Gene expression profiles of breast cancer metastasis according to organ site

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry‐based groups. Second, HER2‐low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype‐related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ‐specific and subtype‐independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.     

Effect of different doses of iron supplementation during pregnancy on maternal and infant health

Currently, there is no consensus regarding the optimum iron supplementation during pregnancy. The aim of this study is to evaluate the effect of different iron supplementation doses (including no supplementation) during pregnancy on the iron status of the mother and on the health of the neonate. A longitudinal study was conducted involving 358 pregnant women and their newborns. Mothers were classified as non-supplemented, low iron supplemented (<60 mg/day), moderate iron supplemented (between 60 and 100 mg/day) or high iron supplemented (>100 mg/day). General clinical and obstetric histories, haemoglobin (Hb), serum ferritin (SF) and transferrin saturation were evaluated in the first, second, third trimesters, and at partum. SF and Hb decreased less sharply in the iron-supplemented groups compared to the non-supplemented group. The higher the doses of iron supplementation, the lower the percentages of iron depletion at partum (p?<?0.001), iron deficiency anaemia (p?<?0.001) and preterm deliveries (p?=?0.009) as well as a higher birth weight of the newborn. However, the group with high supplementation had a greater percentage (27.6 %) of women at risk of haemoconcentration at partum. Our Mediterranean women began gestation with iron stores close to deficit (SF, 28.1 μg/L; 95 % CI 27.9–28.4). With these iron stores, supplementation with iron at daily doses of between 60 and 100 mg appears to be the most beneficial for the health of mother and child. These findings need to be confirmed in further randomised clinical trials.     

Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling

Most patients with tuberous sclerosis complex (TSC) develop cortical tubers that cause severe neurological disabilities. It has been suggested that defects in neuronal differentiation and/or migration underlie the appearance of tubers. However, the precise molecular alterations remain largely unknown. Here, by combining cytological and immunohistochemical analyses of tubers from nine TSC patients (four of them diagnosed with TSC2 germline mutations), we show that alteration of microtubule biology through ROCK2 signalling contributes to TSC neuropathology. All tubers showed a larger number of binucleated neurons than expected relative to control cortex. An excess of normal and altered cytokinetic figures was also commonly observed. Analysis of centrosomal markers suggested increased microtubule nucleation capacity, which was supported by the analysis of an expression dataset from cortical tubers and control cortex, and subsequently linked to under‐expression of Rho‐associated coiled‐coil containing kinase 2 (ROCK2). Thus, augmented microtubule nucleation capacity was observed in mouse embryonic fibroblasts and human fibroblasts deficient in the Tsc2/TSC2 gene product, tuberin. Consistent with ROCK2 under‐expression, microtubule acetylation was found to be increased with tuberin deficiency; this alteration was abrogated by rapamycin treatment and mimicked by HDAC6 inhibition. Together, the results of this study support the hypothesis that loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd     

Obesity and postmenopausal bone loss: The influence of obesity on vertebral density and bone turnover in postmenopausal women

This study was undertaken to evaluate the effect of obesity on the postmenopausal bone mass. Bone mineral density, measured by dual photon absorptiometry of the lumbar spine, serum osteocalcin (OC), fasting urinary calcium to creatinine (Ca:Cr), serum estradiol (E2) dehydroepiandrosterone (DHA) and testosterone (T) were measured in 176 women aged 45–71 years. Women were divided into four groups according to their menopausal status and their weight: 49 perimenopausal, 28 obese perimenopausal, 49 obese postmenopausal. Within each population (perimenopausal and postmenopausal), mean age was the same, only weight was significantly different (p < 0.0001). For the two groups of postmenopausal women mean interval since menopause (YSM) was the same (5.8 ± 3 and 5.4 ± 5 yr). Comparison between groups revealed a significant effect of menopausal status and obesity on BMD and bone turnover. As compared to perimenopausal women, BMD was lower, OC and Ca: Cr higher only in nonobese-postmenopausal women. E2, T, DHA did not differ between the two groups of postmenopausal women. The results of this study suggest that even moderate obesity can play a protective role on postmenopausal bone loss.     

Is Laparoscopic Resection Adequate in Patients with Neuroendocrine Pancreatic Tumors?

Since the first reports with laparoscopic resection of islet cell tumors in 1996, the experience worldwide is still limited, with only short-term outcomes available. Some have suggested that a malignant tumor is a contraindication to laparoscopic resection. Aim The aim of this study was to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach in patients with functioning, nonfunctioning, or overt malignant pancreatic neuroendocrine tumor (PNT). To our knowledge this is the largest single-institution series on this subject to date. Patients and methods A total of 49 consecutive patients (43 women, 6 men; mean age 58 years, range 22–83 years) underwent laparoscopic pancreatic surgery (LPS) from April 1998 to June 2007. Preoperative localization was done by computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and Octreoscan imaging. Other than 9 PNTs localized in the head of the pancreas, all tumors were located in the left pancreas. Malignancy was diagnosed based on the presence of lymph nodes or liver metastasis. There were 33 patients with functioning tumors: 4 with gastrinomas (mean size 1.2 cm), 1 with a glucagonoma (4 cm), 3 with vipomas (3.2 cm), 2 with carcinoids (5.2 cm), 20 with sporadic insulinomas (1.4 cm), 2 with insulinoma/multiple endocrine neoplasia type 1 (MEN-1) (4.4 cm), and 1 with a malignant insulinoma (13 cm). Sixteen patients had a nonfunctioning tumor (mean size 5 cm). The following techniques were performed: laparoscopic spleen-preserving distal pancreatectomy (Lap SPDP), laparoscopic distal pancreatectomy with splenectomy (Lap SxDP) and laparoscopic enucleation (Lap En)/laparoscopic excision (Lap E). Lymph node dissection was performed when malignancy was suspected (Strasberg′s technique). Evaluation criteria included operative and postoperative factors, pathologic data including R0 or R1 resection (the pancreatic transection margin and all transection margins on the specimen were inked). Long-term outcomes were analyzed by tumor recurrence and patient survival. Results Four cases (8.2%) were converted to open surgery. Overall, Lap SPDP, Lap SxDP, and Lap En/Lap E were performed in 15 (33.3%), 8 (17.8%), and 22 (48.9%) patients, respectively. The operative time and blood loss was significantly lower in the Lap En group compared with the other laparoscopic techniques. The group of patients with malignant tumors undergoing Lap SxDP had a longer operating time and greater blood loss compared with the other distal pancreatectomy (Lap DP) techniques. Overall, the postoperative complications were significantly higher in the Lap En group (42.8%) than in the Lap DP (Lap SPDP + Lap SxDP) group (22%). These complications were mainly pancreatic fistula: 8.7% after Lap DP and 38% after Lap En. The overall morbidity was significantly higher after Lap SPDP (26.7%) than after Lap SxDP (12.5%) owing to the occurrence of splenic complications in the Lap SPDP group without splenic vessel preservation two of seven (28.5%). The means and ranges of hospital stay after Lap SPDP, Lap SxDP, and Lap En/Lap E were 5.9 (5–14), 7.5 (5–12), and 5.5 (5–7) days, respectively (NS). Pathology examination of the specimen showed R0 resection in all patients with malignant PNT. The mean time to resumption of previous activities for patients undergoing Lap DP or Lap En was 3 weeks. There were no postoperative (30 days) or hospital deaths. Conclusions This series demonstrates that LPS is feasible and safe in benign-appearing and malignant neuroendocrine pancreatic tumors (NEPTs). The benefits of minimally invasive surgery were manifest in the short hospital stay and acceptable pancreas-related complications in high-risk patients. LPS can achieve negative tangential margins in a high percentage of patients with malignant tumors. Although surgical cure is rare in malignant NEPTs, significant long-term palliation can be achieved in a large proportion of patients with an aggressive surgical approach.     

Considering Variables for the Assignment of Patients with Schizophrenia to a Case Management Programme

The elements and intensity of case management (CM) practices should be established according to patients’ needs. Therefore, greater understanding of patients’ needs in such community-based programmes is essential. This paper addresses this issue by characterizing two groups of patients receiving CM or a standard treatment programme (STP) and identifying the characteristics of patients receiving CM services. We recruited 241 patients with schizophrenia from 10 Adult Mental Health Centres in Barcelona (Catalonia, Spain). We analyzed the profile of new patients included in a clinical, non-intensive CM program against that of patients in a STP. CM patients, compared with STP patients, have a lower educational level and quality of life; greater use of health care services, and higher levels of psychiatric symptoms, disability and unmet needs. Community psychiatric visits, social services, education, physical health and needs were significantly associated with CM services. This study may help in identifying patients’ needs and strengthening the CM programme.     

Socioeconomic Inequalities in Unintended Pregnancy and Abortion Decision

Pregnancy planning allows women to better control their life trajectory and contributes to the future child’s health and development. Many studies that have analyzed socioeconomic inequalities in unintended pregnancy only took into account those pregnancies ending in births. Few of them that analyzed unintended pregnancy, including both induced abortion and births, and its socioeconomic determinants, concluded that unintended pregnancy is more frequent in young, poor, or unmarried women. These inequalities have been poorly studied in Europe, especially in the southern European context. The aim of the present study is to describe socioeconomic inequalities in unintended pregnancy and in abortion decision in Barcelona, Spain. The major findings are that unintended pregnancies accounted for 41% of total pregnancy and of these, 60% ended in abortion. From all pregnancies, the proportion of induced abortion reached 25.6%. Compared to women with university studies, those with primary education uncompleted had more unintended pregnancies (OR = 7.22). When facing an unintended pregnancy, women of lower socioeconomic position are more likely to choose induced abortion, although this is not the case among young or single women. This study reveals deep socioeconomic inequalities in unintended pregnancies and abortion decision in Barcelona, Spain, where the birth rate is very low and the abortion rate is rising. Women in low socioeconomic positions have many more unintended pregnancies than better educated women. Except for young or single women, the lower the socioeconomic position, the higher the proportion of women who choose an induced abortion when facing an unintended pregnancy. Font-Ribera, Pérez, Salvador, and Borrell are with the Health Information Service, Agency of Public Health of Barcelona, Barcelona, Spain; Pérez and Borrell are with the University Pompeu Fabra, Barcelona, Spain; Pérez and Borrell are with the CIBER in Epìdemiology and Public Health (CIBERESP), Barcelona, Spain; Pérez is with the Agency of Public Health of Barcelona, Barcelona, Spain.     

Effect of hormone replacement therapy on age-related increase in carotid artery intima-media thickness in postmenopausal women

The aim of this study was to determine the changes in carotid artery intima-media thickness as measured by B-mode ultrasound in postmenopausal women receiving hormone replacement therapy (HRT) or not. One hundred and fifty-nine healthy postmenopausal women aged 45-65 years were recruited from our menopause clinic. All the selected women were free of cardio-vascular diseases and had no cardio-vascular risk factors. None of the women were receiving lipid-lowering or antihypertensive drugs. Because carotid artery intima-media thickness was shown to be strongly and positively correlated with age in women aged 55 years and older but not before, women were divided into four groups according to age (<55 vs. > or =55 years) and use of HRT (current users vs. never users). All the treated women received non-oral 17beta-estradiol with a non-androgenic progestin and had started HRT within the first year after menopause. Scanning of the right common carotid artery was performed with a B-mode ultrasound imager and thickness of the intima-media complex as well as luminal diameter of the artery were determined using an automated computerized procedure. Within each age group (i.e. <55 or > or =55 years), women had comparable demographic characteristics and only differed by HRT use. Long-term treated women had significantly lower total cholesterol levels than untreated women (P=0.005). Triglycerides, low-density lipids (LDL)-cholesterol and high-density lipids (HDL)-cholesterol levels, systolic and diastolic blood pressure were not significantly different between users and non-users. In women <55 years, no significant difference in carotid intima-media thickness was found between current users (mean 2.5+/-1.4 years) and non users. In older women, the mean values of carotid intima-media thickness were significantly smaller in current users (mean 6.9+/-3.3 years) than in never treated women: 0.50+/-0.05 versus 0.56+/-0.07 mm, P<0.0001. Carotid artery intima-media thickness was significantly correlated to age in never users (r=0.5, P<0.0001) but not in women who were currently receiving HRT (r=0.2, ns). These findings suggest an apparent protective effect of long-term HRT on age-related thickening of the intima-media of the right common carotid artery. This may contribute to explain the apparent cardio-protective effect of HRT after the menopause.