Parity in relation to risk of axillary lymph node involvement in women with breast cancer. Results from Swedish population-based series of 3,472 consecutive cases.

OBJECTIVE: To investigate the association between parity and axillary lymph node involvement (ALNI) at breast cancer diagnosis. METHODS: One surgeon has reviewed all breast cancer cases in Malmo, Sweden, diagnosed 1961-1991. This study includes the 3,472 women who had a first-time diagnosis of unilateral invasive breast cancer, and who had undergone axillary dissection. Information was collected regarding date of birth, date of diagnosis, age at diagnosis, menopausal status, tumour size, histological type, tumour location, type of surgery, stage (ALNI), and parity. Parity was investigated in relation to ALNI using logistic regression analysis, adjusted for potential confounders, yielding odds ratios (OR) with 95% confidence intervals (CI). The analyses were repeated in different strata with regard to birth-years cohort, age at diagnosis, and period of diagnosis. RESULTS: High parity was associated with ALNI, the adjusted OR for ALNI among women with 4 or more children was 1.56 (1.13-2.15). This association was stronger in comparatively old women (> or = 67.45 years), OR 1.78 (1.10-2.88). Considering parity a continuous variable, the OR for ALNI among all women was 1.06 (1.01-1.12). CONCLUSIONS: We conclude that women with 4 or more children had an increased risk of ALNI at breast cancer diagnosis.

Tumour location and axillary lymph node involvement in breast cancer: a series of 3472 cases from Sweden.

AIM: This study investigates the potential relation between breast cancer location and axillary lymph node involvement (ALNI). METHODS: Out of all cases with unilateral first-time diagnosis of invasive breast cancer in Malmö, Sweden, between 1961 and 1991, 3472 underwent axillary dissection. The association between tumour location and ALNI was investigated using logistic regression analysis (adjusted for potential confounders) yielding odds ratios (OR), with a 95% confidence interval. All analyses were repeated in different birth-year cohorts. RESULTS: Outer tumours (upper outer or lower outer quadrants), as compared to inner (upper inner and lower inner quadrants), were associated with a statistically significant risk of ALNI, OR: 1.31 (1.11-1.55). Central tumours were also associated with ALNI, OR: 2.61 (2.08-3.27). Among women born before 1909, corresponding OR:s for outer tumours was 1.61 (1.19-2.18), and for central tumours 3.50 (2.32-5.28). CONCLUSIONS: Outer and central breast tumours are associated with a high risk of axillary lymph node involvement.

Breast conservation surgery, with and without radiotherapy, in women with lymph node-negative breast cancer: a randomised clinical trial in a population with access to public mammography screening.

The effect of postoperative radiotherapy after sector resection for stage I-II lymph node-negative breast cancer was evaluated in a patient population with access to public mammographical screening. 1187 women were randomised to no further treatment or postoperative radiotherapy following a standardised sector resection and axillary dissection. Radiation was administered to a dose of 48-54 Gy. Median age was 60 years, and median size of the detected tumours was 12 mm. Of the women 65% had their tumours detected by mammographical screening. The relative risk (RR) of ipsilateral breast recurrence was significantly higher in the non-irradiated patients compared with the irradiated patients, RR=3.33 (95% Confidence Interval (CI) 2.13-5.19, P<0.001). The corresponding cumulative incidence at 5 years was 14% versus 4%, respectively. Overall survival (OS) was similar, RR=1.16 (95% CI 0.81-1.65, P=0.41), with 5 year probabilities of 93 and 94%, respectively. Recurrence-free survival (RFS) at 5 years was significantly lower in the non-irradiated women, 77% versus 88% (P<0.001). Although women above 49 years of age, whose tumours were detected with mammographical screening, had the lowest rate of ipsilateral breast recurrence in this study, the cumulative incidence of such event amounted to 10% at 5 years if radiotherapy was not given. Such a recurrence rate has been considered as unacceptably high, but is, however, in the same range as that reported after lumpectomy and postoperative radiotherapy in published series.

Increasing incidence of and declining mortality from breast carcinoma. Trends in Malmö, Sweden, 1961-1992.

BACKGROUND: The incidence of breast carcinoma is increasing in most populations, whereas mortality caused by this disease is fairly constant. The authors analyzed the incidence of and mortality from invasive breast carcinoma in a population with access to good medical care, into which mammographic screening was introduced in 1976 and adjuvant therapy in 1978. METHODS: In a consecutive series of patients with invasive breast carcinoma from Malmö, 1961-1991, changes in age-adjusted incidence were analyzed and compared with incidence of the disease in the rest of Sweden. Age-adjusted breast carcinoma mortality was studied for the period 1964-1992. RESULTS: The introduction of mammographic screening was associated with an increase in breast carcinoma incidence. This was restricted to the age group that was eligible for screening (age 45-69 years) and to Stage I disease. Between 1977 and 1992, age-adjusted breast carcinoma mortality decreased in Malmö by 43% (95% CI, 26-56%) as compared with 12% (95% CI, 8-16%) in the rest of Sweden. The decrease was statistically significant in both populations and significantly greater in Malmö than in the rest of Sweden (P < 0.001). In Malmö the decrease was seen in two age groups, age 45-69 years and age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. There were no changes in incidence or mortality among women younger than 45 years in either population. CONCLUSIONS: Breast carcinoma incidence was strongly related to diagnostic activity, especially mammographic screening. The decrease in mortality occurred in temporal relation to the introduction of screening and adjuvant therapy, making a causal relation likely. The difference in results between Malmö and the rest of Sweden indicates an important role for screening in mortality reduction.

Breast cancer as cause of death--a study over the validity of the officially registered cause of death in 2631 breast cancer patients dying in Malmö, Sweden 1964-1992.

The validity of registered official cause of death (COD) concerning breast cancer patients in Malmö 1964-1992 was analysed. There was a high frequency of autopsy in the material and, therefore, the number of diagnostic errors should be low. Found discordance thus mostly reflect the quality of certifying and registration of COD. Of 2631 deaths discordance was found as to underlying COD in 121 cases (4.6%). Ninety-four of these represent outright errors. In 27 there was doubt about the reported COD. The number of discordant cases increased with age at death. Two kinds of systematic bias were found. One was a tendency to report breast cancer as contributing COD in patients with clinical cure. The other was a practice at the Registry to register breast cancer as underlying COD in cases with breast cancer reported as contributing COD. This practice was changed in 1981 causing an artificial decrease in registered breast cancer mortality.

Fibrin adhesive in radical mastectomy.

OBJECTIVE: To find out if fibrin adhesive glue applied locally would reduce the incidence of seroma after modified radical mastectomy for breast cancer. DESIGN: Prospective randomised study. SETTING: City hospital, Sweden. SUBJECTS: 68 women undergoing modified radical mastectomy with axillary clearance for breast cancer. MAIN OUTCOME MEASURES: Amount of postoperative drainage, number of seromas aspirated volumes; length of hospital stay, influence of surgeon operating. RESULTS: Seromas developed in a total of 40/68 patients (59%), 23/36 in the fibrin adhesive group (64%) and 17/32 in the control group (53%); p = 0.5 (95% confidence interval of the difference--0.13 to 0.34). There were no significant differences in the volume of aspirations or in hospital stay. The skill of the surgeon influenced the incidence of seromas, but the differences were not significant (p = 0.5). CONCLUSION: Local application of a fibrin adhesive glue has no effect on the incidence of seroma formation after modified radical mastectomy.

Relation between lightscanning and the histologic and mammographic appearance of malignant breast tumors.

The relation between real-time transillumination (lightscanning) and the histologic appearance of 243 breast carcinomas was evaluated. Lightscanning mainly failed in identifying ductal and lobular carcinomas in situ. The result of lightscanning was also poor regarding small, invasive carcinomas. The absorption patterns in elastosis and scar tissue associated with carcinoma played no important role in the ability of lightscanning to identify a cancer. The relation between the lightscanning and mammographic appearance of 85 breast cancers from the same material was also evaluated. Lightscanning performed poorly in identifying tumors characterized by classifications as compared to tumors with other mammographic appearances. However, the difference was not significant.

Diagnostic accuracy of lightscanning and mammography in women with dense breasts.

The diagnostic accuracy of lightscanning and mammography in 610 breasts with mammographically dense parenchymal patterns was investigated. Lightscanning identified 31 out of 36 cancers and mammography 32. Lightscanning and mammography were in agreement in 28 cases of cancer. One noninvasive lobular carcinoma was not identified by either modality. Four cancers were not correctly identified with lightscanning alone and 3 cancers with mammography alone. Of the 574 breasts without cancer, lightscanning falsely denoted 101 (18%) as possibly being cancerous (false-positives). The corresponding figure for mammography was 25 (4%). Thus, lightscanning, as performed in this study, has the same sensitivity as mammography in detecting cancer in mammographically dense breasts. However, its usefulness is limited by a low predictive value of a positive test (high rate of false-positives).

Lightscanning versus mammography for the detection of breast cancer in screening and clinical practice. A Swedish multicenter study.

State of the art lightscanning of the breast was tested against mammography in 2568 women in a Swedish multicenter study. The study was in two parts. One was in women with symptoms from the breasts (the clinical study) comprising 3178 examined breasts with 198 cancers; the other in asymptomatic women (the screening study) comprising 1909 examined breasts with 126 cancers. In women with symptoms from the breasts, lightscanning did not contribute to clinical examination and mammography. In the screening situation, it was poor to pick up small cancers. Mammography alone falsely diagnosed cancer in 6.9% of the patients whereas lightscan falsely diagnosed cancer in 19.1%. Lightscan was not better than mammography in young women. The study shows that lightscanning in its current form is inferior to standard mammography.

Local administration of human pancreatic secretory trypsin inhibitor prevents the development of experimental acute pancreatitis in rats and dogs.

The objective of this investigation was to test the capacity of recombinant human pancreatic secretory trypsin inhibitor (rhPSTI) to provide prophylaxis against experimental pancreatitis. Acute hemorrhagic pancreatitis was induced by intraductal injection of sodium taurocholate in rats and by intraductal injection of bile in dogs. In one treatment group of rats the injection of taurocholate was preceded by injection of rhPSTI. In a second group of rats the rhPSTI was given intraperitoneally starting 15 min after the induction of acute pancreatitis. The survival rate in a control group of rats was 13%. In contrast, the survival rate in groups receiving rhPSTI intraductally or intraperitoneally was 80% and 63%, respectively. The survival rate in a control group of dogs was 40% at 24 h and 0% at 48 h. In contrast, all the dogs receiving a single intraductal dose of rhPSTI, either immediately before the bile injection or mixed with the bile, survived for up to 6 weeks. Detailed biochemical and immunohistologic studies in the dog indicate that, whereas rhPSTI cannot prevent the initial bile-induced injury, it does prevent the subsequent development of that injury to the point where there is massive damage to the pancreas and the surrounding tissues, and changes in blood chemistry. The development of the initial injury is, therefore, presumed to involve activation of trypsinogen. Since rhPSTI prevents the serious consequences of experimental pancreatic injury by blocking the action of trypsin, and since the pathobiochemistry of human acute pancreatitis also implies an important role for trypsin, it is possible that rhPSTI could protect humans from the pancreatitis that complicates endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.

Malignant cystosarcoma phyllodes in a man treated with polyestradiolphosphate. Case report.

Cystosarcoma phyllodes is a rare breast tumor and only five cases have been previously reported in males. A case of cystosarcoma phyllodes in a man treated with polyestradiolphosphate for prostatic carcinoma and by radiation because of breast tenderness is presented. The tumor showed a malignant stroma histologically and the epithelial component was similar to a ductal carcinoma in situ. Electron microscopy revealed several cell types. The possible relationship to radiation and estrogen therapy is discussed.

Leukocyte elastase alpha 1-proteinase inhibitor complexes may diagnose pancreatic abscesses early.

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated by crossed immunoelectrophoresis of the peritoneal fluid from four patients who developed a pancreatic abscess during an attack of pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important. The appearance of these complexes denotes the liberation of large amounts of leukocyte elastase. This may help explain the pathophysiology and high mortality of the pancreatic abscess, since leukocyte elastase is known to cause degradation of all components of connective tissue and also degradation and activation of many components within the different cascade systems.

Early diagnosis of a pancreatic abscess in acute pancreatitis.

Complexes of alpha 1-proteinase inhibitor and leukocyte elastase could be demonstrated on crossed immunoelectrophoresis of the peritoneal fluid in 4 patients, who developed a pancreatic abscess during an attack of acute pancreatitis. No such complexes were seen in 69 patients with acute pancreatitis without an abscess. The complexes were demonstrable 2-3 days before the abscess was clinically evident. They may thus be diagnostically and therapeutically important.

Crohn's disease and small bowel diverticulosis in two sisters.

Small bowel diverticula may cause abdominal pain, diarrhoea, malabsorption and weight loss. The same symptoms are also seen in Crohn's disease. Two elderly sisters with simultaneous small bowel diverticulosis and Crohn's disease are presented.

Gabexate mesilate (FOY) and aprotinin. A comparative study of the effects on trypsin-induced activation of the kinin and complement systems in vivo and in vitro.

The effect of gabexate mesilate (FOY) was studied in vitro in human and canine serum upon the addition of trypsin, and in vivo in dogs during intravenous trypsin infusion. The effect of FOY was compared with the effect of aprotinin. FOY did not show any protection against trypsin-induced activation of the complement and kinin systems in vitro or in vivo, while aprotinin did. All dogs exhibited signs of circulatory shock together with a consumption of the two main proteinase inhibitors, alpha-macroglobulin and alpha 1-proteinase inhibitor, when intravenous infusions of FOY and trypsin were performed simultaneously. However, all dogs survived without signs of shock if aprotinin was given instead of FOY. The ineffectiveness of FOY in serum is explained by the complete dissociation of FOY trypsin complexes together with a rapid degradation of FOY to inactive metabolites. Although FOY is an effective proteinase inhibitor in defined buffer systems in vitro, the results of the present study indicate that it is not an effective proteinase inhibitor in vivo. Aprotinin protects against trypsin-induced activation reactions, although much higher concentrations are needed in human than in canine serum.

Aprotinin turn-over studies in dog and in man with severe acute pancreatitis.

The elimination of aprotinin after intravenous infusion was exponential until 95% of the dose was cleared from the plasma after 1 h in dogs with bile-induced pancreatitis. The half-life of this part of the elimination was 10 min. The concentration of aprotinin in the peritoneal fluid reached a maximum plateau after 1 h. Direct intra-abdominal infusion of aprotinin was followed by a relatively slow elimination of the inhibitor from the cavity. One hour after the infusion the concentration of aprotinin in the peritoneal exudate was about 50% of the initial value. Four hours later the concentration of inhibitor with unchanged immunoreactivity and inhibiting capacity was still about 25% of the initial value. Based on the results of this experimental study an intraperitoneal dosage schedule for aprotinin was tested in three patients with haemorrhagic pancreatitis. A total amount of 14 X 10(6) KIU was given in repeated dosages during 18 h. This resulted in a minimum level of aprotinin in the peritoneal exudate of about 10 mumol/l. According to our earlier published data this level should largely block trypsin-induced effects relevant in pancreatitis. In conclusion; due to the rapid elimination of aprotinin from plasma, after i.v. application a therapeutically useful concentration is never reached in the peritoneum, while the elimination from the peritoneum is relatively slow, thus providing therapeutically useful concentrations which can be maintained for some time after i.p. application.

On the role of the pancreatic secretory trypsin inhibitor as an inactivator of trypsin-alpha 2-macroglobulin complexes in acute pancreatitis.

High levels of immunoreactive pancreatic secretory trypsin inhibitor (PSTI) were demonstrated in the serum and peritoneal exudates of patients suffering from acute pancreatitis. Trypsin-like immunoreactivity in these fluids was found in complex with alpha 1-antitrypsin and in complex with alpha 2-macroglobulin and also as a free peak correlating to free trypsin(ogen). No trypsin-PSTI complexes or PSTI were demonstrated in the macroglobulin fraction of the peritoneal exudates. Saturated and partially saturated trypsin-alpha 2-macroglobulin complexes were prepared in vitro. PSTI was able to partially inhibit the BzArgNan-cleaving activity of both types of complexes in a slow dose-dependent non-linear reaction. Equilibrium was reached in each case within 1 h, but total inhibition was not reached even with large amounts of PSTI. Partially saturated trypsin-alpha 2-macroglobulin complexes were inhibited more readily than saturated complexes. The results support the concept of PSTI acting as a strictly local inhibitor of trypsin in compartments lacking plasma protease inhibitors.