Occurrence of beta-hexachlorocyclohexane in breast cancer patients.

The residues of polycyclic aromatic hydrocarbon (PAH) and neutral organochlorine compounds in breast fat of 44 breast cancer patients and 33 women free of cancer were determined. No statistically significant differences appeared between the two comparison groups with regard to occurrence of PAH compounds. Of the neutral organochlorine compounds, residues of beta-hexachlorocyclohexane (HCH) were found more frequently in breast cancer patients. After adjusting for age and parity by stepwise logistic regression, beta-HCH remained a significant risk factor of breast cancer. Using a cutoff point for the residue level of beta-HCH in breast adipose tissue of more than 0.1 mg/kg fat, the odds ratio was 10.51 (95% CI, 2.00-55.26).

A new site for totally implanted central venous access system in patients with malignancy: long-term results of 10 cases.

In this study of 10 patients with central venous access system, the reservoir body was implanted in the lower limb. Only one complication was observed per 1,560 days of function time. The anterolateral distal half of the thigh is a good alternative site for the injection port in cancer patients whose jugular veins and veins in the arms are not available owing to a tumour or previous treatments.

Analysis of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen levels in cytosol and KCl-nuclear extracts of breast tumours from tamoxifen treated patients by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).

Tamoxifen, 4-hydroxytamoxifen and desmethyltamoxifen levels were measured in cytosolic and 0.5 M KCl extracted nuclear fractions from a small series of breast tumours from tamoxifen treated patients by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). Tamoxifen and desmethyltamoxifen were the most abundant metabolites. There was a small increment in the relative abundance of 4-hydroxytamoxifen in the nuclear extract over cytosol relative to both tamoxifen and desmethyltamoxifen. Further, there was a selective retention of tamoxifen relative to desmethyltamoxifen in the nuclear extract relative to the cytosol. It is concluded that all three compounds could potentially contribute to estrogen receptor mediated antiestrogenic effects in this target tissue.

Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM).

A method for the analysis of tamoxifen and its metabolites in plasma from tamoxifen treated breast cancer patients, by capillary GC-MS using selected ion monitoring has been developed. Metabolite extraction was carried out on a Sep-pak C18 cartridge and metabolite purification by selective ion exchange chromatographic steps. Satisfactory recovery of radioactive standards through the extraction and purification steps was obtained. The method was shown to be accurate and precise with precision coefficient of variation values ranging from 4.3-11% for tamoxifen and its metabolites. Tamoxifen, 4-hydroxytamoxifen, metabolite Y and N-desmethyltamoxifen were identified with certainty in patient plasma on the basis of GC relative retention times and mass spectral comparison with authentic standards; because of their low abundance in plasma cis-metabolite E and 3,4-dihydroxytamoxifen could only be tentatively identified but identical GC behaviour and a satisfactory comparison of the abundance of key fragment ions was achieved. The tamoxifen and metabolite concentration ranges (ng X ml-1) in the group of patients who received 40 or 80 ng tamoxifen for 14 days were tamoxifen, 307-745; N-desmethyltamoxifen, 185-491; 4-hydroxytamoxifen, 1.4-2.5; 3,4-dihydroxytamoxifen, 0.7-2.0; metabolite Y, 19.0-112; and metabolite E1, 0.9-2.0.

Effect of splenectomy on circulating haematopoietic progenitors in myelofibrosis.

The effect of splenectomy on peripheral blood CFU-GM and BFU-E numbers was studied in a patient with myelofibrosis. The numbers of CFU-GM and BFU-E were twice as high in the splenic venous blood as in the peripheral blood. The number of CFU-GM in peripheral blood decreased to 20% and that of BFU-E to 7% of the presplenectomy level at 1 wk after the operation. The progenitor numbers recovered to reach the presplenectomy level within 4-6 w after splenectomy. This effect of splenectomy was different from that seen in 3 patients with Hodgkin's disease, in whom increased numbers of progenitors were observed after a small initial notch.

Cytochemical demonstration of estrogen binding sites in breast cancer by estradiol covalently linked to horseradish peroxidase.

17 beta-Estradiol-6-carboxymethyloxime was covalently linked to horseradish peroxidase for the cytochemical demonstration of estrogen binding sites in breast cancer tissue. The affinity of the 17 beta-estradiol-horseradish peroxidase (E2-HRP) conjugate for the estrogen receptor in a human myometrial cytosol preparation was reduced by a factor of about 16 relative to that of 17 beta-estradiol. The estradiol concentration of the E2-HRP conjugate used in the incubations was in the range 2 X 10(-9) -1 X 10(-7) mol/l which, when the reduced affinity of the conjugate is taken into account, corresponds to 1 X 10(-10) -7 X 10(-9) mol/l unbound estradiol. The cytochemical reaction was carried out on cytofuge preparations of cell suspensions of breast cancer tissue. The intensity of the cytochemical reaction was microscopically evaluated by scoring. The results were analyzed in a plot allowing the calculation of an apparent score-max and an apparent Kd value. The reaction intensity was reduced to 20-25% of the control level by a 20-fold excess of 17 beta-estradiol. The cytochemical results correlated positively with the content of estrogen receptors in the cytosol as measured by a validated radioligand method.

Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate.

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.

A randomized double-blind study using CaNa2EDTA, a phospholipase A2 inhibitor, in the management of human acute pancreatitis.

In a randomized double-blind study the effect of CaNa2EDTA, a phospholipase A2 inhibitor, was tested as a treatment for acute pancreatitis. CaNa2EDTA was infused intravenously during the first 2 days after admission to hospital, in addition to normal conservative treatment. CaNa2EDTA decreased the serum phospholipase A2 activity and appeared to promote recovery from the illness. To what extent the inhibition of serum phospholipase activity may prevent the progress of severe haemorrhagic pancreatitis or diminish mortality and morbidity in acute pancreatitis should be investigated in further studies.

Determination of axillary nodal status in surgery of breast carcinoma: a prospective study of thirty-five patients.

Thirty-seven axillary status of patients with breast carcinoma was studied with preoperative and peroperative palpation before mastectomy and total axillary dissection. Special attention was paid to the clinical suspiciousness and size of axillary nodes. The preoperative axillary palpation gave false diagnosis of axillary content 27% of the time and peroperative, 19%. Of all 249 nodes studied, 54 were found to contain malignant growth in routine histological examination. Mean diameter of malignant nodes was 12.4 mm and of benign nodes, 6.3 mm. The most clinically suspect axillary lymph node gave correct diagnosis of axillary status in 72% of the cases. The 2 most suspect lymph nodes together were positive in 89%. There was no case with histologically positive axilla where none of the 3 most suspect lymph nodes was malignant. We conclude that at least the 3 most suspect axillary lymph nodes must be removed for histological examination to be sure that axillary metastasizing of breast carcinoma can be found by routine histological examination.

Peroperative fine needle aspiration biopsy of lung tumors.

The feasibility and reliability of peroperative fine needle aspiration biopsy of lung tumors were studied in a series of 54 patients. The postoperative histologic examination confirmed that 47 of the lesions were malignant. The cytologic examination also showed malignancy in 45 of these cases. The accuracy of fine needle cytology thus was 96%. In the two false negative reports the classification was Papanicolaou grades II and III. The cytologic classification of the histologically benign lesions was only grades I or II. Thus there were no false positive cytologic results. No complications arose from the needle biopsies. Peroperative fine needle aspiration biopsy at thoracotomy is rapid, simple and safe, and has a high degree of accuracy. It is diagnostically useful in cases without preoperative confirmation of suspected lung tumor if excisional biopsy is judged to be hazardous or unlikely to yield a definite diagnosis. The method permits the surgeon to assess the extent of a malignancy and can specify the cell type of the tumor.

Phospholipase A2 inhibitors and their possible clinical use in the treatment of acute pancreatitis.

A laboratory method was established for measurement of phospholipase A2 activity in buffer and serum. A series of different phospholipase A2 inhibitors was tested. The most effective inhibitors were Ca2+ chelating compounds like EDTA, DTPA, EGTA, and phytic acid. The calcium salt of EDTA also has some inhibitory effect. Serum phospholipase A2 activity in normal healthy control patients was measured. The activity in 27 patients with acute pancreatitis was tested. The activity was abnormally high in five patients. This activity was in vitro inhibited by EDTA and partly by CaNa2EDTA. The clinical picture of these patients did not differ from that of phospholipase-A2-negative patients. Six patients with acute pancreatitis were treated by intravenous infusion of CaNA2EDTA. Two of them had haemorrhagic pancreatitis and two were suspected of having early haemorrhagic pancreatitis. During the CaNa2EDTA infusion serum amylase and phospholipase A2 activities decreased. All patients recovered. No harmful side effects were noticed.