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DOI： 10.1093/ibd/izac015.090

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Overt hepatic encephalopathy (HE) is one of the complications of liver cirrhosis (LC), which negatively affects the prognosis and quality of life of patients. Small intestinal bacterial overgrowth (SIBO) is significantly associated with LC and its complications, including HE. We investigated the relationship between SIBO and LC, and the difference between hydrogen-producing and methane-producing SIBO (H-SIBO and M-SIBO, respectively). This is a prospective cohort study of 107 cases. Breath measurements of hydrogen and methane concentrations were performed for the diagnosis of SIBO. The study cohort included 81 males with a median age of 70 (40-86) years, and SIBO was detected in 31 cases (29.0%). There were no significant differences between the SIBO positive and SIBO negative groups. Reclassification into H-SIBO (16 cases) and others (91 cases) was performed, and the Child-Pugh score was only derived in the multivariate logistic analysis (P = 0.028, odds ratio 1.39, 95% confidence interval 1.04-1.85). Furthermore, H-SIBO was significantly associated with covert HE in chi-square test (50.0% vs. 24.2%, P = 0.034). In addition, we evaluated the therapeutic response on SIBO of rifaximin in eight covert HE patients. 20% patients with M-SIBO and 67% patients with H-SIBO showed an improvement of the breath test. In conclusion, H-SIBO, but not M-SIBO, is significantly associated with liver function, and rifaximin might be more effective for covert HE with H-SIBO. Therefore, the diagnosis of SIBO, including the classification as H-SIBO and M-SIBO, might help to determine the choice of treatment for HE.

DOI： 10.1371/journal.pone.0264459

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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 (x1) and distance variation per time (x2) 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 x1 and x2, 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 x1 ≥ 1.10 and x2 ≤ 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.

DOI： 10.1038/s41598-021-02268-1

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Jaundice may be persistent in drug-induced liver injury associated with vanishing bile duct syndrome. However, recurrent jaundice is atypical, following bile flow restoration. Here, we report a 28-year-old man with prolonged, recurrent jaundice (more than 300 days) and combined immunodeficiency (CID) of B-cells, T-cells, and natural killer (NK) cells. Hypogammaglobulinemia was observed throughout his hospitalization, and peripheral blood flow cytometry detected a few B-cells (2% of CD19 + cells and 2% of CD20 + cells). We further detected the dysfunction of T-cells and NK cells. Based on these findings, CID was diagnosed. We presumed that hypogammaglobulinemia was related to the jaundice. After regular injections of intravenous immunoglobulin (IVIG), the stool color gradually turned brown. However, the color returned to white as IgG levels decreased. The brown-to-white stool pattern was repeated with another IVIG administration, suggesting that the patient's serum immunoglobulin levels were related to the jaundice. On follow-up, IVIG was performed every two to three weeks, and his total bilirubin improved gradually. Immunoglobulin replacement therapy could be one of the treatment choices for jaundice with CID.

DOI： 10.1007/s12328-021-01347-0

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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 Lactobacillus, 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.

DOI： 10.1016/j.bbrep.2020.100892

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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.

DOI： 10.5152/tjg.2020.19995

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Focal nodular hyperplasia (FNH) is the second most frequent benign liver tumor, and it is a fiber-rich stiff lesion. Typically, FNH can be diagnosed by imaging without biopsy. However, liver biopsy and diagnostic resection may be required to differentiate atypical FNH from other liver tumors, such as hepatocellular adenoma (HCA). Therefore, improved noninvasive diagnostic methods are needed. We experienced 2 cases where combination of magnetic resonance elastography (MRE) and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) helped diagnose FNH. A 36-year-old woman and 17-year-old boy with liver tumors measuring 40 mm in diameter each showed hypointense nodule centers, indicating a central scar, surrounded by hyperintense signals during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. To rule out HCA, we performed MRE and liver biopsy. On MRE, the mean stiffness of the mass was 11.6 kPa (mean stiffness of the background liver was 1.7 kPa) and 11.1 kPa (mean stiffness of the background liver was 2.4 kPa) in the first and second patients, respectively. Histological examination of both specimens showed CK7-positive bile-ductular proliferations, abundant fibrous tissue, and few Ki-67-positive cells. Based on these results, we diagnosed these tumors as FNH. Combination of Gd-EOB-DTPA-enhanced MRI and MRE can evaluate the character and stiffness of lesion and help in the diagnosis of FNH.

DOI： 10.1159/000516552

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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 Bifidobacterium longum 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 B. longum in the intestinal microbiota and caused recovery of muscle atrophy in super-elderly patients with sarcopenia.

DOI： 10.12938/bmfh.2020-063

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Pancreatic pseudocyst-portal vein (PP-PV) fistula, mostly occurring after pseudocyst formation following acute/chronic pancreatitis, is a rare but life-threatening condition. The majority of treatments are based on conservative or surgical interventions. We report the case of a 70-year-old man with a PP-PV fistula and PV thrombosis. We adopted conservative treatment at first due to his mild symptoms. However, after resuming food intake, the patient had severe abdominal pain. Following endoscopic retrograde cholangiopancreatography, we found that the pseudocyst was connected with the PV through the fistula. Subsequently, an endoscopic nasopancreatic drainage (ENPD) catheter was inserted into the main pancreatic duct to establish pancreatic drainage, which resulted in a decrease in the abdominal pain. After the ENPD tube had been exchanged for endoscopic pancreatic stenting, his abdominal pain did not recur. Therefore, this case demonstrated endoscopic treatment as an effective treatment option for PP-PV fistula.

DOI： 10.1159/000510331

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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.

DOI： 10.1002/ccr3.2846

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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.

DOI： 10.12998/wjcc.v8.i11.2092

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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 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 post-treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, P = 0.027). Patients with high VSR had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (P = 0.024). 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.

DOI： 10.1159/000508867

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A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis.

DOI： 10.2169/internalmedicine.4112-19

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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.

DOI： 10.2169/internalmedicine.4437-20

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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.

DOI： 10.2169/internalmedicine.4261-19

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AME Publ Co  

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.

DOI： 10.21037/atm.2020.02.40

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The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

DOI： 10.1186/s41232-020-00121-y

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Fibromuscular dysplasia (FMD) and segmental arterial mediolysis (SAM) are noninflammatory, nonatherosclerotic arterial diseases that cause aneurysm, occlusion, and thromboses. These diseases are rarely seen in mesenteric arterial lesions; however, as they can be lethal if appropriate management is not provided, the accumulation of clinical information from cases is essential. We herein report the cases of a 57-year-old man diagnosed with FMD and a 63-year-old man diagnosed with SAM. We conclude that an early diagnosis with imaging modalities and clinical information followed by the appropriate treatment improves the prognosis of these arterial diseases.

DOI： 10.2169/internalmedicine.3094-19

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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.

DOI： 10.1111/jgh.14691

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DOI： 10.1016/j.gie.2019.05.040

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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.

DOI： 10.1002/ccr3.2275

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DOI： 10.1016/j.gie.2019.04.220

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AIM: A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis. METHODS: Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry. RESULTS: The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores. CONCLUSIONS: The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

DOI： 10.1111/hepr.13356

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BACKGROUND: Achalasia is a well-known esophageal motility disorder, but epidemiological studies in Japan are lacking. We investigated the incidence and period prevalence of achalasia in Japan, including the rate of coexistence of esophageal carcinoma, and evaluated treatment trends. METHODS: To estimate the nationwide number of patients with achalasia, a large-scale insurance claims database from 2005 to 2017 were used for our analyses. Patients with achalasia and coexistence of esophageal carcinoma were identified based on the diagnosis code registered. Interventional treatment was also evaluated. RESULTS: Of the total 5,493,650 populations, 385 were diagnosed with primary achalasia. The incidence was calculated as 0.81-1.37 per 100,000 person-years (male-to-female ratio was almost 1; mean age at diagnosis was 43.3 ± 14.4 years). The period prevalence was 7.0 per 100,000 persons. There were statistically significant trends of increase in the incidence and period prevalence over age groups (all p values < 0.0001). Four men with achalasia developed esophageal carcinoma, and the incidence of esophageal carcinoma with achalasia was estimated as 0.25 per 100 person-years. With regard to intervention, esophageal dilation was performed as a first treatment in 64.7% of patients, with repeat intervention required in 56.9% of these. The proportion of patients treated using peroral endoscopic myotomy (POEM) increased annually to 41.1% in 2017. CONCLUSIONS: In Japan, the incidence and period prevalence of achalasia is comparable to that in other countries. The absolute risk of esophageal carcinoma is rather low. Esophageal dilation has been the mainstay of achalasia treatment, and the role of POEM has increased annually.

DOI： 10.1007/s00535-018-01544-8

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BACKGROUND: Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION: A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS: Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.

DOI： 10.1186/s12876-019-1013-1

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Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease involving the intestine, and Guillain-Barré Syndrome (GBS) is rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. UC and GBS can be caused by immune system abnormalities and can co-exist. To date, there are 7 reported cases of GBS in patients with UC. However, only one patient developed UC after GBS treatment. We report a rare case of UC that appeared after intravenous immunoglobulin therapy for GBS. This case report and literature review will allow accurate and prompt diagnosis of co-existent GBS and UC.

DOI： 10.1007/s12328-019-00939-1

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Language：English   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.gie.2019.03.483

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Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 × 106) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

DOI： 10.1007/s00441-018-02981-w

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BACKGROUND: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of histologic criteria; however, the pathology is considered to be heterogeneous. There is no consensus on the management of this enigmatic disorder with an unknown etiology. PATIENTS AND METHODS: Data for patients diagnosed with EoGE and followed up over a 1-year period were analyzed. Their symptoms, patterns of flares, and type of treatment were documented. The shift in peripheral blood eosinophil levels was also examined. RESULTS: A total of 10 (mean age, 44 years; range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most frequent presenting symptom was abdominal pain, and eight patients were classified with mucosal type of EoGE. Chronic disease or multiple flares were observed in seven out of 10 (70.0%) patients, and all of them had a history of allergy. Four were corticosteroid dependent (three relapsed during corticosteroid tapering and one following corticosteroid withdrawal). One of them received anti-IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four patients with highly elevated initial eosinophil levels at diagnosis, the peripheral eosinophil level correlated with the amelioration and deterioration of their symptoms. The remaining three patients had a single flare without relapse. Two had no history of allergy. CONCLUSION: EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.

DOI： 10.1097/MEG.0000000000001241

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Hepatic progenitor cell (HPC) marker-positive hepatocellular carcinomas (HCCs) have recently been extensively analyzed, and their prognosis has been reported as poor compared to HPC marker-negative HCCs. However, previous studies have analyzed the existence of HPC marker-positive cancer cells only in primary lesions, as well as the recurrence rate and prognosis of such tumors. Here, we are the first to report the behavior of HPC marker-positive cancer cells during vascular invasion and metastasis of an HCC. We concurrently analyzed EpCAM- and/or NCAM-expressing cancer cells in the primary, vascular invasion, and metastatic lesions of an HCC. An HCC which includes EpCAM- and/or NCAM-expressing cancer cells has not been previously reported. EpCAM- and/or NCAM-positive cancer cells invaded the vessels and formed heterogeneous populations of these HPC marker-positive cancer cells with HPC marker-negative cancer cells. The frequency of HPC marker-positive cancer colonies and cells in vessels was higher than that in the primary HCC. In the metastatic lesions, EpCAM-positive cancer cells were more frequently detected than NCAM-positive cancer cells, indicating that EpCAM may be more important than NCAM for cancer cell settlement in the metastatic lesions. Furthermore, bigger metastatic tumors tended to include HPC marker-positive cancer cells, suggesting that HPC marker-positive cancer cells have a growth advantage in the metastatic lesions. These results showed that HPC marker-positive cancer cells would be important for vascular invasion and metastasis and suggested that HPC marker-positive cancer cells are an important target in HCC treatment. (C) 2019 The Author(s) Published by S. Karger AG, Basel.

DOI： 10.1159/000498913

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A 59-year-old woman was diagnosed with primary intestinal lymphangiectasia (PIL), with characteristic findings on capsule enteroscopy and confirmation by histopathological examination of biopsy specimens. We viewed the abnormal jejunal mucosa using a newly developed magnifying single-balloon enteroscope (SIF-Y0007). Conventional observation showed leakage of chyle. However, using this new scope, we could see scattered white villi, representing dilated lymphatic vessels within the intestinal villi protruding from the dilated submucosal lymphoid vessels (D2-40 positive) within an edematous jejunal lesion. This report is the first to describe the white villi in a patient with PIL observed clearly using a newly developed magnifying enteroscope. Technological advancements and the accumulation of reported pathological data would further improve our understanding of the pathophysiological aspects of this disease entity, even in the jejunum.

DOI： 10.1159/000493578

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Introduction: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Material and methods: Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes - IELs) and the underlying lamina propria (lamina propria lymphocytes - LPLs), and then, MAIT cells were analyzed by flow cytometry. Results: Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A+ cells among MAIT cells was significantly increased in the cecum. Conclusions: These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.

DOI： 10.5114/ceji.2019.84020

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DOI： 10.1111/jgh.14312

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The incidence of carcinoid tumor in the small intestine is increasing; however, its preoperative diagnosis is difficult. We recently experienced three cases of multiple carcinoid tumors in the small intestine successfully detected using capsule endoscopy (CE), followed by a pathological diagnosis using double-balloon enteroscopy (DBE). To diagnose multiple carcinoid in the small intestine appropriately, we reviewed the information of five cases reported to date along with our three recent cases. The literature review demonstrated that CE and DBE are useful for detecting and diagnosing small intestinal carcinoids and tumor multiplicity, which aids in determining the appropriate resection range.

DOI： 10.2169/internalmedicine.1700-18

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DOI： 10.1053/j.gastro.2018.09.035

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The vascular diseases including aneurysm, occlusion, and thromboses in the mesenteric lesions could cause severe symptoms and appropriate diagnosis and treatment are essential for managing patients. With the development and improvement of imaging modalities, diagnostic frequency of these vascular diseases in abdominal lesions is increasing even with the small changes in the vasculatures. Among various vascular diseases, fibromuscular dysplasia (FMD) and segmental arterial mediolysis (SAM) are noninflammatory, nonatherosclerotic arterial diseases which need to be diagnosed urgently because these diseases could affect various organs and be lethal if the appropriate management is not provided. However, because FMD and SAM are rare, the cause, prevalence, clinical characteristics including the symptoms, findings in the imaging studies, pathological findings, management, and prognoses have not been systematically summarized. Therefore, there have been neither standard diagnostic criteria nor therapeutic methodologies established, to date. To systematically summarize the information and to compare these disease entities, we have summarized the characteristics of FMD and SAM in the gastroenterological regions by reviewing the cases reported thus far. The information summarized will be helpful for physicians treating these patients in an emergency care unit and for the differential diagnosis of other diseases showing severe abdominal pain.

DOI： 10.3748/wjg.v24.i32.3637

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Georg Thieme Verlag  

Background Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200μm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. Methods This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. Results A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9-144 months) and the median number of CTs was 6 (range 0-24). LVI was found in 21 patients (20.6%), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1%, 97.5%, and 82.1%, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8%, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95% confidence interval 1.39-21.18
P =0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. Conclusions The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up.These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

DOI： 10.1055/s-0043-124433

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BACKGROUND AND AIM: Mucosal-associated invariant T (MAIT) cells constitute a novel subset of innate-like T lymphocytes characterized by a semi-invariant T-cell receptor repertoire capable of recognizing bacterial products. Considering the abundance of MAIT cells in the liver and the possible association between bacterial infections and primary biliary cholangitis (PBC), we aimed to analyze the involvement of MAIT cells in the immunopathogenesis of PBC. METHODS: Peripheral blood and liver biopsy specimens were collected from 25 patients with PBC and 19 patients with chronic viral hepatitis. Surgically removed liver tissues distant from tumors in patients with metastatic liver tumors were used as controls. Mononuclear cells were separated using Ficoll gradient, and the expression of various markers was investigated by flow cytometry. Cytokine production was investigated using blood MAIT cells after stimulation by anti-CD3/CD28-coupled beads with/without interleukin-7 (IL-7). RESULTS: Mucosal-associated invariant T cells were significantly reduced in both the blood and liver of PBC patients compared with those in controls. MAIT cells in the blood of PBC patients expressed significantly lower levels of activation markers and IL-7 receptor. Moreover, MAIT cells in the blood of PBC patients showed impaired production of cytokines, especially tumor necrosis factor alpha, after in vitro stimulation with IL-7. Interestingly, even after biochemical responses were achieved by ursodeoxycholic acid treatment, the frequencies of MAIT cells did not fully recover to normal levels. CONCLUSIONS: These findings suggested that MAIT cells were activated, exhausted, and persistently depleted in PBC patients even after ursodeoxycholic acid treatment, possibly as a consequence of persistent liver inflammation.

DOI： 10.1111/jgh.14076

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Language：English   Publisher：MOSBY-ELSEVIER  

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DOI： 10.1136/gutjnl-2017-315591

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Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment
however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

DOI： 10.3748/wjg.v24.i16.1734

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Behçet’s disease (BD) is a systemic inflammatory disorder involving the oral and genital mucosa, skin, eyes, gastrointestinal tract, joints, vasculature, and nervous. The gastrointestinal lesions accompanying with BD can extend along the full length of the tract, from the mouth to the anus, and show various clinical characteristics which is difficult to be differentiate from the other inflammatory bowel diseases including ulcerative colitis and Crohn’s disease. Hence, the differential diagnosis is difficult and can affect treatment outcomes. We report here, a BD case showing varied gastrointestinal lesions and endoscopic findings. The information, endoscopic findings, differential diagnosis, and treatment approach in this case might help physicians to distinguish from other diseases and to manage similar cases

DOI： 10.1007/s12328-018-0860-6

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DOI： 10.1038/ajg.2017.481

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Background and Aim: Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH). Methods: Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 22 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled. The frequencies of different Tfh subsets in the blood and liver were examined by flow cytometry and immunohistochemical staining. The function of circulating Tfh subsets was examined after in vitro stimulation. Results: In newly diagnosed AIH patients, the frequency of circulating chemokine C-C receptor 7−programmed cell death-1+ Tfh subset was significantly increased compared with that in CHB patients and HC, significantly correlated with clinical parameters, including serum IgG, prothrombin time and albumin levels, and significantly decreased after corticosteroid treatment. In the liver of AIH patients, the frequencies of activated Tfh subsets were significantly increased and positively correlated with those in the blood. Moreover, the ability to produce interleukin-21 and interleukin-17 from circulating Tfh cells was significantly increased in AIH patients compared with HC. Conclusions: These results significantly extend our understanding of Tfh subsets in AIH and suggest a potential role of dysregulated chemokine C-C receptor 7−programmed cell death-1+ Tfh subset in the pathogenesis and disease progression of AIH.

DOI： 10.1111/jgh.13844

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Duodenal gastrointestinal stromal tumors (GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

DOI： 10.4253/wjge.v9.i12.583

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DOI： 10.1002/hep.29266

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.

DOI： 10.1038/s41598-017-15800-z

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DOI： 10.1002/hep.29266

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munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-alpha and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.

DOI： 10.2220/biomedres.38.111

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Background. Dentures and dental instruments are frequently encountered ingested foreign bodies. The aim of the present study was to assess the safety and efficacy of endoscopically removing ingested dental objects. Methods. Twenty-nine consecutive patients with 29 dental objects who were treated at the Niigata University Medical and Dental Hospital from August 2009 to December 2015 were retrospectively reviewed. Characteristics of the patients and the ingested dental objects, the clinical features and findings of radiological imaging tests, and outcomes of endoscopic removal were analyzed. Results. Patients' mean age was 62.9 + 21.0 years. The ingested dental objects included 23 dentures (13 crowns, 4 bridges, 4 partial dentures, and 2 other dentures) and 6 dental instruments. Twenty-seven upper gastrointestinal endoscopies and 2 colonoscopies were performed, and their success rates were 92.6% and 100%, respectively. There were 2 cases of removal failure; one case involved an impacted partial denture in the cervical esophagus, and this case required surgical removal. Conclusions. Endoscopic removal of ingested dentures and dental instruments is associated with a favorable success rate and acceptable complications. The immediate intervention and appropriate selection of devices are essential for managing ingested dental objects.

DOI： 10.1155/2016/3537147

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Progressive liver fibrosis remains a major problem for patients with recurrent chronic hepatitis C (CHC) after liver transplantation (LT). However, the involvement of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in recurrent CHC after LT remains unclear. In the present study, we investigated the status of NK and NKT cells in the liver and peripheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15 patients with CHC, and 7 normal donors for living donor LT. CD56(+) NK cells were separated into two subsets: CD56(+bright) subset, which is identified as major NK cytokine producer, and CD56(+dim) subset, which has greater spontaneous cytotoxicity. We found a significant decrease in the CD56(+bright) subset in the liver of patients with LT-C compared to patients with CHC (P &lt; 0.01) and normal donors (P = 0.03). The expression of inhibitory NK cell receptor NKG2A was significantly increased on intrahepatic CD56(+bright) subset in LT-C patients, and activated CD69(+)CD56(+dim) NK cell subset was significantly increased. in the liver of LT-C patients. Our results suggest that a significant imbalance between CD56(+bright) and CD56(+dim) NK cell subsets in the liver may contribute to the progression of recurrent CHC after LT.

DOI： 10.2220/biomedres.35.177

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Trousseau症候群は、Trousseauによって1865年に報告された、悪性腫瘍に合併する血栓症である。その脳卒中症状は、重篤な神経症状を呈し、直接的に生命予後に関与しうる傍悪性腫瘍症候群の一つとして認識されている。今回、胆管細胞癌に脳卒中症状を呈するTrousseau症候群を合併し死亡した2例を経験したので報告する。症例1は90歳、男性、症例2は58歳、女性でいずれの症例も生活習慣病の危険因子を有し、40mm前後の肝腫瘍で初診、各種画像検査、胆汁細胞診、組織診にて胆管細胞癌の診断となった。経過中、腫瘍の急激な増大、胆道出血を合併し、本症候群を発症しやすい状況であった。担癌患者では、病態が急速に進行する場合、凝固線溶系の異常値などに留意し、抗凝固療法の開始を含む対応が本症候群の発症を予防し、原病に対する治療介入の機会を増やしうる方法論であると考え、報告する。(著者抄録)

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DOI： 10.2957/kanzo.58.528

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