A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

Different Food Preferences in Patients with Gastrointestinal Disorders.

Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusions Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.

Characteristic endoscopic findings in early-stage autoimmune gastritis.

Background and study aims Until recently, autoimmune gastritis (AIG) was usually diagnosed at late stages based on typical endoscopic findings, including corpus-dominant advanced atrophy. Early-stage AIG prior to complete gastric atrophy had rarely been diagnosed due to a lack of knowledge about its endoscopic characteristics. The present study sought to identify the endoscopic characteristics of early-stage AIG, enabling its early diagnosis. Patients and methods The clinical and endoscopic findings of 12 patients diagnosed with early-stage AIG between 2016 and 2021 were retrospectively evaluated. Patients were included if they were: (1) positive for serum anti-parietal cell antibody; (2) diagnosed with histological early-stage AIG; and (3) endoscopically positive for folds on the greater curvature of the gastric corpus. Results Two characteristic endoscopic findings of early-stage AIG were identified: longitudinal alignment of pseudopolyps (i.e., a bamboo joint-like appearance) and swelling of gastric areas with erythema (i.e., a salmon roe-like appearance). Conclusions Endoscopic findings characteristic of early-stage AIG include a bamboo joint-like appearance and a salmon roe-like appearance. Studies in large numbers of patients with long-term follow-up are needed to confirm these findings.

Appendiceal mucocele pathologically classified as appendiceal epithelial hyperplasia and preoperatively diagnosed by contrast-enhanced ultrasonography: A case report.

We report a patient with a mucocele with diffuse wall thickening diagnosed by transabdominal ultrasonography and contrast-enhanced ultrasonography. Transabdominal ultrasonography showed diffuse thickening of the entire appendix wall and an anechoic area that appeared to be fluid collected throughout the appendix lumen. However, the "onion skin sign" was not detected. Contrast-enhanced ultrasonography combined with superb microvascular imaging revealed abundant mucosal blood flow and no abnormal vascular network within the mucosa of the appendix wall. We preoperatively diagnosed a mucocele complicated by acute and chronic appendicitis, and ileocecal resection was performed. Macroscopic and microscopic findings of the resected specimens demonstrated that the appendiceal wall was diffusely thickened, with fibrosis and inflammatory cell infiltration, and that the appendiceal root rumen was narrowed with epithelial hyperplasia. No neoplastic changes were observed. The cause of the appendiceal mucocele was likely fibrosis and stenosis at the root of the appendix due to initial acute appendicitis.

Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study.

AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

Brain activity in response to food images in patients with irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are caused and exacerbated by consumption of fatty foods. However, no study has evaluated brain activity in response to food images in patients with disorders of gut-brain interaction (DGBI). This study aimed to compare food preference and brain activity when viewing food images between patients with DGBI and healthy controls. METHODS: FD and IBS were diagnosed using the ROME IV criteria. Food preference was assessed using a visual analog scale (VAS). Brain activity in the prefrontal cortex (PFC) in response to food images was investigated using functional near-infrared spectroscopy (fNIRS). RESULTS: Forty-one patients were enrolled, including 25 with DGBI. The mean VAS scores for all foods (controls vs. FD vs. IBS: 69.1 ± 3.3 vs. 54.8 ± 3.8 vs. 62.8 ± 3.7, p = 0.02), including fatty foods (78.1 ± 5.4 vs. 43.4 ± 6.3 vs. 64.7 ± 6.1, p < 0.01), were the lowest in patients with FD among all groups. Patients with FD had significantly higher brain activity in the left PFC than those with IBS and healthy controls (mean z-scores in controls vs. FD vs. IBS: - 0.077 ± 0.03 vs. 0.125 ± 0.04 vs. - 0.002 ± 0.03, p < 0.001). CONCLUSIONS: Patients with DGBI, particularly those with FD, disliked fatty foods. The brain activity in patients with DGBI differed from that in healthy controls. Increased activity in the PFC of patients with FD was confirmed.

Diagnostic criteria and endoscopic and histological findings of autoimmune gastritis in Japan.

The Japanese diagnostic criteria for autoimmune gastritis (AIG) were established by the "Study Group on the establishment of diagnostic criteria for type A gastritis," which is related to a workshop associated with the Japan Gastroenterological Endoscopy Society (JGES) and the Committee of AIG Research Group (CARP). The criteria were set as follows: the cases of confirmed diagnosis are patients in whom either the endoscopic or histological findings, or both, meet the requirements for AIG and who are confirmed to be positive for gastric autoantibodies (either anti-parietal cell or anti-intrinsic factor antibodies, or both). The presentation of endoscopic findings of early-stage AIG in the diagnostic criteria was withheld owing to the need for further accumulation and characterization of endoscopic clinical data. Therefore, diagnosis of early-stage AIG only requires histological confirmation and gastric autoantibody positivity. Suspected cases are patients in whom either the endoscopic or histological findings, or both, meet only the requirements for AIG. Histological findings only meet the requirements for early stage. AIG has been underdiagnosed in the past, but our study group's newly proposed diagnostic criteria will enable a more accurate and early diagnosis of AIG. The criteria can be used to stratify patients into various high-risk groups for gastric tumors and pernicious anemia. They would allow the establishment of an appropriate surveillance system in the coming years. Nevertheless, issues such as establishing the endoscopic findings of early-stage AIG and obtaining Japanese insurance coverage for gastric autoantibody tests require attention.

Clinical characteristics and manometric findings of esophageal achalasia-a systematic review regarding differences among three subtypes.

Esophageal achalasia is classified into three subtypes according to manometric findings. Since several factors, including clinical characteristics and treatment response, have been reported to differ among the subtypes, the underlying pathogenesis may also differ. However, a comprehensive understanding regarding the differences is still lacking. We therefore performed a systematic review of the differences among the three subtypes of achalasia to clarify the current level of comprehension. In terms of clinical features, type III, which is the least frequently diagnosed of the three subtypes, showed the oldest age and most severe symptoms, such as chest pain. In contrast, type I showed a higher prevalence of lung complications, and type II showed weight loss more frequently than the other types. Histopathologically, type I showed a high loss of ganglion cells in esophagus, and on a molecular basis, type III had elevated serum pro-inflammatory cytokine levels. In addition to peristalsis and the lower esophageal sphincter (LES) function, the upper esophageal sphincter (UES) function of achalasia has attracted attention, as an impaired UES function is associated with severe aspiration pneumonia, a fatal complication of achalasia. Previous studies have indicated that type II shows a higher UES pressure than the other subtypes, while an earlier decline in the UES function has been confirmed in type I. Differences in the treatment response are also crucial for managing achalasia patients. A number of studies have reported better responses in type II cases and less favorable responses in type III cases to pneumatic dilatation. These differences help shed light on the pathogenesis of achalasia and support its clinical management according to the subtype.

Benefit of Continuation of Low-Dose Imatinib for Gastrointestinal Stromal Tumors despite Adverse Events with Regular-Dose Imatinib.

Tyrosine kinase inhibitors (TKIs) such as imatinib improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). However, treatment options for GISTs are still limited, and the continuation of TKIs is difficult due to adverse events in some cases. The effectiveness of low-dose imatinib is unclear. We report 2 cases to show effectiveness of low-dose imatinib in patients with adverse events. The first case is a male in his early 60s with a history of intestinal GIST resection who was diagnosed with recurrent GIST with peritoneal dissemination. He was started on low-dose imatinib (300 mg) because of a history of subconjunctival hemorrhage after receiving postoperative imatinib. Follow-up contrast-enhanced ultrasonography revealed that the tumors had shrunk in size and number after 2 months of treatment with 300-mg imatinib. He continued this treatment and showed partial response for 8 months. The second case is a female in her late 70s with rectal GIST who was treated with imatinib 400 mg. Due to a severe skin lesion, she changed her treatment to sunitinib 2 months after initiation. However, new metastasis in the liver was confirmed after 4 months of administration of sunitinib. She underwent surgical esection of the rectal tumor to reduce the volume. After the surgery, low-dose imatinib (300 mg) with oral steroids was adopted. Follow-up confirmed the absence of recurrence at the rectum and no increase in hepatic tumor size for 18 months. Aggressive treatment with low-dose imatinib instead of discontinuation or alteration of treatment may benefit patients with unresectable and postoperative GISTs with sensible mutation to imatinib.

A Case of Autoimmune Gastritis and Hepatitis with Enlarging Gastric Polyps after Reducing the Dose of Prednisolone.

Autoimmune gastritis is immune-mediated gastritis that destroys the oxyntic mucosa. Autoimmune hepatitis is an inflammatory liver disease caused by an autoimmune reaction. These diseases share similar pathogeneses as organ-specific autoimmune disorders; however, cases involving both diseases are quite rare and scarcely reported. Herein, we report a patient with concurrent autoimmune gastritis and hepatitis who developed enlargement of hyperplastic polyps and progression of gastric atrophy. The patient was a 79-year-old female referred to our hospital for the treatment of hyperplastic polyps detected on a follow-up upper gastrointestinal endoscopy. The patient's previous upper gastrointestinal endoscopy from 3 years prior revealed small hyperplastic polyps and no mucosal atrophy. However, the current upper gastrointestinal endoscopy revealed three 10-mm red polyps, severe mucosal atrophy in the corpus, and mild atrophy in the antral area. In addition, biopsy samples from the gastric body revealed decreased parietal cells and diffuse lymphocytic infiltration of the deep mucosa. Further, chromogranin A-positive endocrine cell micronests and enterochromaffin-like cell hyperplasia were detected. After confirming the diagnosis of autoimmune gastritis, endoscopic mucosal resection was performed for all the polyps, which were histopathologically diagnosed as hyperplastic polyps without malignancy. Therefore, clinicians should consider autoimmune gastritis for enlarged hyperplastic polyps and gastric atrophy progression.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Development, Disappearance, and Clinical Course of Melanosis Coli: Sex Differences in the Progression of Severity.

Melanosis coli (MC) is an acquired colorectal disorder visualized as colonic mucosa pigmentation. Disease severity is confirmed based on MC depth, shape, and coloration, although the clinical course is not fully understood. This study sought to clarify characteristics of MC development and disappearance and to investigate its clinical course and severity. Contributors to MC grade progression were explored. This study reviewed MC cases discovered via colonoscopy at a single institution over a 10-year period. Of all 216 MC cases, 17 developing and 10 disappearing cases were detected. Anthranoid laxative use was a key factor: 29.4% of the developing cases had used such agents before the initial MC diagnosis, whereas 40% of disappearing cases had discontinued anthranoids prior to detection of MC disappearance. Among 70 grade I cases, progression to grade II occurred in 16 cases during a mean follow-up of 3.67±2.1 years (rate of progression=22.8%). Males more commonly showed progressive than stable grade I cases, and the probability of progression was higher for male than for female cases. An association between anthranoid administration and MC presence was presumed, and grade I MC was found to progress in severity over 5 years.

Two Cases of Acute Gastric Mucosal Lesions Due to Helicobacter pylori Infection Confirmed to be Transient Infection.

Two adult cases of acute gastric mucosal lesions (AGML) caused by Helicobacter pylori infection were confirmed by spontaneous eradication during the follow-up period. The clinical course of the initial infection by H. pylori in adults with AGML remains unclear, whether it is transient or progresses to a persistent infection. In these two reported cases, gastric biopsies at the time of the onset revealed the presence of H. pylori; however, serum H. pylori antibodies performed at the same time were negative. Retesting for H. pylori serum antibody, after six months in one and after two months in the other, was negative, confirming spontaneous eradication.

Artificial Intelligence-Based Diagnostic Support System for Functional Dyspepsia Based on Brain Activity and Food Preference.

Background and aim Disorders of gut-brain interaction (DGBI) are disorders where no organic clinical abnormalities are detected such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). The brain activity of individuals with FD and IBS differs from that of healthy controls. Artificial intelligence can distinguish healthy controls from individuals with DGBI using several biomarkers. This study aimed to establish an artificial intelligence-based diagnostic support system using food preferences and brain activity in patients with DGBI. Methods ROME IV criteria were used to diagnose patients with FD and IBS. Their food preference was scored using a visual analog scale, and brain activity in the prefrontal cortex was investigated using functional near-infrared spectroscopy (fNIRS). The diagnostic model was developed based on the brain activity and visual analog scale scores for food using an artificial neural network model. Results Forty-one participants, including 25 patients with DGBI were enrolled in the study. The accuracy of the artificial intelligence-based diagnostic model using an artificial neural network in differentiating between healthy controls and patients with DGBI and between healthy controls and those with FD were 72.3% and 77.1%, respectively. Conclusions The artificial intelligence-based diagnostic model using brain activity and preference to food images showed sufficiently high accuracy in distinguishing patients with DGBI from healthy controls, and those with FD from healthy controls. Therefore, the fNIRS system provides objective evidence for diagnosing DGBI.

Severe grade of melanosis coli is associated with a higher detection rate of colorectal adenoma.

The severity and distribution of melanosis coli differ among individuals, and the related factors remain unknown. Additionally, their clinical implications have not been sufficiently demon-strated. Thus, we aimed to detect clinical factors related to the severity and range of melanosis coli and elucidate the associations between the grade, location, and detection rate of colorectal neoplasms. Colonoscopy cases performed at our institution from January 2011 to February 2021 were included. Melanosis coli was classified into mild and severe grades. Clinical characteristics and neoplasm detection rates were compared between the mild and severe MC groups and between the right-sided and whole-colon melanosis coli groups. Overall, 236 MC (mild, n = 143; severe, n = 93) cases, of which 50 were right-sided, 5 were left-sided, and 181 were whole-colon melanosis coli cases, were enrolled. The proportion of anthranoid users was higher in the severe melanosis coli group than in the mild melanosis coli group. The adenoma detection rate was higher in the severe melanosis coli and whole-colon melanosis coli groups. The prevalence of neoplasms measuring 5-9 mm and >9 mm was higher in the severe melanosis coli group (p<0.01 and p = 0.04). Severe melanosis coli due to anthranoid usage is associated with colorectal adenoma development.

Helicobacter pylori-Negative Advanced Gastric Cancer Arising from the Gastric Mucosa without Inflammation, Atrophy, or Intestinal Metaplasia.

Gastric cancer is strongly associated with atrophic gastritis associated with Helicobacter pylori infection. The eradication of H. pylori has been reported to improve inflammation of the gastric mucosa, atrophy, and intestinal metaplasia and has also been shown to inhibit the development and growth of gastric cancer. Advanced gastric cancer from H. pylori-negative mucosa without inflammation, atrophy, or intestinal epithelialization is rarely found. We report on two cases of advanced gastric cancer without endoscopic evidence of gastric mucosal atrophy. One case was in the gastric angle 9 years after H. pylori eradication and the other case was in the pylorus of an uninfected stomach. Although gastric cancer is strongly associated with atrophic gastritis caused by H. pylori infection, postoperative histopathological examination of the stomach in both cases showed no inflammation, atrophy, or intestinal metaplasia. Poorly differentiated adenocarcinomas were confirmed at the microscopic level, and both cases were determined to be type 4 using the Borrmann classification. There is a body of evidence showing that H. pylori infection can cause gastric cancer and is the most prevalent infection-induced cancer in the world. The 2 cases here displayed different carcinogenesis than gastric mucosal atrophy caused by H. pylori infection. With the spread of H. pylori eradication treatments and an increasing number of uninfected patients, these case reports can contribute to future strategies for the diagnosis of gastric cancer.

Asymptomatic gangrenous cholecystitis diagnosed using contrast-enhanced ultrasonography in a patient with pancreatic cancer.

A 72-year-old female without abdominal symptoms visited our hospital for routine follow-up while undergoing pancreatic cancer treatment (using TS-1). Her vital signs were normal, and her abdomen was soft and non-tender. Blood test revealed elevated C-reactive protein levels with normal white blood cell count. Computed tomography was performed for follow-up of pancreatic cancer. Contrast-enhanced computed tomography showed partial discontinuity and irregular thickness of the gallbladder wall; however, a definitive diagnosis was not obtained due to unclear imaging. Contrast-enhanced transabdominal ultrasonography revealed intraluminal membranes in the gallbladder and a perfusion defect at the bottom, indicating gangrenous cholecystitis. Surgical resection was performed, and pathological examination showed severe necrosis of the gallbladder wall, consistent with the findings of contrast-enhanced transabdominal ultrasonography.

The role of advanced endoscopy in the management of inflammatory digestive diseases (upper gastrointestinal tract).

The Japan Gastroenterological Endoscopy Society held four serial symposia between 2019 and 2020 on the state-of-the-art of issues related to upper GI inflammatory diseases. This review discusses some of the topics addressed in these symposia. The papers regarding nonerosive reflux disease, recent improvements in intraesophageal pH-impedance monitoring and endoscopic diagnosis using image-enhanced endoscopy have been published. Many publications have addressed its usefulness in endoscopic treatment of gastroesophageal reflux disease such as anti-reflux mucosectomy. In the management of eosinophilic esophagitis, since the symptoms are subjective, objective indicators have been sought, and ultrasonography and high-resolution manometry may be useful tools for evaluation. The natural course of this condition, especially of asymptomatic cases, is not well clarified. Some newly developed anti-acid or anti-inflammatory medicines are now under investigation. With regard to autoimmune gastritis, because of widespread medical examinations, diagnosis of asymptomatic cases has been increasing. Recently, its endoscopic characteristics have become clear and the natural history of these conditions is being elucidated. The Kyoto Classification of Gastritis has been reported to be useful not only for Helicobacter pylori diagnosis but also for identification of risks of gastric cancer. Its usefulness is now recognized in Asia and Europe.