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.     

Temporal trends in primary total hip and knee arthroplasty surgery: results from a UK regional joint register, 1991�C2004

INTRODUCTION

The aim of this study was to evaluate temporal trends in the prevalence of primary total hip and knee replacements (THRs and TKRs) throughout the Trent region from 1991 to 2004.

PATIENTS AND METHODS

The Trent Regional Arthroplasty Study records details of primary THR and TKR prospectively and data from the register were examined. Age and gender population data were provided by the Office for National Statistics.

RESULTS

A total of 26,281 THRs and 23,606 TKRs were recorded during this period. Analysis showed that females had an increased incidence rate ratio (IRR) for both primary THR (IRR = 1.29; 95% CI 1.26–1.33; P < 0.001) and TKR (IRR = 1.17; 95% CI 1.14–1.20; P < 0.001). Patients aged 74–85 years had the largest IRR for both primary THR (IRR = 6.7; 95% CI 6.4–7.0; P < 0.001) and TKR (IRR = 15.3; 95% CI 14.4–16.3; P < 0.001).

CONCLUSIONS

The prevalence of primary TKR increased significantly over time whereas THR remained steady in the Trent region between 1991 and 2004.     

Review: Understanding sorbent dialysis systems

Although maintenance haemodialysis once had the benefit of two distinctly different dialysate preparation and delivery systems – (1) a pre‐filtration and reverse osmosis water preparation plant linked to a single pass proportioning system and (2) a sorbent column dependent dialysate regeneration and recirculation system known as the REDY system – the first came to dominate the market and the second waned. By the early 1990s, the REDY had disappeared from clinical use. The REDY system had strengths. It was a small, mobile, portable and water‐efficient, only 6 L of untreated water being required for each dialysis. In comparison, single pass systems are bulky, immobile and water (and power) voracious, typically needing 400–600 L/treatment of expensively pretreated water. A resurgence of interest in home haemodialysis – short and long, intermittent and daily – has provided impetus to redirect technological research into cost‐competitive systems. Miniaturization, portability, flexibility, water‐use efficiency and ‘wearability’ are ultimate goals. Sorbent systems are proving an integral component of this effort. In sorbent dialysate regeneration, rather than draining solute‐rich dialyser effluent to waste – as do current systems – the effluent repetitively recirculates across a sorbent column capable of adsorption, ion exchange or catalytic conversion of all solute such that, at exit from the column, an ultra‐pure water solution emerges. This then remixes with a known electrolyte concentrate for representation to the dialyser. As the same small water volume can recirculate, at least until column exhaustion, water source independence is assured. Many current technological developments in dialysis equipment are now focusing on sorbent‐based dialysate circuitry. Although possibly déjà vu for some, it is timely for a brief review of sorbent chemistry and its application to dialysis systems.     

Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

Background  

Neuromyelitis optica spectrum disorders (NMOSD) are severe central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM) and/or optic neuritis (ON). A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA) and cell-based IIFA.     

LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling

Introduction

Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has been shown to play a key role in invasion and metastasis of breast carcinoma cells. However, very little is known about its role in normal tissue homeostasis. Here, we investigated the effects of LOXL2 expression in normal mammary epithelial cells to gain insight into how LOXL2 mediates cancer progression.

Methods

LOXL2 was expressed in MCF10A normal human mammary epithelial cells. The 3D acinar morphogenesis of these cells was assessed, as well as the ability of the cells to form branching structures on extracellular matrix (ECM)-coated surfaces. Transwell-invasion assays were used to assess the invasive properties of the cells. Clinically relevant inhibitors of ErbB2, lapatinib and Herceptin (traztuzumab), were used to investigate the role of ErbB2 signaling in this model. A retrospective study on a previously published breast cancer patient dataset was carried out by using Disease Specific Genomic Analysis (DSGA) to investigate the correlation of LOXL2 mRNA expression level with metastasis and survival of ErbB2-positive breast cancer patients.

Results

Fluorescence staining of the acini revealed increased proliferation, decreased apoptosis, and disrupted polarity, leading to abnormal lumen formation in response to LOXL2 expression in MCF10A cells. When plated onto ECM, the LOXL2-expressing cells formed branching structures and displayed increased invasion. We noted that LOXL2 induced ErbB2 activation through reactive oxygen species (ROS) production, and ErbB2 inhibition by using Herceptin or lapatinib abrogated the effects of LOXL2 on MCF10A cells. Finally, we found LOXL2 expression to be correlated with decreased overall survival and metastasis-free survival in breast cancer patients with ErbB2-positive tumors.

Conclusions

These findings suggest that LOXL2 expression in normal epithelial cells can induce abnormal changes that resemble oncogenic transformation and cancer progression, and that these effects are driven by LOXL2-mediated activation of ErbB2. LOXL2 may also be a beneficial marker for breast cancer patients that could benefit most from anti-ErbB2 therapy.     

Abstracts from other journals

The aim of the present study was to clinically evaluate fissure sealants on the occlusal fissures and buccal pits of permanent first and second molars after 20 and 15 years, respectively. The population consisted of 72 children, each of whom had had their four first molars sealed between 1977 and 1980. At the annual examinations, all caries-free, newly erupted second molars were sealed. When sealant was applied to the second molars, the first molars were checked and sealant was reapplied to those that had deficient sealants. At the follow-up, when the subjects were 26–27 years of age, 27 in the original group had moved from the community. Thus, the present result is based on 45 subjects. One hundred and fifty-three sealed first molars and 161 sealed second molars were available for inspection. At the follow-up examination of the first molars 20 years after sealant had been applied, 65% showed complete retention, 22% partial retention without caries, and 1306 caries or restoration in the occlusal fissures or buccal pits. At the 15-year follow-up of the second molars, the corresponding figures were 65%, 30% and 5%, respectively. Of the restored or carious molars, significantly more were found in the mandible than in the maxilla ( P  < 0.001). This longitudinal study showed that pit and fissure sealants, applied during childhood, have a long-lasting, caries-preventive effect.     

雷公藤红素对IL-1和IL-2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E₂(PGE₂)。