The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach.

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood.

The Association of Childhood Maltreatment With Lipid Peroxidation and DNA Damage in Postpartum Women.

Childhood maltreatment (CM) is associated with an increased risk for the development of psychiatric and somatic disorders in later life. A potential link could be oxidative stress, which is defined as the imbalance between the amount of reactive oxygen species (ROS) and the neutralizing capacity of anti-oxidative defense systems. However, the findings linking CM with oxidative stress have been inconsistent so far.

Intergenerational gene × environment interaction of FKBP5 and childhood maltreatment on hair steroids.

Background: The inconsistency in results of cortisol alterations after childhood maltreatment (CM) might arise due to the fact that no study so far considered the effects of environmental factors such as maltreatment load and genetic factors such as the influence of FKBP5 genotype on stress hormone regulation. This study analyzed the interaction between the single nucleotide polymorphism rs1360780 within the FKBP5 gene and the severity of maternal CM experiences (maltreatment load) on hair steroid levels of mother-infant-dyads.

Methods: Hair samples of N = 474 mothers and N = 331 newborns were collected < 1 week after parturition enabling a retrospective assessment of cortisol, cortisone, and dehydroepiandrosterone (DHEA) using mass spectrometry.

Altered hair endocannabinoid levels in mothers with childhood maltreatment and their newborns.

The endocannabinoid (EC) system possesses anti-inflammatory properties and seems to be altered in trauma-exposed individuals. In an intergenerational approach, this study investigated the link between childhood maltreatment (CM) experiences and alterations in the EC system. Hair samples of N = 142 mothers and N = 91 newborns were analyzed, retrospectively assessing EC regulation during the last trimester of pregnancy with four ECs: 1-arachidonoylglycerol (1-AG), N-oleoylethanolamide (OEA), N-stearoylethanolamide (SEA), and N-palmitoylethanolamide (PEA).

Serum profile changes in postpartum women with a history of childhood maltreatment: a combined metabolite and lipid fingerprinting study.

Childhood maltreatment (CM) can increase the risk of adverse health consequences in adulthood. A deeper insight in underlying biological pathways would be of high clinical relevance for early detection and intervention. The untargeted investigation of all detectable metabolites and lipids in biological samples represents a promising new avenue to identify so far unknown biological pathways associated with CM.

Prognostic Significant or Not? The Positive Circumferential Resection Margin in Esophageal Cancer: Impact on Local Recurrence and Overall Survival in Patients Without Neoadjuvant Treatment.

Objective: The aim of this study is to investigate the impact of the circumferential resection margin (CRM) in esophageal cancer on survival and recurrence in patients without pretreatment.

Background: Whereas the infiltration of the proximal or distal resection margin is associated with poor survival and higher recurrence, studies looking at the role of the circumferential resection margin on survival and local recurrence after esophagectomy are conflicting.

Methods: Influence of CRM infiltration according to the College of American Pathologists (CAP) and Royal College of Pathologists (RCP) on long-term survival of 180 patients with resected pT3 tumors and without neoadjuvant therapy was analyzed.

Inflammation in adult women with a history of child maltreatment: The involvement of mitochondrial alterations and oxidative stress.

The experience of maltreatment during childhood is associated with chronic low-grade inflammation in adulthood. However, the molecular mechanisms underlying this pro-inflammatory phenotype remain unclear. Mitochondria were recently found to principally coordinate inflammatory processes via both inflammasome activation and inflammasome-independent pathways.

Circulating Tumor Cells as a Biomarker for Preoperative Prognostic Staging in Patients With Esophageal Cancer.

Objective: We evaluated the prognostic significance of circulating tumor cells (CTCs) in patients with esophageal cancer (EC).

Background: Despite the availability of several preoperative diagnostic techniques, accurate pretreatment staging of EC remains challenging.

Methods: In this single-center, prospective study, peripheral blood samples for CTC analyses were obtained preoperatively from 100 patients who were judged to have resectable EC.

Successful management of esophageal necrosis after endovascular repair of chronic type B aortic dissection.

We report the case of a 65-year-old patient with esophageal necrosis that developed after thoracic endovascular aortic repair (TEVAR) of a previously stented, ruptured chronic type B aortic dissection. The cause of this complication may have been related to an infected mediastinal hematoma causing esophageal compression. Emergent esophagectomy was performed with success.

The potential for targeting HER2 therapeutically in esophageal cancer - a grasp at straws?

Introduction: Human EGFR-2 (HER2) has an impact on cellular proliferation and survival. HER2 overexpression has been shown to be a marker for poorer prognosis in several malignancies. Trastuzumab, a humanized mAb, is successfully used to target HER2 in breast cancer.

Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.

Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion.

Frequent intratumoral heterogeneity of EGFR gene copy gain in non-small cell lung cancer.

Next to EGFR mutation, EGFR gene copy number evaluated by fluorescence in situ hybridization (FISH) emerged as a potential predictive marker for sensitivity to EGFR tyrosine kinase inhibitors, although controversial data exist. As the diagnostic accuracy of predictive biomarkers can be substantially limited by regional differences within tumors, heterogeneity of EGFR gene copy gain in NSCLC was assessed in this study. For this purpose, a novel tissue microarray (TMA) based analysis platform was developed.

Effective inhibition of metastases and primary tumor growth with CTCE-9908 in esophageal cancer.

Background: In spite of multimodular treatment, the therapeutic options for esophageal carcinoma are limited, and metastases remain the leading cause of tumor-related mortality. Expression of the chemokine receptor CXCR4 significantly correlates with poor survival rates in patients with esophageal carcinoma and is associated with lymph node and bone marrow metastases. The aim of this study was to evaluate the effect of the CXCR4 antagonist CTCE-9908 on metastatic homing and primary tumor growth in vitro and in vivo in an orthotopic xenograft model of esophageal cancer.

Intratumoral heterogeneity of KRAS mutation is rare in non-small-cell lung cancer.

Background: Several lines of evidence indicate that mutational activation of KRAS is an early event in the carcinogenesis of non-small cell lung cancer (NSCLC). Nonetheless, previous studies report high frequencies of divergent KRAS mutational status between primary NSCLC and corresponding metastases. This suggests heterogeneity of the primary tumor in respect to its KRAS status.

Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung.

The HER2 protein, encoded by the ERBB2 gene, is a molecular target for the treatment of breast and gastric cancer by monoclonal antibodies or tyrosine kinase inhibitors. While intratumoral heterogeneity of ERBB2 amplification is rare in breast cancer it is reported to be frequent in bladder and colorectal cancer. To address the potential heterogeneity of the HER2 status in adenocarcinomas, squamous cell carcinomas and large cell undifferentiated carcinomas of the lung, 590 tumors were analyzed for HER2 overexpression and ERBB2 amplification using FDA-approved reagents for immunohistochemistry and fluorescence in-situ hybridization (FISH).

Long-term results of primary and secondary resections in patients with retroperitoneal soft tissue sarcoma.

Background And Objectives: The aim of this study was to analyse treatment and long-term outcome for primary and recurrent disease in patients with retroperitoneal soft tissue sarcoma (RSTS).

Methods: Clinicopathological data including tumour stage, grade, and histological subtype, location of the principal tumour, completeness of resection and operative procedure were studied. Kaplan-Meier estimations and Cox regression analyses were performed.

An attempt at validation of the Seventh edition of the classification by the International Union Against Cancer for esophageal carcinoma.

Background: The aim of our study was to investigate the ability of the Seventh edition of the classification by the International Union Against Cancer (UICC) to identify patients at higher risk and to predict the overall survival in patients with esophageal carcinoma.

Methods: Demographic and clinical data of 605 patients, who underwent esophagectomy for esophageal carcinoma between 1992 and 2009, were analyzed. Tumor stage and grade were classified according to the sixth and seventh editions of the UICC classification.

High surgical morbidity following distal pancreatectomy: still an unsolved problem.

Background: High surgical morbidity following distal pancreatectomy, especially pancreatic fistula, remains an unsolved problem. The aim of this study was to identify potential risk factors for surgical morbidity with a focus on the development of pancreatic fistula.

Methods: Clinicopathologic parameters were collected for 283 patients who underwent distal pancreatectomy between January 2000 and May 2010.

Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour.

Aims: Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene (HMOX-1) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.

Perivascular epitheloid cell tumour (PEComa) of the retroperitoneum - a rare tumor with uncertain malignant behaviour: a case report.

Introduction: Perivascular epitheloid cell tumours are rare mesenchymal neoplasms characterized by a proliferation of perivascular cells with an epitheloid phenotype and expression of myomelanocytic markers.

Case Presentation: Here we present the case of a cystic perivascular epitheloid cell tumour of the retroperitoneum associated with multifocal lung lesions. A 27-year-old woman underwent laparotomy to remove a 10 x 6 x 4 cm sized retroperitoneal mass.

Strong impact of micrometastatic tumor cell load in patients with esophageal carcinoma.

Background: To assess the role of immunohistochemically detectable nodal microinvolvement of patients with "curatively" resected esophageal carcinoma.

Methods: In 73 patients with resectable esophageal carcinoma [squamous cell carcinoma (SCC), n = 45 (61.6%); adenocarcinoma (AC), n = 28 (38.

Postpancreatectomy hemorrhage: diagnosis and treatment: an analysis in 1669 consecutive pancreatic resections.

Background: To analyze clinical courses and outcome of postpancreatectomy hemorrhage (PPH) after major pancreatic surgery.

Summary Background Data: Although PPH is the most life-threatening complication following pancreatic surgery, standardized rules for its management do not exist.

Methods: Between 1992 and 2006, 1524 patients operated on for pancreatic diseases were included in a prospective database.