Prognosis of PPH depends mainly on the presence of preceding pancreatic fistula. Decision making as to the indication for nonsurgical interventions should consider time of onset, presence of pancreatic fistula, vascular pathologies, and the underlying disease.

No abstract

This is the first study to report that CTCs detected by an automated immunomagnetic detection system are independent, prognostic indicators of patients' outcome in EC. Thus, implementation of CTCs may improve accuracy of preoperative staging in EC.

The minimal regional LNY of 6 lymph nodes as recommended by the UICC for esophageal carcinoma is far too low to appropriately stage the disease. The LNY and the ratio should be reflected in the next version of the UICC classification.

No abstract

Closure of the pancreatic remnant by using a stapling device was associated with an increased risk of surgical morbidity. With an increasing number of laparoscopic distal pancreatectomies being performed, further studies analyzing the use of stapling devices and newer closure techniques are needed.

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. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CMassociated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation. Childhood maltreatment (CM) is so far an underestimated global phenomenon present in all societies and social classes. CM comprises experiences of physical, sexual and emotional abuse, as well as physical and emotional neglect during childhood and adolescence and constitutes a major threat to the child's mental and physical development with long-term consequences for both mental and somatic health 1-4. The epigenetic alterations in DNA methylation occurring in the aftermath of CM are pivotal for the adaptation to the early life environment 5 , and can thereby affect gene expression levels 6 and molecular responses to environmental stressors. Epigenetic alterations within key player genes of the hypothalamic-pituitary-adrenal (HPA) axis, the main coordinator of the physiological stress response (Fig. 1), are discussed to biologically contribute to health consequences observed in CM-affected individuals 7,8. Accordingly, mounting evidence suggests that CM is associated with alterations in DNA methylation within the glucocorticoid receptor gene (NR3C1) 9-13 and its regulatory co-chaperone FK506-binding protein 51 (FKBP51), which is encoded by the FKBP5 gene 13,14. As depicted in Fig. 1, a balanced regulation between the GR

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). Moderate and strong immunostaining (2 þ , 3 þ ) was seen in 10% of the tumors. ERBB2 amplification was found in 17 (3%) lung cancer patients including 10 cases (2%) with high-level amplification forming gene clusters. ERBB2 amplification was significantly related to histologic subtype and tumor grade, resulting in 12% ERBB2 amplified tumors in the subgroup of high-grade adenocarcinomas. Heterogeneity was analyzed in all highly amplified tumors. For this purpose, all available tumor tissue blocks from these patients were evaluated. Heterogeneity of ERBB2 amplification was found in 4 of 10 tumors as assessed by FISH. These included two tumors with a mixture of low-level and high-level amplification and two tumors with non-amplified tumor areas next to regions with high-level ERBB2 amplification. High-level ERBB2 amplification occurs in a small fraction of lung cancers with a strong propensity to high-grade adenocarcinomas. Heterogeneity of amplification may limit the utility of anti-HER2 therapy in some of these tumors. Further attempts to assess the utility of HER2-targeting therapy in homogeneously amplified lung cancers appear to be justified. Keywords: adenocarcinoma of the lung; ERBB2 gene amplification; fluorescence in-situ hybridization; HER2 expression; heterogeneity; large cell undifferentiated carcinoma of the lung; squamous cell carcinoma of the lungThe human epidermal growth factor receptor 2 gene (ERBB2, HER2/neu) is involved in the development of numerous types of human cancers and has been linked to poor prognosis in many of them. 1-3 The ERBB2 gene product HER2 is the target of an antibody-based therapy (trastuzumab), which has been shown to be remarkably effective in both the metastatic and adjuvant setting for HER2-positive breast cancer 4-6 and in advanced HER2-positive gastric cancer. 7 Moreover, with the tyrosine kinase inhibitor lapatinib which targets both EGFR and HER2 an alternative option for HER2-positive breast cancers has been introduced 8 and is under analysis for other tumor types.