HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway.

In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005-2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3-6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups <34 years, 34-50 years, and >50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone.

Diagnostic validity of fatal cerebral strokes and coronary deaths in mortality statistics: an autopsy study.

Mortality statistics represent important endpoints in epidemiological studies. The diagnostic validity of cerebral stroke and ischemic heart disease recorded as the underlying cause of death in Norwegian mortality statistics was assessed by using mortality data of participants in the Bergen Clinical Blood Pressure Study in Norway and autopsy records from the Gade Institute in Bergen. In the 41 years of the study (1965-2005) 4,387 subjects had died and 1,140 (26%) had undergone a post mortem examination; 548 (12%) died from cerebral stroke and 1,120 (24%) from ischemic heart disease according to the mortality statistics, compared to 113 (10%) strokes and 323 (28%) coronary events registered in the autopsy records. The sensitivity and positive predictive value of fatal cerebral strokes in the mortality statistics were 0.75, 95% confidence interval (CI) [0.66, 0.83] and 0.86 [0.77, 0.92], respectively, whereas those of coronary deaths were 0.87 [0.84, 0.91] and 0.85 [0.81, 0.89] respectively. Cohen's Kappa coefficients were 0.78 [0.72, 0.84] for stroke and 0.80 [0.76, 0.84] for coronary deaths. In addition to female gender and increasing age at death, cerebral stroke was a negative predictor of an autopsy being carried out (odds ratio (OR) 0.69, 95% CI [0.54, 0.87]), whereas death from coronary heart disease was not (OR 1.14, 95% CI [0.97, 1,33]), both adjusted for gender and age at death. There was substantial agreement between mortality statistics and autopsy findings for both fatal strokes and coronary deaths. Selection for post mortem examinations was associated with age, gender and cause of death.

Birth length and weight as predictors of breast cancer prognosis.

BACKGROUND: Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients. METHODS: Information on birth size (weight, length and ponderal index (kg/length (m3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis. RESULTS: Breast cancer patients with birth length > or = 52 cm had nearly twice the risk of dying (hazard ratio, 1.92, 95% confidence interval, 1.09-3.41) from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis.Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival. CONCLUSIONS: Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms.

Estrogen receptor beta--an independent prognostic marker in estrogen receptor alpha and progesterone receptor-positive breast cancer?

Both subtypes of estrogen receptor (ER), ERalpha and ERbeta, are normally present in the mammary gland. The role of ERalpha as a prognostic marker in breast cancer is well established due to the beneficial effect of providing tamoxifen as adjuvant therapy. The role of ERbeta, however, is less clear. To gain insight into the importance of ERbeta in breast cancer, 145 primary breast cancers were examined by immunohistochemistry for ERbeta, and the expression level was compared with ERalpha and progesterone receptor (PR) status. Especially, we wanted to examine the significance of ERbeta in the contrasting ERalpha+/PR+ and ERalpha-/PR- subgroups. In the ERalpha+/PR+ subgroup (dual positive), the survival difference between patients with low, medium and high ER beta level was statistically significant (p = 0.004), with more than 70% of patients with medium and high ERbeta levels surviving 100 months, compared with less than 30% in the group with low ERbeta level. Further, for ERalpha+/PR+ patients there was a reduced risk of fatal outcome by multivariate analysis with increasing ERbeta levels (p(trend) < 0.01 [univariate analysis]; p(trend) = 0.05 [multivariate analysis]). The risk was 31% and 27% for medium and high ERbeta levels, respectively, compared with low ERbeta level, adjusting for standard prognostic factors such as tumor diameter, nuclear tumor grade (quantified by mean nuclear area), lymph node status, and patient age at operation. For patients with ERalpha-/PR- tumors (dual negative), however, there was no association between ERbeta levels and patient outcome. Our findings indicate that ERbeta expression provides independent prognostic information for breast cancers with ERalpha/PR-positive status, a feature typical among screen-detected breast cancers. The role of ERbeta needs to be further evaluated especially in this group of breast cancers.

Unnatural death in the elderly : A forensic study from western norway.

The objective of the study was to determine the unnatural manner and causes of death in older people, defined as individuals at least 60 years of age at the time of death. A series of medico-legally examined deaths in older people, who were examined between January 1, 1999 and December 31, 2003, and whose deaths were considered unnatural after forensic examination were studied. All deaths took place in western Norway, in two whole counties and the north part of a third county, including one large Norwegian city and one medium-sized city on the west coast of Norway. Of the 2425 forensic examinations performed in the time period, 1169 were 60 years or older at the time of death. Of these, 228 deaths were categorized as accidental, suicidal, or homicidal. Drowning was the most common lethal accident in elderly males, whereas fatal traffic accidents were more frequent in women. Alcohol intoxication was very common among male drowning victims, and none of the drowning victims had used a life-saving floating device. None of the elderly traffic victims were intoxicated. Death after a falling accident in the home is probably underreported. Suicide is more common among elderly men than women. Among men, hanging was the most common cause of death, whereas intoxication resultiong from drug overdose and drowning were the most frequent causes of death in women. Cancer was present in 19% of the suicide victims, all men. Serious disease may be a predisposing factor for suicidal behavior. Homicide is uncommon as a manner of unnatural death among the elderly.

Hyperbaric oxygen alone or combined with 5-FU attenuates growth of DMBA-induced rat mammary tumors.

We tested the hypothesis that hyperbaric oxygen (HBO) alone and with chemotherapy (5-FU) attenuates tumor growth of DMBA-induced tumors in rats. Six series were performed: (1) Controls (air and vehicle 0.9% NaCl i.p.), (2) 5-FU (0.2 mg/kg i.p.), (3) HBO (2 bar for 90 min and vehicle), (4) HBO and 5-FU, (5) HBO (11 days) and air (next 12 days), (6) HBO (23 days). All treatments were applied on days 1, 4, 7, 10 (Series 1-4), as well as on days 14, 17 and 23 (Series 5-6). Tumor diameter increased by 76.7 and 41.2% in untreated controls and in the 5-FU group, respectively, after 10 days. Tumor size fell by 17-24.2% in the HBO groups and by 35.5% when combined with 5-FU (P < 0.05 compared to HBO). HBO treatment reduced the total number of blood vessels in the tumors. After completion of HBO treatment tumor size increased, but statistically insignificant, during the next 12 days.