Impact of Endoscopic Surgical Skill Qualification System-certified surgeons as operators in laparoscopic rectal cancer surgery in Japan: A propensity score-matched analysis (subanalysis of the EnSSURE study).

Background: In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) is used to evaluate surgical skills essential for laparoscopic surgery, but whether surgeons with this certification as operators improve the short-term outcomes and prognosis after rectal cancer surgery is unclear. This cohort study was designed to compare the short-term and long-term outcomes of laparoscopic surgery for advanced rectal cancer performed by an ESSQS-certified surgeon versus a surgeon without ESSQS certification.

Methods: The outcomes of cStage II and III rectal cancer surgery cases performed at 56 Japanese hospitals between 2014 and 2016 were retrospectively reviewed.

Less demand on stem cell marker-positive cancer cells may characterize metastasis of colon cancer.

Background: CD44 and CD133 are stem cell markers in colorectal cancer (CRC). CD44 has distinctive isoforms with different oncological properties like total CD44 (CD44T) and variant CD44 (CD44V). Clinical significance of such markers remains elusive.

Short-term outcomes of robot-assisted versus conventional laparoscopic surgery for mid and low rectal cancer after neoadjuvant chemoradiotherapy: a propensity score-matched analysis.

The benefits of robot-assisted laparoscopic surgery (RALS) for rectal cancer remain controversial. Only a few studies have evaluated the safety and feasibility of RALS following neoadjuvant chemoradiotherapy (NCRT). This study aimed to compare the short-term outcomes of RALS versus conventional laparoscopic surgery (CLS) after NCRT for rectal cancer.

Short- and long-term outcomes of robotic-assisted laparoscopic surgery for rectal cancer: A single-center retrospective cohort study.

Introduction: Whether rectal cancer surgery by robotic-assisted laparoscopic surgery provides beneficial advantages remains controversial. Although favorable outcomes in terms of the safety and technical feasibility of robotic-assisted laparoscopic surgery have been demonstrated for rectal cancer, long-term oncological outcomes for robotic-assisted laparoscopic surgery have only been examined in a few studies. This retrospective study of subjects who underwent robotic-assisted laparoscopic surgery evaluated short- and long-term outcomes of consecutive rectal cancer patients.

Skeletal Muscle Changes Assessed by Preoperative Computed Tomography Images Can Predict the Long-Term Prognosis of Stage III Colorectal Cancer.

Background: Myopenia and myosteatosis are reported to be long-term prognostic factors in patients with colorectal cancer (CRC). However, the established parameters are unsuitable for the Japanese population because their body composition is different from that of the Western population.

Objective: We aimed to elucidate the effect of skeletal muscle changes among Japanese adults, measured using preoperative computed tomography (CT) as a prognostic factor in patients with stage III CRC.

Recovery of Liver Sinusoidal Endothelial Cells Following Monocrotaline-induced Liver Injury.

Background/aim: Although the pathology of sinusoidal obstruction syndrome (SOS) is characterized by damage to liver sinusoidal endothelial cells (LSECs), the processes underlying LSEC repair are incompletely understood. The angiopoietin (Ang)/Tie system contributes to angiogenesis. The present study aimed to examine the processes of LSEC repair and the involvement of the Ang/Tie pathway in LSEC recovery.

Prostaglandin E receptor EP4 stimulates lymphangiogenesis to promote mucosal healing during DSS-induced colitis.

In the intestine, the formation of new lymphatic vessels from pre-existing lymphatic vasculature (lymphangiogenesis) is related to the progression of inflammatory bowel disease (IBD). However, it remains unclear whether lymphangiogenesis contributes to mucosal repair after acute colitis. Prostaglandin Ereceptor EP4 suppresses the development of experimental colitis.

Lymphangiogenesis and accumulation of reparative macrophages contribute to liver repair after hepatic ischemia-reperfusion injury.

Hepatic tissue repair plays a critical role in determining the outcome of hepatic ischemia-reperfusion (I/R) injury. Hepatic lymphatics participate in the clearance of dead tissues and contribute to the reparative process after acute hepatic injury; however, it remains unknown whether lymphangiogenesis in response to hepatic inflammation is involved in liver repair. Herein, we determined if hepatic lymphangiogenesis improves liver repair after hepatic I/R injury.

EP3 signaling in dendritic cells promotes liver repair by inducing IL-13-mediated macrophage differentiation in mice.

Macrophage plasticity is essential for liver wound healing; however, the mechanisms underlying macrophage phenotype switching are largely unknown. Dendritic cells (DCs) are critical initiators of innate immune responses; as such, they orchestrate inflammation following hepatic injury. Here, we subjected EP3-deficient (Ptger3 ) and wild-type (WT) mice to hepatic ischemia-reperfusion (I/R) and demonstrate that signaling via the prostaglandin E (PGE) receptor EP3 in DCs regulates macrophage plasticity during liver repair.

WiNTRLINC1/ASCL2/c-Myc Axis Characteristics of Colon Cancer with Differentiated Histology at Young Onset and Essential for Cell Viability.

Background: WiNTRLINC1 is a long non-coding RNA (lncRNA) that positively regulates the Wnt pathway via achaete-scute complex homolog 2 (ASCL2) in colorectal cancer. ASCL2 was recently reported to play a critical role in chemoresistance, however clinical relevance of the WiNTRLINC1/ASCL2 axis remains obscure in colon cancer.

Patients And Methods: WiNTRLINC1/ASCL2 expression was investigated at messenger RNA (mRNA) level in 40 primary colon cancer tissues and the corresponding normal mucosa tissues, together with Wnt-related genes (c-Myc/PRL-3) and other lncRNAs (H19, HOTAIR, and MALAT1).

Thromboxane A receptor signaling in endothelial cells attenuates monocrotaline-induced liver injury.

Sinusoidal obstruction syndrome (SOS) is a major complication of chemotherapy and hematopoietic stem cell transplantation. The early stage of SOS is characterized by liver sinusoidal endothelial cell (LSEC) injury accompanied by platelet aggregation. Thromboxane A (TxA) induces platelet aggregation through the thromboxane prostanoid (TP) receptor.

Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer.

Background: Treatment-resistance genes limiting anticancer therapy have not been well clarified in colorectal cancer (CRC). We explored gene expression profiles to identify biomarkers for predicting treatment resistance to an anticancer drug in CRC.

Methods: Six CRC cell lines were treated with phenylbutyrate (PB).

RAMP1 in Kupffer cells is a critical regulator in immune-mediated hepatitis.

The significance of the relationship between the nervous and immune systems with respect to disease course is increasingly apparent. Immune cells in the liver and spleen are responsible for the development of acute liver injury, yet the regulatory mechanisms of the interactions remain elusive. Calcitonin gene-related peptide (CGRP), which is released from the sensory nervous system, regulates innate immune activation via receptor activity-modifying protein 1 (RAMP1), a subunit of the CGRP receptor.

Epigenetic Status of CDO1 Gene May Reflect Chemosensitivity in Colon Cancer with Postoperative Adjuvant Chemotherapy.

Background: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor gene, and its expression is regulated by promoter DNA methylation in human cancer. The metabolic product mediated by CDO1 enzyme increases mitochondrial membrane potential (MMP), putatively representing chemoresistance. The aim of this study is to investigate the functional relevance of CDO1 gene in colon cancer with chemotherapy.

Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice.

Background & Aims: Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E (PGE) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE generation, in liver injury and repair following hepatic I/R.

Methods: mPGES-1 deficient (Ptges) mice or their wild-type (WT) counterparts were subjected to partial hepatic ischemia followed by reperfusion.

Lymphatic Permeation Predicts Systemic Recurrence in Combination with Vascular Involvement in Laparoscopically Resected N0 Colon Cancer.

High-risk patient selection is required in N0 colon cancer. Although a number of studies have suggested high-risk clinicopathological predictors, most of these are based on analyses in heterogeous patients in terms of surgical procedures. Laparoscopic surgery for colon cancer is becoming a standard procedure worldwide because of its less invasiveness.

DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer.

Background: Minimal residual disease of the peritoneum is challenging for early cancer detection in gastric cancer (GC). Utility of PCR amplification of cancer-derived DNA has been considered feasible due to its molecular stability, however such markers have never been available in GC clinics. We recently discovered cancer-specific methylation of CDO1 gene in GC, and investigated the clinical potential to detect the minimal residual disease.

Homeobox-Only Protein Expression Is a Critical Prognostic Indicator of Pancreatic Neuroendocrine Tumor and Is Regulated by Promoter DNA Hypermethylation.

Objectives: We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET).

Methods: We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance.

Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma.

We have demonstrated that CDO1 methylation is frequently found in various cancers, including esophageal squamous cell carcinoma (ESCC), but its clinical relevance has remained elusive. CDO1 methylation was investigated in 169 ESCC patients who underwent esophagectomy between 1996 and 2007. CDO1 methylation was assessed by Q-MSP (quantitative methylation specific PCR), and its clinical significance, including its relationship to prognosis, was analyzed.

BLT1 signalling protects the liver against acetaminophen hepatotoxicity by preventing excessive accumulation of hepatic neutrophils.

Leukotriene B4 (LTB4) is a potent chemoattractant for neutrophils. Signalling of LTB4 receptor type 1 (BLT1) has pro-inflammatory functions through neutrophil recruitment. In this study, we investigated whether BLT1 signalling plays a role in acetaminophen (APAP)-induced liver injury by affecting inflammatory responses including the accumulation of hepatic neutrophils.

Vascular Endothelial Growth Factor Receptor Type 1 Signaling Prevents Delayed Wound Healing in Diabetes by Attenuating the Production of IL-1β by Recruited Macrophages.

The persistence of proinflammatory macrophages, which are recruited to the granulation tissue, impairs the healing of diabetic wounds. Herein, we examined the role of vascular endothelial growth factor receptor type 1 (VEGFR1) signaling in streptozotocin (STZ)-induced diabetic wound healing. Angiogenesis, lymphangiogenesis, and the healing of full-thickness skin wounds were impaired in STZ-treated wild-type (WT) mice compared with vehicle-treated WT mice, with attenuated recruitment of VEGFR1-positive macrophages expressing vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D to the wound granulation tissue.

Prognostic Significance of Promoter DNA Hypermethylation of cysteine dioxygenase 1 (CDO1) Gene in Primary Breast Cancer.

Using pharmacological unmasking microarray, we identified promoter DNA methylation of cysteine dioxygenase 1 (CDO1) gene in human cancer. In this study, we assessed the clinicopathological significance of CDO1 methylation in primary breast cancer (BC) with no prior chemotherapy. The CDO1 DNA methylation was quantified by TaqMan methylation specific PCR (Q-MSP) in 7 BC cell lines and 172 primary BC patients with no prior chemotherapy.

Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer.

Phenylbutyrate (PB) is a histone deacetylase antagonist that also exhibits antitumor activity. In this study, we used 7 breast cancer cell lines to identify biomarker candidates that predict PB sensitivity in breast cancer.Comprehensive gene expression profiles were compared using microarrays, and the importance of the identified genes to PB sensitivity was confirmed in gene transfection experiments.