Olav A. Haugen

Neuroendocrine differentiation in carcinomas of the prostate. Do neuroendocrine serum markers reflect immunohistochemical findings

The aim of the present study was to examine the correlation between the immunohistochemical findings and the serum markers for neuroendocrine (NE) cells in patients with carcinoma of the prostate. Preoperative serum values of chromogranin A (CgA), chromogranin B (CgB), pancreastatin (Pst), neuron‐specific enolase (NSE), and prostatic specific antigen (PSA) were determined in 22 patients. The tissue specimens were obtained by a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. Immunohistochemistry was performed by using antibodies against CgA, CgB, NSE, serotonin, thyroid‐stimulating hormone (TSH), and somatostatin. Tumor cells with NE differentiation were found in 91% of the cases. No patient had elevated serum values of NSE, despite the presence of NSE‐positive tumor cells in 77% of the tumors. Neither did CgB in serum correlate with the immunohistochemical findings. Elevated serum values of CgA were found in 59% of patients. A positive correlation between the number of CgA‐staining cells and the serum values of CgA was found, as seven out of eight patients with groups of CgA‐positive tumor cells had elevated serum values of CgA. We conclude that CgA, in contrast to NSE, CgB, and Pst, seems to be a useful serum marker in predicting the extent of NE differentiation in prostatic tumors. Prostate 30:1–6, 1997

Long-term effects of inhaled nicotine

Tobacco smoking has been reported to be associated with increased risk of cardiovascular disease and cancer, particularly of the lungs. In spite of extensive research on the health effects of tobacco smoking, the substances in tobacco smoke exerting these negative health effects are not completely known. Nicotine is the substance giving the subjective pleasure of smoking as well as inducing addiction. For the first time we report the effect on the rat of long-term (two years) inhalation of nicotine. The rats breathed in a chamber with nicotine at a concentration giving twice the plasma concentration found in heavy smokers. Nicotine was given for 20 h a day, five days a week during a two-year period. We could not find any increase in mortality, in atherosclerosis or frequency of tumors in these rats compared with controls. Particularly, there was no microscopic or macroscopic lung tumors nor any increase in pulmonary neuroendocrine cells. Throughout the study, however, the body weight of the nicotine exposed rats was reduced as compared with controls. In conclusion, our study does not indicate any harmful effect of nicotine when given in its pure form by inhalation.

Frequency of lymphoceles after open and laparoscopic pelvic lymph node dissection in patients with prostate cancer.

OBJECTIVE To compare the frequencies of pelvic lymphocele formation after laparoscopic and open pelvic lymph node dissection in patients with prostate cancer. MATERIAL AND METHODS A total of 132 patients operated on with pelvic lymph node dissection (PLND) underwent CT scanning of the abdomen and pelvis at a median of 29 days postoperatively. Open pelvic lymph node dissection (OPLND) was performed in 94 patients (71%) and 38 patients (29%) were operated on using a laparoscopic technique (LPLND). The frequency and size of pelvic lymphoceles were registered. Lymphoceles with a horizontal diameter of </=4.9 cm were classified as small and those with a horizontal diameter of >/=5.0 cm were classified as large. RESULTS The overall frequency of lymphoceles was 54%. The frequencies in the OPLND and LPLND groups were 61% and 37%, respectively. A total of 27% of the OPLND patients had large lymphoceles, compared to 8% of the LPLND patients. Three patients (2.3%), all in the OPLND group, had clinically significant lymphoceles. CONCLUSIONS Although the overall frequency of lymphocele formation was high, clinically significant lymphoceles were scarce. LPLND was associated with a statistically significant lower frequency of lymphocele formation compared to OPLND.

Use of neuroendocrine serum markers in the follow‐up of patients with cancer of the prostate

Neuroendocrine (NE) differentiation of prostatic adenocarcinomas has received increasing attention in recent years as a result of possible implications on prognosis and therapy. The incidence of NE cells in tumors has been reported from 10% up to 100%. Several studies have shown chromogranin A (CgA) to be the most reliable serum marker of NE differentiation. We have followed 22 patients with prostatic adenocarcinoma over a 2‐year period. The patients underwent a palliative transurethral resection of the prostate (TURP) because of urinary outflow obstruction. The prostatic tissue specimens were stained immunohistochemically using antibodies against CgA, chromogranin B (CgB), neuron‐specific enolase (NSE), thyroid‐stimulating hormone (TSH), serotonin, and somatostatin. In addition, each specimen was stained with hematoxylin & eosin (H & E), and saffran for tumor grading. Blood samples were taken preoperatively and after 1, 3, 6, and 24 months. The serum values of CgA, CgB, pancreastatin (Pst), NSE, and prostate‐specific antigen (PSA) were determined from each sample. Carcinomas with groups of CgA‐positive cells had higher serum levels of CgA compared to carcinomas with no or only scattered CgA‐positive NE cells. During the 2‐year period, there were no statistical significant variations in serum levels of CgA, NSE, Pst, and PSA. However, there was a significant increase in serum levels of CgB during the same period. P = 0.002, possibly due to an increase in number of NE cells in tumor or to a relative increase in production of CgB in the NE cells. Prostate 31:110–117, 1997.

Characterization of vulnerable plaques by multiphoton microscopy

Cardiovascular disease is the primary cause of death in the United States; the majority of these deaths are caused by the rupture of vulnerable plaques. An important feature of vulnerable plaques is the thickness of the fibrous cap that covers the necrotic core. A thickness of less than 65 microm has been proposed as a value that renders the plaque prone to rupture. This work shows that multiphoton microscopy (MPM) can image the plaque with microm resolution to a depth deeper than 65 microm. The fibrous cap emits primarily second harmonic generation due to collagen, in contrast to the necrotic core and healthy artery, which emits primarily two-photon excited fluorescence from elastin. This gives a good demarcation of the fibrous cap from underlying layers, facilitating the measurement of the fibrous cap thickness. Based on a measure of the collagen/elastin ratio, plaques were detected with a sensitivity of 65% and specificity of 81%. Furthermore, the technique gives detailed information on the structure of the collagen network in the fibrous cap. This network ultimately determines the mechanical strength of the plaque. A mechanical model based on this information could yield a measure of the propensity of the plaque to rupture.

DNA ploidy in intraductal breast carcinomas.

Cellular DNA-ploidy in 74 clinically detected intraductal breast carcinomas (IDCs) was analysed by flow cytometry. The histograms were classified as either diploid or aneuploid, and the DNA ploidy pattern compared with that of invasive breast carcinomas and normal breast tissue. All normal breast tissues were diploid while 28 (38%) of the IDCs were aneuploid, the DNA indices ranging from 1.32 to 2.00. The frequency of aneuploidy in invasive ductal carcinomas (73%) was significantly higher (P = 0.003), DNA index ranging from 1.34 to 2.92, compared with that in IDCs. Retrospectively, 14.5% of the patients had invasive breast cancer 16-166 months after the diagnosis of IDC. Neither DNA ploidy nor histopathological classification alone predicted clinical outcome, but patients with DNA diploid non-comedo IDC had a more favourable course.

Incorporation of contrast media in cultured cells.

Monolayer cultures of human prostatic (PC-3) and cervical (NHIK 3025) carcinoma cells were grown on formvar film and exposed to moderate concentrations of contrast agents for 30 minutes to 4 hours. After the exposure period, the monolayers were quickly frozen, and cryosections were examined by electron microscopy and X-ray microanalysis. Iodine was not detected in control cells, but was found in the cells that had been exposed to iodine-containing contrast media. The amount of intracellular iodine increased with increasing exposure dose and time. Because the cells mostly presented no sign of membrane damage, our findings support the view that contrast media have the ability to enter intact cells.

An Improved Attack on TKIP

Beck and Tews described the first practical cryptographic attack on IEEE 802.11i TKIP in November 2008, and this paper continues this line of protocol cryptanalysis. We show that their attack on TKIP can be used to create an ARP poisoning attack and a cryptographic DoS attack. Moreover, we are able to decrypt DHCP ACK packets, which are over 12 times longer than the ARP packet used by Beck and Tews. Our method of analysis recovers 596 bytes of keystream that can be used in new attacks on other control protocol messages.

Reproductive history and the risk of molecular breast cancer subtypes in a prospective study of Norwegian women

PurposeBreast cancer can be classified into molecular subtypes that differ in clinical characteristics and prognosis. There is some but conflicting evidence that reproductive risk factors may differ between distinct breast cancer subtypes.MethodsWe investigated associations of reproductive factors with the risk for six molecular breast cancer subtypes in a cohort of 21,532 Norwegian women who were born between 1886 and 1928 and followed up for breast cancer incidence between 1961 and 2008. We obtained stored tumor tissue from incident breast cancers and used immunohistochemistry and in situ hybridization to classify 825 invasive tumors into three luminal subtypes [Luminal A, Luminal B (HER2−) and Luminal B (HER2+)] and three non-luminal subtypes [human epidermal growth factor receptor 2 (HER2) subtype, basal-like phenotype (BP) and five negative phenotype (5NP)]. We used Cox regression to assess reproductive factors and risk for each subtype.ResultsWe found that young age at menarche, old age at first birth and low parity were associated with increased risk for luminal breast cancer subtypes. For the HER2 subtype, we either found no association or associations in the opposite direction compared to the luminal subtypes. The BP subtype appeared to have a similar reproductive risk profile as the luminal subtypes. Breastfeeding was associated with a reduced risk for HER2 and 5NP subtypes, but was not associated with any other subtype.ConclusionsThe results suggest that molecular breast cancer subtypes differ in their reproductive risk factors, but associations with non-luminal subtypes are still poorly understood and warrant further study.

Mass screening for cervical cancer in Norway: evaluation of the pilot project

The Norwegian Department of Health and Social Affairs initiated a national screening program for cervical cancer in 1990, with all women aged 25 to 70 years to be offered cervical screening every three years. During the first three years of the program (November 1991–October 1994), all spontaneous cervical cytology in Norway was recorded at the Norwegian Cancer Registry. In addition, women in the counties of Vestfold and Sør-Trøndelag were invited individually to be screened. The aim of the present study was principally to evaluate the organizational aspects of a nationwide, population-based screening program for cervical cancer in Norway. Special attention was paid to the coverage, the attendance rate, and the cytologic findings in the two-county study area. A total of 1,581,379 Pap smears were recorded from November 1991 to October 1994. Most smears were taken from women under age 30 years (31.7 percent). About 25 percent of the women aged 25 to 29 years had more than one normal smear. In the study area, a coverage of about 71 percent in the age group 25 to 69 years was achieved. The pilot project also has shown that it is possible to recruit elderly women into screening. However, no difference was noted between the study and the reference area with regard to findings per smear of precursor lesions (CIN 3, modified SNOMED coding system). The experiences from three years of recording and the implementation of the pilot project have provided useful guidelines for the national screening which began in January 1995.