Trends in treatment and overall survival among patients with proximal esophageal cancer

BACKGROUND The management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation(CRT) have been implemented. The trends in(non-)surgical treatment and its impact on overall survival(OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer,it is therefore essential to gain more insight through real-life studies.AIM To establish trends in treatment and OS in patients with proximal esophageal cancer.METHODS In this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTS In total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%,23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval(CI): 6.4-8.1] in 1989-1994 to 9.5 mo(95%CI: 8.1-10.8) in 2010-2014(logrank P 0.001). In non-metastatic disease, 5-year OS rates improved from 5%(95%CI: 3%-7%) in 1989-1994 to 13%(95%CI: 9%-17%) in 2010-2014(logrank P 0.001). Multivariable regression analysis demonstrated a significant treatment effect over time on survival. In metastatic disease, median OS was 3.8 mo(95%CI:2.5-5.1) in 1989-1994, and 5.1 mo(95%CI: 4.3-5.9) in 2010-2014(logrank P = 0.26).CONCLUSION OS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.     

Strategies to reduce pulmonary complications after esophagectomy

Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.     

HPLC分离测定格列齐特片及其有关物质

目的：建立新的HPLC法分离测定格列齐特征及其有关物质。方法：色谱条件为：Shim-Pack VP-ODS(5um,150mm*4.6mm i.d.)色谱柱;甲醇－0．02mol/L磷酸（用三乙胺调节PH至3．5）,（70：30）为流动相;检测波长为229nm。结果：在50－300ug;/ml的浓度范围内线性关系良好。r=0.9999(n=6);平均回收率为100．5％,RSD为0．17％（n=6),重复进样RSD为0．12％（n=6),格列齐特及其有关物质得到基线分离。结论：本法简便,快速,准确,适用于格列齐特及其制剂的质量控制。     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.      

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation

In a human in-vitro fertilization (IVF) programme, the effect of co- culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.