Feasibility of screening for ovarian cancer using symptoms as selection criteria

OBJECTIVE: Retrospective studies have reported that 95% of women with ovarian cancer have symptoms prior to diagnosis and that women with these symptoms are at an increased risk of ovarian cancer. Failure to recognise these symptoms may result in a delay in referral and diagnosis. We assess the feasibility of screening for ovarian cancer using symptoms as selection criteria. DESIGN: A randomised controlled trial. SETTING: General practices in East London. POPULATION: Three hundred and ninety GPs. METHODS: GPs were randomised by practice, and those in the study group were given rapid access to ultrasound and CA125 test for women, >45 years, suffering from symptoms that may be caused by ovarian cancer. MAIN OUTCOME MEASURES: Symptoms leading to referral, ultrasound and CA125 results and ovarian cancer diagnosis. RESULTS: Seventy nine practices containing 197 GPs were randomised to the study arm. Three hundred and seventeen women were referred, of which 315 were eligible. Women reported the following symptoms: abdominal 87%, gastrointestinal 41% and constitutional 29%. Twenty-three women had abnormal findings on ultrasound: 20 were managed conservatively and 3 surgically. Histology revealed a mucinous cystadenoma, a Brenner tumour and a serous cystadenoma. Incidental findings included endometrial pathology in 13 women and bladder pathology in 2. Ninety five percent of CA125 results were <35 units/ml. CONCLUSIONS: This pilot study confirms the feasibility of screening for ovarian cancer using symptoms as selection criteria. Specificity was high and patient compliance good. Initial concerns about referral volumes and additional investigations and referrals generated were not confirmed. No ovarian cancers were detected in this pilot study, and this may be due to the size of the cohort.     

Community-wide prevention of cardiovascular disease: education strategies of the Minnesota Heart Health Program

The Minnesota Heart Health Program (MHHP) is a research and demonstration project of population-wide primary prevention of cardiovascular disease. Study goals are to achieve reductions in cardiovascular disease risk factors and morbidity and mortality in three education communities compared with three reference communities. The program in the first of the three intervention communities, Mankato, has been operating for 3 of the planned 5 years. Early objectives of the program have been achieved based on data obtained from population-based random samples surveyed in education and comparison communities. After 2 years of participation, Mankato was significantly more exposed to activities promoting cardiovascular disease prevention. In this town of 38,000 inhabitants, 190 community leaders were directly involved as program volunteers, 14,103 residents (over 60% of adults) attended a screening education center, 2,094 attended MHHP health education classes, 42 of 65 physicians and 728 other health professionals participated in continuing education programs offered by MHHP, and distribution of printed media averaged 12.2 pieces per household. These combined educational strategies have resulted in widespread awareness of MHHP and participation by the majority of the Mankato adult population in its education activities.     

Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer.

OBJECTIVE: The purpose of this study was to identify the prognostic impact of unexpected lymph node metastases in patients undergoing resection of pulmonary metastases from colorectal cancer and specify the influence of pulmonary and mediastinal nodal involvement according to the modified Narukes lymph node mapping [Mountain CF, Dresler CM. Regional lymph node classification for lung cancer. Chest 1997;111(6):1718-23.]. METHODS: From January 1993 to December 2003, 175 patients were diagnosed and resected for pulmonary metastases of colorectal cancer. Follow up informations were collected for 169 patients and an analysis of prognostic factors was performed. Ninety-six men (56.8%) and 73 women (43.2%) with a median age of 62 (range 34-81) were identified, 28 (16.7%) patients were found to have lymph node metastases, five of them were identified during a recurrent procedure. Probability of survival was calculated according to the method of Kaplan-Meier. The prognostic influence of lymph node metastases on survival was analyzed with the log-rank test. RESULTS: Median survival was 47.2 months after first metastasectomy. Ten patients with intrapulmonary nodal involvement had a median survival of 86 months whereas 12 patients with hilar and six patients with mediastinal lymph node metastases had a median survival of 24.5 and 34.7 months. The survival difference between pulmonary and hilar/mediastinal metastases was statistically significant (p=0.008/p=0.07). Five year survival with pulmonary, hilar, and mediastinal metastases was 78.5, 0, and 0%, respectively. Perioperative mortality was 0%. CONCLUSIONS: Resection of pulmonary metastases secondary to colorectal cancer is safe and indicated in highly selected patients. Because tumor involvement of lymph nodes has a strong impact on survival; depending on their location, at least a lymph node sampling should always be performed. Adjuvant chemotherapy in case of proven lymph node metastases might be a good option to improve prognosis.     

Central venous sampling for intraoperative parathyroid hormone monitoring: are peripheral guidelines applicable?

Intraoperative parathyroid hormone (PTH) monitoring has become an integral adjunct to minimally invasive parathyroidectomy. Guidelines for predicting therapeutic excision of all hyperactive parathyroid tissue have been routinely based on peripheral blood samples drawn at various time intervals. Whether these same guidelines can be used to predict success based on central blood draws has not been established. The authors wanted to evaluate whether peripheral criteria were applicable when PTH levels were drawn from a central location. Simultaneous peripheral venous (PV) and central venous (CV) PTH samples were drawn from 64 patients undergoing cervical exploration for primary hyperparathyroidism. Median preexcision PTH was significantly higher centrally at 165 pg/mL (interquartile range [IQR], 101-391 pg/mL) versus peripherally 102 pg/mL (interquartile range, 73-156 pg/mL, P < 0.0001). Postexcision PTH was slightly greater in CV (38 pg/mL; IQR, 24-62) than in PV (29 pg/mL; IQR, 22-51; P < 0.0001). The decrease in intraoperative PTH was compared after excision of an initial gland. Fifty-four of the 64 patients had all hyperfunctioning parathyroid tissue removed after initial gland resection. Pre- to postexcision ratios for CV and PV were compared using receiver operating characteristic curve methods, and summarized by area under the curve (AUC). PV (AUC = 0.85) appears to be a slightly more sensitive discriminator than CV (AUC = 0.83), although the difference is not statistically significant (P = 0.5). Despite higher absolute values for CV, both peripheral and central sample sites accurately predict outcomes based on established guidelines for intraoperative PTH monitoring.     

Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses

Epitopes of the circumsporozoite (CS) protein of Plasmodium falciparum, the most pathogenic species of the malaria parasite, have been shown to elicit protective immunity in experimental animals and human volunteers. The mechanisms of immunity include parasite-neutralizing antibodies that can inhibit parasite motility in the skin at the site of infection and in the bloodstream during transit to the hepatocyte host cell and also block interaction with host cell receptors on hepatocytes. In addition, specific CD4+ and CD8+ cellular mechanisms target the intracellular hepatic forms, thus preventing release of erythrocytic stage parasites from the infected hepatocyte and the ensuing blood stage cycle responsible for clinical disease. An innovative method for producing particle vaccines, layer-by-layer (LbL) fabrication of polypeptide films on solid CaCO₃ cores, was used to produce synthetic malaria vaccines containing a tri-epitope CS peptide T1BT* comprising the antibody epitope of the CS repeat region (B) and two T-cell epitopes, the highly conserved T1 epitope and the universal epitope T*. Mice immunized with microparticles loaded with T1BT* peptide developed parasite-neutralizing antibodies and malaria-specific T-cell responses including cytotoxic effector T-cells. Protection from liver stage infection following challenge with live sporozoites from infected mosquitoes correlated with neutralizing antibody levels. Although some immunized mice with low or undetectable neutralizing antibodies were also protected, depletion of T-cells prior to challenge resulted in the majority of mice remaining resistant to challenge. In addition, mice immunized with microparticles bearing only T-cell epitopes were not protected, demonstrating that cellular immunity alone was not sufficient for protective immunity. Although the microparticles without adjuvant were immunogenic and protective, a simple modification with the lipopeptide TLR2 agonist Pam₃Cys increased the potency and efficacy of the LbL vaccine candidate. This study demonstrates the potential of LbL particles as promising malaria vaccine candidates using the T1BT* epitopes from the P. falciparum CS protein.