women undergoing either surveillance or investigation of possible recurrent ovarian cancer at the Centre for Molecular Imaging, The Peter MacCallum Cancer Centre, were invited to take part in a prospective evaluation of the clinical impact of PET/CT. RESULTS: Fifty-six women having 66 scans were available for analysis. All patients had at least 12months follow-up after the PET/CT unless they died before that time. Apart from one equivocal scan, all scans performed in women with a CA125 higher than 35IU/ml had a positive PET/CT. PET/CT altered the known disease distribution in 40 scans (64%). Overall, PET/CT showed less disease in six scans (9%) and more disease in 34 scans (52%). Regardless of the value of CA125, PET/CT identified a sub group of women with apparently localized disease or no definite evidence of disease. This group showed improved survival compared with women shown to have systemic disease. PET/CT resulted in a major change of management plan in 34 patients (58%). CONCLUSION: PET/CT modifies the assessment of the distribution of recurrent ovarian cancer and alters patient management in a substantial proportion of patients. PET/CT appears to offer prognostic information.

CA-125 Antigen↗

Complementary medicine use by Australian women with gynaecological cancer.

AIMS AND OBJECTIVES: Social and cultural factors are identified that impact on complementary therapy use among Australia-born and immigrant women diagnosed with gynaecological cancer. METHODS: A qualitative study design including in-depth interviews with women diagnosed with gynaecological cancer (N=53) and participant observation was conducted. RESULTS: Approximately one-third of women utilized complementary and alternative medicine, with this being determined by current health concerns and health beliefs related to the efficacy of different modalities. Four types of complementary therapy users emerged: consequential, therapeutic, informed and exploratory. CONCLUSION: There was a relatively low uptake of complementary treatments. Choice was influenced by women's socio-demographic background, clinical and personal history, lack of personal experiences of gynaecological cancer among study participants' kin and friends, and lack of popular alternative literature on such cancer.

Adult↗

Treatment decisions: a qualitative study with women with gynaecological cancer.

This qualitative study investigated women's participation in decisions regarding treatment of gynaecological cancer. Thirty women, receiving health care in two tertiary hospitals in Australia, were interviewed face-to-face. For women with gynaecological cancer, the most influential factors in treatment decisions are still the surgeon's recommendation and fear of dying from cancer.

Australia↗

Guidelines following hydatidiform mole: a reappraisal.

OBJECTIVE: The aim of this study was to determine how often patients with complete hydatidiform mole (CHM) who spontaneously achieve normal human chorionic gonadotrophin (hCG) levels subsequently develop persistent or recurrent gestational trophoblast disease. METHODS: Four hundred and fourteen cases of CHM registered at the Hydatidiform Mole Registry of Victoria were reviewed retrospectively after molar evacuation. Maternal age, gestational age, gravidity and parity were determined for each patient, as well as the need for chemotherapy. RESULTS: Among the 414 patients, 55 (13.3%) required chemotherapy for persistent trophoblastic disease. None of the patients whose hCG levels spontaneously fell to normal subsequently developed persistent molar disease. CONCLUSION: Weekly hCG measurements are recommended for all patients until normal levels are achieved. For patients who attain normal hCG levels within 2 months after evacuation, it seems safe to discontinue monitoring once normal levels are achieved. Patients who fail to achieve normal hCG levels by 2 months after evacuation should be monitored with monthly hCG measurements for 1 year after normalisation to assure sustained remission.

Adult↗

Persistent trophoblast disease following partial molar pregnancy.

OBJECTIVE: Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following partial molar pregnancy and to review the present follow-up protocol of patients suffering from partial hydatidiform molar pregnancy (PHM). METHODS: Demographic factors were determined for all 344 cases with a review diagnosis of PHM, included age, history of previous hydatidiform mole, gestation length, hCG levels and compliance with follow-up. FINDINGS: Six of the 344 patients diagnosed with PHM required treatment with single-agent methotrexate and folinic acid rescue. All six patients achieved and maintained a complete biochemical remission after chemotherapy. hCG regression assays were analysed for 235 patients: 225 patients had at least one normal hCG measurement during follow-up, of whom 152 (64.7%) patients obtained normal values within 2 months after evacuation. All patients obtained normal levels within 32 weeks after evacuation of the partial hydatidiform mole. Only 63 (25.6%) patients completed the recommended follow-up program. No patient who achieved normal hCG levels required chemotherapy because of a recurrent gestational trophoblastic tumour. RECOMMENDATIONS: This study indicates that 1.7% of all partial mole pregnancy patients needed treatment for malignant sequelae. In contrast, no patient diagnosed with partial mole had a biochemical or clinical relapse after achieving normal levels of hCG, consistent with previous studies. Patients who have had a partial hydatidiform mole should be followed by hCG assays until normal levels are achieved and then follow-up can be safely discontinued.

Adult↗

Is colposcopy needed following laser ablation for dysplasia?

AIMS: To evaluate the effectiveness of cytology and colposcopy in the follow up of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia (CIN). METHODS: A retrospective analysis of 1784 patients with CIN treated with laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne. Data were collected prospectively in a computerised colposcopy database utilised in the Dysplasia Unit. RESULTS: There was equal distribution in the study population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade intraepithelial neoplasia (HSIL), with no significant age difference in both groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the first year of treatment. Colposcopy was more sensitive in detecting intraepithelial neoplasia (SIL) than cytology, whereas cytology was more specific. No case of cancer was diagnosed on follow up. CONCLUSIONS: CO(2) laser ablation was equally effective in treating different grades of CIN. There is a continuing incidence of recurrent CIN, even up to five years after initial treatment, which suggests that it is necessary for patients to adhere to long-term follow up. The combination of cytology and colposcopic assessment is essential for surveillance of SIL in the initial two years after treatment.

Adult↗

Excessive bleeding and transfusion in a prior cardiac surgery is associated with excessive bleeding and transfusion in the next surgery.

If there is a genetic predisposition to excessive bleeding, there should be an association in excessive blood loss between multiple cardiac surgeries. We retrospectively determined in 174 patients the association of excessive bleeding between 2 cardiac surgeries with cardiopulmonary bypass between January 19, 1990 and June 25, 2002. Excessive bleeding was defined by 2 criteria: (a) postoperating room chest tube blood loss over 24 h more than or equal to 750 mL (chest tube drainage [CTD] > or = 750) and (b) transfusion of any non-red blood cell (RBC) blood products. Logistic regression was used to estimate the association between excessive bleeding at the first and second cardiac procedures. The logistic regression models for CTD > or = 750 in the second surgery determined that CTD > or = 750 in the first surgery compared to CTD < 750 had an unadjusted odds ratio of 2.18 (P = 0.03) and an odds ratio of 2.42 (P = 0.03) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. The logistic regression model for any non-RBC use in the second surgery determined that any non-RBC use in the first surgery compared with no non-RBC use had an unadjusted odds ratio of 2.32 (P = 0.02) and an odds ratio of 2.55 (P = 0.02) when adjusted for age, sex, body surface area, preoperative anticoagulant use, cardiopulmonary bypass duration, and procedure type at second surgery. We conclude that a history of excessive bleeding during the first operation is associated with more than two times increased risk for excessive bleeding in the second surgery.

Adult↗

A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.

PURPOSE: To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). EXPERIMENTAL DESIGN: Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. RESULTS: Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. CONCLUSIONS: rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.

Adult↗

"Like roulette": Australian women's explanations of gynecological cancers.

Drawing on data from interviews and other ethnographic research, we examine how Australian women from different ethnic and cultural backgrounds make sense of having gynecological cancer. Alternative explanatory models often co-exist in a single narrative, but there is significant consistency in the etiology of cancer among Australian-born and immigrant women. In acknowledging the unpredictability of cancer and the prognosis of particular disease, women contextualize their own experience as a matter of luck, outside their control or influence. Most often women relate their own occurrence of cancer to their social setting and relational factors rather than personal behavior, but at the same time, they acknowledge the interaction of external forces and individual factors, particularly in the case of diet and stress. Women can control diet to some extent, although many note the irony of having developed cancer even when they have eaten well. Stress, on the other hand, is largely considered as external to and beyond women's control. Women speak of stress as a characteristic of contemporary social life, as well as their own public and domestic, physical and emotional lives; for these women stress in any of these areas can create physical vulnerability that may result in cancer. Since women associate cancer with loss of control, the idea of cancerous cells out-of-control within their bodies operates as a metonym of women's views of themselves interpersonally and socially.

Adaptation, Psychological↗

Role of integrin receptors for fibronectin, collagen and laminin in the regulation of ovarian carcinoma functions in response to a matrix microenvironment.

Integrins play an important role in cellular matrix interactions requisite for cancer cell adhesion, growth, migration and invasion. In this study, we have investigated the expression of integrin subunits alpha3, alpha6, alphav and beta1 in normal ovaries, benign ovarian tumors and ovarian carcinomas of different pathological grades. The expression of these integrins in ovarian cancer cell lines was also investigated, and their role in sustaining proliferation, adhesion, migration and invasion in cohort with the activation of signaling pathways in response to extracellular matrices (ECM) was evaluated. We demonstrate a differential expression pattern of alpha3, alpha6, alphav and beta1 integrin subunits in ovarian carcinomas compared to normal ovaries and benign ovarian tumors. Ovarian cancer cell lines (Hey, Ovcar3 and Peo.36) demonstrated significantly high expression of alpha3, alpha6, alphav and beta1 integrin subunits. A significant increase in proliferation and adhesion (P<0.05) in response to collagen 1 (Coll) and laminin (LM), ligands for integrin receptor alpha3beta1 and alpha6beta1 was observed in ovarian cancer cell lines. On the other hand, fibronectin (FN), a receptor for alphavbeta1 integrin, increased proliferation in all ovarian cancer cell lines studied but only enhanced adhesion in Hey cell line (P<0.05). Neutralizing antibodies against alpha3, alpha6, alphav and beta1 integrin subunits inhibited ECM-induced proliferation, but increased adhesion to ECM was inhibited by beta1 integrin subunit antibody. No suppression of Coll, LM and FN-induced (Hey cells only) adhesion was observed in the presence of alpha3 or alphav subunit antibodies but LM-induced adhesion was inhibited by blocking alpha6 subunit functions. LM, FN and Coll enhanced chemotactic migration in Hey cells, but direct invasion across ECM was observed only in the presence of LM and Coll. Blocking antibodies against alpha3, alpha6 and beta1 integrin subunits inhibited both chemotactic migration and invasion of Hey cells in response to respective ECM. Adhesion of ovarian cancer cells to FN, Coll and LM activated Ras, Erk and Akt pathways. Neutralizing alphav and beta1 functions did not inhibit FN-induced activation of Ras and Erk pathways but inhibited the Akt pathway. On the other hand, antibodies against alpha6 and beta1 subunits, but not alpha3 subunit, inhibited LM-induced activation of Ras but did not inhibit the downstream Akt pathway. Neutralizing beta1 subunit function however, inhibited LM-induced Erk activation. Coll-induced activation of Ras, Erk and Akt pathways was inhibited by alpha3 and beta1 integrin subunit antibodies. These results indicate that alpha3beta1, alphavbeta1 and alpha6beta1 integrin mediate proliferation, adhesion, migration and invasion of ovarian cancer cells in response to ECM and targeting these integrins to modulate integrin-ECM interactions in tumor cells may be a promising tool to reduce the dissemination of ovarian carcinoma in vivo.

Carcinoma↗

Should the Pap smear be repeated at the first colposcopy visit?

AIM: To determine whether there is any benefit in repeating the Pap smear at the time of colposcopy in women referred to a teaching hospital dysplasia clinic. METHODS: Analysis of a computerised database, and review of literature. RESULTS: Repeating the Pap smear potentially changed management in 2% of women referred with low-grade lesions, and in 7% of those with high-grade lesions. CONCLUSION: Although the literature suggests that the repeat smear may directly affect the quality of the colposcopic examination, repeating the smear in women referred with high-grade squamous intraepithelial (HSIL) smears may be beneficial.

Adult↗

The effect of an extended flexor carpi radialis approach on blood flow to the distal radius: a cadaveric study.

The effect of an extended flexor carpi radialis approach on the blood supply of the radius was examined in six (3 paired) fresh frozen cadaver limbs after injection with India ink and clearing using a modified Spalteholz technique. An extended flexor carpi radialis approach to the distal radius was made in the left limb in each of the three-paired limbs. The right limb served as a nonoperative control. Following perfusion of the arterial vasculature of each limb with India ink, serial transverse sections were cut and the intraosseous blood supply evaluated using a modified Spalteholz technique. Both controls and surgical specimens demonstrated complete cortical penetration from endosteal vessels in the proximal and midsections of the radius. In the distal radius, surgical specimens demonstrated reduced perfusion volarly, however there continued to be perfusion of ink through intact dorsal and ulnar metaphyseal perforating arteries. Persistent vascular perfusion to the distal radius remains through intact endosteal vessels and metaphyseal perforators of extensive surgical soft-tissue stripping.

Aged, 80 and over↗

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX adjuvant in women with cervical intraepithelial neoplasia.

PURPOSE: Persistent infection of cervical epithelium with "high risk" human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX adjuvant (HPV16 Immunotherapeutic) for patients with CIN. EXPERIMENTAL DESIGN: Patients with CIN (n = 31) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. RESULTS: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. CONCLUSIONS: The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX adjuvant is safe and induces vaccine antigen specific cell mediated immunity.

Adjuvants, Immunologic↗

A phase II trial of capecitabine in heavily pre-treated platinum-resistant ovarian cancer.

OBJECTIVE: To determine the activity of capecitabine in women with platinum-resistant ovarian cancer. METHODS: In this multi-centre phase II trial, 35 patients with platinum-resistant ovarian, primary peritoneal or fallopian tube carcinomas were treated with capecitabine 1250 mg/m(2) twice daily for 14 days every 21 days. Platinum resistance was defined as progression within 4 months of completing the last platinum and all patients had previously received a taxane. Response was assessed by both RECIST criteria for patients with measurable disease and CA125 criteria. Responders were defined as patients with measurable disease who achieved a CR or PR according to RECIST criteria, patients without measurable disease who met the CA125 criteria for response and patients with stable measurable disease who met the CA125 criteria for response. RESULTS: Patients had received a median of four prior chemotherapy regimens (range 1-9). The median number of cycles of capecitabine administered was 3 (range 1-10). The response rate using the combined RECIST and CA125 criteria was 9% (95% CI 2-25%). In patients evaluable using RECIST criteria, the response rate was 5% (95% CI 0-25%). In patients evaluable for CA125 response, the response rate was 7% (95% CI 1-22%). The median progression-free survival was 2.3 months, and the median survival was 7.1 months. Treatment was generally well tolerated with most frequent grade 3 toxicities being hand-foot syndrome (17%) and diarrhea (9%). CONCLUSION: Capecitabine is well tolerated but has limited activity in patients with heavily pre-treated platinum-resistant ovarian cancer.

Adult↗

Women with low-grade abnormalities on Pap smear should be referred for colposcopy.

AIM: To assess cytological, colposcopic and histological outcomes in women referred to a teaching hospital dysplasia clinic with low-grade changes on screening Pap smear. METHODS: Analysis of a computerised database. RESULTS: Repeating the Pap test was of little value. Fifteen percent of women with low-grade changes on the referral smear had biopsy proven high-grade change. There was little difference in biopsy proven high-grade change in women referred with an 'abnormal smear of uncertain significance' (23%) or 'an abnormal smear of uncertain significance-possible high-grade change' (24%). CONCLUSIONS: Given these findings and the current medico-legal climate, immediate referral of women with low-grade changes on routine cytology is indicated, and seems a safer option than the more conservative approach of a repeat smear in 6 or 12 months. Further study of the usefulness of separating smears of uncertain significance into high-grade and low-grade categories is warranted. Consumer input into recommendations for management of Pap smear abnormalities is required.

Biopsy↗