Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study.

Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About one third (35%) of the Turkish/Moroccan patients fulfilled criteria for breast cancer genetic counseling, compared to 21% of the comparative group (P = 0.001); this was largely due to a relatively young age at diagnosis in the migrant group (26% <40 years vs 5% in the comparative group, P = 0.0001). Uptake of genetic counseling among eligible patients was 47% in the migrant group and 56% in the comparative group; differences in uptake were seen among the patients diagnosed before 40 years of age (48% in the migrant group vs 81% in the comparative group; P = 0.021). When adjusted for age at diagnosis, ethnicity was associated with discussing referral to genetic counseling and its actual uptake. The Turkish/Moroccan ethnicity appears to be associated with a lower uptake of genetic counseling, mainly caused by the lower uptake in the young age-group. The major barrier to participation in genetic counseling seems to lie within the referral process.

Systemic inflammatory response in acute cholangitis and after subsequent treatment.

OBJECTIVE: To measure the concentrations of endotoxin and inflammatory mediators during an attack of acute cholangitis and see what effect endoscopic treatment had on these mediators. DESIGN: Prospective study. SETTING: University teaching hospital The Netherlands. SUBJECTS: Ten patients with acute cholangitis. INTERVENTIONS: Measurements were made during the attack and 1 week after endoscopic treatment. MAIN OUTCOME MEASURE: Changes in clinical variables, and severity of biliary obstruction. Concentrations of endotoxin, cytokines, and endotoxin binding proteins, in plasma. RESULTS: The causes of cholangitis were obstructed endoprosthesis (n = 4) and stones (n = 6). The median bilirubin concentration during the attack was 70.0 micromol/L (range 14-156) and 14.5 micromol/L (range 9-80) after treatment (p < 0.05). Median (range) plasma endotoxin concentrations were 3.6 pg/ml (3.2-107) and 3.6 (2.4-5), respectively. Concentrations of cytokines were high during the acute attack and significantly lower after treatment: median tumour necrosis factor (TNF) fell from 44.6 pg/ml (range 1.2-403) to 7.3 (0-53); soluble TNF receptor p55 from 4.9 ng/ml (2.7-13.8) to 3.6 (1.4-8.2) and TNF receptor p75 from 11.6 ng/ml (7.1-40.6) to 8.1 (2.9-31.3); interleukin 6 (IL-6) fell from 690 pg/ml (34.1-4594) to 8.2 (0-39.3), IL-8 from 226.2 pg/ml (31.6-712.7) to 21.4 (4.2-63.5) and IL-10 from 33.4 pg/ml (2.7-5605) to 4.7 (0-16.7) (p < 0.03). Values for lipopolysaccharide binding protein and soluble CD14 also fell significantly (p < 0.01) from 86.5 (43.4-200) to 21.5 (11.3-37.5) and from 200 (59-200) to 47.8 (0.47-200), respectively. The concentration of bactericidal permeability increasing protein did not change significantly, being 7.1 (2-18.9) during the acute attack and 4.6 (0.8-17.7) a week later. CONCLUSION: There is a considerable systemic inflammatory response during cholangitis, which is dramatically reduced one week after endoscopic treatment.

Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage.

BACKGROUND: Obstructive jaundice is associated with postoperative complications related to increased endotoxaemia and the inflammatory response. In animals obstructive jaundice is associated with endotoxaemia and cytokine induction, which are reversed by internal biliary drainage. AIMS: To study endotoxaemia and the subsequent inflammatory response in obstructive jaundiced patients and after endoscopic biliary drainage. METHODS: In 15 patients with malignant distal obstructive jaundice, inflammatory and bacteriological parameters were assessed before endoscopic stent placement and after three weeks endoscopic drainage. RESULTS: Drainage reduced bilirubin from 252.5 to 45.1 micromol/l. At baseline low level endotoxaemia was detected (4.3 pg/ml) which was not affected after drainage (4.5 pg/ml). Serum interleukin 8 (IL-8) and endotoxin binding proteins were increased in jaundice and reduced after drainage (IL-8 113.6 to 20.7 pg/ml; lipopolysaccharide binding protein 24.2 to 16.5 microg/ml; sCD14 17.4 to 7.6 microg/ml; bactericidal/permeability increasing protein 2.9 to 1.8 ng/ml). Levels of other cytokines, augmented in animals, were only slightly increased and not changed after drainage (tumour necrosis factor (TNF): 21.7 and 18.4 pg/ml; sTNFr p55/75: 2.9/7.0 and 2.7/5.6 ng/ml; IL-6: 4.2 and 6.1 pg/ml; IL-10: 4.5 and 2.7 pg/ml). Elastase and lactoferrin tended towards reduction after drainage. All bile cultures were positive after stenting. CONCLUSIONS: The effects of obstructive jaundice in humans on endotoxin and cytokines are different from those in animal models. Obstructive jaundice causes alterations in circulating endotoxin binding proteins and IL-8. Concentrations of other mediators (TNF, previously suggested as being responsible for systemic endotoxaemia effects) are low and not affected by drainage.

Treatment with recombinant bactericidal/permeability-increasing protein to prevent endotoxin-induced mortality in bile duct-ligated rats.

BACKGROUND: Operation in patients with obstructive jaundice is associated with substantial morbidity because of increased susceptibility to endotoxin (lipopolysaccharide) and the inflammatory cascade. Different interventions to reduce endotoxemia and cytokine induction, and resulting complications, have been studied. Bactericidal/permeability-increasing protein (BPI) is a naturally occurring endotoxin-binding protein produced in neutrophils. It binds endotoxin, neutralizing the activity and inhibiting cytokine production by mononuclear cells. In experimental endotoxemia in animals and in healthy human volunteers, BPI has shown a protective effect. The aim of this study was to determine whether BPI could protect against increased endotoxin sensitivity in rats with obstructive jaundice and reduce endotoxin-induced mortality. STUDY DESIGN: Male Wistar rats were used. Intraperitoneal Escherichia coli 2mg/kg was given 1 week after sham operation or bile duct ligation (BDL). Three groups were studied: sham, BDL with placebo, and BDL with 5 mg/kg recombinant BPI21. RESULTS: BDL rats were jaundiced (mean bilirubin 186 micromol/L; no difference between BDL rats without or with BPI). Bilirubin remained less than 1 micromol/L in sham-operated rats (p = 0.002). Endotoxin levels were 3.4pg/mL in sham controls and 3.1 pg/mL in BDL rats before administration of lipopolysaccharide (p = NS). Two hours after administration, levels were 615.4ng/mL in placebo BDL rats and 10 times less in BPI-treated BDL rats, at 60.2ng/mL (p=0.03). The same trend was found at 6 hours. At 24 hours, mortality was 1 of 6 in sham-operated rats (15%) versus 8 of 11 in untreated BDL rats (75%). BPI intervention reduced the death rate to 1 of 12 BDL rats (8%) (p = 0.003). CONCLUSIONS: Intraperitoneal recombinant BPI21 in rats having BDL reduced endotoxin-induced mortality from 75% to 8%, a death rate comparable to that in nonjaundiced rats. BPI could be an interesting perioperative treatment in clinical obstructive jaundice.

Staging of ampullary and pancreatic carcinoma: comparison between endosonography and surgery.

BACKGROUND: The aim of the study was to update our previously published data on the clinical TNM staging of ampullary and pancreatic carcinoma by endosonography. METHODS: Endosonography was performed in 70 patients with pancreatic cancer and in 32 patients with ampullary carcinoma. TNM staging was carried out before surgery and compared with findings of histology and/or surgery. RESULTS: Endosonography was accurate in staging the depth of tumor invasion. Early-stage carcinomas could be distinguished from advanced cancers. Nonresectability was accurately assessed on the basis of vascular involvement using real-time ultrasound. Tumor compression due to peritumoral pancreatitis and direct tumor invasion into the base of the mesocolon could not be diagnosed by endosonography. The overall accuracy in tumor staging for pancreatic and ampullary carcinomas was 83.6% and 84.4%, respectively. Endosonography was accurate in diagnosing regional lymph node metastases but not accurate in defining nonmetastatic lymphadenopathy and distant metastases. CONCLUSION: Endosonography was accurate in staging tumor stage and lymph node metastases. Minimally invasive methods of resection for superficial ampullary cancers should be based on endosonography staging.

Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein.

To investigate the effects of a recombinant endotoxin-binding protein, bactericidal/permeability-increasing protein (rBPI23), on cytokine release and neutrophil activation in endotoxemia in humans, 8 volunteers were challenged twice with endotoxin and concurrently received either rBPI23 or placebo in a randomized, placebo controlled, double-blind crossover study, rBPI23 treatment significantly lowered circulating endotoxin levels (P = .02) and resulted in a significant reduction in the release of tumor necrosis factor (TNF), soluble TNF receptors p55 and p75, interleukin (IL)-6, IL-8 (P < .01 for each), and IL-10 levels (P = .02) but did not prevent the endotoxin-induced rise in body temperature. The early endotoxin-induced leukopenia was blunted (P = .08), and neutrophil degranulation, as measured by circulating levels of elastase/alpha 1-antitrypsin complexes (P = .03) and lactoferrin (P < .01), was largely prevented by rBPI23. The results of this study indicate that rBPI23 is capable of neutralizing many of the biologic effects of endotoxin in humans.