Protective effect of proton pump inhibitors and potassium competitive acid blockers against post-gastric endoscopic submucosal dissection bleeding: a single-center, propensity score-matched analysis.

OBJECTIVES: Both potassium-competitive acid blockers (P-CABs) and proton pump inhibitors (PPIs) are known to be protective against bleeding after gastric endoscopic dissection (ESD) for early gastric cancers. The aim was to compare the effect of PPI and P-CAB treatment against bleeding after gastric ESD. MATERIALS AND METHODS: This was a single-center, retrospective analysis. Among 541 patients who underwent gastric ESD during the period from 2014 to 2019, we recruited subjects who were treated with PPIs (intravenous lansoprazole followed by oral esomeprazole) or a P-CAB before and after ESD. The incidence of post-ESD bleeding was compared between treatment groups. The risks associated with post-ESD bleeding were examined by univariate and multivariate analyses after propensity score-matching. RESULTS: The overall incidence of post-ESD bleeding was not significantly different between patients treated with PPIs (n = 362) and those treated with a P-CAB (n = 156) (3.0% vs 2.6%, respectively; p = .77). Even after propensity score matching (n = 153 in each group), the incidence was not significantly different between groups (2.6% vs 2.6%, respectively; p = 1.00). A multivariate analysis revealed that antithrombotic therapy (OR 4.85, 95% CI 1.14-20.57) was an independent factor associated with post-ESD bleeding. CONCLUSIONS: The incidence of post gastric ESD bleeding is not different between patients treated with PPI and patients treated with P-CAB. Antithrombotic therapy is an independent risk factor associated with post-ESD bleeding.

Prognostic nutritional index is an independent prognostic factor for older patients aged ≥ 85 years treated by gastric endoscopic submucosal dissection.

BACKGROUND: Clinical outcomes and prognostic factors for survival after endoscopic submucosal dissection (ESD) in older patients aged ≥ 85 years with early gastric cancer (EGC) are not well defined. The aim of this study was to investigate the clinical outcomes and prognostic factors for survival after ESD in older patients aged ≥ 85 years with EGC. METHODS: Clinical outcomes of 70 patients aged ≥ 85 years with EGC treated with ESD were evaluated retrospectively. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: During the follow-up period, 33 patients died from any cause, none of whom died from gastric cancer. OS probability after 3 years was 90.0%. Univariate analyses revealed that a neutrophil/lymphocyte ratio ≥ 2.6, a prognostic nutritional index (PNI) < 42.5 and low serum albumin value (< 3.5 g/dl) were associated with poor OS. Cox multivariate analysis revealed low PNI (< 42.5) to be an independent prognostic factor associated with OS (hazard ratio; 3.40, 95% confidence interval; 1.47-7.86, P = 0.004). CONCLUSIONS: PNI may be a useful parameter for making the decision to perform ESD for older patients aged ≥ 85 years with EGC.

Molecular alterations in gastric cancer and the surrounding intestinal metaplastic mucosa: an analysis of isolated glands.

BACKGROUND: Intestinal metaplasias (IMs) are generally regarded as pre-neoplastic gastric lesions. However, molecular alterations including genetic and epigenetic changes occurring in individual IM glands are not well defined. AIMS: We sought to identify DNA methylation status, microsatellite instability (MSI) and allelic imbalance (AI) occurring in individual IM glands and non-IM glands within the same mucosa. METHODS: We divided examined isolated gland obtained from GC into 4 components: isolated cancer, antral isolated intestinal metaplastic tissue, antral isolated non-metaplastic gland and isolated non-metaplastic gland derived from the greater curvature of the most distant gastric body without mucosal atrophy. We examined AI and microsatellite instability statuses using PCR-based microsatellite analysis. Next, the DNA methylation status (high methylation epigenome [HME], intermediate methylation epigenome [IME], and low methylation epigenome [LME]) was investigated. DNA methylation analysis of CDKN2A, mir34-b/c and MLHI genes was also performed. RESULTS: Although antral isolated IM glands were characterized by IME, isolated non-IM glands showed LME. In isolated cancer glands, HME was frequently found, compared with isolated non-IM glands. DNA methylation of mir34-b/c was common in isolated cancer and IM glands, whereas DNA methylation of CDKN2A was a rare event in isolated samples. The MLH1 gene was not methylated in isolated non-IM glands. Although multiple AIs were frequently found in isolated cancer glands, a few AIs were detected in isolated IM glands. CONCLUSIONS: We suggest that the DNA methylation status and the status of the mir34-b/c gene among isolated samples of IMs and isolated non-IM glands have an impact on IM development.

Resectability of underwater endoscopic mucosal resection for duodenal tumor: A single-center, retrospective pilot study.

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (U-EMR) has been attracting much attention as treatment for patients with nonampullary duodenal epithelial tumors (NADETs). We aim to compare treatment outcomes, including submucosal resectability, between patients undergoing U-EMR and conventional endoscopic mucosal resection (C-EMR) for NADET. METHODS: We conducted a retrospective review of 38 patients with NADET treated by U-EMR or C-EMR. In the resected specimens, we measured the horizontal length, the vertical distance from the muscularis mucosa to the margin at the deepest site, and the overall submucosal area. The submucosal index (SMI) was defined as the overall submucosal area divided by the largest horizontal length. These values and other treatment outcomes were compared between NADETs resected by U-EMR and C-EMR. RESULTS: The median size of lesions was 7 mm with a range of 3-13 mm. Although the incidence of adverse events and the rates of en bloc and R0 resection were not different in the two groups, the median procedure time was significantly shorter in the U-EMR group (11 min vs 13 min; P = 0.045). The median submucosal depth at the deepest site (1.22 mm vs 1.08 mm; P = 0.38) and the median SMI (0.44 vs 0.41; P = 0.42) were not different between groups. CONCLUSIONS: The resectability between NADETs treated by U-EMR and C-EMR was comparable. These results, together with the shorter procedure time required for U-EMR, suggest that U-EMR may have the potential to be the first choice for small to medium-sized NADET.

Predictive scoring system for advanced liver fibrosis in Japanese patients with severe obesity.

PURPOSE: The aim of this study was to examine the predictive scoring system of advanced liver fibrosis in severely obese Japanese patients. METHODS: Seventy-two patients underwent laparoscopic sleeve gastrectomy and intraoperative liver biopsies. We classified these patients into two groups: Brunt stage ≥ 2 (advanced fibrosis) and 0/1 (none/mild fibrosis). A logistic regression analysis was performed to identify the predictors of advanced fibrosis. RESULTS: Sixteen patients had advanced fibrosis, while 56 had no/mild fibrosis. The prevalence of type 2 diabetes mellitus (T2DM) in advanced fibrosis group was significantly higher than in none/mild fibrosis. An univariate analysis of the factors predicting advanced fibrosis showed significant differences in AST/ALT ratio, serum insulin levels, HOMA-IR, and type IV collagen 7S in the T2DM group. According to a multivariate analysis, type IV collagen 7S was an independent predictor and the cutoff value was 5.6 ng/mL. We created a flow chart; high risk (T2DM and type IV collagen 7S ≥ 5.6 ng/mL), moderate risk (T2DM and type IV collagen 7S < 5.6 ng/mL), and low risk (non-DM). For those at high risk, the sensitivity, specificity, positive predictive value, and negative predictive value were 56.2%, 94.4%, 75.0%, and 87.9%, respectively. CONCLUSION: This classification system has the potential to accurately categorize the risk of liver fibrosis.

Risk for lymph node metastasis in Epstein-Barr virus-associated gastric carcinoma with submucosal invasion.

OBJECTIVES: Epstein-Barr virus-associated gastric cancer (EBVGC) has been reported to be associated with a low risk for lymph node metastasis (LNM). However, the curative criteria for endoscopic submucosal dissection (ESD) for submucosal EBVGC (pT1b-EBVGC) remain unclear. Our study aimed to investigate the risk factors for LNM in pT1b-EBVGC. METHODS: This was a retrospective multicenter study at five institutes in Japan. We reviewed medical records and extracted all pT1b-EBVGC cases that met the following criteria: (i) histologically proven submucosal gastric cancer; (ii) surgical or endoscopic resection between January 2000 and December 2016; and (iii) presence of Epstein-Barr virus (EBV) in tumor cells verified by EBV-encoded small RNA in situ hybridization (EBER-ISH). The association between clinicopathological factors and LNM were assessed using multivariable logistic regression analysis. RESULTS: A total of 185 pT1b-EBVGC cases were included in the analysis. LNM was found in nine cases (4.9%). Multivariable logistic regression analysis demonstrated that lymphatic invasion (OR 9.1; 95% CI 2.1-46.1) and submucosal invasion ≥4000 µm (OR 9.2; 95% CI 1.3-110.3) were significant risk factors for LNM. When we focused on pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 µm, the rate of LNM was 0% (0/96, 95% CI 0-3.8%). CONCLUSIONS: Our findings indicated that lymphatic invasion and submucosal invasion ≥4000 µm were significant risk factors for LNM. ESD could be an appropriate option for pT1b-EBVGC without lymphatic invasion and with submucosal invasion <2000 µm.

Clinicopathological and Molecular Findings of Differentiated-Type Minute Gastric Intramucosal Neoplasia.

BACKGROUND/AIMS: To evaluate gastric early differentiate-type carcinogenesis, we attempted to identify clinicopathological and biological differences in differentiated-type minute intramucosal neoplasia (MIMN), which was defined as a tumor with a diameter of < 5 mm. METHODS: We examined clinicopathological findings and biological factors, including TP53 overexpression, mucin phenotype, Ki-67-positive rate, MLH1, intranuclear accumulation of ß-catenin, and DNA methylation status (low methylation epigenotype [LME], intermediate methylation epigenotype, and high methylation epigenotype [HME]) in MIMNs. In addition, non-MIMNs were also analyzed. In the present study, MIMN and non-MIMN were also examined based on low-grade dysplasia, high-grade dysplasia, and intramucosal cancer (IMC). RESULTS: In clinicopathological findings, there were significant differences in sex ratios and tumor locations between MIMNs and non-MIMNs. Among the examined biological factors, no significant differences in the frequencies of biological factors were observed between the 2 intramucosal neoplasia types. However, the frequency of intranuclear accumulation of ß-catenin was higher in non-MIMNs than in MIMNs. Finally, although the frequency of HME was significantly lower in MIMNs than in non-MIMNs, the opposite was observed for LME. CONCLUSIONS: The current finding suggested that DNA methylation and accumulation of ß-catenin were closely associated with tumor development from MIMN to non-MIMN.

Risk Factors for Post-gastric Endoscopic Submucosal Dissection Bleeding with a Special Emphasis on Anticoagulant Therapy.

BACKGROUND: Little is known about the risk factors for post endoscopic submucosal dissection (post-ESD) bleeding with anticoagulant therapy. AIMS: We aimed to investigate the risk factors for post-ESD bleeding for early gastric cancer (EGC) with an emphasis on anticoagulant therapy. METHODS: We retrospectively analyzed 2355 EGCs, including 137 lesions in patients treated under anticoagulants. Clinicopathological findings were evaluated between lesions in patients with and without anticoagulant therapy with propensity score matching analysis. The factors associated with post-ESD bleeding were analyzed with multivariate analysis with a logistic regression method. RESULTS: After propensity score matching, post-ESD bleeding was significantly more frequent in lesions of patients with than without anticoagulant therapy (11.7% vs 1.5%, respectively; P = 0.001). A univariate analysis revealed that anticoagulant therapy, heparin bridge therapy, undifferentiated type, deep submucosal invasion, and resected specimen size were associated with post-ESD bleeding. A multivariate analysis revealed anticoagulant therapy (OR 23.1, 95% CI 3.61-147.52) and resected specimen size (OR 1.03, 95% CI 1.00-1.06) to be independent factors associated with post-ESD bleeding. CONCLUSIONS: Anticoagulant therapy and resected specimen size were risk factors associated with post-ESD bleeding for EGC.

Immune checkpoint inhibitor-induced diarrhea: Clinicopathological study of 11 patients.

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICI-induced diarrhea aged 46-81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICI-induced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.

Diagnostic algorithm of magnifying endoscopy with crystal violet staining for non-ampullary duodenal epithelial tumors.

OBJECTIVES: Little is known about the usefulness of magnifying endoscopy with crystal violet staining (ME-CV) for the diagnosis of duodenal tumors. We assessed the ability of ME-CV to distinguish Vienna classification (VCL) category 4/5 (C4/5) from category 3 (C3) non-ampullary duodenal epithelial tumors (NADETs). METHODS: A total of 76 NADETs were studied. We retrospectively analyzed the diagnostic values of the white light endoscopy (WLE) scoring system and the ME-CV algorithm with receiver operating characteristic (ROC) curves, and three endoscopists calculated the sensitivity, specificity, accuracy, and the area under the curve (AUC) of each. The diagnostic values were tested among NADETs overall and among subgroups of tumors with gastric, gastrointestinal or intestinal mucin phenotypes. Inter-observer agreement of the diagnostic results was also calculated. RESULTS: According to the VCL, 54 lesions (71.1%) were regarded as C3 and 22 lesions (28.9%) as C4/5. The sensitivity, specificity, accuracy and AUC of ME-CV were higher than those of the WLE scoring system (63.6 vs 54.5, 85.2 vs 75.9, 78.9 vs 69.7, 0.744 vs 0.652, respectively). Inter-observer agreements of the WLE scoring system and ME-CV were both moderate (kappa 0.45 and 0.41). ME-CV had higher sensitivity, specificity, accuracy and AUC than those of the WLE scoring system among the gastric and intestinal phenotypes of NADETs. CONCLUSIONS: ME-CV is appropriate for the diagnosis of C4/5 and C3 NADETs.

Long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection for gastric cancer in elderly patients aged ≥ 75 years.

BACKGROUND: Little is known about the long-term outcomes and prognostic factors with non-curative endoscopic submucosal dissection (ESD) in elderly patients with early gastric cancer. METHODS: Clinicopathological findings and long-term outcomes were evaluated in 87 patients with early gastric cancer (EGC) aged ≥ 75 years who were treated with non-curative ESD. Prognostic factors for overall survival (OS) were analyzed with the Kaplan-Meier method and a Cox proportional hazards model. RESULTS: During the follow-up period, among 27 patients who died of any cause, only one patient died of gastric cancer. OS probabilities after 3 and 5 years were 89.7% and 79.3%, respectively. Univariate analyses revealed that Eastern Cooperative Oncology Group performance status 2-3, Charlson comorbidity index (CCI) ≥ 3, neutrophil/lymphocyte ratio ≥ 3.3, prognostic nutritional index < 44.8, distal tumor location and macroscopically depressed or flat configuration were associated with poor OS. Cox multivariate analysis revealed high CCI (≥ 3) to be an independent prognostic factor associated with OS (hazard ratio: 2.63, 95% confidence interval [CI] 1.06-6.49, P = 0.037). CONCLUSIONS: CCI may be a useful parameter for decision-making regarding additional surgery for elderly patients with gastric cancer treated by non-curative ESD.

Clinicopathological Features and Magnifying Chromoendoscopic Findings of Non-Ampullary Duodenal Epithelial Tumors.

BACKGROUND AND AIMS: We aimed to investigate an association between clinicopathological features, including immunohistochemical mucin phenotypes, and magnifying chromoendoscopic findings with crystal violet staining (ME-CV) in non-ampullary duodenal epithelial tumors (NADETs). METHODS: A total of 55 patients with NADET were divided into 3 groups by mucin phenotype: intestinal, gastrointestinal, or gastric. ME-CV findings were classified into 4 patterns: convoluted, leaf-like, reticular/sulciolar, and pinecone. The clinicopathological features and ME-CV findings were compared among the mucin phenotypes. RESULTS: Tumors of the gastric type were located in the duodenal bulb (p < 0.001), and contained pyloric gland adenoma (p < 0.001) more frequently than the other types. White-light endoscopy indicated that milk-white mucosa was less frequent in tumors of the gastric type than in those of the gastrointestinal type (p = 0.006) and the intestinal type (p < 0.001). ME-CV findings were significantly different between the gastric type and the other type (p = 0.028). Totally, 5 of 8 tumors of the gastric type manifested a pinecone pattern, 4 of which were compatible with pyloric gland adenoma. CONCLUSIONS: The endoscopic findings of NADETs differ according to mucin phenotype. A pinecone pattern under ME-CV may be characteristic of NADETs of the gastric type, especially pyloric gland adenoma.

Molecular subtypes of colorectal cancers determined by PCR-based analysis.

Tumor tissue consists of a heterogeneous cell population. The allelic imbalance (AI) ratio, determined in isolated tumor glands, is a good index of tumor heterogeneity. However, associations of the patterns of AI and microsatellite instability (MSI) development, observed in most cases of colorectal cancer (CRC), with tumor progression have not been reported previously. In this study, we examined whether CRC genetic profiles stratified by a combination of the AI ratio and MSI facilitate categorization of CRC, and whether these genetic profiles are associated with specific molecular alterations in CRC. A crypt isolation method was used to isolate DNA from tumors and normal glands obtained from 147 sporadic CRCs. AI and MSI statuses were determined using PCR-based microsatellite analysis and stratified based on AI ratio and MSI status. DNA methylation status (high methylation, intermediate methylation and low methylation status and mutations in KRAS, BRAF, and TP53 were examined. In addition, mucin markers were immunostained. Based on this analysis, four subgroups were categorized. Subgroup 1 was characterized by a high MSI status and BRAF mutation; subgroup 2 was closely associated with a high AI ratio, which accumulated during the early phases of colorectal carcinogenesis, and TP53 mutation; subgroup 3 was associated with a low AI ratio, seen during the later phases of colorectal carcinogenesis, and KRAS mutation; and subgroup 4 was defined as a minor subgroup. These results confirmed that classification of distinct molecular profiles provides important insights into colorectal carcinogenesis.

Genome-wide analysis of DNA copy number alterations in early and advanced gastric cancers.

To better understand progressive changes in gastric cancer (GC), early and advanced GCs (EGC and AGC, respectively) were examined for copy number alterations (CNAs). A crypt isolation method was used to isolate DNA from tumors and normal glands in 20 AGCs, and fresh tumor samples were obtained from 45 EGCs. We assessed CNAs for differentiated-type GCs using an Infinium HumanCytoSNP-12v2.1 BeadChip in EGCs and AGCs. The most frequent aberrations in EGC were gains at 8q23.3 (42.2%) and 8q23.2 (40%), and loss of heterozygosity (LOH) at 3p14.2 (24.2%), suggesting that these CNAs were involved in the development of EGC. On the other hand, the highest frequencies of gains in AGC were found at 8q24.21 (65%) and 8q24.3 (60%). The most frequent LOHs in AGC were at 11q24.3-25, 11q23.2-24.1, 11q14.1, and 12p11.21-13.33, whereas that in EGC was at 3p14.2. In addition, regions of copy-neutral LOHs in AGC were detected at 11q21, 11q13.3-14.3, 11q11, 11p13-15.3, 12q21.1, 12q12-13.3 and 5q33.3-35.1. Comparisons of gains in EGC and AGC showed significant differences at 12q22-q23.2, 12q21.33, 11p12, 11p14.1, 12q21.31-32.32, 3p12.3, 3p14.1, 10p15.1, 1q24.2 and 2q12.1. Copy neutral LOHs were significantly higher in AGC than in EGC at 14q32.11-32.33, 14q21.3, 14q11.2, 5q11.2, 5q 13.3, 14q21.1-23.2, 14q13.2-13.3, 5q12.1-12.3, 5q11.1, and 17p13.3. The total lengths of the CNAs were significantly greater in AGC than in EGC. We found that the pattern of CNAs in AGC was quite different from that in EGC. We suggest that increasing numbers of CNAs are associated with disease progression from EGC to AGC. © 2016 Wiley Periodicals, Inc.

Clinical outcomes of non-curative endoscopic submucosal dissection with negative resected margins for gastric cancer.

BACKGROUND AND AIMS: There has been little information about the long-term outcomes of patients with early gastric cancer (EGC) treated by non-curative endoscopic submucosal dissection (ESD) with negative resected margins (R0 resection). We aimed to compare the clinical outcomes of non-curative ESD with R0 resection between patients who underwent additional gastrectomy and those who did not. METHODS: Among EGC patients treated by ESD from 2002 to 2010, 66 patients were treated by non-curative ESD with R0 resection. Patients received either additional gastrectomy (group A, n = 45) or were followed up without gastrectomy (group B, n = 21). The clinicopathologic findings and the subsequent clinical course were compared between the 2 groups. RESULTS: Patients in group A were younger than those in group B (68.0 vs 71.0 years, P = .006). The follow-up period was longer in group A than in group B (7.8 vs 5.9 years, P = .011). The percentage of patients who died of any cause was not statistically lower in group A than in group B (13.3% vs 33.3%, P = .06). Although the overall survival rate was higher in group A than in group B (93.3% vs 76.2%, P = .028), disease-specific survival rates did not differ between the 2 groups (97.8% vs 100%, P = .495). A Cox proportional hazards model showed that gastrectomy was not an independent factor associated with overall survival. CONCLUSIONS: Careful follow-up may be an alternative strategy to gastrectomy for a subgroup of patients treated by non-curative ESD with R0 resection.

Dabigatran-induced esophagitis: The prevalence and endoscopic characteristics.

BACKGROUND AND AIM: There have been some descriptions of dabigatran-induced esophagitis in the literature. The aim of this study was to examine the prevalence and endoscopic characteristics of the disease. METHODS: We reviewed the endoscopic database and medical records of 91 patients with dabigatran internal use who underwent upper gastrointestinal endoscopy. The frequency of dabigatran-induced esophagitis and its endoscopic findings were retrospectively analyzed. In addition, the clinical characteristics were compared between patients with dabigatran-induced esophagitis and those without the disease. RESULTS: Dabigatran-induced esophagitis was found in 19 of 91 (20.9%) patients. Of the 19 patients with the esophagitis, 18 (94.7%) showed longitudinally sloughing epithelial casts in the mid and/or lower esophagus, which may be characteristic endoscopic findings of this disease. Symptomatic patients were more frequent in patients with dabigatran-induced esophagitis (68.4%) than those without (37.5%, P = 0.02). Other factors including age, gender, coexistence of hiatal hernia, gastroesophageal reflux disease, or concomitant other medications did not differ between the two groups. CONCLUSIONS: Dabigatran causes the esophageal mucosal injury in approximately 20% of patients. Longitudinally sloughing casts in the distal esophagus are characteristic of dabigatran-induced esophagitis.

Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization.

Colorectal cancers (CRCs) exhibit multiple genetic alterations, including allelic imbalances (copy number alterations, CNAs) at various chromosomal loci. In addition to genetic aberrations, DNA methylation also plays important roles in the development of CRC. To better understand the clinical relevance of these genetic and epigenetic abnormalities in CRC, we performed an integrative analysis of copy number changes on a genome-wide scale and assessed mutations of TP53, KRAS, BRAF, and PIK3CA and DNA methylation of six marker genes in single glands isolated from 39 primary tumors. Array-based comparative genomic hybridization (array-CGH) analysis revealed that genomic losses commonly occurred at 3q26.1, 4q13.2, 6q21.32, 7q34, 8p12-23.3, 15qcen and 18, while gains were commonly found at 1q21.3-23.1, 7p22.3-q34, 13q12.11-14.11, and 20. The total numbers and lengths of the CNAs were significantly associated with the aberrant DNA methylation and Dukes' stages. Moreover, hierarchical clustering analysis of the array-CGH data suggested that tumors could be categorized into four subgroups. Tumors with frequent DNA methylation were most strongly enriched in subgroups with infrequent CNAs. Importantly, Dukes' D tumors were enriched in the subgroup showing the greatest genomic losses, whereas Dukes' C tumors were enriched in the subgroup with the greatest genomic gains. Our data suggest an inverse relationship between chromosomal instability and aberrant methylation and a positive association between genomic losses and distant metastasis and between genomic gains and lymph node metastasis in CRC. Therefore, DNA copy number profiles may be predictive of the metastatic behavior of CRCs.

The effect of granulocyte and monocyte adsorptive apheresis on serum cytokine levels in patients with ulcerative colitis.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn has been reported to be effective as induction therapy in ulcerative colitis (UC). However, the effects of GMA on serial changes in cytokine levels have not been well characterized. We therefore, investigated cytokine levels in UC patients before and after treatment with GMA. A total of 16 patients with active UC, 10 men, and six women, mean age, 42.6 years were included. Fourteen patients had total colitis and two patients had left-sided colitis. The study included nine patients with a chronic intermittent course, six with a chronic continuous course and one with a single episode. The duration of each GMA session was 60 min at a flow rate of 30 mL/min as per study protocol. Serum levels of 17 cytokines were determined simultaneously using a Bio-Plex suspension array system before and after treatment with GMA. Serum interleukin (IL)-10 and macrophage inflammatory protein-1ß levels were increased significantly in UC patients after GMA treatment compared to pre-treatment levels (P < 0.05). In particular, GMA treatment caused a significant increase in serum IL-10 levels compared to pre-treatment in patients with total colitis or with a chronic intermittent UC course. In conclusion, this investigation showed that GMA was associated with a marked increase in serum level of the anti-inflammatory cytokine, IL-10. The rise in circulating IL-10 is interesting, and potentially a significant factor in the efficacy of GMA in patients with inflammatory bowel diseases.

Risk factors of re-bleeding within a year in colonic diverticular bleeding patients.

Background/Aims: Although colonic diverticular bleeding (CDB) is common, few reports have described the effects of antithrombotic agents (ATs) on CDB. This study aimed to clarify the risk factors of re-bleeding within a year in CDB patients. Methods: We retrospectively analyzed the risk of re-bleeding in CDB patients. Among 324 patients who were hospitalized for acute lower gastrointestinal bleeding at our institution during the period from 2015 to 2019, we used 76 patients who were diagnosed as CDB. Risk factors for re-bleeding were determined by Cox proportional hazard models. Results: Of 76 patients analyzed, 32 were taking ATs, nine of whom were taking multiple agents. Twenty-six patients re-bled within a year. Compared with the patients without re-bleeding, patients with re-bleeding within a year had been treated by antithrombotic therapy more frequently (62% vs. 32%, p = 0.013). Cox proportional hazard model revealed that treatment with ATs (hazard ratio 3.89, 95% confidence interval 1.53-10.74, p = 0.004) was an independent risk factor for re-bleeding within a year. Conclusion: ATs were found to be an independent risk factor related to re-bleeding within a year in patients with CDB.