and gene expression in colorectal cancer: comprehensive profiling and clinical value.

Background: The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with / expression in CRC and to determine whether / levels could impact treatment outcomes.

Methods: 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed.

Impact of genetic variants involved in the lipid metabolism pathway on progression free survival in patients receiving bevacizumab-based chemotherapy in metastatic colorectal cancer: a retrospective analysis of FIRE-3 and MAVERICC trials.

Background: Antiangiogenic drug (AAD)-triggered oxygen and nutrient depletion through suppression of angiogenesis switches glucose-dependent to lipid-dependent metabolism. Blocking fatty acid oxidation can enhance AAD-mediated anti-tumor effects in colorectal cancer (CRC). Therefore, we hypothesised that genetic variants in the lipid metabolism pathway may predict clinical outcomes [overall response rate (ORR), overall survival (OS) and progression-free survival (PFS)] in metastatic CRC (mCRC) patients receiving bevacizumab-based first-line treatment.

Mutational analysis of microsatellite-stable gastrointestinal cancer with high tumour mutational burden: a retrospective cohort study.

Background: Genomic signatures contributing to high tumour mutational burden (TMB-H) independent from mismatch-repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status are not well studied. We aimed to characterise molecular features of microsatellite stable (MSS) TMB-H gastrointestinal tumours.

Methods: Molecular alterations of 48 606 gastrointestinal tumours from Caris Life Sciences (CARIS) identified with next-generation sequencing were compared among MSS-TMB-H, dMMR/MSI-H, and MSS-TMB-low (L) tumours, using χ or Fisher's exact tests.

Genetic variants involved in the cGAS-STING pathway predict outcome in patients with metastatic colorectal cancer: Data from FIRE-3 and TRIBE trials.

Background: The activation of stimulator of interferon genes (STING) was reported to enhance cetuximab-mediated natural killer cell activation and dendritic cell maturation. Polymorphisms in genes in the cyclic GMP-AMP synthase (cGAS)-STING pathway may affect innate immune response. Therefore, we hypothesised that genetic variants in the cGAS-STING pathway may predict the efficacy of cetuximab-based treatment in patients with metastatic colorectal cancer.

Germline Polymorphisms in Genes Involved in the Antioxidant System Predict the Efficacy of Cetuximab in Metastatic Colorectal Cancer Patients Enrolled in FIRE-3 Trial.

Background: Reactive oxygen species activate EGFR/RAS/MAPK signaling either through the inactivation of phosphatases or by direct oxidation of kinases. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in antioxidant genes link to the efficacy of cetuximab in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: We analyzed genomic and clinical data from FIRE-3, a phase III trial comparing cetuximab and bevacizumab along with FOLFIRI in untreated mCRC patients.

Molecular characteristics and clinical outcomes of patients with Neurofibromin 1-altered metastatic colorectal cancer.

Loss-of-function alterations of Neurofibromin 1 (NF1) activate RAS, a driver of colorectal cancer. However, the clinical implications of NF1 alterations are largely unknown. We performed a comprehensive molecular profiling of NF1-mutant colorectal cancer using data from 8150 patients included in a dataset of commercial CLIA-certified laboratory (Caris Life Sciences).

Germline polymorphisms in genes maintaining the replication fork predict the efficacy of oxaliplatin and irinotecan in patients with metastatic colorectal cancer.

Background: The TIMELESS-TIPIN complex protects the replication fork from replication stress induced by chemotherapeutic drugs. We hypothesised genetic polymorphisms of the TIMELESS-TIPIN complex may affect the response, progression-free survival (PFS), and overall survival (OS) of cytotoxic drugs in patients with metastatic colorectal cancer (mCRC).

Methods: We analysed data from the MAVERICC trial, which compared FOLFOX/bevacizumab and FOLFIRI/bevacizumab in untreated patients with mCRC.

Large-scale analysis of KMT2 mutations defines a distinctive molecular subset with treatment implication in gastric cancer.

Frequent mutations of genes in the histone-lysine N-methyltransferase 2 (KMT2) family members were identified in gastric cancers (GCs). Understanding how gene mutations of KMT2 family affect cancer progression and tumor immune microenvironment may provide new treatment strategies. A total of 1245 GCs were analyzed using next-generation sequencing, whole transcriptome sequencing, immunohistochemistry (Caris Life Sciences, Phoenix, AZ).

Germ line polymorphisms of genes involved in pluripotency transcription factors predict efficacy of cetuximab in metastatic colorectal cancer.

Background: Cancer stem cells (CSCs) are primarily maintained by a network of pluripotency transcription factors (PTFs). Given a close relationship of CSC regulation with epidermal growth factor receptor and vascular endothelial growth factor signalling, we investigated whether single-nucleotide polymorphisms (SNPs) in PTF genes are related to the efficacy of cetuximab and/or bevacizumab in patients with metastatic colorectal cancer (mCRC).

Patients And Methods: Genomic and clinical data from three independent clinical trial cohorts were tested: cetuximab cohort (FOLFIRI/cetuximab arm in FIRE-3, n = 129), bevacizumab cohort 1 (FOLFIRI/bevacizumab arm in FIRE-3, n = 107) and bevacizumab cohort 2 (FOLFIRI/bevacizumab arm in TRIBE, n = 215).

RNA-Binding Protein Polymorphisms as Novel Biomarkers to Predict Outcomes of Metastatic Colorectal Cancer: A Meta-analysis from TRIBE, FIRE-3, and MAVERICC.

RNA-binding proteins (RBPs) regulate many posttranscriptional cellular activities. Accumulating evidence suggests associations between RBPs with colonic tumorigenesis and chemosensitivity. We investigated the prognostic and predictive values of SNPs of genes encoding RBPs in metastatic colorectal cancer (mCRC), using clinical and genomic data from three randomized clinical trials of standard first-line chemotherapy for mCRC (TRIBE, FIRE-3, and MAVERICC).

The Landscape of Alterations in DNA Damage Response Pathways in Colorectal Cancer.

Purpose: Defective DNA damage response (DDR) is a hallmark of cancer leading to genomic instability and is associated with chemosensitivity. Although the mismatch repair system has been extensively studied, the clinical implications of other mechanisms associated with DDR alterations in patients with colorectal cancer remain unclear. This study aimed to understand DDR pathways alterations and their association with common clinical features in patients with colorectal cancer.

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer.

Background: Immunogenic cell death (ICD) is a tumor cell death involving both innate and adaptive immune responses. Given published findings that oxaliplatin, but not irinotecan, drives ICD, we investigated whether single nucleotide polymorphisms (SNPs) in the ICD pathway are associated with the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer (mCRC).

Methods: Two randomized clinical trials data were analyzed: discovery cohort, FOLFOX/bevacizumab arm (MAVERICC); validation cohort, FOLFOXIRI/bevacizumab arm (TRIBE); and two control cohorts, FOLFIRI/bevacizumab arms (both trials).

Molecular Characterization of Appendiceal Goblet Cell Carcinoid.

Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC.

Feasibility of definitive chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma: A retrospective study.

Purpose: This study was designed to retrospectively analyze the safety and efficacy of chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma.

Methods And Materials: Eligible patients were aged 76 years or older, had a histopathologic diagnosis of esophageal squamous cell carcinoma, and were treated at the Kitasato University Hospital between January 2010 and March 2016. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m on days 1 to 5, repeated every 4 weeks for 2 cycles.

Retrospective Assessment of the Diagnostic Accuracy of the Depth of Invasion by Narrow Band Imaging Magnifying Endoscopy in Patients with Superficial Esophageal Squamous Cell Carcinoma.

Purpose: Treatment strategies for superficial esophageal squamous cell carcinoma (S-ESCC) are determined mainly on the basis of the depth of invasion. We retrospectively studied the accuracy of the depth of tumor invasion, comprehensively assessed using the Japan Esophageal Society (JES) classification.

Methods: The study group comprised 256 patients who underwent narrow band imaging (NBI) magnifying endoscopy, and endoscopic submucosal dissection for S-ESCC.

Correction to: Long-term outcomes of patients with early gastric cancer found to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after endoscopic submucosal dissection.

In Table 1, the second item in the right-hand column "Extra-indication" should be changed to "Out of indication". The correct version of Table 1 is displayed.

Long-term outcomes of patients with early gastric cancer found to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after endoscopic submucosal dissection.

Background: Gastric cancer treatment guidelines recommend additional surgery as the standard treatment for lesions for which endoscopic submucosal dissection (ESD) is not indicated. However, the incidence of lymph-node metastasis is low in most patients.

Methods And Materials: The study comprised 231 patients (231 lesions) who underwent ESD for early gastric cancer (EGC) in our hospital from September 2002 through March 2015 and were found to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after ESD.

Clinical Outcomes in Patients with Cancer of Unknown Primary Site Treated By Gastrointestinal Oncologists.

Objective: To evaluate the clinical outcomes in patients with cancer of an unknown primary site (CUP), who were treated by gastrointestinal oncologists.

Methods: We retrospectively studied 29 patients with CUP who were presented at the Department of Gastroenterology, Kitasato University Hospital from October 2005 to October 2013, and were treated by the gastrointestinal oncologists. The patients were divided into two groups, namely chemotherapy group and symptomatic therapy group, and the clinical characteristics and survival times were compared.

Different clinical characteristics associated with acute bleeding and delayed bleeding after endoscopic submucosal dissection in patients with early gastric cancer.

Background/aims: Few studies have classified risk factors according to the onset time of bleeding after endoscopic submucosal dissection (post-ESD bleeding).

Methods: We studied 1767 consecutive lesions in patients who underwent ESD for early gastric cancer from December 2006 through June 2016. Patients who had a remnant stomach or who had undergone reconstruction with a gastric tube were excluded.

Delayed perforation after endoscopic submucosal dissection for early gastric cancer: Clinical features and treatment.

Perforation is an important procedural complication of endoscopic submucosal dissection (ESD) for early gastric cancer. Although the incidence of delayed perforation after ESD is low, extreme caution is necessary because many cases require surgical intervention. Among 1984 lesions of early gastric cancer treated in our hospital by ESD in 1588 patients from September 2002 through March 2015, delayed perforation developed in 4 patients (4 lesions, 0.