High PTEN gene expression is a negative prognostic marker in human primary breast cancers with preserved p53 function.

PURPOSE: PTEN is an important tumor suppressor in breast cancer. Here, we examined the prognostic and predictive value of PTEN and PTEN pseudogene (PTENP1) gene expression in patients with locally advanced breast cancer given neoadjuvant chemotherapy. METHODS: The association between pretreatment PTEN and PTENP1 gene expression, response to neoadjuvant chemotherapy, and recurrence-free and disease-specific survival was assessed in 364 patients with locally advanced breast cancer given doxorubicin, 5-fluorouracil/mitomycin, or epirubicin versus paclitaxel in three phase II prospective studies. Further, protein expression of PTEN or phosphorylated Akt, S6 kinase, and 4EBP1 was assessed in a subgroup of 187 tumors. RESULTS: Neither PTEN nor PTENP1 gene expression level predicted response to any of the chemotherapy regimens tested (n = 317). Among patients without distant metastases (n = 282), a high pretreatment PTEN mRNA level was associated with inferior relapse-free (RFS; p = 0.001) and disease-specific survival (DSS; p = 0.003). Notably, this association was limited to patients harboring TP53 wild-type tumors (RFS; p = 0.003, DSS; p = 0.009). PTEN mRNA correlated significantly with PTENP1 mRNA levels (r s = 0.456, p < 0.0001) and PTEN protein staining (r s = 0.163, p = 0.036). However, no correlation between PTEN, phosphorylated Akt, S6 kinase or 4EBP1 protein staining, and survival was recorded. Similarly, no correlation between PTENP1 gene expression and survival outcome was observed. CONCLUSION: High intratumoral PTEN gene expression was associated with poor prognosis in patients with locally advanced breast cancers harboring wild-type TP53.

Treatment with aromatase inhibitors stimulates the expression of epidermal growth factor receptor-1 and neuregulin 1 in ER positive/HER-2/neu non-amplified primary breast cancers.

While estrogens have been shown to modulate EGFR/HER-1 and HER-2/neu expression in experimental systems, the effects of estrogen deprivation on expression levels of the HER-receptors and the neuregulin (NRG)1 ligand in breast cancers remain unknown. Here, we measured EGFR/HER-1-4 and NRG1 mRNA in ER positive tumors from 85 postmenopausal breast cancer patients before and after two weeks (n=64) and three months (n=85) of primary treatment with an aromatase inhibitor (AI). In tumors lacking HER-2/neu amplification, quantitative real-time PCR analyses revealed EGFR/HER-1 and NRG1 to vary significantly between the three time points (before therapy, after 2 weeks and after 3 months on treatment; P≤0.001 for both). Pair-wise comparison revealed a significant increase in EGFR/HER-1 already during the first two weeks of treatment (P=0.049) with a further increase for both EGFR/HER-1 and NRG1 after 3 months on treatment (P≤0.001 and P=0.001 for both comparing values at 3 months to values at baseline and 2 weeks respectively). No difference between tumors responding versus non-responders was recorded. Further, no significant change in any parameter was observed among HER-2/neu amplified tumors. Analyzing components of the HER-2/neu PI3K/Akt downstream pathway, the PIK3CA H1047R mutation was associated with treatment response (P=0.035); however no association between either AKT phosphorylation status or PIK3CA gene mutations and EGFR/HER-1 or NRG1 expression levels were observed. Our results indicate primary AI treatment to modulate expression of HER-family members and the growth factor NRG1 in HER-2/neu non-amplified breast cancers in vivo. Potential implications to long term sensitivity warrants further investigations.

Atheroembolization and potential air embolization during aortic declamping in open repair of a pararenal aortic aneurysm: A case report.

INTRODUCTION: When ischemic events ascribable to microembolization occur during open repair of proximal abdominal aortic aneurysms, a likely origin of atheroembolism is not always found. PRESENTATION OF CASE: A 78-year old man with enlargement of the entire aorta underwent open repair for a pararenal abdominal aortic aneurysm using supraceliac aortic clamping for 20min. Then the graft was clamped, the supraceliac clamp was removed, and the distal and right renal anastomoses were also completed. The patient was stable throughout the operation with only transient drop in blood pressure on reperfusion. Postoperatively the patient developed ischemia, attributable to microembolization, in legs, small intestine, gall bladder and kidneys. He underwent fasciotomy, small bowel and gall bladder resections. Intestinal absorptive function did not recover adequately and he died after 4 months. Microscopic examination of hundreds of intestinal, juxtaintestinal mesenteric, and gall bladder arteries showed a few ones containing cholesterol emboli. DISCUSSION: It is unsure whether a few occluded small arteries out of several hundred could have caused the ischemic injury alone. There had been only moderate backbleeding from aortic branches above the proximal anastomosis while it was sutured. Inadvertently, remaining air in the graft, aorta, and aortic branches may have been whipped into the pulsating blood, resulting in air microbubbles, when the aortic clamp was removed. CONCLUSION: Although both atheromatous particles and air microbubbles are well-known causes of iatrogenic microembolization, the importance of air microembolization in open repair of pararenal aortic aneurysms is not known and need to be studied.

The hazard of sharp force injuries: Factors influencing outcome.

The risk of dying from sharp force injury is difficult to ascertain. To the best of our knowledge, no study has been performed in Norway regarding mortality due to sharp force injury or factors that impact survival. Thus, the objective of the present study was to investigate and assess mortality in subjects with sharp force injury. This retrospective study comprises data on 136 subjects (34 female, 102 male) with suspected severe sharp force injury (self-inflicted or inflicted by others) admitted to Haukeland University Hospital between 2001 and 2010. The majority of subjects were intoxicated, and the injury was most often inflicted by a knife. The incidence of sharp force injury in Western Norway is similar to the incidence in other European countries. Almost half of the subjects with self-inflicted injury died. In cases with injury inflicted by another individual, one in five died. Mortality rates were higher in those with penetrating chest injuries than those with penetrating abdominal injuries and higher in cases with cardiac injury compared to pleural or lung injury. Sharp force injury can be fatal, but the overall mortality rate in this study was 29%. Factors influencing mortality rate were the number of injuries, the topographic regions of the body injured, the anatomical organs/structures inflicted, and emergency measures performed.

Deaths from violent causes and accidents in Hordaland County 2003-04.

BACKGROUND: Studies of the epidemiology of deaths from violent causes can provide valuable information for the treatment of traumas. We wished to ascertain whether the victims had survivable injuries and were accessible for treatment at the time of discovery of the injury. The purpose was to identify areas of intervention that may help save lives. MATERIAL AND METHOD: An overview of deaths from violent causes in Hordaland County in 2003 and 2004 was retrieved from the Cause of Death Registry, and information from autopsy records, hospital records and police reports was reviewed. In each case, an assessment was made of whether the injuries were survivable. If the patient was alive and could be reached and treated at the time when the incident was reported, he/she was defined as accessible for treatment. RESULTS: Altogether 191 deaths were included. We assessed the injuries as survivable in 26 cases. A total of 18 of these 26 patients were also assessed as accessible for treatment. All of these 18 patients died from falls or traffic accidents. 11 of the 18 patients were in the age group 75 years or older; this age group accounted for 41 cases (21.5%) of the total material. The records showed that in 12 of these 18 cases, it had been decided following an overall assessment not to initiate, or to discontinue, further life-saving treatment. INTERPRETATION: A small number of patients were deemed to have sustained survivable injuries while also being accessible for treatment. The results indicate that primarily efforts to prevent injuries will help reduce the number of deaths from violent causes.