Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.

Purpose: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen.

Methods: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.

A single blinded randomized controlled trial comparing semi-mechanical with hand-sewn cervical anastomosis after esophagectomy for cancer (SHARE-study).

Objective: The aim was to compare leak rate between hand-sewn end-to-end anastomosis (ETE) and semi-mechanical anastomosis (SMA) after esophagectomy with gastric tube reconstruction.

Background Data: The optimal surgical technique for creation of an anastomosis in the neck after esophagectomy is unclear.

Methods: Patients with esophageal cancer undergoing esophagectomy with gastric tube reconstruction and cervical anastomosis were eligible for participation after written informed consent.

Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial.

Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.

Molecular clonality analysis of esophageal adenocarcinoma by multiregion sequencing of tumor samples.

Background: Intratumor heterogeneity has been demonstrated in several cancer types, following a model of branched evolution. It is unknown to which extent intratumor heterogeneity is applicable to esophageal adenocarcinoma. Therefore the aim of this study was to characterise intratumor heterogeneity in esophageal adenocarcinoma.

Does Routine Endoscopy or Contrast Swallow Study After Esophagectomy and Gastric Tube Reconstruction Change Patient Management?

Background: Anastomotic leakage is a severe complication after esophagectomy. The objective was to investigate the diagnostic and predictive value of routine contrast swallow study and endoscopy for the detection of anastomotic dehiscence in patients after esophagectomy.

Methods: All patients who underwent contrast swallow and/or endoscopy within 7 days after oesophagectomy for cancer between January 2005 and December 2009 were selected from an institutional database.

Polarized release of hepatic microRNAs into bile and serum in response to cellular injury and impaired liver function.

Background & Aims: Extracellular microRNAs (miRNAs) in serum and bile are currently under intense investigation for biomarker purposes in liver disease. However, the directions and pathways by which miRNAs are released from hepatic cells remains largely unknown. Here, we investigated the release of hepatocyte and cholangiocyte-derived miRNAs (HDmiRs and CDmiRs) into blood and bile during various (patho)physiological hepatic conditions.

Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial.

Background: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years.

Methods: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41·4 Gy, given in 23 fractions of 1·8 Gy on 5 days per week) followed by surgery, or surgery alone.

Prednisolone does not affect direct-acting antivirals against hepatitis C, but inhibits interferon-alpha production by plasmacytoid dendritic cells.

Background: Chronic hepatitis C virus (HCV) infection compromises long-term outcomes of liver transplantation. Although glucocorticosteroid-based immunosuppression is commonly used, discussion is ongoing on the effect of prednisolone (Pred) on HCV recurrence and response to antiviral therapy post transplantation. Recently, new drugs (direct-acting antivirals) have been approved for the treatment of HCV, however, it remains unknown whether their antiviral activity is affected by Pred.

Improved body weight and performance status and reduced serum PGE2 levels after nutritional intervention with a specific medical food in newly diagnosed patients with esophageal cancer or adenocarcinoma of the gastro-esophageal junction.

Background: The majority of cancer patients loses weight and becomes malnourished during the course of their disease. Metabolic alterations and reduced immune competence lead to wasting and an increased risk of infectious complications. In the present study, the effect of a nutritionally complete medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides, was investigated on immune function, nutritional status, and inflammation in patients with esophageal cancer and compared with routine care.

Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma.

Objective: Recently, single nucleotide polymorphisms (SNPs) associated with esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE) were identified; rs10419226 (CRTC1), rs11789015 (BARX1), rs2687201 (FOXP1), rs2178146 (FOXF1), rs3111601 (FOXF1), and rs9936833 (FOXF1). These findings indicate that genetic susceptibility could play a role in the initiation of EAC in BE patients. The aim of this study was to validate the association between these previously identified SNPs and the risk of EAC in an independent and large case-control study.

Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk.

Epidemiological studies indicate that vitamin D exerts a protective effect on the development of various solid cancers. However, concerns have been raised regarding the potential deleterious role of high vitamin D levels in the development of esophageal adenocarcinoma (EAC). This study investigated genetic variation in the vitamin D receptor (VDR) in relation to its expression and risk of Barrett esophagus (BE) and EAC.

Human graft-derived mesenchymal stromal cells potently suppress alloreactive T-cell responses.

After organ transplantation, recipient T cells contribute to graft rejection. Mesenchymal stromal cells from the bone marrow (BM-MSCs) are known to suppress allogeneic T-cell responses, suggesting a possible clinical application of MSCs in organ transplantation. Human liver grafts harbor resident populations of MSCs (L-MSCs).

Induction chemotherapy followed by surgery for advanced oesophageal cancer.

Background: Patients with locoregionally advanced oesophageal tumours or disputable distant metastases are referred for induction chemotherapy with the aim to downstage the tumour before an oesophagectomy is considered.

Study Design: Patients who underwent induction chemotherapy between January 2005 and December 2012 were identified from an institutional database. Treatment plan was discussed in the multidisciplinary team.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

Objectives: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT.

Background: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful.

Incisional hernia after liver transplantation: risk factors and health-related quality of life.

The aim of this cross-sectional study was to analyze the incidence of incisional hernia after liver transplantation (LT), to determine potential risk factors for their development, and to assess their impact on health-related quality of life (HRQoL). Patients who underwent LT through a J-shaped incision with a minimum follow-up of three months were included. Follow-up was conducted at the outpatient clinic.

Fatigue after liver transplantation: effects of a rehabilitation program including exercise training and physical activity counseling.

Background: It is hypothesized that increasing physical fitness and daily physical activity can lead to a reduction in fatigue. However, standard medical care following liver transplantation seldom includes rehabilitation that focuses on physical fitness and physical activity.

Objective: The aim of this study was to explore whether a rehabilitation program can reduce fatigue in recipients of liver transplants.

Treatment and outcome of young patients with esophageal cancer in the Netherlands.

Background: Esophageal cancer is increasingly recognized in younger patients. We compared clinicopathological characteristics, treatment, and survival of patients aged ≤50 years with patients aged >50 years diagnosed with esophageal cancer in the Netherlands.

Methods: From the nationwide Netherlands Cancer Registry we identified all patients diagnosed with esophageal cancer between January 2000 and January 2011.

mTOR signaling in liver regeneration: Rapamycin combined with growth factor treatment.

Aim: To investigate the effects of mammalian target of rapamycin (mTOR) inhibition on liver regeneration and autophagy in a surgical resection model.

Methods: C57BL/6 mice were subjected to a 70% partial hepatectomy (PH) and treated intraperitoneally every 24 h with a combination of the mTOR inhibitor rapamycin (2.5 mg/kg per day) and the steroid dexamethasone (2.

Detection of spontaneous tumorigenic transformation during culture expansion of human mesenchymal stromal cells.

Human mesenchymal stem/stromal cells (MSCs) have been explored in a number of clinical trials as a possible method of treating various diseases. However, the effect of long-term cell expansion in vitro on physiological function and genetic stability is still poorly understood. In this study, MSC cultures derived from bone marrow and liver were evaluated for the presence of aberrant cells following long-term expansion.

Location of lymph node involvement in patients with esophageal adenocarcinoma predicts survival.

Background: The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction.

Methods: Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system.

The influence of preoperative weight loss on the postoperative course after esophageal cancer resection.

Objective: Preoperative weight loss might increase the risk of postoperative morbidity and mortality after esophagectomy for cancer. We hypothesized that patients with esophageal cancer with >10% weight loss during the 3 months before their diagnosis would be at an increased risk of postoperative complications, have a longer length of stay, and have worse overall survival.

Methods: In the present hospital-based cohort study, all patients who had undergone surgery for esophageal cancer in 1990 to 2010 at the Erasmus University Medical Center Rotterdam were included.

MicroRNA profiles in graft preservation solution are predictive of ischemic-type biliary lesions after liver transplantation.

Background & Aims: Ischemic-type biliary lesions (ITBL) are the second most common cause of graft loss after liver transplantation. Though the exact pathophysiology of ITBL is unknown, bile duct injury during graft preservation is considered to be a major cause. Here we investigated whether the release of cholangiocyte-derived microRNAs (CDmiRs) during graft preservation is predictive of the development of ITBL after liver transplantation.

Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells.

Recent evidence indicates there is a role for small membrane vesicles, including exosomes, as vehicles for intercellular communication. Exosomes secreted by most cell types can mediate transfer of proteins, mRNAs, and microRNAs, but their role in the transmission of infectious agents is less established. Recent studies have shown that hepatocyte-derived exosomes containing hepatitis C virus (HCV) RNA can activate innate immune cells, but the role of exosomes in the transmission of HCV between hepatocytes remains unknown.

Relationship between the histological appearance of the portal vein and development of ischemic-type biliary lesions after liver transplantation.

Ischemic-type biliary lesions (ITBLs) are a major cause of morbidity after liver transplantation (LT). Their assumed underlying pathophysiological mechanism is ischemia/reperfusion injury of the biliary tree, in which the portal circulation has been proposed recently to have a role. The aim of this study was to investigate whether early histological changes, particularly in the portal vein, predispose patients to ITBLs.