A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer

Complex focal chromosomal rearrangements in cancer genomes, also called “firestorms”, can be scored from DNA copy number data. The complex arm‐wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA‐based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high‐grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER−) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62–2.32) for BCSS, and of 1.49 (95%CI, 1.30–1.71) for OS. Representations of the 70‐gene and the 21‐gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23–1.99) for ER+ and 1.55 (95%CI, 1.11–2.18) for ER− disease. None of the expression‐based predictors were prognostic in the ER− subset. We found that a model including CAAI and the two expression‐based prognostic signatures outperformed a model including the 21‐gene and 70‐gene signatures but excluding CAAI. Inclusion of CAAI in the clinical prognostication tool PREDICT significantly improved its performance. CAAI positive ovarian cancers (52%) also had worse prognosis: HRs of 1.3 (95%CI, 1.1–1.7) for PFS and 1.3 (95%CI, 1.1–1.6) for OS. This study validates CAAI as an independent predictor of survival in both ER+ and ER− breast cancer and reveals a significant prognostic value for CAAI in high‐grade serous ovarian cancer.     

Outcome of Negative-Pressure Wound Therapy for Open Abdomen Treatment After Nontraumatic Lower Gastrointestinal Surgery: Analysis of Factors Affecting Delayed Fascial Closure in 101 Patients

Background

Few studies have focused on the risk factors for failure to achieve fascial closure after use of negative-pressure wound therapy (NPWT) in an open abdomen (OA). We aimed at analyzing possible risk factors for failure of fascial closure and the risk of fistulas after nontrauma lower gastrointestinal (GI) tract surgery treated with OA.

Methods

This retrospective study included 101 nontrauma patients treated with OA from 2007 to 2011. Multivariate analyses of risk factors were performed.

Results

Indications for OA were diffuse peritonitis (n = 47), need for second look (n = 26), failure to achieve fascial closure (e.g., bowel edema) at primary laparotomy (n = 24), and fascial necrosis (n = 4). Of the 101 patients, 61 (60 %) were alive at discharge, with one death possibly related to OA (fistula from an iatrogenic perforation). Delayed fascial closure was obtained in 40 (66 %) of the surviving patients, with 80 % when the indications for OA was need for second look and 72 % in cases of diffuse peritonitis. Compared with need for second look [hazard ratio (HR = 1), 95 % CI], proportional HR for failure of delayed fascial closure were peritonitis 1.96 (1.10–3.49) and failure to achieve fascial closure at primary laparotomy 4.70 (2.17–10.2). In the presence of a stoma the HR was 2.02 (1.13–3.63).

Conclusions

OA using NPWT seems to be a safe procedure, with few procedure-related complications. Failure of fascial closure is related to the indication of OA and the presence of a stoma. Prospective multicenter studies are needed to establish which patients with lower GI surgery benefit from OA.     

The prognostic effect of smoking status on intensively treated acute myeloid leukaemia – A Danish nationwide cohort study

With rising life expectancy, the importance of patient-related prognostic factors and how to integrate such data into clinical decision-making becomes increasingly important. The aim of this study was to evaluate the prognostic impact of smoking status in patients with acute myeloid leukaemia (AML) treated with intensive chemotherapy. We conducted a nationwide cohort study based on data obtained from the Danish National Leukaemia Registry (DNLR). The study comprised Danish patients aged 18–75 years, diagnosed with AML between 1 January 2000 and 31 December 2012. Medical records were reviewed and data on smoking status were collected. A total of 1040 patients (median age 59 years) were included, and 602 patients (58·9%) were categorised as ever-smokers and the remaining as never-smokers. Kaplan–Meier survival estimates revealed that ever-smokers had a significant shorter median overall survival (OS) at 17·2 months [95% CI (14·9;19·1)] compared to never-smokers at 24·5 months (95% CI [19·2;30·7]). Multivariate analysis revealed smoking status as a significant prognostic factor for inferior OS with a hazard ratio (HR) of 1·22 [95% CI (1·04;1·44)]. In conclusion, smoking status was found to be associated with inferior OS in intensively treated AML patients.     

Job strain and cardiovascular risk factors: a cross sectional study of employed Danish men and women.

As part of the World Health Organisation initiated MONICA project, 2000 men and women aged 30, 40, 50, and 60 from the general population were invited to undergo a medical examination with special emphasis on cardiovascular disease. A total of 1504 (75%) participated, 1209 of whom were employed. The participants answered a questionnaire on working, social, and health conditions and underwent clinical examinations that included the measurement of blood pressure and serum cholesterol, triglyceride, high density lipoprotein, fibrinogen, and glycated haemoglobin (HbA1C) concentrations. Using the demand-control model for measuring job strain suggested by Karasek, the employed people were classified according to those who had suffered job strain and those who had not in two different ways. The subjective classification was based on the participants' statements regarding demand and control in their jobs whereas the objective classification was based on job title and mode of payment. More women than men were classified as having high strain jobs. After adjusting for age and sex no significant association was found between coronary risk factors and subjective job strain. A tendency for an association between fibrinogen and job strain was found. Body mass index and HbA1C concentration were significantly associated with objective job strain independent of confounders.