Prevalence and Risk Factors of Constipation Symptoms among Patients Undergoing Colonoscopy: A Single-Center Cross-Sectional Study.

INTRODUCTION: Constipation is one of the most common gastrointestinal symptoms. It may compromise quality of life and social functioning and result in increased healthcare use and costs. We aimed to evaluate the prevalence and risk factors of constipation symptoms, as well as those of refractory constipation symptoms among patients who underwent colonoscopy. METHODS: Over 4.5 years, patients who underwent colonoscopy and completed questionnaires were analyzed. Patients' symptoms were evaluated using the Gastrointestinal Symptoms Rating Scale. RESULTS: Among 8,621 eligible patients, the prevalence of constipation symptoms was 33.3%. Multivariate analysis revealed female sex (odds ratio [OR] 1.7, P < 0.001), older age (OR 1.3, P < 0.001), cerebral stroke with paralysis (OR 1.7, P = 0.009), chronic renal failure (OR 2.6, P < 0.001), ischemic heart disease (OR 1.3, P = 0.008), diabetes (OR 1.4, P < 0.001), chronic obstructive pulmonary disease (OR 1.5, P = 0.002), benzodiazepine use (OR 1.7, P < 0.001), antiparkinsonian medications use (OR 1.9, P = 0.030), and opioid use (OR 2.1, P = 0.002) as independent risk factors for constipation symptoms. The number of patients taking any medication for constipation was 1,134 (13.2%); however, refractory symptoms of constipation were still present in 61.4% of these patients. Diabetes (OR 1.5, P = 0.028) and irritable bowel syndrome (OR 3.1, P < 0.001) were identified as predictors for refractory constipation symptoms. CONCLUSIONS: Constipation occurred in one-third of patients, and more than half of patients still exhibited refractory symptoms of constipation despite taking laxatives. Multiple medications and concurrent diseases seem to be associated with constipation symptoms.

Miliary tuberculosis diagnosed by diffuse hepatic uptake on PET/CT and transjugular liver biopsy.

The patient was an 81-year-old man. In his 20s, he had been treated with pharmacotherapy for pulmonary tuberculosis for 1 year. He presented to the Department of Respiratory Medicine with a chief complaint of dyspnea. The possibility of respiratory disease appeared to be low, but hepatic impairment was detected. The patient was thus referred to our department. Though the cause of hepatic impairment was unknown, the soluble interleukin-2 receptor level was elevated, suggesting malignant lymphoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) revealed diffuse, homogenous, intense FDG uptake in the entire liver, and transjugular liver biopsy confirmed the diagnosis. Histopathological examination revealed an epithelioid granuloma, and auramine staining was positive for bacilli suggestive of tuberculosis. CT revealed diffuse micronodular shadows in the lung, yielding a diagnosis of miliary tuberculosis. Therefore, the patient was prescribed antituberculosis medication by the Department of Respiratory Medicine. His subsequent clinical course was good. The miliary (hepatic) tuberculosis was typical based on the diffuse, homogenous, intense FDG uptake throughout the liver observed on PET-CT.

Main causes of death in advanced biliary tract cancer.

BACKGROUND: There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC. METHODS: We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020. We classified the main causes of death based on laboratory data, imaging studies, and medical records. The main causes of death evaluated included liver failure, cholangitis, cachexia, other causes associated with tumor progression, and complications. We also analyzed survival rates for each main cause of death. RESULTS: After excluding patients who were lost to follow-up, living patients, and patients who had no records of laboratory data within 30 days before the date of death, 108 patients were analyzed. The main cause of death was cholangitis in 33 (30.6%), cachexia in 22 (20.4%), liver failure in 10 (9.3%), other causes associated with tumor progression in 18 (16.7%), and complications in 25 (23.2%) patients. Median overall survival (OS) was 334.0 days in the chemotherapy group and 75.0 days in the best supportive care (BSC) group. Survival analyzed according to the main cause of death was significantly different between the chemotherapy and BSC groups; OS for cachexia, cholangitis, liver failure, other causes associated with tumor progression, and complications, respectively, were 453.0, 499.0, 567.0, 205.0, and 327.5 days (p = 0.003) in the chemotherapy group and 219.0, 69.0, 34.0, 93.0, and 56.0 days (p = 0.001) in the BSC group. CONCLUSION: The main causes of death in patients with advanced BTC are cholangitis, cachexia, liver failure, other causes associated with tumor progression, and complications. Other causes associated with tumor progression in the chemotherapy group, and liver failure in the BSC group as the main causes of death shortened the survival of BTC patients.

[FIP1L1::PDGFRA-positive chronic eosinophilic leukemia presenting with multiple ulcers of oral cavity and gastrointestinal tract].

A 66-year-old man developed multiple erosions and pain in the lips and mouth, fever, and black stools. There was persistent bleeding from the lip erosions. When he was admitted to our hospital, his white blood cell count increased to 53,420/µl with 3% eosinophils, and hemoglobin decreased to 3.1 g/dl. Bone marrow biopsy revealed an elevated eosinophil level (24.0%) with markedly toxic granules. Gastrointestinal endoscopy revealed multiple ulcers and erosions in the pharynx, esophagus, stomach, and colon. Histopathological diagnosis indicated nonspecific inflammation with poor infiltration of eosinophils. Bone marrow FISH test was positive for 4q12 deletion (FIP1L1::PDGFRA), leading to the diagnosis of FIP1L1::PDGFRA-positive chronic eosinophilic leukemia. Following initiation of oral administration of imatinib 100 mg/day, the number of eosinophils decreased rapidly, and normalized 2 days after the start of imatinib. The mucosal lesions showed significant improvement and were diagnosed as leukemia-associated lesions. Based on the clinical course of our patient, multiple oral cavity and gastrointestinal ulcers could be the initial presentation in this leukemia.

Molecular and clinicopathological analysis of three cases of gastric juvenile polyposis.

Background and Aim: Juvenile polyposis (JP) is a rare disease known to be associated with mutations either in SMAD4/BMPR1A. JP is known to often develop into malignant tumors, with a reported probability of 9-50%. However, the mechanisms of its carcinogenesis are not fully understood. We tried to elucidate the mechanisms of malignant transformation underlying this condition in three cases of gastric JP. Methods: We selected polyps from each patient displaying varying degrees of atypia and their nearby normal polyps and compared them using immunohistochemistry, Sanger sequencing, and loss of heterozygosity (LOH) analysis of SMAD4, BMPR1A, and TP53. Results: Two of the three cases were suspected of having germline SMAD4 mutations based on their familial medical histories; the remaining case was found to have a SMAD4 germline mutation following preoperative genetic testing. All three cases were shown to present with both SMAD4 positive and negative areas across each lesion, with the neoplastic lesions tending to show stronger nuclear SMAD4 expression. This expression was closely associated with the SMAD4 LOH status; however, we also noted paradoxical SMAD4 expression in the neoplastic lesions despite the biallelic inactivation of SMAD4 revealed in the genetic evaluation. Conclusions: These data suggest that strong nuclear expression of SMAD4, even when seemingly paradoxical, seems to be closely associated with dysplastic polyps in JP. Complete inactivation of SMAD4 was not shown to be essential for the development of dysplastic polyps in gastric JP, and other pathways seemed to be involved in the acquisition of the malignant phenotype.

Clinicopathological and mutational analysis of esophageal basaloid squamous cell carcinoma.

Esophageal basaloid squamous cell carcinoma (EBSCC) is a poorly differentiated variant of esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinicopathological and molecular biological characteristics of EBSCC and enrolled 58 patients with EBSCCs. Clinicopathological factors including age, sex, tumor size and location, gross tumor type (superficial, protrusive, ulcerative, and unclassifiable), lymphovascular invasion, infiltrative growth, intramural invasion, TNM stage, and dominant histological type were examined. EBSCCs were classified into four types (solid, cribri, microcystic, and tubular) according to the dominant histology. Next-generation sequencing (NGS) of a cancer hotspot panel was performed in 19 cases. NGS identified TP53 as the most frequently mutated gene, and copy number variation analysis revealed the most frequent loss of heterozygosity (LOH) at the ataxia telangiectasia mutated (ATM) and retinoblastoma 1 (RB1) loci. Target sequencing for TP53 was performed for the remaining 39 cases. We also performed LOH analysis for TP53, ATM, and RB1 and immunohistochemical staining for p53, ATM, and Rb in all cases. The rates of TP53 mutations and LOH and p53 aberrant expression were high (79.3%, 63.2%, and 72.4%, respectively); however, the frequencies were similar to those reported for ESCC. LOH rates of the RB1 and ATM loci were also high (55.3% and 67.2%, respectively). Overall survival rate was 66.5%, and recurrence-free survival rate was 55.0%. Only conventional clinicopathological factors had a prognostic impact in EBSCC; the microcystic type had the poorest prognosis. Our findings could be useful in developing novel treatment strategies for EBSCC.

Gastrointestinal endoscopy trends in a designated hospital for specified infectious diseases in Japan during the dawn of the "living with COVID-19" era.

January 2020 marked the very early period of SARS-CoV-2's arrival in Japan. At the time, we immediately and strictly adopted the use of enhanced PPE, including a N95, gown, gloves, eye protection, and an apron, during every endoscopic procedure for every patient, with or without COVID-19. One reason why we use enhanced PPE for every patient is because all endoscopic procedures should be considered aerosol-generating procedures, and another reason is that asymptomatic patients with COVID-19 cannot be identified during a pandemic. The volume of endoscopic screening/surveillance endoscopies decreased markedly, but therapeutic endoscopies did not decrease. In contrast, urgent endoscopic hemostasis has increased more than ever. The most common reason for the increase might be that the lack of protective equipment and the need for medical staff to deal with an unknown virus, creating a pandemic panic in emergency medicine.

[Successful treatment with cidofovir for disseminated adenovirus infection accompanied by hemophagocytic syndrome and meningitis in an allogeneic hematopoietic stem cell transplantation recipient].

A 65-year-old woman received bone marrow transplantation from an HLA-DRB1 one locus mismatched donor for high-risk myelodysplastic syndrome. On day 237 after transplantation, she developed recurrent acute gastrointestinal graft-versus-host disease and adenoviral hemorrhagic cystitis. Hence, the methylprednisolone (mPSL) dose was increased to 2 mg/kg, and mesenchymal stem cells were administered. After the dose was tapered, she developed high fever, gross hematuria, and progressive pancytopenia. Then, the serum LDH, ferritin, and hepatobiliary enzyme levels of the patient increased, and hemophagocytosis was observed based on bone marrow examination. The adenovirus DNA level in the plasma was 6.3×106 copies/ml on day 278, and the volume of cerebrospinal fluid increased. Hence, the patient was diagnosed with meningitis and disseminated adenovirus infection. On day 288, cidofovir was administered at a dose of 1 mg/kg three times a week for 8 doses. The mPSL dose was again increased to 2 mg/kg for the treatment of hemophagocytic syndrome. Then, the patient's symptoms gradually improved, and the adenovirus viral load became negative on day 369. Based on the clinical course of our patient, cidofovir is useful for severe adenovirus infection.

Molecular Characteristics of Lymphocyte-predominant Triple-negative Breast Cancer.

BACKGROUND/AIM: Tumor-infiltrating lymphocytes (TILs) are considered a prognostic marker for triple-negative breast cancer (TNBC). Immune checkpoint inhibitor (ICI)-based treatments are more effective for tumors with PD-L1-positive TILs, suggesting crucial roles of TILs in the local tumor immunity. However, factors attracting TILs are still largely unknown. Focusing on tumor antigenicity, we examined TNBC samples to identify the characteristics of TIL-high tumors. PATIENTS AND METHODS: Nine treatment-naïve TNBCs (TIL-high: five, TIL-low: four) were subjected to next-generation sequencing (NGS). Loss of heterozygosity (LOH) of PTEN was also analyzed. RESULTS: A variety of copy number variations were observed, and no genes differed significantly between TIL-high and -low groups. However, PTEN loss was more frequently observed in the TIL-high group: 60% compared to 25% in TIL-low tumors. NGS correlated well with LOH analysis in identifying PTEN loss. All three tumors with PTEN loss in the TIL-high group showed high PD-L1. All nine samples were microsatellite-stable. CONCLUSION: Frequent PTEN loss and high expression of PD-L1 in TIL-high TNBC suggest that PTEN mutation may be a biomarker for ICIs.

Molecular and clinicopathological features of appendiceal mucinous neoplasms.

Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.

Endoscopic resection for gastrointestinal tumors (esophageal, gastric, colorectal tumors): Japanese standard and future prospects.

Endoscopic resection (ER) techniques such as polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely accepted as a less invasive treatment for gastrointestinal (GI) tumors. Since there is a limit to the size that can be resected by EMR and it is often divided, it is not possible to accurately evaluate the degree of cancer progression, and the cancer remains or causes recurrence. ESD is a technology that overcomes these weaknesses. ER techniques are considered for tumors that have a very low possibility of lymph node metastasis and are suitable for en-bloc resection. As ESD became more widespread, the difficulty of treating ESD was gradually resolved by the development of technology and equipment, the curative resection rate increased, and the complication rate decreased. ER techniques have become the standard treatment for early cancer and precancerous lesions in Japan, and the therapeutic indications are expanding day by day. The indications for whether endoscopic treatment can be performed are defined by the guidelines for each organ such as the esophagus, stomach, and colorectum. In the coming aging society, it is also necessary to evaluate the indications for endoscopic treatment and invasive treatment. In addition, recent advances in endoscopic technology are making it possible to remove submucosal tumors that previously required surgery. In this review, we summarize the recent Japanese standard indications of ER for each GI location and future prospects of ER.

Clinicopathological and mutational differences between tumors with multiple metastases and single lung metastasis in colorectal cancer.

Cancer metastasis, particularly multiple metastatic cancer, is a significant event that affects patient prognosis. However, single metastasis can be treated by partial resection, although the clinicopathological and molecular profile of single lung metastasis has not been thoroughly elucidated. The present study examined tumor heterogeneity by comparing the mutation status between primary colorectal cancer (CRC) and corresponding metastatic lesions to identify prognostic factors associated with single lung metastasis and multiple metastases. The present study enrolled 31 cases of CRC; 20 cases with multiple metastases and 11 cases with single lung metastasis. Clinicopathologically, all cases with multiple metastases were tubular adenocarcinoma, and 3/11 cases with single metastasis were mucinous adenocarcinoma originating from the left side, the remaining 8 cases were tubular adenocarcinoma from the left side. CRC cases with multiple metastases exhibited more frequent vascular invasion, but not lymphatic invasion, than those with single lung metastasis. Furthermore, CRC with multiple metastases was associated with strong tumor budding (P=0.04). Patients with CRC with multiple metastases had lower recurrence-free survival rates compared with those with single lung metastasis (P=0.02). However, there was no significant difference between these two groups in terms of overall survival rates. A next-generation sequencing cancer hotspot panel was used to analyze a heterochronous multiple metastases case, including brain metastasis. Sanger sequencing, immunohistochemistry and microsatellite instability were examined for all 31 cases to reveal the molecular features. KRAS and TP53 mutation signatures were largely preserved throughout the metastatic events. TP53/APC mutations and overexpression of p53 appeared to be associated with the presence of lymphovascular invasion and strong tumor budding, respectively, although these differences were not statistically significant. Early relapses in patients with CRC could be a sign for eventual multiple metastases, although these may not affect the overall survival of patients with CRC. Considerable mutational changes were seemingly rare during metastatic events in patients with CRC.

Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation.

BACKGROUND: Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colorectal malignancy with expression of enteroblastic markers (glypican 3, SALL4, AFP); however, the clinicopathological and epidemiological features are not fully elucidated. AIMS: The aims of this study were to elucidate and establish the molecular and clinicopathological characteristics of CAED. MATERIALS AND METHODS: In addition to three cases recently diagnosed as CAED, colorectal carcinoma (CRC) with expression of enteroblastic markers were selected by using immunohistochemistry (IHC) on tissue microarrays of 988 advanced CRC. We employed next-generation sequencing (NGS) and Sanger sequencing for the detection of genetic alterations. IHC for p53 and HER2, HER2-FISH and MSI status was also investigated. Survival analyses for clinicopathological parameters were performed using Kaplan-Meier methods. RESULTS: Thirty-nine cases (4.0%) were positive for at least one enteroblastic marker. Histological evaluation of the total of 42 cases revealed that 10 contained tumour cells with clear cytoplasm. Enteroblastic marker-positive cases had aggressive behaviour and poor prognosis. NGS revealed TP53 as the most frequently mutated gene. The rate of HER2-positive cases and MSI-H cases was 9.5% (four of 42) and 12.2% (five of 41), respectively. Among these 42 cases, there were no molecular and clinicopathological differences according to the presence of tumour cells with clear cytoplasm. CONCLUSIONS: Enteroblastic marker-positive CRC could be grouped together as CAED regardless of clear cell cytoplasm. Using this definition, the frequency of CAED is 4.0% and has a poorer prognosis than that for conventional CRCs. HER2 targeted therapy would be a meaningful treatment for CAED, and CAEDs contain both MSI-H and MSI-stable CRCs, although the MSS phenotype is dominant.

[Successful delivery after chemotherapy for acute myeloid leukemia diagnosed in the second trimester].

Development of acute myeloid leukemia (AML) during pregnancy is rare, and the available data are limited to small retrospective reports. Currently, no guidelines exist for the management of AML during pregnancy in Japan. A 26-year-old female was diagnosed with AML at 19 weeks of gestation, received chemotherapy with daunorubicin and cytarabine, and achieved complete remission. Following the first consolidation therapy, she gave birth to a 1964-g female infant by cesarean section at 33 weeks of gestation. One week later, she was initiated on the second consolidation therapy; however, she developed a pelvic abscess during neutropenia. She underwent urgent surgery for open drainage and recovered soon after surgery. She has been in complete remission for eight months, and the daughter is healthy. Chemotherapy delivered after the second trimester rarely causes congenital malformations and may not require the termination of pregnancy. The clinical course of the present case suggests that chemotherapy can be performed safely and effectively in pregnant patients with AML after the trimester and babies.

Molecular and clinicopathological analyses of esophageal carcinosarcoma with special reference to morphological change.

The molecular pathogenesis of esophageal carcinosarcoma (ECS) has not been fully investigated. This study includes 16 consequent cases of surgically resected ECS. Genetic alterations were independently examined for carcinoma in situ, carcinomatous, and sarcomatous areas. Six cases were analyzed by next-generation sequencing, and the remaining cases were analyzed by Sanger sequencing for TP53, PTEN, and INI1. Sarcomatous components in 3 cases showed histologically heterogenous feature of osteosarcoma. Lymph node metastasis was found in 12 out of 16 cases. Survival analysis revealed 5-year overall survival rate of 59.9%, and the median survival time was 5.37 years. TP53 was the most frequently mutated gene, being identified in 11 of 16 patients (68.8%), 7 of whom (63.6%) had the same mutations in both carcinomatous and sarcomatous areas. Almost complete concordance was found between p53 immunohistochemistry and TP53 missense mutations. Five-year overall survival tended to be worse for patients with p53 overexpression, although the data was not significant (p = 0.186). Nine of 16 patients (56.3%) showed loss of heterozygosity (LOH) at the INI1 locus, and this LOH status was consistent with both components. However, interestingly, INI1 expression was preserved in all cases. In addition, copy number variation analysis revealed gene amplification in several tyrosine kinase receptors. Accumulation of mutations in tumor suppressor genes such as TP53 and INI1 seemed to occur during ECS development.

Frequent loss of heterozygosity of SMAD4 locus and prognostic impacts of SMAD4 immunohistochemistry in gastric adenocarcinoma with enteroblastic differentiation.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare variant of gastric adenocarcinoma. Clinicopathologically, GAED is known to be aggressive and is characterized by frequent vascular invasion, lymphatic invasion, and liver metastasis even in early stages. SMAD4 was identified as a frequently deleted gene in GAED by copy number variation analysis in our previous next-generation sequencing study; therefore, we examined the clinicopathological impacts of SMAD4 in 51 cases of GAEDs (early: 17, advanced: 34). We performed Sanger sequencing for SMAD4 mutations and loss of heterozygosity (LOH) analysis of the SMAD4 locus, in addition to immunohistochemistry for SMAD4, to determine its clinicopathological correlations and impacts on survival. The frequency of LOH at the SMAD4 locus was 45.1%, and it was significantly higher in GAED compared to in conventional gastric adenocarcinoma. SMAD4 mutations were not found in any case. Reduced SMAD4 expression was found in 60.8% of cases; it was significantly correlated with advanced stages and lymph node metastasis and showed trends of larger tumor size and lymphatic invasion. Reduced SMAD4 expression in metastatic lymph nodes was found in 21 of 36 cases. Survival analysis revealed that reduced SMAD4 expression significantly affected the patient's overall survival (OS) and recurrence-free survival (RFS), although multivariate analysis showed that only liver metastasis and lymphatic infiltration (Ly+) were independent prognostic factors for OS and RFS. The SMAD4 locus is one of the susceptibility genes in this tumor, although SMAD4 mutation was not detected. Furthermore, the inactivation of SMAD4 appeared to contribute to the aggressiveness of GAED.

[Philadelphia chromosome-positive acute lymphoblastic leukemia relapsing with an anterior chamber lesion of the eye].

A 48-year-old Filipino woman underwent umbilical cord blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia under non-remission status. Left aqueous humor puncture was performed owing to the development of left eye pain and exacerbation of anterior eye chamber inflammation 72 days after the transplantation; this revealed the relapse of leukemia in the anterior chamber. Subsequently, the patient tested positive for peripheral blood minimal residual disease. Therefore, doctors should take note that anterior chamber disease may appear as a non-typical relapse of leukemia.

TP53 inactivation and expression of methylation-associated proteins in gastric adenocarcinoma with enteroblastic differentiation.

Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare variant of aggressive adenocarcinoma. We demonstrated previously that GAED is genetically characterized by frequent TP53 mutation. In this study, we aimed to further clarify the mechanism of inactivation of TP53 in GAED in the light of promoter methylation of TP53, and expression of methylation-associated proteins such as Ten-eleven translocation (TET) 1 and 5-hydroxymethylcytosine (5-hmc) in addition to ATM mutations. We analyzed 51 cases of GAED. The ATM mutation was detected in only one case. Promoter methylation of TP53 was detected in 18% and frequency of loss of heterozygosity (LOH) at TP53 locus was 37.2%. Reduced TET1 expression was found in 29 cases (56.9%) and was significantly associated with advanced stage (p = 0.01), lymph node metastasis (p = 0.04), and macroscopic type (p = 0.01). Reduced 5-hmc expression was found in 28 cases (54.9%) and was significantly associated with advanced stage (p = 0.01), gender (p = 0.01), tumor location (p = 0.03), tumor size (p = 0.01), and lymph node metastasis (p = 0.01). Among 9 cases with TP53 promoter methylation, reduced expression of TET1 was observed in 6 cases, and reduced expression of 5-hmc was observed in 5 cases. Reduced expression of both TET1 and 5-hmc was significantly associated with adverse clinical outcomes. In summary, promoter methylation of TP53 is partly involved in loss of p53 expression. Aberrant methylation by reduced TET1 and 5-hmc may be involved in the development of aggressive GAED.

White opaque substance visualized by magnifying narrow-band imaging is associated with intragastric acid conditions.

BACKGROUND AND STUDY AIMS: The presence of white opaque substance (WOS) is an endoscopic marker of intestinal metaplasia. Considering that the nature of WOS is absorbed lipid droplets, lipase plays an important role in the lipid absorption process and is inactivated at strong acidity. WOS may only be present in a hypochlorhydria state following Helicobacter pylori infection, and, thus, may not be highly sensitive marker, especially in H. pylori- eradicated patients. We investigated the relationship between WOS and gastric acid conditions. PATIENTS AND METHODS: A total of 501 patients were retrospectively evaluated for the presence of WOS at 2 regions of interest using magnifying narrow-band imaging. The pH level of collected gastric juice was also measured. Study end points were (1) prevalence of WOS and its relationship with gastric juice pH in 3 groups: H. pylori- uninfected , H. pylori- infected, and H. pylori -eradicated; (2) the relationship between prevalence of WOS and gastric juice pH before and after proton pump inhibitor (PPI) administration in 29 H. pylori -eradicated cases. RESULTS: Prevalence of WOS was 0 % (0 /206), 28.4 % (31/109), and 3.2 % (6/186) in the H. pylori -uninfected, H. pylori -infected, and H. pylori -eradicated groups, respectively. Mean gastric juice pH was significantly higher in WOS-positive cases than in WOS-negative cases in the H. pylori -infected and H. pylori -eradicated groups ( P  < 0.0001). Mean gastric juice pH increased from 1.1 to 6.9 after PPI administration and WOS prevalence increased from 0 % (0/29) to 45 % (13/29) of cases. CONCLUSION: The prevalence of WOS is closely associated with the neutralization of intragastric pH.