Endoscopic and histological risk stratification for gastric cancer using gastric intestinal metaplasia.

BACKGROUND AND AIM: Intestinal metaplasia (IM) of the gastric mucosa is strongly associated with the risk of gastric cancer (GC). This study was performed to investigate the usefulness of endoscopic and histological risk stratification for GC using IM. METHODS: This was a post-hoc analysis of a multicenter prospective study involving 10 Japanese facilities (UMINCTR000027023). The ridge/tubulovillous pattern, light blue crest (LBC), white opaque substance (WOS), endoscopic grading of gastric IM (EGGIM) score using non-magnifying image-enhanced endoscopy, and operative link on gastric IM assessment (OLGIM) were evaluated for their associations with GC risk in all patients. RESULTS: In total, 380 patients (115 with GC and 265 without GC) were analyzed. The presence of an LBC (limited to antrum: odds ratio [OR] 2.4 [95% confidence interval 1.1-5.0], extended to corpus: OR 3.6 [2.1-6.3]), the presence of WOS (limited to antrum: OR 3.0 [1.7-5.3], extended to corpus: OR 4.2 [2.1-8.2]), and histological IM (limited to antrum: OR 3.2 [1.4-7.4], extended to corpus: OR 8.5 [4.5-16.0]) were significantly associated with GC risk. Additionally, the EGGIM score (5-8 points: OR 8.8 [4.4-16.0]) and OLGIM (stage III/IV: OR 12.5 [6.1-25.8]) were useful for stratification of GC risk. The area under the receiver operating characteristic curve value for GC risk was 0.740 for OLGIM and 0.706 for EGGIM. CONCLUSIONS: The LBC, WOS, EGGIM, and OLGIM were strongly associated with GC risk in Japanese patients. This finding can be useful for GC risk assessment in daily clinical practice.

Young Patient with X-linked Agammaglobulinemia Presents with Advanced Gastric Cancer and Extensive Atrophic Gastritis.

X-linked agammaglobulinemia (XLA) is associated with an increased risk of gastrointestinal cancers including gastric cancer (GC). We herein report the case of a 30-year-old male patient with XLA who developed GC and extensive atrophic gastritis. He tested positive in the urea breath test, thus indicating the presence of Helicobacter pylori. Distal gastrectomy and chemotherapy were performed without any complications; however, the died two years after this diagnosis. Immunoglobulin deficiency makes these patients susceptible to progressive atrophic gastritis and the associated risk of GC. Therefore, patients with XLA are advised to undergo an evaluation for Helicobacter pylori infection as well as monitoring for GC.

Multiple gastric neuroendocrine tumors in a patient with parietal cell dysfunction and adenosine triphosphatase H+/K+ transporting subunit alpha gene variant.

A 47-year-old woman presented with multiple gastric tumors, each up to 10 mm in diameter, in the gastric body and fundus without mucosal atrophy. White spots and numerous transparent, light-brownish, small, and rounded spots were observed in the background gastric mucosa. Biopsy specimens obtained from the tumors revealed gastric neuroendocrine tumors. The patient exhibited hypergastrinemia and achlorhydria and tested negative for serum parietal cell antibody, intrinsic factor antibody, and Helicobacter pylori infection. Moreover, no additional lesions were detected on imaging. These findings were inconsistent with Rindi's classification. The tumor was resected via endoscopic submucosal resection. Histopathological examination revealed gastric neuroendocrine tumors G2 infiltrating the submucosa with no atrophy of the gastric mucosa, dilated fundic glands, parietal cell protrusions, and hyperplasia of enterochromaffin-like cells. Immunohistochemically, the parietal cells were negative for both α- and ß-subunits of H+/K+ ATPase, suggesting parietal cell dysfunction. A genomic variant was identified in adenosine triphosphatase H+/K+ transporting subunit alpha. After 7 years of treatment, there was no evidence of residual or metastatic lesions. Modification of adenosine triphosphatase H+/K+ transporting subunit alpha may be a significant factor in the pathogenesis of multiple gastric neuroendocrine tumors in the context of gastric parietal cell dysfunction.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Is blue light imaging without magnification satisfactory as screening for esophageal squamous cell carcinoma? Post-hoc analysis of multicenter randomized controlled trial.

OBJECTIVES: Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. METHODS: This was a post-hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. RESULTS: This study identified ESCC in 49 of 699 cases. Of these cases, nine (18.4%) were missed by BLI but detected by LCE. In per-patient analysis, the sensitivity of BLI was lower than that of LCE following BLI (83.7% vs. 100.0%; P = 0.013), whereas the specificity and accuracy of BLI were higher (88.2% vs. 81.2%; P < 0.001 and 87.8% vs. 82.5%; P < 0.001, respectively). No significant endoscopic characteristics were identified, but the color difference was lower in BLI than in LCE (21.4 vs. 25.1; P = 0.003). CONCLUSION: LCE following BLI outperformed BLI in terms of sensitivity in patients with high-risk ESCC. Therefore, LCE, in addition to BLI, would still be required in screening esophagogastroduodenoscopy even by expert endoscopists.

Acceptability, Safety, and Feasibility of Transnasal and Peroral Ultrathin Endoscopy Using GAGLESS Mouthpieces: A Prospective Randomized Trial.

BACKGROUND/AIM: Esophagogastroduodenoscopy (EGD) is an effective screening method for early detection of gastric cancer. The GAGLESS mouthpiece has a structure that widens the pharyngeal cavity and suppresses the pharyngeal reflex. This study aimed to investigate the acceptability, safety, and feasibility of transnasal and peroral ultrathin endoscopy using GAGLESS mouthpieces (Clinical Trial Number: UMIN000036922). PATIENTS AND METHODS: This study was a multicenter, prospective, randomized, open-label trial performed using a questionnaire. The study included 101 consecutive patients who visited the participating medical institutions between June 2019 and March 2022 (median age=47 years, range=24-87 years; all male). Patients aged ≥20 years at the time of consent acquisition who were the first to undergo EGD were included in the study. The primary endpoint was the degree of distress during EGD, as determined using a visual analog scale (VAS). RESULTS: The VAS score during endoscopic passage through the pharynx was significantly better in the transnasal endoscopy group than in the oral endoscopy group (2.420 vs. 4.092, p=0.001). There was no significant difference in the VAS scores between the two groups during anesthesia or throughout the examination. Compared with nasal endoscopy, oral endoscopy with a GAGLESS mouthpiece did not reduce the VAS score but did significantly improve gastric visibility. CONCLUSION: For patients in whom there was difficulty in inserting a nasal endoscope, using a GAGLESS mouthpiece rather than a conventional mouthpiece may be more useful in reducing pain.

Clinical outcomes of endoscopic submucosal dissection for esophageal squamous cell carcinoma with esophageal varices: Multicenter retrospective study.

OBJECTIVES: Clinical outcomes of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) with esophageal varices (EVs) are obscure. We aimed to elucidate the clinical outcomes of ESD for ESCC with EVs in a multicenter, retrospective study. METHODS: We established a retrospective cohort of 30 patients with ESCC complicating EVs, who underwent ESD at 11 Japanese institutions. Rates of en bloc resection and R0 resection, procedure time, and adverse events were evaluated as indicators of the feasibility and safety of ESD. Additional treatment, recurrence, and metastasis of the lesions were evaluated as indicators of the long-term efficacy of ESD. RESULTS: Portal hypertension was caused by cirrhosis, of which alcohol was the most common cause. En bloc resection was achieved in 93.3% and R0 resection in 80.0% of the patients. The median procedure time was 92 min. Adverse events included a case of uncontrolled intraoperative bleeding leading to discontinuation of ESD and a case of esophageal stricture due to extensive resection. During the follow-up period of a median for 42 months, a patient with local recurrence and another patient with liver metastasis were observed. One patient died of liver failure after receiving chemoradiotherapy as an additional treatment after ESD. No patient died of ESCC. CONCLUSION: This multicenter, retrospective cohort study demonstrated the safety and efficacy of ESD for ESCC with EVs. Further studies are needed to establish appropriate treatment methods for EVs before ESD and additional treatments for patients with insufficient ESD.

Modulation of AMPK/ TET2/ 5-hmC axis in response to metabolic alterations as a novel pathway for obesity-related colorectal cancer development.

Obesity is a major risk factor for colorectal cancer (CRC). Sustained hyperglycemia destabilizes tumor suppressor ten-eleven translocation (TET) 2, which is a substrate of AMPK, thereby dysregulating 5-hydroxymethylcytosine (5-hmC). However, the role played by this novel pathway in the development of obesity-related CRC is unclear. In this study, we aimed to evaluate the expression levels of TET2 and 5-hmC in obesity-related CRC and the effects of TET2 expression on the proliferation of CRC cells. To this end, surgically resected CRC samples from seven obese patients (Ob-CRC) and seven non-obese patients (nOb-CRC) were analyzed, and expression levels of the TET family and 5-hmC were compared between the groups. A decrease was observed in TET2 mRNA levels and 5-hmC levels in Ob-CRC compared to that in nOb-CRC. Furthermore, we used CRC cell lines to investigate the relationship between insulin, proliferation, and TET expression and AMPK. In cell lines, glucose and insulin treatments suppressed the expression of TET2 and increased cell proliferation. Downregulation of TET2 using siRNA also induced cell proliferation. An AMPK activator inhibited insulin- or glucose-stimulated cell proliferation and restored TET2 expression. We propose the AMPK-TET2-5-hmC axis as a novel pathway and potential therapeutic target in obesity-related CRC development.

Blue light imaging and linked color imaging as a screening mode for esophageal squamous cell carcinoma in high-risk patients: Multicenter randomized trial.

OBJECTIVES: Blue light imaging (BLI) and linked color imaging (LCI) are superior to conventional white light imaging for detecting esophageal squamous cell carcinoma (ESCC). Hence, we compared their diagnostic performances in ESCC screening. METHODS: This open-labeled, randomized controlled trial was performed at seven hospitals. Patients with a high risk of ESCC were randomly assigned to the BLI group (BLI followed by LCI) and LCI group (LCI followed by BLI). The primary end-point was the detection rate of ESCC in the primary mode. The main secondary end-point was its miss rate in the primary mode. RESULTS: In total, 699 patients were enrolled. The detection rate of ESCC did not significantly differ between the BLI and LCI groups (4.0% [14/351] vs. 4.9% [17/348]; P = 0.565); however, the number of patients with ESCC tended to be smaller in the BLI group (19 vs. 30). Notably, the miss rate of ESCC was lower in the BLI group (26.3% [5/19] vs. 63.3% [19/30]; P = 0.012) and LCI detected no ESCCs missed by BLI. The sensitivity was higher in BLI (75.0% vs. 47.6%; P = 0.042); on the other hand, the positive predictive value in BLI tended to be lower (28.8% vs. 45.5%; P = 0.092). CONCLUSIONS: The detection rates of ESCC did not significantly differ between BLI and LCI. Although BLI may have the potential to be advantageous over LCI for the diagnosis of ESCC, it is still unclear whether BLI is superior to LCI, and a further large-scale study is needed. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT1022190018-1).

Smoking history and severe atrophic gastritis assessed by pepsinogen are risk factors for the prevalence of synchronous gastric cancers in patients with gastric endoscopic submucosal dissection: a multicenter prospective cohort study.

BACKGROUND: No studies have evaluated the relationship between lifestyle and synchronous gastric cancers (SGCs) in patients with endoscopic submucosal dissection (ESD) for early gastric cancers (EGCs). Using data from the Tohoku gastrointestinal (GI) study, we aimed to identify factors associated with SGCs. METHODS: Tohoku GI study is a multicenter prospective cohort study investigating the relationship between lifestyle and metachronous gastric cancers. Patients who had a schedule to undergo ESD for primary EGCs were enrolled. We used logistic regression analysis to examine the relationship of 15 candidate factors, including lifestyle, with the prevalence of SGCs in this study. RESULTS: Of 850 patients between 2016 and 2019, 16.0% (136 patients) had SGCs. In multivariate analysis, smoking history (odds ratio [OR], 1.93; p = 0.048) and severe atrophic gastritis assessed by pepsinogen (OR, 1.92; p = 0.004) were risk factors for the prevalence of SGCs. Regarding smoking, current smoking (OR, 2.33; p = 0.021), but not former smoking (OR, 1.76; p = 0.098), was a significant risk factor for its prevalence. In the stratified analysis, severe atrophic gastritis assessed by pepsinogen was a risk factor in patients without Helicobacter pylori (H. pylori) eradication (OR, 2.10; p = 0.002), but not a risk factor in those with H. pylori eradication (OR, 0.75; p = 0.737). CONCLUSION: Smoking history was a risk factor for the prevalence of SGCs in patients with ESD for EGCs, and severe atrophic gastritis assessed by pepsinogen was also a risk factor when H. pylori was not eradicated.

Endoscopic Diagnosis of Eosinophilic Esophagitis: Basics and Recent Advances.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease, characterized by esophageal dysfunction and intense eosinophil infiltration localized in the esophagus. In recent decades, EoE has become a growing concern as a major cause of dysphagia and food impaction in adolescents and adults. EoE is a clinicopathological disease for which the histological demonstration of esophageal eosinophilia is essential for diagnosis. Therefore, the recognition of the characteristic endoscopic features with subsequent biopsy are critical for early definitive diagnosis and treatment, in order to prevent complications. Accumulating reports have revealed that EoE has several non-specific characteristic endoscopic findings, such as rings, furrows, white exudates, stricture/narrowing, edema, and crepe-paper esophagus. These findings were recently unified under the EoE endoscopic reference score (EREFS), which has been widely used as an objective, standard measurement for endoscopic EoE assessment. However, the diagnostic consistency of those findings among endoscopists is still inadequate, leading to underdiagnosis or misdiagnosis. Some endoscopic findings suggestive of EoE, such as multiple polypoid lesions, caterpillar sign, ankylosaurus back sign, and tug sign/pull sign, will aid the diagnosis. In addition, image-enhanced endoscopy represented by narrow band imaging, endocytoscopy, and artificial intelligence are expected to render endoscopic diagnosis more efficient and less invasive. This review focuses on suggestions for endoscopic assessment and biopsy, including recent advances in optical technology which may improve the diagnosis of EoE.

Intramural esophageal dissection with eosinophilic esophagitis.

Intramural esophageal dissection (IED), like esophageal perforation, is a rare complication of eosinophilic esophagitis (EoE). A 44-year-old woman who had experienced EoE for 8 years complained of food impaction, severe neck pain, and odynophagia as well as consulted the emergency unit. She was diagnosed with IED with mediastinal emphysema by enhanced computed tomography. After admission, she was treated conservatively with noninvasive treatment, including fasting, intravenous feeding, and antibiotics. Only nine cases of IED with EoE have been previously reported. All were male, and our patient was the first female patient from Asia. Urgent endoscopy was conducted in eight cases, of which three were worse after endoscopy, and in one case, total esophagectomy was conducted due to subsequent esophageal perforation. We did not perform urgent endoscopy on our patient because of a potentially increased risk of esophageal perforation through the procedure. When patients with EoE complain of severe retrosternal pain, odynophagia, or dysphagia, IED should be considered in addition to food impaction.

Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non-alcohol drinkers.

BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

OBJECTS: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB. METHODS: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents. RESULTS: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). CONCLUSIONS: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.

Atypical jejunal follicular lymphoma with severe stricture.

The typical macroscopic appearance of gastrointestinal follicular lymphoma (FL) are multiple white granules or small white polyps, called multiple lymphomatous polyposis type, and subsequent mass lesions with or without ulceration; however, an ulcer type with a stricture is extremely rare. We report a case of a 79-year-old male with severe jejunal stricture due to FL with an uncommon chromosomal translocation t(2;18)(p12;q21). The patient was treated with jejunectomy subsequent rituximab monotherapy with a favorable response. The presence of the stricture made its endoscopic diagnosis confusing; however, it was certainly accompanied by the distinctive white granules on the surface of the tumor as seen in typical FL. With the possibility of an FL with stricture in mind, it is important to collect subtle endoscopic findings of the surrounding mucosa carefully, in order to arrive at an accurate endoscopic diagnosis and eventually to the proper therapeutic option.

Kyoto classification risk scoring system and endoscopic grading of gastric intestinal metaplasia for gastric cancer: Multicenter observation study in Japan.

OBJECTIVES: The usefulness of endoscopic and histological risk assessment for gastric cancer (GC) has not been fully investigated in Japanese clinical practice. METHODS: In this multicenter observation study, GC and non-GC patients were prospectively enrolled in 10 Japanese facilities. The Kyoto classification risk scoring system, the Kimura-Takemoto endoscopic atrophy classification, the endoscopic grading of gastric intestinal metaplasia (EGGIM), the operative link on gastritis assessment (OLGA) and the operative link on gastric intestinal metaplasia assessment (OLGIM) were applied to all patients. The strength of an association with GC risk was compared. In addition, important endoscopic findings in the Kyoto classification were identified. RESULTS: Overall, 115 GC and 265 non-GC patients were analyzed. Each risk stratification method had a significant association with GC risk in univariate analysis. In multivariate analysis, OLGIM stage III/IV (odds ratio [OR] 2.8 [95% CI 1.5-5.3]), high EGGIM score (OR 1.8 [1.0-3.1]) and opened-type Kimura-Takemoto (OR 2.5 [1.4-4.5]) had significant associations with GC risk. In the Kyoto classification, opened-type endoscopic atrophy, invisible regular arrangement of collecting venules (RAC), extensive (>30%) intestinal metaplasia in the corpus in image-enhanced endoscopy, and map-like redness in the corpus were independent high-risk endoscopic findings. The modified Kyoto classification risk scoring system using these four findings demonstrated a better area under the receiver operating characteristic curve value (0.750, P = 0.052) than that of the original Kyoto classification (0.706). CONCLUSIONS: The OLGIM stage III/IV, high EGGIM score and open-typed Kimura-Takemoto had strong association with GC risk in Japanese patients. The modified Kyoto classification risk scoring system may be useful for GC risk assessment, which warrants further validation. (UMIN000027023).

Novel genomic alteration in superficial esophageal squamous cell neoplasms in non-smoker non-drinker females.

Alcohol consumption and smoking pose a significant risk for esophageal squamous cell neoplasia (ESCN) development in males; however, ESCN is often diagnosed in non-drinking and non-smoking females. The mechanisms underlying these differences remain elusive, and understanding them can potentially identify novel pathways involved in ESCN development. We performed short-read sequencing to identify somatic variants on a cancer panel targeting 409 genes using DNA extracted from the superficial squamous cell carcinoma (ESCC) tissues and adjacent non-neoplastic epithelium (NE), and immunohistochemical staining of the protein encoded by the target gene. All male patients (n = 117) were drinkers or smokers, whereas 45% of the female patients (n = 33) were not. Somatic variants were compared among three age-matched groups: 13 female ESCC patients with smoking and drinking habits (known-risk group, F-KR), 13 female ESCC patients without these habits (unknown-risk group, F-UR), and 27 males with ESCC and smoking and drinking habits (M-KR). In the NE, the frequencies of CDKN2A variants were significantly higher in F-UR than in F-KR and M-KR. In both ESCC and NE, p14ARF was significantly overexpressed in F-UR than in the other groups. In conclusion, CDKN2A might be important in ESCC development, independent of known risk factors.

A simple prediction score for in-hospital mortality in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality. METHODS: We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores. RESULTS: We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05). CONCLUSIONS: We derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available ( https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android).

Characteristics of the gut microbiome profile in obese patients with colorectal cancer.

BACKGROUND AND AIM: Obesity affects the gut microbiome, which in turn increases the risk for colorectal cancer. Several studies have shown the mechanisms by which some bacteria may influence the development of colorectal cancer; however, gut microbiome characteristics in obese patients with colorectal cancer remain unclear. Therefore, this study evaluated their gut microbiome profile and its relationship with metabolic markers. METHODS: The study assessed fecal samples from 36 consecutive patients with colorectal cancer and 38 controls without colorectal cancer. To identify microbiotic variations between patients with colorectal cancer and controls, as well as between nonobese and obese individuals, 16S rRNA gene amplicon sequencing was performed. RESULTS: Principal coordinate analysis showed significant differences in the overall structure of the microbiome among the study groups. The α-diversity, assessed by the Chao1 index or Shannon index, was higher in patients with colorectal cancer versus controls. The relative abundance of the genera Enterococcus, Capnocytophaga, and Polaribacter was significantly altered in obese patients with colorectal cancer, whose serum low-density lipoprotein concentrations were positively correlated with the abundance of the genus Enterococcus; among the most abundant species was Enterococcus faecalis, observed at lower levels in obese versus nonobese patients. CONCLUSIONS: This study demonstrated several compositional alterations of the gut microbiome in patients with colorectal cancer and showed that a reduced presence of E. faecalis may be associated with obesity-related colorectal cancer development. The gut microbiome may provide novel insights into the potential mechanisms in obesity-related colorectal carcinogenesis.

Long-term endoscopic surveillance for Barrett's esophagus in Japan: Multicenter prospective cohort study.

OBJECTS: Although a recent study showed the cancer incidence of Barrett's esophagus (BE) to be 1.2%/year in 251 patient-years in Japan, the long-term outcomes remain unclear. The present study estimated the cancer risk of BE in Japan using our original prospective multicenter cohort. METHODS: A total of 98 patients with BE of maximum length of ≥2 cm were enrolled during the period of 2010-2012 and received at least one follow-up endoscopy over 5 years thereafter. Cancer incidence rates with 95% confidence interval for occurrence of esophageal adenocarcinoma (EAC) were calculated as the number of events divided by patient-years of follow-up and were expressed as %/year. RESULTS: Overall, the median endoscopic follow-up period was 59.9 (first and third quartiles, 48.5-60.8) months, constituting a total of 427 patient-years of observation. Since two EAC cases developed, the cancer incidence was 0.47% (0.01%-1.81%)/year. The cancer incidence was 0.39% (-0.16% to 2.44%) in 232 patient-years and 0.31% (-0.13% to 1.95%)/year in 318 patient-years for 55 cases with specialized intestinal metaplasia and 70 with BE ≥3 cm (maximum), respectively. At the end of follow-up, 12 of 92 patients (13.0%) died, but none died from EAC. CONCLUSION: This is the largest prospective follow-up study with endoscopy to investigate the incidence of EAC in unequivocal BE with the maximum length of ≥2 cm in Japan. Although a further large-scale study will be required to validate our results, the cancer risk of BE in Japan would be lower than previously reported (0.47% vs 1.2%/year).