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Objectives: Long‐term outcomes of gastric subepithelial lesions have not been elucidated. To reveal the natural history, we initiated a prospective, 10‐year follow‐up of patients with small (≤20 mm) gastric subepithelial lesions in September 2014. Here, we report the results of an interim analysis of a prospective observational study. Methods: In total, 567 patients with 610 lesions were prospectively registered between September 2014 and August 2016. The location, size, morphology, and number of subepithelial lesions were recorded on a web‐based case report form. This study has been conducted as an Academic Committee Working Group of the Japan Gastroenterological Endoscopy Society. Results: The endoscopic follow‐up period was 4.60 ± 1.73 years (mean ± standard deviation), and survival data were investigated for 5.28 ± 1.68 years. This interim analysis revealed that the estimated cumulative incidence of a size increase ≥5 mm, after accounting for patients' death and resection of the tumor as competing risk events, was 4.5% at 5 years. In addition, the estimated cumulative incidence of lesion size increase ≥5 mm or resection of lesions was 7.9% at 5 years, and that of size increase ≥10 mm or resection of lesions was 4.5% at 5 years. Conclusion: These results indicate that approximately one in 13 patients with small (≤20 mm) gastric subepithelial lesions may require resection or further investigation for increased tumor size (≥5 mm) within 5 years. [ABSTRACT FROM AUTHOR]

Background and Aim: Bleeding is an inevitable and often severe complication after endoscopic sphincterotomy (EST). We aimed to investigate the factors associated with post‐EST bleeding in patients treated with anticoagulants. Methods: The data of patients who underwent EST at 15 hospitals between July 2015 and June 2017 were extracted. We investigated the incidence of post‐EST bleeding and risk factors for bleeding in patients treated with anticoagulants. Results: One hundred forty‐nine patients undergoing EST who met the inclusion criteria were included in this study. The total‐EST bleeding (bleeding occurring during or after EST) rate did not differ between the heparin replacement (8.0%, 6/75) and continuation (16.6%, 2/12; P = 0.37) groups of warfarin users. The total‐EST‐bleeding rate in the heparin replacement group (12.9%, 4/31) was significantly higher than that in the continuation group (0%, 0/31; P = 0.016) in direct oral anticoagulant (DOAC) users. The rate of total‐EST bleeding with continuation of DOAC (0%, 0/31) was significantly lower with continuation of warfarin (16.6%, 2/12; P = 0.021). During‐EST bleeding (bleeding occurring during EST) (P = 0.0083) and precut (P = 0.033) were significant risk factors for post‐EST bleeding in all 149 patients. Heparin replacement was only a significant risk factor for total‐EST bleeding (P = 0.033) in DOAC users. Conclusion: Heparin replacement was a significant risk factor for post‐EST bleeding in DOAC users; however, there was no significant difference between the bleeding rate of heparin replacement and that of continuation groups in patients taking warfarin. During EST and precut were significant risk factors for post‐EST bleeding in all patients treated with anticoagulants. [ABSTRACT FROM AUTHOR]

To determine the endoscopic and clinical features of localized gastric amyloid light-chain (AL) amyloidosis, we retrospectively examined the characteristics of nine patients (eight men and one woman) encountered by the hospitals in our network. Lesions were predominantly flat and depressed with surface vascular dilatation (n=5); others were characterized by subepithelial lesions (n=2), mucosal color change (n=1), and a mass-like morphology with swollen mucosal folds (n=1). Colonoscopy (n=7), video capsule enteroscopy (n=2), serum (n=5) and urine immunoelectrophoresis (n=4), and bone marrow examination (n=3) were performed to exclude involvement of organs other than the stomach. As treatment for gastric lesions of AL amyloidosis, one patient each underwent endoscopic submucosal dissection (n=1) and argon plasma coagulation (n=1), while the remaining seven patients underwent no specific treatment. During a mean follow-up of 4.2 years, one patient died 3.2 years after diagnosis, but the cause of death, which occurred in another hospital, was unknown. The remaining eight patients were alive at the last visit. In conclusion, although localized gastric AL amyloidosis can show various macroscopic features on esophagogastroduodenoscopy, flat, depressed lesions with vascular dilatation on the surface are predominant., Competing Interests: No potential conflict of interest relevant to this article was reported.

A 75-year-old man was admitted to our hospital for further examination of swollen lymph nodes and a possible gastric submucosal tumor. He had persistent fever and anorexia. Blood examination showed anemia, thrombocytopenia, and elevated lactate dehydrogenase and soluble interleukin 2 receptor levels. Swollen lymph nodes and splenomegaly were evident on computed tomography, and the submucosal tumor was revealed by esophagogastric endoscopy. Cervical lymph node biopsy and endoscopic biopsy were performed, which revealed a diagnosis of intravascular lymphoma. In Asian countries, patients with intravascular lymphoma often have hemophagocytic syndrome without lesions of the central nervous system or skin, which is called the Asian variant of intravascular lymphoma. In this case, the patient had no indicative lesions and had no evidence of the hemophagocytic syndrome. He also had lymph node swelling and a gastric submucosal tumor, which are rare in intravascular lymphoma. The patient was treated with chemotherapy (R-CHOP;rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone), and complete response was demonstrated (based on the Response Evaluation Criteria for Solid Tumours [RECIST] guideline). In cases of possible intravascular lymphoma, gastrointestinal endoscopy and biopsy should be considered because they are a useful diagnostic strategy.

Sarcoidosis is a systemic disease characterized by the formation of non-caseating granulomas in multiple organs. In the diagnosis of sarcoidosis, imaging modalities such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) are useful;however, there are few reports of MRI imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB) MRI. A 46-year-old Japanese female with suspected pulmonary sarcoidosis was admitted to our hospital because low-density mottles in the liver were observed incidentally by chest CT. The low-density mottles were not enhanced at the arterial phase or portal phase by abdominal CT and MRI, and decreased uptake was observed in the hepatobiliary phase of Gd-EOB MRI. No hematological disorder was observed except for a slight increase of biliary enzymes. The lesion was diagnosed as liver sarcoidosis by the liver biopsy. Since the patient refused steroid therapy, we prescribed ursodeoxycholic acid (UDCA). 600mg/day. The serum levels of biliary enzymes were normalized and the abdominal CT findings gradually improved after the initiation of UDCA medication. Gd-EOB MRI showed unique hypointense areas in the liver at the hepatobiliary phase, which might be useful in the diagnosis of liver sarcoidosis.

Aim: To investigate the capacity for 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma., Methods: This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011. Data for endoscopic, radiological, and biological examinations performed were retrospectively reviewed from clinical records. A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value (SUVmax). Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed, patients were subdivided into two groups. To identify potential predictive factors for 18F-FDG positivity, these two groups were compared with respect to gender, age at diagnosis of lymphoma, histopathological grade, pattern of follicular dendritic cells, mitotic rate, clinical stage, soluble interleukin-2 receptor levels detected by 18F-FDG-PET, lactate dehydrogenase (LDH) levels, hemoglobin levels, bone marrow involvement, detectability of gastrointestinal lesions by computed tomography (CT) scanning, and follicular lymphoma international prognostic index (FLIPI) risk., Results: Involvement of follicular lymphoma in the stomach, duodenum, jejunum, ileum, cecum, colon, and rectum was identified in 1, 34, 6, 3, 2, 3, and 6 patients, respectively. No patient had esophageal involvement. In total, 19/41 (46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract. In contrast, false-negative 18F-FDG uptake was detected in 24 patients (58.5%), while false-positive 18F-FDG uptake was detected in 5 patients (12.2%). In the former case, 2/19 patients had both 18F-FDG-positive lesions and 18F-FDG-negative lesions in the gastrointestinal tract. In patients with 18F-FDG avidity, the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4 (median: 4.7). For the 18F-FDG-negative (n = 22) and -positive (n = 19) groups, there were no differences in the male to female ratios (10/12 vs 4/15, P = 0.186), patient age (63.6 ± 2.4 years vs 60.1 ± 2.6 years, P = 0.323), presence of histopathological grade 1 vs 2 (20/2 and 17/2, P = 1.000), follicular dendritic cell pattern (duodenal/nodal: 13/5 vs 10/3, P = 1.000), mitotic rate (low/partly high, 14/1 vs 10/3, P = 0.311), clinical stage according to the Ann Arbor system (stages IE and IIE/other, 15/7 vs 15/4, P = 0.499), clinical stage according to the Lugano system (stages I and II-1/other, 14/8 vs 14/5, P = 0.489), soluble interleukin-2 receptor levels (495 ± 78 vs 402 ± 83, P = 0.884), LDH levels (188 ± 7 vs 183 ± 8, P = 0.749), hemoglobin levels (13.5 ± 0.3 vs 12.8 ± 0.4, P = 0.197), bone marrow involvement (positive/negative, 1/8 vs 1/10, P = 1.000), detectability by CT scanning (positive/negative, 1/16 vs 4/13, P = 0.335), and FLIPI risk (low risk/other, 16/6 vs 13/6, P = 0.763), respectively in each case., Conclusion: These findings indicate that it is not feasible to predict 18F-FDG-avidity. Therefore, 18F-FDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients, and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.

The artificial ascites technique is often used during radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) treatment because it prevents visceral damage and improves visualization by minimizing interference of the lungs and mesentery. This study determined the efficacy and safety of RFA using the artificial ascites technique in HCC patients. We examined 188 HCC patients who were treated by RFA and fulfilled the Milan criteria. Treatment outcomes (complete ablation rate, local recurrence rate, complication rate, liver function including total bilirubin level, alanine aminotransferase level, albumin level, and prothrombin time) were compared among patients divided into 3 groups based on the volume of artificial ascites injected:Group I (n = 86), no artificial ascites injected;Group II (n = 35), < 1,000 ml artificial ascites injected;and Group III (n = 67), > 1,000 ml artificial ascites injected. No significant difference was observed in complete ablation or local recurrence rates among the 3 groups, or in the extent of liver function damage after RFA. Artificial ascites disappeared within 7 days; additional diuretics were needed only in 5 (all from Group III) of 102 patients. No serious complications such as intestinal perforation or intraperitoneal bleeding were observed. Thus, we found that artificial ascites injection during RFA is effective and safe, and can be used to prevent major procedural complications.

Objective: This study aimed to evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC) in the caudate lobe, where RFA is considered to be difficult., Materials and Methods: Of a total of 810 patients treated by ultrasound-guided radiotherapy between July 2002 and May 2010, medical records of 50 consecutive patients with HCC in the caudate lobe were reviewed in this retrospective study. Twenty-two tumors were found to be in the paracaval portion and 28 in the Spiegel lobe. We retrospectively reviewed the procedures, treatment effect, and complications., Results: For all paracaval tumors and eight Spiegel lobe tumors, we used the intercostal approach, and for the remaining Spiegel tumors (n = 20) we used the pass-the-left approach. We found that all tumors were successfully treated, and the local recurrence rate after 2 years was 12%. Cases of mortality or major complications after RFA were absent., Conclusion: RFA appears to be an effective treatment modality for HCC in the caudate lobe.

A 53-year-old man suffering from infectious endocarditis developed a rupture of the mitral valve tendinous cord. Consequently a mitral valvoplasty was performed. Forty days later, the patient presented with sudden and severe epigastralgia and hematemesis, and was rushed to our hospital. An arterial phase of an abdominal contrast-enhanced CT showed a mass 3 cm in diameter which was strongly enhanced along the side of the hepatic portal region and therefore it was thought to be an aneurysm. An abdominal angiography revealed an aneurysm of the right hepatic artery. As a result, an embolization with coils was performed. Nine months after treatment, CT examination of the abdomen revealed that the aneurysm had completely disappeared.

Background/aims: To evaluate the association of the immunosuppressive effects of transforming growth factor-beta1 (TGF-beta1) with abnormalities in immune regulation in autoimmune hepatitis (AIH), we investigated the serum level of TGF-beta1 and expression of TGF-beta receptor type II (TbetaRII) in peripheral blood mononuclear cells (PBMC) in patients with AIH., Methodology: Twenty-two patients with AIH were included in this study. Serum levels of total TGF-beta1 were determined using a specific enzyme-linked immunosorbent assay (ELISA). The expression levels of TbetaRII mRNA were semi-quantitatively determined by ribonuclease (RNase) protection assay specific for TbetaRII., Results: The mean serum level of TGF-beta1 in patients with AIH (230+/-95 ng/mL) was higher than that of healthy controls (137+/-81 ng/mL, p=0.012). The expression level of TbetaRII mRNA in PBMC obtained from AIH patients (0.131+/-0.046) was lower than that in PBMC of patients with chronic hepatitis C (0.186+/-0.074, p=0.019) and that of healthy subjects (0.188+/-0.060, p=0.013)., Conclusions: The present study of TbetaRII mRNA expression in PBMC from patients with AIH suggested that the decreased expression of TbetaRII might contribute partially to abnormalities in immune regulation observed in patients with AIH, despite concomitant up-regulation of TGF-beta1 production.

In patients with hepatocellular carcinoma (HCC), natural killer (NK) cell activity decreases significantly, and the reduced activity may be associated with the progression of HCC. In this study we evaluated the effects of pulsing with interleukin (IL)-2 and/or IL-12 on the activation of freshly isolated peripheral blood lymphocytes (PBL) derived from patients with HCC. PBL obtained from 9 HCC patients, 4 liver cirrhosis patients, and 9 normal subjects were cultured in the presence of IL-2 and/or IL-12. After 24 h of incubation, the levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha presented in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). The IFN-gamma and TNF-alpha production of PBL pulsed by a combination of IL-2 and IL-12 was significantly higher than those of PBL stimulated by either IL-2 or IL-12 alone. The mRNA encoding perforin, granzyme B, as well as IFN-gamma and TNF-alpha, were markedly enhanced in PBL stimulated with a combination of IL-12 and IL-2. The pulsing procedure of IL-12 in combination with IL-2 resulted in the increase of IFN-gamma and TNF-alpha, and the expression of perforin and granzyme B mRNA in PBL obtained from HCC patients, as well as in those obtained from normal subjects. These results indicate that adoptive immunotherapy based on PBL pulsed with a combination of IL-2 and IL-12 may be a promising adjunctive strategy for HCC treatment.

Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.