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.

An Unusual Small Bowel Phytobezoar Successfully Resolved by Double-balloon Enteroscopy.

We herein report a very unusual case of small bowel obstruction caused by phytobezoar in a 69-year-old woman who consumed a large amount of bracken. The patient presented with nausea and vomiting. Computed tomography revealed an air-filled foreign body in the jejunum that had likely caused the small bowel obstruction. A fibrous foreign body diagnosed as a phytobezoar was detected using double-balloon enteroscopy. The obstruction was successfully resolved by crushing the phytobezoar repeatedly using a snare. Small bowel obstructions caused by phytobezoars are often treated with surgical interventions. However, endoscopic fragmentation using a snare is a minimally invasive treatment alternative.

Linked color imaging improves the diagnostic accuracy of eosinophilic esophagitis.

Objectives: To assess the usefulness of linked color imaging (LCI), a recently developed image-enhanced endoscopy technique, in the endoscopic diagnosis of eosinophilic esophagitis (EoE). Methods: Thirty white light images (WLIs) and 30 WLI+LCI images collected from patients with and without EoE were randomly and blindly reviewed by 10 endoscopists, including four experts (Exs) and six non-Exs. Edema, ring, exudate furrows, and strictures were rated on the adjusted EoE endoscopic reference score; the diagnosis of EoE was assessed. Using the kappa value, inter- and intra-observer agreements were analyzed among endoscopists. Results: WLI+LCI images had a higher diagnostic accuracy for EoE than WLIs (0.85 vs. 0.70, respectively), especially in non-Exs or endoscopists with no experience with EoE patients. Inter-observer agreement for WLI+LCI images statistically surpassed WLIs for furrows (kappa, 0.73 vs. 0.67, respectively; p = 0.0013), stricture (kappa, 0.51 vs. 0.39, respectively; p = 0.0072), and diagnosis (kappa, 0.67 vs. 0.57, respectively; p < 0.0001) of EoE. The increase in inter-observer agreement in WLI+LCI images allowed for a reduction in the differences between the Exs and non-Ex endoscopists. Intra-observer agreement for WLI+LCI images surpassed WLIs for a ring (kappa, 0.62 vs. 0.43, p = 0.0052), and a similar trend was found in exudates, furrows, and diagnosis irrespective of the Exs or non-Exs. Conclusions: LCI can contribute to the improvement of the endoscopic diagnosis for EoE, with "moderate" to "substantial" consistency, by enhancing the visibility of abnormal findings, leading to reduced diagnostic disparities among endoscopists.

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.

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.

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.

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.

Small-bowel Capsule Endoscopic Features in Patients with Eosinophilic Gastroenteritis: Three Case Reports.

Eosinophilic gastroenteritis (EGE) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes and presents with a variety of gastrointestinal manifestations. Important diagnostic evidence for EGE can be provided by endoscopy; however, the specific small-bowel capsule endoscopic (SBCE) findings remain unknown. We herein report the SBCE findings of three cases of EGE as well as those of the previous cases. The most common findings in patients with EGE were multiple erythema and erosions with surrounding redness on SBCE; these findings should be considered for the diagnostic evaluation for EGE.