Publications by authors named "Junji Yokoyama"

66 Publications

New cine magnetic resonance imaging parameters for the differential diagnosis of chronic intestinal pseudo-obstruction.

Sci Rep 2021 Nov 26;11(1):22974. Epub 2021 Nov 26.

Division of Gastroenterology, Graduate School of Medical and Dental Sciences, Niigata University, 757-1, Asahimachidori, Chuo-ku, Niigata-city, Niigata, 951-8510, Japan.

Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder whose diagnosis currently relies on subjective imaging assessments. Cine magnetic resonance imaging (MRI) may potentially improve the quantitative analysis of gastrointestinal motility; however, suitable CIPO detection parameters should be determined. Cine MRI was performed in seven patients with CIPO and 11 healthy controls. The logarithm of the Mahalanobis distance (x) and distance variation per time (x) were used as the original parameters to determine CIPO diagnostic thresholds. Furthermore, the correlation between cine MRI findings and CIPO severity was investigated. Threshold values of α = 1.10 and β = 0.15 for x and x, respectively, produced a CIPO diagnosis sensitivity of 1.00 (7/7) and specificity of 0.82 (9/11). The resulting error was 0.11 (2/18). The two parameters were correlated (Pearson's correlation coefficient: - 0.52). Any of the intestinal tracts of patients with severe CIPO requiring home parenteral nutrition belonged to the region defined by x ≥ 1.10 and x ≤ 0.15. Cine MRI is effective for the quantitative evaluation of small intestinal motility and CIPO diagnosis when using the abovementioned parameters and can be useful for treatment decision-making. However, these parameters have a wide distribution in healthy volunteers; this may complicate the detection of other disorders.
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http://dx.doi.org/10.1038/s41598-021-02268-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626471PMC
November 2021

Rapid progression of colonic mucinous adenocarcinoma with immunosuppressive condition: A case report and review of literature.

World J Clin Cases 2021 Oct;9(30):9182-9191

Division of Gastroenterology and Hepatology, Niigata University, Niigata 9518510, Japan.

Background: Colorectal mucinous adenocarcinoma is a rare subtype of colorectal cancer and is characterized by an abundance of mucin in the tumor. In addition, the colorectal mucinous adenocarcinoma often demonstrates poor differentiation in the histology of tumor cells and poor prognosis compared with those with adenocarcinoma. Here, we present the case of a young woman with colonic mucinous adenocarcinoma showing significantly rapid progression within four months of immunosuppressant therapy for Henoch-Schönlein purpura.

Case Summary: Here we report a rare case of ascending colon mucinous adenocarcinoma with lymph node and liver metastases which developed and progressed rapidly within four months during the treatment of Henoch-Schönlein purpura using corticosteroids. The systemic screening examinations showed no tumors before the immunosuppressant therapy. Fortunately, the patient was successfully treated with chemotherapy.

Conclusion: While no direct evidence that the immunosuppressants accelerated the tumor development, the case presenta tion and review of the literature demonstrated that surveillance for malignancies before and during treatment with immunosuppressive agents is essential.
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http://dx.doi.org/10.12998/wjcc.v9.i30.9182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567511PMC
October 2021

Rapid Onset of Weight Gain and Liver Dysfunction Successfully Treated With Nutrition and Exercise.

Cureus 2021 Jul 21;13(7):e16530. Epub 2021 Jul 21.

Gastroenterology and Hepatology, Niigata University, Niigata, JPN.

Physical inactivity is one of the causes of most metabolic syndromes. The incidence of metabolic syndrome is expected to increase in the near future because of the reduced opportunities for exercise caused by COVID-19. Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD in the world. NAFLD is characterized by excessive triglyceride (TG) accumulation in the hepatocytes due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Thus far, no study quantitatively assessed the liver fat deposition after a rapid decline in physical activity. Herein, we describe a case of a 17-year-old Japanese boy with severe fat infiltration of the liver, due to a rapid decline in physical activity, treated at our facility. Our rehabilitation and nutritional support teams administered appropriate exercise and nutrition support to reduce weight and improve liver dysfunction. Our findings support dietary changes and exercise therapy to manage such cases.
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http://dx.doi.org/10.7759/cureus.16530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378298PMC
July 2021

Increase in muscle mass associated with the prebiotic effects of 1-kestose in super-elderly patients with sarcopenia.

Biosci Microbiota Food Health 2021 20;40(3):150-155. Epub 2021 Feb 20.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata 951-8510, Japan.

Sarcopenia causes functional disorders and decreases the quality of life. Thus, it has attracted substantial attention in the aging modern world. Dysbiosis of the intestinal microbiota is associated with sarcopenia; however, it remains unclear whether prebiotics change the microbiota composition and result in the subsequent recovery of muscle atrophy in elderly patients with sarcopenia. This study aimed to assess the effects of prebiotics in super-elderly patients with sarcopenia. We analyzed the effects of 1-kestose on the changes in the intestinal microbiota and body composition using a next-generation sequencer and a multi-frequency bioimpedance analysis device. The population was significantly increased in the intestine after 1-kestose administration. In addition, in all six patients after 12 weeks of 1-kestose administration, the skeletal muscle mass index was greater, and the body fat percentage was lower. This is the first study to show that administration of a prebiotic increased the population of in the intestinal microbiota and caused recovery of muscle atrophy in super-elderly patients with sarcopenia.
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http://dx.doi.org/10.12938/bmfh.2020-063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279888PMC
February 2021

A case of -negative early gastric adenocarcinoma with gastrointestinal phenotype.

Endosc Int Open 2021 Jun 27;9(6):E863-E866. Epub 2021 May 27.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with ; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an infection. This case may potentially help explain gastric cancer development in the absence of infection.
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http://dx.doi.org/10.1055/a-1396-3854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159579PMC
June 2021

Rapid decline in visceral adipose tissue over 1 month is associated with poor prognosis in patients with unresectable pancreatic cancer.

Cancer Med 2021 07 16;10(13):4291-4301. Epub 2021 May 16.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Background: Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer.

Methods: We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross-sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated.

Results: In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16-6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13-5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis.

Conclusion: Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short-term assessment of body composition changes may be a rational approach to predict prognosis in these patients.
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http://dx.doi.org/10.1002/cam4.3964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267120PMC
July 2021

Comparison of Oral and Esophageal Microbiota in Patients with Achalasia Before and After Peroral Endoscopic Myotomy.

Turk J Gastroenterol 2021 01;32(1):42-52

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background/aims: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC.

Materials And Methods: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared.

Results: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC.

Conclusions: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.
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http://dx.doi.org/10.5152/tjg.2020.19995DOI Listing
January 2021

Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge.

Int J Mol Sci 2021 Jan 31;22(3). Epub 2021 Jan 31.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength that occurs with aging or in association with various diseases. The condition is prevalent worldwide and occurs more frequently in patients with chronic diseases owing to the intrinsic relationship of muscles with glucose, lipid, and protein metabolism. Liver cirrhosis is characterized by the progression of necro-inflammatory liver diseases, which leads to fibrosis, portal hypertension, and a catabolic state, which causes loss of muscle tissue. Sarcopenia is of significant concern in the state of liver cirrhosis because sarcopenia has been associated with higher mortality, increased hospital admissions, worse post-liver transplant outcomes, decreased quality of life, and increased risk for other complications associated with cirrhosis. Therefore, sarcopenia is also an important feature of liver cirrhosis, representing a negative prognostic factor and influencing mortality. An increased understanding of sarcopenia could lead to the development of novel therapeutic approaches that could help improve the cognitive impairment of cirrhotic patients; therefore, we present a review of the mechanisms and diagnosis of sarcopenia in liver disease and existing therapeutic approaches.
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http://dx.doi.org/10.3390/ijms22031425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867020PMC
January 2021

Evaluation of intestinal microbiota, short-chain fatty acids, and immunoglobulin a in diversion colitis.

Biochem Biophys Rep 2021 Mar 30;25:100892. Epub 2020 Dec 30.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially , which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.
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http://dx.doi.org/10.1016/j.bbrep.2020.100892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797511PMC
March 2021

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis: A case report.

World J Clin Cases 2020 Nov;8(22):5821-5830

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 9518510, Japan.

Background: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized.

Case Summary: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.

Conclusion: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716308PMC
November 2020

Esophageal High-Resolution Manometry for Diagnosing the Severity of the Chronic Intestinal Pseudo-Obstruction: A Case Series.

Dig Dis Sci 2021 11 12;66(11):3960-3967. Epub 2020 Nov 12.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.

Background: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized.

Aim: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease.

Methods: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement.

Results: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility.

Conclusions: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.
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http://dx.doi.org/10.1007/s10620-020-06701-9DOI Listing
November 2021

Rare case of circumferential esophageal peeling.

Clin Case Rep 2020 Jul 13;8(7):1306-1308. Epub 2020 Apr 13.

Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata Japan.

This report highlights the easy peeling of the esophageal epithelium with Nikolsky phenomenon after swallowing the foreign body and the healing status of the esophagus only 3 days later in a patient of pemphigus vulgaris.
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http://dx.doi.org/10.1002/ccr3.2846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364067PMC
July 2020

Monitoring chronological change by liver-to-spleen attenuation ratio for secondary hepatic steatosis for a short term.

Clin J Gastroenterol 2020 Dec 27;13(6):1219-1224. Epub 2020 Jun 27.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.

Parenteral nutrition-associated liver disease (PNALD) causes hepatic steatosis and moderate liver enzyme elevation due to lack of enteral nutrition and deficiency of some nutrients. However, the period for recovery from PNALD after a nutritional intervention is unknown with no report. Herein, we report a case of a 44-year-old Japanese woman with severe fatty infiltration of the liver due to malnutrition. Our nutritional support team administered appropriate total parenteral, especially fat and carnitine, nutrition to improve her malnutrition. Chronological changes in liver-to-spleen attenuation ratio were also considered because of her disease state. Computed tomography demonstrated improved attenuation of the liver, and the liver enzymes level normalized after 5 weeks from appropriate nutrition. Understanding the nutritional condition of a patient may help in elucidating an appropriate treatment strategy.
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http://dx.doi.org/10.1007/s12328-020-01165-wDOI Listing
December 2020

Cytapheresis for pyoderma gangrenosum associated with inflammatory bowel disease: A review of current status.

World J Clin Cases 2020 Jun;8(11):2092-2101

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis clinically characterized by the presence of painful skin ulcerations with erythematous. As it is frequently associated with inflammatory bowel diseases, including ulcerative colitis, gastroenterologists should be familiar with the disease including therapeutic options. Therefore, we have conducted a review focusing on the cytapheresis for PG in cases of inflammatory bowel diseases. A literature search was conducted to extract studies published in the last 20 years, with information on demographics, clinical symptoms, treatment, and the clinical course from a total of 22 cases reported and our recent case. In most patients, cytapheresis was associated with improvement or resolution of PG after failure of conventional therapeutic options such as corticosteroids, antibiotics, immunosuppressive agents and immunoglobulin. Based on the information summarized, cytapheresis is helpful in the majority of patients with PG refractory to medical treatment associated with inflammatory bowel diseases and could be further studied in a multicenter, randomized trial.
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http://dx.doi.org/10.12998/wjcc.v8.i11.2092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281039PMC
June 2020

Visceral Adipose Tissue Index and Hepatocellular Carcinoma Are Independent Predictors of Outcome in Patients with Cirrhosis Having Endoscopic Treatment for Esophageal Varices.

Dig Dis 2021 25;39(1):58-65. Epub 2020 May 25.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background: The relationship between the amount of adipose tissue and advanced-stage liver cirrhosis with esophageal varices (EV) is unknown. We aimed to reveal the prognostic significance of adipose tissues in patients with liver cirrhosis.

Methods: We enrolled 87 patients with EV who received initial endoscopic treatment and underwent scheduled treatments in our hospital. Computed tomography (CT) images were obtained of a 5-mm slice at the umbilical level. We evaluated the effect of mortality based on the visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue ratio (VSR).

Results: Cox hazard multivariate analysis showed that the presence of hepatocellular carcinoma (HCC; hazard ratio [HR]: 4.650, 95% confidence interval [CI]: 1.750-12.353, p = 0.002), γ-GTP (HR: 1.003, 95% CI: 1.001-1.006, p = 0.026), and VATI (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) significantly affected mortality. Cox hazard multivariate analysis for liver-related death was also significantly affected by HCC (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) and VATI (HR: 1.052, 95% CI: 1.019-1.086, p = 0.002). The difference between the Child-Pugh scores 12 months after treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, p = 0.027). Patients with high VATI had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (p = 0.044).

Conclusion: Our findings suggest that VATI measured by CT could significantly predict mortality in cirrhosis patients through decreasing liver function and increasing HCC frequency, and appropriately controlling VATI could improve their prognosis.
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http://dx.doi.org/10.1159/000508867DOI Listing
February 2021

Esophageal Ulcers Associated with Ulcerative Colitis: A Case Series and Literature Review.

Intern Med 2020 Aug 23;59(16):1983-1989. Epub 2020 May 23.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.

Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esophageal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18 previously reported cases are summarized. This case series and literature review will encourage the accurate diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.
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http://dx.doi.org/10.2169/internalmedicine.4437-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492127PMC
August 2020

Variation in small bowel transit time on capsule endoscopy.

Ann Transl Med 2020 Mar;8(6):348

Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.

Background: Small bowel motility remains inadequately understood because of the complex and various functions as well as its anatomical position. The aimed of the study was to investigate the small bowel transit time (SBTT) of capsule endoscopy (CE) and to analyze the clinical factors affecting SBTT.

Methods: SBTT was analyzed in patients who underwent small bowel CE. Factors contributing to SBTT and CE retention were investigated.

Results: Among 397 patients enrolled in this study, 336 (84.6%) completed CE. The mean SBTT (± standard deviation) was 282.1±132.2 min. According to the univariate and multivariate analyses, aging and small bowel stenosis extended SBTT. In 38 patients who underwent multiple CE studies, considerable variation in SBTT were observed [mean of standard deviations (SDs) =97.97 min, SD of the SDs =81.99 min]. CE retention was observed in 61 patients (13.3%), and it was statistically associated to small bowel lesion.

Conclusions: Aging and small bowel stenosis were associated with longer SBTT. Furthermore, SBTT analyzed by CE should be interpreted carefully considering the intra-individual differences in SBTT.
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http://dx.doi.org/10.21037/atm.2020.02.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186741PMC
March 2020

Small Intestinal Bacterial Overgrowth Diagnosed by a Breath Test and Improved by Rifaximin in a Patient with Hepatic Encephalopathy and Alcoholic Liver Cirrhosis.

Intern Med 2020 Aug 23;59(15):1849-1853. Epub 2020 Apr 23.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.

A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.
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http://dx.doi.org/10.2169/internalmedicine.4593-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7474984PMC
August 2020

Rare Genotype of His/His in NUDT15 Codon 139 and Thiopurine-associated Adverse Events in a Case of Ulcerative Colitis.

Intern Med 2020 Jul 9;59(13):1611-1613. Epub 2020 Apr 9.

Division of Gastroenterology, Niigata University Medical and Dental Hospital, Japan.

Thiopurine drugs are commonly used to treat immunologic diseases. However, the narrow therapeutic safety margin demands evidence-based precision medicine approaches. NUDT15 variants are associated with thiopurine-induced adverse events, particularly in Asians. We herein report a rare genotype of His/His in NUDT15 codon 139 in a case of ulcerative colitis and review the relevant literature. The patient experienced severe thiopurine-associated adverse events, including leukopenia and alopecia. There is no literature on the His/His genotype in NUDT15 codon 139, and our case suggests cautious use or the contraindication of thiopurines for patients with this genotype.
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http://dx.doi.org/10.2169/internalmedicine.4261-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402964PMC
July 2020

Advanced squamous cell carcinoma in an asymptomatic, large, epiphrenic esophageal diverticulum.

Clin J Gastroenterol 2020 Aug 27;13(4):477-482. Epub 2020 Jan 27.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata , Niigata, 951-8510, Japan.

An asymptomatic epiphrenic diverticulum (ED) was diagnosed in a man undergoing annual esophagogastroduodenoscopy (EGD) at another hospital 40 years before he presented to our hospital at age 63 years for his annual EGD. However, because substantial food retention was found in the ED, we could not confirm a lesion. After the retained food was removed endoscopically, a second EGD showed a reddish, flat lesion with an elevated mass within the ED. Endoscopic ultrasonography indicated that the elevated mass was deep in the submucosal layer. An esophagram showed that the ED was approximately 80 mm in diameter, which is considered large. An endoscopic biopsy of the lesion confirmed squamous cell carcinoma. Total esophagectomy was performed. Microscopic examination revealed well-differentiated to moderately differentiated squamous cell carcinoma invading the adventitia at the elevated lesion. The final pathological stage was pT3N0M0. There was no evidence of recurrence for 3 years during the quarterly follow-up examinations. To our knowledge, this case involved the longest asymptomatic term (40 years) since the ED was detected. A review of 18 reported cases of carcinoma in an ED indicated that advanced cancer has a poor prognosis. Periodic follow-up of ED patients is essential for early diagnosis.
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http://dx.doi.org/10.1007/s12328-020-01098-4DOI Listing
August 2020

Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review.

World J Clin Cases 2019 Nov;7(21):3553-3561

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8122, Japan.

Background: Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date.

Case Summary: We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses.

Conclusion: The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.
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http://dx.doi.org/10.12998/wjcc.v7.i21.3553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854407PMC
November 2019

Wavy mucosal tear in the sigmoid colon.

Clin Case Rep 2019 Sep 7;7(9):1825-1826. Epub 2019 Aug 7.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University Niigata Japan.

Although linear mucosal tears have been reported, we found a relatively rare case of wavy mucosal tear in collagenous colitis. This may be related to the mutual weak adhesiveness between the epithelium and collagen band. This complication necessitates great care to be taken while performing colonoscopy in patients suspected of collagenous colitis.
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http://dx.doi.org/10.1002/ccr3.2275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745364PMC
September 2019

Change in body composition in patients with achalasia before and after peroral endoscopic myotomy.

J Gastroenterol Hepatol 2020 Apr 24;35(4):601-608. Epub 2019 Nov 24.

Division of Gastroenterology, Niigata University Medical and Dental Hospital, Niigata, Japan.

Background And Aim: Patients with achalasia experience weight loss because of dysphagia caused by impaired relaxation of the lower esophageal sphincter. This study aimed to use dual bioelectrical impedance analysis (BIA) to determine the change in bodyweight and body composition in patients with achalasia before and after peroral endoscopic myotomy (POEM).

Methods: Patients with achalasia who underwent POEM from 2013 to 2018 (n = 72) were retrospectively analyzed for change in bodyweight before and after 3 months. Additionally, change in body composition was prospectively investigated in the final 10 of 72 patients using non-radiation dual BIA.

Results: Twenty patients (27.8%) were underweight (body mass index < 18.5) before undergoing POEM. No clinical parameters were identified to be associated with the underweight condition before POEM and be predictive of an increase in bodyweight after POEM. Low visceral fat volume observed on dual BIA correlated closely with the result obtained using computed tomography (Pearson correlation coefficient: r = 0.850, P < 0.01). Patients with achalasia had a statistically significant increase in visceral (P < 0.01) and subcutaneous fat volumes (P < 0.01) after POEM. Skeletal muscle mass index slightly increased (P = 0.02), although the value after POEM was still low. No blood biomarkers were indicators for low bodyweight or low visceral fat volume.

Conclusions: Dual BIA is an effective non-invasive tool to evaluate the change in body composition of underweight patients with achalasia. Skeletal muscle volume was not enough after POEM, although a rapid increase in the intra-abdominal fat volume was observed. Additional studies are warranted to understand the pathological implications.
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http://dx.doi.org/10.1111/jgh.14847DOI Listing
April 2020

Efficacy of gelatin hydrogels incorporating triamcinolone acetonide for prevention of fibrosis in a mouse model.

Regen Ther 2019 Dec 10;11:41-46. Epub 2019 May 10.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Introduction: Triamcinolone acetonide (TA), a steroid, is often used clinically to prevent dysfunctions associated with fibrosis. The objective of this study was to examine whether TA can be suspended in a gelatin sheet for tissue engineering using a mouse skin wound model.

Methods: TA was suspended in biodegradable gelatin and freeze-dried in a sheet form. The sheet was analyzed for homogeneity and controlled release of TA by high-performance liquid chromatography. We made two skin wounds on the dorsal side of mice. Gelatin sheets with TA (TA sheet) and without TA (control sheet) were attached to each skin wound. To determine the efficacy of the prepared TA sheet on the skin wounds, TA-sheet versus TA-injection experiments were conducted. Hematoxylin and eosin staining was performed to assess the grade of epithelialization and alpha smooth muscle actin (α-SMA) immunohistochemical staining was conducted to evaluate myofibroblast infiltration.

Results: In the TA-release test , 7.7 ± 2.3% of TA was released from the sheet by 24 h. After replacing the initial phosphate-buffered saline (PBS) with collagenase PBS, the amount of released TA increased over time. The wound area/original skin wound area after 15 days with the TA sheet was significantly larger than that with the control sheet (26.9 ± 5.5% vs 10.7 ± 2.6%, p = 0.023). The α-SMA positive area/whole area with the TA sheet was significantly lower than that with the control sheet (4.65 ± 0.66% vs 7.24 ± 0.7%, p = 0.023). Furthermore, the α-SMA positive area/whole area with the TA sheet was significantly lower than that with TA injection (5.32 ± 0.45% vs 7.93 ± 0.75%, p = 0.013).

Conclusions: We developed a TA sheet and confirmed both the homogeneity of the suspended TA and controlled-release of the TA in the presence of collagenase . The TA sheet caused less myofibroblast infiltration into the tissue than the control sheet or TA injection did.
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http://dx.doi.org/10.1016/j.reth.2019.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518320PMC
December 2019

Evaluating the effect of injecting triamcinolone acetonide in two sessions for preventing esophageal stricture after endoscopic submucosal dissection.

Endosc Int Open 2019 Jun 17;7(6):E764-E770. Epub 2019 May 17.

Niigata University Medical and Dental Hospital, Division of Gastroenterology and Hepatology, Niigata, Japan.

Several previous reports indicate that endoscopic injection of triamcinolone acetonide (TA) after widespread endoscopic submucosal dissection (ESD) is effective for preventing esophageal stricture. We investigated the efficacy of injecting TA in two sessions for preventing stricture formation post-ESD. Sixty-six consecutive patients with widespread mucosal defects that affected more than three-fourths of the circumference of the esophagus were included. The study group (n = 40) received TA injections over two sessions: immediately after and 14 days after ESD. The control group (n = 26) did not receive a TA injection. This study was performed retrospectively against historical controls. The primary endpoint of this study was frequency of stricture after TA injection. The secondary endpoint was number of required endoscopic balloon dilations (EBDs) after TA injection. The post-ESD stricture rate among patients who had subcircumferential mucosal defects was 45.7 % in the study group (16/35 patients), which was significantly lower than the rate of 73.9 % in the control group (17/23 patients;  = 0.031). The number of EBD procedures required was significantly lower in the study group (median 0, range 0 - 7) than in the control group (median 4, range 0 - 20;  < 0.001). There was no significant difference between the study and control groups among the patients who had full circumferential mucosal defects. This study showed that performing two sessions of TA injection is an effective and safe treatment for prevention of esophageal stricture following subcircumferential ESD.
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http://dx.doi.org/10.1055/a-0894-4374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525005PMC
June 2019

Overlap in disease concept of functional esophageal disorders and minor esophageal motility disorders.

J Gastroenterol Hepatol 2019 Nov 7;34(11):1940-1945. Epub 2019 Jun 7.

Division of Gastroenterology, Niigata University Medical and Dental Hospital, Niigata, Japan.

Background And Aim: Functional gastrointestinal disorders are the most common disorders in gastroenterology and are currently considered as gut-brain interaction disorders with multiple related factors including motility disturbance. However, high-resolution manometry (HRM) had revealed a new disease concept known as minor esophageal motility disorders. This study aimed to investigate the correlation between functional esophageal disorders (FEDs) and minor esophageal motility disorders.

Methods: Functional esophageal disorders were diagnosed using upper endoscopy, pH monitoring, and HRM, to exclude achalasia, esophago-gastric junction outflow obstruction, and other major esophageal motility disorders. FEDs with or without minor esophageal motility disorders were compared using the Chicago classification.

Results: Twelve healthy volunteers also subjected to HRM showed no minor esophageal motility disorders. Of the 40 patients with FEDs, 15 (37.5%) were diagnosed with minor esophageal motility disorders. Characteristics were not different between patients with and without minor esophageal motility disorders (sex: P = 0.609, age: P = 0.054, body mass index: P = 0.137, and presence of psychiatric disorders: P = 0.404). The type and location of symptoms were not related to the comorbidity rate of minor esophageal motility disorders (P = 0.744 and 0.094). No patients with FEDs developed major esophageal motility disorders.

Conclusions: Minor esophageal motility disorders were frequently observed in FEDs, but the causal relationship between esophageal symptoms remains unclear. The disease concepts of FEDs and minor esophageal motility disorders are considered to overlap and are both independent of major esophageal motility disorders.
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http://dx.doi.org/10.1111/jgh.14691DOI Listing
November 2019

Management of endoscopic submucosal dissection for ulcerative colitis-associated neoplasia: Tips and pitfalls.

Dig Endosc 2019 Apr;31 Suppl 1:44-45

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan.

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http://dx.doi.org/10.1111/den.13324DOI Listing
April 2019

Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment.

World J Gastroenterol 2019 Mar;25(12):1457-1464

Division of Gastroenterology, Niigata University Medical and Dental Hospital, Niigata 951-8510, Japan.

Esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into three types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former two disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, particularly when it is located closer to the oral orifice. Since the condition itself is not malignant, minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including peroral endoscopic myotomy (POEM). However, the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. In this paper, we review the pathophysiology of each type of diverticulum and the current state-of-the-art treatment based on our experience.
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http://dx.doi.org/10.3748/wjg.v25.i12.1457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441918PMC
March 2019

Diverse perspectives to address for the future treatment of heterogeneous hepatocellular carcinoma.

Heliyon 2019 Mar 11;5(3):e01325. Epub 2019 Mar 11.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.

Hepatocellular carcinomas (HCCs), which often arise from chronic liver damage, have poor conditional 5-year survival and are recognized as heterogeneous tumors. Considering the heterogeneity of HCCs, diverse perspectives need to be addressed for treating such tumors, besides the findings of conventional imaging modalities and tumor markers. Data from the latest technologies, such as liquid biopsy, and the detection of the presence of cancer cells with stem/progenitor cell markers, gene mutations and diverse pathways, crosstalk with immune cells and cancer-associated fibroblasts, and mechanisms of epithelial-mesenchymal transition provide diverse lines of information. Integration of these data with clinical data might be necessary to develop effective therapies for precision medicine. Here, we review several aspects of dealing with the complexity of heterogeneous HCCs.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416651PMC
March 2019

Utility of measuring paraesophageal varices using computed tomography to select endoscopic treatment for patients with esophageal varices.

Dig Endosc 2019 May 29;31(3):335. Epub 2019 Mar 29.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

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http://dx.doi.org/10.1111/den.13383DOI Listing
May 2019
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