Nuria Giménez

Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients

SummaryTo evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence, serial serum determinations of both antigens were performed in 1023 patients (follow-up: 1–10 years, mean 6.2 years) with primary breast cancer (CA 15.3 in 533 cases) and no evidence of residual disease (NED) after radical treatment (radical mastectomy or simple mastectomy and radiotherapy). 246 patients developed metastases during follow-up.Results: CEA and CA 15.3 were elevated (> 10 ng/ml or > 60 U/ml, respectively) prior to diagnosis in 40% (98/246) and 41% (37/91) of the patients with recurrence, with a lead time of 4.9 ± 2.2 and 4.2 ± 2.3 months, respectively. When patients with locoregional recurrences were excluded, sensitivity improved to 46% (CEA) and 54% (CA 15.3), and to 64% with both tumor markers (CEA and/or CA 15.3). Higher levels of both CEA and CA 15.3 at diagnosis of recurrence, higher sensitivity in early diagnosis of relapse, and a higher lead time were found in ER+ (CEA) or PgR+ patients (CA 15.3) than in those that were negative for these receptors in the primary tumor (p < 0.001). Specificity of the tumor markers was 99% for both CEA (777 NED patients) and for CA 15.3 (444 NED patients), respectively. In conclusion, CEA and CA 15.3 are useful tools for early diagnosis of metastases, mainly in those patients with ER+ or PR+ tumors.

Carcinoembryonic antigen in staging and follow-up of patients with solid tumors.

The presence of a tumor antigen in human colonic carcinomas and their metastases was described about 25 years ago. This antigen, called carcinoembryonic antigen (CEA), is one of the first known tumor markers. Since then, many more have been described, but CEA, determined alone or in combination with others, is still one of the most used. CEA is not organ specific and abnormal values may be found in a wide range of carcinomas, especially those with gastrointestinal involvement. CEA assay should not be used for cancer diagnosis because its sensitivity in patients without cancer metastases is low. In addition, abnormal CEA values may be found in patients with benign diseases. However, the probability of malignancy increases directly with CEA concentration. Its main clinical applications are prognosis, early diagnosis of recurrence and follow-up of patients with carcinomas. In a wide range of malignancies, CEA serum levels are clearly related to tumor stage. Presurgical CEA serum levels are a well-established prognostic factor in colorectal, breast and lung cancer. Patients presenting with increased preoperative CEA serum levels have both a shorter disease-free interval and lower survival than those with normal CEA levels. In the early diagnosis of recurrence, CEA also plays an important role: in about 70-85% of patients with colorectal tumors and in 40-50% with breast cancer, CEA serial increase is the first sign of tumor recurrence. In patients with disseminated tumors, serial determinations are also a useful tool for therapy monitoring: CEA values decrease with effective treatment while stable or increasing values are observed when treatment is not effective.

Evaluation of [−2] proPSA and Prostate Health Index (phi) for the detection of prostate cancer: a systematic review and meta-analysis

Abstract The usefulness of %[−2] proPSA and Prostate Health Index (phi) in the detection of prostate cancer are currently unknown. It has been suggested that these tests can distinguish prostate cancer from benign prostatic diseases better than PSA or %fPSA. We performed a systematic review and meta-analysis of the available scientific evidence to evaluate the clinical usefulness of %[−2] proPSA and phi. Relevant published papers were identified by searching computerized bibliographic systems. Data on sensitivity and specificity were extracted from 12 studies: 10 studies about %[−2] proPSA (3928 patients in total, including 1762 with confirmed prostate cancer) and eight studies about phi (2919 patients in total, including 1515 with confirmed prostate cancer). The sensitivity for the detection of prostate cancer was 90% for %[−2] proPSA and phi, while the pooled specificity was 32.5% (95% CI 30.6–34.5) and 31.6% (95% CI 29.2–34.0) for %[−2] proPSA and phi, respectively. The measurement of %[−2] proPSA improves the accuracy of prostate cancer detection in comparison with PSA or %fPSA, particularly in the group of patients with PSA between 2 μg/L and 10 μg/L. Similar results were obtained measuring phi. Using these tests, it is possible to reduce the number of unnecessary biopsies, maintaining a high cancer detection rate. Published results also showed that %[−2] proPSA and phi are related to the aggressiveness of the tumor.

Use of Axillary Ultrasound, Ultrasound-Fine Needle Aspiration Biopsy and Magnetic Resonance Imaging in the Preoperative Triage of Breast Cancer Patients Considered for Sentinel Node Biopsy

We assessed the diagnostic yield of axillary ultrasound, alone or in combination with fine-needle aspiration axillary biopsy and magnetic resonance imaging in patients with invasive breast carcinoma compared with final axillary histology by sentinel node biopsy or by axillary lymph node dissection. From January 2003 to March 2009, 520 axillary ultrasound examinations and 105 axillary magnetic resonance imaging studies were included. Compared with final axillary histology, ultrasound fine-needle aspiration showed positive predictive value of 87%, negative predictive value of 82%, sensitivity of 53% and specificity of 100%. In cases of negative ultrasound, the rate of positive nodes was 17% (micro-metastases excluded). Ultrasound examination of the axilla, combined with fine-needle aspiration as appropriate must be included in the preoperative work-up of patients considered for sentinel node biopsy to definitively establish such an indication while minimizing the risk of false-negative sentinel node. Axillary magnetic resonance imaging did not improve the preoperative work-up.

Study of a new tumor marker, CYFRA 21-1, in malignant and nonmalignant diseases

The diagnostic value of a new tumor marker, CYFRA 21-1, was studied in the sera of 50 controls, 206 patients with benign diseases and 469 patients with malignancies. Fifty controls showed mean serum concentrations of 1.2 +/- 0.5 ng/ml. Using 3.3 ng/ml as the cutoff, abnormal CYFRA levels were found in 13.1% of patients with benign diseases, mainly in those with liver cirrhosis (29.4%) or renal failure (20.8%), and in 44.4% (180/405) of patients with active cancer. Neither healthy subjects nor no evidence of disease (64 cases) patients had serum levels higher than this limit. CYFRA 21-1 results were significantly higher in patients with active cancer than in those with benign diseases or without active tumors (p < 0.0001). CYFRA serum levels were significantly higher in patients with metastases (59.5%) than in those with locoregional disease (33.7%; p < 0.001). CYFRA 21-1 sensitivity in patients with lung cancer was related to tumor histology with abnormal levels in 65.6% of patients with non-small cell lung cancer and in 25% of patients with small cell lung cancer (p < 0.0001). In breast cancer, CYFRA 21-1 concentrations were significantly higher in patients with metastases and in patients with primary tumors but with nodal involvement (p < 0.001).

CYFRA 21-1 in lung cancer: comparison with CEA, CA 125, SCC and NSE serum levels

CYFRA 21–1, CEA, CA 125, SCC and NSE serum levels were determined in 50 healthy subjects and in 189 patients with primary lung cancer (101 with locoregional disease, 68 with recurrence and 20 patients with no evidence of residual disease (NED). Abnormal CYFRA 21–1 serum levels were found in 53.6% (90/168) of the patients with active cancer. Neither healthy subjects nor NED patients had abnormal serum levels. CYFRa 21–1 serum concentrations were significantly higher in patients with active cancer than in healthy subjects or in NED patients (p < 0.0001). CYFRA 21–1 sensitivity was related to tumor histology with abnormal levels in 64.7% of patients with NSCLC and in 30% of patients with SCLC (P <0.0001). In NSCLC, serum CYFRA 21–1 concentrations were also related to histological type, the highest values being found in squamous cell carcinomas and LCLC and the lowest in adenocarcinomas (p < 0.04). There was also a clear relationship between CYFRA 21–1 and tumor extension, with significantly higher values in patients with metastases than in those without metastases (p < 0.0001). Abnormal CEA values were found in 49.1%, CA 125 in 39%, SCC in 27.8% and NSE in 21.3% of the patients with active cancer. With respect to histological type, CYFRA was elevated in 68.3% of squamous cell carcinomas (CEA: 46.7%, SCC: 50%, CA 125:31.7%, NSE: 11.7%), in 54.8% of adenocarcinomas (CEA: 62%, SCC: 26.2%, CA 125: 59.5%, NSE: 9.5%), in 78.6% of LCLC (CEA: 64.3%, SCC: 28.6%, CA 125: 78.6%, NSE: 7.1%) and in 30% of SCLC (CEA: 37.7%, SCC: 3.8%, CA 125:20.8%, NSE: 45.3%). In summary, CYFRA 21–1 is the most sensitive tumor marker in patients with lung cancer, especially in NSCLC patients.

Effectiveness of a multiple intervention strategy for the control of the tiger mosquito (Aedes albopictus) in Spain.

This study was undertaken to evaluate the effectiveness of four complementary and combined strategies to minimize the presence of the invasive mosquito Aedes albopictus, firmly established in Sant Cugat del Vallès, Catalonia, Spain. A quasi-experimental design including six neighbourhoods was performed in 2008-2009. The abundance of mosquitoes was monitored through ovitraps. The multiple intervention strategy consisted of four actions: source reduction; larvicide treatments (Bacillus thuringiensis israelensis and diflubenzuron); adulticide treatments (alfacipermetrin); and cleaning up uncontrolled landfills. The results showed the number of eggs significantly reduced in the areas with intervention. In 2008, the accumulate median of eggs was 175 and 272 in the intervention and control areas, respectively. In 2009, these medians were 884 and 1668 eggs. In total, 3104 households were visited and 683 people were interviewed. During inspections inside the houses, the cooperation of citizens in 2009 was 16% higher than that in 2008 (95% CI 13-19%). These findings suggest that the strategy was effective in reducing the number of eggs. Citizen cooperation, an essential factor for success, was observed through a high level of collaboration by the home owners, who allowed entry into their private dwellings. This study could be a model for controlling the populations of Ae. albopictus in the Mediterranean region.

Prognostic Significance of SCC Antigen in the Serum of Patients with Head and Neck Cancer

SCC antigen (Ag) is a tumor-associated Ag (TAA) obtained from squamous cell carcinoma of the uterine cervix. This study reports the evaluation of this TAA in patients with head and neck malignant diseases and its possible prognostic value. Serum samples from 28 patients with benign head and neck diseases from 399 patients with cancer were obtained prior to treatment. SCC Ag serum levels were determined by radioimmunoassay using 2.5 ng/ml as the upper limit of normality. Elevated SCC Ag serum levels were found in 14% of 28 patients with benign diseases, in 29% of 217 patients with primary tumors, in 48% of 46 patients with recurrence (43% in locoregional, 64% in metastases) and in 4% of 136 patients with no evidence of disease. In patients with primary tumors, SCC Ag serum levels were related to nodal involvement and tumor location with significantly higher levels in node-positive patients (p = 0.001) and in tumors located in the nasopharynx and piriform sinus (p = 0.02). Presurgical SCC Ag serum levels in patients with primary tumors had prognostic value with shorter disease-free survival in those patients with abnormal values of this TAA (p < 0.001), in both, node-negative and node-positive patients (p < 0.01). Multivariate analyses showed that SCC Ag is a significant independent predictor of disease-free survival even when other prognostic factors are considered. In conclusion, pretreatment SCC Ag serum levels are an independent prognostic indicator in patients with head and neck malignancies.

Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. A single institution survey spanning 1998 to 2010

As far as recent breast cancer molecular subtype classification is concerned, much work has dealt with clinical outcomes for triple negative and Her2 patients. Less is known about the course of patients in the remaining subtypes. Molecular classification based on immunohistochemistry is widely available and correlates well with genetic microarray assessment, but at a lower cost. The aim of our investigation was to correlate immunohistochemical subtypes of breast cancer with clinical characteristics and patient outcomes. Since 1998, 1167 patients operated for 1191 invasive breast tumours were included in our database. Patients were regularly followed up until March 2010. Disease-free survival, overall mortality, and breast cancer-specific mortality at 5 years were calculated for the cohort. 72% of tumours were ER+PR±HER2- group, 13% triple negative (ER-PR-HER2-), 10% ER+PR±HER2+ group, and 5% Her2 (ER-PR-HER2+). Cancer-specific survival was 94.2% for the ER+PR+HER2- subtype, 84.8% for the Her2 subtype, 83.3% for the ER+PR-HER2- subtype, and 78.6% for triple negatives. Distant metastases prevalence ranged from 7% to 22% across subtypes, increasing stepwise from ER+PR+HER2-, ER+PR+HER2+, ER+PR-HER2-, ER+PR-HER2+, ER-PR-HER2+ through triple negative. Small, low-grade tumours with low axillary burden were more likely to belong to the ER+PR±HER2- group. Conversely, larger high-grade tumours with significant axillary burden were more likely to belong to Her2 or triple negative groups. ER+PR±HER2- group patients with negative PR receptors performed more like Her2 or triple negative than like the rest of ER+PR±HER2± groups patients. Molecular classification of breast tumours based only on immunohistochemistry is quite useful on practical clinical grounds, as expected. ER+PR±HER2- group patients with negative PR receptors seem to be at high risk and deserve further consideration.

Llegada de Aedes albopictus a España: un nuevo reto para la salud pública

Introduccion: En el Centro de Atencion Primaria de Sant Cugat del Valles (Barcelona) se detecto un espectacular aumento de consultas por picaduras de insectos. El posterior estudio de las especies del area permitio identificar a Aedes albopictus. Objetivo: Analizar las consultas por picaduras de insecto (1998-2004). Metodos: Estudio descriptivo transversal retrospectivo. Consultaron 2.760 pacientes durante el periodo 1998-2004. Resultados: Se detecto un continuo aumento de consultas por picaduras, hasta alcanzar las 16 consultas por 1.000 habitantes. Los pacientes tenian una media de edad de 32 anos, y un 62% eran mujeres. El 71% de las lesiones se localizaron en las extremidades y se infectaron el 19% de ellas. El 67% de los pacientes recibio tratamiento sistemico. Conclusiones: La atencion primaria alerto sobre el llamativo aumento de consultas por picaduras de insecto. El colectivo de pacientes que consulto por este motivo fue mayoritariamente femenino, joven, recibio con frecuencia tratamiento sistemico y presento un elevado porcentaje de complicaciones locales.